This page is still under construction.

This page is still under construction.

This is an overview of atrial fibrillation and its management.

What is it?

Atrial fibrillation (AF or A Fib) is a relatively common heart disorder. AF is an "irregular, rapid contraction of the atria."

The human heart is made up of four chambers (two atria and two ventricles) that normally work together to pump the blood throughout the body.

In AF, however, the atria beat out of rhythm with the rest of the heart. In fact, the atria may beat as many as 350 to 400 times a minute during AF compared with the 60 to 100 times a minute normally. These irregular, rapid contractions make it difficult for the left atrium to empty blood into the left ventricle, which then pumps the blood to the body.

Who gets AF?

It may surprise you, but AF affects more than 2 million Americans. In fact, as many as 9% of Americans over the age of 65 may have atrial fibrillation.

How do you get AF?

AF can occur in otherwise healthy individuals. But in most cases AF is associated with underlying heart disease or, occasionally, with thyroid disorders.

What are the risks of AF?

Even if your AF is barely noticeable, you must be aware of the possible dangers. If left untreated, AF can lead to serious consequences.

• Stroke - AF may increase your risk of stroke more than five times. As a result of AF, approximately 75,000 strokes occur every year. Because the rapidly contracting atrium cannot empty properly, blood pools in the atrium and a clot may form.. If these clots break free they can lodge in an artery of the brain and cut off the blood supply to that area. This condition, known as stroke, can result in brain damage or death.

• Heart Failure - AF may be associated with heart failure - a condition in which the heart is unable to pump enough blood to support the rest of the tissues of the body.

The good news is... Many people continue to live normal lives with AF. The following is a list of some of the ways your doctor can help manage your AF:

• Returning your heart rate to normal - In many cases, your doctor will be able to use electrical stimulation or medication to restore your normal heart rhythm or slow the heart rate.

• Preventing stroke - Treatment programs may be used to help prevent harmful clots from forming in the left atrium during AF. As a result, these treatments may help reduce the risk of stroke that is often associated with AF.

This page is still under construction.

This page is still under construction.

Factor V Leiden: A common inherited abnormality in the Factor V molecule. Factor V Leiden doesnít interact with Protein C and Protein S. Factor V Leiden canít be inhibited by Protein C and Protein S. Too much Factor V is thereby present and this accelerates clotting by excessively activating prothrombin to form the active clot promoting substance thrombin. Thrombin in turn activates soluble fibrinogen causing it to become insoluble and form fibrin clot.

The activation of inert prothrombin to the active pro-clotting agent thrombin is a point of tight biologic control. To generate active thrombin, the body requires two other clotting proteins, called Factor V and Factor VIII. It also requires that Factor V and Factor VIII assemble in close proximity to each other, usually on the surface of a blood cell called a platelet, and that calcium and certain fatty substances be available. Nature has created a complex regulatory because of the extreme importance of regulating blood fluidity and clotting.

Factor V and Factor VIII can be inhibited by a combination of two other proteins known as Protein C and Protein S. Protein C and Protein S act as natural anticoagulants, limiting the clotting process. Some people have an abnormal Factor V molecule called Factor V Leiden. Unlike normal Factor V, Factor V Leiden cannot be efficiently inhibited by Protein C and Protein S. Because Factor V Leiden cannot be inhibited by Protein C and Protein S, an excess amount of Factor V is present in the body, leading to excess thrombin formation which in turn causes excessive and undesired clot formation. The factor V Leiden gene mutation is the most common of all hypercoagulable states so far described and affects 3%-5% of the population.

Resistance to Activated Protein C and Factor V Leiden

Activated protein C (APC) is a natural anticoagulant that attenuates clotting by inactivating the two cofactors in the clotting pathway, factor Va and VIIIa. The molecular defect responsible for resistance to APC is a point mutation at one of the APC cleavage sites in the factor V gene, changing amino acid 506 from Arg to Gln. This mutation increases the risk of venous thrombosis 10-fold in heterozygotes and 50-fold in homozygotes. Factor V Leiden is the most common cause of inherited thrombosis risk yet identified in individuals of Northern European ancestry, and is present in up to 40% to 50% of such patients with familial thrombophilia. Other ethnic groups have a much lower prevalence of the mutation. Factor V Leiden appears to increase risk synergistically in individuals with other risk factors for venous thromboembolism, such as age, oral contraceptive use, hyperhomocysteinemia, and defects in other natural anticoagulants.

Diagnosis of Resistance to Activated Protein C/Factor V Leiden

Testing for this syndrome can be performed by a PTT-based screening test and by molecular analysis of the factor V gene. The PTT-based test for resistance to APC is performed by comparing a patient's PTT with APC added with a PTT without APC added. The test results are reported as a ratio: PTT with APC added/PTT without APC added. The first-generation APC resistance test suffered from low specificity and could not be used in patients on heparin or Coumadin. More recent versions that dilute the patient plasma into factor V-deficient plasma appear to have resolved these difficulties.

Molecular diagnosis of Factor V Leiden is performed by isolating genomic DNA from patient white blood cells and amplifying the region of the factor V gene flanking the mutation site using the polymerase chain reaction. The amplified DNA is analyzed by restriction enzyme digestion. With this method, patients are classified a wild type (normal), heterozygous for Factor V Leiden, or homozygous for Factor V Leiden.

Approximately 10% of venous thrombosis patients with resistance to APC do not have Factor V Leiden. Some of these individuals appear to have linked polymorphisms in the factor V gene associated with the resistant phenotype. The molecular mechanism of resitance of APC in such individuals and risk of thrombosis of the subset of patients remain to be determined.

Protein C: A protein that inactivates Factor V and Factor VIII, thus decreasing thrombin generation and limiting clotting. A deficiency in Protein C, which is usually inherited, will lead to excess clot formation because too much active Factor V and Factor VIII are present leading to excess thrombin formation and excess clotting.

Protein S: A protein that serves as a helper for Protein C, thus decreasing thrombin generation and limiting clotting. A deficiency in Protein S, which is usually inherited, will lead to excess clot formation because too much active Factor V and Factor VIII are present leading to excess thrombin formation and excess clotting.

This page is still under construction.

Anti-thrombin: Limits thrombin activity and clot formation. A deficiency which is usually inherited, will cause the patient to clot excessively because too much active thrombin is present.

This page is still under construction.

This page is still under construction.

Prothrombin 20210A: A recently described inherited abnormality which causes the body to make too much prothrombin. This leads to excess thrombin generation, and excess production of fibrin (the substance clots are made of).

This page is still under construction.