Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.

Objectives: Acquired coagulopathy may be associated with bleeding risk. Approaches to restore haemostasis include administration of coagulation factor concentrates, but there are concerns regarding potential prothrombotic risk. The present study assessed the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) versus activated PCC (aPCC) and recombinant factor VIIa (rFVIIa), using three preclinical animal models.

Tissue distribution of rIX-FP after intravenous application to rodents.

Background: Hemophilia B is caused by coagulation factor IX (FIX) deficiency. Recombinant fusion protein linking coagulation FIX with recombinant albumin (rIX-FP; Idelvion ) is used for replacement therapy with an extended half-life. A previous quantitative whole-body autoradiography (QWBA) study investigating the biodistribution of rIX-FP indicated equal biodistribution, but more prolonged tissue retention compared with a marketed recombinant FIX product.

Correlation of coagulation markers and 4F-PCC-mediated reversal of rivaroxaban in a rabbit model of acute bleeding.

Introduction: Rivaroxaban is an oral, selective direct factor Xa inhibitor approved for several indications in patients at risk of thrombotic events. One limitation of its clinical use is the lack of data pertaining to its reversal in situations where urgent response is critical (e.g.

Effective reversal of edoxaban-associated bleeding with four-factor prothrombin complex concentrate in a rabbit model of acute hemorrhage.

Background: Edoxaban is an oral, selective direct factor Xa inhibitor approved in Japan for venous thromboembolism prevention after orthopedic surgery. Data are lacking regarding reversal strategies for edoxaban; this study assessed whether four-factor prothrombin complex concentrate (Beriplex/Kcentra; CSL Behring GmbH, Marburg, Germany) can effectively reverse its effects on hemostasis using a previously described rabbit model.

Methods: The study comprised assessments of thrombin generation in vitro, pharmacokinetic parameters, and edoxaban reversal in vivo.

Thrombotic safety of prothrombin complex concentrate (Beriplex P/N) for dabigatran reversal in a rabbit model.

Introduction: In vivo animal data have shown prothrombin complex concentrate (PCC) to be effective in preventing bleeding induced by excessive plasma levels of the direct thrombin inhibitor dabigatran. This animal model study was designed to determine the risk of thrombosis associated with administration of a PCC (Beriplex P/N) to reverse dabigatran-induced bleeding.

Materials And Methods: Anesthetized rabbits were treated with initial 0, 75, 200 or 450 μg kg(-1) dabigatran boluses followed by continuous infusions to maintain elevated plasma dabigatran levels.

Characterization of the coagulation deficit in porcine dilutional coagulopathy and substitution with a prothrombin complex concentrate.

Background: In this study, we used a porcine model to investigate whether impaired coagulation and severe arterial or venous bleeding could be normalized by substitution with a prothrombin complex concentrate (PCC), Beriplex P/N, containing coagulation factors II, VII, IX, and X.

Methods: Dilutional coagulopathy was induced in anesthetized pigs by fractionated blood withdrawal (approximately 65% of total volume), followed by erythrocyte retransfusion and volume substitution with a total of 1000 mL of hydroxyethyl starch (Infukoll 6%). Animals were randomized to no treatment, treatment with placebo, or treatment with 35 U/kg PCC.

The effect of fibrinogen concentrate administration on coagulation abnormalities in a rat sepsis model.

Disseminated intravascular coagulation is a disorder that affects the function of the clotting system and is frequently associated with sepsis or septic shock. One of its leading symptoms is the decrease in circulating fibrinogen. We investigated the effect of fibrinogen concentrate (Haemocomplettan P) on fibrinogen plasma levels, coagulation parameters and mortality in a rat model of sepsis-induced disseminated intravascular coagulation.