hematology surgery #8
Sickle cell anemia diagnosis
(+) HgbS on hemoglobin electrophoresis is definitive The baseline complete blood count (CBC) and peripheral blood smear in individuals with SCD typically shows the following findings: Hemoglobin level approximately 8 to 10 g/dL Hematocrit approximately 20 to 30 percent Polychromasia and reticulocytosis (typical reticulocyte count approximately 3 to 15 percent) Sickled cells Howell Jolly bodies (nuclear remnants that have not been phagocytosed, due to reduced splenic function) Mildly increased white blood cell (WBC) count in some cases The RBC indices typically show normochromic, normocytic cells, unless there is coexistent thalassemia or iron deficiency, in which case microcytosis and hypochromia may be present. A high percentage of reticulocytes may cause mild macrocytosis.
Iron deficiency treatment
- ferrous sulfate 325 mg three times daily - docusate sodium 100mg twice daily as needed for constipation
Patient will present as → a 45-year-old female with a long history of a heart murmur with one week of increasing fatigue and low-grade fevers. She had a dental cleaning two weeks ago. She denies any hematuria, neurological symptoms, or changes in the appearance of her hands and fingernails. Her past medical history is otherwise insignificant. On physical exam, her temperature is 38.1 C (100.6 F), heart rate is 92/min, blood pressure is 118/67, and respiratory rate is 16/min. She appears fatigued but in no acute distress. Cardiac auscultation reveals a grade III/VI holosystolic murmur heard best at the cardiac apex in the left lateral decubitus position. Pulmonary, abdominal, and extremity exams are within normal limits. An echocardiogram is performed and is shown here. The patient is admitted and started on empiric IV antibiotics. Three days later, 4/4 blood cultures grow Streptococcus viridans that is highly sensitive to penicillin.
Acute and subacute bacterial endocarditis
Iron deficiency anemia symptoms
Adults: pallor, fatigue, weakness, dypsnea, pica, pagophagia Infants: decreased learning ability, altered motor function, reduced dopamine receptors, reduced serotonin -Fatigue -Tachycardia -Palpitations -Tachypnea on exertion -Smooth tongue -Brittle nails -Koilonychia (spoon nails) -Cheilosis -Pica -Plummer-Vinson syndrome (esophageal web formation causing dysphagia)
hemophilia
An X-linked recessive disorder in which blood fails to clot properly, leading to excessive bleeding if injured. X-linked recessive so will affect males (most of the time) Factor VIII in Hemophilia A Factor IX in Hemophilia B (Christmas Disease) Hemarthrosis, bruising, and bleeding ↑ PTT, normal PT, and platelets, with ↓ Factor VIII or IX on assay Treatment involves the replacement of factor VIII or IX Hemophilia is a hereditary bleeding disorder caused by a deficiency in one of two blood clotting factors: factor VIII or factor IX. Clotting factors are proteins that interact to help the blood clot, stopping the bleeding. There are two forms of hemophilia. Hemophilia A, which accounts for about 80% of all cases, is a deficiency in clotting factor VIII Hemophilia B is a deficiency in clotting factor IX Remember: Hemophilia A = "Aight" and B comes after A which is factor NINE The bleeding patterns and consequences of these two types of hemophilia are similar. Hemophilia is caused by several different gene abnormalities. They are X-linked, which means that the gene abnormalities are inherited through the mother and that nearly everyone with hemophilia is male.
Patient will present as → a 62-year-old male with a history of chronic kidney disease complains of weight loss, fatigue, and weakness. Iron studies reveal decreased serum iron, increased ferritin, and decreased TIBC. Peripheral blood smear shows normochromic RBCs.
Anemia of chronic disease
Idiopathic thrombocytopenic purpura
Antiplatelet antibodies Idiopathic thrombocytopenic purpura (ITP) is a blood disorder characterized by an abnormal decrease in the number of platelets in the blood Autoimmune antibody reaction to platelets which results in splenic platelet destruction often after an acute infection Symptoms of thrombocytopenia which may include easy bruising, mucosal bleeding, purpura, and petechial rashes Typically, ITP is chronic in adults, but it is usually acute and self-limited in children Primary immune thrombocytopenia (ITP): immune-mediated thrombocytopenia without an underlying condition Secondary ITP: immune-mediated thrombocytopenia with an underlying condition (e.g., HIV infection) Often presents 1-2 weeks after a viral infection - associated with HIV, HCV, SLE, CLL
What laboratory finding supports a diagnosis of mononucleosis?
Atypical lymphocytosis on white blood cell differential
Autoimmune Hemolytic Anemia
Autoantibodies bind to the patient's own erythrocytes, leading to premature red cell destruction (hemolysis) Warm and cold types Warm (90%) - immunoglobulin (Ig)G, that bind preferentially to the red cells at 37°C, Cold (10%) < 37° C anemia pallor, dyspnea acrocyanosis and livedo reticularis Mild splenomegaly is typical + Direct Coombs Test ↑ Retic ↑ LDH ↓ Haptoglobin ↑ Bilirubin (indirect) Dependent on disease severity Rituximab Glucocorticoids, cyclophosphamide, cyclosporine,
G6PD deficiency treatment
Avoidance of triggers (see list of drugs in previous tab) and supportive care During acute hemolysis, treatment is supportive; transfusions are rarely needed. Patients are advised to avoid drugs or substances that initiate hemolysis.
Disseminated Intravascular Coagulation (DIC) symptoms
Bleeding and oozing at catheter sites and mucosal surfaces, petechiae and ecchymoses, hypotension and tachycardia
Iron deficiency diagnosis
CBC Reticulocyte count: low RDW: high Iron Studies Decreased serum iron, ferritin, and transferrin saturation Increased TIBC Ferritin <15 ng/mL (diagnostic)
Folate (Vitamin B9) deficiency diagnosis
CBC and serum vitamin B12 and folate levels CBC may indicate megaloblastic anemia indistinguishable from that of vitamin B12 deficiency. If serum folate is < 3 deficiency is likely A normal methylmalonic acid (MMA) level may differentiate folate deficiency from vitamin B12 deficiency because MMA levels rise in vitamin B12 deficiency but not in folate deficiency.
Epstein-Barr virus infections diagnosis
CBC with a peripheral blood smear reveals atypical lymphocytes often constitute > 10% of total leukocyte count Monospot (mononucleosis rapid slide agglutination test for heterophile antibodies)Appears in the first two weeks of illness, usually slow decline over 6 months - detects 85% of cases in adolescents/adults Heterophile antibodies may not appear early in the illness (click here) Up to 10% of patients with acute EBV infection may have no heterophile response 3 weeks into the illness The heterophile response is less common in infants and children and should not be used in children < 4 years of age In the case of an early infection, an individual can simply undergo the Monospot test again at a later time, after the infection progresses a bit, but for young children, testing for EBV-specific antibodies is the next step
Von Willebrand Disease diagnosis
CBC with platelet count and coagulation studies during the initial evaluation for excessive bleeding or bruising Individuals with VWD generally have a normal CBC, normal platelet count, and↑ bleeding time Individuals with VWD may have a normal or prolonged aPTT and a normal PT Those with significant bleeding may have evidence of iron deficiency (microcytic anemia) Screening tests for VWD include VWF antigen (VWF: Ag), a VWF activity (VWF: Act) test, and a factor VIII activity level Patient will have ↓ von Willebrand's factor (vWF)Because von Willebrand factor is the protein that carries clotting factor VIII in the blood, the level of factor VIII may also be decreased
sleep apnea treatment
CPAP Management of obstructive sleep apnea Behavior modification: which includes weight loss and exercise, avoiding alcohol and sedatives, and sleeping in a nonsupine position Mild to moderate OSA: Positive airway pressure therapy If the patient refuses or there are issues with compliance, an oral appliance can be offered Severe OSA: Continuous positive airway pressure (CPAP) provides positive pressure, thus preventing occlusion of the upper pharynx. This is the preferred therapy for the majority of patients because it is noninvasive and has proven efficacy. It is poorly tolerated by some due to noise and discomfort Uvulopalatopharyngoplasty—removal of redundant tissue in oropharynx to allow more airflow Tracheostomy is a last resort for those in whom all other therapies have failed or who have life-threatening OSA (severe hypoxemia or arrhythmias) Management of obesity hypoventilation syndrome Weight loss +/- CPAP at night For patients with OHS who fail or do not tolerate first-line therapies in whom aggressive attempts have been made to optimize PAP therapy, options include tracheostomy for the treatment of sleep-disordered breathing and bariatric surgery or rarely medication for weight loss
What is the latent finding in iron deficiency anemia?
Change in the indices - microcytic/hypochromic changes in the RBC
Acute and subacute bacterial endocarditis diagnosis
Diagnosis requires demonstration of microorganisms in blood and usually echocardiography Blood cultures (before antibiotics are started) 3 sets at least 1 hour apart EKG at regular intervals LABS: CBC, ESR, RF A transesophageal echocardiogram is the gold standard
Patient will present as → a 43-year-old alcoholic man who arrives at the hospital with alcohol withdrawal. He confabulates and trembles uncontrollably. He is started on supportive therapy for now. Bloodwork comes back with macrocytic megaloblastic anemia, an increased homocysteine, normal methylmalonic acid, and decreased folate. He is immediately started on folic acid supplementation.
Folate (Vitamin B9) deficiency
Disseminated Intravascular Coagulation (DIC)
Complex, acquired disorder in which clotting and hemorrhage simultaneously occur abnormal activation of the proteins involved in blood coagulation, causing small blood clots to form in vessels and cutting off the supply of oxygen to distal tissues Abnormal activation of the coagulation sequence, leading to the formation of microthrombi throughout the microcirculation. This causes the consumption of platelets, fibrin, and coagulation factors Fibrinolytic mechanisms are activated, leading to hemorrhage. Therefore, bleeding and thrombosis occur simultaneously
Patient will present as → a 35-year-old woman comes to your office with a 1-year history of "aching and hurting all over." She also complains of a chronic headache, difficulty sleeping, and generalized fatigue. When questioned carefully, she describes "muscle areas tender to touch." Although the pain is worse in the back, there really is no place free of pain. She also describes headaches, generalized abdomen pains, and some constipation.
Fibromyalgia
Patient will present as → a 69-year-old female who presents for evaluation of fatigue. She has a history of lung cancer and has undergone several rounds of chemotherapy in the last four months. For the past three weeks, she has experienced SOB with exertion and generalized malaise. Her temperature is 99.4°F, blood pressure is 94/66 mmHg, pulse is 108/min, and respirations are 19/min. On exam, she is pale appearing with diffuse petechia and gingival bleeding.
DIC
Disseminated Intravascular Coagulation (DIC) diagnosis
DX: Diagnosis is based on clinical and laboratory findings, including thrombocytopenia, coagulation factor consumption, and fibrinolysis ↓ Platelets, ↑ bleeding time, ↑ PT, ↑ aPTT, (+) D-dimer ↓ factors V and VIII
Hemolytic Uremic Syndrome diagnosis
Diagnosed by triad of anemia, thrombocytopenia, and renal failure Proteinuria, hematuria, urinary casts; ↑ BUN/creatinine; ↓ H&H, ↑ reticulocyte count
G6PD deficiency diagnosis
Diagnosis is made by G6PD assay HEINZ BODIES and BITE CELLS on smear Hemolysis labs: ↑ indirect bilirubin, ↓ haptoglobin, and↑ lactate dehydrogenase
Polymyalgia rheumatica diagnosis
ESR is markedly elevated, usually > 50, temporal arteritis is confirmed by biopsy
Epstein-Barr virus infections
Epstein Barr mononucleosis is a viral illness characterized by a classic triad of fever + lymphadenopathy + pharyngitis + atypical lymphocytes Most people are carriers of the Epstein-Barr virus, but may not have developed an active infection from the virus. The incubation period is 30-50 days, transmission via oropharyngeal secretions and saliva - "The kissing disease" Pt will present with the classic triad of fever + Lymphadenopathy + Pharyngitis Maculopapular rash develops in 80% of patients treated with ampicillin Pt may also have left upper quadrant pain secondary to splenomegaly and are at risk for splenic rupture - incidence of ~1 in 1,000 patients with only 50% of those secondary to blunt trauma.
Patient will present as → a 14-year-old boy with 3-days of sore throat, fever, and generalized malaise. On exam, he has a temperature of 102.2 F (39.0 C), BP 96/50, and a diffuse exudate on both tonsils. He also is noted to have palpable splenomegaly, swollen painful lymph nodes, and mild hepatomegaly. Labs show leukocytosis of 12,000/mm3 with 50% neutrophils, 12% monocytes, and 38% lymphocytes. The rapid pharyngeal streptococcal screen is negative.
Epstein-Barr virus infections
Hemolytic uremic syndrome is caused by
Escherichia coli O157:H7
Fibromyalgia
Fibromyalgia is a common, incompletely understood nonarticular disorder characterized by generalized aching (sometimes severe); widespread tenderness of muscles, areas around tendon insertions, and adjacent soft tissues; muscle stiffness; fatigue; mental cloudiness; poor sleep; and a variety of other somatic symptoms. Most common in middle-aged women May affect 3-10% of population, age 20-50, F > M Associated with hypothyroidism, RA, or sleep apnea Clinical manifestations include diffuse pain that is worse in the morning, extreme fatigue, stiffness, painful, tender joints, and SLEEP DISTURBANCES, symptoms often worsened with physical and psychological stress
Folate (Vitamin B9) deficiency treatment
Folate deficiency is treated with folate supplements, folate-fortified food items, by stopping the offending medications or limiting alcohol consumption. Folate 400 to 1000 μg po once/day replenishes tissues and is usually successful even if deficiency has resulted from malabsorption The normal requirement is 400 μg/day. (Caution: In patients with megaloblastic anemia, vitamin B12 deficiency must be ruled out before treating with folate. If vitamin B12 deficiency is present, folate supplementation can alleviate the anemia but does not reverse, and may even worsen, neurologic deficits) CDC recommends that women consume 4,000 mcg of folic acid each day one month before becoming pregnant and through the first 3 months of pregnancy
Patient will present as → a 20-year-old healthy male who was treated 4 days ago for an MRSA skin infection with sulfamethoxazole-trimethoprim (Bactrim). The infection is improving but he is increasingly weak and his sclera have turned yellow. Today his hemoglobin is 11 g/ dL (13.5 to 18 g/ dL) and his MCV is 85 (80 to 100 fL); the corrected reticulocyte count is elevated, he has increased indirect bilirubin and decreased haptoglobin. The peripheral smear demonstrates bite cells and Heinz bodies.
G6PD deficiency
G6PD deficiency pearls
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic defect common in blacks that can result in hemolysis after acute illnesses or intake of certain drugs. Drugs that commonly cause hemolysis in patients with G6DP deficiency: Antimalarials: primaquine, pamaquine Analgesics: phenacetin, acetylsalicylic acid Others: sulfonamides, dapsone Oxidative Stress (infection or drug-induced) + African American Male + Heinz bodies Heinz Bodies! X-linked (look for males), damaged hemoglobin (G6PD protects RBC membrane) causes HEINZ BODIES and BITE CELLS on smear Look for a trigger event: Antimalarials, sulfa drugs, ASA, febrile illness - causes the breakdown of RBCs 10% of male blacks in the U.S are affected Here is a wonderful board review pearl: Favism - Ingestion of, or exposure to, fava beans may cause a devastating intravascular hemolysis in patients with G6DP deficiency. "
Hemophilia diagnosis
History, physical exam Decreased factor VIII or IX Prolonged activated partial thromboplastin time ( PTT) • Can be *diagnosed through amniocentesis* • Genetic testing of family members to identify carriers • Diagnosis on basis of hx, laboratory tests (labs), and examination • Labs: low levels of factor VIII or IX, prolonged PTT • Normal: platelet count, prothrombin time (PT), and fibrinogen
Sickle Cell Anemia Treatment
Hydroxyurea Treatment: Crises are treated with analgesics and other supportive measures (oxygen, hydration). Transfusions are occasionally required. "Salmonella is a common cause of osteomyelitis in patients with sickle cell anemia. Reasonable empiric treatment consists of vancomycin and ciprofloxacin." Vaccines against bacterial infections, prophylactic antibiotics, and aggressive treatment of infections prolong survival. Hydroxyurea may decrease the frequency of crises.
Idiopathic thrombocytopenic purpura diagnosis
ITP is suspected in patients with isolated thrombocytopenia and otherwise normal CBC and peripheral blood smear Primary ITP: isolated thrombocytopenia (e.g., < 100,000/μL) without a known cause Secondary ITP: isolated thrombocytopenia (e.g., < 100,000/μL) with an underlying condition (e.g., positive for HIV infection) (+) Direct Coombs Test
Patient will present as → a 42-year-old male complaining of easy bruising and gingival bleeding. He reports his symptoms began one day prior to presentation and has never occurred before. Medical history is significant for a recent diagnosis of hepatitis C infection. On physical exam, there is mild bleeding of the gums. There are petechiae throughout the chest, arms, and legs. There is no evidence of splenomegaly on the abdominal exam. A complete blood count is significant for a platelet count of 24,000/μL (normal 150,000 - 400,000/μL) and peripheral blood smear demonstrates enlarged platelets. He has a + Direct Coombs Test. He is started on corticosteroids.
Idiopathic thrombocytopenic purpura
Acute and subacute bacterial endocarditis
Infective endocarditis is an infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi It causes fever, heart murmurs, petechiae, anemia, embolic phenomena, and endocardial vegetations. Acute bacterial endocarditis: Infection of normal valves with a virulent organism (S. aureus) Subacute bacterial endocarditis: Indolent infection of abnormal valves with less virulent organisms (S. viridans) Endocarditis with intravenous drug users - Staphylococcus aureus Prosthetic valve endocarditis - Staphylococcus epidermidis Vegetations may result in valvular incompetence or obstruction, myocardial abscess, or mycotic aneurysm. Candida is a slow-growing organism. Most common source is a contaminated line. It typically causes large vegetations in endocarditis.Large vegetation endocarditis in the early post-valve replacement period (2 months post-surgery) is most likely due to fungus, that is, Candida infection. Amphotericin B is recommended followed by several weeks of antifungals that carry fewer adverse events. HACEK organisms tend to grow on native valves Staphylococcus aureus causes smaller vegetations; it is more common in injection drug users Streptococcus viridans is the most common cause of endocarditis. It typically occurs as a late complication of valve replacement and presents as small vegetations and embolic events. Endocarditis can occur at any age. Men are affected about twice as often as women. IV drug abusers and immunocompromised patients are at the highest risk. Most patients with a new murmur or change in an existing murmur; signs of heart failure (rales, edema) if valve function compromised Peripheral stigmata of IE: Splinter hemorrhages in fingernail beds Osler nodes painful lesions on fleshy portions of extremities "Roth spots" retinal hemorrhages Janeway lesions (cutaneous evidence of septic emboli) Palatal or conjunctival petechiae Splenomegaly hematuria (due to emboli or glomerulonephritis)
Hemolytic Uremic Syndrome
a condition in which hemolytic anemia and thrombocytopenia cause acute renal failure and possibly death
Hereditary Spherocytosis
Inherited dysfunction or deficiency in one of the erythrocyte membrane proteins (spectrin, ankyrin, band 3 protein, or protein 4.2) → spherocytic erythrocytes are sequestered and destroyed in the spleen Autosomal dominant Mild jaundice Mild-moderate anemia Malaise, abdominal discomfort in LUQ Signs: Splenomegaly CBC: anemia MCV: decreased Reticulocyte count, LDH, indirect bilirubin, stool urobilinogen: elevated Wright-stained smear: spherocytes Hgb: 4-6 g/dL (low) EDW: elevated Peripheral smear: spherocytes Osmotic fragility: increased Coombs test: negative Splenectomy Indicated even when anemia compensated and asymptomatic Delay operation until children are age 6 Cholecystectomy if gallstones present Complications: Hypoplastic crises: follow acute viral illness → profound anemia, headache, nausea, pancytopenia, hypoactive marrow, pigmented gallstones
Sleep Apnea and Obesity Hypoventilation Syndrome pearls
Intermittent obstruction of the airflow (typically at the level of the oropharynx) produces periods of apnea during sleep Each apneic period is usually 20 to 30 seconds long (but may be longer) and results in hypoxia, which arouses the patient from sleep. This occurs multiple (sometimes hundreds of) times overnight. Risk factors Obesity (especially around the neck): nonobese patients can also have OSA Structural abnormalities: enlarged tonsils, uvula, soft palate; nasal polyps; hypertrophy of muscles in the pharynx; deviated septum; deep overbite with a small chin Family history Alcohol and sedatives worsen the condition Hypothyroidism (multifactorial) Presents as: Snoring and daytime sleepiness due to disrupted nocturnal sleep Personality changes, decreased intellectual function, decreased libido, morning headaches, polycythemia Repeated oxygen desaturation and hypoxemia can lead to systemic and pulmonary HTN as well as cardiac arrhythmias Obesity-hypoventilation syndrome (OHS) (historically described as the Pickwickian syndrome) Consists of the triad of obesity (BMI > 30), sleep-disordered breathing, and chronic hypercapnia (PCO2 > 45 mmHG) during wakefulness in the absence of other known causes of hypercapnia Signs and symptoms of obesity hypoventilation syndrome (OHS) are essentially the same as OSA. These two diseases are often concurrent.
Patient will present as → a 30-year-old obese white female presents with fatigue and generalized weakness for several weeks. Physical exam reveals pale nail beds, spoon nails, mucosal pallor, and an atrophic tongue. Upon further questioning, the patient reveals a "craving for ice and inanimate objects." Laboratory data shows a microcytic, hypochromic appearance to the RBCs, an elevated TIBC, low serum iron of 16 µg/dl, and low plasma ferritin of 12 µg/dl.
Iron deficiency
What is the earliest finding in iron deficiency anemia?
Low serum ferritin (stores are low)
Acute and subacute bacterial endocarditis treatment
Management - treatment consists of prolonged antimicrobial treatment and sometimes surgery IV antibiotics (based on the organism and its susceptibility) Sometimes valve debridement, repair, or replacement Initial therapy before organism identification (but after adequate blood cultures have been obtained) should be broad-spectrum to cover all likely organisms. Typically, patients with native valves and no IV drug abuse receive ampicillin 500 mg/h continuous IV infusion plus nafcillin 2 g IV q 4 h plus gentamicin 1 mg/kg IV q 8 h .Patients with a prosthetic valve receive vancomycin 15 mg/kg IV q 12 h plus gentamicin 1 mg/kg q 8 h plus rifampin 300 PO q 8 h. IV drug abusers receive nafcillin 2 g IV q 4 h.In all regimens, penicillin-allergic patients require substitution of vancomycin 15 mg/kg IV q 12 h. Antibiotic prophylaxis to prevent recurrent endocarditis is recommended: 2 g of Amoxicillin 30-60 minutes before the procedure
Von Willebrand Disease
Most common genetic bleeding disorder, autosomal dominant ↓von Willebrand's factor (vWF) and ↓ Factor VIII Patients may present with excessive bleeding after a cut or increased menstrual bleeding. You can differentiate this from hemophilia by lack of hemarthrosis, small amounts of superficial bleeding, common to have bleeding with a minor injury, and petechiae. Treat with DDAVP (desmopressin) or in cases of excessive bleeding a transfusion of concentrated blood clotting factors containing von Willebrand factor. Von Willebrand disease is a hereditary deficiency or abnormality of the blood protein von Willebrand factor, which affects platelet function. The von Willebrand factor is found in plasma, platelets, and the walls of blood vessels. When the factor is missing or defective, platelets cannot adhere to the vessel wall at the site of an injury. As a result, bleeding does not stop as quickly as it should. The patient will present with: Often, a person with von Willebrand disease has a parent who has a history of bleeding problems. Typically, a child bruises easily or bleeds excessively after a cut, tooth extraction, or surgery. A young woman may have increased menstrual bleeding. Bleeding may worsen at times. On the other hand, hormonal changes, stress, pregnancy, inflammation, and infections may stimulate the body to increase production of von Willebrand factor and temporarily improve the capacity of platelets to stick to the blood vessel wall and stop bleeding.
What test establishes the diagnosis of OSA?
Nocturnal PSG, or sleep study
Anemia of chronic disease diagnosis
Normal or ↓ MCV, ↓ TIBC, Normal or ↑ Ferritin (because it is not being transported and utilized) ↓ serum erythropoietin levels in anemia of renal failure
Idiopathic thrombocytopenic purpura treatment
Observation in patients with a platelet count > 30,000/μL and no bleeding. Corticosteroids initial treatment for patients with a platelet count < 30,000/μL. Intravenous immunoglobulins (IVIG) for patients with a platelet count < 30,000/μL who have contraindications to corticosteroids, are refractory to corticosteroid treatment, or are bleeding or have a high risk of bleeding that will need a rapid increase in platelet count. Splenectomy second-line treatment for patients with refractory ITP.
Polymyalgia rheumatica treatment
Patients respond quickly to low dose corticosteroid therapy, which may be required for up to 2 years and slowly tapered Methotrexate may also be used
Patient will present as → a 62-year-old female complaining of headaches, muscle pain, and weakness. She has no history of headaches but has now started experiencing them every morning for the past two weeks. She reports feeling very weak and tired in the mornings and cannot even raise her arms to brush her hair. Physical exam shows that she has normal strength and a normal range of movement. Passive range of motion is limited in all directions and she has difficulty rising out of the exam room chair. Erythrocyte sedimentation rate is elevated.
Polymyalgia rheumatica
Polymyalgia rheumatica
Polymyalgia rheumatica (PMR) is an idiopathic inflammatory condition causing painful synovitis, bursitis, and tenosynovitis - aching stiffness of proximal joints (shoulder, hip, neck) in patients > 50 years old. PMR is closely related to giant cell arteritis - a headache may indicate giant cell arteritis. Presents with bilateral proximal joint pain (vs muscle pain in polymyositis) and stiffness of the pelvic and shoulder girdle: difficulty combing hair, putting on coat getting out of the chair. Stiffness is more prominent in the morning. On physical exam patient will have normal muscle strength, reduced active and passive range of movement, and joint swelling may be appreciated.
Hemophilia treatment
Replacing the missing clotting factors. Replacement therapy. blood transfusion.
Disseminated Intravascular Coagulation (DIC) risk factors
Risk factors include infection, obstetric complications, trauma, malignancy, sepsis, acute pancreatitis, transfusions
Sickle cell anemia pearls
Sickled cells on peripheral smear + HgbS on hemoglobin electrophoresis Chronic hemolytic anemia occurring almost exclusively in black people, caused by homozygous inheritance of HgbS Sickle-shaped RBCs clog capillaries, causing organ ischemia. Acute exacerbations (crises) may develop frequently Very High Retic count (especially in crisis) that can be used to monitor event (reticulocyte count will ↓ as the patient improves) Diagnosis requires (+) HgbS on hemoglobin electrophoresis is definitive Hb SS = disease Hb SA = trait. Two parents with sickle cell trait have a 1 in 4 chance of having a child with Hb SS disease. Treat with high flow oxygen, pain control during crisis, and supportive transfusion when HGb is less than 6.
Patient will present as → a 49-year-old man who is brought to your office by his partner, who is concerned about his daytime sleepiness. Last week, the patient fell asleep while stopped at a red light. She says that he snores loudly and sometimes stops breathing for a few seconds while sleeping. His past medical history is significant for hypertension. He has a 20-pack-year history of smoking. His temperature is 98.6 F, heart rate is 86/min, blood pressure is 148/98 mm Hg, respiratory rate is 12/min. On physical exam, he is obese. His lungs are clear and his lower extremity exam is within normal limits.
Sleep Apnea
Thrombotic thrombocytopenic purpura diagnosis
TTP:↓ Platelets + anemia + schistocytes (RBC fragments) Hemolytic Uremic Syndrome (HUS): ↓ Platelets + anemia + renal failure TTP-HUS is suspected in patients with suggestive symptoms, thrombocytopenia, and anemia. If the disorder is suspected, urinalysis, peripheral blood smear, reticulocyte count, serum LDH, renal function tests, serum bilirubin (direct and indirect), and Coombs test are done. The diagnosis is suggested by Thrombocytopenia and anemia Fragmented RBCs on the blood smear indicative of microangiopathic hemolysis (schistocytes: helmet cells, triangular RBCs, distorted-appearing RBCs) Evidence of hemolysis (falling Hb level, polychromasia, elevated reticulocyte count, elevated serum LDH and bilirubin, reduced haptoglobin) Negative direct antiglobulin (Coombs) test Otherwise unexplained thrombocytopenia and microangiopathic hemolytic anemia are sufficient evidence for a presumptive diagnosis. Schistocytes (RBC Fragments)
Patient will present as → a 10-year-old boy with a chief complaint of paleness presents to your office. On physical exam, you note conjunctival pallor bilaterally and he has splenomegaly. Lab data show these results: Hb: 8.5 (normal 12-17.5), MCV 72 (normal 80-100), MCH 22.5 (normal 25-34), WBC: 50,000, Plt: 650,000 (normal 150,000 - 400,000). Hemoglobin electrophoresis shows an increase in the amount of Hgb A2 and normal Hgb F.
Thalassemia
Thrombotic thrombocytopenic purpura
Thrombotic Thrombocytopenia (TTP): Purpura and "FAT RN"- Fever, Anemia, Thrombocytopenia, Renal failure, Neurological symptoms Triggers: drugs (quinine, ticlopidine, clopidogrel, and cyclosporine), SLE, infections, AIDS, and malignancies. Diagnostic studies: CBC normal except low platelets. Schistocytes (RBC fragments) on smear. (-) Coombs test
Von Willebrand Disease treatment
Treat with DDAVP (desmopressin) If excessive bleeding occurs, a transfusion of concentrated blood clotting factors containing von Willebrand factor (intermediate-purity factor VIII concentrates) may be given.
Vitamin B12 deficiency treatment
Treatment for B12 deficiency is replacement: usually IM (if pernicious anemia) or sublingual
Epstein-Barr virus infections treatment
Treatment is supportive, and antibiotics are not helpful in treating this viral infection Analgesics increased fluid intake, and rest will help to relieve some of the symptoms. Warm salt water gargles can help with the sore throat Limit activity (contact sports) for a period of time to prevent splenic rupture. Experts generally recommend that athletes not participate in contact or vigorous sport activities for at least the first three to four weeks of the illness The symptoms of the infection may last for several (1-4) weeks. A patient will not contract mononucleosis again after the initial exposure to the Epstein-Barr virus
Anemia of chronic disease treatment
Treatment of underlying disorder Recombinant EPO and iron supplements Treat with exogenous erythropoietin analogs (epoetin alfa (Procrit, Epogen) should only be initiated if the hemoglobin is < 10 gm/dl and these agents must be stopped once hemoglobin is > 11 gm/dl due to increased chance of MI and stroke.
Hemophilia A and B treatment
Treatment often involves the replacement of factor VIII or IX People who have hemophilia should avoid situations that might provoke bleeding and should avoid drugs (for example, aspirin and probably also nonsteroidal anti-inflammatory drugs) that interfere with the function of platelets. They should be conscientious about dental care so that they will not need to have teeth extracted.
Patient will present as → a 38-year-old man with a history of gastric bypass for morbid obesity comes to your office with a hemoglobin level of 10 g/ dL. His MCV is 111 mm3. His ferritin level is 35 mcg/ L, and his red cell distribution width is high. His reticulocyte count is high. Further questioning reveals mild anorexia, diarrhea, glossitis, and distal paresthesia. On exam, you notice she has a swollen red tongue.
Vitamin B12 deficiency
Hemolytic Uremic Syndrome treatment
With children, treatment is usually supportive, results usually in complete recovery. With adults, prognosis is guarded, as HUS usually develops in chronic life-threatening conditions. *PROMPT treatment-residual renal involvement can occur Renal dialysis (hemodialysis or peritoneal) Medications (to treat complications, ie, HTN, hyperkalemia) Administration of blood products
Disseminated Intravascular Coagulation (DIC) treatment
cryoprecipitate, FFP, platelet transfusions if < 10,000/μL, heparin for thrombosis, treat cause
Hemophilia Etiology
hereditary bleeding disorder caused by defective coagulation factor hemophilia A- factor VIII deficiency, most common hemophilia B- factor IX deficiency sex-linked- transmitted to male by female carrier; recessive trait
Thalassemia
is a form of inherited autosomal recessive blood disorder characterized by abnormal formation of hemoglobin Both thalassemia and iron deficiency anemia are hypochromic and microcytic. Thalassemia tends to be more hypochromic and microcytic than iron deficiency Very ↓ MCV on the exam with a normal TIBC and Ferritin (normal iron stores), a normal to low reticulocyte count and a (+) HB Electrophoresis. The blood smear is virtually diagnostic, with many nucleated erythroblasts; target cells; small, pale RBCs; and punctate and diffuse basophilia A quick way to differentiate the two anemias is to examine the RBC count. In iron deficiency, the number will be low. In thalassemia, the number will be normal to high
anemia of chronic disease
normocytic, normochromic Anemia of chronic disease is a multifactorial anemia often coexistent with iron deficiency. Diagnosis generally requires the presence of chronic infection, inflammation, or cancer; microcytic or normocytic anemia; and values for serum transferrin receptor and serum ferritin that are between those typical for iron deficiency and sideroblastic anemia. Normal/Normocytic or ↓ MCV, ↓ TIBC, and Normal or ↑ Ferritin (because it is not being transported and utilized) Some transferrin is converted to lactoferrin which cannot transport ferritin and this results in a ↓ TIBC (transferrin transports iron). ↑ Ferritin because it is not being transported to the bone marrow. The most common causes are (a) chronic renal failure and (b) anemia resulting from connective tissue disorders. Seen in many different types of diseases: RA, SLE, HIV, CA, Cirrhosis, Chronic Infections etc. Anemia of Renal Failure: Erythropoiesis is impaired because of decreases in both erythropoietin (EPO) production and marrow responsiveness to EPO Presence of renal insufficiency or failure + ↓ serum erythropoietin levels
Hemolytic Uremic Syndrome symptoms
often last 1-15 days -Gastroenteritis (bloody diarrhea and vomiting) -Fever, irritability, fatigue -Oliguria or hematuria, peripheral edema or ascites -Hypertension, pallor, small bruises in lining of mouth -CNS development in ~20% of children (seizures, confusion, etc.) Classic triad: -Hemolytic anemia: damage from partial occlusion of RBCs -Thrombocytopenia: platelets cluster in areas of endothelial damage -Acute renal failure: glomerular filtration decreases Children with: -diarrheal illness -kidney disease -positive stool culture of E. coli -purpura
Thrombotic thrombocytopenic purpura treatment
plasmapheresis Plasmapheresis (plasma exchange) is treatment of choice Plasma exchange is continued daily until evidence of disease activity has subsided, as indicated by a normal platelet count, which may require several days to many weeks. Adults with TTP are also given corticosteroids In patients with HUS refractory to plasma exchange and/or corticosteroids and worsening renal insufficiency, complement inhibition with eculizumab can sometimes reverse the renal insufficiency.
Hemolytic Uremic Syndrome risk factors
predominantly seen in children w/recent hx gastroenteritis
Hemophilia symptoms
prolonged bleeding, especially into joint cavities Hemarthrosis, bruising, and bleeding: The main symptom is excessive bleeding. The bleeding may be into a joint or muscle, inside the abdomen or head, or from cuts, dental procedures, or surgery.
Sleep apnea diagnosis
sleep study (polysomnography) Polysomnography (overnight sleep study in a sleep laboratory) confirms the diagnosis of obstructive sleep apnea and can distinguish OSA from CSA Home sleep apnea testing (HSAT) may be an acceptable alternative for patients who are strongly suspected of having OSA and who do not have medical comorbidities (eg, heart failure or lung disease)
Thalassemia treatment
α-Thalassemia Mild thalassemia: no treatment needed Moderate disease: folate, avoid oxidative stress Severe disease: Blood transfusions: weekly if severe anemia Iron chelating agents: Deferoxamine - prevents iron overload and removes excess iron Splenectomy in some cases (stops RBC destruction) Bone marrow transplantation is the definitive treatment in major β-Thalassemia Trait (minor): no medical care usually Major Blood transfusions: weekly if severe anemia Iron chelating agents: Deferoxamine - prevents iron overload and removes excess iron Splenectomy in some cases (stops RBC destruction) Bone marrow transplantation is the definitive treatment in major
Thalassemia diagnosis
α-Thalassemia ↓ MCV (microcytic), normal TIBC, normal Ferritin (normal iron stores), a normal to low reticulocyte count and a (+) HgB Electrophoresis. Peripheral smear: target and teardrop cells, basophilic stippling; ↑ RBC count (normal iron stores) ↓ MCV (microcytic) HGB Electrophoresis: normal Hgb ratios in adults with alpha thalassemia β-Thalassemia ↓ MCV (microcytic), normal TIBC, normal Ferritin (normal iron stores), a normal to low reticulocyte count and a (+) HgB Electrophoresis. Peripheral smear: target and teardrop cells, basophilic stippling, nucleated RBCs - suspect thalassemia in patients with microcytosis and normal iron with increased RBC count (similar to iron deficiency anemia but normal iron) HGB Electrophoresis:Trait (minor) ↑ HbA2 or ↑ HgbF ↓ HgbA Major (Cooley's) ↑ HbA2 or ↑ HgbF (up to 90%) little to no HgbA X-rays: skull bossing "hair on end appearance" due to extramedullary hematopoiesis
Vitamin B12 deficiency pearls
↑ MCV (macrocytic) + Hypersegmented neutrophils, neuropathy (loss of proprioception and ↓ vibratory sense), ↑ Methylmalonic acid in early B12 loss Vitamin B12 deficiency can be malabsorptive (ETOH, gastric bypass) but may also be secondary to ↓ intrinsic factor (pernicious anemia) Pernicious anemia + schilling test + ↓ intrinsic factor and parietal cell antibodies Check antibody to intrinsic factor; positive test is confirmatory for Pernicious Anemia, but sensitivity is only 50-70%
Vitamin B12 deficiency diagnosis
↑ MCV (macrocytosis) and Hypersegmented neutrophils on blood smear Normal folate MMA (methylmalonic acid) ↑ Homocysteine ↑
Hemophilia A and B diagnosis
↑ PTT and normal platelet count and function Corrected with mixing studies ⇒ indicates a factor deficiency Note, if PTT does not correct with mixing studies indicates lupus anticoagulant or factor inhibitor Normal PT Normal bleeding time Most specific test: functional assay for factor VIII or IX to confirm the diagnosis of hemophilia and determine its type and severity.
Folate (Vitamin B9) deficiency pearls
↓ Folate, ↑ MCV (macrocytic anemia) There are two megaloblastic macrocytic anemias (folate deficiency and vitamin B12 deficiency). Unlike ↓ vitamin B12, folate deficiency has no neurological symptoms Folate deficiency is common. It may result from inadequate intake, malabsorption, or use of various drugs. Deficiency causes megaloblastic anemia (indistinguishable from that due to vitamin B12 deficiency) Maternal deficiency increases the risk of neural tube birth defects
Iron deficiency pearls
↓ MCV (microcytic), ↑ TIBC, ↓ Ferritin (low iron stores) ↓ MCH (hypochromic) Iron deficiency is the most common cause of anemia and usually results from blood loss In men, the most frequent cause is chronic occult bleeding, usually from the GI tract. In premenopausal women, menstrual blood loss is a common cause Another possible cause of blood loss in men and women is chronic intravascular hemolysis Fatigue with exercise, palpitations, shortness of breath, weakness, headaches, and tinnitus Tachycardia, tachypnea on exertion, pallor, glossitis, angular cheilitis, pica, koilonychia, jaundice, and splenomegaly RBCs tend to be microcytic and hypochromic, and iron stores are low as shown by low serum ferritin and low serum iron levels with high serum total iron binding capacity "Lead poisoning is a common question on the PANCE/PANRE look for Basophilic stippling and remember treatment is with EDTA." Other causes of ↓ MCV include lead poisoning (look for this in a patient with neurological symptoms), sideroblastic anemia, basophilic stippling, and thalassemia. Treatment is with EDTA.
Hemolytic Uremic Syndrome (HUS)
↓ Platelets + anemia + renal failure (associated with E.coli O157: H7 and diarrheal illness in child) Presentation: Suspect HUS if renal failure in children with a prodrome of diarrhea associated with thrombocytopenia on the CBC Look for E. Coli 0157 - children with exposure to E.coli (ground beef)ChildrenSevere kidney problems
