Clinical review: Prothrombin complex concentrates--evaluation of safety and thrombogenicity

Abstract

Prothrombin complex concentrates (PCCs) are used mainly for emergency reversal of vitamin K antagonist therapy. Historically, the major drawback with PCCs has been the risk of thrombotic complications. The aims of the present review are to examine thrombotic complications reported with PCCs, and to compare the safety of PCCs with human fresh frozen plasma. The risk of thrombotic complications may be increased by underlying disease, high or frequent PCC dosing, and poorly balanced PCC constituents. The causes of PCC thrombogenicity remain uncertain but accumulating evidence indicates the importance of factor II (prothrombin). With the inclusion of coagulation inhibitors and other manufacturing improvements, today's PCCs may be considered safer than earlier products. PCCs may be considered preferable to fresh frozen plasma for emergency anticoagulant reversal, and this is reflected in the latest British and American guidelines. Care should be taken to avoid excessive substitution with prothrombin, however, and accurate monitoring of patients' coagulation status may allow thrombotic risk to be reduced. The risk of a thrombotic complication due to treatment with PCCs should be weighed against the need for rapid and effective correction of coagulopathy.

Figure 1

Coagulation factors accumulate differently when a prothrombin complex concentrate is administered repeatedly. Illustration of how coagulation factors accumulate differently when a prothrombin complex concentrate (PCC) is administered repeatedly due to their different half-lives. The example shows the theoretical accumulation of factors in plasma sampled immediately after dosing when 40 units/kg four-factor PCC is given every 12 hours to a 70 kg patient.

Figure 2

Coagulation inhibitor levels of different prothrombin complex concentrates. Protein C, protein S and protein Z contents of different prothrombin complex concentrates (PCCs) [9].