There are 5 germline mutations that lead to hypercoagulability in the general population including: Factor V Leiden ( FVL), Prothrombin G20210A ( F2A), Protein C Deficiency ( PCD), Protein S Deficiency ( PSD), and Antithrombin Deficiency ( ATD). Typical guidance is to defer testing, as it is thought not to change management.
We present a case of a patient who was found to be compound heterozygous mutations for FVL and F2A, who presented with two episodes of arterial thromboembolism resulting in cerebrovascular accident (CVA). A 63-year-old male with past medical history of hypertension, a CVA four years prior, and medication non-compliance presents with new onset left sided hemiparesis after an episode of convulsions. MRI and CT imaging of the head revealed ischemic CVA secondary to thromboembolism in the right posterior cerebral artery’s (PCA), P1 branch. Following administration of tissue plasminogen activator (tPA) he had rapid symptom improvement. This second ischemic CVA prompted a workup which was notable for: negative echocardiogram, negative 30-day cardiac monitor, CT chest negative for malignancy, no significant vascular findings, negative for antiphospholipid syndrome, but genetic testing revealed the patient to be heterozygous for FVL and F2A mutations. He was started on apixaban 5 mg twice daily for ongoing secondary prevention. Though medication compliance continues to be difficult, after being placed on direct anticoagulant (DOAC), he has not had recurrent venous or arterial thrombotic events. A small case series found double heterozygosity for FVL and F2A further increases the risk of venous thromboembolism up to 17% or more in a lifetime.
Although current recommendations advocate against testing for specific mutations in most cases as it is likely not to change management1, this case suggests that it may be of some benefit in patients that have a workup that does not yield a clear etiology, especially in cryptogenic stroke which is typically managed with aspirin rather than direct oral anticoagulant.