Thromb Haemost 2008; 99(01): 64-70
DOI: 10.1160/TH07-07-0438
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Increased thrombin generation and fibrinogen level after therapeutic plasma transfusion: Relation to bleeding

Saskia E. M Schols
1   Department of Biochemistry (CARIM), Maastricht University
2   Department of Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands
,
Paola E. J. van der Meijden
1   Department of Biochemistry (CARIM), Maastricht University
,
René van Oerle
1   Department of Biochemistry (CARIM), Maastricht University
2   Department of Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands
,
Joyce Curvers
3   Catharina Hospital, Eindhoven, The Netherlands
,
Johan W. M Heemskerk
1   Department of Biochemistry (CARIM), Maastricht University
,
Elisabeth C. M. van Pampus
2   Department of Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands
› Author Affiliations
Further Information

Correspondence to:

Johan W. M. Heemskerk
Department of Biochemistry (CARIM), Maastricht University
P.O. Box 616, 6200 MD Maastricht, The Netherlands
Phone: +31 43 3881671   
Fax: +31 43 3884159   

Publication History

Received: 03 July 2007

Accepted after major revision: 07 October 2007

Publication Date:
24 November 2017 (online)

 

Summary

In a clinical setting, fresh frozen plasma (FFP) is transfused to diluted patients with complicated surgery or trauma, as guided by prolonged conventional coagulation times or low fibrinogen levels. However, the limited sensitivity of these coagulation tests may restrict their use in measuring the effect of transfusion and hence predicting the risk of perioperative bleeding. We used the more sensitive, calibrated automated thrombogram (CAT) method to evaluate the result of therapeutic FFP transfusion to 51 patients with dilutional coagulopathy. Thrombin generation was measured in pre- and post-transfusion plasma samples in the presence of either platelets or phospholipids. For all patients, the transfusion led to higher plasma coagulation factor levels, a shortened activated partial thromboplastin time, and a significant increase in thrombin generation (peak height and endogenous thrombin potential). Interestingly, thrombin generation parameters and fibrinogen levels were higher in posttransfusion plasmas from patients who stopped bleeding (n=32) than for patients with ongoing bleeding (n=19). Plasmas from 15 of the 19 patients with ongoing bleeding were markedly low in either thrombin generation or fibrinogen level. We conclude that the thrombin generation method detects improved haemostatic activity after plasma transfusion. Furthermore, the data suggest that thrombin generation and fibrinogen are independent determinants of the risk of perioperative bleeding in this patient group.


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  • References

  • 1 Johansson PI, Hansen MB, Sorensen H. Transfusion practice in massively bleeding patients: time for a change?. Vox Sang 2005; 89: 92-96.
  • 2 Stanworth SJ, Brunskill SJ, Hyde CJ. et al. Is fresh frozen plasma clinically effective?. Br J Haematol 2004; 126: 139-152.
  • 3 Hardy JF, de Moerloose P, Samama CM. The coagulopathy of massive transfusion. Vox Sang 2005; 89: 123-127.
  • 4 Bux J. Transfusion-related acute lung injury (TRALI): a serious adverse event of blood transfusion. Vox Sang 2005; 89: 1-10.
  • 5 Holland LL, Brooks JP. Toward rational fresh frozen plasma transfusion. The effect of plasma transfusion on coagulation test results. Am J Clin Pathol 2006; 126: 133-139.
  • 6 Spahn DR, Rossaint R. Coagulopathy and blood component transfusion in trauma. Br J Anaesth 2005; 95: 130-139.
  • 7 Luddington RJ. Thrombelastography/thromboelastometry. Clin Lab Haematol 2005; 27: 81-90.
  • 8 Sorensen B, Ingerslev J. Tailoring haemostatic treatment to patient requirements. An update on monitoring haemostatic response using thromboelastography. Haemophilia 2005; 11: 1-6.
  • 9 Barrowcliffe TW. Factor VIII and thrombin generation assays: relevance to pharmacokinetic studies in haemophilia A. Haemophilia 2006; 12 S4: 23-29.
  • 10 Nieuwenhuys CMA, Feijge MAH, Béguin S. et al. Monitoring hypocoagulant conditions in rat plasma: factors determining the endogenous thrombin potential of tissue factor-activated plasma. Thromb Haemost 2000; 84: 1045-1051.
  • 11 Vanschoonbeek K, Feijge MAH, Paquay M, Rosing J, Saris W, Kluft C. et al. Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation. Arterioscler Thromb Vasc Biol 2004; 24: 1734-1740.
  • 12 Matthes GA. Options and cost effectiveness of multicomponent blood collection. Transfus Apher Sci 2002; 27: 115-121.
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  • 14 Chowdhury P, Saayman AG, Paulus U. et al. Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol 2004; 125: 69-73.
  • 15 Hemker HC, Giesen P, Al Dieri R. et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33: 4-15.
  • 16 Rosing J, Tans G, Govers-Riemslag JW. et al. The role of phospholipids and factor Va in the prothrombinase complex. J Biol Chem 1980; 255: 274-283.
  • 17 Vanschoonbeek K, Feijge MAH, van Kampen RJ, Kenis H, Hemker HC, Giesen PLA. et al. Initiating and potentiating role of platelets in tissue factor-induced thrombin generation in the presence of plasma. J Thromb Haemost 2004; 2: 476-484.
  • 18 Van der Meijden PEJ, Feijge MAH, Giesen PLA. et al. Platelet P2Y12 receptors enhance signalling towards procoagulant activity and thrombin generation. A study with healthy subjects and patients at thrombotic risk. Thromb Haemost 2005; 93: 1128-1136.
  • 19 Abdel-Wahab OI, Healy B, Dzik WH. Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion 2006; 46: 1279-1285.
  • 20 Al Dieri R, Alban S, Béguin S. et al. Thrombin generation for the control of heparin treatment, comparison with the activated partial thromboplastin time. J Thromb Haemost 2004; 2: 1395-1401.
  • 21 Hardy JF, de Moerloose P, Samama CM. Massive transfusion and coagulopathy: pathophysiology and implications for clinical management. Can J Anaesth 2006; 53: S40-S58.
  • 22 Hemker HC, Al Dieri R, de Smedt E. et al. Thrombin generation, a function test of the haemostaticthrombotic system. Thromb Haemost 2006; 96: 553-561.
  • 23 Heemskerk JWM, Bevers EM, Lindhout T. Platelet activation and blood coagulation. Thromb Haemost 2002; 88: 186-193.
  • 24 Fries D, Haas T, Klingler A. et al. Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy, a porcine model. Br J Anaesth 2006; 97: 460-467.
  • 25 Kheirabadi BS, Crissey JM, Deguzman R. et al. In vivo bleeding time and in vitro thrombelastography measurements are better indicators of dilutional hypothermic coagulopathy than prothrombin time. J Trauma 2007; 62: 1352-1359.

Correspondence to:

Johan W. M. Heemskerk
Department of Biochemistry (CARIM), Maastricht University
P.O. Box 616, 6200 MD Maastricht, The Netherlands
Phone: +31 43 3881671   
Fax: +31 43 3884159   

  • References

  • 1 Johansson PI, Hansen MB, Sorensen H. Transfusion practice in massively bleeding patients: time for a change?. Vox Sang 2005; 89: 92-96.
  • 2 Stanworth SJ, Brunskill SJ, Hyde CJ. et al. Is fresh frozen plasma clinically effective?. Br J Haematol 2004; 126: 139-152.
  • 3 Hardy JF, de Moerloose P, Samama CM. The coagulopathy of massive transfusion. Vox Sang 2005; 89: 123-127.
  • 4 Bux J. Transfusion-related acute lung injury (TRALI): a serious adverse event of blood transfusion. Vox Sang 2005; 89: 1-10.
  • 5 Holland LL, Brooks JP. Toward rational fresh frozen plasma transfusion. The effect of plasma transfusion on coagulation test results. Am J Clin Pathol 2006; 126: 133-139.
  • 6 Spahn DR, Rossaint R. Coagulopathy and blood component transfusion in trauma. Br J Anaesth 2005; 95: 130-139.
  • 7 Luddington RJ. Thrombelastography/thromboelastometry. Clin Lab Haematol 2005; 27: 81-90.
  • 8 Sorensen B, Ingerslev J. Tailoring haemostatic treatment to patient requirements. An update on monitoring haemostatic response using thromboelastography. Haemophilia 2005; 11: 1-6.
  • 9 Barrowcliffe TW. Factor VIII and thrombin generation assays: relevance to pharmacokinetic studies in haemophilia A. Haemophilia 2006; 12 S4: 23-29.
  • 10 Nieuwenhuys CMA, Feijge MAH, Béguin S. et al. Monitoring hypocoagulant conditions in rat plasma: factors determining the endogenous thrombin potential of tissue factor-activated plasma. Thromb Haemost 2000; 84: 1045-1051.
  • 11 Vanschoonbeek K, Feijge MAH, Paquay M, Rosing J, Saris W, Kluft C. et al. Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation. Arterioscler Thromb Vasc Biol 2004; 24: 1734-1740.
  • 12 Matthes GA. Options and cost effectiveness of multicomponent blood collection. Transfus Apher Sci 2002; 27: 115-121.
  • 13 O’Shaughnessy DF, Atterbury C, Bolton Maggs P. et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol 2004; 126: 11-28.
  • 14 Chowdhury P, Saayman AG, Paulus U. et al. Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol 2004; 125: 69-73.
  • 15 Hemker HC, Giesen P, Al Dieri R. et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33: 4-15.
  • 16 Rosing J, Tans G, Govers-Riemslag JW. et al. The role of phospholipids and factor Va in the prothrombinase complex. J Biol Chem 1980; 255: 274-283.
  • 17 Vanschoonbeek K, Feijge MAH, van Kampen RJ, Kenis H, Hemker HC, Giesen PLA. et al. Initiating and potentiating role of platelets in tissue factor-induced thrombin generation in the presence of plasma. J Thromb Haemost 2004; 2: 476-484.
  • 18 Van der Meijden PEJ, Feijge MAH, Giesen PLA. et al. Platelet P2Y12 receptors enhance signalling towards procoagulant activity and thrombin generation. A study with healthy subjects and patients at thrombotic risk. Thromb Haemost 2005; 93: 1128-1136.
  • 19 Abdel-Wahab OI, Healy B, Dzik WH. Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion 2006; 46: 1279-1285.
  • 20 Al Dieri R, Alban S, Béguin S. et al. Thrombin generation for the control of heparin treatment, comparison with the activated partial thromboplastin time. J Thromb Haemost 2004; 2: 1395-1401.
  • 21 Hardy JF, de Moerloose P, Samama CM. Massive transfusion and coagulopathy: pathophysiology and implications for clinical management. Can J Anaesth 2006; 53: S40-S58.
  • 22 Hemker HC, Al Dieri R, de Smedt E. et al. Thrombin generation, a function test of the haemostaticthrombotic system. Thromb Haemost 2006; 96: 553-561.
  • 23 Heemskerk JWM, Bevers EM, Lindhout T. Platelet activation and blood coagulation. Thromb Haemost 2002; 88: 186-193.
  • 24 Fries D, Haas T, Klingler A. et al. Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy, a porcine model. Br J Anaesth 2006; 97: 460-467.
  • 25 Kheirabadi BS, Crissey JM, Deguzman R. et al. In vivo bleeding time and in vitro thrombelastography measurements are better indicators of dilutional hypothermic coagulopathy than prothrombin time. J Trauma 2007; 62: 1352-1359.