In the second scenario discussed at the workshop, the woman who underwent preimplantation screening in the first scenario has developed a health problem 5 years later:

The individual is seen at 40 years of age with progressive left lower extremity swelling and pain. Evaluation reveals an unprovoked deep vein thrombosis in her left lower extremity. She will be treated as an outpatient with low-molecular-weight heparin and warfarin. Targeted testing includes CYP2C9 and VKORC gene analysis.

Deep vein thrombosis is a common condition, said Frederick Chen of the University of Washington, when he introduced the case. About a half-million patients per year in the United States get a blood clot in the leg. About one-quarter of them end up with a clot that travels to the lung, causing a pulmonary embolism (Beckman et al., 2010). Clinicians are well trained and accustomed to dealing with this condition, which he suggested may change the bar for a new technology or medication to be used in treating a thromboembolism.


Various risk factors are associated with deep vein thrombosis in 40-year-old women, said Michael Murray, clinical chief in the Genetics Division of the Department of Medicine at Brigham and Women’s Hospital. These factors include smoking, pregnancy, immobility, extended travel, surgery, hypertension, obesity, and cancer. Genetic factors may also be involved, including the prothrombin mutation and Factor V Leiden.

Warfarin is thought to impede the synthesis of clotting factors, specifically through inhibition of the vitamin K epoxide reductase complex C1 subunit (VKORC1). Therapeutic use effectively lowers the amount of active vitamin K-dependent clotting factor by approximately 30 to 50 percent. The effects of anticoagulation therapy generally occur within 24 hours, with peak effect taking up to 96 hours.

As a result, clinicians give doses of warfarin and then have to wait 2 to 3 days to determine the effect. The goal is to achieve an international normalized ratio (INR) between 2 and 3 to minimize the risk of either clot complications or bleed complications. “It is a very unwieldy tool,” said Murray.

The U.S. Food and Drug Administration (FDA) label for warfarin explains its pharmacogenomics (Bristol-Myers Squibb, 2010):

A meta-analysis of 9 qualified studies including 2775 patients (99% Caucasian) was performed to examine the clinical outcomes associated with CYP2C9 gene variants in warfarin-treated patients [Sanderson et al.,

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