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An episode of DVT without a provoking factor used to be considered an indication for testing for hypercoagulability. However, current approach to this question is to consider such testing unreliable and not to use it for clinical decision making.

Hypercoagulable states can be defined as a group of inherited or acquired conditions associated with a predisposition to venous thrombosis, arterial thrombosis, or both. Venous thromboembolic disease is the most common clinical manifestation resulting from hypercoagulable states. A number of inherited conditions can not be tested for; however, unfortunately there are no accepted guidelines as to what constitutes indications for such testing.The American College of Medical Genetics and the College of American Pathologists state that this testing is appropriate to use widely because the polymorphisms that predispose to thromboses are fairly widespread; however, they have listed the situations in which thrombophilia testing should not be used. These include: for general screening, routine during pregnancy, routine screening prior to the use of oral contraceptives, prenatal or newborn screening , testing of asymptomatic children, routine testing in adults with an arterial thrombosis.

Hypercoagulable states can be defined as a group of inherited or acquired conditions associated with a predisposition to venous thrombosis, arterial thrombosis, or both. Venous thromboembolic disease is the most common clinical manifestation resulting from hypercoagulable states. A number of inherited conditions can not be tested for; however, unfortunately there are no accepted guidelines as to what constitutes indications for such testing. The American College of Medical Genetics and the College of American Pathologists state that this testing is appropriate to use widely because the polymorphisms that predispose to thromboses are fairly widespread; however, they have listed the situations in which thrombophilia testing should not be used. These include: for general screening, routine during pregnancy, routine screening prior to the use of oral contraceptives, prenatal or newborn screening , testing of asymptomatic children, routine testing in adults with an arterial thrombosis. (Bates SM., 2008)

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) (2011) Working Group found adequate evidence to recommend against routine testing for Factor V Leiden (FVL) and/or prothrombin 20210G>A (PT) in the following circumstances: (1) adults with idiopathic venous thromboembolism (VTE). In such cases, longer term secondary prophylaxis to avoid recurrence offers similar benefits to patients with and without one or more of these mutations. (2) Asymptomatic adult family members of patients with VTE and an FVL or PT mutation, for the purpose of considering primary prophylactic anticoagulation. Potential benefits are unlikely to exceed potential harms. The overall certainty of these findings was deemed “moderate.” The evidence was insufficient to determine whether FVL/PT testing might have clinical utility in some circumstances, such as for identifying FVL homozygosity among asymptomatic family members of adults with idiopathic VTE or counseling patients about the risks and benefits of antithrombotic therapy. Based on the available evidence, the certainty of net health benefit was deemed “low.” The recommendations do not extend to patients with other risk factors for thrombosis, such as contraceptive use, as the evidence review that serves as the basis for the recommendations focused primarily on idiopathic VTE.

“Screening for hypercoagulable states in patients with VTE  Individuals with VTE should be screened in the presence of any of the following conditions: (a) age under 50 years; (b) recurrent VTE; (c) positive family history of VTE in first-degree relative; (d) recurrent fetal loss; (e) DVT and/or PE while on the birth control pill or hormone replacement; or (f) while pregnant/postpartum… Screening tests for hypercoagulable states can be affected by multiple conditions and therapies (e.g., medications, pregnancy, infections, active thrombotic process). Because it is unlikely that the detection of a hematologic abnormality will alter the intensity of anticoagulant therapy, screening for a hypercoagulable state 12 months after the anticoagulant therapy has been stopped is recommended… Individuals who develop VTE and have a hypercoagulable state do not usually need lifelong anticoagulation. If there is no VTE, and the hypercoagulable state was detected during routine screening, the decision to treat should be based on individual risk factors and the type of hypercoagulable state. Many patients, however, may benefit from prophylaxis during high-risk periods (e.g., surgery and pregnancy).”

“Most patients with venous thromboembolism do not require thrombophilia testing, since the results will not affect management. Testing may be considered in younger patients with weak provoking factors, a strong family history, or recurrence at a young age.” (Connors, J. M., 2017).

“Although patients with hypercoagulable risk factors are at a great risk for developing a thrombotic event, not all patients with hypercoagulable risk factors will develop clinically relevant thrombosis; conversely, not all patients with thrombosis will have an identifiable hypercoagulable state” (Nakashima, M. O., & Rogers, H. J., 2014).   

2. Does genetic testing and gene analysis, coagulation Factor V gene analysis, Leiden Variant need/have final approval from the appropriate regulatory bodies for this diagnosis?

The genetic testing and gene analysis, coagulation Factor V gene analysis, Leiden Variant need final approval from the appropriate regulatory bodies for this diagnosis    

3. Is this patient a good candidate for genetic testing and gene analysis, coagulation Factor V gene analysis, Leiden Variant ?

No. Family history alone is not considered a good reason for thrombophilia testing. An episode of DVT without a provoking factor used to be considered an indication for testing for hypercoagulability. However, current approach to this question is to consider such testing unreliable and not to use it for clinical decision making. Family history in the absence of clotting events is not an accepted reason for testing. Therefore, this is not a good candidate for genetic testing and gene analysis, coagulation Factor V gene analysis, Leiden Variant.

PEER REVIEWED PUBLICATION/LITERATURE:

Bates SM, Greer IA, Pabinger I, Sofaer S, Hirsh J. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. Jun 2008;133(6 suppl):844S-886S.

Connors, J. M. (2017). Thrombophilia Testing and Venous Thrombosis. N Engl J Med 2017; 377:1177-1187September 21, 2017

Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: routine testing for factor V Leiden (R506Q) and prothrombin (20210>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members. Genet Med 2011:13:6776.Moll S. Who should be tested for thrombophilia? Genet Med 2011:13:19-20.

Nakashima, M. O., & Rogers, H. J. (2014). Hypercoagulable states: an algorithmic approach to laboratory testing and update on monitoring of direct oral anticoagulants. Blood research, 49(2), 8594. doi:10.5045/br.2014.49.2.85

Prosciak, M. P. et al. (2017). Hypercoagulable states: A concise review. DOI: 10.4103/IJAM.IJAM_18_17