Platelets and Platelet Disorders
Platelets and platelet disorders
Thrombocytopenia has four mechanisms: reduced production (marrow failure, chemotherapy, alcohol, B12 deficiency, congenital), increased destruction (ITP, TTP, DIC, HIT, drug-induced, post-transfusion purpura), sequestration (hypersplenism), and dilution after massive transfusion. Confirm true thrombocytopenia on smear, because EDTA-induced clumping and large platelets can mislead.
Immune thrombocytopenia is a diagnosis of exclusion: isolated thrombocytopenia, otherwise normal counts, no splenomegaly, often large platelets. Treat for bleeding, not the platelet count. TTP is an emergency: microangiopathic hemolysis with schistocytes, thrombocytopenia, neurologic or renal symptoms, fever, and ADAMTS13 activity <10%; treat with urgent plasma exchange. HUS follows Shiga-toxin E. coli diarrhea with renal failure predominating; atypical HUS involves complement dysregulation. HIT is caused by IgG against platelet factor 4–heparin complexes, typically 5–10 days after heparin exposure, causes thrombosis more than bleeding, and is managed by stopping heparin, giving a non-heparin anticoagulant, and avoiding platelet transfusion. DIC shows prolonged PT/aPTT, low fibrinogen, elevated D-dimer, and schistocytes in sepsis, obstetric catastrophe, or malignancy.
Platelet function disorders: Bernard-Soulier syndrome (GPIb-IX-V deficiency, giant platelets, absent ristocetin aggregation), Glanzmann thrombasthenia (GPIIb/IIIa deficiency, normal ristocetin but absent response to ADP or collagen), storage pool disease, uremia, aspirin effect, and von Willebrand disease (low VWF antigen and activity, prolonged PFA-100 closure). Evaluation uses aggregometry, PFA-100, and flow cytometry.
Trap: platelet transfusion in TTP can worsen microvascular thrombosis; reserve it for life-threatening bleeding.
Rule of thumb: thrombocytopenia plus schistocytes plus organ injury means TTP/HUS until proven otherwise; send ADAMTS13 and arrange plasma exchange.