Supplement issueProthrombin Complex Concentrates: Indications, Contraindications, and Risks: A Task Force Summary
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Definition and Use of PCC
Prothrombin complex concentrates (PCCs) are plasma products containing mainly the plasma-clotting factors prothrombin, factors VII, IX, and X, the inhibitors proteins C and S, and protein Z. They are used primarily for substitution therapy in cases of acquired disorders of hemostasis. Previously, PCCs containing primarily factors II, IX, and X mainly have been used for the treatment of hemophilia B; they are being replaced by highly purified factor IX concentrates or by recombinant factor IX
Production of PCC
PCCs are produced from the cryoprecipitate supernatant of large plasma pools or from the plasma supernatant after the removal of antithrombin and factor XI, using ion exchange chromatography and precipitation techniques. Moist or dry heat, pasteurization, the solvent-detergent process, or nanofiltration are applied to remove or to inactivate viruses.
To reduce or prevent the activation of the clotting factors during the production process or to prevent intravascular activation of coagulation,
Quality Standards
In order to assure efficacy and to avoid thromboembolic complications and disseminated intravascular coagulation (DIC) subsequent to the administration of PCCs, certain quality criteria must be met. Thromboembolic complications and DIC observed in connection with the administration of PCCs have been attributed to activated clotting factors VII, IX, and X in the PCC product, overloading with prothrombin and factor X, and lack of the inhibitors protein C, as well as protein S in its functionally
General Aspects
Since PCC is a plasma product containing mainly vitamin K-dependent proteins, the use of PCCs have to be limited primarily to the treatment of prothrombin complex factor deficiencies, but only in clinical situations where other therapeutic measures are not indicated or do not lead to the expected therapeutic effect. Various clinical situations (e.g., tooth extractions, cerebral bleeding) demand different target plasma levels of one or more prothrombin complex factors necessary to prevent or
Disseminated Intravascular Coagulation
In patients suffering from DIC, the administration of PCC is not recommended because of the procoagulant capacity of the product. Except in life-threatening situations when the substitution of coagulation factor deficiency by fresh frozen plasma is not sufficient enough or cannot be given because of a threat of hypervolemia, PCC might be used. Under these circumstances it is very important to administer antithrombin and preferably heparin before the administration of PCC.
Heparin-Induced Thrombocytopenia Type II
Since all PCC
Side Effects
The following side effects have been observed in connection with the administration of PCC:
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thromboembolism (deep vein thrombosis, pulmonary embolism, arterial thrombosis [e.g., myocardial infarction])
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DIC allergic reactions
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anaphylactic reactions
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HIT II generation of clotting factor or inhibitor antibodies
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transmission of infectious diseases (e.g., hepatitis C virus [HCV])
Dosage and Administration of PCC
The amount of PCC administered to patients with bleedings induced by vitamin K-deficiency or overdose of oral anticoagulants is different from that administered to patients suffering from impaired liver function or congenital prothrombin or factor X deficiency.
Laboratory Analysis and Practical Approaches in PCC Administration
Before the administration of PCC, a prothrombin complex factor deficiency must be safeguarded by a laboratory analysis. A prolongation of the prothrombin time alone is not sufficient laboratory evidence to confirm a prothrombin complex factor deficiency. The prothrombin time may be prolonged in a great number of different coagulation disturbances. For instance, a prolonged prothrombin time may result from impaired fibrin polymerization caused by fibrinogen degradation products, or may occur in
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Diagnosis, therapeutic advances, and key recommendations for the management of factor X deficiency
2021, Blood ReviewsCitation Excerpt :However, there remains a lack of consensus among evidence-based recommendations regarding PCC use in different countries, as well as insufficient evidence to establish differences in efficacy and safety between three- and four-factor PCCs [47]. Concerns associated with PCC administration for factor X deficiency include the unknown concentrations of factors II, VII, and X and the increased risk of thrombosis [1,9,51]. The risk of thrombosis with PCCs appears be related to differences in product quality, the dose administered, infusion rates, and/or patient characteristics/risk profile, with thrombotic events associated with PCC administration observed more frequently among patients with acquired hemostatic disorders than in those with hereditary coagulation deficiencies [9,48,51].
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