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Hematology Board Review Alice Ma, MD

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  • 1. Hematology Board ReviewHematology Board Review Alice Ma, MDAlice Ma, MD Assistant Professor of MedicineAssistant Professor of Medicine Hematology-OncologyHematology-Oncology June 7, 2007June 7, 2007
  • 2. Case 1Case 1 • 68 y.o. woman from Minnesota seen68 y.o. woman from Minnesota seen in ER for fatigue, DOE, and episodicin ER for fatigue, DOE, and episodic dark urine. Dark urine noteddark urine. Dark urine noted following extended periods of time infollowing extended periods of time in the cold. No medicationsthe cold. No medications • PEX. T nl, HR 90, BP 110/75PEX. T nl, HR 90, BP 110/75 • Hgb 7.1, retic count 18%. NormalHgb 7.1, retic count 18%. Normal indices, normal remainder of CBCindices, normal remainder of CBC • Lab notes sample appearsLab notes sample appears agglutinated, and clumping of RBCsagglutinated, and clumping of RBCs on smear.on smear.
  • 3. Case 1Case 1 • 68 y.o. woman from68 y.o. woman from MinnesotaMinnesota seenseen in ER for fatigue, DOE, andin ER for fatigue, DOE, and episodicepisodic dark urinedark urine. Dark urine noted. Dark urine noted following extended periods of time infollowing extended periods of time in the coldthe cold. No medications. No medications • PEX. T nl, HR 90, BP 110/75PEX. T nl, HR 90, BP 110/75 • Hgb 7.1,Hgb 7.1, retic count 18%.retic count 18%. NormalNormal indices, normal remainder of CBCindices, normal remainder of CBC • Lab notesLab notes sample appearssample appears agglutinated, and clumping of RBCsagglutinated, and clumping of RBCs on smear.on smear.
  • 4. Case 1Case 1 • Which of the following is the mostWhich of the following is the most important study for establishing theimportant study for establishing the diagnosis in this patient?diagnosis in this patient? – A. Osmotic fragilityA. Osmotic fragility – B. Cold Agglutinin screenB. Cold Agglutinin screen – C. Serum complement determinationC. Serum complement determination – D. Sucrose hemolysis testD. Sucrose hemolysis test – E. G6PD determinationE. G6PD determination
  • 5. Case 1Case 1 • A - No, since this is for hereditaryA - No, since this is for hereditary spherocytosis.spherocytosis. • Buzzwords for HSBuzzwords for HS – Recurrent jaundiceRecurrent jaundice – Early pigment gallstones, cholecystectomyEarly pigment gallstones, cholecystectomy – Autosomal dominant, so + FHxAutosomal dominant, so + FHx – SplenomegalySplenomegaly – Increased osmotic fragilityIncreased osmotic fragility
  • 6. Case 1Case 1 • B - Cold agglutinin Screen. YesB - Cold agglutinin Screen. Yes • Buzzwords for cold agglutinin disease:Buzzwords for cold agglutinin disease: – Recurrent hemolysis in the coldRecurrent hemolysis in the cold – RBC clumping on smearRBC clumping on smear – DAT (+) for C3/complement, (-) for IgGDAT (+) for C3/complement, (-) for IgG – May follow infection with mycoplasmaMay follow infection with mycoplasma or monoor mono – IgM mediatedIgM mediated – No benefit from steroids or splenectomyNo benefit from steroids or splenectomy – Keep warmKeep warm
  • 7. Case 1Case 1 • C. Sucrose Hemolysis test. No. ThisC. Sucrose Hemolysis test. No. This is for PNHis for PNH • Buzzwords for PNHBuzzwords for PNH – Dark/red urine in early AMDark/red urine in early AM – May have clots and/or pancytopeniaMay have clots and/or pancytopenia – May follow chemo/aplastic anemiaMay follow chemo/aplastic anemia – Tests:Tests: • sucrose hemolysis testsucrose hemolysis test • Acidified serum hemolysis test (Ham’s test)Acidified serum hemolysis test (Ham’s test) • Flow cytometry for CD55/CD59Flow cytometry for CD55/CD59 • Urine hemosiderin positiveUrine hemosiderin positive
  • 8. Case 1Case 1 • E. G6PD determinationE. G6PD determination • Buzzwords for G6PD deficiencyBuzzwords for G6PD deficiency – African-American or MediterraneanAfrican-American or Mediterranean – X-linkedX-linked – Hemolysis follows infection or drugsHemolysis follows infection or drugs – Susceptible to aplastic crisis after parvoSusceptible to aplastic crisis after parvo – Drugs - sulfa/dapsone/antimalarialsDrugs - sulfa/dapsone/antimalarials – Heinz bodies (need special stain)Heinz bodies (need special stain) – Bite cellsBite cells Blister cellsBlister cells
  • 9. More Hemolytic Anemia BuzzwordsMore Hemolytic Anemia Buzzwords • Warm AIHAWarm AIHA – SpherocytesSpherocytes – Positive DAT, IgG positive, C3 positivePositive DAT, IgG positive, C3 positive – Associated with CLL, NHL, SLEAssociated with CLL, NHL, SLE – Treat with steroids first, splenectomyTreat with steroids first, splenectomy second.second. • Drug-related AIHADrug-related AIHA – Spherocytes.Spherocytes. – Positive DAT, usually for C3 only.Positive DAT, usually for C3 only.
  • 10. Case 2Case 2 • 22 y.o. man brought from work to ER22 y.o. man brought from work to ER for abdominal pain and fever.for abdominal pain and fever. • Two recent episodes of red urineTwo recent episodes of red urine • Previously treated for syphilisPreviously treated for syphilis • Works as a butcher’s assistant,Works as a butcher’s assistant, unloading refrigerated meat trucksunloading refrigerated meat trucks • PEx - chronically ill. Nl Temp and BPPEx - chronically ill. Nl Temp and BP
  • 11. Case 2Case 2 • 22 y.o. man brought from work to ER22 y.o. man brought from work to ER for abdominal pain and fever.for abdominal pain and fever. • TwoTwo recent episodes ofrecent episodes of red urinered urine • Previously treated forPreviously treated for syphilissyphilis • Works as a butcher’s assistant,Works as a butcher’s assistant, unloadingunloading refrigeratedrefrigerated meat trucksmeat trucks • PEx - chronically ill. Nl Temp and BPPEx - chronically ill. Nl Temp and BP
  • 12. Case 2Case 2 • Laboratory studiesLaboratory studies – Hgb 4.0Hgb 4.0 – WBC nl. Nl diff except for NRBCsWBC nl. Nl diff except for NRBCs – Plts nlPlts nl – Rapid Plasma reagin test - positiveRapid Plasma reagin test - positive – U/A. Strongly positive for hemoglobin.U/A. Strongly positive for hemoglobin. No intact erythrocytesNo intact erythrocytes
  • 13. Case 2Case 2 • Which of the following is the mostWhich of the following is the most appropriate diagnostic study for thisappropriate diagnostic study for this patient’s hemolytic anemia?patient’s hemolytic anemia? – A. Donath-Landsteiner testA. Donath-Landsteiner test – B. Sickle Cell PreparationB. Sickle Cell Preparation – C. Urine Hemosiderin preparationC. Urine Hemosiderin preparation – D. Heinz body preparationD. Heinz body preparation
  • 14. Case 2Case 2 • B. Sickle Cell preparation - noB. Sickle Cell preparation - no • U/A shouldn’t be red, may haveU/A shouldn’t be red, may have microscopic hematuria, notmicroscopic hematuria, not hemoglobinuriahemoglobinuria • No association with syphilisNo association with syphilis • Peripheral smear should showPeripheral smear should show sickled cells, especially if pt is quitesickled cells, especially if pt is quite ill nowill now
  • 15. Case 2Case 2 • C - urine hemosiderin determination.C - urine hemosiderin determination. No, since we know that there isNo, since we know that there is hemoglobin in the urine. Urinehemoglobin in the urine. Urine hemosiderin is useful if there is thehemosiderin is useful if there is the suspicion for chronic intravascularsuspicion for chronic intravascular hemolysis, as in PNH, valvehemolysis, as in PNH, valve hemolysis, AAA/aortic dissectionhemolysis, AAA/aortic dissection hemolysis.hemolysis.
  • 16. Case 2Case 2 • D. Heinz body preparation - noD. Heinz body preparation - no • This is useful if there is suspicion forThis is useful if there is suspicion for oxidative stress, usually from drugs.oxidative stress, usually from drugs. • bite cell hemolytic anemiabite cell hemolytic anemia • Usually G6PD deficiency, but ifUsually G6PD deficiency, but if oxidative stress is bad enough,oxidative stress is bad enough, anyone can get Heinz bodyanyone can get Heinz body hemolytic anemia.hemolytic anemia. • African americans with G6PDAfrican americans with G6PD deficiency can have falsely nl G6PDdeficiency can have falsely nl G6PD levels immediately after hemolysislevels immediately after hemolysis
  • 17. Case 2Case 2 • A - Donath Landsteiner test - correctA - Donath Landsteiner test - correct • Paroxymal Cold HemoglobinuriaParoxymal Cold Hemoglobinuria (PCH)(PCH) – Episodic cold-induced intravascularEpisodic cold-induced intravascular hemolysishemolysis – DAT positive only for ComplementDAT positive only for Complement – Seen in pediatrics, also classically withSeen in pediatrics, also classically with syphilis, now most are idiopathicsyphilis, now most are idiopathic – IgG antibody binds only in the cold, butIgG antibody binds only in the cold, but fixes complement. No spherocytesfixes complement. No spherocytes – Special test for DL antibody detection.Special test for DL antibody detection.
  • 18. Case 3Case 3 • 22 y.o. man seen in the ER for red22 y.o. man seen in the ER for red urine and fatigue. 3 days ago,urine and fatigue. 3 days ago, started on TMP-SMZ for UTI.started on TMP-SMZ for UTI. • Hbg 6.5 retic 18%Hbg 6.5 retic 18% • Blood smear - polychromatophilia,Blood smear - polychromatophilia, blister cellsblister cells • G6PD - low normalG6PD - low normal
  • 19. Case 3Case 3 • In order to confirm the diagnosis,In order to confirm the diagnosis, which of the following should bewhich of the following should be done?done? – A. repeat G6PD determination in 1A. repeat G6PD determination in 1 monthmonth – B. perform osmotic fragility testB. perform osmotic fragility test – C. perform sucrose hemolysis testC. perform sucrose hemolysis test – D. perform bone marrow aspirateD. perform bone marrow aspirate
  • 20. Case 3Case 3 • Two normal forms of enzyme. MostTwo normal forms of enzyme. Most prevalent type isprevalent type is BB. 20% of healthy. 20% of healthy Africans have typeAfricans have type AA.. • Deficiency is X-linked.Deficiency is X-linked. • In Africans, mutant protein isIn Africans, mutant protein is A-A-, which is, which is unstable and loses activity as the red cellunstable and loses activity as the red cell ages.ages. • Mediterranean variant has baseline lowMediterranean variant has baseline low activityactivity • Low G6PD activity results in low levels ofLow G6PD activity results in low levels of NADPH and reduced glutathione, whichNADPH and reduced glutathione, which are required to protect hemoglobin fromare required to protect hemoglobin from oxidative damage.oxidative damage.
  • 21. Case 3Case 3 • Typically, hemolysis can be triggered byTypically, hemolysis can be triggered by drugs or infections.drugs or infections. • Anemia is maximal 7-10 d after exposure.Anemia is maximal 7-10 d after exposure. In individuals with A-, reticulocytosisIn individuals with A-, reticulocytosis begins to compensate for the anemia,begins to compensate for the anemia, despite continuation of the drug.despite continuation of the drug. • Immediately after a hemolytic episode,Immediately after a hemolytic episode, G6PD levels in the with A- may be normal,G6PD levels in the with A- may be normal, since the mature cells have been lysed,since the mature cells have been lysed, and only younger cells with normal G6PDand only younger cells with normal G6PD levels, are present. Need to repeat in 1levels, are present. Need to repeat in 1 monthmonth
  • 22. Case 3 - blister cellsCase 3 - blister cells
  • 23. Case 4Case 4 • A 27-year-old woman is referred to you forA 27-year-old woman is referred to you for evaluation of thrombocytopenia, which wasevaluation of thrombocytopenia, which was discovered incidentally during an evaluation for lifediscovered incidentally during an evaluation for life insurance.insurance. • She is healthy, active, and taking no medications.She is healthy, active, and taking no medications. • Findings on the history and physical examinationFindings on the history and physical examination are normal.are normal. • The complete blood count results are normal,The complete blood count results are normal, except for a platelet count of 72,000/L.except for a platelet count of 72,000/L. • The blood chemistry profile is normal, urinalysis isThe blood chemistry profile is normal, urinalysis is normal, and the test for HIV is negative.normal, and the test for HIV is negative. • Examination of the peripheral blood smear isExamination of the peripheral blood smear is normal except for the mild thrombocytopenia.normal except for the mild thrombocytopenia.
  • 24. Case 4Case 4 • What is the most appropriate management for thisWhat is the most appropriate management for this patient?patient? (A)(A) Suspect ITP. do no further diagnosticSuspect ITP. do no further diagnostic studies other than a repeat completestudies other than a repeat complete blood count in 1 month.blood count in 1 month. (B)(B) Suspect ITP; begin prednisone, 1 mg/kg/dSuspect ITP; begin prednisone, 1 mg/kg/d (C)(C) Suspect ITP or possibly myelodysplasia;Suspect ITP or possibly myelodysplasia; do a bone marrow aspiration and biopsy.do a bone marrow aspiration and biopsy. (D)(D) Suspect the possibility of lymphoma; do aSuspect the possibility of lymphoma; do a CT of the chest and abdomen forCT of the chest and abdomen for lymphadenopathy.lymphadenopathy. (E)(E) Doubt the history and suspect alcoholism;Doubt the history and suspect alcoholism; do a liver and spleen ultrasonography.do a liver and spleen ultrasonography.
  • 25. Case 4Case 4 • In the absence of any gold standardIn the absence of any gold standard tests to diagnose ITP, the diagnosistests to diagnose ITP, the diagnosis can only be based on thecan only be based on the observation of thrombocytopeniaobservation of thrombocytopenia without other hematologicwithout other hematologic abnormalities.abnormalities. • Also, recognize that the goal forAlso, recognize that the goal for treatment of ITP is only to preventtreatment of ITP is only to prevent bleeding, which is not an issue inbleeding, which is not an issue in this woman with mildthis woman with mild thrombocytopenia.thrombocytopenia.
  • 26. Case 4Case 4 • Prednisone therapyPrednisone therapy – the initial choice for adults with ITPthe initial choice for adults with ITP – does not induce a curedoes not induce a cure – may only provide a temporary remission ormay only provide a temporary remission or provide symptomatic relief until a spontaneousprovide symptomatic relief until a spontaneous remission occurs.remission occurs. • Therefore, prednisone is not indicated inTherefore, prednisone is not indicated in the absence of thrombocytopenia thatthe absence of thrombocytopenia that poses no hemostatic risk.poses no hemostatic risk. • Prednisone may be appropriate if thePrednisone may be appropriate if the platelet count is less than 20,000 toplatelet count is less than 20,000 to 30,000/L.30,000/L.
  • 27. Case 4Case 4 • When there are no other hematologicWhen there are no other hematologic abnormalities on routine CBC and onabnormalities on routine CBC and on peripheral blood smear, examination of theperipheral blood smear, examination of the bone marrow does not provide additionalbone marrow does not provide additional important information.important information. • It is unnecessary to routinely do a boneIt is unnecessary to routinely do a bone marrow examination in the evaluation of amarrow examination in the evaluation of a patient with suspected ITP.patient with suspected ITP. • If pt were older or had abnormal countsIf pt were older or had abnormal counts other than plts, marrow exam may haveother than plts, marrow exam may have been appropriate.been appropriate.
  • 28. Case 4Case 4 • Other etiologies for thrombocytopeniaOther etiologies for thrombocytopenia such as occult liver disease withsuch as occult liver disease with hypersplenism or occult lymphoma mayhypersplenism or occult lymphoma may be considered, but in the absence of abe considered, but in the absence of a suggestive history or physicalsuggestive history or physical examination, these possibilities warrantexamination, these possibilities warrant no further diagnostic evaluation.no further diagnostic evaluation. • Alcohol excess itself may causeAlcohol excess itself may cause thrombocytopenia due to marrowthrombocytopenia due to marrow suppression.suppression.
  • 29. Case 5Case 5 • A 76-year-old man presents to the emergencyA 76-year-old man presents to the emergency department with numerous ecchymoses anddepartment with numerous ecchymoses and bleeding from the gums.bleeding from the gums. • He has been previously well, and he takes noHe has been previously well, and he takes no medications.medications. • There is a history of uncomplicatedThere is a history of uncomplicated appendectomy and cholecystectomy.appendectomy and cholecystectomy. • On physical examination, he has extensiveOn physical examination, he has extensive bruising, and there is oozing from intravenousbruising, and there is oozing from intravenous puncture sites. In addition, he has a swollen,puncture sites. In addition, he has a swollen, painful left knee.painful left knee.
  • 30. Case 5Case 5 • Laboratory studies:Laboratory studies: • Platelet countPlatelet count 264,000/264,000/µµLL • Activated partialActivated partial 112 sec112 sec thromboplastin timethromboplastin time • Prothrombin timeProthrombin time 11 sec11 sec • Plasma fibrinogenPlasma fibrinogen 2.4 g/L2.4 g/L • A 1:1 mix of patient and normal plasma doesA 1:1 mix of patient and normal plasma does not correct the prolonged activated partialnot correct the prolonged activated partial thromboplastin time.thromboplastin time. • The patient had an activated partialThe patient had an activated partial thromboplastin time of 28 seconds at the timethromboplastin time of 28 seconds at the time of his appendectomy 12 years ago.of his appendectomy 12 years ago.
  • 31. Case 5Case 5 The most likely cause of this patient’sThe most likely cause of this patient’s coagulopathy is:coagulopathy is: (A)(A) Disseminated intravascular coagulationDisseminated intravascular coagulation (B)(B) A lupus anticoagulantA lupus anticoagulant (C)(C) Factor XII deficiencyFactor XII deficiency (D)(D) Acquired prothrombin inhibitorAcquired prothrombin inhibitor (E)(E) Acquired factor VIII inhibitorAcquired factor VIII inhibitor
  • 32. Case 5Case 5 • The patient has an acquired coagulationThe patient has an acquired coagulation disorder that is associated with bleeding.disorder that is associated with bleeding. • Although disseminated intravascularAlthough disseminated intravascular coagulation (DIC) is associated withcoagulation (DIC) is associated with prolongation of the activated partialprolongation of the activated partial thromboplastin time, this diagnosis isthromboplastin time, this diagnosis is unlikely given the normal platelet count,unlikely given the normal platelet count, prothrombin time and fibrinogen level.prothrombin time and fibrinogen level. Also there is no associated systemicAlso there is no associated systemic illness that could provoke DIC.illness that could provoke DIC. • Factor XII deficiency is ruled out by theFactor XII deficiency is ruled out by the presence of bleeding, because factor XIIpresence of bleeding, because factor XII deficiency does not cause bleeding.deficiency does not cause bleeding.
  • 33. Case 5Case 5 • Lupus anticoagulants are notLupus anticoagulants are not associated with hemorrhage unlessassociated with hemorrhage unless there is associated deficiency ofthere is associated deficiency of prothrombin. This possibility isprothrombin. This possibility is excluded by the normal PT; theexcluded by the normal PT; the normal PT rules out an acquirednormal PT rules out an acquired prothrombin inhibitor.prothrombin inhibitor. • Therefore, the most likely diagnosisTherefore, the most likely diagnosis is an acquired inhibitor againstis an acquired inhibitor against factor VIII.factor VIII.
  • 34. Case 5Case 5 • Acquired inhibitors against factor VIII areAcquired inhibitors against factor VIII are uncommon. They can occur post partum or inuncommon. They can occur post partum or in association with lymphoproliferative diseases orassociation with lymphoproliferative diseases or autoimmune disorders. They also can occurautoimmune disorders. They also can occur without any associated condition.without any associated condition. • Patients frequently present with massivePatients frequently present with massive bleeding.bleeding. • Treatment is aimed at 1) bypassing the inhibitorTreatment is aimed at 1) bypassing the inhibitor by using factor VIIa, porcine factor VIII (providedby using factor VIIa, porcine factor VIII (provided that the inhibitor does not cross-react), orthat the inhibitor does not cross-react), or activated prothrombin complex concentrates;activated prothrombin complex concentrates; and 2) lowering the antibody levels usingand 2) lowering the antibody levels using plasmapheresis or immunosuppression.plasmapheresis or immunosuppression. • Postpartum factor VIII inhibitors will often resolvePostpartum factor VIII inhibitors will often resolve spontaneously.spontaneously.
  • 35. Case 6Case 6 • A previously healthy 50-year-old man is admitted toA previously healthy 50-year-old man is admitted to the hospital with a 2-week history of fatigue andthe hospital with a 2-week history of fatigue and dyspnea.dyspnea. • He is currently taking propranolol, clonidine, andHe is currently taking propranolol, clonidine, and ranitidine for hyper-tension and peptic ulcer.ranitidine for hyper-tension and peptic ulcer. • Physical examination, including blood pressure, isPhysical examination, including blood pressure, is normal. He is mentally alert.normal. He is mentally alert.
  • 36. Case 6Case 6 • Laboratory evaluation:Laboratory evaluation: • Hgb 4.6 g/dL, Hct 14%, WBC 10,800/L, normalHgb 4.6 g/dL, Hct 14%, WBC 10,800/L, normal differential, Plts 21K.differential, Plts 21K. • Cre 0.8 mg/dL, T bili 2.8 mg/dL, Dbili 0.4 mg/dl,Cre 0.8 mg/dL, T bili 2.8 mg/dL, Dbili 0.4 mg/dl, LDH 2463 U/L.LDH 2463 U/L. • Examination of the blood smear showsExamination of the blood smear shows fragmented erythrocytes andfragmented erythrocytes and polychromatophilia.polychromatophilia. • The direct antiglobulin test is negative.The direct antiglobulin test is negative. • Coagulation studies (prothrombin time,Coagulation studies (prothrombin time, activated partial thromboplastin time, andactivated partial thromboplastin time, and fibrinogen) are normal.fibrinogen) are normal.
  • 37. Case 6Case 6 What is the most appropriate management forWhat is the most appropriate management for this patient?this patient? (A)(A) Suspect TTP and initiate plasma exchangeSuspect TTP and initiate plasma exchange therapy.therapy. (B)(B) Suspect autoimmune thrombocytopenia andSuspect autoimmune thrombocytopenia and hemolytic anemia (Evans syndrome), and initiatehemolytic anemia (Evans syndrome), and initiate prednisone treatment, 1 mg/kg per day.prednisone treatment, 1 mg/kg per day. (C)(C) Suspect disseminated carcinoma, and initiate aSuspect disseminated carcinoma, and initiate a workup that includes chest radiographs, boneworkup that includes chest radiographs, bone marrow examination, and abdominal CT scan.marrow examination, and abdominal CT scan. (D)(D) Suspect drug-induced thrombocytopenia andSuspect drug-induced thrombocytopenia and hemolytic anemia, and discontinue the threehemolytic anemia, and discontinue the three medications he is taking.medications he is taking. (E)(E) Suspect pernicious anemia, and do a boneSuspect pernicious anemia, and do a bone marrow evaluation to confirm megaloblasticmarrow evaluation to confirm megaloblastic hematopoiesis.hematopoiesis.
  • 38. Case 6Case 6 • The answer is A - even though theThe answer is A - even though the patient does not have renalpatient does not have renal manifestations, neurologicmanifestations, neurologic symptoms, or fever, he does havesymptoms, or fever, he does have microangiopathic hemolytic anemiamicroangiopathic hemolytic anemia and thrombocytopenia. Moreover,and thrombocytopenia. Moreover, he is not in DIC, since his PT/PTT arehe is not in DIC, since his PT/PTT are normal. Recognize that not everynormal. Recognize that not every patient with TTP will have “thepatient with TTP will have “the pentad” at the time of presentation,pentad” at the time of presentation, though many will have allthough many will have all symptoms--shortly before dying!!symptoms--shortly before dying!!
  • 39. Case 7Case 7 • A 65-year-old man underwent bilateralA 65-year-old man underwent bilateral knee replacement surgery 5 days ago.knee replacement surgery 5 days ago. • His mobilization has been slow because ofHis mobilization has been slow because of persistent pain, and he is only now gettingpersistent pain, and he is only now getting up in a chair.up in a chair. • Because of a previous history of acuteBecause of a previous history of acute proximal venous thrombosis complicatingproximal venous thrombosis complicating a cholecystectomy 8 years ago, he hasa cholecystectomy 8 years ago, he has been given subcutaneous heparin threebeen given subcutaneous heparin three times daily in doses sufficient to achievetimes daily in doses sufficient to achieve an activated partial thromboplastin time ofan activated partial thromboplastin time of 35 sec.35 sec.
  • 40. Case 7Case 7 • There are no clinical signs of freshThere are no clinical signs of fresh hemorrhage although ecchymoses andhemorrhage although ecchymoses and hematomas from the first ICU day are stillhematomas from the first ICU day are still evident.evident. • There are no signs of hemorrhage fromThere are no signs of hemorrhage from mucous membranes, needle stick sites, ormucous membranes, needle stick sites, or tubes.tubes. • The hemoglobin is 12.5 Gm/dl, the whiteThe hemoglobin is 12.5 Gm/dl, the white blood count is 4,500/ micro liter, noblood count is 4,500/ micro liter, no fragmented cells are seen, no plateletfragmented cells are seen, no platelet clumping is noted on the peripheral bloodclumping is noted on the peripheral blood smear, the BUN is 35, the creatinine 1.6,smear, the BUN is 35, the creatinine 1.6, the LDH is 180 (normal 84 - 197).the LDH is 180 (normal 84 - 197).
  • 41. Case 7Case 7 – The most likely cause of theThe most likely cause of the thrombocytopenia is:thrombocytopenia is: • (A)(A) RanitidineRanitidine • (B)(B) SepsisSepsis • (C)(C) HeparinHeparin • (D)(D) Crystalloid given during surgeryCrystalloid given during surgery • (E)(E) None of the aboveNone of the above
  • 42. Case 7Case 7 The best management approach for the patient is:The best management approach for the patient is: (A)(A) Stop the ranitidine because it is theStop the ranitidine because it is the cause of the thrombocytopenia.cause of the thrombocytopenia. (B)(B) Obtain blood cultures, and culture anyObtain blood cultures, and culture any drainage from the left knee incisiondrainage from the left knee incision before starting antibiotic therapy.before starting antibiotic therapy. (C)(C) Stop the heparin.Stop the heparin. (D)(D) Send serum and plasma for studies toSend serum and plasma for studies to exclude heparin-inducedexclude heparin-induced thrombocytopenia; continue thethrombocytopenia; continue the heparin until the results are available.heparin until the results are available. (E)(E) Continue heparin, but follow theContinue heparin, but follow the platelet count daily and give plateletplatelet count daily and give platelet transfusions if the count falls belowtransfusions if the count falls below 20,000/L.20,000/L.
  • 43. Case 7Case 7 • The answers are c) and c). ThisThe answers are c) and c). This patient has HIT, unless provenpatient has HIT, unless proven otherwise. Need to stop theotherwise. Need to stop the heparin--may need to start alternateheparin--may need to start alternate anticoagulation. Remember that 30-anticoagulation. Remember that 30- 50% of pts with HIT will go on to50% of pts with HIT will go on to develop thrombosis, so stop thedevelop thrombosis, so stop the heparin, then send off tests!!heparin, then send off tests!! • Ranitidine is blamed too much forRanitidine is blamed too much for thrombocytopenia, but it’s easythrombocytopenia, but it’s easy enough to stop.enough to stop.
  • 44. Case 8Case 8 • You are asked to provide a consultationYou are asked to provide a consultation for a 22 year old man withfor a 22 year old man with thrombocytopenia.thrombocytopenia. • He was admitted to the ICU following aHe was admitted to the ICU following a motorcycle accident in which he sustainedmotorcycle accident in which he sustained head trauma, a ruptured spleen, twohead trauma, a ruptured spleen, two fractured ribs, and a fractured pelvis.fractured ribs, and a fractured pelvis. • On the fourth ICU day the platelet count isOn the fourth ICU day the platelet count is reported to be 2,000reported to be 2,000
  • 45. Case 8Case 8 • Which of the following is the most likelyWhich of the following is the most likely diagnosis?diagnosis? A.A. Disseminated intravascular coagulationDisseminated intravascular coagulation B.B. Post-splenectomy thrombocytopenia.Post-splenectomy thrombocytopenia. C.C. Thrombotic thrombocytopenic purpuraThrombotic thrombocytopenic purpura D.D. Pseudothrombocytopenia.Pseudothrombocytopenia.
  • 46. Case 8Case 8 • Remember that multiple traumaRemember that multiple trauma predisposes to DIC. The answer is Apredisposes to DIC. The answer is A
  • 47. Case 9Case 9 • A 62 y.o man presents for evaluationA 62 y.o man presents for evaluation of elevated cholesterol from healthof elevated cholesterol from health fair screening. No PMHx, No meds,fair screening. No PMHx, No meds, no FHx. Non-smoker. Pexno FHx. Non-smoker. Pex unremarkable, including normal vitalunremarkable, including normal vital signs, no nodes, no HSM.signs, no nodes, no HSM. • CBC shows Hgb 14.2, Plts 300, butCBC shows Hgb 14.2, Plts 300, but WBC 290.WBC 290. • Diff 1% neutrophils, 99%Diff 1% neutrophils, 99% lymphocytes.lymphocytes. • Peripheral smear shownPeripheral smear shown
  • 48. Copyright ©2003 American Society of Hematology. Copyright restrictions may apply. Maslak, P. ASH Image Bank 2003;2003:100690 Case 9 peripheral smearCase 9 peripheral smear
  • 49. Case 9Case 9 • Flow cytopmetry of peripheralFlow cytopmetry of peripheral blood shows a monoclonalblood shows a monoclonal population of mature B cells. Whatpopulation of mature B cells. What is the next most appropriate step?is the next most appropriate step? a.a. ObservationObservation b.b. Bone marrow biopsyBone marrow biopsy c.c. Refer for treatment with fludarabineRefer for treatment with fludarabine d.d. Refer for treatment with rituximabRefer for treatment with rituximab e.e. Begin prednisoneBegin prednisone
  • 50. Case 9- AnswerCase 9- Answer • This patient has CLL. CLL is staged usingThis patient has CLL. CLL is staged using the Rai system, wherethe Rai system, where – Stage 0 - lymphocytosis onlyStage 0 - lymphocytosis only – Stage 1 - adenopathyStage 1 - adenopathy – Stage 2 - HSMStage 2 - HSM – Stage 3 - anemia (not AIHA)Stage 3 - anemia (not AIHA) – Stage 4 - thrombocytopeniaStage 4 - thrombocytopenia • Patients need treatment only for anemia orPatients need treatment only for anemia or thrombocytopenia or for symptomaticthrombocytopenia or for symptomatic adenopathy.adenopathy. • Treatment does not affect mortality.Treatment does not affect mortality.
  • 51. Case 9 - other factsCase 9 - other facts • Patients with CLL can develop AIHAPatients with CLL can develop AIHA (30% risk over the lifetime of(30% risk over the lifetime of disease) or ITP (5-10%)disease) or ITP (5-10%) • Pts with CLL are at increased risk forPts with CLL are at increased risk for solid tumors (lung, breast, gastric)solid tumors (lung, breast, gastric)
  • 52. Case 10Case 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 WBCHis CBC shows: Hgb 14.1 gm WBC 250,000/ul. Platelet count 217,000/ul.250,000/ul. Platelet count 217,000/ul. • The differential shows 50% segs,The differential shows 50% segs, 18%bands, 16% lymphs, 4% monos, 2%18%bands, 16% lymphs, 4% monos, 2% eos, 4% basos, 4% metamyelocytes, 2%eos, 4% basos, 4% metamyelocytes, 2% myelocytes, rare promyelocytes andmyelocytes, rare promyelocytes and blasts.blasts. • The peripheral smear is shown.
  • 53. Copyright ©2004 American Society of Hematology. Copyright restrictions may apply. Maslak, P. ASH Image Bank 2004;2004:101019 Case 10 peripheral smearCase 10 peripheral smear
  • 54. Case 10Case 10 • Which of the following bestWhich of the following best represents the patient’s likelyrepresents the patient’s likely cytogenetic abnormalitycytogenetic abnormality – A. t(15;17)A. t(15;17) – B. t(8;14)B. t(8;14) – C. t(16;16)C. t(16;16) – D. t(9;22)D. t(9;22) – E. t(4;11)E. t(4;11)