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Acquired bleeding model induced by dilutional coagulopathy in the rabbit

Introduction

Severe traumatic or intraoperative blood loss necessitates massive transfusion. This blood loss and the dilution of coagulation factors result in insufficient haemostasis. Treatments to enhance the haemostatic capacity need to be evaluated. An acquired bleeding model due to a dilutional coagulopathy was developed in the rabbit to estimate the contribution of PCC (Beriplex P/N; CSL Behring) on haemorrhage.

Methods

Rabbits were anesthetised using isofluran and were mandatorily ventilated. The animals were instrumented to monitor the cardiovascular and respiratory system. Dilutional coagulopathy was induced by phased blood withdraw, salvaged erythrocyte retransfusion and volume substitution with hydroxyethyl starch. After the dilutional procedure the bleeding was inflicted by cutting the lateral kidney pole. To characterise the model, animals were allocated to groups: I, sham operation (no dilution, placebo treatment; n = 5); II, negative control (dilution, placebo treatment; n = 7); III, PCC 25 U/kg intravenously (dilution, verum treatment; n = 6). Coagulation factor activity, thrombin generation (TGA), prothrombin time (PT) and the bleeding from the kidney wound were assessed.

Results

Rabbits without a dilutional coagulopathy demonstrated rapid onset of haemostasis. Post-injury blood loss (BL) and time to haemostasis (TH) were 4.7 ± 2.4 ml and 4.4 ± 1.1 minutes, respectively. After the dilution procedure coagulation factors were reduced to less than 50% of baseline. Haemostasis deteriorated after colloid transfusion (BL 60.0 ± 25.9 ml, TH 19.1 ± 2.2 min). The TGA showed normal lag phase but only 50% of the normal peak thrombin level. The PT was prolonged after the dilution about 1.8-fold. Using PCC treatment it was demonstrated that the peak thrombin level was corrected (P < 0.0001) and the BL (21.5 ± 11.1 ml; P < 0.01) as well as TH (12.4 ± 1.4 min; P < 0.01) were decreased significantly.

Conclusion

In this rabbit model of a dilutional coagulopathy it was demonstrated that a dilution of coagulation factors of more than 50% affects TGA, PT and bleeding. Restoration of coagulation factors II, VII, IX and X using PCC corrects the TGA and reduces BL and TH. This model could be used to investigate new drugs in dilutional coagulopathy.

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Pragst, I., Doerr, B., Kaspereit, F. et al. Acquired bleeding model induced by dilutional coagulopathy in the rabbit. Crit Care 13, P437 (2009). https://doi.org/10.1186/cc7601

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Keywords

  • Blood Loss
  • Prothrombin Time
  • Coagulation Factor
  • Thrombin Generation
  • Hydroxyethyl Starch