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Dakila P. De los Angeles, M.D., FPCS, FPSGS Department of Surgery UST Faculty of Medicine & Surgery
Cross-linked fibrin: ultimate step in the coagulation cascade Synthesis of coagulation factors in the liver
(factors II, VII, IX & X)
Anticoagulant Agents
Antiplatelet agents
Aspirin Dipyridamole ADP-inhibitors
Clopidogral
Anticoagulant Agents
Vitamin K antagonists Coumarin derivatives
Warfarin, Acenocoumarol, phenprocoumon Block carboxylation of factors II, VII, IX & X Prothrombin time (PT) International Normalized Ratio (INR)
Increasing INR - increasing intensity of anticoagulation
Side-effect: bleeding
Anticoagulant Agents
Heparin
Glycosaminoglycans, 4-20 kDa Binds to antithrombin III Immediate effect after IV administration aPTT for monitoring
RCTs on the Efficacy and Safety of LMWH in the Prevention of Postoperative Venous Thromboembolism in Patients Undergoing General Surgery, Ortho Surgery and Trauma Surgery (Level 1 evidence)
Type of Surgery # of Trials # of Patients Incidence of venous thromboemb olism (95% CI) RRR of postop venous thromboemb olism Increase in bleeding complication s (95% CI) Increase in major bleeding complication s (95% CI)
12 30 5
5% 21% 28%
16% 7% 11%
3% -1% 0%
Prohemostatic Agents
Platelets Transfusion guidelines for platelet concentrates
Platelet count <10 x 109/l Platelet count <50 x 109/l with demonstrated bleeding or a planned surgical/ invasive procedure Documented platelet dysfunction eg. Prolonged BT Bleeding patients or patients undergoing a surgical procedure who require >10 units of packed red cells
Prohemostatic Agents
Plasma Fresh or frozen plasma contains all coagulation factors Transfusion guidelines
Correction of multiple or specific coagulation factor deficiencies in bleeding patients or if surgical/invasive procedure is planned Volume replacement in case of severe bleeding to avoid massive transfusion of gelatin or crystalloid solutions Thrombocytopenic thrombotic purpura
Prohemostatic Agents
Prothrombin complex concentrates (PCC)
Contain vitamin K-dependent coagulation factors For immediate reversal of coumarin therapy If global replenishment of coagulation factors is necessary and large volumes of plasma are not tolerated
Prohemostatic Agents
Cryoprecipitate Contains mainly vWF, factor VIII, and fibrinogen High likelihood of transmission of infectious agents
Prohemostatic Agents
Desmopressin, DDAVP Deamino-D-arginine vasopressin
Vasopressin analogue Induces release of vWF Potentiates primary hemostasis Treatment of bleeding in patients with von Willebrand disease or mild hemophilia A
Impaired primary hemostasis
Uremia, liver cirrhosis, aspirin-associated bleeding
Prohemostatic Agents
Recombinant Factor VIIa
Potent procoagulant activity Still undergoing clinical trial
Prohemostatic Agents
Antifibrinolytic agents
Aprotinin - inhibits activity of various serine proteases (plasmin, coagulation factors or inhibitors, and constituents of the kallikrein-kinin system)
Contraindicated in DIC, patients with renal failure
Lysine analogues
-aminocaproic acid, tranexamic acid Competitive binding to the lysine-binding site of a fibrin clot - prevents plasminogen binding Contraindicated in DIC
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Conditions Associated with an Enhanced Risk of Perioperative Bleeding Congenital coagulation abnormalities
von Willebrand Disease
Most frequent primary hemostatic defect 1:25,000 for severe 1 to 5:1,000 for mild vWF - carrier and stabilizing factor of plasma factor VIII Lifelong bleeding tendency Treatment: desmopressin, vWF concentrate
Conditions Associated with an Enhanced Risk of Perioperative Bleeding Congenital coagulation abnormalities
Thrombocytopathies
Glycoprotein Ib deficiency Glycoprotein Iib/IIIa deficiency Syndrome of Bernard Soulier Glanzman thrombasthenia
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Conditions Associated with an Enhanced Risk of Perioperative Bleeding Congenital coagulation abnormalities
Thrombocytopathies
Hemophila A & B (factor VIII & IX) Best known congenital defects Severe type - spontaneous bleeding tendency Moderate type - bleeding after trauma Major surgical intervention - administer coagulation factor concentrate for 7 to 10 days
If associated with portal hypertension and splenomegaly - serious thrombocytopenia In cirrhosis - impaired platelet function Increased risk of perioperative bleeding
Assess platelet count, BT, aPTT, PT Tx: Vitamin K, plasma, PCC,
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Conditions Associated with an Enhanced Risk of Perioperative Bleeding Immune thrombocytopenia, ITP
Autoantibodies against glycoproteins Increased platelet destruction/removal results in splenomegaly
Human immunoglobulin - rapid but short-lived Platelet transfusion
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Conditions Associated with an Enhanced Risk of Perioperative Bleeding Myeloproliferative disorders Lymphoproliferative disorders Malignancies
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Finding
Thrombocytopenia
Potential Cause
ITP Impaired platelet production DIC HIT vonWillebrand dse, thrombocytopathy Uremia, liver failure, myeloproliferative disorder, etc Coagulation factor deficiency (VIII, IX, XI, XII) Use of heparin Coagulation factor deficiency (VII) Vitamin K deficiency Mild hepatic insufficiency
Further test
Antiplatelet antibodies, thrombopoietin CBC, bone marrow analysis aPTT, PT, fibrin degradation products HIT test Plalelet aggregation test, vWF _ Measure coagulation factor _ Measure coagulation factor Measure F VII & F V or administer vitamin K and repeat after 1-2 days _ Measure coagulation factor _ Measure coagulation factor Platelets, fibrin degradation products _
Prolonged BT
aPTT up, PT ok
PT up, aPTT ok
Coagulation factor deficiency (X, V, II, or fibrinogen) Use of oral anticoagulants Severe hepatic insufficiency DIC Loss/dilution caused by excessive bleeding/massive transfusion
Management of Postoperative Bleeding Know if bleeding is a result of systemic hemostatic defect or a local problem in surgical hemostasis Global coagulation screening
Platelet count, PT, aPTT If tests are abnormal, replace factors REOPERATE!
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