2012, Görlinger Klaus

Transcription

1 Gerinnungsmanagement der Gegenwart - wie gehen wir heute vor? 25. Allander Gerinnungsrunde am 15. März 2012 Klaus Görlinger Universitätsklinikum Essen klaus@goerlinger.net

2 CSL Behring GmbH Octapharma AG Tem International GmbH Conflicts of interest Verum Diagnostica GmbH Instrumentation Laboratory

3 Transfusion strategies Formula driven: 1:1:1-concept Lab-driven Individualized POC-driven

4 Results:... Patients arrived in the ICU 6.8 ± 0.3 hours after admission. Coagulopathy, present at hospital admission (pre-icu INR, 1.8 ± 0.2) persisted at ICU admission (initial ICU INR, 1.6 ± 0.1).... In the ICU during resuscitation mean INR decreased to 1.4 ± 0.03 within 8 hours, indicating moderate coagulopathy.... The ratio of FFP:PRBC was 1:1.... Statistical analysis found severity of coagulopathy (INR) at ICU admission associated with survival outcome (p = 0.02). 1: hours to achieve an INR < 1.5!

5 Conclusion:... More aggressive pre-icu intervention to correct coagulopathy may be effective in decreasing RPBC requirement during ICU resuscitation, and, because of the association with increased mortality, could improve outcome.... We think that treatment of coagulopathy can be improved with the development of standardized protocols, both empiric and data driven.!!

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7 Exposure to ABO-compatible plasma results in an increase in overall complications (53.5% vs 40.5%, P =.002), in particular ARDS (19.4% vs 9.2%, P =.0011) and sepsis (38.0% vs 28.9%, P =.02). There is a stepwise increase in the complication rate as exposure increases (reaching 70.0% for patients receiving more than 6 U; these patients also had a 4-fold increase in ARDS).

8 86082 Swedish patients receiving their first plasma transfusion (follow up of 14 days) Transfusion of 5 or more units of AB0-compatible but non-identical plasma was associated with an increased mortality by 15% compared to recipients of only AB0-identical plasma

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12 Results: A high ratio of FFP:RBC in the 15 TASH group was independently associated with survival, with an odds-ratio of 2.5 ( ), while the <15TASHgroupwas associated with increased multi-organ failure, 47% vs. 38%, (P < 0.005).

13 DO YOU HAVE THE BLEEDING UNDER CONTROL??? Will this patient bleed?

14 ROTEM analysis enables rapid detection of most coagulation disorders; this study demonstrates the additional benefit of MT risk stratification using results available within 10 minutes after CT.

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21 Why does the patient bleed?

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23 Pyramid of therapy in coagulopathy rfviia FVIII / FXIII Platelets PCC (or FFP) Fibrinogen (or Cryo) Hyperfibrinolysis? Aspirin? Oral anticoagulants? Heparin? Basic conditions (T C > 34ºC; ph > 7,2; Ca i > 1 mmol/l; Hb > 8 g/l) Surgical stanching (Compression bandage; MAST; pelvic compression; packing)

24 Trauma Algorithm Waydhas C, Görlinger K. Unfallchirurg. 2009; 112(11): Bleeding patient! Preconditions Tranexamic acid Fibrinogen or Cryo Platelets PCC or FFP Protamine Platelet function? FXIII or rfviia

25 Coagulation factors, anticoagulants, FDPs ROTEM parameters Platelets, fibrinogen, colloids Fibrinolytic enzymes, fibrinolysis inhibitors, F XIII A10 = Amplitude 10 min after CT

26 Regression-analysis and Bland-Altman analysis for ExTEM measurements from 866 patients undergoing non-cardiac surgery

27 Regression-analysis and Bland-Altman analysis for FibTEM measurements from 866 patients undergoing non-cardiac surgery

28 Standard coagulation test results were available after a median of 53 min [inter-quartile range (IQR): min], whereas 10 min values of ROTEM results were available online after 23 min (IQR: min).

29 Postpartum haemorrhage with hyperfibrinolysis Intraoperative Substitution: 58 min 2 g tranexamic acid 4 g fibrinogen 3000 IU PCC 1 U pooled PC 4 g fibrinogen 6 U PRBC 28 min 41 min

30 ROTEM after haemodiltution by 50% with Ringer solution, Gelafundin 4% and HAES-steril 10% 50% B, 50% RINGER PT 51 % ATIII 19 % Fib 103 mg/dl PT 108 % ATIII 90 % Fib 218 mg/dl 50% B, 25% R, 25% GELA 50% B, 25% R, 25% HAES PT 54 % ATIII 23 % Fib 100 mg/dl PT 58 % ATIII 23 % Fib 110 mg/dl

31 Transfusion 2010

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33 Diffuse bleeding after protamine (CABG surgery + AVR): calculated goal-directed therapy with Fibrinogen concentrate 5 min 34 min Targeted increase in MCF FIB = 8 mm 50 mg/kg x 80 kg = 4 g Fibrinogen Alternative: 16 U FFP?

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35 Motorbike accident with open leg fracture and severe bleeding: goal-directed therapy with Prothrombin Complex Concentrate 2 min 19 min 175 cm, 110 kg INR Quick (PT in %) 27% 44% 2000 IU PCC Alternative: 12 U FFP?

36 Diffuse bleeding after protamine (CABG surgery + MVR): goal-directed therapy with Prothrombin Complex Concentrate 2 min 28 min 180 cm, 78 kg ACT 162 s INR 2.8 Quick 25% 25% x 80 kg = 2000 IU PCC Alternative: 12 U FFP? ACT 114 s INR 1.5 Quick 50%

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43 115 patients with coagulopathy 44 patients (38.3%) received FFP transfusion INR was corrected in 16 of 44 patients (36%) Median dose of FFP in patients with corrected INR was 17 ml/kg Median dose of FFP in patients without corrected INR was 10 ml/kg New onset of acute lung injury (ALI) was more frequent in the transfused group (18% vs 4%; p = 0.021) Conclusion: The risk-benefit ratio of FFP transfusion in critically ill medical patients with coagulopathy may not be favorable!

44 Advantages of Fibrinogen concentrate and PCC against FFP Rapid, effective, and well predictable increase in coagulation factor activity Applicable in a small volume without the risk of transfusion-associated circulatory overload (TACO) No risk of TRALI and mistransfusion (both responsible for most fatal cases of transfusionrelated adverse events) Effective viral inactivation / elimination (no reported case of viral transmission within the last ten years)

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46 ROTEM - and Multiplate -based algorithms for perioperative POC coagulation management -62% RBC -66% MT -95% FFP -66% Plt. +66% LTX % RBC -79% FFP -65% Plt. +16% Cases -8.4% RBC -58% MT -98% FFP +115% Plt. +32% Cases

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48 Intraoperative transfusion requirements for LTX per case at University Hospital Essen, Germany (incidence; median [25 th / 75 th percent.] {90 th ; 95 th ; max}) LTX: 162 in 2010 RBC: 65%; 2 U/LTX [0 /4] {8; 10; 40} PC: 20%; 0 U/LTX [0 /0] {2; 2; 8} FFP: 17%; 0 U/LTX [0 / 0] {3; 5; 34} CRYO: 0%; 0 U/LTX [0 / 0] {0; 0; 0} rfviia: 0%; 0 mg/ltx [0 / 0] {0; 0; 0}

49 4.0% 96.0% Mean age: 53.7 ± 11.3 y 315 male and 180 female (36.4%)

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51 % Safety and efficacy of prothrombin complex and fibrinogen concentrates in liver transplantation recipients (2-year period): 163 male, 103 female (38.7%); mean age y; mean MELD score p=0.73 4,5 3,6 p=0.4 0,6 0,6 p= % p=0.78 HAT PVT MI PE ST CAE 1,3 0,9 p= p=0.31 7,1 4,5 156 patients (59%) received CFC Study group Control group 110 patients (41%) did not receive any CFC

52 Cummulative cost saving compared to 1999 in visceral surgery and liver transplantation at University Hospital Essen, Germany 1999 = year before implementation of ROTEM diagnostic = 1,765, Euro Cost-saving per year compared to Cost-saving

53 Preise: 85/E 65/E 250/E 288/g 126/500IE 44/500IE 527/1250IE für POC-Diagnostik

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55 (1,718 patients in 2004 and 2,147 in 2009; = 25%)

56 Platelet function? Tranexamic acid Preconditions Cardiovascular Algorithm Görlinger K, et al. Appl Cardiopulmon Pathophysiol 2009; 13(2): Bleeding patient! Protamine Fibrinogen or Cryo 4F-PCC or FFP Platelets FXIII or rfviia

57 Antifibrinolytics Aprotinin Tranexamic acid

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60 Recurrent thromboembolic events Sufficient (!?) oral anticoagulation and i.v. heparinisation: Quick 18%; INR 3.5; PTT 62,8 s; Fibrinogen 6.56 g/l

61 Tissue factor (TF) formation in the vascular space is a key molecular event leading to DIC.

62 Anesth Analg 2005; 100: ,4% 8,4% Confirmed thrombotic complications 0% 6,3% Myocardial infarction

63 = 23,23 x 2147 = ,81

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65 1188 patients aged 18+ having cardiac surgery at the Heath Center of the Klinikum Augsburg in 2006; 6% with excessive hemorrhage. Excessive postoperative hemorrhage was defined as: Drainage loss 200 ml/h in any 1 hour (or part thereof) after a 30 min stabilization period within the first 6 h after surgery or Drainage loss 2 ml/kg/h for 2 consecutive hours in the first 6 hours after surgery

66 Variable Postop stroke (n, %) Total cohort (n=1.188) No Bleeding (n=1.112) Bleeding (n=76) p Bleeding vs. No Bleeding 58 (4.9) 46 (4.1) 12 (15.8) LOS ICU (d) 4.1 +/ / /-5.3 < Postop haemofiltration (n, %) In-hospitalmortality (n, %) 30-day-mortality (n, %) 188 (15.8) 165 (14.8) 23 (30.3) (6.1) 56 (5.0) 16 (21.1) < (6.6) 61 (5.5) 17 (22.4) <0.0001

67 Cost Components All Patients (n=1,188) (Cost in ) No Bleeding (n=1,112) (Cost in ) Bleeding (n=76) (Cost in ) P value Surgery-related* (mean SD) 2,304 ( 669) 2,274 ( 615) 4,018 ( 1,753) < Post OR Complications# (mean SD) 208 ( 848) 178 ( 785) 652 ( 1,429) < Re-exploration for bleeding (mean SD) 230 ( 842) 112 ( 600) 1,956 ( 1,635) < Cost of blood products (mean SD) 134 ( 346) 93 ( 257) 732 ( 730) < Cost of Total ICU stay (mean SD) 4,370 ( 6,779) 4,150 ( 6,699) 7,582 ( 7,172) < Total Cost (mean SD) 8,499 ( 7862) 8,027 ( 7,557) 15,404 ( 8,986) < 0.001

68 The treatment of bleeding is to stop the bleeding! Treatment... and to avoid of trauma-related thromboembolic hemorrhage events!... to reduce transfusion requirements and transfusion-related adverse events!... to safe patient s life and hospital costs!

69 Massive transfusion protocols are essential but massive transfusion avoiding algorithms are superior!

70 We can transfuse FFP early in order to stop bleeding or we can stop bleeding early in order to avoid FFP transfusion!