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The Role of Prothrombin in Blood Clotting

Prothrombin is one of several factors essential to the process of blood coagulation (blood clotting). While a lack of prothrombin can cause bleeding disorders, so too can many other factors, such as genetic mutation or other blood disorders. As doctors attempt to diagnose and find the cause of blood disorders, they use the "prothrombin time" test to help them determine the proper course of treatment.

Prothrombin and Other Clotting Factors

For blood to clot normally, several key events must take place in a process known as the "coagulation cascade." During this process, proteins called "factors" act at different times in various ways to prevent excessive bleeding. These factors, some of which the liver produces, include:

factor II (prothrombin)
factor V
factor VII
factor IX
factor X.

Circulating blood platelets in conjunction with these clotting factors produces a meshed network that stops blood flow. A lack or inaction of any of the above blood factors can result in excessive blood loss or excessive blood clot (thrombus) formation. While losing too much blood can cause a person to bleed to death, floating blood clots that obstruct proper blood flow can cause potentially fatal heart attacks and strokes.

How Blood Clots in Healthy Individuals

Here is a basic outline of the process by which blood clots in healthy people without blood disorders:

Injury occurs and causes bleeding.
The von Willebrand factor and collagen spark the platelets into action.
Platelets unite, or "aggregate," at the injury site.
The “coagulation cascade” begins.
Factor VII becomes factor VIIa, meaning it is activated.
Factor VIIa and the "tissue factor" activate factor X, which becomes factor Xa.
Factor Xa activates prothrombin, also known as factor II.
Factor II becomes Iia, also known as "thrombin.”
Thrombin activates factors I and Ia, also referred to as fibrin.
Fibrin, in conjunction with the platelet aggregation, forms a mesh at the clot site.
Factor XIII responds and stops blood flow entirely by finishing up the clot.

Of course, other proteins come into play in this complex production. Because each step in this chain of events relies on the successful completion of the previous step to move forward, any disruption of this process results in a bleeding disorder.

Prothrombin Deficiencies

Prothrombin production depends on a healthy level of vitamin K in the liver. Any lack of prothrombin can either result from a congenital (present from birth) or developed condition. While a congenital factor II deficiency (known as hypoprothrombinemia) is very rare, the acquired form (dyspothrombinemia) is more common.

Patients can develop dyspothrombinemia if they have taken anticoagulant medications, suffer from liver disease or have a vitamin K deficiency. Patients with general vitamin K deficiency may have a lack of this essential nutrient due to:

antibiotic use
an inability of the stomach or intestines to absorb vitamin K
obstruction in bile ducts preventing proper liver function.

Symptoms of a prothrombin deficiency include:

excessive bruising
heavy menstrual periods
internal muscle hemorrhage
nose bleeds.

Prothrombin Complex Concentrates (PPCs)

Prothrombin complex concentrates, or PPCs, are a combination of the clotting factors II, VII, IX and X that doctors use to treat some bleeding disorders. The amount of factor II included in PPC varies, as it is a plasma product obtained from donated blood. Administered intravenously, prothrombin complex concentrates can be effective against hemorrhaging during surgery for patients with bleeding disorders.

Excess Levels of Prothrombin

While prothrombin deficiencies prevent the blood from clotting, excess levels of factor II in the blood can cause excessive or unexpected clotting, or thrombophilia. Caused by gene mutation (known as 20210), high levels of prothrombin can cause obstructive blood clots in the leg (known as deep vein thrombosis) or in the chest (known as pulmonary embolism). Both of these thrombophilia complications can be fatal if left untreated.

Thrombophilia treatment may require patients to:

get massages regularly
regularly exercise (to improve circulation)
take anticoagulant medication
wear compression stockings (to prevent clotting and aid blood flow).

The Prothrombin Time Test

The prothrombin time (PT) test, a measure of how long the clotting process takes, can identify deficiencies in factors I, II, V, VII and X that are causing bleeding disorders. Similarly, the PT test can monitor the effectiveness of some anti-coagulation medications, such as warfarin.

The test itself is simple and involves a typical blood draw. At the lab, doctors use the international normalized ratio (INR) as the standard against which they gauge the results of various patients’ PT test results.

The PT test can provide a false reading if the patient has:

a diet high in vitamin K (These include diets high in broccoli, liver and green tea.)
any illness or condition that causes extreme fluid loss (i.e., diarrhea, vomiting)
recently consumed alcohol
recently taken a laxative
recently taken over-the-counter drugs (i.e., aspirin)
recently taken prescription medications (i.e., birth control pills, hormone replacement therapy, etc.)
undergone a heart valve replacement surgery (Proteins in the body recognize this valve as an intruder and respond by attempting to attack it and coagulate.).

A reduction in the levels of vitamin K can help treat excess levels of prothrombin, thereby preventing unusual coagulation.

Resources

Drug Information Online (1998).Anti-Inhibitor Coagulant Complex (Systemic). Retrieved September 22, 2007, from the Drugs.com Web site: http://www.drugs.com/mmx/anti-inhibitor-coagulant-complex.html.

Louisiana Hemophilia Foundation (2007). Factor II Deficiency. Retrieved September 22, 2007, from the Louisianahemophilia.org Web site: http://www.louisianahemophilia.org/factor_ii_deficiency.htm.

National Hemophilia Foundation (n.d.). Factor II Deficiency. Retrieved September 22, 2007, from the Hemophilia.org Web site: http://www.hemophilia.org/bleeding_disorders/hemophilia

_factor_II.htm.