Hematology - Part 1
Hematology - Part 1Andrea Lu, MDAssociate Program DirectorMay 2020
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B. Copyright 2020 American Society of Hematology. Copyright restrictions may apply.
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E (left), F (right). Copyright 2020 American Society of Hematology. Copyright restrictions may apply.
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H (left). I (right). Copyright 2020 American Society of Hematology. Copyright restrictions may apply.
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These images were originally published in ASH Image Bank.A.B.C.D.E.F.G.H.I.J.K.Maslak, Peter. Howell-Jolly Bodies. ASH Image Bank. 2008; 3677. 2020 American Society of Hematology.Lyndsay McLeod-Kennedy; Mike Leach. Dapsone Poisoning. ASH Image Bank. 2019; 62761 2020 American Societyof Hematology.Maslak, Peter, Southern L. Microangiopathic hemolytic anemia. ASH Image Bank. 2009; 40409. 2020 AmericanSociety of Hematology.Venkataraman, G. Teardrop Cells (Dacrocytes) 2. ASH Image Bank. 2017; 61023. 2020 American Society ofHematology.Kraus, Teresa. Hypersegmented Neutrophil. ASH Image Bank. 2015; 60047. 2020 American Society of Hematology.Maslak, Peter, Southern L. Neutrophils 1. ASH Image Bank. 2002; 1592. 2020 American Society of Hematology.Jafari P, Venkataraman G. Target Cells. ASH Image Bank. 2019; 62464. 2020 American Society of Hematology.Scordino T. Burr Cells or Echinocytes. ASH Image Bank. 2016; 60291. 2020 American Society of Hematology.Scordino T. Acanthocytes. ASH Image Bank. 2015; 60266. 2020 American Society of Hematology.Blood Work. Pseudothrombocytopenia. ASH Image Bank. 2012; 12960. 2020 American Society of Hematology.
Anemia
MKSAP 24A 28-year-old woman is evaluated for decreased exercise tolerance and ice cravings for the pastseveral weeks. Medical history is notable for Crohn colitis diagnosed 6 years ago. Her symptomsflared 3 months ago with increased abdominal pain and diarrhea, and she began therapy withazathioprine and infliximab. Her only other medication is ferrous sulfate tablets, 325 mg once daily,which she has been taking for 6 weeks after being diagnosed with iron deficiency anemia; herhemoglobin level at that time was 8.2 g/dL.On physical examination, vital signs are normal. She is thin, with pale conjunctivae and nail beds.Cardiac exam reveals a grade 2/6 systolic flow murmur. The remainder of the examination isunremarkable.Laboratory studies show a hemoglobin level of 7.5 g/dL and a serum ferritin level of 1 ng/mL .
Which of the following is the most appropriate treatment?A. Intravenous iron preparationB. Oral iron in a liquid preparationC. Oral iron tablets three times dailyD. Sustained-release iron preparation
Iron Deficiency AnemiaCausesPhysical ExamTreatmentBlood LossPallorIV Iron if absorption is aconcernDecreased absorptionPica-After gastricsurgeriesCeliac diseaseH. pyloriAI atrophic gastritisIncreased requirementsGlossitisStomatitisKoilonychiaHgb usually increases few weeksContinue treatment 3 -6months after Hgbnormalizes
Inflammatory Anemia & Anemia of Kidney DiseaseConditionMCVSerum Fe% satTIBCFerritinFe malLow/NormalNormal/Elevated-Treatment of AoCD: treat underlying diseaseAoKD: treat if Hgb 10Burr CellsComplications of ESAs: worsening HTN, volumeoverload, thrombotic complications
MKSAP 56A 56-year-old man is brought to the ER after being found lyingunresponsive in the local train station. Medical history is significant forchronic alcohol dependence. He is homeless. The patient is a frequentvisitor to the ER for minor trauma and ailments; his last visit was 6months ago. Until that time, the patient lived in various shelters andreceived at least one nutritious meal per day. His whereabouts and livingcircumstances since that time are unknown. His medical history isotherwise not significant, and at his last visit to the ER, he was taking nomedications.On exam, vital signs are normal. The patient is disheveled, cachectic, andmalodorous. He moans in response to painful stimuli and moves allextremities. He has poor dentition. Hepatomegaly is noted.Hypersegmented neutrophils are seen on the peripheral blood smear.Hgb7.4 g/dLWBC4200 /µLMCV110 fLPlatelet97,000Reticulocytecount1% oferythrocytesBlood alcohollevel500 mg/dL
MKSAP 58Which of the following is the most likely cause of this patient'sanemia?A.B.C.D.Cobalamin deficiencyFolate deficiencyInflammatory anemiaIron deficiency
Folate and Vitamin B12 DeficiencyCauses of Folate Deficiency-DietaryEtOH useDecreased sed Need/IncreasedCell Turnover-PregnancyHemolysisPsoriasisCauses of Vit B12 Deficiency-DietaryMalabsorption--IBDPancreatic insufficiencySIBOPernicious anemiaMedications-PPIsMetforminNitrous oxide
Folate and Vitamin B12 Deficiency-Homocysteine, MMA--Intrinsic Factor Abs, Parietal Cells AbsTreatment for Vitamin B12 Deficiency--Elevated in vitamin B12 deficiency, MMA normal in folate deficiencyOral 1000-2000 µg dailyCan see increased reticulocytes and decreased LDH/Bili in a few daysHypersegmented PMNs disappear 2 weeksPancytopenia improves 2-4 weeksHgb increases 1 g/weekTreatment for Folate Deficiency-Exclude vitamin B12 deficiencyFolate 1-5 mg PO qDay
MKSAP 43A 22-year-old woman undergoes routine evaluation forchronic anemia, which was diagnosed 6 years ago.Medical history is otherwise unremarkable, but a maternalaunt also has anemia. Her only medication is acombination oral contraceptive pill. On physicalexamination, vital signs are normal. Nohepatosplenomegaly is noted.Hemoglobin electrophoresis reveals a normal pattern ofmigration of hemoglobin A and normal levels ofhemoglobin A2 and hemoglobin F.Hgb10 g/dLMCV67 fLFerritin200 ng/mLIron150 µg/dLTIBC340 µg/dL
Which of the following is the most likely diagnosis?A.B.C.D.E.Inflammatory anemiaIron Deficiencyα - thalassemia silent carrierα - thalassemia traitβ - thalassemia minor
Thalassemias-Disruption in the normal alpha globin and beta globin productionAlpha-Thal: African and SE Asian DescentBeta - Thal: Mediterranean countries, SE Asian, Indian, PakistanThink Thalassemia when Iron overload MicrocytosisLow MCV/Microcytosis, normal RDWPBS will show microcytosis, nucleated RBCs, target cellsWill need folate supplementationAvoid iron supplementation
Alpha Thalassemiasɑ-Thal minima/silent carrier(SIngle Gene Deletion)-ɑ-Thal minor/trait(Two Deletions)normal clinicallyNormalelectrophoresis/labsno treatmentHydrops Fetalis(4 Deletions)-In utero/neonatal demise-Mild Hemoglobin H Disease(Three Deletions)--severe anemiaAbnormalelectrophoresis(hgb H)At risk for ironoverload
Beta Thalassemiasβ-Thal major/Transfusion Dependent-Symptoms 6 mos. ofageOrganomegalyBony abnormalitiesIron OverloadHbA2 (5% or more);HbF (up to 95%); noHbAβ-Thal intermedia/Non transfusiondependent-Symptoms 2-4 y.oVaried clinicalpresentationHbA2 (4% or more);HbF (up to 50%)β-Thal Minor-Mild anemiaUsuallyasymptomaticHbA2 (4% or more);HbF (up to 5%)
MKSAP 21A 52-year-old man is evaluated in the ER for decreased exercisetolerance and yellowing of the eyes for the past 3 days. He wasdiagnosed with leprosy 6 days ago and began antibacterial therapy4 days ago. His CBC at that time was normal. He is a Haitianimmigrant. Medications are dapsone, rifampicin, and clofazimine.On exam, temperature is 36.7 C, BP is 125/75 mm Hg, HR is100/min, and RR is 18/min. He has icteric sclerae. Cardiac examreveals a grade 2/6 systolic flow murmur. Multiple raisederythematous papules with decreased sensation are noted on theback and hands. No organomegaly is observed.Examination of the peripheral blood smear shows bite cells. Thedirect antiglobulin (Coombs) test is negative.HaptoglobinUndetectedHgb5.6 g/dLWBC5,600/µLPlatelet223,000Retic Count12%
Which of the following is the most appropriate immediatemanagement?A.B.C.D.E.Administer prednisoneAdminister rituximabDiscontinue dapsoneMeasure ADAMTS13 activityMeasure glucose-6-phosphate dehydrogenase level
G6PD Deficiency-Hemolysis occurs 2-3 days after triggeringevent/exposureMedications--Foods--Fava beansChemicals--DapsonePrimaquineMethylene blueNitrofurantoinPyridiumRasburicaseNaphthalene (mothballs)Infections-Only transfuse if severelysymptomaticTest 3 months after incitingevent
Hereditary Spherocytosis-Affected patients usually well compensateduntil triggering event (ex: infection, nutritionaldeficiencies)--Ex: ParvovirusElevated MCHCMay see splenomegaly, pigment gallstonesTest: Osmotic Fragility Test, Flow CytometryIf severe, will need splenectomy-Give all the required immunizations!
Sickle Cell AnemiaEvidence-BasedManagement of SickleCell Disease: ExpertPanel Report, 2014
Sickle Cell Anemia Rapid initiation of opioids for vaso-occlusive crisis Use of incentive spirometry in hospitalized patients Use of analgesics and physical therapy for treatment of avascular necrosis Use of ACE inhibitors in patients with microalbuminuria Regular ophthalmologic examinations and referral for laser photocoagulation for retinopathy Use of echocardiography to evaluate signs of pulmonary hypertension Hydroxyurea for patients with more than 3 vaso-occlusive crises per year, for those with pain orchronic anemia interfering with daily activities, or those with recurrent acute chest syndrome Preoperative transfusion to serum hemoglobin level of 10 g/dL for surgeries requiring generalanesthesia Assess for iron overload and begin oral iron chelation if necessary
Sickle Cell Disease - Vaso-occlusive Crisis-Opiates are preferred analgesic (avoid meperidine)Incentive spirometry every 2-4 hours, encourage ambulationKeep O2 sat 95%HydrationOral L-Glutamine and crizanlizumab are also used to prevent pain crisis
Sickle Cell Anemia - Acute Chest Syndrome-ACS: fever, tachypnea, hypoxia, SOB, pulmonary infiltrateCan be caused by infections, VTE/thrombosis, fat embolismIncreased frequency in patients with SCD asthma, or with prior ACS eventsOxygen therapy, bronchodilators (goal O2 sat 95%)Antibiotics if infection present (IV cephalosporin, oral macrolide)pRBC transfusionExchange transfusion-Other indications: acute stroke, acute retinal artery occlusion
Warm Autoimmune Hemolytic Anemia-Causes--Coombs test: positive for IgGTreatment:--IdiopathicInfections: HIV, HCVAI disorders: SLE, RAMalignancy: CLL, MMMedications: Penicillin, cephalosporin, methyldopaSteroidsIVIGRituximabSplenectomy 30% can have thromboembolic diseaseE. Uthman, MD - https://www.flickr.com/photos/euthman/2989437967
MKSAPA 32-year-old woman is hospitalized with progressiveexertional dyspnea. She has noted dark urine for the last weekand yellowing of her skin for several days. Medical history isunremarkable, and she takes no medications.On exam, temperature is 36.7 C, blood pressure is 100/70 mmHg, pulse rate is 100/min, and respiration rate is 18/min. Ictericsclera and skin are noted. Cardiac exam reveals a grade 2/6systolic flow murmur. No lymphadenopathy orhepatosplenomegaly is present.A peripheral blood smear shows erythrocyte agglutination. Adirect antiglobulin (Coombs) test is positive for C3. Diagnostictesting for Mycoplasma and Epstein-Barr virus is negative.HaptoglobinUndetectableHemoglobin4.8 g/dLWBC8200/µLMCV134 fLPlatelet230,000Reticulocyte count12% oferythrocytesTotal Bilirubin6.7 mg/dLDirect Bilirubin1.2 mg/dLLDH660 U/LUrinalysisDipstick positive for4 blood; 0-1leukocytes/hpf, and0 erythrocytes/hpf
Which of the following is the most appropriate treatment?A.B.C.D.Intravenous immune globulinPrednisoneRituximabSplenectomy
Cold Agglutinin Disease-Causes--Infections: Mycoplasma, EBVMalignancy: LymphomasCoombs test: C3Treatment-Avoid cold temperaturesRituximab, fludarabineSteroids, IVIG, splenectomy NOT helpful
Paroxysmal Nocturnal Hemoglobinuria (PNH)-Characterized by episodic hemolysis, pancytopenia, thrombosis (esp inatypical locations)Other symptoms: abdominal pain, discolored urinePatients with PNH are at higher risk for leukemia or myelodysplasiaDiagnosis with flow cytometry (test for CD55, CD59)Treatment: folate, steroids, eculizumab-Will need meningococcal vaccination
MKSAP (16) 56A 35 year-old woman is evaluated for new-onsetthrombocytopenia. She is gravida 1 at 36 weeks’ gestation.Her pregnancy has been otherwise uncomplicated. Shetakes only a prenatal vitamin.On exam, temperature is normal, BP is 110/65 mmHg, pulseis 100/min, and respiration rate is 22/min. There are noecchymoses or petechiae. Abdominal exam discloses noright upper quadrant pain. She has a gravid uterus.Neurologic exam is normal, and there is no peripheraledema.No schistocytes or platelet clumping is seen on theperipheral blood smear.Hemoglobin11.0 g/dLLeukocyte count9500/µLMCV85 fLPlatelet count95,000/µLFibrinogen350 mg/dLALTNormalASTNormalUrinalysisNormal
Which of the following is the most appropriate management?A.B.C.D.E.CorticosteroidsEmergent delivery of the fetusIntravenous immune globulinPlasma exchangeRepat CBC in 1-2 weeks
ThrombocytopeniaDecreased ProductionExamples:-Aplastic atic tumorsInfectionsToxinsIncreased tructionSequestrationExamples:-Splenomegaly
Immune-Mediated Thrombocytopenia-Always rule out pseudothrombocytopeniaAssociated Conditions--Autoimmune (SLE, RA)Infections: HIV, HCV, H. Pylori,Malignancy: CLL, lymphomaTest for HIV, HCVAntiplatelet antibody testing is not recommended because of low sensitivityTreatment if bleeding or if counts 30,000 with steroids vs IVIGTreatment-First line: Steroids, IVIGSecond line: splenectomy, rituximabOther agents: Eltrombopag, romiplostim
Heparin-Induced Thrombocytopenia-Type 1: non-immune mediated, occurs within first few days of exposureType 2: occurs 5-10 days after exposure 2/2 Abs against platelet factor 4Signs: thrombosis/VTEs, arterial thrombosis, skin necrosis at site of injection4T scoring systemScreening test & Confirmatory testIf on differential/high 4T score, stop heparinAlternative anticoagulants: argatroban, bivalirudin, fondaparinuxTransition to warfarin (Can also consider DOAC)Patients should be instructed to avoid heparin for life
MKSAP 51A 42-year-old man is admitted to the hospital with an acutechange in mental status and fever of 2 days' duration. Medicalhistory is noncontributory, and he takes no medications.On physical examination, temperature is 38.2 C, bloodpressure is 108/70 mm Hg, pulse rate is 104/min, andrespiration rate is 18/min. Oxygen saturation is 96% breathingambient air. He is agitated and disoriented to place and time.Petechiae are noted on his shins. The remainder of theexamination is normal.The direct antiglobulin (Coombs) test is negative.Haptoglobin20 mg/dLHemoglobin10.2 t6.8% oferythrocytesCreatinine1.4 mg/dLLDH1600 U/L
Therapy should be immediately initiated pending results of which of the followingstudies?A.B.C.D.ADAMTS13 activityCoagulation studiesPeripheral blood smearStool culture and testing
Thrombotic Thrombocytopenic Purpura-MAHA thrombocytopeniaMild renal failurenausea/vomiting, abdominal pain; Fevers, neuro symptomsInherited or acquired deficiency in ADAMTS13--Acquired: cyclosporine, gemcitabine, bevacizumab, quinine, ecstasy, cocaineADAMTS13 level 10% TTPDo not wait for levels to come back before starting treatmentTreatment-Plasma exchangeSteroidsRituximab if refractory
Hemolytic Uremic Syndrome-Renal failure, MAHA, thrombocytopeniaClassic: after acute diarrheal illness (Shigella, O157:H7 E Coli)Complement Mediated: w/o diarrhea, complement-mediated--Associated with medications, AI disorders (ex: SLE), Infections (ex: HIV, influenza,S. pneumoniae)Treatment-HUS: Plasma ExchangeComplement mediated: Eculizumab
MKSAP 2A 68-year-old man is evaluated for epistaxis, gumbleeding, and easy bruising of 3 months' duration.Medical history is notable for anxiety, depression, andhyperlipidemia. Medications are atorvastatin,citalopram, a multivitamin, and ginkgo biloba.On physical examination, vital signs are normal; BMI is21. Scattered petechiae and several small ecchymosesare visible on the anterior thigh. The examination isotherwise normal.aPTTNormalHemoglobin14.8 timeNormal
Which of the following is the most appropriate diagnostic test to perform next?A.B.C.D.E.Fibrinogen levelMixing studies for PT and aPTTPeripheral blood smear reviewPlatelet Function Analyzer-100Serum protein electrophoresis
PT/INR - sensitive to II, VII, XPTT - sensitive to VIII, IX, XI, XIIThrombin time - fibrinogen to fibrinclot conversionPlatelet Function Analyzer-100 platelet function
MKSAP 71A 64-year-old woman is evaluated in the emergency departmentfor large ecchymoses, bleeding gums, and a hematomaextending from her upper thigh to her knee. Medical history issignificant for chronic lymphocytic leukemia, which has beenasymptomatic and managed expectantly. She has experiencedno previous bleeding symptoms and has no family history ofbleeding disorders. She takes no medications.On physical exam, other than a pulse rate of 104/min, vitalsigns are normal. Ecchymoses are present on her arms andlegs. Small cervical and axillary lymph nodes are palpable.Other examination findings are normal.aPTT88 saPTT mixing study64 sHemoglobin10.8 g/dLWBC65,000/µLPlatelet215,000/µLPT11.5 sFactor VIII1%
Administration of which of the following is the most appropriatemanagement?A.B.C.D.Activated factor VIICryoprecipitateDesmopressinFresh frozen plasma
Congenital Hemophilia-Hemophilia A (VIII), Hemophilia B (IX)Congenital: X-linkedMild (5-40%), Moderate (1-5%), severe ( 1%)Symptoms: hemarthrosis, bleeding into deep muscles, excessive/delayedbleeding after traumaNormal PT, prolonged PTT that corrects with mixing studyTreatment-Inactivated factor concentratesAntifibrinolytic agents: Tranexamic acid, ε-aminocaproic acidMild hemophilia A: desmopressin
Congenital HemophiliaDeficiencyInheritanceLabs affectedTreatmentVIIAutosomal PTFFP/PCCXAutosomal /- PTT /- PTFFP/PCCXI (aka Hem C)Autosomal PTTFFP, factor XIXIIAutosomal PTTNo risk for bleedingXIIIAutosomal /- Thrombin timecryo/FactorXIII
Acquired Hemophilia-2/2 antibodies to clotting factors, most common factor VIIIAssociated with:--pregnancy/postpartum stateMalignancyAI disorders: SLE, RAMedications: PCNs, IFNs, etcNormal PTT, prolonged PTT that does not correct with mixing studyBethesda assay to quantify inhibitorManagement-Do NOT give factor VIIIActivated factor VIIImmunosuppression: steroids, cyclophosphamide
Von Willebrand Disease-Both genetic and acquired cases--Symptoms: bleeding gums, epistaxis, menorrhagia, easy bruising3 types--Type I: Most common, mucocutaneous bleedingType II: 2/2 dysfunctional vWFType III: most severe (jt and deep muscle bleeding)Labs: normal coagulation factors*, prolonged closure time on PFA-100--Acquired: valvular heart dz, ECMO, LVADsProlonged PTT can be seen in severe deficiencyManagement-Type 1: DesmopressinType 2 &3: vWF concentratesCan give antifibrinolytic agents after surgery
MKSAP 73A 26-year-old man undergoes follow-up evaluation after hospitalization for deep venousthrombosis last week. He reports no recent travel, surgery, or immobilization. He has a sisterwho was diagnosed with an unprovoked deep venous thrombosis 1 year ago at 35 years ofage. Medical history is otherwise unremarkable. His only medication is rivaroxaban.On physical examination, vital signs are normal. The exa
MKSAP 24 A 28-year-old woman is evaluated for decreased exercise tolerance and ice cravings for the past several weeks. Medical hi
Liquichek Hematology-16 Control A hematology reference control used in monitoring determinations of blood cell values on Sysmex and Abbott 3 part differential hematology analyzers. 105 day shelf life at 2-8 C 14 day open-vial stability at 2-8 C Liquichek Hematology-16T Control Liquichek Reticulocyte Control (S)
5. Learn the scope and practices of “Special Hematology” testing and how it is utilized to diagnose hematologic disorders. 6. Complete general/special hematology experience checklist. 4. Clinical experience in Hematology/Performance of Bone Marrows (with Hematology/Oncology Division) (1 day, Wednesday of first rotation week)
Hematology, 12th ed., by J.P. Greer et al (Eds), Lippincott Williams & Wilkins, 2008 (two volumes). This is an encyclopedic clinical reference book in hematology. The large multi-authored work, Williams Hematology, 8th ed, MA Lichtman et al (Eds), McGraw-Hill, 2006 i
for 18 hematology tests are shown for men in. Table 1 and for women in Table 2. The mean of hematology tests of the BP and WP sample for men and for women, respectively, were similar. As expected, the BP mean red blood cell-related hematology tests (hemoglobin, hematocrit, and red blood cell
3.3.2 Hematology and Blood Chemistry Examination The results of the CTVT blood hematology and chemical examination in domestic dogs are shown in Table 1. Table 1. Hematology examination Examination Result Normal range Hematology White blood cell (103/ L) 47.1 16.0 -17.0 Red blood cell (106/ L) 1.12 5.5 -8.5
This work demonstrates the performance of Exigo H400 4-part hematology analyzer in comparison with a more technically advanced 5-part reference analyzer in complete blood count (CBC) analyses of patient samples taken from the normal routine screening. . the Sysmex XT-2000iV 5-part hematology analyzer and associated reagents, calibrator .
A hematology reference control used in monitoring determinations of blood cell values on Sysmex and Abbott 3-part differential hematology analyzers . Blood cells in plasma-like fluid 105 day shelf life at 2-8ºC 14 day open-vial stability at 2-8ºC Parameters Granulocytes (GRAN) Hematocrit (HCT) Hemoglobin (Total)
Required Text(s): Course Notes, SAVMA Recommended Text(s): Canine and Feline Cytology: A Color Atlas and Interpretation Guide, 3rd Edition (2015). Raskin & Meyer Diagnostic Cytology and Hematology of the Dog and Cat, 4th Edition (2013). Cowell & Tyler Diagnostic Cytology and Hematology of the Horse, (2001). Cowell & Tyler Exotic Animal Hematology & Cytology, (2015).
