ANTICOAGULATION FOR CALF THROMBOSIS

Anticoagulation for an isolated calf deep vein thrombosis (DVT) appears to decrease the risk for pulmonary embolism (PE) or proximal DVT by two thirds, but quadruples the risk of bleeding, according to a study published online July 20 in JAMA Surgery.

"[O]ur study may add weight to arguments for routine inclusion of the calf deep veins in ultrasonography studies and therapeutic anticoagulation for isolated calf DVTs," write Garth H Utter, MD, from the University of California, Davis, Medical Center in Sacramento, and colleagues.

Isolated calf DVTs, which occur distal to the popliteal vein, represent about half of all DVTs and may contribute to more dangerous proximal DVTs. However, no consensus exists on the most appropriate management for isolated calf DVT. Approaches include no treatment with monitoring, follow-up with serial imaging, and anticoagulation. At this time, no high-quality evidence exists to support best practices in treating isolated calf DVTs.

The current study included all adults who had received ultrasound diagnoses of an isolated calf DVT between January 2010 and December 2013 at the vascular laboratory of the University of California, Davis. The study excluded those who were already receiving anticoagulation or had contraindications to it, had a venous thromboembolism in the last 180 days, or had been diagnosed with a PE at the time of the first DVT.

The analysis included 384 patients (162 women [42.2%], 222 men [57.8%]), with a mean age of 60 years. Of those participants, clinicians intended to treat 63% (n = 243) with anticoagulation; the remaining 141 patients served as a control group in the analysis. Anticoagulation included warfarin (n = 182; 75.2%), low-molecular-weight heparin (enoxaparin or dalteparin; n = 43 [17.7%]), continuous heparin infusion (n = 15; 6.2%), and rivaroxaban and bivalirudin (n = 1; 0.4% for each). Among 156 patients not intended to receive indefinite anticoagulation and for whom the actual duration of anticoagulation was known, 90.5% received adequate anticoagulation for a mean of 106 days.

Receiving anticoagulation significantly decreased the odds of developing a proximal DVT or PE within 180 days of being diagnosed with an isolated calf DVT (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.14 - 0.83).

Among untreated patients, 7 (5.0%) developed proximal DVTs and six (4.3%) developed PEs. Among anticoagulation patients, four (1.6%) developed proximal DVTs and four (1.6%) developed PEs.

However, anticoagulation more than quadrupled the odds of bleeding (OR, 4.35; 95% CI, 1.27 - 14.9).

After sensitivity analyses and adjusting for age, sex, care setting, existing cancer, and history of DVT or PE, the findings remained about the same (DVT or PE OR, 0.33 [95% CI, 0.12 - 0.87]; bleeding OR, 4.87 [95% CI, 1.37 - 17.3]).

One hemorrhagic stroke occurred in the anticoagulation group and resulted in death.

The authors mention several limitations, including the retrospective, observational nature of the study and the lack of standardized indications for testing proximal DVT and PE.

They conclude, "[R]andomized studies are needed to draw firmer conclusions. Because the benefits of anticoagulation seem modest, we recommend attention to the risk for bleeding when determining whether anticoagulation is appropriate."

In an invited commentary, Xuan-Binh D. Pham, MD, and Christian de Virgilio, MD, both from the Harbor University of California, Los Angeles, Medical Center in Torrance, write that the study adds "valuable information" about the treatment of isolated calf DVT.

They also point out that those with a muscular branch DVT (soleal or gastrocnemius) and those with a provoked DVT benefited the most, and that research is inconsistent on this subject.

"Utter and colleagues provide further evidence that anticoagulation should strongly be considered in patients with provoked muscular branch DVT, because some calf DVT clearly can propagate and lead to PE," they emphasize. "This recommendation must be tempered by the sobering fact that anticoagulation can lead to life-threatening bleeding. We agree with the authors that a multi-institutional, prospective, randomized study is needed to better answer this question."

A randomized trial evaluating the efficacy of low-molecular-weight heparin for treating distal DVTs is currently underway.

The authors and editorialists have disclosed no relevant financial relationships.

JAMA Surg. Published online July 20, 2016.