From the FDA Drug Label
For patients with a first episode of DVT or PE who have documented deficiency of antithrombin, deficiency of Protein C or Protein S, or the Factor V Leiden or prothrombin 20210 gene mutation, homocystinemia, or high Factor VIII levels (>90th percentile of normal), treatment for 6 to 12 months is recommended and indefinite therapy is suggested for idiopathic thrombosis
- Key Point: The patient has Factor V Leiden deficiency and failed NOAC therapy.
- Alternative Anticoagulant: Coumadin (warfarin) can be considered as an alternative anticoagulant for this patient.
- Dosage and Administration: The dosage and administration of warfarin must be individualized for each patient according to their PT/INR response to the drug, with a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations 1.
From the Research
For patients with Factor V Leiden deficiency who have failed NOAC therapy, Coumadin (warfarin) may not be the best alternative due to its limitations and potential for increased risk of thrombosis in certain cases, as suggested by a case report of a patient with Factor V Leiden mutation taking warfarin who presented with chronic thrombosis of the inferior vena cava 2. Instead, low molecular weight heparin (LMWH) such as enoxaparin (Lovenox) is often recommended as an alternative anticoagulant. Enoxaparin is typically administered as a subcutaneous injection, with dosing based on body weight (approximately 1 mg/kg twice daily or 1.5 mg/kg once daily). This medication works by enhancing antithrombin's inhibition of factor Xa and thrombin, providing anticoagulation through a different mechanism than NOACs or warfarin. Some key points to consider when using LMWH in patients with Factor V Leiden deficiency include:
- LMWH is particularly valuable for Factor V Leiden patients because it doesn't rely on vitamin K antagonism like warfarin or directly target specific coagulation factors like NOACs.
- For long-term management, fondaparinux (Arixtra), a synthetic pentasaccharide that selectively inhibits factor Xa, may also be considered at doses ranging from 5-10 mg subcutaneously once daily based on weight.
- Both options require regular monitoring of anti-Xa levels rather than INR, and patients should be educated on self-injection techniques if these medications will be used long-term.
- Renal function should be assessed before initiating either therapy as dosage adjustments may be necessary for patients with impaired kidney function, as noted in a study on the use of NOACs in patients with severe inherited thrombophilia 3. It's also important to note that the use of direct oral anticoagulants (DOACs) can interfere with coagulation assays used to diagnose thrombophilia, and therefore, caution should be exercised when interpreting these results, as highlighted in a recent review on inherited thrombophilia in the era of DOACs 4.