Coagulation tests CBC- complete blood count PT/INR- prothrombin time and international normalized ratio aPTT- activated partial thromboplastin time

PT/INR Measures extrinsic & common pathways Range: <1.5x control = no ↑ bleeding risk > 2.5x control = risk of spont. bleeding Thromboplastin + (TF + phospholipid) + Ca++ + plasma Measure clotting time INR: [(PT patient)/(PT lab mean)]ISI

aPTT Measures intrinsic and common pathways Range: <1.5x control = no ↑ bleeding risk > 2.5x control = risk of spont. bleeding Phospholipid mixture + surface activating agent (glass) + plasma, then + Ca++ Measure clotting time

Mixing studies Determines cause of prolonged PT and aPTT Factor deficiency vs. presence of an inhibitor Patient plasma diluted 1:1 with normal plasma Tests repeated immediately with 1 aliquot & 1 hr after incubation at 37ºC with a 2nd aliquot If PT or aPTT corrected, then patient has factor deficiency If PT or aPTT not corrected, then an inhibitor likely present Antibodies to clotting factors time dependent Other inhibitors not

Platelet disorders Thrombocytopenia- platelet counts of <50,000 cells/uL ↓ platelet production: destruction of marrow Thrombotic thrombocytopenia purpura: endothelial cells produce ↑ ULvWF that isn’t processed normally into vWF multimers → platelet aggregation & RBC destruction Heparin-induced thrombocytopenia: non-immune = transient ↓ in platelet count, and immune = IgG binds to platelet factor 4, triggered by i.v. administration of heparin, can → arterial thrombosis Idiopathic thrombocytopenic purpura: IgG to platelet glycoprotein receptors → opsonization & phagocytosis of platelets

Platelet disorders Thrombocytosis- platelet counts of 500,000 – 1,000,000 cells/uL Reactive thrombocytosis: caused by surgery, infection, blood loss, iron deficiency or splenectomy; platelets normalize after cause corrected Essential thrombocytosis: thrombocythemia resulting from clonal stimulation of megakaryocytes or myeloproliferative disorders (myeloid cancers)

Platelet disorders Genetic- Glanzmann thrombasthenia: auto. recessive, receptor doesn’t bind fibrinogen Bernard-Soulier syndrome: auto. recessive, mutation in vWF receptor, giant platelets Pseudo-vWD: increased binding of platelets to vWF, which ↓ vWF in plasma May-Hegglin: auto. dominant, giant platelets & thrombocytopenia

von Willebrand disease (vWD) vWF secreted by platelets & endothelia Stored in α-granules in platelets Mediates platelet adhesion in injury & stabilzes factor VIII in plasma Synthesized as large monomer that is processed into multimers of different sizes Defect in vWF → ↑ mucocutaneous bleeding, ↑ bleeding after surgery/trauma 3 types: 1 & 2 are autosomal dominant 3 is autosomal recessive