Hemostasis and Thrombosis Issues

Pharmacy TimesNovember 2012 Cough & Cold
Volume 78
Issue 11

Factor V Leiden thrombophilia and the comparative risks of oral anticoagulants are discussed.

Factor V Leiden thrombophilia and the comparative risks of oral anticoagulants are discussed.

Factor V Leiden Thrombophilia

Factor V Leiden thrombophilia, an increased tendency to form abnormal blood clots, is the most commonly inherited clotting disorder.1 It is estimated that between 3% and 8% of people of European descent carry 1 copy of the Factor V Leiden mutation in each cell, and about 1 in 5000 people have 2 copies.2

Factor V Leiden thrombophilia is caused by a mutation in the F5 gene, a gene that is integral in the production of a protein called coagulation factor V. Coagulation factor V is important in the coagulation process because it prevents clots from becoming too large by slowing down clotting. Activated protein C (APC), the protein that normally inactivates coagulation factor V, does not work properly in people with factor V Leiden thrombophilia. This results in the clotting process remaining active longer than usual in these patients, increasing their chance of developing abnormal blood clots.2

Factors that increase the risk of clotting complications in factor V Leiden patients include advanced age, obesity, smoking, pregnancy, and the use of oral contraceptive pills (OCPs) or estrogen replacement therapy, to name a few.2 In general, people with factor V Leiden have a higher than average risk of developing a deep venous thrombosis (DVT) and pulmonary embolism (PE). DVTs occur most often in the legs but may develop in other parts of the body.

Women who take OCPs and have factor V Leiden have about a 35-fold increased risk of developing a DVT or PE compared with women without the condition and those who do not take OCPs.1 Also, women with this mutation are 2 to 3 times more likely to have multiple second or third trimester miscarriages. Factor V Leiden mutation may also increase the risk of other complications during pregnancy, including preeclampsia, slow fetal growth, and placental abruption.

Anticoagulation therapy includes warfarin or 1 of the newer anticoagulants.1 Unless additional risk factors exist, it is not usually recommended that people with factor V Leiden receive lifelong anticoagulants if they have had only 1 DVT or PE.

Any Significant Differences Between Newer Oral Anticoagulants?

In a recent study utilizing an indirect comparison of newer oral anticoagulants, there were no profound differences reported between apixaban, rivaroxaban, and dabigatran.5 Major comparison points researchers reported include:

Risk of stroke and systemic embolism—No significant differences were found between apixaban and the 110- and 150-mg doses of dabigatran or between apixaban and rivaroxaban. A comparison between dabigatran 150 mg and rivaroxaban showed a 26% reduction in the risk of stroke or systemic embolism favoring dabigatran (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.56-0.97).

Risk of hemorrhagic stroke— When compared with rivaroxaban, dabigatran significantly reduced the risk of hemorrhagic stroke by 56% and nondisabling stroke by 40%.

Risk of major bleeding—For apixaban, a decrease of 26% was seen when compared with dabigatran 150 mg (HR 0.74; 95% CI 0.61-0.91) and 34% when compared with rivaroxaban (HR 0.66; 95% CI 0.54-0.81). Dabigatran 110 mg reduced the risk of major bleeding 23% compared with rivaroxaban (HR 0.77; 95% CI 0.83-0.94). There was no difference in major bleeding between apixaban and dabigatran 110 mg or between dabigatran 150 mg and rivaroxaban.

Although these data have some merit, the study’s methodology must be considered when interpreting these results. The researchers used the Bucher method for comparing the different agents, in which each agent in question was compared with warfarin and then the hazard ratios for safety and efficacy were calculated to compare the agents with each other.5

Ideally, a randomized, controlled, head-to-head clinical trial comparing the agents should be used to determine the relative safety and efficacy of the agents. Because researchers understood that this scenario was unlikely to occur, indirect comparison was an alternative. One disadvantage of indirect comparison studies is that data from previous studies with different agents sometimes prove inconsistent with data from direct head-to-head randomized clinical trials.6 Although the merits of indirect comparison studies can be debated, they provide some insight into how these drugs compare with each other.

Mr. Brown is professor emeritus of clinical pharmacy and a clinical pharmacist at Purdue University College of Pharmacy, Nursing, and Health Sciences, Department of Pharmacy Practice, in West Lafayette, Indiana. This column’s information is based on current studies and references, but it may be changed without notice with newer studies or with different patient populations.


1. Ornstein DL, Cushman M. Cardiology patient page, Factor V Leiden. Circulation. 2003; 107: e94.-e97.

2. Factor V Leiden thrombophilia. Genetics Home Reference website. http://ghr.nlm.nih.gov/condition/factor-v-leiden-thrombophilia. Accessed October 20, 2012.

3. Juul K, Tybjaerg-Hansen A, Schnohr P, et al. Factor V Leiden and the risk for venous thromboembolism in the adult Danish population. Ann Intern Med. 2004: 3;140(5):330-337.

4. Calderwood CJ, Greer IA. The role of factor V Leiden in maternal health and the outcome of pregnancy. Curr Drug Targets. 2005;6(5):567-576.

5. Lip GY, Larsen TB, Skjøth F, Rasmussen LH. Indirect comparisons of new oral anticoagulant drugs for efficacy and safety when used for stroke prevention in atrial fibrillation. J Am Coll Cardiol. 2012; 60:738-746.

6. O’Riordan M. No profound difference between oral anticoagulants, comparison suggests. The Heart.org website. www.theheart.org/article/1435557.do

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