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Blood Bank

Cytopenias

Cytopenias are conditions where one or more blood cell lines are low. We’ll look at Anemia (low red cells/hemoglobin), Thrombocytopenia (low platelets), and Neutropenia (low neutrophils), focusing on why they happen (Pathophysiology), how we figure out the cause (Detection), and what we do about it (Treatment)

Cytopenias: An Overview

Cytopenias indicate a problem with blood cell production, survival, or loss. Identifying the specific cell line(s) affected and the underlying mechanism (immune vs. non-immune, production vs. destruction) is crucial for diagnosis and management

Cytopenia Cell Line Affected Primary Consequence
Anemia Red Blood Cells (RBCs) / Hemoglobin (Hgb) Tissue Hypoxia (Reduced O2 delivery)
Thrombocytopenia Platelets (Plt) Bleeding Risk
Neutropenia Neutrophils (ANC) Infection Risk (Bacterial/Fungal)

Anemia: Too Few Red Blood Cells / Too Little Hemoglobin

Pathophysiology

  • Decreased Production
    • Non-Immune: Nutritional deficiency (Iron, B12, Folate), Bone marrow failure/suppression (Aplastic anemia, CKD - low EPO, Anemia of Chronic Disease, Chemo/Radiation, Infiltration), Inherited defects (Thalassemia)
  • Increased Destruction (Hemolysis)
    • Non-Immune: Intrinsic RBC defects (Membranopathies - Spherocytosis; Enzymopathies - G6PD def; Hemoglobinopathies - Sickle Cell), Extrinsic factors (MAHA - TTP/HUS/DIC, Mechanical valves, Infections, Toxins)
    • Immune: Antibodies +/- Complement destroy RBCs
      • Alloimmune: HTR, HDFN
      • Autoimmune: WAIHA (IgG), CAD (IgM+C3d), PCH (IgG+C3d)
      • Drug-Induced: Various mechanisms (Hapten, Immune Complex, Autoantibody induction)
  • Blood Loss
    • Acute: Trauma, Surgery -> Hypovolemia initially
    • Chronic: Slow GI bleed, Menstruation -> Iron Deficiency Anemia

Detection

  • CBC: Low Hgb/Hct. RBC Indices (MCV, MCHC) classify as micro/normo/macrocytic, hypo/normochromic
  • Reticulocyte Count: Key! High suggests destruction/loss; Low suggests production problem
  • Peripheral Smear: Essential for morphology (size, shape, color, inclusions like schistocytes, spherocytes, sickle cells)
  • Specific Tests: Iron studies, B12/Folate, Hemolysis markers (LDH, Bili, Haptoglobin), Hb Electrophoresis, Enzyme assays
  • Immunohematologic Tests: DAT (detects in vivo coating - IgG/C3d), IAT (detects plasma Abs), Elution (identifies coating Ab) - Crucial for immune causes!
  • Bone Marrow Exam: Assesses production, infiltration

Treatment

  • Treat Underlying Cause: Nutrient replacement, stop offending drug, manage chronic disease, immunosuppression for AIHA (steroids, Rituximab), Hydroxyurea for Sickle Cell
  • Supportive Care: EPO for CKD/ACD
  • Red Blood Cell Transfusion: Key supportive therapy for symptomatic anemia or critical Hgb levels. Requires careful compatibility testing, especially challenging in AIHA. Antigen-negative blood essential for alloantibodies (HTR/HDFN)

Thrombocytopenia: Too Few Platelets

Pathophysiology

  • Decreased Production
    • Non-Immune: Bone marrow failure/suppression (Aplastic anemia, Chemo/Radiation, Alcohol), Infiltration (Leukemia), Nutritional (severe B12/Folate), Inherited syndromes
  • Increased Destruction / Consumption
    • Non-Immune: DIC, TTP, HUS, Mechanical destruction, Hypersplenism (Sequestration)
    • Immune: Antibodies destroy platelets
      • Autoimmune: ITP (primary or secondary)
      • Alloimmune: NAIT, PTP
      • Drug-Induced: DITP (various drugs), HIT (Heparin-PF4 complex Abs - prothrombotic!)
  • Pseudothrombocytopenia: In vitro clumping artifact (EDTA-dependent)

Detection

  • CBC: Low platelet count
  • Peripheral Smear: Essential to confirm low count, rule out clumping/pseudothrombocytopenia, assess size (giant platelets in ITP, Bernard-Soulier)
  • Coagulation Studies (PT/aPTT/Fibrinogen/D-dimer): Important if DIC suspected
  • ADAMTS13 Activity: For TTP diagnosis
  • Bone Marrow Exam: Assess megakaryocytes if production defect suspected
  • Specialized Immune Testing: HIT assays (Immunoassay & Functional), HPA antibody testing (NAIT/PTP). Platelet autoantibody tests for ITP generally not useful

Treatment

  • Treat Underlying Cause: Stop drug, treat infection/malignancy, Plasma Exchange (TTP!), Non-heparin anticoagulants (HIT!)
  • Immune Modulation (for ITP/NAIT/PTP): Corticosteroids, IVIg, Rituximab, TPO-RAs, Splenectomy (ITP)
  • Platelet Transfusion: For active bleeding or prophylaxis at very low counts (<10-20k). Transfused platelets rapidly destroyed in ITP. Avoid in TTP/HIT unless life-threatening bleed. Special requirements for NAIT/PTP (HPA-matched) or immune refractoriness (HLA-matched)

Neutropenia: Too Few Neutrophils

Pathophysiology

  • Decreased Production
    • Non-Immune: Congenital (SCN, Cyclic), Acquired marrow failure/suppression (Chemo/Radiation, Drugs, Aplastic anemia, Alcohol), Infiltration (Leukemia), Nutritional (severe B12/Folate/Copper)
  • Increased Destruction / Consumption / Margination
    • Non-Immune: Overwhelming sepsis, Hypersplenism (Sequestration), Pseudoneutropenia (margination shift)
    • Immune: Antibodies destroy neutrophils
      • Autoimmune: AIN (primary in infants, secondary in SLE, RA, etc.)
      • Alloimmune: NAN
      • Drug-Induced: DIIN

Detection

  • CBC w/ Differential: Low Absolute Neutrophil Count (ANC). Note severity (mild/mod/severe <500)
  • Serial CBCs: If cyclic pattern suspected
  • Peripheral Smear: Confirm differential, assess morphology
  • Bone Marrow Exam: Assess cellularity, granulopoiesis (maturation arrest common in immune/congenital forms), rule out infiltration
  • Specialized Testing: Neutrophil antibody testing (AIN/NAN), Genetic testing (congenital), Autoimmune markers

Treatment

  • Treat Underlying Cause: Stop drug, treat infection/malignancy
  • Infection Prevention/Management: Prompt broad-spectrum antibiotics for febrile neutropenia (medical emergency!). Prophylactic antimicrobials sometimes. Patient education
  • Granulocyte Colony-Stimulating Factor (G-CSF): Mainstay for many causes (Chemo-induced, Congenital, AIN) to boost neutrophil production
  • Immunosuppression (for AIN): Steroids, IVIg, Rituximab
  • Granulocyte Transfusion: Very rarely used, specific indications/risks

Overall Clinical Relevance

Cytopenias are common laboratory findings requiring careful investigation. The clinical presentation (hypoxia symptoms vs. bleeding vs. infections), CBC results (indices, other cell lines), reticulocyte count, and peripheral smear morphology provide crucial initial clues. Specific testing, including immunohematology (DAT/IAT/Elution) and bone marrow evaluation, is often needed to pinpoint the cause. Treatment must be directed at the underlying pathophysiology, with blood component therapy (RBCs, Platelets, rarely Granulocytes) serving as vital supportive care