Prothrombin complex concentrate (PCC), also known as factor IX complex, is a medication made up of

blood clotting factor Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism ...

s II, IX, and X. Some versions also contain

factor VII Coagulation factor VII (, formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade, and in humans is coded for by the gene ''F7''. It is an enzyme of the serine protease class. Once bound to tis ...

. It is used to treat and prevent bleeding in hemophilia B if pure factor IX is not available. It may also be used for reversal of

warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent ...

therapy. It is given by slow injection into a vein. Common side effects include

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermat ...

, headache, vomiting, and sleepiness. Other serious side effects include

blood clots A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...

which may result in a

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which m ...

, stroke,

pulmonary embolism Pulmonary embolism (PE) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include shortness of breath, chest pain particularly upon breathing ...

, or

deep vein thrombosis Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and e ...

. Antibodies may form after long term use such that future doses are less effective. Prothrombin complex concentrate came into medical use in the 1960s. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It is made from human plasma. Recombinant factor IX is also available in a stand-alone preparation. In the United States a dose of PCC costs about US$900. A number of different formulations are available globally.

Medical uses

Prothrombin complex concentrate reverses the effects of

and other

vitamin K antagonist Vitamin K antagonists (VKA) are a group of substances that reduce blood clotting by reducing the action of vitamin K. The term "vitamin K antagonist" is technically a misnomer, as the drugs do not directly antagonise the action of vitamin K in ...

anti-coagulants and is used in cases of significant bleeding in people with a

coagulopathy Coagulopathy (also called a bleeding disorder) is a condition in which the blood's ability to coagulate (form clots) is impaired. This condition can cause a tendency toward prolonged or excessive bleeding (bleeding diathesis), which may occur sp ...

. It is also used when such a person must undergo an emergency operation. Other uses include a deficiency of one of the included clotting factors, either congenital or due to

liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the s ...

, and

hemophilia Haemophilia, or hemophilia (), is a mostly hereditary, inherited genetic disorder that impairs the body's ability to coagulation, make blood clots, a process needed to hemostasis, stop bleeding. This results in people bleeding for a longer ti ...

. Several guidelines, including those from the

American College of Chest Physicians The American College of Chest Physicians (CHEST) is a medical association in the United States consisting of physicians and non-physician specialists in the field of chest medicine, which includes pulmonology, critical care medicine, and sleep med ...

, recommend prothrombin complex concentrate for warfarin reversal in people with serious bleeding. 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.

Contraindications

The package insert states that prothrombin complex concentrate is contraindicated in patients with disseminated intravascular coagulation, a pathological activation of coagulation, 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 Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the trea ...

, they are contraindicated in patients with

heparin-induced thrombocytopenia Heparin-induced thrombocytopenia (HIT) is the development of thrombocytopenia (a low platelet count), due to the administration of various forms of heparin, an anticoagulant. HIT predisposes to thrombosis (the abnormal formation of blood clots ...

Chemistry

Prothrombin complex concentrate contains a number of blood clotting factors. Typically this includes factor II, IX, and X. Some versions also contain

protein C Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and cell death and maintain ...

, and

protein S Protein S (also known as PROS) is a vitamin K-dependent plasma glycoprotein synthesized in the liver. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b-binding protein (C4BP). In ...

Heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the trea ...

may be added to stop early activation of the factors.

History

The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) announced its approval in 2013. The FDA approved Kcentra's orphan drug status in December 2012.

References

External links