hematology board review alice ma, md

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

Case 1Case 1

• 68 y.o. woman from Minnesota seen 68 y.o. woman from Minnesota seen in ER for fatigue, DOE, and episodic in ER for fatigue, DOE, and episodic dark urine. Dark urine noted dark urine. Dark urine noted following extended periods of time in following 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%. Normal Hgb 7.1, retic count 18%. Normal

indices, normal remainder of CBCindices, normal remainder of CBC• Lab notes sample appears Lab notes sample appears

agglutinated, and clumping of RBCs agglutinated, and clumping of RBCs on smear.on smear.

Case 1Case 1

• 68 y.o. woman from 68 y.o. woman from MinnesotaMinnesota seen seen in ER for fatigue, DOE, and in ER for fatigue, DOE, and episodic episodic dark urinedark urine. Dark urine noted . Dark urine noted following extended periods of time in following 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%. Normal Normal

indices, normal remainder of CBCindices, normal remainder of CBC• Lab notes Lab notes sample appears sample appears

agglutinated, and clumping of RBCs agglutinated, and clumping of RBCs on smear.on smear.

Case 1Case 1

• Which of the following is the most Which of the following is the most important study for establishing the important 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

Case 1Case 1

• A - No, since this is for hereditary A - 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 fragility Increased osmotic fragility

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 mycoplasma May follow infection with mycoplasma

or monoor mono– IgM mediatedIgM mediated– No benefit from steroids or splenectomyNo benefit from steroids or splenectomy– Keep warmKeep warm

Case 1Case 1

• C. Sucrose Hemolysis test. No. This C. 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

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 cells Blister cells

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, splenectomy Treat 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.

Case 2Case 2

• 22 y.o. man brought from work to ER 22 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

Case 2Case 2

• 22 y.o. man brought from work to ER 22 y.o. man brought from work to ER for abdominal pain and fever.for abdominal pain and fever.

• TwoTwo recent episodes of recent episodes of red urinered urine

• Previously treated for Previously treated for syphilissyphilis

• Works as a butcher’s assistant, Works as a butcher’s assistant, unloading unloading refrigeratedrefrigerated meat trucks meat trucks

• PEx - chronically ill. Nl Temp and BPPEx - chronically ill. Nl Temp and BP

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

Case 2Case 2

• Which of the following is the most Which of the following is the most appropriate diagnostic study for this appropriate 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

Case 2Case 2

• B. Sickle Cell preparation - noB. Sickle Cell preparation - no

• U/A shouldn’t be red, may have U/A shouldn’t be red, may have microscopic hematuria, not microscopic hematuria, not hemoglobinuriahemoglobinuria

• No association with syphilisNo association with syphilis

• Peripheral smear should show Peripheral smear should show sickled cells, especially if pt is quite sickled cells, especially if pt is quite ill nowill now

Case 2Case 2

• C - urine hemosiderin determination. C - urine hemosiderin determination. No, since we know that there is No, since we know that there is hemoglobin in the urine. Urine hemoglobin in the urine. Urine hemosiderin is useful if there is the hemosiderin is useful if there is the suspicion for chronic intravascular suspicion for chronic intravascular hemolysis, as in PNH, valve hemolysis, as in PNH, valve hemolysis, AAA/aortic dissection hemolysis, AAA/aortic dissection hemolysis.hemolysis.

Case 2Case 2

• D. Heinz body preparation - noD. Heinz body preparation - no• This is useful if there is suspicion for This 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 if Usually G6PD deficiency, but if

oxidative stress is bad enough, oxidative stress is bad enough, anyone can get Heinz body hemolytic anyone can get Heinz body hemolytic anemia.anemia.

• African americans with G6PD African americans with G6PD deficiency can have falsely nl G6PD deficiency can have falsely nl G6PD levels immediately after hemolysislevels immediately after hemolysis

Case 2Case 2

• A - Donath Landsteiner test - correctA - Donath Landsteiner test - correct

• Paroxymal Cold Hemoglobinuria Paroxymal Cold Hemoglobinuria (PCH)(PCH)– Episodic cold-induced intravascular Episodic cold-induced intravascular

hemolysishemolysis– DAT positive only for Complement DAT positive only for Complement – Seen in pediatrics, also classically with Seen in pediatrics, also classically with

syphilis, now most are idiopathicsyphilis, now most are idiopathic– IgG antibody binds only in the cold, but IgG 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.

Case 3Case 3

• 22 y.o. man seen in the ER for red 22 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

Case 3Case 3

• In order to confirm the diagnosis, In order to confirm the diagnosis, which of the following should be which of the following should be done?done?– A. repeat G6PD determination in 1 A. 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

Case 3Case 3

• Two normal forms of enzyme. Most Two normal forms of enzyme. Most prevalent type is prevalent type is BB. 20% of healthy . 20% of healthy Africans have type Africans have type AA..

• Deficiency is X-linked.Deficiency is X-linked.• In Africans, mutant protein is In Africans, mutant protein is A-A-, which is , which is

unstable and loses activity as the red cell unstable and loses activity as the red cell ages. ages.

• Mediterranean variant has baseline low Mediterranean variant has baseline low activity activity

• Low G6PD activity results in low levels of Low G6PD activity results in low levels of NADPH and reduced glutathione, which NADPH and reduced glutathione, which are required to protect hemoglobin from are required to protect hemoglobin from oxidative damage.oxidative damage.

Case 3Case 3

• Typically, hemolysis can be triggered by Typically, 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-, reticulocytosis In 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 G6PD and only younger cells with normal G6PD levels, are present. Need to repeat in 1 levels, are present. Need to repeat in 1 monthmonth

Case 3 - blister cellsCase 3 - blister cells

Case 4Case 4

• A 27-year-old woman is referred to you for A 27-year-old woman is referred to you for evaluation of thrombocytopenia, which was evaluation of thrombocytopenia, which was discovered incidentally during an evaluation for life discovered 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 examination Findings 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 is The 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 is Examination of the peripheral blood smear is normal except for the mild thrombocytopenia. normal except for the mild thrombocytopenia.

Case 4Case 4

• What is the most appropriate management for this What is the most appropriate management for this patient?patient?

(A)(A) Suspect ITP. do no further diagnostic Suspect ITP. do no further diagnostic studies other than a repeat complete studies other than a repeat complete blood count in 1 month.blood count in 1 month.

(B)(B) Suspect ITP; begin prednisone, 1 Suspect ITP; begin prednisone, 1 mg/kg/dmg/kg/d

(C)(C) Suspect ITP or possibly Suspect ITP or possibly myelodysplasia; myelodysplasia; do a bone marrow aspiration do a bone marrow aspiration and biopsy.and biopsy.

(D)(D) Suspect the possibility of lymphoma; Suspect the possibility of lymphoma; do a do a CT of the chest and abdomen for CT 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.

Case 4Case 4

• In the absence of any gold standard In the absence of any gold standard tests to diagnose ITP, the diagnosis tests to diagnose ITP, the diagnosis can only be based on the can only be based on the observation of thrombocytopenia observation of thrombocytopenia without other hematologic without other hematologic abnormalities. abnormalities.

• Also, recognize that the goal for Also, recognize that the goal for treatment of ITP is only to prevent treatment of ITP is only to prevent bleeding, which is not an issue in bleeding, which is not an issue in this woman with mild this woman with mild thrombocytopenia. thrombocytopenia.

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 or may only provide a temporary remission or

provide symptomatic relief until a spontaneous provide symptomatic relief until a spontaneous remission occurs. remission occurs.

• Therefore, prednisone is not indicated in Therefore, prednisone is not indicated in the absence of thrombocytopenia that the absence of thrombocytopenia that poses no hemostatic risk. poses no hemostatic risk.

• Prednisone may be appropriate if the Prednisone may be appropriate if the platelet count is less than 20,000 to platelet count is less than 20,000 to 30,000/L. 30,000/L.

Case 4Case 4

• When there are no other hematologic When there are no other hematologic abnormalities on routine CBC and on abnormalities on routine CBC and on peripheral blood smear, examination of the peripheral blood smear, examination of the bone marrow does not provide additional bone marrow does not provide additional important information. important information.

• It is unnecessary to routinely do a bone It is unnecessary to routinely do a bone marrow examination in the evaluation of a marrow examination in the evaluation of a patient with suspected ITP. patient with suspected ITP.

• If pt were older or had abnormal counts If pt were older or had abnormal counts other than plts, marrow exam may have other than plts, marrow exam may have been appropriate.been appropriate.

Case 4Case 4

• Other etiologies for thrombocytopenia Other etiologies for thrombocytopenia such as occult liver disease with such as occult liver disease with hypersplenism or occult lymphoma may hypersplenism or occult lymphoma may be considered, but in the absence of a be considered, but in the absence of a suggestive history or physical suggestive history or physical examination, these possibilities warrant examination, these possibilities warrant no further diagnostic evaluation. no further diagnostic evaluation.

• Alcohol excess itself may cause Alcohol excess itself may cause thrombocytopenia due to marrow thrombocytopenia due to marrow suppression. suppression.

Case 5Case 5

• A 76-year-old man presents to the emergency A 76-year-old man presents to the emergency department with numerous ecchymoses and department with numerous ecchymoses and bleeding from the gums. bleeding from the gums.

• He has been previously well, and he takes no He has been previously well, and he takes no medications. medications.

• There is a history of uncomplicated There is a history of uncomplicated appendectomy and cholecystectomy.appendectomy and cholecystectomy.

• On physical examination, he has extensive On physical examination, he has extensive bruising, and there is oozing from intravenous bruising, 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.

Case 5Case 5

• Laboratory studies:Laboratory studies:

• Platelet countPlatelet count 264,000/264,000/LL• Activated partial Activated partial 112 sec 112 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 does A 1:1 mix of patient and normal plasma does not correct the prolonged activated partial not correct the prolonged activated partial thromboplastin time. thromboplastin time.

• The patient had an activated partial The patient had an activated partial thromboplastin time of 28 seconds at the time thromboplastin time of 28 seconds at the time of his appendectomy 12 years ago.of his appendectomy 12 years ago.

Case 5Case 5

The most likely cause of this patient’s The most likely cause of this patient’s coagulopathy is:coagulopathy is:

(A)(A) Disseminated intravascular Disseminated intravascular coagulationcoagulation

(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

Case 5Case 5

• The patient has an acquired coagulation The patient has an acquired coagulation disorder that is associated with bleeding. disorder that is associated with bleeding.

• Although disseminated intravascular Although disseminated intravascular coagulation (DIC) is associated with coagulation (DIC) is associated with prolongation of the activated partial prolongation of the activated partial thromboplastin time, this diagnosis is thromboplastin 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 systemic Also there is no associated systemic illness that could provoke DIC. illness that could provoke DIC.

• Factor XII deficiency is ruled out by the Factor XII deficiency is ruled out by the presence of bleeding, because factor XII presence of bleeding, because factor XII deficiency does not cause bleeding. deficiency does not cause bleeding.

Case 5Case 5

• Lupus anticoagulants are not Lupus anticoagulants are not associated with hemorrhage unless associated with hemorrhage unless there is associated deficiency of there is associated deficiency of prothrombin. This possibility is prothrombin. This possibility is excluded by the normal PT; the excluded by the normal PT; the normal PT rules out an acquired normal PT rules out an acquired prothrombin inhibitor. prothrombin inhibitor.

• Therefore, the most likely diagnosis Therefore, the most likely diagnosis is an acquired inhibitor against factor is an acquired inhibitor against factor VIII.VIII.

Case 5Case 5

• Acquired inhibitors against factor VIII are Acquired inhibitors against factor VIII are uncommon. They can occur post partum or in uncommon. They can occur post partum or in association with lymphoproliferative diseases or association with lymphoproliferative diseases or autoimmune disorders. They also can occur autoimmune disorders. They also can occur without any associated condition. without any associated condition.

• Patients frequently present with massive Patients frequently present with massive bleeding. bleeding.

• Treatment is aimed at 1) bypassing the inhibitor Treatment is aimed at 1) bypassing the inhibitor by using factor VIIa, porcine factor VIII (provided by using factor VIIa, porcine factor VIII (provided that the inhibitor does not cross-react), or that the inhibitor does not cross-react), or activated prothrombin complex concentrates; activated prothrombin complex concentrates; and 2) lowering the antibody levels using and 2) lowering the antibody levels using plasmapheresis or immunosuppression. plasmapheresis or immunosuppression.

• Postpartum factor VIII inhibitors will often resolve Postpartum factor VIII inhibitors will often resolve spontaneously.spontaneously.

Case 6Case 6

• A previously healthy 50-year-old man is admitted to A previously healthy 50-year-old man is admitted to the hospital with a 2-week history of fatigue and the hospital with a 2-week history of fatigue and dyspnea. dyspnea.

• He is currently taking propranolol, clonidine, and He 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, is Physical examination, including blood pressure, is normal. He is mentally alert.normal. He is mentally alert.

Case 6Case 6

• Laboratory evaluation: Laboratory evaluation: • Hgb 4.6 g/dL, Hct 14%, WBC 10,800/L, normal Hgb 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 shows Examination of the blood smear shows fragmented erythrocytes and fragmented 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, and activated partial thromboplastin time, and fibrinogen) are normal.fibrinogen) are normal.

Case 6Case 6

What is the most appropriate management for What is the most appropriate management for this patient?this patient?

(A)(A) Suspect TTP and initiate plasma Suspect TTP and initiate plasma exchange therapy.exchange therapy.

(B)(B) Suspect autoimmune Suspect autoimmune thrombocytopenia and hemolytic anemia (Evans thrombocytopenia and hemolytic anemia (Evans syndrome), and initiate prednisone treatment, 1 syndrome), and initiate prednisone treatment, 1 mg/kg per day.mg/kg per day.

(C)(C) Suspect disseminated carcinoma, Suspect disseminated carcinoma, and initiate a workup that includes chest and initiate a workup that includes chest radiographs, bone marrow examination, and radiographs, bone marrow examination, and abdominal CT scan.abdominal CT scan.

(D)(D) Suspect drug-induced Suspect drug-induced thrombocytopenia and hemolytic anemia, and thrombocytopenia and hemolytic anemia, and discontinue the three medications he is taking.discontinue the three medications he is taking.

(E)(E) Suspect pernicious anemia, and do a Suspect pernicious anemia, and do a bone marrow evaluation to confirm megaloblastic bone marrow evaluation to confirm megaloblastic hematopoiesis.hematopoiesis.

Case 6Case 6

• The answer is A - even though the The answer is A - even though the patient does not have renal patient does not have renal manifestations, neurologic manifestations, neurologic symptoms, or fever, he does have symptoms, or fever, he does have microangiopathic hemolytic anemia microangiopathic hemolytic anemia and thrombocytopenia. Moreover, he and thrombocytopenia. Moreover, he is not in DIC, since his PT/PTT are is not in DIC, since his PT/PTT are normal. Recognize that not every normal. Recognize that not every patient with TTP will have “the patient with TTP will have “the pentad” at the time of presentation, pentad” at the time of presentation, though many will have all though many will have all symptoms--shortly before dying!!symptoms--shortly before dying!!

Case 7Case 7

• A 65-year-old man underwent bilateral A 65-year-old man underwent bilateral knee replacement surgery 5 days ago. knee replacement surgery 5 days ago.

• His mobilization has been slow because of His mobilization has been slow because of persistent pain, and he is only now getting persistent pain, and he is only now getting up in a chair. up in a chair.

• Because of a previous history of acute Because of a previous history of acute proximal venous thrombosis complicating proximal venous thrombosis complicating a cholecystectomy 8 years ago, he has a cholecystectomy 8 years ago, he has been given subcutaneous heparin three been given subcutaneous heparin three times daily in doses sufficient to achieve times daily in doses sufficient to achieve an activated partial thromboplastin time of an activated partial thromboplastin time of 35 sec.35 sec.

Case 7Case 7

• There are no clinical signs of fresh There are no clinical signs of fresh hemorrhage although ecchymoses and hemorrhage although ecchymoses and hematomas from the first ICU day are still hematomas from the first ICU day are still evident. evident.

• There are no signs of hemorrhage from There are no signs of hemorrhage from mucous membranes, needle stick sites, or mucous membranes, needle stick sites, or tubes. tubes.

• The hemoglobin is 12.5 Gm/dl, the white The hemoglobin is 12.5 Gm/dl, the white blood count is 4,500/ micro liter, no blood count is 4,500/ micro liter, no fragmented cells are seen, no platelet fragmented cells are seen, no platelet clumping is noted on the peripheral blood clumping 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).

Case 7Case 7

– The most likely cause of the The most likely cause of the thrombocytopenia is:thrombocytopenia is:• (A)(A) RanitidineRanitidine• (B)(B) SepsisSepsis• (C)(C) HeparinHeparin• (D)(D) Crystalloid given during Crystalloid given during

surgerysurgery• (E)(E) None of the aboveNone of the above

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 the Stop the ranitidine because it is the cause of the thrombocytopenia.cause of the thrombocytopenia.

(B)(B) Obtain blood cultures, and culture Obtain blood cultures, and culture any any drainage from the left knee incision drainage 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 to Send serum and plasma for studies to

exclude heparin-induced exclude heparin-induced thrombocytopenia; continue the thrombocytopenia; continue the heparin until the results are available.heparin until the results are available.

(E)(E) Continue heparin, but follow the Continue heparin, but follow the platelet count daily and give platelet platelet count daily and give platelet transfusions if the count falls below transfusions if the count falls below 20,000/L.20,000/L.

Case 7Case 7

• The answers are c) and c). This The answers are c) and c). This patient has HIT, unless proven patient has HIT, unless proven otherwise. Need to stop the otherwise. Need to stop the heparin--may need to start alternate heparin--may need to start alternate anticoagulation. Remember that 30-anticoagulation. Remember that 30-50% of pts with HIT will go on to 50% of pts with HIT will go on to develop thrombosis, so stop the develop thrombosis, so stop the heparin, then send off tests!!heparin, then send off tests!!

• Ranitidine is blamed too much for Ranitidine is blamed too much for thrombocytopenia, but it’s easy thrombocytopenia, but it’s easy enough to stop.enough to stop.

Case 8Case 8

• You are asked to provide a consultation You are asked to provide a consultation for a 22 year old man with for a 22 year old man with thrombocytopenia. thrombocytopenia.

• He was admitted to the ICU following a He was admitted to the ICU following a motorcycle accident in which he sustained motorcycle accident in which he sustained head trauma, a ruptured spleen, two head 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 is On the fourth ICU day the platelet count is reported to be 2,000reported to be 2,000

Case 8Case 8

• Which of the following is the most likely Which of the following is the most likely diagnosis?diagnosis?

A.A. Disseminated intravascular Disseminated intravascular coagulation coagulation

B.B. Post-splenectomy Post-splenectomy thrombocytopenia.thrombocytopenia.

C.C. Thrombotic thrombocytopenic Thrombotic thrombocytopenic purpurapurpura

D.D. Pseudothrombocytopenia. Pseudothrombocytopenia.

Case 8Case 8

• Remember that multiple trauma Remember that multiple trauma predisposes to DIC. The answer is Apredisposes to DIC. The answer is A

Case 9Case 9

• A 62 y.o man presents for evaluation A 62 y.o man presents for evaluation of elevated cholesterol from health of elevated cholesterol from health fair screening. No PMHx, No meds, fair screening. No PMHx, No meds, no FHx. Non-smoker. Pex no FHx. Non-smoker. Pex unremarkable, including normal vital unremarkable, including normal vital signs, no nodes, no HSM.signs, no nodes, no HSM.

• CBC shows Hgb 14.2, Plts 300, but CBC 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

Case 9Case 9

• Flow cytopmetry of peripheral Flow cytopmetry of peripheral blood shows a monoclonal blood shows a monoclonal population of mature B cells. What population 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

Case 9- AnswerCase 9- Answer

• This patient has CLL. CLL is staged using This 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 - thrombocytopenia Stage 4 - thrombocytopenia

• Patients need treatment only for anemia or Patients need treatment only for anemia or thrombocytopenia or for symptomatic thrombocytopenia or for symptomatic adenopathy.adenopathy.

• Treatment does not affect mortality.Treatment does not affect mortality.

Case 9 - other factsCase 9 - other facts

• Patients with CLL can develop AIHA Patients with CLL can develop AIHA (30% risk over the lifetime of disease) (30% risk over the lifetime of disease) or ITP (5-10%)or ITP (5-10%)

• Pts with CLL are at increased risk for Pts with CLL are at increased risk for solid tumors (lung, breast, gastric)solid tumors (lung, breast, gastric)

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 WBC His 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 and myelocytes, rare promyelocytes and blasts.blasts.

• The peripheral smear is shown.

Case 10Case 10

• Which of the following best Which of the following best represents the patient’s likely represents 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)

hematology board review alice ma, md

Documents