| Combination of | |
|---|---|
| Factor II | Blood clotting factor |
| Factor VII | Blood clotting factor |
| Factor IX | Blood clotting factor |
| Factor X | Blood clotting factor |
| Clinical data | |
| Trade names | Kcentra, others |
| Other names | factor IX complex |
| AHFS/Drugs.com | Monograph Monograph |
| License data | |
| Routes of administration | Intravenous |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
| CAS Number | |
| DrugBank | |
Prothrombin complex concentrate (PCC), also known as factor IX complex, sold under the brand name Kcentra among others, is a combination medication made up of blood clotting factors II, IX, and X [9] (3-factor PCC) or, when also containing factor VII as does Kcentra, 4-factor PCC. [10] It is used to treat and prevent bleeding in hemophilia B if pure factor IX is not available. [9] [11] It may also be used for reversal of warfarin therapy. [11] It is given by slow injection into a vein. [9] . Another product, activated prothrombin complex concentrate or FEIBA (Factor Eight Inhibitor Bypassing Agent), may be used for acquired hemophilia. [12]
Common side effects include allergic reactions, headache, vomiting, and sleepiness. [9] [13] Other serious side effects include blood clots which may result in a heart attack, stroke, pulmonary embolism, or deep vein thrombosis. [13] Antibodies may form after long term use such that future doses are less effective. [11]
Prothrombin complex concentrate came into medical use in the 1960s. [14] It is on the World Health Organization's List of Essential Medicines. [15] [16] It is made from human plasma. [13] Recombinant factor IX is also available in a stand-alone preparation. [17]
Prothrombin complex concentrate reverses the effects of warfarin and other vitamin K antagonist anti-coagulants and is used in cases of significant bleeding in people with a coagulopathy. It is also used when such a person must undergo an emergency operation. [18] Other uses include a deficiency of one of the included clotting factors, either congenital or due to liver disease, and hemophilia. [18] Several guidelines, including those from the American College of Chest Physicians, recommend prothrombin complex concentrate for warfarin reversal in people with serious bleeding. [19] [20] [21] [22]
For rapid anticoagulation reversal for surgery, four-factor prothrombin complex concentrate reduces international normalized ratio (INR) and decreases bleeding during surgery when compared with administration of fresh frozen plasma. No differences in thromboembolic event was found. [23]
The package insert states that prothrombin complex concentrate is contraindicated in patients with disseminated intravascular coagulation, a pathological activation of coagulation, [24] because giving clotting factors would only further fuel this process. However, if the PCC is given because factor levels are low, it can restore normal coagulation. As PCC products contain heparin, they are contraindicated in patients with heparin-induced thrombocytopenia. [24]
Prothrombin complex concentrate contains a number of blood clotting factors. Typically this includes factor II, IX, and X. [9] Some versions also contain factor VII, protein C, and protein S. [10] [24] Heparin may be added to stop early activation of the factors. [10]
The US Food and Drug Administration (FDA) announced its approval in 2013. [25] The FDA approved Kcentra's orphan drug status in December 2012. [25] [26]
In the United States a dose of prothrombin complex concentrate costs about US $3200 [27] though one study described the cost as $11 650. [28] The Australian National Blood Authority sets Prothrombinex (500 IU) at around AUD$327. [29]
A number of different formulations are available globally. [30]
An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which help keep the bite area unclotted long enough for the animal to obtain blood.
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin.
Warfarin is an anticoagulant used as a medication under several brand names including Coumadin. While the drug is described as a "blood thinner", it does not reduce viscosity but rather inhibits coagulation. Accordingly, it is commonly used to prevent blood clots in the circulatory system such as deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who have atrial fibrillation, valvular heart disease, or artificial heart valves. Less commonly, it is used following ST-segment elevation myocardial infarction (STEMI) and orthopedic surgery. It is usually taken by mouth, but may also be administered intravenously.
Prothrombin is encoded in the human by the F2 gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin.
The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the extrinsic pathway and common pathway of coagulation. This blood test is also called protime INR and PT/INR. They are used to determine the clotting tendency of blood, in such things as the measure of warfarin dosage, liver damage, and vitamin K status. PT measures the following coagulation factors: I (fibrinogen), II (prothrombin), V (proaccelerin), VII (proconvertin), and X.
Coagulation factor VII is a protein involved in coagulation and, in humans, is encoded by gene F7. It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, it is converted to factor VIIa, which in turn activates factor IX and factor X.
Coagulation factor X, or Stuart factor, is an enzyme of the coagulation cascade, encoded in humans by F10 gene. It is a serine endopeptidase. Factor X is synthesized in the liver and requires vitamin K for its synthesis.
Coagulation factor V, also less commonly known as proaccelerin or labile factor, is a protein involved in coagulation, encoded, in humans, by F5 gene. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor. Factor V deficiency leads to predisposition for hemorrhage, while some mutations predispose for thrombosis.
Argatroban is an anticoagulant that is a small molecule direct thrombin inhibitor. In 2000, argatroban was licensed by the US Food and Drug Administration (FDA) for prophylaxis or treatment of thrombosis in people with heparin-induced thrombocytopenia (HIT). In 2002, it was approved for use during percutaneous coronary interventions in people who have HIT or are at risk for developing it. In 2012, it was approved by the UK Medicines and Healthcare products Regulatory Agency for anticoagulation in people with heparin-induced thrombocytopenia Type II (HIT) who require parenteral antithrombotic therapy.
Fresh frozen plasma (FFP) is a blood product made from the liquid portion of whole blood. It is used to treat conditions in which there are low blood clotting factors or low levels of other blood proteins. It may also be used as the replacement fluid in plasma exchange. Using ABO compatible plasma, while not required, may be recommended. Use as a volume expander is not recommended. It is administered by slow injection into a vein.
Rivaroxaban, sold under the brand name Xarelto among others, is an anticoagulant medication used to treat and prevent blood clots. Specifically it is used to treat deep vein thrombosis and pulmonary emboli and prevent blood clots in atrial fibrillation and following hip or knee surgery. It is taken by mouth.
Warfarin-induced skin necrosis is a condition in which skin and subcutaneous tissue necrosis occurs due to acquired protein C deficiency following treatment with anti-vitamin K anticoagulants.
Dabigatran, sold under the brand name Pradaxa among others, is an anticoagulant used to treat and prevent blood clots and to prevent stroke in people with atrial fibrillation. Specifically it is used to prevent blood clots following hip or knee replacement and in those with a history of prior clots. It is used as an alternative to warfarin and does not require monitoring by blood tests. In a meta analysis of 7 different studies, there was no benefit of dabigatran over warfarin in preventing ischemic stroke; however, dabigatran were associated with a lower hazard for intracranial bleeding compared with warfarin, but also had a higher risk of gastrointestinal bleeding relative to warfarin. It is taken by mouth.
Hypercoagulability in pregnancy is the propensity of pregnant women to develop thrombosis. Pregnancy itself is a factor of hypercoagulability, as a physiologically adaptive mechanism to prevent post partum bleeding. However, when combined with an additional underlying hypercoagulable states, the risk of thrombosis or embolism may become substantial.
Direct factor Xa inhibitors (xabans) are anticoagulants, used to both treat and prevent blood clots in veins, and prevent stroke and embolism in people with atrial fibrillation (AF).
Vitamin K reactions are adverse side effects that may occur after injection with vitamin K. The liver utilizes vitamin K to produce coagulation factors that help the body form blood clots which prevent excessive bleeding. Vitamin K injections are administered to newborns as a preventative measure to reduce the risk of hemorrhagic disease of the newborn (HDN).
Edoxaban, sold under the brand name Lixiana among others, is an anticoagulant medication and a direct factor Xa inhibitor. It is taken by mouth.
Apixaban, sold under the brand name Eliquis, is an anticoagulant medication used to treat and prevent blood clots and to prevent stroke in people with nonvalvular atrial fibrillation through directly inhibiting factor Xa. Specifically, it is used to prevent blood clots following hip or knee replacement and in those with a history of prior clots. It is used as an alternative to warfarin and does not require monitoring by blood tests or dietary restrictions. It is taken by mouth.
Prothrombin G20210A is a genetic condition that increases the risk of blood clots including from deep vein thrombosis, and of pulmonary embolism. One copy of the mutation increases the risk of a blood clot from 1 in 1,000 per year to 2.5 in 1,000. Two copies increases the risk to up to 20 in 1,000 per year. Most people never develop a blood clot in their lifetimes.
Direct thrombin inhibitors (DTIs) are a class of anticoagulant drugs that can be used to prevent and treat embolisms and blood clots caused by various diseases. They inhibit thrombin, a serine protease which affects the coagulation cascade in many ways. DTIs have undergone rapid development since the 90's. With technological advances in genetic engineering the production of recombinant hirudin was made possible which opened the door to this new group of drugs. Before the use of DTIs the therapy and prophylaxis for anticoagulation had stayed the same for over 50 years with the use of heparin derivatives and warfarin which have some well known disadvantages. DTIs are still under development, but the research focus has shifted towards factor Xa inhibitors, or even dual thrombin and fXa inhibitors that have a broader mechanism of action by both inhibiting factor IIa (thrombin) and Xa. A recent review of patents and literature on thrombin inhibitors has demonstrated that the development of allosteric and multi-mechanism inhibitors might lead the way to a safer anticoagulant.
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