I.

Coagulation and Fibrinolysis A. Coagulation 1. Coagulation cascade maybe activated by intrinsic or extrinsic reactions a. PTT may be lengthened with deficiencies of factors w/in intrinsic pathway VIII, IX, XI, XII b. PT/INR prolonged with deficiency within extrinsic and common pathways factors VII, X, V, II i. Factor 7 has shortest life and is K dependent ii. Decline in factor 7 may be due to warfarin therapy or early sign of vitamin K deficiency or liver disease c. Clotting factors from both pathways dependent on vitamin k i. Vitamin k deficiency can lengthen PTT and PT/INR 2. Coagulation factors maintained 3x concentration needed a. Congenital and acquired conditions have lower CF concentrations below 30% b. Condition that lower concentrations of anti thrombotic factors (protein C, protein S, and antithrombin) result in hypercoagulable states (thrombophilia) i. Protein C serine protease that inhibits factors Va and VIIIa ii. Protein S cofactor for protein C c. Thrombin circulates as inactive prothrombin i. Thrombin cleaved by factor X serine protease cleave fibrinogen into fibrin ii. Activates favors 5, 8 and 9 iii. Binds to thrombomodulin to induce protein C to inactivate factors 5a ad 8a as negative feedback iv. Thrombin produced inflammation, infection, low blood flow, endothelial damage and platelet activation d. Antithrombin (aT3) non vitamin K depend factor that is inhibitor of thrombin and potentiated by heparin B. Fibrinolysis 1. Balance between clotting and fibrinolysis 2. Web of fibrin polymers during clotting also entangles plasminogen from circulation a. Plasminogen is converted to plasmin by plasminogen activator released by endo b. Activation promoted by thrombin and urokinase c. Recombinant tissue plasminogen activator (t-PA) is used to promote fibrinolytic activity and removed newly formed clots following thrombosis i. Help establish circulation and prevents ischemic damage 3. Plasmin lysed cross-linked fibrin and single fibrin monomers into D dimers and fibrin split products a. D dimers specifically derived from fibrin mesh that was stabilized by factor XIII b. D dimers may indicate DIC, DVT or PE 4. Like thrombin, plasmin activity regulated by both 2-antiplasmin and 2macroglobulin

5. Antifibrinolytics used to treat excessive bleeding C. Coagulopathies 1. Pathology divided into increased bleeding and clotting 2. Excess hemorrhage von Willebrand disease, hemophilias, liver failure, Dilutional coagulopathies and IDC 3. Hemophilia hereditary, decreased of a specific component of coagulation cascade a. Hemophilia A (Classic) most common, no factor 8 b. Hemophilia B (Christmas disease), 2nd most common, no factor 9 c. Hemophilia C: no factor 11, autosomal recessive, relatively mild 4. Liver synthesize all but one of the clotting factors impair liver function may manifest as coagulopathy a. Infectious causes Hep A, B, C, EBV, cytomegalovirus, herpes, parvovirus b. Hepatotoixins: acetaminophen, salicylates, methanol, a and isoniazid c. Metabolic disorders 5. Dilutional coagulopathy occurs when platelets and CF are essentially washed out by aggressive fluid resuscitation or multiple RBC transfusions w/o plasma replenishment 6. DIC hemorrhagic condition w/ simultaneous activation of thrombin and plasmin a. Pregnancy, infection, malignancy, inflammation b. Bclotting factorsa re consumed ina cycle of ucntrolled thrombosis and firniolysis c. Lab findings: low paletles, low fibrnogem, proonged PT/INR, actaivated PTT and posititve Ddimer 7. Thrombophilias may be primary (factor V Leiden, antithrombin deficiency, protein C or S deficiency) or acquired (DIC) a. ctor V Leiden common herdditary thrombophilia resulting fom a single point mutation that removes the cleavage sie for protein C from factor 5, protein C no longer able to cleave activated factor 5. Congenital and acquired conditions have lower CF concentrations below 30%) i. Protein C serine protease that inhibits factors Va and VIIIa ii. Protein S cofactor for protein C iii. Thrombin circulates as inactive prothrombin 8. a. Factor V Leiden common herdditary thrombophilia resulting fom a single point mutation that removes the cleavage sie for protein C from factor 5, protein C no longer able to cleave activated factor 5. Congenital and acquired conditions have lower CF concentrations below 30% ) i. Protein C serine protease that inhibits factors Va and VIIIa ii. Protein S cofactor for protein C b. c.

d. e. f. g. h. i.

Fljdlkfjsd Antithrombin (AT) deficiency Protein C deficiency Protein S deficiency Antiphospholipid syndrome antibodies are directed against membrane phospholipids

i. Vitamin k deficiency can lengthen PTT and PT/INR 9. Coagulation factors maintained 3x concentration needed a. Congenital and acquired conditions have lower CF concentrations below 30% b. Condition that lower concentrations of anti thrombotic factors (protein C, protein S, and antithrombin) result in hypercoagulable states (thrombophilia) i. Protein C serine protease that inhibits factors Va and VIIIa ii. Protein S cofactor for protein C c. Thrombin circulates as inactive prothrombin i. Thrombin cleaved by factor X serine protease cleave fibrinogen into fibrin ii. Activates favors 5, 8 and 9 iii. Binds to thrombomodulin to induce protein C to inactivate factors 5a ad 8a as negative feedback iv. Thrombin produced inflammation, infection, low blood flow, endothelial damage and platelet activation