Hemostasis and Surgical Bleeding

Dakila P. De los Angeles, M.D., FPCS, FPSGS Department of Surgery UST Faculty of Medicine & Surgery

Chemokine: PDGF, PTGF- 1, EGF Blood coagulation Extrinsic & intrinsic pathway Tissue factor-factor VII pathway

Discuss the essentials of hemostasis and Surgical bleeding

Explain the processes involved in hemostasis Discuss the evaluation of surgical patient as a hemostatic risk Describe the more common congenital/acquired hemostatic problems Discuss types of local hemostasis Discuss proper use of blood products in transfusion therapy

Hemostatic System In Vivo

Primary hemostasis Fibrin formation Removal of fibrin Primary hemostasis von Willebrand factor Sufficient hematocrit

Thrombin key enzyme in activation of coagulation Activator of platelet aggregation Cross-linked fibrin: ultimate step in the coagulation cascade Synthesis of coagulation factors in the liver (factors II, VII, IX & X) Natural anticoagulant mechanisms Tissue factor pathway inhibitor (TFPI) Protein C, Protein S Antithrombin III Fibrinolysis Fibrinolytic system Conversion of plasminogen to plasmin Plasminogen activators tPA, uPA Present in endothelial cells Released by hypoxia and acidosis Inhibition of fibrinolytic system PAI-1, 2-antiplasmin

Primary hemostasis Platelet activation Arachidonic acid converted to thromboxane A2 Release of proteins from platelet storage granules Platelet agonist: ADP, serotonin Coagulation factors: vWF, coagulation factor V Heparin-binding proteins: platelet factor 4, thromboglobulin

Anticoagulant Agents

Antiplatelet agents Aspirin Dipyridamole ADP-inhibitors Clopidogral Glycoprotein receptor IIb/IIIa inhibitor Ticlopidine, Tirofiban, Abciximax 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 Heparin Glycosaminoglycans, 4-20 kDa Binds to antithrombin III Immediate effect after IV administration aPTT for monitoring Low Molecular Weight Heparin 4-6 kDa More favorable antithrombotic effect, less bleeding complications No need for frequent monitoring and dose adjustments Side-effect: bleeding, heparin-induced thrombocytopenia (HIT) 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)
Incidence of venous thromboembolism (95% CI) Type of Surgery # of Trial # of Patient RRR of postop venous thrombo embolis m 80% 71% 44% Increase In bleeding Complic a Tions (955 CI) 16% 7% 11% Increas e In Major Bleedin g Compli cation 3% -1% 0%

Bleeding patients or patients undergoing a surgical procedure who require >10 units of packed red cells 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 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 Cryoprecipitate Contains mainly vWF, factor VIII, and fibrinogen High likelihood of transmission of infectious 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 Recombinant Factor VIIa Potent procoagulant activity Still undergoing clinical trial 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

General Ortho Trauma

12 30 5

4386 4712 437

5% 21% 28%

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

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

Thrombocytopathies Glycoprotein Ib deficiency Glycoprotein Iib/IIIa deficiency Syndrome of Bernard Soulier Glanzman thrombasthenia Incidence hard to estimate Increased bleeding time Desmopressin, platelet transfusion 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 Liver Failure Low levels of coagulation factors Vitamin K deficiency Biliary tract obstruction 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,

High morbidity and mortality from bleeding Myeloproliferative disorders Lymphoproliferative disorders Malignancies

Identification of Patients at Risk for Bleeding

Medical history Physical examination Routine coagulation test NOT necessary Preop screening strategy Platelet count, PT, aPTT BT, vWF assay Factor XIII, 2-antiplasmin
Finding
ITP Impaired platelet production DIC HIT vonWillebrand dse, thrombocytopathy Prolonged BT Uremia, liver failure, myeloproliferative disorder, etc Coagulation factor deficiency (VIII, IX, XI, XII) Use of heparin Coagulation factor deficiency Vitamin K deficiency Mild hepatic insufficiency Coagulation factor deficiency (X, V, II, or fibrinogen) Use of oral anticoagulants Both PT/ aPTT up Severe hepatic insufficiency DIC Loss/dilution caused by excessive bleeding/massive transfusion

Potential Cause

Further test
Antiplatelet antibodies, thrombopoietin CBC, bone marrow analysis aPTT, PT, fibrin degradation products HIT test Plalelet aggregation test, vWF _

Thrombocytopenia

Renal failure Impaired platelet adhesion, aggregation and release Low hematocrit - impaired primary hemostasis Desmopressin +/- platelet concentrate Correction of anemia, hemodialysis Vitamin K deficiency Cofactor for factors II, VII, IX, & X Inadequate dietary intake Insufficient adsorption Loss of storage sites Prolongs global coagulation times particularly prothrombin time Vitamin K intravenously PCC for immediate correction Immune thrombocytopenia, ITP Autoantibodies against glycoproteins Increased platelet destruction/removal results in splenomegaly Human immunoglobulin - rapid but short-lived Platelet transfusion Low incidence of major bleeding complications after appropriate preoperative preparation acquired hemophilia Development of autoantibodies to a coagulation factor in patients being treated for congenital coagulation factor deficiency after transfusion of coagulation factor concentrates Rare but serious disorder

aPTT up, PT ok

Measure coagulation factor Measure coagulation factor Measure F VII & F V or administer vitamin K and repeat after 1-2 days Measure coagulation factor _

PT up, aPTT ok

Measure coagulation factor Platelets, fibrin degradation products _

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!