This month, Keith McCrae, MD, discusses the appropriate length of anticoagulation for a provoked DVT.
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I have always given 6 months of anticoagulation for provoked deep vein thrombosis (DVT) in the thigh and 3 months of anticoagulation for provoked or unprovoked DVT in the calf. Over the last several years, I’ve noticed a trend toward giving 3 months of anticoagulation for any provoked DVT. In what situation would you give 6 months of anticoagulation for provoked thromboembolism? I would certainly give 6 months of anticoagulation for an extensive pulmonary embolism (PE), but I’m uncomfortable giving only 3 months of anticoagulation for a DVT in the thigh.
The crux of this question is whether 3 months of anticoagulation is acceptable for a provoked DVT, and whether it is ever preferable to give 6 months of anticoagulation for a provoked thromboembolism.
The first recommendation of the American Society of Hematology’s (ASH’s) 2014 Choosing Wisely campaign was, “Do not treat with an anticoagulant for more than 3 months in a patient with a first venous thromboembolism (VTE) occurring in the setting of a major transient risk factor.”¹ This evidence-based recommendation is based on the low risk of recurrent VTE following 3 months of anticoagulant therapy in patients with VTE. The authors of this recommendation considered major transient risk factors to include events such as surgery, trauma, or an intravascular catheter for more than 3 months.
A more detailed response to this issue is provided in a large meta-analysis by Boutitie, et al.² The goal of this meta-analysis was to “identify the shortest length of treatment that reduced the risk of recurrence to its lowest value after stopping treatment.” The meta-analysis included data from 2,925 patients with a mean follow-up of 1.4 years per patient. Variables of primary interest were recurrence rates within 0 to 6 months, 7 to 24 months, and 0 to 24 months after stopping anticoagulation. Forty percent of included patients had provoked VTE and 60% had unprovoked VTE. Distal DVT was present in 20%, proximal in 52%, and pulmonary embolism in 29%.
Key findings of this study are as follows:
- For all participants, the risk of VTE recurrence was higher in those treated for 1.0-1.5 months compared with those treated for 3, 6, 12, or 27 months; however, the incidence of recurrence was similar in all groups treated for 3 months or longer. The risk of recurrence was approximately twice as high in patients with proximal VTE or PE compared with distal DVT and was also higher in patients with PE versus DVT, although this occurred largely in the first 6 months after stopping therapy in patients treated for 1.0-1.5 months.
- For patients with provoked VTE, there were no differences in overall recurrence rates for those treated for 1.0-1.5, 3, or 6 months (no patients with provoked VTE were treated for 12 or 27 months); however, recurrence rates in the first 6 months were greater in those treated for 1.0-1.5 months.
- For patients with unprovoked VTE, the risk for recurrence was approximately twice that of provoked VTE and higher in patients treated for 1.0-1.5 months compared with patients treated for 3 months or longer, with the risk greatest in the first 6 months after stopping therapy. There was a trend toward a higher recurrence rate in those treated for 3 months compared with those treated for 6 months or longer, although this difference was only significant during the first 6 months after stopping therapy.
Thus, for provoked VTE, these studies do not support treatment beyond 3 months, consistent with the ASH Choosing Wisely recommendations. However, this recommendation is applicable to patients with major transient risk factors. As noted in the Choosing Wisely recommendations, more prolonged treatment may be considered in patients with non-major transient risk factors such as pregnancy, immobilization during travel, or hormonal therapy (and perhaps many others). In these cases, the duration of anticoagulation should be determined on an individual basis.
- Hicks LK, Bering H, Carson KR, et al. The ASH Choosing Wisely campaign: five hematologic tests and treatments to question. Blood. 2013;122:3879-83.
- Boutitie F, Pinede L, Schulman S, et al. Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants’ data from seven trials. BMJ. 2011;342:d3036.
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NEXT MONTH'S CLINICAL DILEMMA
I have a patient with newly diagnosed chronic lymphocytic leukemia (CLL) who has normal cytogenetics. The presenting features were fever and hypoxia that led to 2 weeks of hospitalization; bronchoscopy revealed pneumocystis pneumonia. The patient is HIV negative and is now doing well without any typical criteria for CLL treatment. He has received intravenous immune globulin twice for an IgG level of 200 mg/dL. Is hypogammaglobulinemia alone an indication for treatment for CLL, in the absence of other symptoms or cytopenias?
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