Treating DVT: Answers to 7 key questions
Complex recommendations for anticoagulant therapy raise questions for family physicians. Here are the evidence-based answers you need to manage DVT patients successfully.
5. How should i proceed when a patient taking warfarin also needs antiplatelet medications?
Monitor warfarin more frequently in such patients and target the lower end of the INR therapeutic range (2-2.5).9 Keep an eye on your patient’s overall medication regimen and avoid medications like nonsteroidal anti-inflammatory drugs (NSAIDs) that increase bleeding risk. If NSAIDs must be used, avoid chronic use, high doses, and NSAIDs with a long half-life. You may also want to consider referral to an anticoagulation clinic.
Many of these patients have cardiac conditions for which dual antiplatelet therapy is recommended. For example, patients with coronary stents may need aspirin and clopidogrel for a specified period of time. They may have underlying atrial fibrillation or valve replacement requiring warfarin therapy. Data examining triple therapy (aspirin, clopidogrel, and warfarin) are primarily limited to patients with acute coronary syndrome or those who have had percutaneous coronary intervention. Unfortunately, the data are also retrospective, based on a small sample, and inconsistent.10 In these patients, you need to weigh the increased risk of bleeding against the proven preventive value of each of these modalities.
For patients with stents, current guidelines recommend a lower dose of aspirin and discontinuation of clopidogrel after a certain length of time, depending on the type of stent.10,11 However, 1 study showed that aspirin dose and INR values did not influence bleeding risk in patients on triple therapy.12
It is imperative that you counsel patients on triple therapy to report the first sign of bleeding.
6. What is the best approach when a patient’s INR is elevated?
You’ll need to minimize the risk of bleeding while at the same time ensuring adequate levels of anticoagulation. You can use oral vitamin K (phytonadione [Mephyton]) to reverse the effects of warfarin without inducing warfarin resistance. Avoid subcutaneous administration; the effects are unpredictable and response is delayed.4
Send patients with active or life-threatening bleeding to the emergency department. Reserve intravenous vitamin K administration for patients who are bleeding or have an INR >20. The ACCP guidelines provide recommendations on managing elevated INRs in patients receiving warfarin (TABLE 4).4
TABLE 4
Managing elevated INR
| For any INR above therapeutic range | Monitor more frequently and resume anticoagulation at an appropriately adjusted dose when the INR is at a therapeutic level. |
| INR above therapeutic range, but ≤5.0 and no significant bleeding | Lower the dose or omit a dose; INR only minimally above therapeutic range or associated with a transient causative factor may not require dose reduction. |
| INR >5.0 but <9.0, and no significant bleeding | Omit 1 to 2 doses. Alternatively, if the patient is at increased risk of bleeding, omit a dose and administer vitamin K (1-2.5 mg) orally. If more rapid reversal is required because the patient requires urgent surgery, vitamin K (<5 mg orally) will reduce INR within 24 hours. If INR remains high, give additional vitamin K (1-2 mg) orally. |
| INR ≥9.0 | Hold warfarin therapy and administer vitamin K (2.5-5 mg orally); INR will be reduced substantially in 24-48 hours. Administer additional vitamin K if necessary. |
| Serious bleeding regardless of INR | Hold warfarin and give vitamin K (10 mg by slow IV infusion). may repeat in 12 hours if necessary. Administer FFP, PCC, or rVIIa if necessary. |
| Life-threatening bleeding | Hold warfarin. Administer vitamin K (10 mg by slow IV infusion). May repeat if necessary. Administer FFP, PCC, or rVIIa along with vitamin K. |
| FFP, fresh frozen plasma; INR, international normalized ratio; PCC, prothrombin complex concentrate; rVIIa, recombinant factor Viia. | |
| Adapted from: Ansell J, et al. Chest. 2008.4 | |
7. What new anticoagulants are on the horizon?
Several alternative treatments for DVT are currently in clinical trials, and 1 recently received FDA approval.
Ximelagatran, a direct thrombin inhibitor, appeared to hold promise as an oral anticoagulant, but was denied FDA approval and eventually withdrawn by its manufacturer when reports of hepatotoxicity and possible myocardial ischemia surfaced.13,14 Other oral treatment options to be aware of include another direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors apixaban and rivaroxaban.
Dabigatran (Pradaxa), an oral direct thrombin inhibitor similar to ximelagatran, received FDA approval last month for stroke prevention in atrial fibrillation. One study, RE-COVER, studied dabigatran vs warfarin for the treatment of acute VTE—both lower extremity DVT and PE. This noninferiority trial compared dabigatran 150 mg twice daily with daily warfarin adjusted to achieve an INR of 2.0 to 3.0, with the 6-month recurrence of VTE as the primary outcome. Dabigatran was found to be as effective as warfarin at preventing recurrent or fatal VTE. There was no difference in major bleeding between the dabigatran and warfarin groups, although the dabigatran group did show more major or clinically relevant nonmajor bleeding. No differences in other adverse events were observed between the 2 groups.15
