PC604 Module 3B test 1

Idiopathic Thrombocytopenia Purpura

(isolated thrombocytopenia with normal bone marrow) (primarily a disease of increased peripheral platelet destruction with most patients having antibodies to specific platelet membrane glycoproteins) (ITP is a decrease in the number of circulating platelets in the absence of toxic exposure or disease associated with a low platelet count) Immune thrombocytopenia purpura (ITP) may be either acute or chronic. ITP is an autoimmune disorder in which IgG autoantibody (IgM and IgA have also been involved) is formed and binds to and destroys the platelets. The acute form is most common in children and young adults and is usually preceded by a viral infection. Chronic ITP is more common in females between 20 and 40 years. The individual most commonly presents with mucosal or skin bleeding that is often manifested as menorrhagia, purpura, petechiae, and bleeding gums. The antibody-coated platelets are removed from the circulation by mononuclear phagocytes in the spleen

Siderblastic anemia high risk groups

Acquired from: drugs, ingestion of ethanol, lead, chloramphenocol, antituberculosis agents. Myelodysplastic syndrome (MDS); Nutritional deficiencies (Copper, B6); hypothermia; idiopathic. Congential: X-linked; autosomal recessive (rare); Mitochondrial Disorders; Pearson Syndrome; DIDMOAD Syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness)--responsive to B1 thiamine.

Eosinophilia (an absolute increase in the total number of circulating eospinophils): Causes

Allergic disorders associated with asthma, hay fever, parasitic invasion, and drug reactions are frequently the cause of eosinophilia. Chemotactic factor of anaphylaxis (CTF-A) and histamine release from mast cells attract eosinophils to the area. Allergy, Infection (parasites [trichinosis, hookworm] chronic [fungal, leprosy, Tb], Malignancy (CML, lung, stomach, ovary, Hodgkin disease) Dermatosis (pemphigus, exfoliative dermatosis [drug-induced]) Drugs (Digitalis, heparin, streptomycin, tryptophan [eosinophilia-myalgia syndrome], penicillins, propranolol). Eosinophilia results most commonly from parasitic invasion and ingestion or inhalation of toxic foreign particles.

Pernicious Anemia : insufficient influence of vitamin B12 on developing cells because of deficient intrinsic factor (IF); antibodies develop against parietal cells; gastrectomy or ilectomy threrapies; chronic gastritis.

Also pernicious anemia is a Congenital or acquired deficiency of Intrinsic Factor (IF); genetic disorder of DNA synthesis

Differentiate Post-hemorrhagic Anemia and Hemolytic anemia

Both are Normocytic-Normochromic Anemia (normal MCH and MCHC), characterized by insufficient numbers of normal erythrocytes.

Neutrophilia, which is increase in neutrophil count , most often with increased total WBCs): causes

CAUSE: Inflammation or tissue necrosis (e.g., surgery, burns, MI, pneumonitis; rheumatic fever, rheumatoid arthritis) ACUTE INFECTIONS (bacterial: gram-positive staphylococci, streptococci, pneumococci; meningococci, gonoccocci; gram-negative; bacilli: E.coli, Pseudomonas aeruginosa, Actinomycces), certain fungi (coccidioides), spirochetes, viruses (rabies, polio, herpes zoster, smallpox, varicella), rickettsia, parasites. Physiologic (Exercise, extreme heat or cold, third-trimester pregnancy, emotional distress) Hematologic (Acute hemorrhage, hemolysis, myeloproliferative disorder, chronic granulocytic leukemia) Drugs or chemicals (Epinephrine, steroids, heparin, histamine, endotoxin) Metabolic (Diabetes--acidosis, eclampsia, gout, thyroid storm) Neopplasm (Liver, GI tract, bone marrow) Also with furuncles, abscesses, tonsillitis, appendicitis, otitis media, osteomyelitis, cholecystitis, salpingitis, meingitis, diphtheria, plague, peritionitis. Noninfectious inflammation: burns, postop state, acute MI, acute attacks of gout, acute glomerulonephritis, rheumatic fever, parathyroid fever, collagen vascular diseases, hypersensitivity reactions. Do not usually see neutrophilia/leukocytosis with typhoid fever, parathyroid fever, mumps, measles, TB.

The effect of liver disease on coagulation, including vitamin K deficiency

Coagulation is impaired when there is a deficiency of vitamin K because of insufficient production of prothrombin synthesis of clotting factors II, VII, IX, and X, often associated with liver diseases. A deficiency of vitamin K, which is necessary for normal synthesis of the clotting factors by the liver, is an acquired coagulation defect. The most common cause of vitamin K deficiency is parenteral nutrition in combination with broad-spectrum antibiotics that destroy normal gut flora. Rarely is a deficiency caused by lack of dietary intake; however, bulimia can suppress vitamin K-dependent activity. Individuals with liver disease have a broad range of hemostasis dearrangements that may be characterized by defects in the clotting or fibrinolytic systems and by platelet function. The usual sequence of events is an initial reduction in clotting factors, which parallels the degree of parenchymal cell damage or destruction. Factor VII is the first to decline because of its rapid turnover, followed by declines in prothrombin and factor X. Factor IX levels are less affected and do not decline until liver destruction is well advanced. Disorders of coagulation are usually caused by defects or deficiencies of one or more clotting factors.

Iron deficiency anemia

Diminished absorbable dietary iron-- insufficient intake; hemorrhage most common loss of excess loss of body iron, but may occur with hemoglobinuria from intravascular hemolysis. Iron uptake is in the proximal small bowel. Bleeding causes iron depletion.

Pernicious anemia clinical manifestations

Fatigue, weakness, dyspnea, pallor; digestive symptoms from lack of HCl and enzymes; glossitis; peripheral neuropathy; tingling numbness; loss of vibratory sense

Infectious mononucleosis: clinical manifestations

Flulike symptoms, such as headache, malaise, fatigue, arthralgia, fever, chills, may appear in 3 to 5 days and vary in severity for the next 7 to 20 days. The individual will develop the classic triad of symptoms: fever, pharyngitis, and lymphadenopathy of the cervical lymph nodes. Splenomegaly is clincially evident 50% of the time and demonstrated radiographically 100% of the time. IM is usually self-limiting, and recovery occurs in a few weeks. Diagnosis is based on at least 50% lymphocytes and at least 10% atypical lymphocytes in the blood in the presence of clasic symptoms confirmed by a positive serologic test. Heterophile antibodies are a heterogenous group of IgM antibodies that are agglutins against the nonhuman (sheep or horse) and are detected by the monospot test.

Describe the RBC deficit seen in glucose-6-phosphate dehydrogenase (G6PD) deficiency

G6PD is an X-linked recessive disorder tha is fully expressed in homozygous males. G6PD is primarily a problem in blacks, Sephardic Jews, Greeks, Iranians, Chinese, Filipinos, and Indonesians. G6PD is caused by a defect of an enzyme that enables eythrocytes to maintain normal function in the presence of certain substances, such as sulfa drugs, salicylates, quinolones, antimalarials, and fava beans. Exposure to these substances causes hemolysis, often very severe, that resolves when the offending substance is removed. G6PD deficiency is an inherited enzyme deficiency in erythrocytes that results in a disruption of a common pathway of glycolysis, shortening the erythrocyte life span. The five classes of G6PD deficiency include low, normal, or increased levels of the enzyme. The disease is highly polymorphic with more than 300 variants. Acute hemolysis from G6PD deficiency is linked to the development of Heinz bodies, which are composed of denatured hemoglobin. Males at risk for G6PD should be tested before they are exposed to certain oxidant drugs. Most individuals with G6PD defiiency are asymptomatic. Symptomatic patients are almost exclusively males, due to the X-linked patttern of inheritance, but female carriers can be clincially affected due to unfavorable lyonization, where random inactivation of an X-linked chromosome in certain cells created a population of G6PD deficient RBCs coexisting with normal RBCs. Abnormal RBC breakdown in G6PD can manifest as prolonged neonatal jaundice, possibly leading to kernicterus.

Hemophilia in children

Hemophilia, which is spontaneous bleeding, is rare in the first year of life; although recurrent bleeding, both spontaneous and following minor trauma, is a lifelong problem. Hemophilia A, the most common of the hemophilias, is caused by factor VIII deficiency. Hemophilia B is caused by factor IX deficiency. Both hemophilia A and B are X-linked and limited to males, being transmitted by through the female to the second generation. Hemophilia C occurs as an autosomal recessive disease and occurs equally in males and females. Bleeding is less severe than in hemophilia A and B. Hematoma formation is a more common problem during the first year of life and may be due to injections, firm holding, or the many accidents that occur in the development of movement in children. These accidents may also precipitate bleeding in the joints. Spontaneous hematuria and epistaxis are bothersome but rarely serious. Life-threatening intracranial, cervical, and abdominal bleeding may result from childhood injury. Hemophilia A is an X-linked, recessive disorder caused by deficiency of functional plasma clotting factor VIII (FVIII), which may be inherited or arise from spontaneous mutation. The development of inhibitory antibodies to FVIII can result in acquired hemophilia A or can complicate the treatment of genetic cases. Laboratory studies for suspected hemophilia include the following: • Complete blood cell count • Coagulation studies • FVIII assay Expected laboratory values are as follows: • Hemoglobin/hematocrit: Normal or low • Platelet count: Normal • Bleeding time and prothrombin time: Normal • Activated partial thromboplastin time (aPTT): Significantly prolonged in severe hemophilia, but may be normal in mild or even moderate hemophilia Normal values for FVIII assays are 50-150%. Values in hemophilia are as follows: • Mild: >5% • Moderate: 1-5% • Severe: < 1%

Explain the Virchow triad

Hypercoagulability results from a deficiency of anticoagulation proteins. Secondary causes are conditions that promote venous stasis. The triad of Virchow refers to three factors that can cause spontaneous thrombus formation: (1) loss of vessel wall integrity, (2) blood flow abnormalities, and (3) blood constituent alteration. Elements essential to thrombosis: blood stasis (secondary to immobility, congestive heart failure, vein compressions), alteration to a vein wall (secondary to previous thrombosis, vein inflammation/infection, direct vein wall trauma, varicose veins) and blood hypercoagulability (e.g. antiphospholipid syndrome, hyperhomocysteinemia, lower-limb surgery/trauma, childbirth, polycythemia, neoplastic disease, oral contraceptives); thrombosis requires a minimum of two of the three elements

Iron deficiency anemia in children

IDA is the most common blood disorder in infancy and childhood; the highest incidence occurs between 6 months and 2 years of age. Iron deficiency anemia develops when body stores of iron drop too low to support normal red blood cell (RBC) production. Inadequate dietary iron, iron absorption, bleeding, or loss of body iron in the urine may be the cause. Patients with iron deficiency anemia may report the following: •Fatigue and diminished capability to perform hard labor •Leg cramps on climbing stairs •Craving ice (in some cases, cold celery or other cold vegetables) to suck or chew •Poor scholastic performance •Cold intolerance •Reduced resistance to infection •Altered behavior (eg, attention deficit disorder) •Dysphagia with solid foods (from esophageal webbing) •Worsened symptoms of comorbid cardiac or pulmonary disease •Impaired growth in infants •Pallor of the mucous membranes (a nonspecific finding) •Spoon-shaped nails (koilonychia) •A glossy tongue, with atrophy of the lingual papillae •Fissures at the corners of the mouth (angular stomatitis) •Splenomegaly (in severe, persistent, untreated cases) •Pseudotumor cerebri (a rare finding in severe cases Hemoglobin less than 5 will see: pallor, tachycardia, systolic murmur. Hgb 6-10 (mild to moderate): will see some cellular changes. Long standing chronic anemia: widening of the skull sutures

Idiopathic Thrombocytopenia Purpura in children

ITP is the most common thrombocytopenic purpura of childhood. Antiplatelet antibodies attach to platelets that are then sequestered in the spleen, where they are destroyed by mononuclear phagocytes. Destruction far exceeds production, and thrombocytopenia occurs. Classic symptoms of bruising and petechiae are usually preceded 1 to 4 weeks earlier by a viral illness that may cause sensitization of the platelets and trigger an antibody response. High levels of IgG have been found on the platelets of affected children. The acquired antibody-mediated hemorrhagic diseases include ITP, autoimmune neonatal thrombocytopenia, and autoimmune vascular purpura. ITP, the most common of the childhood thrombocytopenic purpuras, is a disorder of platelet consumption in which antiplatelet antibodies bind to the plasma membranes of platelets. This results in platelet sequestration and destruction by mononuclear phagocytes at a rate that exceeds the ability of the bone marrow to produce them.

The NP is talking with the MD about a patient with abdominal pain. THe NP tells the MD that there is a shift to the left in the white blood cell count. What does this mean?

Increased immature neutrophils (bands)

Bleeding is the most common cause of

Iron deficiency, either from parasitic infection (hookworm) or other causes of blood loss.

Sally is a 22 year old with heavy menstrual bleeding each month. She is complaining of fatigue. The CBC reveals that she probably has iron-deficiency anemia. You expect her mean corpuscular volume (MCV) to be ____

Low

Which lab tests woud you expect to find from a person with IDA

Low serum iron Increased Total Iron Binding Capacity Low serum Ferritin Increased Reticulocyte Count

If the average RBC is large, then the anemia is

MACROCYTIC. (MCV is increased)

If the average RBC size is small, the anemia is

MICROCYTIC. (MCV is decreased)

Folate deficiency anemia

Macrocytic-Normochromic: large, abnormally shaped erythrocytes but normal hemoglobin concentrations. Increased MCV, normal MCHC. Primary cause: dietary folate deficiency.

Pernicious anemia (B12 deficiency)

Macrocytic-normochromic anemia: large, abnormally shaped erythrocytes but normal hemoglobin concentrations. INCREASED MCV.

The indices include

Mean corpuscular Volume (MCV), the Mean Coprpuscular Hemoglobin (MCH), and the Mean Corpuscular Hemoglobin Concentration (MCHC).

Dietary sources of cobalmin

Meat and milk are the main sources. Because body stores of cobalamin usually exceed 1000 mcg and the daily requirement is about 1 mcg, strict adherance to a vegetarian diet for more than 5 yrars usually is required to produce findings of cobalamin deficiency

Iron Deficiency Anemia

Microcytic-Hypochromic (Lower MCV, Lower MCHC). Excessive bleeing that depletes iron; poor diet; possible H. Pylori infection. High risk groups: pregnant women, adolescents, children (6 mo to 2 years), elderly, individuals with chronic blood loss. Iron is essential for multiple metabolic processes, including oxygen transport, DNA synthesis, and electron transport.

Anemia of Iron deficiency (IDA)

Microcytic-Hypochromic (low MCV, low MCHC). Etiology: excessive bleeding that depletes iron; poor diet; possible H. pylori infection. Symptoms: fatigue, wakness, pallor, dyspnea

Differentiate anemia of chronic disease and iron deficiency anemia

Microcytic-Hypochromic anemias are characterized by abnormally small RBCs with insufficient hemoglobin content. This disorder results from disorders of (1) iron metabolism (IDA), (2) porphyrin and heme synthesis (Sideroblastic anemia), or globin synthesis (thalassemia). IDA is the most common type of anemia worldwide. It usually develops slowly, with gradual insidious onset of symptoms. Fatigue, weakness, dyspnea, alteration of various epithelial tissues, and vague neuromuscular complaints result.

Sideroblastic anemia

Microcytic-Hypochromic. Lower MCV, Lower MCHC. Dysfunctional iron uptake by erythroblasts; decreased heme synthesis; enzyme genetic.

Hemolytic anemia: etiology

Normocytic-Normochromic (normal MCH and MCHC) anemias are characterized by insufficient numbers of normal erythrocytes (other normal MCH and MCHC--anemia of chronic disease and Post-hemorrhage)). Hemolytic anemia is a result of excessive destruction of erythrocytes and may be acquired or hereditary. Of the acquired forms, autoimmune reaction (immunohemolytic) and drug-induced hemolysis are the most common. Premature destruction (lysis) of mature erythrocytes in the circulation. Increased fragility of erythrocytes.

Anemia of chronic disease (ACD)

Normocytic-Normochromic (normal MCV and MCHC). Etiology: bacterial toxins; cytokines from activated macrophages and lymphocytes suppress progenitor cells; reduced iron via lactoferrin. Abnormally increased demand for new erythrocytes. Primary cause: chronic infection or inflammation; malignancy. Symptoms: mild because of disability caused by chronic condition.

Polycythemia Vera

Primary polycythemia vera is known as polycythemia vera. Most primary absolute polycythemias are acquired and occur at various ages; however, there are some that are hereditary, present at birth, and identified as familial and congenital polycythemias

Basophilia

Quite rare and is generally seen as a response to inflammation and hypersensitivity reactions of the immediate type. An increase in basophils is also seen in chronic myeloid leukemia and myeloid metaplasia. Basophilia is seen in hypersensitivity reactions because of high content of histamine and subsequent release. Cause: inflammation (infection--measles, chickenpox; hypersensitivity reaction [immediate]) Hematologic (myeloproliferative disorders [CML, polycythemia vera, Hodgkin lyphoma, hemolytic anemia]) Endocrine (Myxedemia, antithyroid therapy)

Anemia is present when either Hgb or the Hct is low. If Hx & PE suspect anemia, then the CBC should be drawn. Most CBCs include:

Red blood cell count, white blood cell count and differential, indicies, and the RBC distribution width. This test will guide what other tests should be done. Examples: reticulocyte count, peripheral blood smear, iron studies, Hgb electrophoresis, serum folate, and serum B12

Sickle cell anemia in children

Sickle Cell Disease (SCD) is an inherited, autosomal recessive disorder most common in the U.S. among Blacks. The disease is characterized by the presence of hemoglobin S (HbS) within the erythrocytes. This hemoglobin becomes elongated and sickle shaped whenever it is deoxygenated or dehydrated. Polymerization stiffens the sickled erythrocyte and changes the cell to an inflexible obstacle that starves tissues. Acute complications or crises occur in sickle cell disease and may be provoked by infection, exposure to cold, low PO2, acidosis, or localized hypoxemia. Infections are frequent in childhood and may generate various degrees of other triggers. Vaso-occlusive crises result from a "log jam" effect produced by stiff, sickled erythrocytes in the microcirculation. Symptoms include symmetric swelling of the hands and feet, which may be the first clinical manifestation in infancy. In older children, swollen painful joints, priapism, severe abdominal pain from infarctions of abdominal organs, and strokes may occur. Other complications include sickle cell retinopathy, renal necrosis, and necrosis of the femoral head. Sequestration-large amounts of blood in liver/spleen- these pools can contain as much as one fifth of the blood volume, and thus precipitate shock. Up to a 50% mortality rate has been reported with these crises. Aplastic crisis, a transient cessation in RBC production resulting in acute anemia, occurs as a result of viral infection, almost always with parvovirus B19, which is the virus responsible for the common childhood infection known as Fifth Disease. The virus causes temporary shutdown of RBC production in the bone marrow, or reticulocytosis. However, hemolysis, a component of SCD, continues. The outcome is a severe drop in hemoglobin with an extremely low reticulocyte count. • Acute and chronic pain in any body part: The most common clinical manifestation of SCD is vaso-occlusive crisis; pain crises are the most distinguishing clinical feature of SCD • Bone pain: The long bones of the extremities are often involved, often due to bone marrow infarction • Anemia: Universally present, chronic, and hemolytic in nature • Aplastic crisis: Serious complication due to infection with B19V • Splenic sequestration: Characterized by the onset of life-threatening anemia with rapid enlargement of the spleen and high reticulocyte count Sickle cell disease (SCD) usually manifests early in childhood. For the first 6 months of life, infants are protected largely by elevated levels of Hb F; soon thereafter, the condition becomes evident. The most common clinical manifestation of SCD is vaso-occlusive crisis. A vaso-occlusive crisis occurs when the microcirculation is obstructed by sickled RBCs, causing ischemic injury to the organ supplied and resultant pain. Pain crises constitute the most distinguishing clinical feature of sickle cell disease and are the leading cause of emergency department visits and hospitalizations for affected patients. Approximately half the individuals with homozygous Hb S disease experience vaso-occlusive crisis. The frequency of crisis is extremely variable. Some have as many as 6 or more episodes annually, whereas others may have episodes only at great intervals or none at all. Each individual typically has a consistent pattern for crisis frequency. Pain crises begin suddenly. The crisis may last several hours to several days and terminate as abruptly as it began. The pain can affect any body part. It often involves the abdomen, bones, joints, and soft tissue, and it may present as dactylitis (bilateral painful and swollen hands and/or feet in children), acute joint necrosis or avascular necrosis, or acute abdomen. With repeated episodes in the spleen, infarctions and autosplenectomy predisposing to life-threatening infection are usual. The liver also may infarct and progress to failure with time. Papillary necrosis is a common renal manifestation of vaso-occlusion, leading to isosthenuria (ie, inability to concentrate urine). Severe deep pain is present in the extremities, involving long bones. Abdominal pain can be severe, resembling acute abdomen; it may result from referred pain from other sites or intra-abdominal solid organ or soft tissue infarction. Reactive ileus leads to intestinal distention and pain. The face also may be involved. Pain may be accompanied by fever, malaise, and leukocytosis. Bone pain is often due to bone marrow infarction. Certain patterns are predictable, since pain tends to involve bones with the most bone marrow activity and because marrow activity changes with age. During the first 18 months of life, the metatarsals and metacarpals can be involved, presenting as dactylitis or hand-foot syndrome. As the child grows older, pain often involves the long bones of the extremities, sites that retain marrow activity during childhood. Proximity to the joints and occasional sympathetic effusions lead to the belief that the pain involves the joints. As marrow activity recedes further during adolescence, pain involves the vertebral bodies, especially in the lumbar region. Although the above patterns describe commonly encountered presentations, any area with blood supply and sensory nerves can be affected. Triggers of vaso-occlusive crisis: • Often, no precipitating cause can be identified. However, because deoxygenated hemoglobin S (HbS) becomes semisolid, the most likely physiologic trigger of vaso-occlusive crises is hypoxemia. This may be due to acute chest syndrome or accompany respiratory complications • Dehydration can precipitate pain, since acidosis results in a shift of the oxygen dissociation curve (Bohr effect), causing hemoglobin to desaturate more readily. Hemoconcentration also is a common mechanism. • Another common trigger is changes in body temperature—whether an increase due to fever or a decrease due to environmental temperature change. Lowered body temperature likely leads to crises as the result of peripheral vasoconstriction. Patients should wear proper clothing and avoid exposure to ensure normal core temperature. Chronic pain in SCD • Many individuals with SCD experience chronic low-level pain, mainly in bones and joints. Intermittent vaso-occlusive crises may be superimposed, or chronic low-level pain may be the only expression of the disease. Anemia • Anemia is universally present. It is chronic and hemolytic in nature and usually very well tolerated. While patients with an Hb level of 6-7 g/dL who are able to participate in the activities of daily life in a normal fashion are not uncommon, their tolerance for exercise and exertion tends to be very limited. • Anemia may be complicated with megaloblastic changes secondary to folate deficiency. These result from increased RBC turnover and folate utilization. Periodic bouts of hyperhemolysis may occur. • Children exhibit few manifestations of anemia because they readily adjust by increasing heart rate and stroke volume; however, they have decreased stamina, which may be noted on the playground or when participating in physical education class.

Serum iron may be elevated in

Sideroblasic anemia

Hemolytic anemia: symptoms

Splenomegaly; jaundice; childhood skeletal abnormalities.

Post-hemorrhagic anemia: etiology and symptoms

Sudden and acute blood loss; depletion of body iron. Acute or chronic hemorrhage that stimulates increased eythropoiesis, which eventually depletes body iron. Severity depending on the amount of hemorrhage. Restoration of blood volume by plasma expanders or transfusions may diminsh subjective symptoms of anemia. Hemoglobin restoration may take 6 to 8 weeks. SX: shock; acidosis

The steps in lab testing needed to determne the cause of anemia. Anemia is defined as low hemoglobin or hematocrit. What will the reticulocyte production index tell the provider about a patient's anemia?

The RPI is to assess whether the bone marrow is producing an appropriate response to an anemic state. Reticulocyte production should increase in response to any loss of red blood cells. It should increase within 2 to 3 days of a major acute hemorrhage, and reach its peak in 6 to 10 days. If reticulocyte production is not raised in response to anemia, then the anemia may be due to an acute cause with insufficient time to compensate, or there is a defect with RBC production in the bone marrow. Marrow defects include nutritional deficiencies (iron, folate, or B12), or insufficient erythropoietin, the stimulus for RBC production. Reticulocytopenia, or "aplastic crisis," is the term for an abnormal decrease in reticulocytes in the body.

Thalassemia in children

The alpha- and beta-thalassemias are inherited autosomal recessive disorders that cause an impaired rate of synthesis or decrease of one of the two chains—alpha or beta—of adult hemoglobin. Beta-thalassemia is more common than alpha-thalassemia. Beta-thalassemia has slowed or defective synthesis of the beta globin chain and is prevalent among Greeks, Italians, some Arabs, and Sephardic Jews. Alpha-thalassemia, wherein the alpha chain is affected, is most common among Chinese, Vietnamese, Cambodians, and Laotians. Both thalassemias are common amoung blacks. The effects range from mild microcytosis to death in utero, and the pathophysiology depends on the number of defective genes and the mode of inheritance. Pathophysiology: The fundamental defect in beta-thalassemia is the uncoupling of alpha and beta chain synthesis. The free alpha chains are unstable and easily precipitated in the cell. Most erythroblasts that contain precipitates are destroyed by mononuclear phagocytes in the marrow, and this results in ineffective erythropoeisis and anemia. Individuals with beta-thalassemia minor, which is the mild form, are usually asymptomatic. People with beta-thalassemia major, which is the severe form, may become quite ill; anemia is severe and results in significant cardiovascular overload with high-output congestive heart failure. Today, blood transfusion can increase life span by a decade or two. Death is usually caused by hemochromatosis. There are differing forms of alpha-thalassemia, and the type depends on the number of defective genes. The severity is variable. Individuals who inherit the mildest form of alpha-thalassemia, caused by the alpha trait, usually are symptom free or have mild microcytosis. Alpha-thalassemia major causes hydrops fetalis and fulminant intrauterine CHF. The fetus has a grossly enlarged heart and liver. Diagnosis usually is made postmortem. In children with thalssemia major, cardiovascular compromise causes death by 5 to 6 years of age if untreated. Clinical Manifestations: Fatigue, weakness dyspnea, pallor; hepatomegaly and splenomegaly; fetal intrauterine congestive heart failure. Individuals who are carriers or who have thalassemia minor generally have few symptoms and require no specific treatment. The thalassemias are a heterogeneous group of hereditary hypochromic anemias of varying severity. Basic genetic defects include abnormalities of messenger ribonucleic acid (mRNA) processing or deletion of genetic materials, resulting in a decrease in the chains for hemoglobin. The diagnosis of thalassemia is made through studies such as bone marrow examination, hemoglobin electrophoresis, and iron count. The CBC count and peripheral blood film examination results are usually sufficient to suspect the diagnosis

DIC

The development of DIC is generally associated with three pathologic processes: endothelial damage; exposure to tissue factor (TF), which complexes with factor VII; and direct activation of factor X. Gram-negative sepsis, septic shock, hypoxia, and low-flow states associated with cardiopulmonary arrest can damage the endothelium and precipitate DIC by activating the intrinsic clotting pathway. Endotoxins of gram-negatives activate both intrinsic and extrinsic clotting pathways. Release of TF is associated with burns, brain injury, myocardial infarctions, surgeries, obstetrical accidents, and malignancies. Excessive amounts of TF in the circulation activate the clotting pathways. Activation of factor X is stimulated by various substances that enter the bloodstream. Pancreatic and hepatic enzymes and venom from snakebites act in this manner. DIC also can be precipitated by blood transfusion. Transfused blood dilutes the clotting factors and the circulating, naturally occurring antithrombins. In DIC, the extrinsic system is most often involved. When either the intrinsic or the extrinsic system is activated, widespread, unrestricted coagulation occurs throughout the body and leads to thrombic events within the vasculature. The clotting factors are consumed as widespread clotting develops. Thrombosis in the presence of hemorrhage comprises this paradoxical alteration. The amount of thrombin that enters the systemic circulation during DIC greatly exceeds the ability of the body's naturally occurring antithrombins. The obstruction that results from the circulatory deposition of thrombin interferes with blood flow and causes widespread organ hypoperfusion that can lead to ischemia, infarction, and necrosis with manifestations of multisystem organ dysfunction.

Describe hemolytic disease of the newborn (also called Erythroblastosis fetalis) as an alloimmune disease

The two major causes of hemolytic disease of the newborn are blood type incompatibility (ABO) and Rh factor incompatibility. Blood type incompatibility of hemolytic disease of the newborn (HDN) is a mild form of hemolytic disease; Rh incompatibility is potentially much more severe. Blood type incompatibility in the mother occurs when maternal antibodies to fetal erythrocytes are formed because of a prior incompatible pregnancy, other antigenic factors, or exposure of the mother to fetal erythrocytes during pregnancy. Incompatibility in the infant occurs when sufficient antibody, usually IgG, crosses the placenta from the mother to the infant when maternal antibodies attach to and damage fetal erythrocytes. ABO incompatibility occurs in 20% to 25% of pregnancies, with only 1 in 10 cases producing HDN. Usual causes are a type O mother with a type A or B infant, or a type B mother with a type A infant. Hemolysis in the newborn is usually limited and requires no treatment; however, mild hemolysis may contribute to hyperbilirubinemia. Rh incompatibility occurs in less than 10% of pregnancies and rarely is a problem during the first pregnancy; the first pregnancy initiates sensitization. Anti-Rh antibodies are formed only in response to the presence of incompatible (Rh-positive) red blood cells (RBCs) to the blood of an Rh-negative mother. Usually this exposure occurs as fetal blood is mixed with mother's blood at the time of delivery. A problem develops if the baby is Rh positive, having inherited the Rh antigens from the father. The mother's immune system responds by making anti-Rh antibodies to the baby's Rh-positive status. Rh incompatibility becomes a greater problem with subsequent pregnancies when maternal antibodies cross the placenta into fetal blood. It should be noted that HDN caused by Rh incompatibility occurs in only 5% of pregnancies after 5 or more pregnancies. In the most severe form, Rh incompatibility can lead to hydrops fetalis with severe anemia, edema, central nervous system damage, and fetal death. Because the maternal antibodies remain in the neonate's circulatory system after birth, erythrocyte destruction can continue. This causes hyperbilirubinemia icterus neonatorum (neonatal jaundice) shortly after birth. HDN results from incompatibility between the maternal and the fetal blood, which may involve differences in Rh factors or blood type (ABO). Maternal antibodies enter the fetal circulation and cause hemolysis of fetal erythrocytes. Because the immature liver is unable to conjugate and excrete the excess bilirubin that results from the hemolysis, icterus neonatorum, or kernicterus or both can develop. Indirect Coombs: to detect antibodies in maternal blood

The peripheral blood smear will confirm cell size and shape.

This microscopic exam of blood cells tells the provider abnout abnormalities that cannot be detected by automated cell counters.

What serious complications may result from deep vein thrombosis?

Thromboembolitic disease results from a fixed (thrombus) or moving (embolus) clot that blocks flow within a vessel, denying nutrients to tissues distal to the occlusion; death can result when clots obstruct the blood flow to the heart, brain, or lungs. DVT is the formation of a blood clot (thrombus) in a deep vein, predominantly in the legs. Non-specific signs may include pain, swelling, redness, warmness, and engorged superficial veins. Pulmonary embolism, a potentially life-threatening complication, is caused by the detachment (embolization) of a clot that travels to the lungs.

Shift to the left

When the demand for neutrophils exceeds the circulatory supply, the marrow releases immature neutrophils and other leukocytes into the blood; this is called shift to the left, or a leukomoid reaction, because morphologic findings in blood smears are similar to those of individuals with leukemia. As infection or inflammation diminishes, granulopoiesis replenishes the circulating granulocytes, and the levels return back to normal.

leukopenia

a decrease in leukocytes in the blood

Thrombocytopenia: acquired

acquired is more common and may occur because of decreased production secondary to viral infections, drugs, nutritional deficiencies, chronic renal failure, aplastic anemia, radiation therapy, or bone marrow infiltration by cancer. Most common deficiencies are the result of increased platelet consumption. One example is heparin-induced thrombocytopenia, which is an adverse drug reaction caused by IgG against heparin-platelet factor 4 complex. ITP is a major cause of platelet destruction, often affecting females, and results in hemorrhaging that ranges from minor development of petechiae to major bleeding from mucosal sites. Thrombocytopenia exists in primary and secondary forms and is commonly associated with autoimmune diseases and viral infections; bacterial sepsis with DIC also results in thrombocytopenia.

embolus

air, detached blood clot, or foreign body that travels in the blood stream and gets stuck in the blood stream

leukocytosis

an increase in the number of leukocytes in the blood

Macrocytic-normochromic (or megaloblastic-normochromic) anemia

anemias characterized by larger than normal RBCs with normal levels of hemoglobin. They most commonly are caused by deficiency of vitamin B12 (pernicious anemia) or folate.

Microcytic-hypochromic anemias

are characterized by abnormally small RBCs with insufficient hemoglobin content. This disorder results from disorders of (1) iron metabolism (Iron Deficiency Anemia), (2) porphyrin and heme synthesis (Sideroblastic anemia), or globin synthesis (Thalassemia)

Normocytic-normochromic anemias

are characterized by insufficient numbers of normal erythrocytes. Included in this category are aplastic, posthemorrhagic, and hemolytic anemias, and Anemia of Chronic Disease.

Iron deficiency anemia (IDA) is usually the result of

blood loss or poor nutritional intake. Individuals at highest risk for developing IDA are older adults, women, infants, and those living in poverty. Anemia is also recognized as part of the nonspecific acute phase response to any type of inflammation. Once the source of blood loss is identified and corrected, oral iron replacement therapy can be initiated.

Sideroblastic anemia pathophysiology

congenital dysfunction of iron metabolism in erythroblasts, acquired dysfunction of iron metabolism as a result of drugs or toxins. Dysfunctional iron uptake by erythroblasts and defective porphyrin and heme synthesis

Anemia of Chronic Disease (ACD) results from

decreased erythropoiesis secondary to chronic diseases. The anemia is mild to moderate and one of the most common conditions encountered in medicine. Mechanisms associated with ACD include: (1) decreased erythrocyte lifespan, (2) reduced production of erythropoietin, (3) ineffective bnone marrow response to erythropoietin, and (4) iron sequestration in macrophages. In particular, the proinflammatory cytokine IL-6 increases hepatocyte release of hepcidin, which suppresses ferroportin transport of iron out of macrophages.

Cobalamin deficiency (vitamin B12) may result from

dietary insufficiency of vitamin B12; disorders of the stomach, small bowel, and pancreas; certain infections; and abnormalities of transport, metabolism, and utilization.

Thrombocytopenia

exists when the platelet count is below 100K. It results from decreased platelet production, increased consumption, or both. The condition may be congenital or acquired and may be primary or secondary. Hemorrhage from minor trauma can occur with counts of 50K or less. Spontaneous bleeding can occur with counts between 10K and 15K. Severe bleeding results if the count is below 10K, such bleeding can be fatal if it occurs in the GI tract, respiratory system, or CNS.

Classic pernicious anemia produces cobalamin deficiency due to

failure of the stomach to secrete IF (intrinsic factor). Cobalamin is freed from meat in the acidic milieu of the stomach where it binds R factors in competition with IF. CbI is freed from R factors in the duodenum by proteolytic digestion of the R factors by pancreatic enzymes. The IF-CBI complex transits to the ileum where it is bound to ileal receptors. The IF-CBI enters the ileal absorptive cell, and the CBI is released and enters the plasma.

Iron deficiency anemia (IDA) typical symptoms

fatigue, weakness, dyspnea, pallor

Sideroblastic anemia clinical manifestations

fatigue, weakness, dyspnea, pallor; mild hepatomegaly and splenomegaly; eythropoietic hemochromatosis

thrombus

fibrous blood clot formed in a vessel that remains attached to its site of origin

koilonychias

fingernails that are brittle and spoon shaped

Reticulocytes are

immature RBCs and they are larger than mature RBCs When anemia occurs, the bone marrow will respond by producing more RETICULOCYTES. If the bone marrow does NOT respond, the cause may be APLASTIC or PERNICIOUS ANEMIA.

Sarah, age 80, has pernicious anemia. Before treatment, you would expect her mean corpuscular volume to be ____

increased. In pernicious anemai (B12 deficiency), the peripheral blood usually shows a macrocytic anemia with a mild leukopenia and thrombocytopenia. The mean cell volume (MCV) and mean cell hemoglobin (MCH) are increased, with a mean corpuscular hemoglobin concentration (MCHC) within the normal range.

Folate deficiency anemia

inhibits DNA synthesis. High risk groups: chronically malnourished individuals. Folate deficiency anemia: lack of folate for erythropoiesis; premature cell death.

Hypoxemia

insufficient oxygenation of arterial blood

Serum iron may be low in

iron deficiency anemia

MCH and MCHC will be low in

iron deficiency anemia when the deficiency is CHRONIC. This finding is termed Microcytic, Hypochromic

Serum ferritin is an indicator of

iron stores and it is the most accurate diagnostic test for diagnosis of iron deficiency

DIC

is a complex syndrome that results from a variety of clinical conditions that release tissue factor causing an increase in fibrin and thrombin activitiy in the blood and producing augmented clot formation and accelerated fibrinolysis. Sepsis is a condition that is often associated with DIC. DIC is characterized by a cycle of intravascular clotting followed by active bleeding caused by the initial consumption of coagulation factors and diffuse fibrinolysis. Diagnosis of DIC is based on measurement in the blood of end products characteristic of dysfunctional coagulation activity. The D-dimer test is the most reliable and specific test for the diagnosis of DIC. D-dimer is a neoantigen produced by plasmin lysis of cross-linked fibrin clots. Monoclonal antibodies are formed against D-dimer antigen and identified. This documents the acitivity of thrombin (cross-linking) and plasmin (fibrinolysys)

Monocytopenia

is a decrease in monocytes, is rare but has been identified with hairy cell leukemia and prednisone therapy.

Infectious Mononucleosis (IM)

is an acute infection of B lymphocytes. The most common etiologic virus is the EBV, however, cytomegalovirus (CMV), other viruses, and several bacteria have been identified as causitive agents for this disease. Approx 50% to 80% of children by age 4 years and more than 90% of adults are infected with EBV, but are asymptomatic. Symptomatic IM usually affects young adults between the ages of 15 and 35. Transmission of EBV is usually through saliva, hence the term "kissing disease." The virus also may be present in other mucosal secretions, as well as blood. Aerosal transmission does NOT occur. The infection begins with invasion of B lymphocytes that possess an EBV receptor site. The virus infects the oropharynx, nasopharynx, and salivary epithelial cells. Infection of B cells permits the virus to enter the blood which spreads the infection systemically. The proliferation of clones of B and T cells and the removal of dead and damaged lymphocytes are largely responsible for the swelling of the cervical lymphoid tissues. The proliferation of B and T cells is responsible for the rise in absolute lymphocyte count and the presence of atypical lymphocytes which are actually CD8 cytotxic T cells.

Lymphocytosis (increase in the proportion of lymphocytes in the blood)

is rare in acute bacterial infections and OCCURS MOST OFTEN in acute VIRAL infections especially inthose caused by the Epstein-Barr virus (EBV). Cause: Physiologic (4 months to 4 years of age) Acute infection (infectious mononucleosis, CMV infection, pertusis, hepatitis, myoplasma pneumonia, typhoid) Chronic infection (congenital syphilis, tertiary syphilis) Endocrine (Thyrotoxicosis, adrenal insufficiency) Malignancy (ALL, CLL, Lymphosarcoma cell leukemia)

Basopenia

is seen in hyperthyroidism (Graves disease), acute infection, and longterm therapy with steroids, and (physiologic:) during ovulation and pregnancy and stress. Basopenia (or basocytopenia) is a form of agranulocytosis associated with a deficiency of basophils. One cause is uticaria.

Pernicious anemia

lack of vitamin B12 (cobalamin) for erythropoiesis; abnormal DNA and RNA synthesis in the erythroblast; premature cell death.

Lymphocytopenia

may be associated with neoplasias, immune deficiencies, and destruction by drugs. It may be that the lymphocytopenia associated with heart failure and other acute illnesses is caused by elevated levels of cortisol. Lymphocytopenia is a major problem with persons with AIDS. The lymphocytopenia seen with this condition is caused by HIV, which is cytopathic for helper T lymphocytes. Cause: immunodeficiency syndrome (AIDS, agammaglobulinemia) Lymphocyte destruction (Steroids [Cushing syndrome], radiation, chemotherapy, Hodgkin lymphoma, CHF, renal failure, TB, SLE, aplastic anemia)

Neutropenia, which is low neutrophillic count, may be caused by

may be decreased or ineffective neutrophil production, because the bone marrow is producing other formed elements. Also, autoimmunity, reduced neutrophil survival, and abnormal neutrophil distribution and sequestration in tissues leads to neutopenia. Exists when neutrophil count is less than 2000/mcL. If the entire granulocyte count is extremely low, less than 500/mcL, a very serious condition called agranulocytosis or granulocytopenia results. The usual CAUSE of agranulocytosis is interference with hematopoiesis in the bone marrow or increased cell destruction in the circulation. Chemotherapeutic agents used in the treatment of hematologic and other malignancies and some drugs cause bone marrow suppression. Clinical manifestations: respiratory infection, general malaise, septicemia, fever, tachycardia, and ulcers in the mouth and colon.

Polycythemia vera (PV) is a

neoplastic, nonmalignant condition characterized by splenomegaly and increases in RBC, WBCs, and platelets. It is a myeloproliferative disorder characterized by excessive proliferation of erythrocyte precursors in the bone marrow. ERYTHROCYTOSIS is the most serious complication and the essential manifestation for diagnosis. Clonal prolilferation of erythroid progenitors occurs in the bone marrow, independent of eythropoietin, although the cells express a normal erythropoietin receptor. PV-affected individuals have an acquired mutation in Janus kinase (JAK2). This kinase increases the activiity of the erythropoietin receptor and is also self-regulating, so JAK2 activity diminishes over time. Thus, the erythropoietin receptors are active regardless of the level of erythropoietin.

Macrocytic anemias (MCV increased) are usually

normochromic

hemolysis

red blood cell breakdown

Poikilocytosis

red blood cells in various shapes

anisocytosis

red blood cells in various sizes

Polycythemia vera (PV) clinical manifestations

result from marrow erythropoiesis causing increased cellularity of the blood, which increases blood volume and viscosity. Circulatory alterations prevalent in PV, caused by thick, sticky blood, give rise to specific manifestations, such as PLETHORA (ruddy, red color of the face, hands, feet, ears and mucous membranes) and engorgement of the retinal and cerebral vessels. Individuals also experience headache, drowsiness, delirium, mania, psychotic depression, chorea, and visual disturbances. Death from cerebral thrombosis is approx 5 times greater in individuals with PV. A unique feature of PV and potentially instrumental in DX is extreme, painful itching upon exposure to water (aquagenic pruritis)

In anemia of chronic disease

serum ferritin will be high or normal, and the TIBC low and serum transferrin saturation will be low.

In iron deficiency that has become chronic

serum ferritin will be low, TIBC will be high, and the transferrin saturation will be low

Iron studies other than serum iron include

serum ferritin, total iron binding capacity (TIBC), and transferrin saturation.

In adults, pernicious anemia is associated with

severe gastic atrophy and achlohydria, which are irreversible. Coexistent iron deficiency is common because achlorohydria prevents solubuilization of dietary ferric iron from foodstuffs. Autoimmune phenomena and thyroid disease frequently are observed. Patients with pernicious anemia a have a 2- to 3-fold increased incidence of gastic carcinoma.

MCV is

the average size or volume of the RBCs and is used as the starting point in classifying an anemia.

megaloblasts

unusually large stem cells in bone marrow

Monocytosis

which is an increase in monocytes, is often transient and correlates poorly with disease states. When present, it is most commonly associated with bacterial infections during the late stages of recovery, when moncytes are needed to phagocytize any surviving microorganism and debris. Monocytosis is seen in chronic infections such as tuberculosis and subacute bacterial endocarditis. Infection: Bacterial, recovery phase Hematologic: Myeloproliferative disorders, Hodgkin disease, agranulocytosis. Physiologic: normal newborn.