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Articles by F Szlam
Total Records ( 2 ) for F Szlam
  D Bolliger , F Szlam , R. J Molinaro , N Rahe Meyer , J. H Levy and K. A. Tanaka
  Background

Replacement of fibrinogen is presumably the key step in managing dilutional coagulopathy. We performed an in vitro study hypothesizing that there is a minimal fibrinogen concentration in diluted whole blood above which the rate of clot formation approaches normal.

Methods

Blood samples from six healthy volunteers were diluted 1:5 v/v with saline keeping haematocrit at 24% using red cell concentrates. We measured coagulation factors and thrombin generation in plasma at baseline and after dilution. Thromboelastometry was used to evaluate (i) speed and quality of clot formation in diluted samples supplemented with fibrinogen 50–300 mg dl–1 and (ii) clot resistance to fibrinolysis. Diluted and undiluted samples with no added fibrinogen served as controls.

Results

Coagulation parameters and platelets were reduced by 74–85% after dilution. Peak thrombin generation was reduced by 56%. Adding fibrinogen led to a concentration-dependent improvement of all thromboelastometric parameters. The half maximal effective concentration (EC50) for fibrinogen replacement in haemodiluted blood was calculated to be 125 mg dl–1. Adding tissue plasminogen activator, 0.15 µg ml–1, led to a decrease of clot firmness and lysis time.

Conclusions

The target plasma concentration for fibrinogen replacement was predicted by these in vitro results to be greater than 200 mg dl–1 as only these concentrations optimized the rate of clot formation. This concentration is twice the level suggested by the current transfusion guidelines. Although improved, clots were prone to fibrinolysis indicating that the efficacy of fibrinogen therapy may be influenced by co-existing fibrinolytic tendency occurring during dilutional coagulopathy.

  D Bolliger , F Szlam , J. H Levy , R. J Molinaro and K. A. Tanaka
  Background

Fibrinolysis contributes to coagulopathy after major trauma and surgery. We hypothesized that progressive haemodilution is responsible, at least in part, for increased fibrinolytic tendency of blood clot.

Methods

The study was performed in two parts. First, whole blood (WB) samples collected from six healthy, consented volunteers were diluted in vitro with either saline or fresh-frozen plasma (FFP) to 40% and 15% of baseline. We quantified factor levels related to coagulation and fibrinolysis, and measured endogenous thrombin generation in undiluted control plasma samples and in samples diluted with saline or FFP. Additionally, thromboelastometry was used to assess susceptibility to fibrinolysis after adding tissue plasminogen activator in undiluted WB samples and in samples diluted with saline before and after substitution of fibrinogen or FFP. Secondly, as a model of in vivo haemodilution, we evaluated the same parameters before and after operation in nine consented patients undergoing off-pump coronary artery bypass surgery.

Results

The dilution with saline caused dose-dependent decreases in plasma levels of coagulation and antifibrinolytic factors, and in thrombin generation. In FFP-supplemented samples, factor levels and thrombin generation were maintained within normal ranges. Fibrinolytic tendency was significantly higher after haemodilution with saline independent of fibrinogen substitution compared with FFP. Similarly, increased tendency for fibrinolysis was also observed in the in vivo haemodilution.

Conclusions

We demonstrated in vitro and in vivo that progressive haemodilution decreases endogenous antifibrinolytic proteins including 2-antiplasmin and thrombin-activatable fibrinolysis inhibitor, resulting in increased fibrinolytic tendency. Therefore, early fluid replacement therapy with FFP might be advantageous after massive haemorrhage.

 
 
 
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