Chpt 29-Management of Nonhematologic Disorders

Gerontologic considerations

Evidence suggests that inflammation may have a significant role in the development of anemia in older adults. Higher-than-normal levels of inflammatory cytokines are found in older adults, and this pro-inflammatory state may predispose older adults to frailty. Frailty is manifested by weight loss, impaired mobility, generalized weakness, and loss of balance and is strongly associated with anemia of inflammation. Erythropoietin levels may not rise as expected in response to decreased hemoglobin

Pathophysiology

Lack of folic acid or B12 Folic acid is stored in the body as compounds known as folates. Folate stores are smaller than those of vitamin B12 and can be depleted within months if dietary intake of folate is deficient Folate is found in green vegetables and liver. Folate deficiency is rarely seen in patients who consume uncooked vegetables. Alcohol ingestion increases folic acid requirements and it is not uncommon for those with alcohol abuse disorder to have a diet deficient in folate and other nutrients. Folic acid requirements are also higher in those with liver disease, chronic hemolytic anemias, and in women who are pregnant because erythrocyte production is increased with these conditions. Small bowel diseases such as celiac disease may interfere with normal absorption of folic acid

Lymphopenia

Lymphopenia is defined as a lymphocyte count less than 1500/mm3. It may occur as a result of exposure to ionizing radiation, long-term use of corticosteroids, uremia, infections (particularly viral infections), neoplasms (breast and lung cancer and advanced Hodgkin disease), and some protein-losing enteropathies which may cause lymphocytes from the GI tract to be lost When lymphopenia is mild, there are no serious sequelae, but when it is severe, it can result in bacterial infections (due to reduced B lymphocytes) or in opportunistic infections (due to reduced T lymphocytes). T-lymphocyte depletion is frequently associated with viral infections, including human immune deficiency virus (HIV). Excessive or prolonged use of alcohol can also impair lymphocyte production; lymphocyte counts can improve when alcohol intake is discontinued

Pathophysiology

Most often it is classified according to whether the decreased number of erythrocytes is associated with hypoproliferation (decreased production), hemolysis (increased destruction), or loss of cells through bleeding. Hypoproliferative anemias occur when the bone marrow produces an inadequate number of erythrocytes. Decreased erythrocyte production results in a low or inappropriately normal reticulocyte (i.e., immature RBC) count. Causes of hypoproliferative anemia may include bone marrow damage from chemicals (e.g., benzene) or medication (e.g., chloramphenicol), lack of important factors that promote erythrocyte production such as erythropoietin, or lack of nutrients, including iron, vitamin B12 and folic acid. In hemolytic anemias, premature destruction of erythrocytes results in the liberation of hemoglobin from the erythrocytes into the plasma; the released hemoglobin is converted in large part to bilirubin and, therefore, the bilirubin concentration rises. The increased erythrocyte destruction leads to tissue hypoxia, which in turn stimulates erythropoietin production. This increased production is reflected in an increased reticulocyte count as the bone marrow responds to the loss of erythrocytes. Hemolysis (destruction of RBCs with release of cellular components into the circulation) can result from an abnormality within the erythrocyte itself (e.g., sickle cell disease [SCD], glucose-6-phosphate dehydrogenase [G-6-PD] deficiency), within the plasma (e.g., immune hemolytic anemias), or from direct injury to the erythrocyte within the circulation (e.g., hemolysis caused by a mechanical heart valve) The ability of the bone marrow to respond to the decrease in erythrocytes by producing reticulocytes. The degree to which immature erythrocytes proliferate in the bone marrow and their ability to mature (as seen in a bone marrow biopsy). The presence or absence of end products of erythrocyte destruction in the circulation (e.g., increased bilirubin level, decreased haptoglobin level).

Complication for Sickle Cell Disease

Spleen Primary site of sickling → infarctions → ↓ phagocytic function of macrophages Autosplenectomy; ↑ infection (especially pneumonia, osteomyelitis) Abdominal pain; fever, other signs of infection Lungs Infection Pulmonary infiltrate Chest pain; dyspnea Infarction → ↑ pulmonary pressure → pulmonary hypertension ↑ sPLA2b Chest pain; dyspnea Central nervous system Infarction Stroke Weakness; cognitive dysfunction, speech and swallowing dysfunction Kidney Sickling → damage to renal medulla Hematuria; inability to concentrate urine; kidney injury Dehydration Heart Anemia Tachycardia; cardiomegaly → heart failure Weakness, fatigue, dyspnea Bone ↑ Erythroid production Widening of medullary spaces and cortical thinning Ache, arthralgias Infarction of bone Osteosclerosis → avascular necrosis Bone pain, especially hips Liver Hemolysis Jaundice and gallstone formation; hepatomegaly Abdominal pain Skin and peripheral vasculature ↑ Viscosity/stasis → infarction → skin ulcers Skin ulcers; ↓ wound healing Pain Eye Infarction Scarring, hemorrhage, retinal detachment ↓ Vision; blindness Penis Sickling → vascular thrombosis Priapism → impotence Pain, impotence

Clinical Manifestations

Bleeding can range from mild to severe. The severity does not necessarily correlate with the platelet count or with tests that measure coagulation (prothrombin time [PT], activated partial thromboplastin time [aPTT]). However, results from these tests may be useful in determining the etiology of the bleeding disorder when abnormalities are present For example, an elevated PT in the setting of a normal aPTT and platelet count may suggest factor VII deficiency, whereas an elevated aPTT in the setting of a normal PT and platelet count is suggestive of von Willebrand disease (vWD) or hemophilia. Ecchymoses, particularly on the extremities, are frequently evident. Patients with platelet dysfunction are at increased risk for bleeding after trauma or invasive procedures (e.g., dental extraction, biopsy).

Anemia

Condition characterized by a lower-than-normal hemoglobin concentration. Fewer than the normal number of red blood cells (RBCs), also called erythrocytes, are present in the circulation. Subsequently, less oxygen reaches the tissues, causing a variety of signs and symptoms. Rather than a disease state, anemia is a sign of an underlying disorder. It is the most common of all hematologic conditions and is prevalent throughout the world

Hypoproliferative anemia

The hypoproliferative anemias include iron deficiency anemia, anemias in renal disease, anemia of inflammation, aplastic anemia, and megaloblastic anemias. Iron deficiency anemia results when the intake of dietary iron is inadequate for synthesis of hemoglobin. The body is able to store about one fourth to one third of its iron requirements, and it is not until those stores are depleted that iron deficiency anemia develops. Iron deficiency anemia may occur when total body iron stores are adequate, but the amount of iron delivered to the erythroid precursors is inadequate. This is referred to as functional iron deficiency Prevalent in developing countries where iron stores may be chronically depleted because of lack of sources for iron-rich foods and from blood loss associated with intestinal parasites Iron deficiency anemia is also common among adults in the United States, with the most common cause being blood loss. Blood loss should always be considered as the cause of iron deficiency anemia until proven otherwise. The most common cause of this anemia in men and postmenopausal women is GI bleeding from ulcers, gastritis, tumors, or inflammatory bowel disease. The most common causes of iron deficiency anemia in premenopausal women are menorrhagia (i.e., excessive menstrual bleeding) and pregnancy with inadequate iron intake. Patients with chronic alcohol abuse and patients who take aspirin, steroids, or nonsteroidal anti-inflammatory drugs (NSAIDs) may have chronic blood loss from the GI tract, leading to iron loss and subsequent anemia. Other causes include iron malabsorption, as seen after gastrectomy or bariatric surgery, or from celiac disease and inflammatory bowel diseases

Causes of neutropenia

Decreased Production of Neutrophils •Aplastic anemia, due to medications or toxins •Chemotherapy •Metastatic cancer, lymphoma, leukemia •Myelodysplastic syndromes •Radiation therapy Ineffective Granulocytopoiesis •Megaloblastic anemia Increased Destruction of Neutrophils •Bacterial infections •Hypersplenism •Immunologic disorders (e.g., systemic lupus erythematosus) •Medication induceda •Viral disease (e.g., infectious hepatitis, mononucleosis)

Clinical Manifestations

ITP is often asymptomatic; the low platelet count frequently is an incidental finding. Platelet counts of less than 30,000/mm3 are not uncommon. Common signs of thrombocytopenia include easy bruising, heavy menses, and petechiae on the extremities or trunk Patients who experience only bruising and petechiae tend to have fewer complications from bleeding than those with bleeding from mucosal surfaces, such as the GI tract and respiratory system (sometimes described as "wet purpura"). Patients with wet purpura have a greater risk of life-threatening bleeding which requires immediate aggressive treatment to reduce complications Severe thrombocytopenia, characterized by platelet count less than 20,000/mm3, a prior history of minor bleeding episodes, and advanced age, is a risk factor for severe bleeding. Despite low platelet counts, platelets are typically immature yet very functional, with the ability to adhere to endothelial surfaces and each other. This may explain why spontaneous bleeding does not always occur. Treatment is not necessary unless bleeding becomes severe or if surgery or another invasive procedure is required

Causes of hemolytic anemia

Inherited Hemolytic Anemia Sickle cell disease Thalassemia Red Blood Cell Membrane Abnormality Acanthocytosis Hereditary elliptocytosis Hereditary spherocytosis Stomatocytosis Enzyme Deficiencies Glucose-6-phosphate dehydrogenase deficiency Acquired Hemolytic Anemia Antibody Related Autoimmune hemolytic anemia Iso-antibody/transfusion reaction Cold agglutinin disease Not Antibody Related Disseminated intravascular coagulation Hypersplenism Infection Bacterial Parasitic Liver disease Mechanical heart valve Microangiopathic hemolytic anemia Paroxysmal nocturnal hemoglobinuria Toxins Trauma Uremia

Stroke

Ischemic stroke is most common, especially in young children and older adults, while hemorrhagic stroke is more common in young adults. The mechanisms vary but often result from decreased blood flow due to anemia, hemolysis, and increased hypoxic stress. Silent cerebral infarction occurs in about 40% of patients with SCD who have strokes, resulting in neurocognitive decline RBC transfusion to reduce amount of hemoglobin S to less than 30% to reduce cerebral edema

Nursing management

Nurses in all settings can play a crucial role in assessing the severity of neutropenia and in preventing and managing complications, which most often include infections. Knowledge of risk factors for developing infection is an integral part of nursing care, particularly for those who work with patients who have cancer. Patient education is equally important, particularly at the time of discharge from the hospital or in the outpatient setting so that the patient can put an appropriate self-care plan into effect, including knowing when to seek medical attention. Patients at risk for neutropenia should have blood drawn for a CBC with differential; the frequency is based on the suspected duration and severity of the neutropenia. To assess the severity of neutropenia and risk for infection, nurses must assess the ANC

Nursing management

Patients with aplastic anemia are at high risk for problems associated with deficiencies of erythrocytes, leukocytes, and platelets. Thorough assessment for signs of infection and bleeding are critical Nursing care includes monitoring for side effects of therapy, including hypersensitivity reactions while administering ATG. Patients who require long-term cyclosporine therapy should be monitored for long-term effects, including renal and liver dysfunction, hypertension, pruritus, visual changes, tremor, and skin cancer. Education regarding drug-drug interactions between ATG and many other drugs is necessary. Patients should be informed that stopping immunosuppressive therapy abruptly is not recommended.

Nursing management

Patients with hemochromatosis frequently limit their iron intake; however, this is not typically effective as lone therapy. They should be advised to avoid taking additional iron supplements. Vitamin C supplementation should also be limited because it enhances iron absorption. Patients with hemochromatosis must be careful to avoid substances that might impair liver function including excessive alcohol ingestion. Other body systems should be monitored for evidence of organ dysfunction, particularly the endocrine and cardiac systems, so that appropriate interventions can be initiated without delay. Children of patients who are homozygous for the HFE gene mutation should be screened for the mutation. Patients who are heterozygous for the gene do not develop the disease but should be advised that they may transmit the gene to their children.

Platelet defects

Quantitative platelet defects (i.e., thrombocytopenia, thrombocytosis) are not uncommon, however qualitative defects may also occur. Despite normal platelet counts, when qualitative defects are present, platelets do not function normally. A platelet function analyzer is used to evaluate platelet function. This technique is valuable for rapid screening. Examination of platelet morphology with the peripheral blood smear in the laboratory can also identify possible qualitative defects. Platelet morphology is frequently hypogranular and pale and may also be larger than normal Aspirin may induce a platelet disorder. Even small amounts of aspirin can reduce normal platelet aggregation and increase bleeding time for several days after ingestion. Although this typically does not cause bleeding in most people, patients with thrombocytopenia and coagulation disorders such as hemophilia can experience significant bleeding after ingestion of aspirin, especially in conjunction with trauma and invasive procedures.

Anemia in Renal Disease

Severe until GFR is less than 30 mL/min Anemia contributes to increased cardiac output, reduced oxygen utilization, decreased cognition and ability to concentrate, reduced immune responsiveness, and reduced libido. Anemia may be more severe in patients with both CKD and diabetes

Assessment

The health history and physical examination provide important data about the type of anemia involved, the extent and type of symptoms it produces, and the impact of the symptoms on the patient's life. Weakness, fatigue, and general malaise are common symptoms, and pallor of the skin and mucous membranes (conjunctivae, oral mucosa) are common signs Jaundice, angular cheilitis (inflammation and fissures in the corners of the mouth), and brittle, concave, ridged nails may be associated with megaloblastic anemia (characterized by abnormally large, nucleated RBCs) or hemolytic anemia. The tongue may be sore and beefy red in megaloblastic anemia, and smooth and red with iron deficiency anemia. Patients with iron deficiency anemia often experience pica, a craving for ice, starch, or dirt Restless leg syndrome is common with iron deficiency anemia Medication history because some medications may depress bone marrow activity, induce hemolysis, interfere with folate metabolism, or cause GI irritation that leads to bleeding. An accurate social history should include alcohol intake, noting the amount consumed and the duration of alcohol use. Family history is also important since some types of anemia are inherited. The nurse should also inquire about athletic endeavors since extreme forms of exercise such as marathon running may influence erythropoiesis and erythrocyte survival A nutritional assessment is needed because it may indicate deficiencies in essential nutrients such as iron, vitamin B12, and folate. People who follow strict vegetarian diets and do not supplement with vitamin B12 are at risk for megaloblastic anemia. Older adults may also have decreased intake of foods rich in vitamin B12 or folate. Cardiac status should be assessed carefully. When hemoglobin levels are low, the heart attempts to compensate by pumping faster and harder to deliver more oxygen to hypoxic tissue. This increased cardiac workload can result in symptoms including tachycardia, palpitations, dizziness, orthopnea, and exertional dyspnea. Heart failure may eventually develop, evidenced by cardiomegaly (an enlarged heart), hepatomegaly (an enlarged liver), and peripheral edema. GI assessment may reveal complaints of nausea, vomiting (with specific questions regarding the appearance of any emesis [e.g., looks like "coffee grounds"]), melena (dark stools), diarrhea, anorexia, and glossitis (inflammation of the tongue). Stool should be tested for occult blood. Women should be asked about their menstrual periods (e.g., excessive flow, other vaginal bleeding) and the use of iron and vitamin supplements during pregnancy. Neurologic examination is important because pernicious anemia with vitamin B12 deficiency affects the function of the central and peripheral nervous systems (see later discussion). Examination should include assessment for the presence and extent of peripheral numbness and paresthesia, ataxia, impaired coordination, and confusion. Delirium can sometimes result from other types of anemia, particularly in older adults. It is important to monitor relevant laboratory results over time and note any changes

Assessment and diagnostic

A careful history and physical examination are essential to aid in excluding other causes of thrombocytopenia and identify sites of bleeding. Patients should be tested for hepatitis C and HIV, if not previously done to rule them out as potential causes. Bone marrow aspirate may reveal an increased number of megakaryocytes. The severity of the thrombocytopenia is highly variable. H. pylori infection is associated with ITP, and treatment to eradicate the infection may improve the platelet count. The correlation between H. pylori infection and ITP is not clear; it is postulated that the presence of the H. pylori organism may stimulate an autoimmune reaction

Gerontologic considerations

Anemia is the most common hematologic condition affecting older adults, particularly those admitted to hospitals and in long-term care facilities. The overall prevalence of anemia is 17% in older adults, including approximately 10% of community-dwelling older adults, 45% of nursing homes residents, and 40% of those who are hospitalized. Most have mild anemia with hemoglobin level of 11 g/dL or higher, but even mild anemia may be associated with decreased functional ability and increased morbidity and mortality. Mild anemia in older adults is associated with decreased physical performance, decreased mobility, increased frailty, increased depression, increased risk of falls, and delirium Association between anemia and cognitive decline. Older adults with anemia are more likely to have fatigue, dyspnea, and confusion because of reduced cardiac reserve and inability to respond with an increase in heart rate and increased cardiac output. Those with preexisting renal and cardiac disease and those who have had recent surgery are at increased risk for morbidity and mortality when anemic

Pathophysiology

Aplastic anemia is a life-threatening condition associated with bone marrow failure evidenced by pancytopenia (i.e., anemia, neutropenia, and thrombocytopenia; lower-than-normal counts of erythrocytes, neutrophils, and platelets) It can be acquired, or in rare cases, congenital, but most cases are idiopathic (i.e., without apparent cause). It may also be associated with certain medications, chemicals, or radiation damage. Agents that have been associated with bone marrow aplasia include benzene and benzene derivatives (i.e., airplane glues, paint remover, dry cleaning solutions). Certain toxic materials, including inorganic arsenic, glycol ethers, plutonium, and radon, have also been suggested as possible causes. Nonviral hepatitis may be a precipitating factor in about 10% of cases.

Clinical Manifestation

Chronic hemolysis and thrombosis. Sickled cells hemolyze rapidly and have a shortened lifespan. Anemia is typically present with hemoglobin values between 5 and 11 g/dL Jaundice is often present. The bone marrow expands early in life to compensate for the resulting anemia, sometimes causing enlargement of the bones in the face and skull. Chronic anemia is often associated with tachycardia, cardiac murmurs, and cardiomegaly. Arrhythmias and heart failure may also occur, especially in adults. Any organ can be affected by thrombosis, but those areas with slower circulation are frequently involved, including the lungs, spleen, and central nervous system (CNS). All tissues and organs can be affected by thrombosis in the microcirculation caused by the sickling process leading to hypoxia and tissue damage and necrosis. Patients with SCD are particularly susceptible to infections, especially pneumonia and osteomyelitis. Additional complications of SCD include stroke, kidney injury, impotence, and pulmonary hypertension

Polycythemia

increased volume of RBCs. The term is used when the hematocrit is elevated (more than 55% in males and 50% in females). Dehydration can cause elevated hematocrit but not usually to the level seen with polycythemia. Polycythemia is classified as either primary or secondary. Primary polycythemia, also known as polycythemia vera, is a myeloproliferative neoplasm Secondary polycythemia is caused by excessive production of erythropoietin. This may occur in response to a reduced amount of oxygen, which acts as a stimulus for production. Heavy smoking, obstructive sleep apnea (OSA), chronic obstructive pulmonary disease (COPD), severe heart disease, or conditions such as living at high altitudes or exposure to low levels of carbon monoxide may be responsible for increased erythropoietin production. Certain hemoglobinopathies (e.g., hemoglobin Chesapeake), in which the hemoglobin has a high affinity for oxygen, or genetic mutations that cause abnormally high erythropoietin levels may also increase erythropoiesis (Prchal, 2016b). Secondary polycythemia can also occur from certain neoplasms that stimulate erythropoietin production (e.g., renal cell carcinoma), excessive use of exogenous erythropoietin, and androgen use.

Sickle cell crisis

Acute vaso-occlusive crisis This very painful condition is the result of accumulation of erythrocytes and leukocytes in the microcirculation restricting blood flow to the tissue and causing hypoxia, inflammation, and necrosis. Substances released after tissue perfusion is restored include free radicals and free plasma hemoglobin, which cause oxidative damage to the blood vessel. As a result, the endothelial tissues in the vessel become dysfunctional Aplastic crisis results from infection with the human parvovirus. The hemoglobin level falls rapidly and the marrow cannot compensate, as evidenced by an absence of reticulocytes. Sequestration crisis results when sickled cells are pooled in organs. In young children, the most common site of sequestration is the spleen; however, in many children with SCD over 10 years of age, the spleen has been infarcted and is no longer functional Liver and lungs involved

Anemia of inflammation

Anemia of inflammation describes anemia associated with chronic diseases including inflammation, infection, and malignancy. This classification was previously known as anemia of chronic disease This classification also includes anemia of critical illness that can develop within days after the onset of serious illness, and the anemia associated with aging. Many chronic inflammatory diseases are associated with normochromic, normocytic anemia (i.e., RBCs are of normal color and size). These disorders include rheumatoid arthritis, chronic infections, and many cancers. It is important that the underlying condition be identified so that it can be treated appropriately. The anemia of inflammation is usually mild to moderate and not progressive. The hemoglobin level does not usually fall below 9 g/dL and bone marrow samples have normal cellularity and normal stores of iron. Erythropoietin levels are low and iron use is blocked by erythroid cells (cells that are or will become mature RBCs). Erythrocyte survival may also be shortened. Many patients with anemia of inflammation have few symptoms related to their anemia and do not require treatment. Treatment of the underlying disorder allows iron stored in the bone marrow to be utilized, promoting increased RBC production and facilitating the rise of hemoglobin levels. Iron supplementation is not beneficial for these patients.

Medical Management

Anemia often occurring in infancy and crises beginning as early as 1 or 2 years of age. Some children die in the first few years of life as a result of infection; however, outcomes have improved considerably in recent years. Average life expectancy is lower than the general population, rarely exceeding the sixth decade. Young adults often experience multiple, severe complications from their disease. A subgroup of patients experiences a decrease in symptoms and complications after age 30; however, at present there is no means to predict who will fall into this group. Death is most often caused by cardiac, lung, kidney, or neurologic complications, or from infection. Treatment of SCD is the focus of continued research. In addition to aggressive management of symptoms, including pain, and complications, there are a few primary treatment modalities.

Megaloblastic anemias

Anemias associated with vitamin B12 or folic acid deficiency cause the same bone marrow and peripheral blood changes because both are needed for normal DNA synthesis. The erythrocytes produced with these nutritional deficiencies are abnormally large, thus they are termed megaloblastic red blood cells. Other cells from the myeloid stem cell lines (nonlymphoid leukocytes and platelets) are also abnormal. Bone marrow analysis shows hyperplasia (an abnormal increase in the number of cells) and the precursor erythroid and myeloid cells are abnormally large and irregular in appearance. Many of these abnormal cells are destroyed within the bone marrow leading to an insufficient number of mature cells entering the peripheral blood. Over time, pancytopenia may develop. Cells that enter the circulation are often irregularly shaped; neutrophils are hypersegmented, and platelets may be abnormally large. Erythrocytes are abnormally shaped and shapes can vary greatly; this is known as poikilocytosis. Because erythrocytes are very large, the MCV is very high, often exceeding 110 fL. Megaloblastic anemias usually develop over months, allowing the body to compensate; thus, symptoms do not often occur until the anemia is severe Light skin-pale yellow from pallor and mild jaundice from RBC hemolysis

Substances that impair platelet function

Angiotensin-converting enzyme inhibitors Angiotensin receptor blockers Antibiotics Beta-lactams Cephalosporins Penicillins Beta-blockers Calcium channel blockers Chemotherapeutic agents Mithramycin Vincristine Diuretics Ethacrynic acid Furosemide HMG-CoA reductase inhibitors (i.e., "statins") Atorvastatin Simvastatin Methylxanthines Aminophylline Theophylline Milrinone Misoprostol Nitrates Isosorbide Nitroglycerin Phosphodiesterase inhibitors Pentoxyfilline Sildanafil Tadalafil Protease inhibitors Ritonavir Tipranavir Phenytoin Selective serotonin reuptake inhibitors Fluoxetine Fluvoxamine Paroxetine Sertraline Tricyclic antidepressants Doxepin Imipramine Tyrosine kinase inhibitors Dasatinib Imatanib Valproic acid Food and Food Additives Caffeine Ethanol (Alcohol) Fish oils Garlic Ginger Grape juice Over-the-Counter and Herbal Supplements Ginkgo biloba Ginseng Saw palmetto Vitamin C and E NSAIDs can also impair platelet function, but the effects are not as prolonged as with aspirin (4 days vs. 7 to 10 days). Other causes of platelet dysfunction include end-stage renal disease, MDS, multiple myeloma, cardiopulmonary bypass, herbal remedies, and other medications

Aplastic anemia

Aplastic anemia is a rare disease caused by a decrease in or damage to bone marrow stem cells, damage to the microenvironment within the bone marrow, and replacement of marrow with fat. Stem cell damage is caused by the body's T cells, which mediate an attack on the bone marrow resulting in aplasia (i.e., markedly reduced hematopoiesis). Therefore, in addition to severe anemia, significant neutropenia (i.e., lower-than-normal neutrophil count) and thrombocytopenia (i.e., lower-than-normal platelet count) also occur.

Assessment and Diagnostic

Aplastic anemia occurs in some situations when a medication or chemical is ingested in toxic amounts; however, it may occur even when medications are taken at the recommended dosage. This is known as an idiosyncratic reaction in those who are highly susceptible, possibly due to a genetic defect in the biotransformation of the medication or elimination process. The CBC reveals pancytopenia. Patients may have neutrophil counts less than 1,500/mm3, hemoglobins less than 10 g/dL, and platelet counts less than 50,000/mm3 A bone marrow biopsy typically reveals an extremely hypoplastic or aplastic bone marrow (i.e., with few or no cells), often replaced with fat.

Nursing Management

Assessment of patients who have or are at risk for megaloblastic anemia includes inspection of the skin, tongue, and mucous membranes. Mild jaundice may be evident and is best seen in the sclera with natural lighting. Vitiligo and premature graying of the hair are frequently present in those with pernicious anemia. Careful neurologic assessment is important to identify neurologic complications. Assessment should include tests of position, vibration sense, and cognitive function. The nurse should pay close attention to the patient's gait and stability with ambulation. Safety is a concern when gait, coordination and position sense are affected. Physical and occupational therapy referrals may be needed to assist in obtaining assistive devices and making sure patients are instructed in their use. When sensation is impaired, patients should be instructed to avoid excessive heat and cold. Mouth and tongue soreness may impair nutritional intake. The nurse may instruct the patient to choose soft bland foods that are less likely to cause further discomfort.

Assessment and Diagnostic findings

Bone marrow aspiration and biopsy are used to identify platelet deficiency associated with decreased production. A number of genetic causes of thrombocytopenia have been identified. Autosomal dominant, autosomal recessive, and X-linked mutations are among such disorders. When platelet destruction is the cause of thrombocytopenia, the bone marrow shows increased megakaryocytes and normal or increased platelet production as the body attempts to compensate for the decreased platelets in the circulation. Screening for hepatitis B or C, which can cause thrombocytopenia, should be done. An important cause to exclude is pseudothrombocytopenia. Platelets aggregate and clump in the presence of ethylenediaminetetraacetic acid (EDTA), the anticoagulant present in the tube used for CBC collection. This clumping can be seen 0.8% to 1.25% of the population. Manual examination of the peripheral smear can easily detect platelet clumping as the cause of thrombocytopenia. Redrawing the blood in a tube anticoagulated with citrate rather than EDTA, followed by rapid analysis of the platelet count can provide a more accurate count.

Medical Management

Folate deficiency is easily treated in most cases by increasing the amount of folic acid in the diet and taking 1 mg of folic acid daily as a supplement. Folic acid can be given intramuscularly to those people with conditions associated with malabsorption. While many multivitamin supplements contain folic acid, the amount may not be enough to replace body stores completely. When folate deficiency is associated with alcohol abuse, supplementation should continue as long as the patient is consuming alcohol. Vitamin B12 deficiency is treated with vitamin B12 replacement. People who follow a vegan diet can prevent or treat deficiency with oral supplements with vitamins or fortified soy milk. When deficiency is caused by impaired absorption or absence of intrinsic factor (i.e., pernicious anemia), replacement is typically given by monthly intramuscular injections. It is possible to treat patients with oral preparations in the absence of intrinsic factor but much larger doses are required. Intranasal sprays and gels are also available options to avoid the need for intramuscular injections. As vitamin B12 is replaced, the reticulocyte count rises, often within 1 week, and within 4 to 8 weeks blood counts return to normal. The tongue begins to feel better and appears less red after several days. Recovery from neurologic symptoms takes more time, and, if the neuropathy is severe, the patient may not fully recover. To prevent a recurrence of pernicious anemia, vitamin B12 supplementation must continue for life.

Hereditary Hemochromatosis

Hereditary hemochromatosis is a genetic condition characterized by excess iron absorption from the GI tract. Normally, the GI tract absorbs 1 to 2 mg of iron daily, but in those with hereditary hemochromatosis, this rate is significantly increased. The excess iron is deposited in various organs, especially the liver, skin, and pancreas; and less frequently, the heart, testes, and thyroid gland. Eventually, affected organs become dysfunctional. Although hereditary hemochromatosis is diagnosed in 1% to 6% of the U.S. population, the actual prevalence is unknown because it is not always recognized. The genetic defect associated with hemochromatosis is most commonly seen as a specific mutation (C282Y homozygosity) of the HFE gene

Neutropenia

Neutropenia is defined as a neutrophil count less than 2,000/mm3. It is the result of decreased production of neutrophils or increased destruction of cells. Neutrophils are essential in preventing and limiting bacterial infection. A patient with neutropenia is at increased risk for infection from both exogenous and endogenous sources (the GI tract and skin are common endogenous sources). The risk for infection is based not only on the severity of the neutropenia but also on its duration. The actual number of neutrophils, known as the absolute neutrophil count (ANC), is determined by a simple mathematical calculation using information from the CBC and differential The risk for infection increases proportionately with a decrease in the neutrophil count. The risk is low when the ANC is greater than 1000/mm3, and high when less than 500/mm3 and greatest when less than 100/mm3

Clinical Manifestation

Patients with iron deficiency primarily have symptoms of anemia. If the deficiency is severe or prolonged, they may also have a smooth, red tongue; brittle and ridged nails; and angular cheilosis. These signs subside after iron replacement therapy. The health history may be significant for multiple pregnancies, GI bleeding, and pica

Medical and Nurse Management

Platelet dysfunction that is associated with a medication requires stopping the medication when possible, especially when bleeding occurs. If platelet dysfunction is present, bleeding may be prevented by transfusion of platelets prior to an invasive procedure. Antifibrinolytic agents (e.g., aminocaproic acid) may be needed to prevent significant bleeding after procedures; desmopressin, a synthetic vasopressin analogue, can reduce the duration of bleeding and improve hemostasis for some patients Patients with platelet dysfunction should be instructed to avoid substances that can interfere with platelet function. These include OTC medications such as aspirin and NSAIDs, as well as some herbal preparations, nutritional supplements, and alcohol. Patients should notify all health care providers, including dentists, of their underlying condition before undergoing any invasive procedure so that measures to reduce risk for bleeding can be implemented. Maintaining good oral hygiene is important to promote good dental health and reduce risk for gingival bleeding.

Medical and Nurse management

Secondary thrombocytopenia is usually managed with treatment of the underlying disease. If platelet production is impaired, platelet transfusion may be needed to increase the platelet count and stop bleeding or prevent spontaneous hemorrhage. If excessive platelet destruction occurs, transfused platelets may also be destroyed. The most common cause of increased platelet destruction is immune thrombocytopenic purpura (ITP) Splenectomy When determining nursing interventions, the nurse considers the cause of the thrombocytopenia, the likely duration, and overall condition of the patient. Education is an important intervention to promote safety and should include fall prevention, particularly for older adults and those who are frail. Interventions for patients with secondary thrombocytopenia are the same as those for a patient with cancer who is at risk for bleeding

Clinical Manifestations

Signs and symptoms of bleeding disorders vary according to the type of defect. A careful history and physical examination can be useful in determining the source of the hemostatic defect. Abnormalities of the vascular system are sources of localized bleeding, usually into the skin. Because platelets are primarily responsible for stopping bleeding from small vessels, patients with decreased platelets develop petechiae, often in clusters. These lesions can be seen on the skin and mucous membranes and occur throughout the body In contrast, coagulation factor defects do not tend to cause superficial bleeding because the primary hemostatic mechanisms are still intact. Instead, bleeding occurs deeper within the body (e.g., subcutaneous or intramuscular hematomas, hemorrhage into joint spaces). External bleeding diminishes very slowly when local pressure is applied; it frequently recurs several hours after pressure is removed

Assessment and diagnostics

The patient with sickle cell trait usually has a normal hemoglobin level, normal hematocrit, and normal blood smear. Conversely, the patient with SCD has a low hematocrit and sickled cells on the blood smear. The white blood cell count and platelet count are often elevated as a result of a chronic inflammatory state Abnormal hemoglobin- Hemoglobin electrophoresis

Clinical Manifestations

Tissue damage is seldom evident until middle age because the accumulation of iron in body organs occurs gradually. Symptoms of weakness, lethargy, arthralgia, and weight loss are common and occur earlier in the course of the disease. The skin may appear hyperpigmented or bronze in color from melanin deposits and hemosiderin, an iron-containing pigment. Cardiac arrhythmias and cardiomyopathy can occur, with resulting dyspnea and edema. Endocrine dysfunction can be manifested as hypothyroidism, diabetes, and hypogonadism with testicular atrophy, diminished libido, and impotence. Cirrhosis is common in later stages of the disease, shortens life expectancy, and is a risk factor for hepatocellular carcinoma

Medical Management

Treatment of neutropenia varies depending on its etiology. If the neutropenia is medication induced, the offending agent should be discontinued immediately whenever possible. Treatment of an underlying neoplasm can temporarily make the neutropenia worse, but after bone marrow recovery, treatment may improve it. Corticosteroids may be used if the neutropenia is caused by an immunologic disorder. The use of growth factors such as granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor can be effective in increasing neutrophil production when the cause is reduced cell production. Withholding or reducing the dose of chemotherapy or radiation therapy may be necessary when the neutropenia is caused by these cancer treatments; however, when treatment is potentially curative, administration of growth factors is preferable so that the maximum antitumor effect of the cancer treatment can be achieved. If the neutropenia is associated with fever, it is assumed that the patient has an infection. Cultures of blood, urine, and sputum, as well as a chest x-ray are obtained. Broad-spectrum antibiotics are initiated immediately after cultures are obtained to ensure adequate treatment of infectious organisms. After culture and sensitivity results are obtained, the antibiotic regimen may be changed.

Assessment and Diagnostics

A number of studies are performed to determine the type and cause of the anemia. Initial evaluation includes hemoglobin, hematocrit, reticulocyte count, and RBC indices, including mean corpuscular volume (MCV), and red cell distribution width (RDW). Other studies may include iron studies (serum iron level, total iron-binding capacity [TIBC], percent saturation, and ferritin), serum vitamin B12, folate levels, haptoglobin, and erythropoietin levels The remaining complete blood count (CBC) values are also useful in determining if the anemia is an isolated condition or associated with another hematologic condition such as leukemia (i.e., malignancy of the WBCs) or myelodysplastic syndrome (MDS). Bone marrow aspiration may be performed to asses for cellular abnormalities. Additional studies such as colonoscopy or upper endoscopy may be performed to determine if underlying conditions causing the anemia are present. Lesions in the gastrointestinal (GI) tract including ulcers, polyps, or tumors may be sources of blood loss.

Pulmonary Hypertension

Diagnosis is difficult in the early stages and is usually delayed until irreversible damage occurs. Symptoms include fatigue, dyspnea on exertion, dizziness, chest pain, or syncope. Pulse oximetry is usually normal and breath sounds are often clear to auscultation until the condition is quite advanced. Pulmonary artery pressures are elevated above baseline but are generally lower than seen with idiopathic or hereditary pulmonary hypertension. Screening of patients with SCD with Doppler echocardiography may be helpful in identifying increased pulmonary artery pressure High levels of the amino-terminal form of brain natriuretic peptide can be a biomarker for pulmonary hypertension in people with SCD and serve as a predictor of mortality CT scan of chest- microvascular pulmonary occlusion and decrease lung perfusion may appear normal

Bleeding disorders

The failure of normal hemostatic mechanisms can result in bleeding which may be severe. Bleeding is commonly provoked by trauma; however, in certain circumstances, it can occur spontaneously. The causes of bleeding disorders can be categorized based upon whether there is a deficiency of platelets or a defect in the platelets, or based upon whether there is an inherited or acquired coagulation factor abnormality, or based upon a defect in the vasculature. When the cause is platelet or coagulation factor abnormalities, bleeding can occur anywhere in the body. When the source is a vascular abnormality the site of bleeding is more localized. Some patients may have simultaneous defects in more than one hemostatic mechanism.The bone marrow may be stimulated to increase platelet production. This can be a reactive response to significant bleeding, or a more general response to increased hematopoiesis, as in iron deficiency anemia. Sometimes an increase in platelets does not result from increased platelet production, but from a loss of platelet pooling in the spleen. The spleen typically holds about one third of circulating platelets at any time. If the spleen is absent (e.g., after splenectomy) the platelet reservoir is lost, and an abnormally high number of platelets enter the circulation. Eventually the rate of platelet production slows to reestablish a more normal platelet level.

Nursing interventions

The most common symptom and complication of anemia is fatigue. Fatigue is often the symptom with the greatest negative impact on the patient's ability to function and subsequent quality of life. Fatigue is often described as overwhelming or oppressive. The sensation of fatigue may be severe even when the anemia is not severe enough to warrant transfusion. Fatigue may interfere with the patient's ability to engage in work as well as pleasurable activities with family and friends. Significant distress can stem from the inability to meet life's demands and responsibilities and the need to rely on others for assistance. Nursing interventions can focus on assisting the patient to prioritize activities to establish a balance between activity and rest that is acceptable to the patient. Patients with chronic anemia will need assistance in establishing a program of activity and exercise to avoid deconditioning associated with inactivity. It is also important to assess for other conditions that may contribute to fatigue, such as pain, depression, and sleep disturbances. Adequate nutrition- iron, Vit B12, folic acid, and protein lacking can cause anemia Limit alcohol For example, patients with anemia who receive long-term transfusion therapy are at risk for iron overload from their transfusions. In this situation chelation therapy is implemented to reduce accumulation of excess iron Patients with severe anemia, with acute blood loss from hemorrhage or severe hemolysis, may not tolerate decreased blood volume or reduced circulating erythrocytes. Lost volume can be replaced with transfusions or intravenous fluids based on symptoms and laboratory test results. Supplemental oxygen may be needed, especially if there is underlying cardiac or pulmonary disease. Monitoring the patient's vital signs and pulse oximetry, especially with activity, is an important nursing action. Medications, including antihypertensive drugs, may need to be adjusted or withheld based on the patient's vital signs. A significant complication of anemia is heart failure associated with chronic diminished blood volume and the heart's compensatory effort to increase cardiac output. Patients with anemia should be assessed for signs and symptoms of heart failure In megaloblastic anemias associated with folate or vitamin B12 deficiency, there is potential for neurologic complications. Neurologic assessment of patients with megaloblastic anemia should be performed. Patients may complain of paresthesias, often manifested by numbness and, as the anemia progresses, symptoms worsen and other signs become apparent. Position and vibration sense may be diminished. Difficulty maintaining balance and gait disturbances may occur. Mental status changes, beginning with confusion and progressing to more severe memory changes and delirium can occur with severe folate or vitamin B12 deficiency

Clinical Manifestations

The onset of symptoms of aplastic anemia is often insidious. Complications stemming from bone marrow failure may occur before the diagnosis is made. Typical complications include infection and symptoms of anemia, including fatigue, pallor, and dyspnea. Purpura (bruising) associated with thrombocytopenia may develop. Any combination of these signs and symptoms should prompt a CBC and hematologic evaluation. Lymphadenopathy and splenomegaly may also occur. Retinal hemorrhages are common.

Management

When secondary polycythemia is mild, treatment may not be necessary. When treatment is necessary, however, it involves treating the primary condition. If the cause cannot be corrected (e.g., treatment of OSA or improving function with smoking cessation), therapeutic phlebotomy may be needed for symptom management and to reduce blood viscosity and volume. Therapeutic phlebotomy is not indicated when the cause for the elevated RBC count is an appropriate response to tissue hypoxia

Vit B12 deficiency

Deficiency of vitamin B12 can occur in several ways. Inadequate dietary intake is unusual but sometimes can occur in people who follow a vegan diet and do not consume any meat or dairy products. Impaired absorption from the GI tract is more common, especially in older adults. Nearly 20% of older adults have low vitamin B12 levels; 5% to 10% have symptoms related to vitamin B12 deficiency. Vitamin B12 deficiency can occur in patients with disorders such as inflammatory bowel disease, or in patients who have had GI surgery such as ileal resection, bariatric surgery, or gastrectomy. Use of metformin for treatment of type 2 diabetes as well as chronic use of histamine blockers, antacids, and proton pump inhibitors to reduce gastric acid can also inhibit vitamin B12 absorption Absence of intrinsic factor also impairs vitamin B12 absorption. When associated with lack of intrinsic factor, the anemia is referred to as pernicious anemia. Intrinsic factor is normally secreted by cells in the gastric mucosa; it binds to vitamin B12 and transports it to the ileum where it is absorbed. Without intrinsic factor, vitamin B12 taken orally cannot be absorbed and deficiency with associated anemia eventually results. Diseases of the pancreas and ileum may impair absorption even when adequate intrinsic factor and vitamin B12 are present. Pernicious anemia tends to run in families. It is typically a disease of adults, especially older adults. The body typically has large stores of vitamin B12 so years may pass before deficiency results in anemia. The body is able to compensate over time and the anemia is often severe before the patient becomes symptomatic. Because patients with pernicious anemia and low vitamin B12 levels have an increased incidence of gastric cancer they may benefit from screening for gastric cancer with endoscopy at regular intervals

Assessment and diagnosis and medical management

Diagnostic laboratory findings include an elevated serum ferritin and high serum transferrin saturation. CBC values are often normal. The definitive diagnostic test for hemochromatosis was formerly a liver biopsy but that test has been replaced by testing for the associated genetic mutation. Therapy often involves the removal of excess iron with therapeutic phlebotomy (removal of whole blood via venipuncture). Each unit of blood removed results in a decrease of 200 to 250 mg of iron. Initial treatment typically involves weekly removal of one unit of whole blood. As the ferritin level decreases, the frequency of phlebotomy can be decreased. The goal is to maintain an iron saturation between 10% and 50% and a serum ferritin level of less than 100 mcg/L Evaluation of iron studies should be repeated regularly and phlebotomy resumed when the ferritin level rises. CBCs and iron panel tests should be performed at regular intervals during treatment to ensure that the patient is not becoming anemic. If moderate anemia occurs, a delay in phlebotomy is often adequate to correct the problem. Aggressive removal of excess iron can prevent organ dysfunction and the complications associated with organ damage. Fatigue, skin pigmentation changes, and fibrosis are partially reversed by achieving and maintaining normal ferritin levels. Screening for hepatocellular carcinoma includes monitoring alpha-fetoprotein levels and serial abdominal ultrasounds

Hemolytic Anemia

Erythrocytes have a shortened lifespan; thus, their number in the circulation is reduced. Fewer erythrocytes result in decreased available oxygen, causing hypoxia, which in turn stimulates an increase in erythropoietin release from the kidney. Erythropoietin then stimulates the bone marrow to compensate by producing new erythrocytes and releasing some of them into the circulation somewhat prematurely as reticulocytes. If the red cell destruction persists, the hemoglobin is broken down excessively; the majority of the heme is converted to bilirubin, conjugated in the liver, and excreted in the bile. Hemolytic anemias are far less common than other forms of anemia with approximately 5% of all anemias caused by hemolysis. The mechanisms of erythrocyte breakdown vary, but common laboratory features are characteristic of hemolytic anemia. These include elevated reticulocyte count, increased fraction of indirect (unconjugated) bilirubin, and decreased haptoglobin (a binding protein for free hemoglobin) as additional hemoglobin is released from the cells. Anemia worsens if hemolysis persists and the bone marrow is unable to replace the destroyed cells. Hemolytic anemia is associated with a variety of conditions. Inherited forms include SCD, thalassemias, G-6-PD deficiency, and hereditary spherocytosis. Acquired forms include immune hemolytic anemia, non-immune-mediated paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic anemia, heart valve-related hemolysis and anemias associated with hypersplenism.

Pharmacologic therapy

For patients with SCD, hydroxyurea is a chemotherapeutic agent that is effective in increasing levels of fetal hemoglobin (i.e., hemoglobin F), which in turn decreases the formation of sickled cells. It is the only drug currently approved by the FDA for treatment of SCD. Studies have demonstrated that patients with SCD who received hydroxyurea experienced fewer episodes of painful crisis, had a lower incidence of acute chest syndrome, and needed fewer transfusion Side effects of the drug include chronic lowering of the leukocyte count, teratogenesis, and potential for later development of a malignancy. Patients' response to the drug can vary widely. The incidence and severity of side effects are variable. Adherence to the prescribed treatment regimen may be difficult for some patients. Patients with SCD often require daily folic acid supplements to maintain the amount needed for increased erythropoiesis to counteract the effects of hemolysis. Infections are common and should be treated promptly with the appropriate antibiotics. Pneumococcal pneumonia is common in children with SCD while in adults, Staphylococcus aureus infection is more common, involving bones and joints Vaccination against flu and pneumococcal Acute chest syndrome is managed by prompt treatment with antibiotics. Incentive spirometry has been shown to significantly reduce the incidence of pulmonary complications. In severe cases, bronchoscopy may be needed to identify the source of acute chest syndrome symptoms. Hydration is important but must be monitored carefully to avoid fluid overload. Corticosteroids may also be helpful. Transfusion can reduce hypoxia. Pulmonary function should be monitored carefully to detect symptoms of pulmonary hypertension as soon as possible so that therapies, including hydroxyurea and HSCT, can be of the greatest benefit.

Supportive therapy

Hydration is critical during a painful crisis. Oral hydration may be sufficient if the patient is able to maintain adequate intake. IV hydration may be needed if the patient is unable to consume 2 to 3 L of fluid during a crisis episode. Supplemental oxygen may also be needed. Another significant problem for people with SCD is fatigue. Fatigue can interfere with ability to perform effectively at work and school and reduce quality of life. Its causes, as with pain, may be multifactorial. Fatigue may occur in response to hypoxia associated with low levels of normal hemoglobin and decreased capacity to carry oxygen with sickled cells. Endothelial cells in the blood vessels become inflamed as a result of hypoxia. Inflammatory cytokines are increased in patients with SCD resulting in reduced muscle strength and decreased exercise capacity, increased resting energy expenditure, and sleep disturbances, all exacerbating fatigue. Sleep disturbances and depression are common and contribute to fatigue Working with patients who have multiple episodes of severe pain and fatigue can be challenging. Health care providers must recognize that patients with SCD are confronted with lifelong experiences with severe pain and fatigue that impair physical and social functioning that may be associated with depression and helplessness. Patients without adequate sources of support may have more issues with coping.

Reproductive Disorders

Hypogonadism with associated low testosterone levels, delayed puberty, low libido, erectile dysfunction, and infertility occur frequently in men with SCD Episodes of priapism (prolonged penile erection, without sexual stimulation) also contribute to significant pain and decreased libido. Over time, repeated episodes lead to permanent damage and erectile dysfunction, thereby making priapism a medical emergency that needs early recognition and treatment to preserve normal sexual function Fertility problems in women are not well described. Contraception is important when hydroxyurea is used in SCD treatment because of its teratogenic effects. Concerns about infertility may be associated with poor adherence to hydroxyurea therapy. Although most pregnancies complicated by maternal SCD are likely to result in live births, these pregnancies are at increased risk of obstetrical and fetal complications, as well as medical complications of SCD

Classified Anemia

Hypoproliferative (Resulting from Defective RBC Production) Iron deficiency (microcytic) ↓ MCV, ↓ reticulocytes ↓ Iron, % saturation, ferritin ↑ TIBC Vitamin B12 deficiency (megaloblastic) ↑ MCV ↓ Vitamin B12 Folate deficiency (megaloblastic) ↑ MCV ↓ Folate Decreased erythropoietin production (e.g., from chronic kidney disease) Normal MCV ↓ Erythropoietin level ↑ Creatinine ↑ Ferritin, % saturation ↓ Iron, TIBC ↓ Erythropoietin level (usually) Cancer/inflammation Normal MCV Bleeding (Resulting in RBC Loss) Bleeding from gastrointestinal tract, epistaxis (nosebleed), trauma, bleeding from genitourinary tract (e.g., menorrhagia) ↓ Hgb and Hct (Note: Hgb and Hct may be normal if measured soon after bleeding starts) ↓ MCV (normal MCV initially) ↑ Reticulocytes ↓ Iron, % saturation, ferritin (later) Hemolytic (Resulting from RBC Destruction) Altered erythropoiesis (sickle cell disease, thalassemia, other hemoglobinopathies) ↓ MCV ↑ Reticulocytes Fragmented RBCs (various shapes) Hypersplenism (hemolysis) ↑ MCV Drug-induced anemia ↑ Presence of spherocytes Autoimmune anemia ↑ Presence of spherocytes Mechanical heart valve-related anemia Fragmented red cells

Immune Thrombocytopenia

ITP is a condition that affects people of all ages but is most common in children and young women. This disorder is also referred to as idiopathic thrombocytopenic purpura, and immune thrombocytopenia. Primary ITP occurs as an isolated disorder while secondary ITP is associated with other disorders including autoimmune disorders (e.g., antiphospholipid antibody syndrome), viral infections (e.g., hepatitis C, HIV), and some drugs (e.g., cephalosporins, sulfonamides, furosemide). A platelet count less than 100,000/mm3 with no explicable cause is the primary criterion for the diagnosis Primary ITP is an acquired immune disorder characterized by thrombocytopenia that results from pathologic antiplatelet antibodies, impaired production of megakaryocytes, and T-cell-mediated destruction of platelets. Secondary ITP is associated with other underlying disorders, including autoimmune disease (systemic lupus erythematosus or rheumatoid arthritis), HIV infection, Helicobacter pylori infection, or underlying immune dysregulation syndromes, such as common variable immunodeficiency. The majority of adults with ITP (approximately 80%) have primary ITP. With both types of ITP, antiplatelet antibodies develop and bind to the patient's platelets. The antibody-bound platelets are then destroyed by the reticuloendothelial system (RES) and tissue macrophages. The body attempts to compensate for the platelet destruction by increasing platelet production within the bone marrow

Nurse management

If taking iron on an empty stomach causes GI distress, the patient may need to take it with meals. However, this may reduce absorption by as much as 40%, therefore increasing the time needed to replenish iron stores. Antacids and dairy products should be avoided with iron as they can greatly diminish its absorption. Polysaccharide iron complex preparations are available. These reduce GI toxicity but are more expensive. Liquid forms of iron that cause less GI distress are also available. Oral iron replacement therapy may change the color of the stool but should not cause a false-positive result for occult blood on stool analysis. IV supplementation may be used when the patient's iron stores are very low, if the patient cannot tolerate oral forms of iron, or both. The nurse must be aware of the type of parenteral formulation of iron ordered so that risk for anaphylaxis can be determined. High-molecular formulations are associated with a much higher risk for anaphylaxis and are seldom used. Administering a test dose of low-molecular formulations of iron dextran is recommended by many manufacturers. The nurse must assist the patient in understanding the need for repeated doses to replenish iron stores or to maintain iron stores in the setting of chronic blood loss, such as hemodialysis or chronic GI bleeding.

Medical Management

In other situations, treatment with immunosuppressive therapy using antithymocyte globulin (ATG) and androgens or cyclosporine is useful in managing the disease ATG is a purified gamma-globulin solution that is obtained from rabbits or horses immunized with human T lymphocytes. Side effects of such therapy include fever and chills. There is risk for anaphylaxis with associated bronchospasm and hypotension requiring emergency treatment. Serum sickness, associated with rash, fever, arthralgias, and pruritus may occur in some patients but can be prevented or reduced in some cases with premedication with corticosteroids Serum sickness resolves slowly, often over a few weeks when it occurs. Immunosuppressive therapies prevent T cells from destroying stem cells. If relapse does occur, resuming the same immunosuppressive therapy may induce another remission but the response rate is usually reduced Corticosteroids may be beneficial in the short-term; however, in aplastic anemia, long-term use is associated with bony abnormalities including aseptic necrosis and osteopenia. Supportive therapies play a critical role in the management of aplastic anemia. All potentially offending medications should be discontinued. Transfusions with PRBCs and platelets are frequently required Aggressive treatment of infections is necessary. Deaths associated with aplastic anemia are most often caused by bacterial or fungal infection and bleeding. Prophylaxis against invasive fungal infection is needed for patients who are severely neutropenic. Patients who become lymphopenic after ATG require prophylaxis for pneumocystis pneumonia.

Medical Management

Management of anemia is directed toward correcting or controlling the cause of the anemia; if the anemia is severe, the erythrocytes that are lost or destroyed may be replaced with a transfusion of packed red blood cells (PRBCs). Management of the various types of anemia is covered in the discussions that follow.

Medical and Nurse management

Management varies based on the underlying bleeding disorder. If bleeding is significant, transfusion of blood products may be indicated. The specific blood product used is determined by the underlying defect and the extent of blood loss. If fibrinolysis is excessive, hemostatic agents such as aminocaproic acid can be useful to inhibit the process, but this agent must be used cautiously because excessive inhibition of fibrinolysis can lead to thrombosis. A patient scheduled for an invasive procedure may need to have transfusions of select blood products to reduce risk for excessive bleeding. Patients who have bleeding disorders or who have the potential for development of such disorders as a result of disease or therapeutic agents must be educated to monitor themselves frequently and carefully for signs of bleeding. They should understand the importance of avoiding activities that increase the risk for bleeding, such as contact sports. The skin should be examined for evidence of bleeding, including petechiae and ecchymoses (bruises) and the nose and gums should also be examined for bleeding. When bleeding disorders are severe, patients who are hospitalized are monitored for bleeding by testing all drainage and excreta (feces, urine, emesis, and, gastric drainage) for obvious and occult blood.

Acute chest syndrome

Manifested by fever; respiratory distress that is manifested with tachypnea, cough and wheezing; and new infiltrates on the chest x-ray Infection with atypical bacteria including Chlamydia pneumoniae and Mycoplasma pneumoniae and viruses, including influenza, are often the cause. Other causes of acute chest syndrome include pulmonary thromboembolism, pulmonary fat embolism, bone marrow embolism, and pulmonary infarction. The patient's clinical condition can deteriorate very quickly leading to respiratory failure. Medical management includes blood transfusion, antibiotics, bronchodilators, inhaled nitric oxide, and when respiratory failure occurs, mechanical ventilation. Risk for acute chest syndrome can be reduced through immunization against influenza and pneumococcal pneumonia, and with use of incentive spirometry during vaso-occlusive crises, and with blood transfusion perioperatively

Nursing management

Nursing care includes a thorough assessment of the patient's lifestyle to determine risks for bleeding associated with activities. A careful medication history should also be obtained, including use of over-the-counter (OTC) medications, herbs, and nutritional supplements. The nurse must be alert to sulfa-containing medications and others that may interfere with platelet function (e.g., aspirin, NSAIDs). The nurse must assess for a history of recent viral illness and reports of headache, visual disturbances, and other symptoms that may indicate intracranial bleeding. Patients admitted to the hospital with wet purpura and low platelet counts should have neurologic assessment included with their vital sign measurements. Injections and rectal medications should be avoided. Rectal temperature measurements should also be avoided because they may cause trauma to the rectal mucosa and stimulate bleeding. There is evidence that patients with ITP experience an increase in fatigue when compared to those without the disease that is not associated with the duration of the disease, corticosteroid use, bleeding, or low platelet counts Patient and family education should address signs of exacerbation (e.g., petechiae and ecchymoses), how to contact appropriate health care personnel, the name and type of medications inducing ITP (if appropriate) current medical treatment (name of medications, side effects, tapering schedule, if indicated), frequency of monitoring for the platelet count, and follow-up appointments. The patient should be instructed to avoid all agents that interfere with platelet function, including herbal therapies and OTC medications. The patient should avoid constipation, straining, and vigorous flossing of the teeth. Electric razors should be used for shaving and soft-bristled toothbrushes should be used for dental hygiene. Patients and their partners should be counseled to avoid vigorous sexual intercourse when platelet counts are low. Patients who are receiving long-term corticosteroids should understand that they are at increased risk for complications including osteoporosis, proximal muscle wasting, cataract formation, and dental caries Bone mineral density should be monitored and benefit from vit C,D, and bisphosphonate

Medical Management

Oral iron supplementation is often the primary mode of treatment for iron deficiency anemia. Several oral iron preparations, including ferrous sulfate, ferrous gluconate, and ferrous fumarate, are available. Ferric maltol, another oral preparation, was approved by the U.S. Food and Drug Administration (FDA) in 2019 for use in iron deficiency anemia in those with inflammatory bowel disease. After taking oral iron preparations, hemoglobin typically begins to increase within a few weeks and the anemia may be corrected within a few months. Replenishing iron stores takes several months so it is important that patients continue taking oral iron supplements for 6 to 12 months. If oral iron is poorly absorbed or poorly tolerated, or large amounts of supplemental iron are needed, intravenous (IV) iron may be given in repeated doses Initial evidence has shown that ferric maltol is not inferior to parenteral iron and may be an alternative for patients who cannot tolerate other oral preparations or do not wish to have parenteral iron; however, it is unknown whether use of ferric maltol will decrease demands for parenteral iron preparations

Nurse management

Preventive education is important for women who are menstruating and for those who are pregnant. Food sources rich in iron include organ meats (e.g., beef or calf's liver, chicken liver), other meats, beans (e.g., pinto, black, and garbanzo beans), leafy green vegetables, raisins, and molasses. Eating iron-rich foods with a source of vitamin C (e.g., orange juice) improves iron absorption. The nurse assists the patient in selecting healthy diet options. Nutritional counseling can be provided for those who have an inadequate diet. Patients with history of strict vegetarian or other diets lacking in essential nutrients should be counseled about how to meet their dietary needs. The nurse also encourages the patient to continue the prescribed therapy for as long as needed to replenish iron stores even when fatigue and other symptoms have resolved. Oral iron is best absorbed on an empty stomach, making it important for patients to be instructed to take the supplement approximately 1 hour before or 2 hours after meals. The least expensive, standard form of oral iron, ferrous sulfate, is tolerated by most patients. GI side effects, including constipation, cramping, nausea, and vomiting may result in difficulty adhering to the prescribed regimen. Decreasing the frequency of administration or taking iron supplements with food may reduce symptoms but will diminish iron absorption, thus, it may take longer to replete iron stores. Taking iron with vitamin C can enhance absorption, but it may also increase the frequency of side effects Some iron formulations have been designed to limit GI side effects by adding stool softeners to reduce constipation or sustained release formulations to reduce gastritis and nausea. However, enteric-coated tablets may be poorly absorbed. Slow release formulations are absorbed beyond the duodenum; however, the duodenum is the site where maximum iron absorption takes place

Transfusion therapy

RBC transfusions have been shown to be highly effective in several situations: in an acute exacerbation of anemia (e.g., aplastic crisis, severe vaso-occlusive crisis), in the prevention of severe complications from anesthesia and surgery, in improving the response to infection (when it results in exacerbated anemia), in the case of acute chest syndrome and multiple organ dysfunction syndrome (MODS), and in thwarting the cerebral edema from a stroke. Transfusions are also effective in diminishing episodes of sickle cell crisis in pregnant women, although such transfusions do not improve fetal survival. Ongoing transfusion therapy may be effective in preventing or managing complications from SCD by keeping the HbS level to less than 30% Transfusions are not without risks, so it is important to consider the risks of complications versus benefits. Complications include difficulty with venous access, which necessitates placement of a vascular access device, and the concomitant risk for access site infection and thrombosis. Additional risks include other infections, particularly hepatitis; delayed hemolytic transfusion reactions; and iron overload that requires treatment with chelating agents. Iron overload is very likely with long-term/ongoing transfusion therapy, causing deposition of iron in vital organs, including the liver, heart, pancreas, kidneys, and pituitary gland. It is sometimes difficult to distinguish organ damage associated with the disease process from damage associated with iron overload. Iron chelation therapy, aimed at keeping iron levels at near normal, reduces complications An additional complication of transfusion therapy is increased blood viscosity without reduction in the concentration of hemoglobin S. Exchange transfusion, where some of the patient's blood is removed and replaced by RBC transfusion, may reduce the risk of increasing blood viscosity Repeated transfusions may result in development of multiple antibodies to other blood antigens, making cross matching increasingly difficult, and lead to increased risk for hemolytic transfusion reaction. This phenomenon is referred to as alloimmunization Some patients who are alloimmunized have an increased risk of avascular necrosis, end-organ damage, and death. Hemolytic transfusion reaction may mimic the signs and symptoms of sickle cell crisis. A distinguishing feature of a hemolytic reaction versus sickle cell crisis is that the patient becomes more anemic after the transfusion than before. Close observation after hemolytic transfusion reaction is needed and further transfusion should be avoided until after the hemolytic process subsides. Patients are supported with corticosteroids, such as prednisone, intravenous immunoglobulins (IVIG) and erythropoietin alfa.

Thrombocytopenia

Reduced production of platelets in the bone marrow, increased destruction of platelets, or increased consumption of platelets (e.g., the use of platelets for clot formation) Bleeding and petechiae rarely occur with platelet counts greater than 50,000/mm3, but excessive bleeding can occur after surgery or other trauma. When platelet counts fall to 20,000/mm3 or less, petechiae may occur. Additionally, nasal and gingival bleeding, excessive menstrual bleeding, and excessive bleeding from surgery or dental extractions can occur. Spontaneous and potentially fatal bleeding in the CNS or GI tract can occur when platelet counts fall to less than 5000/mm3. If platelet function is abnormal as a result of disease (e.g., MDS) or medications (e.g., aspirin) the risk of bleeding may be much greater even when the platelet count is mildly reduced.

Sickle Cell Disease

SCD is an autosomal recessive disorder caused by inheritance of the sickle hemoglobin (HbS) gene. It is associated with severe hemolytic anemia. The HbS gene results in production of a defective hemoglobin molecule that causes the erythrocyte to change shape when exposed to low oxygen tension. In some circumstances, even the oxygen level in venous blood can cause this change. The erythrocyte usually has a round, biconcave, pliable shape which in SCD can easily become rigid and sickle shaped. The long, rigid cells can subsequently adhere to the walls of small blood vessels where they accumulate, causing decreased blood flow to the tissues and organs in that region. When blood flow is severely reduced, ischemia or infarction of the tissue can cause severe pain, swelling, and fever referred to as a sickle cell crisis. Because the sickling process takes time, if the patient is exposed to adequate amounts of oxygen, the process can be reversed before the cell membranes become too rigid, allowing the erythrocytes to return to their normal shape. Sickle cell crises are intermittent and can be triggered by cold because of vasoconstriction that slows blood flow. African descent

Assessment and Diagnostic

Serum levels of both folic acid and vitamin B12 are analyzed. Small amounts of folate can increase the serum folate level; therefore, measurement of the amount of folate within the red blood cells is a more sensitive test to determine true folate deficiency although it is not commonly performed. The traditional method of determining the cause of vitamin B12 deficiency was the Schilling test, but in recent years this has been replaced by other testing methods. A vitamin B12 assay is usually the initial test performed but the reliability of the results is sometimes questionable, when vitamin B12 levels are not unequivocally low. Elevated methylmalonic acid and homocysteine levels are more sensitive for the diagnosis of vitamin B12 deficiency An intrinsic factor antibody test is often more useful in determining the presence of pernicious anemia. A positive test indicates that antibodies are present that interfere with the binding of the intrinsic factor-vitamin B12 complex to receptors in the ileum, preventing absorption. While not specific for only pernicious anemia, it is useful in helping arrive at the diagnosis.

Clinical Manifestations

Several factors influence the development of symptoms associated with anemia. The severity of the anemia, the rapidity with which the anemia developed, the duration (chronicity) of the anemia, metabolic requirements of the patient, the presence of other conditions, such as cardiac or pulmonary disease, and complications or related features of the condition that produced the anemia are some of these factors. In general, the more quickly the anemia develops, the more severe the symptoms (Bunn, 2017a). An otherwise healthy patient may be able to tolerate as much as a 50% reduction in hemoglobin over several months without pronounced symptoms or significant incapacity; however, a rapid loss of 30% of the hemoglobin over minutes may lead to profound vascular collapse in the same person. A patient who gradually becomes anemic, such as a woman experiencing heavy menses over several months with hemoglobin levels between 9 and 11 g/dL, may have few or no symptoms except for slight tachycardia on exertion or fatigue. People who are more active or who have significant life demands are more likely to have symptoms than those who are more sedentary. Patients with hypothyroidism with decreased oxygen demands may be asymptomatic without tachycardia or dyspnea with a hemoglobin of 10 g/dL. Similarly, those with co-existing cardiac, vascular, or pulmonary disease may develop pronounced symptoms of anemia (e.g., dyspnea, chest pain, muscle pain, or cramping) with a higher hemoglobin level than those without concurrent health problems. Some anemias, such as SCD, or autoimmune diseases are often complicated by other abnormalities that do not result from the anemia but are inherent with the associated disease. Pain and other symptoms may overshadow those caused by the anemia. Complications of severe anemia include heart failure, paresthesias, and delirium. Patients with underlying heart disease are more likely to have angina and symptoms associated with heart failure than those without heart disease. Complications of specific types of anemia are included in the description of each type.

Clinical Manifestations

Severity of neutropenia: Risk for infection is proportional to severity of neutropenia. •Duration of neutropenia: Increased duration of neutropenia leads to increased risk for infection. •Nutritional status: Decreased protein stores lead to decreased immune response and anergy. •Deconditioning: Decreased mobility leads to decreased respiratory effort, leading to increased pooling of secretions. •Lymphocytopenia; disorders of lymphoid system (chronic lymphocytic leukemia, lymphoma, and myeloma): Decreased cell-mediated and humoral immunity. •Invasive procedures: Breaks in skin integrity create increased opportunities for organisms to enter blood system. •Hypogammaglobinemia: Decreased antibody formation. •Poor hygiene: Increased organisms on skin and mucous membranes, including perineum. •Poor dentition; mucositis: Decreased endothelial integrity leads to increased opportunity for organisms to enter blood system. •Antibiotic therapy: Increased risk for superinfection, often fungal. •Certain medications: See text. •Severity of thrombocytopenia: Risk increases when platelet count decreases; usually not a significant risk until platelet count drops below 10,000/mm3, or less than 50,000/mm3 with trauma or when an invasion procedure is performed. •Duration of thrombocytopenia: Risk increases when duration increases (e.g., risk is less when duration is transient as after chemotherapy than when duration is prolonged as with decreased cell production by bone marrow). •Sepsis: Mechanism unclear; appears to cause increased platelet consumption. •Increased intracranial pressure: Increased blood pressure leads to rupture of blood vessels. •Liver dysfunction: Decreased synthesis of multiple clotting factors. •Renal dysfunction: Decreased platelet function. •Dysproteinemia: Protein coats surface of platelet, leading to decreased platelet function; protein causes increased blood viscosity, which leads to stretching of capillaries an increased risk for rupture and bleeding. •Alcohol abuse: Suppressive effect on bone marrow results in deceased platelet production and impaired platelet function; impaired liver function results in decreased production of clotting factors.

Supportive therapy

Supportive care is essential for patients with SCD. Pain management is a significant problem. Acute pain is most often associated with vaso-occlusive crisis and is the frequent reason for hospitalization and emergency department visits in people with SCD. Pain may also be neuropathic in nature stemming from damage or inflammation of nerves as seen with avascular necrosis and leg ulcers. Chronic non-neuropathic pain may result from CNS dysfunction, including CNS sensitivity to peripheral afferent pain signals, or differences in psychosocial aspects of pain perception. Pain severity may interfere with ability to work, even when patients do seek assistance with pain management from health care providers. Aspirin may be useful in patients with mild pain; it decreases inflammation and risk for potential thrombosis (because it inhibits platelet adhesion). NSAIDs are useful for moderate pain or in combination with opioid analgesics. While there is no risk of developing tolerance to NSAIDs there is a "ceiling effect" by which increased doses do not improve analgesia but increase the risk for adverse effects. NSAID use must be monitored carefully because of the risk for renal dysfunction and GI bleeding. Severe acute pain is most often treated with parenteral opioids Neuropathic pain can be effectively managed with gabapentinoids, tricyclic antidepressants, and serotonin and norepinephrine reuptake inhibitors. With chronic pain management, the principal goal is to maximize functioning; pain may not be completely eliminated without sacrificing function. This concept may be difficult for patients to understand and ongoing education and support is often needed. Nonpharmacologic pain management strategies are important in this setting. Such strategies include physical therapy including heat, massage and exercise; occupational therapy; cognitive and behavioral therapies, including distraction and relaxation techniques; and support groups

Clinical Manifestation

Symptoms of folic acid and vitamin B12 deficiencies are similar, and the two anemias may coexist. However, the neurologic manifestations of vitamin B12 deficiency do not occur with folic acid deficiency, and they persist if vitamin B12 is not replaced. Therefore, careful distinction between the two anemias must be made. After the body's stores of vitamin B12 are depleted, the patient may begin to show signs and symptoms of the anemia. However, because the onset and progression of the anemia are so gradual, the body can compensate well until the anemia is severe, so the typical manifestations of anemia (weakness, listlessness, fatigue) may not be apparent initially. The hematologic effects of vitamin B12 deficiency are accompanied by effects on other organ systems, particularly the GI tract and nervous system. Patients with pernicious anemia develop a smooth, sore, red tongue and mild diarrhea. They are extremely pale, particularly in the mucous membranes. They may become confused; more often, they have paresthesias in the extremities (particularly numbness and tingling in the feet and lower legs). They may have difficulty maintaining their balance because of damage to the spinal cord, and they also lose position sense (proprioception). These symptoms are progressive, although the course of illness may be marked by spontaneous partial remissions and exacerbations. Without treatment, heart failure associated with severe anemia may result, often leading to death several years after onset of symptoms

Patient education

Take iron on an empty stomach (1 hour before or 2 hours after a meal), preferably with orange juice or other source of vitamin C. Iron absorption is reduced by food, especially dairy products. •Reduce gastrointestinal distress by using the following schedule when more than one tablet per day is prescribed: Take one tablet per day for the first few days, then increase to two tablets per day, then three tablets per day in divided doses. This allows gradual adjustment to the iron. If unable to tolerate oral supplements due to gastrointestinal distress despite using this intervention, a reduced amount of iron may be used rather than stopping it completely. Reduced doses will require that the treatment duration is extended to adequately replenish iron stores. •Increase intake of foods rich in vitamin C to enhance iron absorption (citrus fruits and juices, strawberries, tomatoes, broccoli). •Note that stool will be dark in color and often appear black. •Eat foods high in fiber to reduce problems with constipation. A stool softener may be needed. •Be aware that liquid iron preparations may stain the teeth. They may be taken through a straw or by placing the spoon at the back of the mouth. Rinse the mouth thoroughly after each dose.

Assessment and Diagnostic findings

The definitive method of establishing the diagnosis of iron deficiency anemia is bone marrow aspiration The aspirate is stained to detect iron, which is at a low level or even absent. However, few patients with suspected iron deficiency anemia undergo bone marrow aspiration. In many patients, the diagnosis can be established with other tests, particularly in patients with a history of conditions that predispose them to this type of anemia. A strong correlation exists between laboratory values that measure iron stores and hemoglobin levels. After iron stores are depleted (as reflected by low serum ferritin levels), the hemoglobin level falls. The diminished iron stores cause small erythrocytes to be produced by the marrow. Therefore, as the anemia progresses, the MCV, which measures the size of the erythrocytes, also decreases. Hematocrit and RBC levels are also low in relation to the hemoglobin level. Other laboratory tests that measure iron stores are useful but not as precise as ferritin levels. Typically, patients with iron deficiency anemia have a low serum iron level and an elevated TIBC, which measures the transport protein supplying the marrow with iron as needed (also referred to as transferrin) Infection and inflammatory conditions, can also cause a low serum iron level and TIBC, as well as an elevated ferritin level. If these are suspected, measuring the soluble transferring receptor can aid in differentiating the cause of anemia. This test result will be increased in the setting of iron deficiency, but not in chronic inflammation

Treatment

The mainstay of short-term therapy is the use of immunosuppressive agents. These agents block the binding receptors on macrophages to reduce platelet destruction. The American Society of Hematology recommends dexamethasone or prednisone in adults with newly diagnosed ITP as the types of corticosteroids that might be selected for initial therapy. Continuous long-term use of corticosteroids is not recommended because of the risk for side effects Platelet counts typically begin to rise within a few days after initiating treatment with corticosteroids. The platelet count tends to decrease once the corticosteroid dose is tapered but may remain sufficiently adequate to prevent bleeding. IVIG is commonly used to treat ITP. It renders its effect by binding to the receptors on macrophages. However, the need for high doses of IVIG and its high cost are disadvantages. The effects of treatment are transient in most cases. Another approach to treatment of chronic ITP is the use of anti-D immunoglobulin in patients who are Rh (D) positive. The exact mechanism of action is unknown, but it is theorized that the anti-D binds to the patient's erythrocytes, which are in turn destroyed by the body's macrophages. The receptors in the RES may become flooded with sensitized erythrocytes, which then reduce the number of antibody-coated platelets. This then results in a transient reduction of hematocrit and an increased number of platelets in some patients with ITP Second line treatment- splenectomy to increase platelet count Risk for infection- receive vaccines- pnuemo, flu, and meningococcal- 2 weeks prior Other management strategies include use of monoclonal antibodies, such as rituximab. Patients may have long lasting effects with increased platelet counts for up to 1 year after treatment. Unfortunately, when the response dwindles, platelets may fall to unsafe levels, making additional treatment necessary. Two thrombopoietin receptor agonists are available for treatment of refractory ITP. These include romiplostim and eltromopag. Romiplostim is given as a weekly subcutaneous injection and eltromopag is given orally. The response varies widely, and treatment must be continued indefinitely

Medical Management

The primary goal of treatment is to achieve a platelet count high enough to maintain hemostasis. Because the risk for bleeding does not typically increase until the platelet count is less than 30,000/mm3, a patient whose platelet count exceeds 30,000/mm3 to 50,000/mm3 may be carefully monitored without immediate intervention. However, if the platelet count is less than 30,000/mm3 or if bleeding occurs, the goal is to improve the patient's platelet count and not to cure the disease. The decision to treat is made based upon the severity of bleeding (if any) and not solely on the platelet count. Potential treatment side effects, the patient's lifestyle, activity level, concurrent use of medications, and treatment preferences are also considered. A person with a sedentary lifestyle can tolerate a low platelet count more safely than a more active person; however, increasing age is also associated with increased risk for bleeding and mortality Treatment for ITP usually involves several approaches. If the patient is taking a medication known to be associated with ITP (e.g., quinine, sulfa-containing drugs), then that medication should be discontinued. Transfusions are often ineffective because antiplatelet antibodies bind with transfused platelets, causing them to be destroyed. Platelet counts may drop even further after platelet transfusion. Thus, despite extremely low platelet counts, platelet transfusions may result in catastrophic bleeding in patients with wet purpura. Aminocaproic acid, a fibrinolytic enzyme inhibitor that slows the dissolution of blood clots, may be useful for patients with significant mucosal bleeding that is resistant to other treatments.