Hemostasis

1. Hemostasis Shaina Eckhouse 10/12/2010

2. Objectives • Biology of Hemostasis • Congenital Hemostasis Defects • AquiredHemostasis Defects • Hypercoagulable States • Venous thromboembolism • Transfusion • Evaluation of the Surgical Patient at Hemostatic Risk

3. Name that Movie

4. Biology of Hemostasis • Complex process that prevents or terminates blood loss from a disrupted intravascular space • Major physiologic events • Vascular constriction • Platelet plug formation • Fibrin formation • fibrinolysis

5. Biology of Hemostasis • Vascular Constriction • Initial vascular response to injury • Vasoconstriction linked to platelet plug formation • TXA2 • ET • 5-HT • Bradykinin & Fibrinopeptides

6. Biology of Hemostasis • Platelet Function • 150-400K circulating platelets • ~30% sequestered in the spleen • Thrombopeptin, IL-1, IL-6 mediate platelet production

7. Biology of Hemostasis • Platelets play an integral role in: • Formation of a hemostatic plug • Contributes to thrombin formation

8. Biology of Hemostasis • VC + platelet plug formation = PRIMARY HEMOSTASIS • Reversible • Not associated with secretion

9. Biology of Hemostasis

10. Biology of Hemostasis • Intrinsic Pathway • All the components leading to the fibrin clot formation are intrinsic to the circulating plasma • Elevated PTT associated with an abnormality in the intrinsic clotting pathway

11. Biology of Hemostasis • Extrinsic Pathway • Requires exposure of tissue factor on the surface of the injured vessel wall • Starts with Factor VII • Abnormality of the extrinsic pathway is associated with an elevated PT

12. Biology of Hemostasis

13. Biology of Hemostasis • Fibrinolysis = lysis of the fibrin clot • Plasminogen Plasmin degrades fibrin, Factor V and VIII • Plasminogenplasmin by several activators—tPA, (kalikrein increases release of tPA), uPA, factor XII • Plasminogen levels rise due to exercise, venous occlusion, and anoxia • Breakdown of the clot permits restoration of blood flow and fibrin clot in vessel wall may be replaced with collagen • Antithrombin III • Binds and inhibits thrombin and factors IX, X, XI • Protein C • Vitamin K-dependent • Degrades fibrinogen and factors V and VIII • Protein S • Vitamin K-dependent • Protein C cofactor

14. Biology of Hemostasis • How do SCDs work? • The squeeze stimulates the release of tPA from the endothelial cells of vessels. Induction of fibrinolysis. • (tPA is selective for fibrin-bound plasminogen and converts to plasmin; therefore, fibrinolysis occurs mostly at the site of clot formation.)

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16. Congenital Hemostatic Defects • Coagulation Factor Deficiencies • Hemophilia • Factor VIII deficiency = Hemophilia A • Sex-linked recessive • Both prolonged aPTT and PT • Need level to be 100% pre-op and 30% post-op • Crosses placenta • Hemophiliac Joint • No aspiration; ice; ROM exercises, factor VIII concentrate or cryoprecipitate • Factor IX deficiency = Hemophilia B/Christmas Disease • Sex-linked recessive • Need level 50% pre-operatively • Prolonged aPTT and normal PT • Tx-factor IX concentrate or cryoprecipitate

17. Congenital Hemostatic Defects • von Willibrand’s Disease • MOST COMMON congenital bleeding disorder • Low levels of vWFvariable decrease in Factor VIII due to loss of the carrier protein • vWF is necessary for normal platelet aggregation; therefore deficiency presents in a similar fashion to platelet disorders • Prolonged bleeding time, possible abnormal PTT, normal PT • Types- • I-partial quantitative deficiency (AD) • II-qualitative defect (AD) • III-total deficiency (AR) • Tx—intermediate purity factor VIII or DDAVP (Type I or II only)

18. Congenital Hemostatic Defects • Platelet disorders • Glanzmann’s thrombocytopenia—deficiency in GIIbIIIa receptor of platelets; therefore, platelets cannot bind to each other • Tx-platelets • Bernard Soulier—Gp1b receptor deficiency; therefore, platelets cannot bind collagen via vWF • Tx-platelets

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20. Acquired Hemostatic Defects • Anticoagulation • Heparin—potentiates ATIII action • Reversed with administration of protamine (1mg protamine for every 100u heparin received) • Follow aPTTwant 1.5-2.5x upper limit of nl (60-90) • Does not cross placental barrier • Lovenox—potentiates ATIII and inhibits both thrombin and Factor Xa • “more reliable therapeutic anticoagulation can be achieved” • Drug effect can be determined by anti-Xa assay • No definitive reversal • Warfarin (Coumadin) • Inhibits Vitamin K synthesis • Reversed by FFP or Vitamin K administration • Follow INR/PT

21. Acquired Hemostatic Defects • Why do we bridge with heparin or Lovenox when initially starting Coumadin? • Protein C and S are inhibited before factors II, VII, IX and X which makes the patient relatively hypercoaguable for 5-7 days

22. Acquired Hemostatic Defects • Antiplatelet Medications • Asprin—Platelet cyclooxygenase is irreversibly inhibited ; decreases TXA2 which promotes platelet aggregation • Plavix (Clopidogrel)—ADP receptor antagonist • Pentoxifylline—inhibits platelet aggregation and decreases viscosity of blood; used in treatment of peripheral arterial disease

23. Acquired Hemostatic Defects • Heparin Induced Thrombocytopenia • 2/2 antiplatelet Ab (IgG) that results in platelet destruction • Platelet count falls to <100K or by <50% in 5-7 days if first exposure or in 1-2 days if re-exposure • High incidence of platelet aggregation and thrombosis (white clot) • If suspected— • STOP heparin • Start alternate anticoagulation (lepirudin or argatroban)

24. Acquired Hemostatic Defects • Disseminated Intravascular Coagulation • Systemic process producing both thrombosis and hemorrhage • Exposure of blood to procoagulants • Formation of fibrin in the circulation • Fibrinolysis • Depletion of clotting factors • end-organ damage • Dx= decreased platelets, prolonged PT and aPTT, low fibrinogen, high fibrin split products, high D-dimer • Treat the underlying disease (sepsis, trauma, burns, malignancy)

25. Acquired Hemostatic Defects • Thrombocytopenia • MOST COMMON abnormality of hemostasis • Variety of etiologies (ITP, TTP, HUS, SLE, lymphoma, secondary hypersplenism, portal HTN, uremia…) • In setting of massive transfusion—exchange of 1L of blood volume (~11units) decreases platelet count from 250K to 80K. Associated impaired ADP-stimulated aggregation if >10units of blood transfused.

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27. Hypercoagulable States • Factor V Leiden Deficiency • MOST COMMON congenital hypercoagulable disorder • AD • Leiden variant of Factor V cannot be inactivated by Protein C • Increased risk for DVT, spontaneous abortion • Tx = heparin or warfarin

28. Hypercoagulable States • AT-III deficiency • Spontaneous venous thrombosis • Heparin does not work on these patients unless pretreated by FFP • Tx: AT-III concentrated • Antiphospholipid Antibody Syndrome • Presence of lupus anticoagulant that bind to phospholipids and proteins on the cell membrane an interfere with clotting; HOWEVER, associated with thrombosis and habitual abortions (prolonged PTT in the face of a hypercoagulable state) • Tx: Heparin, coumadin

29. Hypercoagulable States • Amicar • Aminocaproic acid • Inhibits fibrinolysis by inhibiting plasmin • Indications: DIC, persistent bleeding following CPB, thrombolytic overdose • Aprotinin • Inhibits fibrinolysis by inhibiting activation of plasminogen to plasmin

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31. Venous thromboembolism • DVT and PE • Virchow’s triad = stasis, endothelial injury, hypercoagulability • Treatment for DVT • 1st= warfarinx 6months • 2nd= warfarinx 1year • 3rd or significant PE = lifetime warfarin • Greenfield filters • For patients with contraindications to anticoagulation • Documented PE while on anticoagulation • Free-floating iliofemoral clot • IVC or femoral DVT • Patients who have undergone previous pulmonary embolectomy • PE most commonly caused by DVT in iliofemoral region

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33. Transfusion • PRBCs • 1unit=~250mL • Storage life ~35days • 1unit increases Hgb by 1 and Hct by 3 • Fever without hemolysis is the most common transfusion reaction (1 in 6,000) • Usually recipient antibody reaction against WBCs in donor blood • Acute Hemolytic reactions occur 1 in 35,000 • Caused by ABO incompatibility or Ab mediated usually from human error (Ab in recipient binding to surface Ag on donor RBC) • Sx=hypotension, fever, dyspnea, chest pain, low back pain • Tx=fluids, diuretics, HCO3, histamine blockers, pressors

34. Transfusion • Platelets • 50-100 billion in 50mL plasma • Can be stored for ~7 days (viability declines after 3 days) • Each platelet concentration should raise circulating platelets by >5,000 (4-6 pack of platelets shound increase platelets by 20-30K) • Febrile nonhemolytic reactions more common than with PRBCs (incidence is ~30%) • Antiplatelet antibodies develop in 20% of patients after 10-20 transfusions • Indictions in active bleeding: plt<50K or plt<100K in setting of ICH; trauma victims who have received multiple transfusion • Contraindicated in HIT and TTP

35. Transfusion • FFP • ~250 mL collected from 1 unit whole blood by apheresis • Stored between -18 and -30 degree C and is good for 1 year • Dose is ~10-15mL/kg • Contains all coagulation factors, protein C, protein S, and AT-III (only blood product with factor V) • Indications-warfarin overdose, liver failure, dilutionalcoagulopathy associated with massive transfusion • Highest risk of TRALI—important to distinguish from volume overload. Tx=supportive

36. Name that movie

37. Evaluation of the Surgical Patient at Hemostatic Risk • Preoperative Assessment • History • Bruises without apparent injury • Prolonged bleeding after injury • PMHx—liver disease, congenital or acquired bleeding disorders • Medications • Labs—CBC, Coagulation panel, T&S or T&C • Intraoperative and Postoperative • Ineffective local hemostasis • Complications of blood transfusion • Consumptive coagulopathy • Fibrinolysis

38. Questions?