Thrombocytopenia

Thrombocytopenia is defined as a platelet count <150,000/μL. Mechanisms are classified into three categories: (1) Decreased production: bone marrow failure (aplastic anemia, myelodysplastic syndrome, leukemia), bone marrow infiltration (myelofibrosis, metastatic cancer), chemotherapy/radiation, severe B12 or folate deficiency, chronic alcohol use (direct marrow toxicity), viral infections (HIV, HCV, parvovirus B19). (2) Increased destruction: immune-mediated (ITP — autoantibodies against platelet glycoproteins GP IIb/IIIa and GP Ib/IX; HIT — heparin-PF4 antibody complex activating platelets paradoxically causing thrombosis), thrombotic microangiopathies (TTP — ADAMTS13 deficiency causing ultra-large vWF multimers that trap platelets; HUS — Shiga toxin-mediated endothelial damage), DIC (consumptive coagulopathy), infections (sepsis, malaria), drug-induced (heparin, quinine, vancomycin, linezolid, sulfonamides). (3) Sequestration: hypersplenism (portal hypertension, infiltrative splenomegaly) — the enlarged spleen traps up to 90% of circulating platelets (normal spleen sequesters ~30%). (4) Dilutional: massive transfusion (replacement of >1 blood volume with RBCs and crystalloid without platelets). Clinical significance correlates with severity: mild (100-150K, rarely symptomatic), moderate (50-100K, prolonged bleeding with trauma), severe (20-50K, spontaneous mucocutaneous bleeding), critical (<10-20K, risk of spontaneous intracranial hemorrhage).