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Dr. Parag H. Mehta
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Board Review · Medicine Simplified

Hematology

8 high-yield topics. Open a topic to review its pearls.

Anemia

Microcytic, normocytic, macrocytic

First Steps

  • First test for evaluating anemia: reticulocyte count
  • Unexplained iron deficiency: do colonoscopy

Microcytic (MCV <80)

  • Iron deficiency: low ferritin (<20 diagnostic), high RDW, pencil cells; associations: PICA, Plummer-Vinson, koilonychia, restless legs
  • Thalassemia: target cells, teardrop cells, basophilic stippling; low MCV disproportionate to Hgb, normal RDW
  • Sideroblastic: ringed sideroblasts; causes lead, INH, alcohol, copper deficiency
  • Lead poisoning: basophilic stippling (old building, gout, headache)

Anemia of Chronic Disease

  • Low serum iron, low TIBC, low transferrin saturation, normal/high ferritin
  • Bone marrow stores NOT depleted
  • Treatment: erythropoietin and iron when symptomatic
  • EPO with Hgb >10 increases HTN and CVA risk

Macrocytic (MCV >100)

  • B12 deficiency: usually MCV >110, posterior column signs (vibration/proprioception), hypersegmented neutrophils; check MMA level
  • Folate deficiency: no neuro symptoms; check homocysteine
  • Pernicious anemia: intrinsic factor antibodies, Schilling test
  • Myelodysplastic syndrome (MCV 100-110): elderly, cytopenias, Pelger-Huet, ringed sideroblasts

Hemostasis Disorders

Bleeding and hemolytic anemias

Coombs Test

  • Direct: patient RBC + anti-IgG/anti-C3 detects antibodies on RBCs
  • Warm antibody: IgG, extravascular, idiopathic/drugs/lymphoma → steroids, splenectomy
  • Cold antibody: IgM, intravascular, infections (EBV, mycoplasma) → immunosuppressants (NO splenectomy/steroids)

Microangiopathic Hemolytic Anemias

  • HUS: young, GI symptoms, renal failure, schistocytes, E. coli O157:H7 — NO antibiotics, supportive
  • TTP: fever, low platelets, renal dysfunction, neuro, hemolysis — plasma exchange (platelets contraindicated)
  • HELLP: 3rd trimester → deliver baby

Other Hemolytic Anemias

  • Hereditary spherocytosis: spectrin deficiency, osmotic fragility test, folic acid + splenectomy
  • G6PD deficiency: X-linked, bite cells, oxidative stress (sulfonamides, dapsone, fava beans)
  • PNH: dark morning urine, CD55 assay/flow cytometry, splenic thrombosis, → eculizumab

Aplastic Anemia

  • Reticulocyte count ~0, hypocellular marrow
  • Causes: idiopathic, PNH, radiation, drugs (chloramphenicol, sulfonamides), parvovirus B19
  • Parvovirus aplastic crisis in sickle cell: diagnose parvovirus IgM, treat IVIG
  • Treatment: BMT (young) or immunosuppressives (older)

Hypercoagulable States

Inherited and acquired thrombophilia

Inherited

  • Factor V Leiden: APC resistance, most common inherited disorder
  • Prothrombin G20210A
  • Protein C/S deficiency: warfarin skin necrosis risk
  • Antithrombin III deficiency: heparin resistance

Acquired

  • Antiphospholipid syndrome: lupus anticoagulant, prolonged PTT not corrected by mixing
  • Malignancy, pregnancy/OCP, immobility, surgery
  • Do NOT do hypercoagulable workup for first DVT with known cause

Hemochromatosis

Iron overload

Key Points

  • Transferrin saturation >55% (best screening test)
  • Ferritin usually >1000
  • HFE gene testing if transferrin saturation elevated
  • Manifestations: DM (pancreas), hyperpigmentation (skin), cardiomyopathy, abnormal LFTs, hypogonadism, arthropathy (1st MCP)
  • Try phlebotomy before chelating agents

Sickle Cell Anemia

Trait, disease, crises

Management

  • Most important prognostic factor: level of Hgb F (higher is better)
  • Treatment: folic acid; hydroxyurea if >3 crises/year (increases Hgb F)
  • Vaccinate: H. flu, meningococcus, pneumovax
  • Osteomyelitis: Salmonella

Acute Chest Syndrome

  • Chest pain, fever, decreased O2 sat, infiltrate on x-ray
  • Failure to respond to antibiotics
  • Treatment: exchange transfusion + correct hypoxia
  • May require early intubation

Variants

  • Trait (Hb AS): Hb S <50%, crisis in severe hypoxia, papillary necrosis
  • Disease (Hb SS): Hb S 75-95%, functional asplenia, vaso-occlusive crises
  • Hb SC: aseptic necrosis of hip, splenomegaly, target cells
  • Exchange transfusion for stroke or operative procedures

Myeloproliferative Disorders

PV, ET, CML, myelofibrosis

Overview

  • Polycythemia vera: elevated RBC mass, low EPO, JAK2 mutation, pruritus after bathing; phlebotomy + hydroxyurea
  • Essential thrombocytosis: platelets >600K, thrombosis/bleeding risk
  • Myelofibrosis: teardrop cells, marrow fibrosis
  • CML: Philadelphia chromosome (BCR-ABL), low LAP score, imatinib

Leukemias

Acute and chronic

Acute Leukemias

  • AML: Auer rods, myeloperoxidase positive; APL (M3) → DIC risk, ATRA
  • ALL: children, TdT positive, CNS involvement, tumor lysis

Chronic Leukemias

  • CLL: elderly, smudge cells, hypogammaglobulinemia, warm autoimmune hemolysis
  • CML: Philadelphia chromosome, splenomegaly, blast crisis

Transfusion Medicine

Reactions and products

Transfusion Reactions

  • Acute hemolytic: ABO incompatibility, fever/flank pain/hypotension — stop transfusion
  • Febrile non-hemolytic: most common, cytokines
  • IgA deficiency: anaphylaxis risk, give IgA-deficient blood
  • TRALI: acute lung injury within 6 hours
  • Multiple transfusions: low calcium (citrate)