Plasminogen Activators • Increasingly used for therapeutic applications, i.e. lysis of thrombus in grafts. • Caution for hemorrhagic complications. • Monitoring tests – Thrombin-time – Fibrinogen (<100 mg/dL → bleeding) – FDP (>100 U/dl → bleeding) Disseminated Intravascular Coagulation • Manifestation of underlying process with activation of coagulation and fibrinolysis. • Associated with sepsis, hemolysis, ischemia, hypoperfusion, brain injury, obstetrical emergencies, snake bite, malignancy. • Low-grade to fulminant presentations. • Laboratory abnormalities – Abnormal PT/PTT. – Decreased fibrinogen and platelets. – Elevated FDP and D-dimer. Disseminated Intravascular Coagulation • Treatment of underlying condition critical. • Heparin. • Washed PRBC, platelets, AIII, fluids as needed. • Epsilon-aminocaproic acid – Competitively binds lysine binding sites of plasminogen. • Activated protein C – Zigris. Uremia • May cause bleeding complications secondary to abnormal platelet function. • Decrease in aggregation and adhesiveness. • Main treatment is adequate dialysis. • Cryoprecipitate, DDAVP, and estrogens may help. Liver Disease • Synthesis of all coagulation factors except VIII decreased. • Biliary obstruction → vitamin K deficiency. • Decreased fibrinogen synthesis. • Platelet dysfunction and thrombocytopenia. • Chronic low-grade DIC (poor hepatic clearance). • Treatment with FFP as needed in severe liver dysfuction. Multiple Transfusion • Massive transfusion = patient’s blood volume in 24 hours or >10 units in a few hours. • Bleeding from dilutional thrombocytopenia and hypothermia. • Platelet transfusion may be needed (routine replacement contraindicated). • FFP when defective coagulation cascade suspected. • Packed RBCs – Nonfunctional WBCs and platelets. – Decreased V and VIII. – Transfusion based on clinical situation not solely on hematocrit. – Leukocyte reduced RBCs for febrile reactions and to delay HLA alloimunication. – Irradiated RBCs to prevent graft vs. host. • Platelets – Transfuse for <10,000/mm 3 (prophylaxis). – <50,000 with bleeding or planned surgery. Blood Component Transfusion Blood Component Transfusion • Fresh frozen plasma – Contains all coagulation factors. – Treatment of multiple or specific deficiency with abnormal PT and/or PTT. – Solvent detergent plasma – inactivated enveloped viruses (HIV, Hep B and C). • Cryoprecipitate – Contains fibrinogen, VIII, XIII, vWF, fibronectin – Useful in Hemophilia A, vWF, hypofibrinogenemia, and uremic bleeding. Risk of Infection • HIV 1:200,000 to 1:2,000,000 • Hepatitis B 1:30,000 to 1:250,000 • Hepatitis C 1:30,000 to 1:150,000 • HTLV 1:250,000 to 1:2,000,000 • Malaria, Yersinia, Babesia, Trypanosoma cruzi 1:1 million Transfusion Reaction • 2-5% will experience an adverse reaction. • Usually febrile reaction to antigens or pyrogens. • Most serious involve complement mediated RBC destruction (ABO incompatibility), release of vasoactive substances, and DIC. • May present with fever, dizziness, hypotension, hematuria, oozing, bronchospasm, chest tightness, lower back pain. . Intravascular Coagulation • Treatment of underlying condition critical. • Heparin. • Washed PRBC, platelets, AIII, fluids as needed. • Epsilon-aminocaproic acid – Competitively binds lysine binding sites of plasminogen. •. (>100 U/dl → bleeding) Disseminated Intravascular Coagulation • Manifestation of underlying process with activation of coagulation and fibrinolysis. • Associated with sepsis, hemolysis, ischemia, hypoperfusion,. snake bite, malignancy. • Low-grade to fulminant presentations. • Laboratory abnormalities – Abnormal PT/PTT. – Decreased fibrinogen and platelets. – Elevated FDP and D-dimer. Disseminated Intravascular Coagulation •