Prothrombin complex coagulation

Prothrombin complex concentrate, cryoprecipitate and fresh frozen plasma, commonly-used coagulation factor products. 

Prothrombin complex is the combination of Factors E, VE, DC, and X. It is indicated for individuals with hemophdia B. In a typical production process, the supernatant resulting from the separation of cryoprecipitate is filtered to remove particles and applied to an anion-exchange column. The coagulation factors are eluted, ultrafiltered, and exposed to 60°C for 10 h for virus inactivation. This is followed by diafiltration, ultrafiltration, and sterile filtration. 

The risk of disseminated intravascular coagulation and other thrombotic events appears to be less with factor VII than with activated prothrombin complex products (1,18). However, disseminated intravascular coagulation after infusion of recombinant factor Vila has been reported (19,20). 

This may explain the effectiveness of treating patients with hemophilia who have inhibitors with high doses of factor VIII. Another approach involves the use of prothrombin complex concentrate to treat bleeding episodes in patients with factor VIII inhibitors (38) however, thromboembolic complications related to higher doses of prothrombin complex concentrate have been described, although these are relatively rare (39,40). Thrombotic events are extremely rare when highly purified factor IX is used. Activated prothrombin complex concentrate is also effective in patients with factor VIII inhibitors (41). Serious complications are rare, but disseminated intravascular coagulation has been reported (42). 

In 42 patients who required immediate reversal of oral anticoagulant therapy by prothrombin complex concentrate, no laboratory and clinical evidence for coagulation activation was found (7). The authors suggested that the concentration of protein C within the prothrombin complex concentrate is an important factor for preventing thrombosis. The activated form of protein C is an important natural anticoagulant. 

The administration of prothrombin complex concentrate to reverse anticoagulant treatment has been associated with thrombotic complications, such as disseminated intravascular coagulation (8). However, such complications have typically occurred in patients with liver failure or after repeated treatment, such as in patients with hemophilia B treated with prothrombin complex concentrate (9). 

Rodie PH, Stirling C, Mayne EE, Ludlam CA. Thrombosis and disseminated intravascular coagulation following treatment with the prothrombin complex concentrate, DEFIX. Thromb Haemost 1999 81(4) 667. 

The coumarin anticoagulants are employed in therapy to depress blood coagulation and to prevent thrombosis in diseases of the coronary artery and in other conditions [419]. These compounds act only in vivo by blocking the synthesis of four proteins in the prothrombin complex (factors II = prothrombin, VII = proconvertin, IX = plasma thromboplastin component, and X = Stuart-Prower factor) necessary for the normal blood coagulation process. These proteins are... 

Cardiovascular The main adverse effect of prothrombin complex concentrates is a risk of thrombosis, as patients taking oral anticoagulants have prothrombotic susceptibility factors [31, 33 ]. Reported thromboembolic complications include ischemic stroke, venous thromboembolism (venous thrombosis or pulmonary embolism), myocardial infarction, and disseminated intravascular coagulation [32 ]. 

Chowdary P, Nair D, Davies N, Malde R, Gatt A. Anaphylactic reaction with prothrombin complex concentrate in a patient with IgA deficiency and anti-IgA antibodies. Blood Coagul Fibrinolysis 2010 21(8) 764-5. 

Hematologic Historically, there was concern that prothrombin complex concentrates were associated with thrombotic events such as stroke, myocardial infarction, pulmonary embolism, deep venous thrombosis, and disseminated intravascular coagulation. These events resulted mainly from the use of prothrombin complex concentrates as source of factor IX in patients with hemophilia B, and in particular after surgery, but the reported incidence is low and there is considerable evidence that the risk of thrombosis has been minimized with current prothrombin complex concentrates by reduced use of activated factors and the... 

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