Archief Roodbont

September 15, 2011 (Amsterdam, the Netherlands) — Results of a small study published online September 6, 2011 in Circulation show that prothrombin complex concentrate (PCC) appears to be an effective antidote for rivaroxaban that could be used to stop or prevent serious bleeding in patients taking this new anticoagulant. However, the same study showed that PCC has no influence on dabigatran [1].

Dabigatran, a direct thrombin inhibitor, and rivaroxaban, a direct factor Xa inhibitor, have shown promise as anticoagulants that can be prescribed in fixed doses and do not require frequent monitoring. But so far, no human studies have assessed whether prohemostatic agents can stop the anticoagulant effect of either drug in the patient suffering a major bleed or undergoing emergency surgery, according to study authors, Dr Elise Eerenberg (Academic Medical Center, Amsterdam, the Netherlands) and colleagues. PCC is a good candidate for an antidote because it contains the coagulation factors II, VII, IX, and X in a high concentration and enhances thrombin generation, Eerenberg et al explain.

The researchers randomized 12 healthy male volunteers to either 20 mg of rivaroxaban twice a day or 150 mg of dabigatran twice a day for two and a half days, followed by either a single 50-IU/kg dose of PCC or a similar dose of saline. After 11 days, the patients repeated this procedure with the other anticoagulant treatment.

Rivaroxaban induced a significant prolongation of the prothrombin time (15.8 vs 12.3 seconds at baseline; p<0.001) that was immediately and completely reversed by the PCC to an average of 12.8 seconds (p<0.001). The endogenous thrombin potential, a measure of blood coagulability, was inhibited by rivaroxaban (51% vs 92% at baseline, p<0.002) and normalized with PCC (114%, p<0.001), while the saline had no effect.

Dabigatran also increased the activated partial thromboplastin time, ecarin clotting time, and thrombin time, but PCC did not restore coagulability of the blood to the baseline levels in any of these coagulation tests. "The question of how the effect of dabigatran can be antagonized remains unanswered," the authors explain. They suggest that other strategies for reversing dabigatran could include repeated doses of PCC, recombinant factor VIIa, or a combination of PCC and recombinant factor VIIa, but these strategies have yet to be investigated in trials.

This was the first study to investigate the effect of PCC for reversal of these new anticoagulant agents in humans, according to the authors, and it "may have important clinical implications," but the effects of PCC in patients with bleeding events while treated with anticoagulants will have to be studied in further trials.

This study was supported by an unrestricted research grant from Sanquin, the Netherlands, which also supplied PCC.

# posted by roodbont @ 2:17 AM