Prothrombin Complex Concentrate

DeWitt, Richard T.

doi:10.1001/archinte.1977.03630210083025

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…Only six treatment episodes were reported until 1977. [32][33][34][35] For a long time, the clinical success of PCCs in the management of patients with inhibitors was attributed to the activated prothrombin complex enzyme in addition to the zymogen content of the concentrates. 36 Therefore, in the early 1970s, the so-called auto-FIX concentrates were developed as a new therapeutic approach for treating HA patients with inhibitors.…”

Section: Development Of Activated Prothrombin Complex Concentratementioning

confidence: 99%

Origins, Development, Current Challenges and Future Directions with Activated Prothrombin Complex Concentrate for the Treatment of Patients with Congenital Haemophilia with Inhibitors

Brackmann

Schramm²,

Oldenburg

et al. 2020

Hamostaseologie

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Congenital haemophilia A (HA) is caused by deficiency of coagulation factor VIII (FVIII) activity, leading to spontaneous or traumatic bleeding events. While FVIII replacement therapy can treat and prevent bleeds, approximately 30% of patients with severe HA develop inhibitor antibodies that render FVIII replacement therapy ineffective. The bypassing agents (BPAs), activated prothrombin complex concentrate (aPCC) and recombinant activated FVII, first approved in 1977 and 1996, respectively, act to generate thrombin independent of pathways that involve factors IX and VIII. Both may be used in patients with congenital haemophilia and inhibitors (PwHIs) for the treatment and prevention of acute bleeds and quickly became standard of care. However, individual patients respond differently to different agents. While both agents are approved for on-demand treatment and perioperative management for patients with congenital haemophilia with inhibitors, aPCC is currently the only BPA approved worldwide for prophylaxis in PwHI. Non-factor therapies (NFTs) have a mechanism of action distinct from BPAs and have reported higher efficacy rates as prophylactic regimens. Nonetheless, treatment challenges remain with NFTs, particularly regarding the potential for synergistic action on thrombin generation with concomitant use of other haemostatic agents, such as BPAs, for the treatment of breakthrough bleeds and in perioperative management. Concomitant use of NFTs with other haemostatic agents could increase the risk of adverse events such as thromboembolic events or thrombotic microangiopathy. This review focuses on the origins, development and on-going role of aPCC in the evolving treatment landscape in the management of PwHI.

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Section: Development Of Activated Prothrombin Complex Concentratementioning

confidence: 99%

Origins, Development, Current Challenges and Future Directions with Activated Prothrombin Complex Concentrate for the Treatment of Patients with Congenital Haemophilia with Inhibitors

Brackmann

Schramm²,

Oldenburg

et al. 2020

Hamostaseologie

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“…Early in their history, the clinical use of prothrombin complex concentrates (PCCs) was extended beyond their basic use as a substitution therapy for patients with prothrombin complex protein deficiencies and factor (F)IX deficiency (haemophilia B) to the treatment of bleeding in patients with inhibitory antibodies against FVIII [1,2]. For a long time the clinical success of PCCs in the management of patients with inhibitors was primarily attributed to the activated prothrombin complex enzymes they contain in addition to zymogens [3].…”

Section: History Of Activated Prothrombin Complex Concentratesmentioning

confidence: 99%

FEIBA^®: mode of action

et al. 2004

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FEIBA (factor eight inhibitor bypassing activity) has a history of more than 30 years of successful use in controlling bleeding in haemophilic patients who have developed inhibitory antibodies against factor (F)VIII or FIX. Recently it was shown that FEIBA contains the proenzymes of the prothrombin complex factors, prothrombin, FVII, FIX and FX, but only very small amounts of their activation products, with the exception of FVIIa, which is contained in FEIBA in greater amounts. FEIBA controls bleeding by induction and facilitation of thrombin generation, a process for which FV is crucial. A number of biochemical in vitro and in vivo studies have shown that FXa and prothrombin play a critical role in the activity of FEIBA. Consequently, they are considered to be key components of this product. The prothrombinase complex has been found to be a major target site for FEIBA. Apart from prothrombin and FXa, FEIBA contains other proteins of the prothrombin complex, which could also facilitate haemostasis in haemophilia patients with inhibitors.

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“…In 1972, the clinical application of prothrombin complex concentrates (PCC) was extended beyond their basic use as a substitution therapy for patients with prothrombin complex protein deficiencies, particularly haemophilia B (FIX deficiency), to the treatment of inhibitors in patients with haemophilia A [7,8]. These pooled‐plasma products contain all of the vitamin K‐dependent coagulation proenzyme protein factors II (FII), VII (FVII), IX (FIX), and X (FX) and inhibitors protein C and protein S, together with minimal quantities of their respected activated components [9–11].…”

Section: Introductionmentioning

confidence: 99%

The history of FEIBA: a lifetime of success in the treatment of haemophilia complicated by an inhibitor

Négrier

Gomperts

Oldenburg³

2006

Haemophilia

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The development of alloantibodies that inhibit the function of factor VIII (FVIII) or factor IX (FIX) is the most serious complication associated with the treatment of haemophilia. Bleeding events in patients with high-titre inhibitors generally cannot be managed with factor replacement therapy and require alternative strategies for haemostatic support. For over 30 years, the activated prothrombin complex concentrate (aPCC) FEIBA has been used to bypass the need for FVIII and FIX and control bleeding in inhibitor patients. Several large clinical studies have shown that FEIBA provides effective haemostasis in at least 80% of acute bleeding episodes and is well tolerated. Current limitations of bypassing therapy include a lack of laboratory assays to monitor treatment and an unpredictable haemostatic effect.

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Prothrombin Complex Concentrate

Cited by 5 publications

References 14 publications

Origins, Development, Current Challenges and Future Directions with Activated Prothrombin Complex Concentrate for the Treatment of Patients with Congenital Haemophilia with Inhibitors

Origins, Development, Current Challenges and Future Directions with Activated Prothrombin Complex Concentrate for the Treatment of Patients with Congenital Haemophilia with Inhibitors

FEIBA^®: mode of action

The history of FEIBA: a lifetime of success in the treatment of haemophilia complicated by an inhibitor

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Prothrombin Complex Concentrate

Cited by 5 publications

References 14 publications

Origins, Development, Current Challenges and Future Directions with Activated Prothrombin Complex Concentrate for the Treatment of Patients with Congenital Haemophilia with Inhibitors

Origins, Development, Current Challenges and Future Directions with Activated Prothrombin Complex Concentrate for the Treatment of Patients with Congenital Haemophilia with Inhibitors

FEIBA®: mode of action

The history of FEIBA: a lifetime of success in the treatment of haemophilia complicated by an inhibitor

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Product

Resources

About

FEIBA^®: mode of action