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The Biology of Bleeding and Clotting to Death

The Biology of Bleeding and Clotting to Death. Jeffrey H. Lawson, MD, PhD Director, Vascular Surgery Research Lab Director of Clinical Trials in Vascular Surgery Duke University Medical Center Durham, North Carolina. What Are the Challenges of Hemostasis in Surgery?.

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The Biology of Bleeding and Clotting to Death

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  1. The Biology of Bleeding and Clotting to Death Jeffrey H. Lawson, MD, PhD Director, Vascular Surgery Research Lab Director of Clinical Trials in Vascular Surgery Duke University Medical Center Durham, North Carolina

  2. What Are the Challenges of Hemostasis in Surgery? • Who is likely to bleed or clot too much? • How do we optimize the physiology of the patient? • Which topical agents are effective? • Which biologic agents are effective? When? How much? How not to overshoot? Thrombosis Clotting Post-op Recovery Surgery BleedingHemorrhage

  3. Bleeding, Clotting, and Surgery • D&C for 2 years at Duke University = 358 complications • Total bleeding and thrombosis complications: 197/358 = 55% • 114 of 358 cases could not be well adjudicated with respect to complications  Well-documented data reveal 197/244 = 81% • Total perioperative bleeding complications: 131/244 = 54% • Total perioperative thrombosis complications: 75/244 = 31% • Total deaths: 67 • Bleeding as cause of death: 18/67 = 27% • Thrombosis as cause of death: 22/67 = 33% D&C=dilation and curettage.

  4. Coagulation Cascade: Tissue Factor Pathway VII(VIIa) XIII II X XIIIa IIa Xa TF·VIIaCa2:PL Va·Xa Ca2:PL IIa FN (cross-linked) TF·VII(VIIa) IXaß VIIa Fn Xa IIa TF (IXα) V VIIIa-IXaßCa2:PL XIa Fg IXaß XaPL XI IIa IX Xa IIa VIII

  5. The Problem Most complications are at the dark interface between: • Biology • Clinical skill • Medical therapy • Sick patients

  6. Hemostasis “The arrest of bleeding”  Stedman’s Medical Dictionary But is hemostasis more than that?

  7. Hemostasis In surgery—hemostasis is … • About bleeding • About clotting • About timing • About balance

  8. Hemostasis“Life in the Balance” Bleedingto Death Clottingto Death Trauma Major Surgery Hemophilia Stroke MI Thrombosis Lawson JH, et al. Semin Hematol. 2004;41(suppl 1):55-64.

  9. Hemostasis “Too thick or too thin”  Dr. Richard McCann Hemostasis in cardiovascular surgery “Knowing when to be thick and when to be thin”

  10. Hemostasis • Blood coagulation • Anticoagulation • Fibrinolysis • Antifibrinolysis • Vascular tone and blood flow • Endothelial cells and platelets

  11. Keeping on Center Antifibrinolytic Activity Procoagulant Activity Normal Hemostasis Bleeding Clotting Anticoagulant Activity Fibrinolytic Activity Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl):55-64.

  12. What About Hemostatic Swings During Surgery? Thrombosis Clotting Post-op Recovery Surgery BleedingHemorrhage Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl 1):55-64.

  13. Keeping on Center Factor V falls IIase increase Antifibrinolytic Activity Procoagulant Activity TF increase Normal Hemostasis PAI-1 increase Bleeding Clotting Anticoagulant Activity Fibrinolytic Activity Inflammatory Cytokines Heparin falls t-PA increase Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl):55-64.

  14. Keeping on Center Topical Hemostatics Purified Factors, FFP, Cryo, PLTs Aminocaproic acid, Aprotinin Antifibrinolytic Activity Procoagulant Activity Normal Hemostasis Bleeding Clotting Anticoagulant Activity Fibrinolytic Activity t-PA, SK, UPA Heparin, Warfarin LMWH, Argatroban FFP=fresh frozen plasma; Cryo=cryoprecipitate; PLTs=platelets; SK=streptokinase; UPA=urinary-type plasminogen activator; LMWH=low-molecular-weight heparin. Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl):55-64.

  15. Operative Management Thrombosis Clotting Physiology and Good Surgery Bleeding Topical Hemostatic Agents Hemorrhage Systemic Biologic Therapies Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl):55-64.

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