Hemostasis and Surgical Bleeding

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

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

Hemostatic System In Vivo

Primary hemostasis
von Willebrand factor Sufficient hematocrit

Hemostatic System In Vivo

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 Chemokine: PDGF, PTGF- 1, EGF

Hemostatic System In Vivo

Blood coagulation
Extrinsic & intrinsic pathway Tissue factor-factor VII pathway

Hemostatic System In Vivo

Blood coagulation
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)

Hemostatic System In Vivo

Natural anticoagulant mechanisms

Tissue factor pathway inhibitor (TFPI) Protein C, Protein S Antithrombin III

Hemostatic System In Vivo

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

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

Anticoagulant Agents
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)
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)

General Surgery Ortho Surgery Trauma Surgery

12 30 5

4386 4712 437

5% 21% 28%

80% 71% 44%

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

Incidence hard to estimate Increased bleeding time Desmopressin, platelet transfusion

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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

Conditions Associated with an Enhanced Risk of Perioperative Bleeding

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,

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Conditions Associated with an Enhanced Risk of Perioperative Bleeding Renal failure

Impaired platelet adhesion, aggregation and release Low hematocrit - impaired primary hemostasis Desmopressin +/- platelet concentrate Correction of anemia, hemodialysis

Conditions Associated with an Enhanced Risk of Perioperative Bleeding 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

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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

Low incidence of major bleeding complications after appropriate preoperative preparation

Conditions Associated with an Enhanced Risk of Perioperative Bleeding 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 High morbidity and mortality from bleeding

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Conditions Associated with an Enhanced Risk of Perioperative 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

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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

Both PT/ aPTT up

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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