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Hematology Board Review Alice Ma, MD






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    Hematology Board Review Alice Ma, MD Hematology Board Review Alice Ma, MD Presentation Transcript

    • Hematology Board Review Alice Ma, MD Assistant Professor of Medicine Hematology-Oncology June 7, 2007
    • Case 1
      • 68 y.o. woman from Minnesota seen in ER for fatigue, DOE, and episodic dark urine. Dark urine noted following extended periods of time in the cold. No medications
      • PEX. T nl, HR 90, BP 110/75
      • Hgb 7.1, retic count 18%. Normal indices, normal remainder of CBC
      • Lab notes sample appears agglutinated, and clumping of RBCs on smear.
    • Case 1
      • 68 y.o. woman from Minnesota seen in ER for fatigue, DOE, and episodic dark urine . Dark urine noted following extended periods of time in the cold . No medications
      • PEX. T nl, HR 90, BP 110/75
      • Hgb 7.1, retic count 18%. Normal indices, normal remainder of CBC
      • Lab notes sample appears agglutinated, and clumping of RBCs on smear.
    • Case 1
      • Which of the following is the most important study for establishing the diagnosis in this patient?
        • A. Osmotic fragility
        • B. Cold Agglutinin screen
        • C. Serum complement determination
        • D. Sucrose hemolysis test
        • E. G6PD determination
    • Case 1
      • A - No, since this is for hereditary spherocytosis.
      • Buzzwords for HS
        • Recurrent jaundice
        • Early pigment gallstones, cholecystectomy
        • Autosomal dominant, so + FHx
        • Splenomegaly
        • Increased osmotic fragility
    • Case 1
      • B - Cold agglutinin Screen. Yes
      • Buzzwords for cold agglutinin disease:
        • Recurrent hemolysis in the cold
        • RBC clumping on smear
        • DAT (+) for C3/complement, (-) for IgG
        • May follow infection with mycoplasma or mono
        • IgM mediated
        • No benefit from steroids or splenectomy
        • Keep warm
    • Case 1
      • C. Sucrose Hemolysis test. No. This is for PNH
      • Buzzwords for PNH
        • Dark/red urine in early AM
        • May have clots and/or pancytopenia
        • May follow chemo/aplastic anemia
        • Tests:
          • sucrose hemolysis test
          • Acidified serum hemolysis test (Ham’s test)
          • Flow cytometry for CD55/CD59
          • Urine hemosiderin positive
    • Case 1
      • E. G6PD determination
      • Buzzwords for G6PD deficiency
        • African-American or Mediterranean
        • X-linked
        • Hemolysis follows infection or drugs
        • Susceptible to aplastic crisis after parvo
        • Drugs - sulfa/dapsone/antimalarials
        • Heinz bodies (need special stain)
        • Bite cells
      Blister cells
    • More Hemolytic Anemia Buzzwords
      • Warm AIHA
        • Spherocytes
        • Positive DAT, IgG positive, C3 positive
        • Associated with CLL, NHL, SLE
        • Treat with steroids first, splenectomy second.
      • Drug-related AIHA
        • Spherocytes.
        • Positive DAT, usually for C3 only.
    • Case 2
      • 22 y.o. man brought from work to ER for abdominal pain and fever.
      • Two recent episodes of red urine
      • Previously treated for syphilis
      • Works as a butcher’s assistant, unloading refrigerated meat trucks
      • PEx - chronically ill. Nl Temp and BP
    • Case 2
      • 22 y.o. man brought from work to ER for abdominal pain and fever.
      • Two recent episodes of red urine
      • Previously treated for syphilis
      • Works as a butcher’s assistant, unloading refrigerated meat trucks
      • PEx - chronically ill. Nl Temp and BP
    • Case 2
      • Laboratory studies
        • Hgb 4.0
        • WBC nl. Nl diff except for NRBCs
        • Plts nl
        • Rapid Plasma reagin test - positive
        • U/A. Strongly positive for hemoglobin. No intact erythrocytes
    • Case 2
      • Which of the following is the most appropriate diagnostic study for this patient’s hemolytic anemia?
        • A. Donath-Landsteiner test
        • B. Sickle Cell Preparation
        • C. Urine Hemosiderin preparation
        • D. Heinz body preparation
    • Case 2
      • B. Sickle Cell preparation - no
      • U/A shouldn’t be red, may have microscopic hematuria, not hemoglobinuria
      • No association with syphilis
      • Peripheral smear should show sickled cells, especially if pt is quite ill now
    • Case 2
      • C - urine hemosiderin determination. No, since we know that there is hemoglobin in the urine. Urine hemosiderin is useful if there is the suspicion for chronic intravascular hemolysis, as in PNH, valve hemolysis, AAA/aortic dissection hemolysis.
    • Case 2
      • D. Heinz body preparation - no
      • This is useful if there is suspicion for oxidative stress, usually from drugs.
      • bite cell hemolytic anemia
      • Usually G6PD deficiency, but if oxidative stress is bad enough, anyone can get Heinz body hemolytic anemia.
      • African americans with G6PD deficiency can have falsely nl G6PD levels immediately after hemolysis
    • Case 2
      • A - Donath Landsteiner test - correct
      • Paroxymal Cold Hemoglobinuria (PCH)
        • Episodic cold-induced intravascular hemolysis
        • DAT positive only for Complement
        • Seen in pediatrics, also classically with syphilis, now most are idiopathic
        • IgG antibody binds only in the cold, but fixes complement. No spherocytes
        • Special test for DL antibody detection.
    • Case 3
      • 22 y.o. man seen in the ER for red urine and fatigue. 3 days ago, started on TMP-SMZ for UTI.
      • Hbg 6.5 retic 18%
      • Blood smear - polychromatophilia, blister cells
      • G6PD - low normal
    • Case 3
      • In order to confirm the diagnosis, which of the following should be done?
        • A. repeat G6PD determination in 1 month
        • B. perform osmotic fragility test
        • C. perform sucrose hemolysis test
        • D. perform bone marrow aspirate
    • Case 3
      • Two normal forms of enzyme. Most prevalent type is B . 20% of healthy Africans have type A .
      • Deficiency is X-linked.
      • In Africans, mutant protein is A- , which is unstable and loses activity as the red cell ages.
      • Mediterranean variant has baseline low activity
      • Low G6PD activity results in low levels of NADPH and reduced glutathione, which are required to protect hemoglobin from oxidative damage.
    • Case 3
      • Typically, hemolysis can be triggered by drugs or infections.
      • Anemia is maximal 7-10 d after exposure. In individuals with A-, reticulocytosis begins to compensate for the anemia, despite continuation of the drug.
      • Immediately after a hemolytic episode, G6PD levels in the with A- may be normal, since the mature cells have been lysed, and only younger cells with normal G6PD levels, are present. Need to repeat in 1 month
    • Case 3 - blister cells
    • Case 4
        • A 27-year-old woman is referred to you for evaluation of thrombocytopenia, which was discovered incidentally during an evaluation for life insurance.
        • She is healthy, active, and taking no medications.
        • Findings on the history and physical examination are normal.
        • The complete blood count results are normal, except for a platelet count of 72,000/L.
        • The blood chemistry profile is normal, urinalysis is normal, and the test for HIV is negative.
        • Examination of the peripheral blood smear is normal except for the mild thrombocytopenia.
    • Case 4
        • What is the most appropriate management for this patient?
          • (A) Suspect ITP. do no further diagnostic studies other than a repeat complete blood count in 1 month.
          • (B) Suspect ITP; begin prednisone, 1 mg/kg/d
          • (C) Suspect ITP or possibly myelodysplasia; do a bone marrow aspiration and biopsy.
          • (D) Suspect the possibility of lymphoma; do a CT of the chest and abdomen for lymphadenopathy.
      • (E) Doubt the history and suspect alcoholism; do a liver and spleen ultrasonography.
    • Case 4
      • In the absence of any gold standard tests to diagnose ITP, the diagnosis can only be based on the observation of thrombocytopenia without other hematologic abnormalities.
      • Also, recognize that the goal for treatment of ITP is only to prevent bleeding, which is not an issue in this woman with mild thrombocytopenia.
    • Case 4
      • Prednisone therapy
        • the initial choice for adults with ITP
        • does not induce a cure
        • may only provide a temporary remission or provide symptomatic relief until a spontaneous remission occurs.
      • Therefore, prednisone is not indicated in the absence of thrombocytopenia that poses no hemostatic risk.
      • Prednisone may be appropriate if the platelet count is less than 20,000 to 30,000/L.
    • Case 4
      • When there are no other hematologic abnormalities on routine CBC and on peripheral blood smear, examination of the bone marrow does not provide additional important information.
      • It is unnecessary to routinely do a bone marrow examination in the evaluation of a patient with suspected ITP.
      • If pt were older or had abnormal counts other than plts, marrow exam may have been appropriate.
    • Case 4
      • Other etiologies for thrombocytopenia such as occult liver disease with hypersplenism or occult lymphoma may be considered, but in the absence of a suggestive history or physical examination, these possibilities warrant no further diagnostic evaluation.
      • Alcohol excess itself may cause thrombocytopenia due to marrow suppression.
    • Case 5
        • A 76-year-old man presents to the emergency department with numerous ecchymoses and bleeding from the gums.
        • He has been previously well, and he takes no medications.
        • There is a history of uncomplicated appendectomy and cholecystectomy.
        • On physical examination, he has extensive bruising, and there is oozing from intravenous puncture sites. In addition, he has a swollen, painful left knee.
    • Case 5
        • Laboratory studies:
              • Platelet count 264,000/  L
              • Activated partial 112 sec thromboplastin time
              • Prothrombin time 11 sec
              • Plasma fibrinogen 2.4 g/L
        • A 1:1 mix of patient and normal plasma does not correct the prolonged activated partial thromboplastin time.
        • The patient had an activated partial thromboplastin time of 28 seconds at the time of his appendectomy 12 years ago.
    • Case 5
        • The most likely cause of this patient’s coagulopathy is:
          • (A) Disseminated intravascular coagulation
          • (B) A lupus anticoagulant
          • (C) Factor XII deficiency
          • (D) Acquired prothrombin inhibitor
          • (E) Acquired factor VIII inhibitor
    • Case 5
      • The patient has an acquired coagulation disorder that is associated with bleeding.
      • Although disseminated intravascular coagulation (DIC) is associated with prolongation of the activated partial thromboplastin time, this diagnosis is unlikely given the normal platelet count, prothrombin time and fibrinogen level. Also there is no associated systemic illness that could provoke DIC.
      • Factor XII deficiency is ruled out by the presence of bleeding, because factor XII deficiency does not cause bleeding.
    • Case 5
      • Lupus anticoagulants are not associated with hemorrhage unless there is associated deficiency of prothrombin. This possibility is excluded by the normal PT; the normal PT rules out an acquired prothrombin inhibitor.
      • Therefore, the most likely diagnosis is an acquired inhibitor against factor VIII.
    • Case 5
      • Acquired inhibitors against factor VIII are uncommon. They can occur post partum or in association with lymphoproliferative diseases or autoimmune disorders. They also can occur without any associated condition.
      • Patients frequently present with massive bleeding.
      • Treatment is aimed at 1) bypassing the inhibitor by using factor VIIa, porcine factor VIII (provided that the inhibitor does not cross-react), or activated prothrombin complex concentrates; and 2) lowering the antibody levels using plasmapheresis or immunosuppression.
      • Postpartum factor VIII inhibitors will often resolve spontaneously.
    • Case 6
        • A previously healthy 50-year-old man is admitted to the hospital with a 2-week history of fatigue and dyspnea.
        • He is currently taking propranolol, clonidine, and ranitidine for hyper-tension and peptic ulcer.
        • Physical examination, including blood pressure, is normal. He is mentally alert.
    • Case 6
        • Laboratory evaluation:
          • Hgb 4.6 g/dL, Hct 14%, WBC 10,800/L, normal differential, Plts 21K.
          • Cre 0.8 mg/dL, T bili 2.8 mg/dL, Dbili 0.4 mg/dl, LDH 2463 U/L.
        • Examination of the blood smear shows fragmented erythrocytes and polychromatophilia.
        • The direct antiglobulin test is negative.
        • Coagulation studies (prothrombin time, activated partial thromboplastin time, and fibrinogen) are normal.
    • Case 6
        • What is the most appropriate management for this patient?
          • (A) Suspect TTP and initiate plasma exchange therapy.
          • (B) Suspect autoimmune thrombocytopenia and hemolytic anemia (Evans syndrome), and initiate prednisone treatment, 1 mg/kg per day.
          • (C) Suspect disseminated carcinoma, and initiate a workup that includes chest radiographs, bone marrow examination, and abdominal CT scan.
          • (D) Suspect drug-induced thrombocytopenia and hemolytic anemia, and discontinue the three medications he is taking.
          • (E) Suspect pernicious anemia, and do a bone marrow evaluation to confirm megaloblastic hematopoiesis.
    • Case 6
      • The answer is A - even though the patient does not have renal manifestations, neurologic symptoms, or fever, he does have microangiopathic hemolytic anemia and thrombocytopenia. Moreover, he is not in DIC, since his PT/PTT are normal. Recognize that not every patient with TTP will have “the pentad” at the time of presentation, though many will have all symptoms--shortly before dying!!
    • Case 7
        • A 65-year-old man underwent bilateral knee replacement surgery 5 days ago.
        • His mobilization has been slow because of persistent pain, and he is only now getting up in a chair.
        • Because of a previous history of acute proximal venous thrombosis complicating a cholecystectomy 8 years ago, he has been given subcutaneous heparin three times daily in doses sufficient to achieve an activated partial thromboplastin time of 35 sec.
    • Case 7
      • There are no clinical signs of fresh hemorrhage although ecchymoses and hematomas from the first ICU day are still evident.
      • There are no signs of hemorrhage from mucous membranes, needle stick sites, or tubes.
      • The hemoglobin is 12.5 Gm/dl, the white blood count is 4,500/ micro liter, no fragmented cells are seen, no platelet clumping is noted on the peripheral blood smear, the BUN is 35, the creatinine 1.6, the LDH is 180 (normal 84 - 197).
    • Case 7
        • The most likely cause of the thrombocytopenia is:
          • (A) Ranitidine
          • (B) Sepsis
          • (C) Heparin
          • (D) Crystalloid given during surgery
          • (E) None of the above
    • Case 7
        • The best management approach for the patient is:
          • (A) Stop the ranitidine because it is the cause of the thrombocytopenia.
          • (B) Obtain blood cultures, and culture any drainage from the left knee incision before starting antibiotic therapy.
          • (C) Stop the heparin.
          • (D) Send serum and plasma for studies to exclude heparin-induced thrombocytopenia; continue the heparin until the results are available.
          • (E) Continue heparin, but follow the platelet count daily and give platelet transfusions if the count falls below 20,000/L.
    • Case 7
      • The answers are c) and c). This patient has HIT, unless proven otherwise. Need to stop the heparin--may need to start alternate anticoagulation. Remember that 30-50% of pts with HIT will go on to develop thrombosis, so stop the heparin, then send off tests!!
      • Ranitidine is blamed too much for thrombocytopenia, but it’s easy enough to stop.
    • Case 8
      • You are asked to provide a consultation for a 22 year old man with thrombocytopenia.
      • He was admitted to the ICU following a motorcycle accident in which he sustained head trauma, a ruptured spleen, two fractured ribs, and a fractured pelvis.
      • On the fourth ICU day the platelet count is reported to be 2,000
    • Case 8
          • Which of the following is the most likely diagnosis?
            • A. Disseminated intravascular coagulation
            • B. Post-splenectomy thrombocytopenia.
            • C. Thrombotic thrombocytopenic purpura
            • D. Pseudothrombocytopenia.
    • Case 8
      • Remember that multiple trauma predisposes to DIC. The answer is A
    • Case 9
      • A 62 y.o man presents for evaluation of elevated cholesterol from health fair screening. No PMHx, No meds, no FHx. Non-smoker. Pex unremarkable, including normal vital signs, no nodes, no HSM.
      • CBC shows Hgb 14.2, Plts 300, but WBC 290.
      • Diff 1% neutrophils, 99% lymphocytes.
      • Peripheral smear shown
    • Copyright ©2003 American Society of Hematology. Copyright restrictions may apply. Maslak, P. ASH Image Bank 2003;2003:100690 Case 9 peripheral smear
    • Case 9
      • Flow cytopmetry of peripheral blood shows a monoclonal population of mature B cells. What is the next most appropriate step?
        • Observation
        • Bone marrow biopsy
        • Refer for treatment with fludarabine
        • Refer for treatment with rituximab
        • Begin prednisone
    • Case 9- Answer
      • This patient has CLL. CLL is staged using the Rai system, where
        • Stage 0 - lymphocytosis only
        • Stage 1 - adenopathy
        • Stage 2 - HSM
        • Stage 3 - anemia (not AIHA)
        • Stage 4 - thrombocytopenia
      • Patients need treatment only for anemia or thrombocytopenia or for symptomatic adenopathy.
      • Treatment does not affect mortality.
    • Case 9 - other facts
      • Patients with CLL can develop AIHA (30% risk over the lifetime of disease) or ITP (5-10%)
      • Pts with CLL are at increased risk for solid tumors (lung, breast, gastric)
    • Case 10
      • A 25 y.o. man is referred to you for evaluation of high WBC found on routine testing. PMHx, FHx negative. SHx- he is a marine and just returned from Iraq PEx shows no hepatomegaly, but a spleen tip is palpable in the LUQ
      • His CBC shows: Hgb 14.1 gm WBC 250,000/ul. Platelet count 217,000/ul.
      • The differential shows 50% segs, 18%bands, 16% lymphs, 4% monos, 2% eos, 4% basos, 4% metamyelocytes, 2% myelocytes, rare promyelocytes and blasts.
      • The peripheral smear is shown.
    • Copyright ©2004 American Society of Hematology. Copyright restrictions may apply. Maslak, P. ASH Image Bank 2004;2004:101019 Case 10 peripheral smear
    • Case 10
      • Which of the following best represents the patient’s likely cytogenetic abnormality
        • A. t(15;17)
        • B. t(8;14)
        • C. t(16;16)
        • D. t(9;22)
        • E. t(4;11)