Diese Präsentation wurde erfolgreich gemeldet.
Wir verwenden Ihre LinkedIn Profilangaben und Informationen zu Ihren Aktivitäten, um Anzeigen zu personalisieren und Ihnen relevantere Inhalte anzuzeigen. Sie können Ihre Anzeigeneinstellungen jederzeit ändern.

Haemostasis

Haemostasis

  • Als Erste(r) kommentieren

Haemostasis

  1. 1. The Physiology of Hemostasis Ira A. Shulman, MD Professor and Vice Chair of Pathology Keck School of Medicine of USC Medical Director of Transfusion Service USC Norris Cancer Hospital Los Angeles, California
  2. 2. 2 Activity Goals In this presentation, you will learn about: • Essential scientific components of hemostasis • The causes of and approximate frequencies of excessive surgical bleeding • How surgical complications, regardless of surgery type, can be attributed to bleeding and clotting • The importance of determining which patients are at greatest risk for surgical coagulopathy • How achieving optimal hemostasis can be viewed as a “balancing act”
  3. 3. 3 Prevalence of Uncontrolled Bleeding Surgical Discipline Uncontrolled Bleeding Rate Cardiovascular 5%-7% post-op1 General 1.9% laparoscopic cholecystectomy2 Obstetric 3.9% (vaginal); 6.4% (cesarean)3,4 Orthopedic 2%-6.3% hip/knee arthroplasty5-7 Urologic 4%-8% TURP8 ; 3.3%-9.9% URL9 Trauma 30%-40%10,11 1. Despotis GJ, et al. Anesth Analg. 1996;82:13-21. 2. Erol DD, et al. Internet J Anesth. 2005;9:2. 3. Combs CA, et al. Obstet Gynecol. 1991;77:69-76. 4. Combs CA, et al. Obstet Gynecol. 1991;77:77-82. 5. Hull R, et al. N Engl J Med. 1993;329:1370-1376. 6. Leclerc JR, et al. Ann Intern Med. 1996;124:619-626. 7. Strebel N, et al. Arch Intern Med. 2002;162:1451-1455. 8. Daniels PR. Nat Clin Pract Urol. 2005;2:343-350. 9.Rosevear HM, et al. J Urol. 2006;176:1458- 1462. 10. Holcomb JB. Crit Care. 2004;8(suppl 2):S57-S60. 11. Sauaia A, et al. J Trauma. 1995;38:185-193. TURP=transurethral prostatic resection.
  4. 4. 4 Definition of Hemostasis Hemostasis: “The arrest of bleeding” Stedman’s Medical Dictionary Hemostasis: “Life in the balance” Lawson JH, et al. Semin Hematol. 2004;41(suppl 1):55-64. • Trauma • Major surgery • Hemophilia • Stroke • Myocardial infarction (MI) • Thrombosis Bleeding to Death Clotting to Death
  5. 5. 5 Definition of Significant Bleeding • >2 L blood loss in an adult within first 24 post-op hours1  Volume of acute blood loss/patient weight >30 mL/kg  Volume of acute blood loss >40%-50% total blood volume • Surgical or vascular component: corrected by surgical intervention or embolization2 • Coagulopathic component: more difficult to control due to several interrelated mechanisms2  Consumption of coagulation factors and platelets  Dilution of coagulation factors  Metabolic disorders (eg, hypothermia, acidosis) 1. Despotis GJ, et al. Ann Thorac Surg. 2000;70(suppl 2):S20-S32. 2. Vincent J-L, et al. Crit Care. 2006;10:1-12.
  6. 6. 6 Reasons for Uncontrolled Bleeding Patient-related • Advanced age • Small body size • Gender • Pre-op anemia (low RBC volume) • Antiplatelet or antithrombotic drugs • Hypothermia • Acidosis • Systemic inflammatory response syndrome (SIRS) • Comorbidities:  Congestive heart failure  Hypertension  Chronic obstructive pulmonary disease  Peripheral vascular disease  Diabetes mellitus  Renal failure Procedure-related • Prolonged operation • CABG • Emergency/trauma • Surgical-site bleeding • Surgical skill Ferraris VA, et al. Ann Thorac Surg. 2007;83:S27-S86. RBC=red blood cell; CABG=coronary artery bypass graft.
  7. 7. 7 Surgery Post-op Recovery Thrombosis Clotting Bleeding Hemorrhage Can We Predict Who Will Bleed? Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl 1):55-64. • Who is likely to bleed or clot too much? • How do we optimize the patient’s physiology? • Which topical agents are effective? • Which biologic agents are effective? There Is a Difference Between Who Is at Risk and Who Will Bleed
  8. 8. 8 Patients at Risk for Surgical Bleeding Certain patients are at higher risk for surgical bleeding, including: • Patients taking  Long-acting anticoagulant therapy  Clopidogrel • Patients undergoing  Repeat surgical procedures  Oncologic surgery  Aortic surgery  Cardiac surgery  Neurologic procedures or neurosurgery  Radical prostatectomy • Dialysis patients • Trauma patients Ferraris VA, et al.. Ann Thorac Surg. 2007;83:S27–S86; Disorders of Hemostasis. In: Harrison’s Internal Medicine. New York, NY: Mc-Graw Hill; 2007. Available at: http://www.accessmedicine.com/resourceToc.aspx?resourceID=4. Tanaka KA, et al. Anesthesiology. 2003;98:1513-1515.
  9. 9. 9 Conditions Associated With Coagulopathy • Hemophilia • Platelet disorders • Liver disease • Uremia • Disseminated intravascular coagulation (DIC) • Dilutional coagulopathy • Anticoagulant treatment • Acidosis • Hypothermia • Extracorporeal circuits Ferraris VA, et al.. Ann Thorac Surg. 2007;83:S27–S86. Disorders of Hemostasis. In: Harrison’s Internal Medicine. New York, NY: Mc-Graw Hill; 2007. Available at: http://www. accessmedicine.com/resourceToc.aspx?resourceID=4.
  10. 10. 10 Thienopyridines Such as Clopidogrel and Postoperative Bleeding • Evidence is more compelling than for aspirin1  11 studies of clopidogrel and CABG  All studies show increased bleeding when clopidogrel given within 5 days of CABG — some with increased mortality • ACC/AHA and STS/SCA guidelines recommend stopping clopidogrel for 5 days before surgery (if possible)1,2 1. Ferraris VA, et al. Ann Thorac Surg. 2005;79:1454-1461. 2. Braunwald E, et al. J Am Coll Cardiol. 2002;40:1366-1374. CABG=coronary artery bypass graft.
  11. 11. 11 Traditional Model of Hemostasis Intrinsic Pathway Extrinsic Pathway factor XII HMK PK factor XI factor XIa factor IX factor IXa factor VIIIa PL, Ca+2 factor X factor Xa factor Va PL, Ca+2 prothrombin thrombin fibrinogen fibrin factor VIIa tissue factor PL, Ca+2 factor X Adapted from Hoffman M, et al. Thromb Haemost. 2001;85:958-965.
  12. 12. 12 Vascular Spasm Currie D. Available at: http://faculty.etsu.edu/currie/hemostasis.htm. Accessed May 6, 2008. Blood vessel Vascular spasm Region of trauma
  13. 13. 13 Platelet Plug Formation—Primary Hemostasis Reprinted with permission from Rinder C. In: Spiess BD, et al, eds. Perioperative Transfusion Medicine. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:chap 8. ©2005 Lippincott Williams & Wilkins http://lww.com Platelet adhesion to subendothelial vWF vWF=von Willebrand factor; GP=glycoprotein.
  14. 14. 14 Platelet Plug Formation—Primary Hemostasis Reprinted with permission from Rinder C. In: Spiess BD, et al, eds. Perioperative Transfusion Medicine. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:chap 8. ©2005 Lippincott Williams & Wilkins http://lww.com
  15. 15. 15 Vascular Endothelium Serves As a “Front Line” Defense Against Pathologic Thrombosis This figure was published in Semin Hematol, Vol 41(suppl 1), Lawson JH, et al, “Challenges for Providing Effective Hemostasis,” pp 55-64, ©Elsevier 2004.
  16. 16. 16Hoffman M, et al. Blood Coag Fibrinol. 1998;9(suppl 1):S61-S65. TF-Bearing Cell Activated Platelet Platelet TF VIIIa Va VIIIa Va Va VIIa TF VIIa Xa X II IIa IX V Va II VIII/vWF VIIIa II IXa X IX X IXa IXa VIIa Xa IIa IIa Xa Evolving Model of Hemostasis TF=tissue factor; vWF=von Willebrand factor.
  17. 17. 17 Fibrinolysis tPA=tissue plasminogen activator; PAI-1=plasminogen activator inhibitor 1; AP=anti-plasmin; PAP=plasmin-anti-plasmin complexes. Reprinted with permission from Chandler WL. In: Spiess BD, et al, eds. Perioperative Transfusion Medicine. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:chap 7. ©2005 Lippincott Williams & Wilkins http://lww.com Endothelium Endothelium tPA PAI-1 tPA-PAI-1 PAP AP D-dimerPlasmintPA + Plasminogen
  18. 18. 18 Putting It All Together Reprinted with permission from Chandler WL. In: Spiess BD, et al, eds. Perioperative Transfusion Medicine. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:chap 7. ©2005 Lippincott Williams & Wilkins http://lww.com Wound: collagen and tissue factor exposure Fibrin formation, clot stabilization Platelet binding and coagulation initiation Platelet contraction, wound healing, fibrin removal Platelet aggregation Wound healed
  19. 19. 19 Normal Hemostasis Is a Balance Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl 1):55-64. • Trauma • Major surgery • Hemophilia • Stroke • MI • Thrombosis Bleeding to Death Clotting to Death • Blood coagulation • Anticoagulation • Fibrinolysis • Antifibrinolysis • Vascular tone and blood flow • Endothelial cells and platelets
  20. 20. 20 “Keeping on Center”: Moving Toward Normal Hemostasis Normal Hemostasis Procoagulant Activity Anticoagulant Activity Fibrinolytic Activity Antifibrinolytic Activity Bleeding Clotting Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl):55-64.
  21. 21. 21 “Keeping on Center” (cont) Topical Hemostatics Purified Factors, FFP, Cryo, PLTs Aminocaproic acid Tranexamic acid Heparin, Warfarin LMWH, Argatroban t-PA, SK, UPA Normal Hemostasis Bleeding Clotting FFP=fresh frozen plasma; Cryo=cryoprecipitate; PLTs=platelets; SK=streptokinase; UPA=urinary-type plasminogen activator; LMWH=low-molecular-weight heparin. Procoagulant Activity Anticoagulant Activity Fibrinolytic Activity Antifibrinolytic Activity Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl):55-64.
  22. 22. 22Adapted from Reed RL, et al. Circ Shock. 1990;32:141-152. ** ** ** ** **P<.0001 vs clotting time at 37o C. Temperature (o C) Temperature (o C) ** ** ** * * **P<.0001 vs clotting time at 37o C. 20 22 24 26 28 30 32 23 25 27 29 31 33 35 37 ThrombinTime(sec) Temperature (o C) **P<.0001 vs clotting time at 37o C. *F<.005 vs clotting time at 37o C. ** ** * Effect of Temperature on Test Results of aPTT, TT, and PT aPTT=activated partial thromboplastin time; PT=prothrombin time; TT=thrombin time. 25 30 35 40 45 50 55 60 65 70 23 25 27 29 31 33 35 37 39 aPTT(sec) 10 12 14 16 18 20 22 24 26 23 25 27 29 31 33 35 37 39 ProthrombinTime(sec) * *
  23. 23. 29 volunteers had 2 U RBC removed by apheresis (re-infusion of PRP) 11 received back autologous RBC 18 did not receive back their RBC Valeri et al. Transfusion 2001;41:977-83. Effect of 2-unit RBC apheresis or plateletspheresis on bleeding time 0 1 2 3 4 5 6 7 8 9 RBCs Platelets BTat35°C Apheresis Hct: 41 35 (15%)↓ 40 40 Platelet count: 220 200 (9%)↓ 238 163 (32%)↓ Apheresis Return of RBCs Apheresis Return of RBCs Does Anemia Induce Reversible Platelet Dysfunction? Before apheresis 0.50 1.00 1.50 2.00 1 Hour TX1 TX2 1 DAY 2 DAY 3 DAY 7 DAY TemplateBT(ratioafter:beforeapheresis) 0.70 0.80 0.90 1.00 1.10 Before apheresis 1 Hour TX1 TX2 1 DAY 2 DAY 3 DAY 7 DAY PeripheralVenousHct (ratioafter:beforeapheresis)
  24. 24. 24 • During room-temperature storage in the blood bank, platelets express a number of glycoprotein ligands, making them prothrombotic1-3 • Platelets excrete granules containing cell signaling compounds that are capable of triggering reactions in WBCs, endothelial cells, and other native platelets3,4 • This complex activation biology is recognized as part of the platelet storage lesion4 • In certain circumstances, platelet transfusions might increase risk of stroke or death5 1. Spiess BD. Transfusion. 2007;47:354–356; 2. Seghatchian MJ, et al. Transfus Sci. 1997;18:103-107; 3. Van der Planken MG, et al. Ann Hematol. 1999;78:1-7; 4. Seghatchian J, et al. Transfus Med Rev. 1997;11:130-144; 5. Spiess BD, et al. Transfusion. 2004;44:1143-1148. The Platelet “Storage Lesion” and the Potential Prothrombotic Effect of Platelets
  25. 25. 25 Thrombosis Clotting Bleeding Hemorrhage Physiology and Good Surgery Topical Hemostatic Agents Systemic Biologic Therapies Achieving Optimal Operative Hemostasis Adapted from Lawson JH, et al. Semin Hematol. 2004;41(suppl):55-64.
  26. 26. 26 Hemostasis: Final Thoughts • Many surgical complications, regardless of surgery type, can be attributed to bleeding and clotting • It is important to determine which patients are at greatest risk for surgical coagulopathy • Achieving optimal hemostasis involves a balancing act, whereby patients must be kept from bleeding or clotting to death through transfusional and nontransfusional therapies

×