1. Hemostasis and heavy bleeding M Hellgren Sahlgrenska University Hospital Gothenburg

2. 1999-2009 SU 1999 2009

3. Damage Repair

4. Platelets leucocyte Von Willebrand factor erytrocyte Vasoconstriction What happens at the vessel wall? Baghaei & Stigendal 2009

5. VWF GPIb Fibrin GPIIb/IIIa (Fibrinogen receptor) GPIIb/IIIa (Fibrinogen receptor) Collagen GPIa/IIa Plateletplug ( 10min ) Baghaei & Stigendal 2009 Blood Coagulation starts

6. Platelet aggregation Platelet aggregation

7. Blood Coagulation TF FVIIa FXa Thrombin Fibrinogen Fibrin FXIa FIXa FVIIIa FVa FXIIIa PK- INR APTT Initiation Amplification Baghaei & Stigendal 2009 Platelet

8. Fibrinogen

10. Collet, J.-P. et al. J. Biol. Chem. 2003;278:21331-21335

11. Fibrinogen Fibrin Fibrinogen-,fibrin degradation products D-dimers Plasminogen urokinase PAI-1 tPA PAI-2 TAFI Faktor V Plasmin Faktor VIII alfa 2 antiplasmin

12. Fibrinolysis at different fibrin net Collet JP et al. Aretrioscler Thromb Vasc Biol.2000;20:1354-61

13. Platelet plug Initiation thrombin-fibrin Amplification thrombin-fibrin Fibrinolysis D-dimer Fibrin

14. Hemostasis during pregnancy Bleeding Thrombosis

15. Hemostasis during pregnancy

16. Kjellberg et al 1999 F 1+2 Soluble fibrin D-dimer

17. Hellgren-81

19. Laboratory Analyses Global tests Laboratory Analyses Thromboelastogram APTT Sonoclot PK (INR) Platelets Fibrinogen D-dimer Antithrombin Blood sampling each (2) - 4-6:e hours

20. Routine laboratory analyses Third trimester Hemostasis APTT, s normal/short normal PK, INR < 0.9 < 1.6 Platelets, x 10 9 /L > 100 > 50 Fibrinogen, g/L > 3.0 g/l > 2.0 - 2.5 D-dimer, mg/L < 2.0 mg/L ?? Antithrombin, kIE/L > 0.80 >0.80

21. Thromboelastograph

22. Thromboelastography (TEG)

23. TEG Normal values r = reaction time 6-9 min MA = maximal amplitude 50-70 mm α° = speed of fibrin formation > 50° α°α° r MA Kang et al: Anesth Analg 1985:64:888-896 CoagulationFibrinolys

24. Thromboelastography

25. Platelet function Bleeding time ; prolonged = increased bleeding Multiplate: aggregation (ASA and platelet inhibitors ) Platelet adhesion (hereditary defect)

26. Acquired coagulation disorders Lokal consumption Dilution DIC Decreased synthesis Primary fibrinolys Sekundary fibrinolys Thrombocytopathy

27. Hemostasis disorders

29. Fibrinogen and heavy obstetric bleeding Charbit-et al 2007

30. Coagulation analyses 0-24h Charbit et al 2006

31. Abruptio placentae h, post partum 0 4 12 36 HB, g/L 127 88 81 91 TPK, x10 9 /L 75 66 96 78 APTT,s 46 47 37 37 Fib, g/L - 0.5 2.0 3.0 PK(INR) <0.9 1.3 1.2 1.0 AT,IE/L 0.60 0.48 1.03 0.97 D-dimer, mg/L >8 >8 1.2 0.5-1.0

33. Bleeding 25 L E-conc plasma platelets Cristalloids and colloids

34. Blood and plasmaproducts Bleeding Transfusion Less than 2-2,5 L Erythrocytes More than 2-2,5L Ery:plasma 1:1 Platelets each 4

35. Treatment Erythrocyte concentrat HB > 100 g/L Fresh frosen plasma factor V, VIII, other factors, inhibitors Stored plasma stabile factorerand inhibitors Platelet concentrate at bleeding > 80-100x10 9 /L Fibrinogen >2-2,5 g /L Cyklokapron 20-30 mg /kg body weight iv Concomittant administration! 4:4:1 4 g fibrinogen

36. Fibrinolysis and uterine contractions t-PA Uterine contractions D-dimer

37. R-FVIIa (Novoseven®) NovoNordisk

38. Register study from Northern Europe 2000-2004 n=113 improvement ( % ) 97 treatment80 16 prophylaxis 75 4 thromboembolism 5 death One myocardial infarction Bleeding from arterial aneurysm and liver Hypovolemic shock Sepsis Brain damage Alfirevic et al Obstet Gynecol 2007;110:1270-8

39. Novoseven aktivated factor VII 0,1 mg / kg b.w. Antithrombin < 0.5 IU/ L Temperature <35° C, pH<7.2 and normal Ca + + Other factor koncentrate in collaboration with expert in blood coagulations Additional treatment

40. Desmopressin (Octostim) Desmopressin v Willebrands factor FVIII, t-PA ASA dextran thrombocytopaties von Willebrands disease uremia liver cirrhosis