Approach to Anemia

• Step 1: Kinetic view

  • Low retic → ↓ production (iron, B12/folate lack, marrow failure)

  • High retic → ↑ destruction/loss (hemolysis, blood loss, splenic sequestration)

• Step 2: Morphologic view (MCV)

  • Microcytic (< 80) → iron deficiency vs thalassemia

  • Normocytic (80-100) → early iron-def, anemia of inflammation, CKD, hemolysis

  • Macrocytic (> 100) → B12/folate lack, MDS, liver, alcohol, drugs

Microcytic Anemia Essentials

• Iron deficiency

  • Buzz: pica, restless legs, low ferritin (< 40); reactive thrombocytosis common

  • Must do: search for occult blood → EGD/colonoscopy

• Anemia of inflammation (chronic disease)

  • High ferritin, low TIBC, low/normal iron sat; treat underlying cause ± EPO

• Thalassemia traits

  • Disproportionately low MCV (eg 55) with mild anemia

  • β-trait: ↑ HbA₂ on electrophoresis. α-trait: normal electrophoresis

  • Never give iron unless deficient

Macrocytic Anemia Essentials

• B12 deficiency

  • Clues: neuropathy, other autoimmune disease, pernicious anemia (IF Ab)

  • Borderline B12? Check MMA + homocysteine (both ↑)

• Folate deficiency

  • Clues: alcoholism, pregnancy, rapid cell turnover, MTX

  • Only homocysteine ↑ (MMA normal). No neurologic signs

• Smear hallmark: macro-ovalocytes + hypersegmented neutrophils

Hemolytic Anemias

Rapid identifiers

• Hourglass spherocytes + ↑ MCHC → hereditary spherocytosis

• Bite cells + Heinz bodies → G6PD

• Schistocytes + normal PT/PTT → TTP/HUS

• Schistocytes + prolonged PT/PTT → DIC

• Clot + heparin exposure → HIT (stop heparin, start argatroban)

Bleeding & Clotting Framework

• Primary hemostasis (platelets)

  • Superficial mucocutaneous bleeding

  • Low number: ITP (isolated), TTP/HUS/DIC/HIT (plus hemolysis)

  • Poor function: von Willebrand disease → prolonged bleeding time ± PTT; treat with DDAVP

• Secondary hemostasis (coag factors)

  • Deep soft-tissue / hemarthrosis

  • Interpret PT/PTT + mixing study

    • PT only ↑ → factor VII/VK/Liver/Warfarin

    • PTT only ↑ → factors VIII, IX, XI, XII or inhibitor

    • Mix corrects → deficiency (eg hemophilia A)

    • Mix fails → inhibitor (APLS if clot; acquired VIII inhibitor if bleed)

  • Oddballs

    • Normal labs yet bleed → factor XIII defect

    • High PTT, no bleed → factor XII defect

Transfusion Reactions (know the calls)

Bone Marrow & Hematologic Malignancies

• Aplastic anemia →  young, pancytopenia, hypocellular marrow; treat with transplant or ATG/cyclosporine

• Myelodysplastic syndrome (MDS) →  older, pancytopenia, hypercellular dysplastic marrow; risk AML; 5q- deletion responds to lenalidomide

• Acute leukemias

  • AML: blasts > 20 %, ± auer rods (M3/APL t(15;17)→ treat with ATRA; watch DIC)

  • ALL: blasts + CNS, nodes, hepatosplenomegaly; common in children

  • Hyperleukocytosis → leukostasis → emergent leukapheresis

• Myeloproliferative neoplasms

  • CML: very high WBC with all myeloid stages; t(9;22) (BCR-ABL); treat with TKIs (imatinib etc)

  • Polycythemia vera & Essential thrombocythemia: JAK2+ (≈100 % PV, 50 % ET); treat phlebotomy or hydroxyurea

• Chronic lymphocytic leukemia (CLL)

  • Elderly, asymptomatic lymphocytosis + smudge cells; observe unless symptomatic; Richter transformation risk

• Lymphomas

  • Aggressive (DLBCL, Burkitt) → symptomatic; curable with chemo (R-CHOP, high-grade regimens)

  • Indolent (follicular, marginal zone)→ often watch-and-wait

  • Hodgkin: Reed-Sternberg “owl-eye” cells; ABVD; late toxicities (CAD, hypothyroid)

• Plasma-cell disorders

  • Multiple myeloma: CRAB signs, M-spike on SPEP/UPEP, rouleaux; treat with chemo ± ASCT, bisphosphonates

  • MGUS (< 3 g/dL, < 10 % plasma cells, no CRAB)→ yearly follow-up

  • Waldenström (IgM spike) → hyperviscosity; consider plasmapheresis

High-Yield One-Liners

• Iron-deficiency with platelets > 450 k  → reactive thrombocytosis, not leukemia

• Sickle cell crisis + low retic → aplastic crisis (parvovirus B19)

• Splenic sequestration crisis occurs in SC disease, not SS

• Platelets < 30 k + bleeding → treat ITP (steroids IVIg); don’t transfuse unless life-threatening bleed

• Never give platelets in TTP or HIT

• Pregnant DVT → treat with low-molecular-weight heparin

• Back pain, anemia, creatinine rise, total protein ↑ → order SPEP + UPEP for myeloma work-up