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Comparison of prothrombin complex concentrate and fresh frozen plasma on thrombin generation and hemorrhage in experimental dilutional coagulopathy

Introduction

Thrombin, the key enzyme of blood clotting, is responsible for the conversion of fibrinogen to fibrin, and for the activation coagulation factors and platelets. Sufficient thrombin generation (TG) is therefore crucial for hemostasis. In an experimental dilutional coagulapathy in pigs with subsequent bone or spleen injury, the effect of a substitution therapy with prothrombin complex concentrate (PCC) (Beriplex P/N; CSL Behring) or autologous porcine fresh frozen plasma (pFFP) on TG and hemorrhage was evaluated.

Methods

A dilutional coagulopathy was induced in 44 anaesthetized pigs. Erythrocytes were retransfused, the lost volume was replaced by hydroxyethyl starch. Animals were randomized to the following two study groups – A: bone injury, (1) placebo (n = 7), (2) PCC 25 U/kg (n = 7), (3) 15 ml/kg pFFP (pFFP15, n = 7), or (4) 40 ml/kg pFFP (pFFP40, n = 4); B: spleen injury, (1) placebo (n = 7), (2) PCC 25 U/kg (n = 6), or (3) 15 ml/kg pFFP (n = 6). A 3 mm bone injury was performed by drilling a hole into the femur neck. A spleen incision was created by a scalpel blade. Blood loss (BL) and the time to hemostasis (TH) were determined. TG, the prothrombin time (PT) and coagulation factor levels were measured.

Results

The dilutional coagulopathy led to a decrease in circulating coagulation factors, a prolonged PT and a decreased TG. The substitution with PCC and pFFP normalized the impaired PT, but only PCC could normalize the TG. PCC but not pFFP could restore the decreased plasma levels of coagulation factors of the prothrombin complex to sufficiently high levels. In the placebo group, TH and BL after bone injury were 90.0 ± 27.4 minutes and 625 ± 330 ml, and were 82.8 ± 24.5 minutes and 757 ± 251 ml after spleen injury. After substitution therapy with PCC, a significantly faster TH of 39.6 ± 9.8 minutes (P = 0.0004) and a decreased BL of 191 ± 119 ml (P = 0.0127) was observed after bone injury. After spleen injury, TH was 45.3 ± 9.1 minutes (P = 0.0129) and BL was 356 ± 175 ml (P = 0.0152). Neither dose of pFFP could correct hemorrhage.

Conclusion

Substitution with PCC but not FFP could normalize TG and provide sufficient coagulation factors to reduce hemorrhage. In both models of either venous or arterial injury, TH and BL were significantly decreased by PCC. It was concluded that the correction of TG correlates with hemostasis from a trauma injury.

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Dickneite, G., Pragst, I. Comparison of prothrombin complex concentrate and fresh frozen plasma on thrombin generation and hemorrhage in experimental dilutional coagulopathy. Crit Care 12, P225 (2008). https://doi.org/10.1186/cc6446

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Keywords

  • Blood Loss
  • Prothrombin Time
  • Coagulation Factor
  • Hydroxyethyl
  • Fresh Freeze Plasma