Successful emergency reversal of phenprocoumon anticoagulation with prothrombin complex concentrate: a prospective clinical study

Abstract

The present prospective study was designed to evaluate the effectiveness and safety of prothrombin complex concentrate (PCC) for emergency reversal of oral anticoagulation with phenprocoumon, a long-acting coumarin. Patients were eligible for study entry if they required emergency reversal of phenprocoumon anticoagulation because they needed invasive surgical or diagnostic procedures or were actively bleeding. Patients received one or more infusions of pasteurized nanofiltered PCC (Beriplex P/N). Primary study endpoints were changes in International Normalized Ratio, Quick value, factors II, VII, IX and X, and protein C 10, 30 and 60 min following PCC infusion. Eight adult patients were enrolled, seven requiring urgent invasive procedures and one experiencing intracranial bleeding. In the first infusion, patients received a median 3600 IU PCC at median infusion rate 17.0 ml/min. Mean (SD) baseline International Normalized Ratio was 3.4 (1.2). The International Normalized Ratio 10 min after PCC infusion declined to 1.3 or less in seven of eight patients and to 1.4 in one patient. After PCC infusion, the Quick value increased by a mean of 57% [confidence interval (CI), 45-69%], circulating factor II concentration by 85% (CI, 68-103%), factor VII by 51% (CI, 40-62%), factor IX by 61% (CI, 47-76%), factor X by 115% (CI, 95-135%) and protein C by 100% (CI, 82-117%). Clinical effectiveness of PCC treatment was rated 'very good' in seven patients and 'satisfactory' in one. No thromboembolic or other adverse events occurred. PCC treatment rapidly, effectively and safely reversed phenprocoumon anticoagulation in patients undergoing urgent invasive procedures or actively bleeding.

Impact of infusion speed on the safety and effectiveness of prothrombin complex concentrate

“…In any case, coumarin therapy is routinely prescribed for patients whose medical conditions place them at high risk for thrombosis, and nonetheless, the occurrence of thrombotic events following PCC infusion for coumarin therapy reversal has been rare. No thromboembolic or other adverse events were encountered during a recently reported study in which the median rate of Beriplex P/N infusion (17.0 mL min −1 ) was more than twice that employed in the present study [24]. This study furnishes the first direct demonstration that the important clinical advantages of rapid PCC infusion can be secured without sacrificing safety or effectiveness.…”

“…The study was designed to determine the magnitude of INR decrease at 30 min, but not its rapidity. As demonstrated in another study of emergency coumarin therapy reversal with Beriplex P/N, the desired INR reduction can be achieved by as soon as 10 min post-infusion [24]. Further studies with sampling earlier than 30 min would be needed to Box bottoms and tops depict lowest and highest quartiles, respectively, error bars the lowest and highest deciles, and horizontal lines within the boxes the medians.…”

“…In contrast, the lower volumes of PCC can generally be administered within 10 to 60 min [16][17][18][19][20][21][22][23][24][25][26][27]. Consequently, international normalized ratio (INR) can be very rapidly decreased with PCC, and critical time can be saved under emergency circumstances [24].…”

“…Consequently, international normalized ratio (INR) can be very rapidly decreased with PCC, and critical time can be saved under emergency circumstances [24]. Accordingly, the most recent update from the British Committee for Standards in Haematology recommends that, for reversal of anticoagulation in patients with major bleeding, PCC should be administered in preference to FFP [9].…”

Approach to and management of the acute stroke patient with atrial fibrillation: A literature review

“…45 Prothrombin Complex Concentrates (PCCs) PCCs contain vitamin K dependent coagulation factors II, VII, IX, and X, the factors deficient in warfarin therapy. 44,46 Therefore, a PCC dose of 25 to 59 U/kg has been used in life-threatening bleeding, resulting in a decrease in the median INR from 3.8 to 1.3 immediately after administration. 42 PCCs should always be given with vitamin K. Thrombotic events have been described with the infusion of PCCs, but no clear guidelines have been published.…”