Platelet disorders

Thrombocytopenia, a platelet count below 150,000/microL, is a laboratory finding rather than a single disease, so evaluation starts with the smear to exclude pseudothrombocytopenia and identify the can't-miss consumptive emergencies TTP, HIT, and DIC before working through production, destructive, and sequestration causes. Management treats the underlying cause, reserves platelet transfusion for bleeding or procedural thresholds, and specifically avoids platelet transfusion in TTP and HIT except for life-threatening hemorrhage.

Immune thrombocytopenia is an acquired isolated thrombocytopenia from antiplatelet autoantibody-mediated destruction plus impaired marrow production, presenting with mucocutaneous bleeding and no splenomegaly. It is a diagnosis of exclusion made by a normal smear and normal other cell lines, and treatment is driven by bleeding risk, starting with glucocorticoids with or without IVIG or anti-D.

Heparin-induced thrombocytopenia is an immune, prothrombotic drug reaction in which IgG antibodies against platelet factor 4-heparin complexes activate platelets, causing venous and arterial thrombosis alongside a paradoxical falling platelet count. The danger is clotting, not bleeding, so management is to stop all heparin immediately and start a non-heparin anticoagulant while avoiding platelet transfusion and premature warfarin.

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy caused by severe ADAMTS13 deficiency that lets ultralarge von Willebrand factor multimers drive platelet microthrombi; the key dyad of microangiopathic hemolytic anemia plus thrombocytopenia without another cause mandates the PLASMIC score, an ADAMTS13 activity and inhibitor level, and emergent plasma exchange started before results return.

Disseminated intravascular coagulation is a secondary, systemic activation of coagulation and fibrinolysis, most often from sepsis, that simultaneously consumes platelets and clotting factors, causing microvascular thrombosis and bleeding. Diagnosis rests on a laboratory constellation, thrombocytopenia, prolonged PT and aPTT, low fibrinogen, and elevated D-dimer, in a predisposing clinical setting, and management centers on treating the underlying trigger while replacing blood components only for active or high-risk bleeding.

Von Willebrand disease is the most common inherited bleeding disorder, caused by deficient or dysfunctional von Willebrand factor, producing mucocutaneous bleeding from impaired platelet adhesion plus a mild secondary factor VIII deficiency. Diagnosis rests on the vWF antigen, ristocetin cofactor activity, and factor VIII activity panel, and management centers on desmopressin for type 1, vWF concentrate for severe or desmopressin-unresponsive disease, and antifibrinolytics for mucosal bleeding.

The approach to a bleeding patient starts by using the bleeding pattern, the platelet count, and the PT/aPTT to localize the defect to primary hemostasis (platelets or von Willebrand factor), secondary hemostasis (coagulation factors), or a combined process such as DIC or liver disease. A mixing study then separates a factor deficiency, which corrects, from an inhibitor, which does not, and directs the specific factor or von Willebrand assay that confirms the diagnosis.

Antiplatelet agents block platelet activation and aggregation to prevent arterial thrombosis. Aspirin irreversibly inhibits cyclooxygenase-1, and P2Y12 inhibitors such as clopidogrel, ticagrelor, and prasugrel block adenosine diphosphate-driven platelet activation. Aspirin 81 mg daily anchors secondary prevention, and dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor is first-line after acute coronary syndrome or coronary stenting.