Management and Outcomes of Isolated Distal Deep Vein Thromboses: A Questionable Trend toward Long-Lasting Anticoagulation Treatment. Results from the START-Register

Background Isolated distal deep vein thromboses (IDDVT) are frequently diagnosed; however, their natural history and real risk of complications are still uncertain. Though treatment is still not well standardized, international guidelines recommend no more than 3 months of anticoagulation therapy. We investigated how Italian clinicians treat IDDVT patients in their real life in our country. Methods Baseline characteristics and clinical history of the patients enrolled in the prospective, observational, multicenter START-Register for a first IDDVT or proximal DVT (PDVT) were analyzed. Results Overall, 412 IDDVT patients were significantly younger, with better renal function, and more frequent major transient risk factors, when compared with 1,173 PDVT patients. The anticoagulation duration was >180 days in 52.7% of IDDVT patients (70.7% in PDVT). During treatment, bleeding occurred in 5.6 and 2.8% patient-years in IDDVT and PDVT, respectively (p = 0082). Bleeding was more frequent in IDDVT than PDVT patients treated with warfarin (6.8 vs. 3.2 patient-years, p = 0.0228, respectively). Thrombotic complications occurred in 1.1 and 2.4% patient-years in IDDVT and PDVT patients, respectively. Analyzing together the two groups, 66.1% of bleeds and 86.1% thrombotic complications occurred after 90 days anticoagulation treatment. Conclusion The large majority of IDDVT patients received anticoagulation for more than 3 months. Most bleeding and thrombotic complications occurred after the first 90 days of anticoagulation therapy. These results indicate that an extended anticoagulation beyond 90 days in IDDVT patients is associated with increased risk of complications. Whether an extended treatment may lower recurrences after anticoagulation withdrawal should be assessed by specifically designed studies.

Calf deep vein thrombosis – clinical relevance, diagnostic approaches and therapeutic options

Summary. Isolated distal deep vein thromboses (IDDVT) represent up to 50 % of legs deep vein thromboses (DVT). However, since their natural history is to date unknown, the need to diagnose and treat them is a matter of debate. The diagnostic strategy based on the assessment of pre-test probability and D-dimer demonstrated a scarse efficiency for IDDVT. The choice between a proximal and a complete ultrasonographic approach should be guided by the clinical context, the local expertise and the patient characteristics. Randomized and observational studies have analyzed the need of therapy and compared different regimens of anticoagulation, with conflicting results. Systematic reviews and meta-analyses tend to support the usefulness of an anticoagulant treatment, even if the optimal dose and duration are not still defined. A careful stratification of the patient’s profile, taking into account risk factors for proximal extension, recurrence and bleeding should address the therapeutic approach, which must always be discussed with an adequately informed patient. Further studies aimed to clarify the natural history of IDDVT, and to assess safety and efficacy of lower intensity and shorter duration protocols are urgently needed.

288Thrombotic events in bleeding patients treated with andexanet alpha: an ANNEXA-4 sub-study

Background/Introduction Andexanet alfa (“andexanet”) was developed as a specific reversal agent for patients with major bleeding while using factor Xa (FXa) inhibitors. While thrombotic events (TEs) have been reported in patients receiving andexanet, the scope, nature, and timing of these events have not been fully characterized. Purpose The ANNEXA-4 study was a prospective, single-arm, open-label clinical trial that evaluated the safety and efficacy of andexanet in patients with acute major bleeding. In this secondary analysis, the occurrence of TEs was investigated. Methods Patients presenting with acute major bleeding within 18 hours after their last dose of FXa inhibitor were treated with andexanet. Safety outcomes, including TEs (reviewed by an adjudication committee), were evaluated at 30 days. Results Among 352 patients treated with andexanet, 34 (9.7%) experienced one or more TEs (Table). Strokes and deep vein thromboses were the most frequent TE types. Compared to patients with arterial TEs, patients with venous TEs were more likely to have been originally anticoagulated for venous thromboembolism. Median time to first TE was 10.5 days (Figure); time to event was shorter for arterial TEs than for venous TEs. TEs were nonfatal for most patients. Subgroups by age, bleed type, baseline anti-fXa activity, FXa inhibitor dose, and andexanet dose were not associated with the occurrence of TEs. Of the 34 TE patients, 26 (76.4%) had TEs before restart of any (full or prophylactic) anticoagulation; all first TEs occurred in patients not receiving oral anticoagulation. No TEs occurred after resumption of oral anticoagulation (N=100). Table 1. Thrombotic event characteristics Characteristic Result (n/N [%]) TE type Strokes 14/352 (4.0%) Deep vein thromboses 13/352 (3.7%) Myocardial infarctions 7/352 (2.0%) Pulmonary embolisms 5/352 (1.4%) Transient ischemic attacks 1/352 (0.3%) Bleed type Intracranial 23/227 (10.1%) Gastrointestinal 7/90 (7.8%) Other 4/35 (11.4%) Arterial TEs Anticoagulated for AF 17/22 (77.3%) Anticoagulated for VTE 6/22 (27.3%) Venous TEs Anticoagulated for AF 11/18 (61.1%) Anticoagulated for VTE 8/18 (44.4%) Median time to first TE 10.5 days Arterial 6 days Venous 15 days Outcome Fatal 7/34 (20.6%) Nonfatal 27/34 (79.4%) AF = atrial fibrillation; n = number of patients with TEs; N = total number of patients for each characteristic; TE = thrombotic event; VTE = venous thromboembolism. Figure 1. Thrombotic Events Over Time Conclusions In patients with FXa inhibitor-associated acute major bleeding treated with andexanet, TEs occurred a rate not unexpected given the high thrombotic risk of the population. No factors predictive of TEs were identified. Resumption of anticoagulation was associated with fewer TEs. Acknowledgement/Funding Study funded by Portola Pharmaceuticals, Inc.

Ultrasound assisted endovascular treatment of acute venous thromboses

Summary. Deep vein thromboses lead to post thrombotic syndrome in up to 50% of patients, which entails significant morbidity and socioeconomic costs. Endovascular treatment of iliofemoral deep vein thrombosis aims to reduce the development and the severity of post thrombotic syndrome. This case series of four cases demonstrates that acute and chronic thrombotic stenoses or occlusions can be safely managed by ultrasound guided endovascular treatment minimizing the number of interventions, bleeding risk and radiation exposure.