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

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.

The secondary prevention of venous thromboembolism: Towards an individual therapeutic strategy.

After the anticoagulant withdrawal, a substantial proportion of patients with venous thromboembolism will develop recurrent events. Whether to consider an extended treatment depends on the risk of recurrence and bleeding risk. The assessment of the individual risk profile remains a difficult task. Several basal and post-basal factors modulate the risk of recurrence and may help clinicians to select patients who can benefit from the extended therapy. During the year 2017, new evidence regarding the post-basal factors was provided by the Morgagni and Scope studies. Another interesting novelty was the VTE-BLEED score, the first bleeding risk score that obtained the external validation in venous thromboembolism setting. In secondary prevention, the use of direct oral anticoagulants is growing instead of vitamin K antagonist. Even at lower doses, direct oral anticoagulants showed to be effective and safe, to reduce all-cause mortality and seemed to be superior to placebo for the composite outcome of fatal bleeding and fatal recurrence. After the recently published Einstein-Choice trial, the role of aspirin has become truly marginal as rivaroxaban 10 mg showed a bleeding risk similar to aspirin 100 mg but a greater effectiveness reducing the relative risk of recurrence by about 70%. Another option for secondary prevention could be sulodexide, with a lower protective effect than direct oral anticoagulants but an interesting safety profile. In conclusion, in our opinion, an individual strategy taking into account the risk of recurrence, bleeding risk, therapeutic options and patient preferences is the most appropriate approach to secondary prevention of venous thromboembolism.

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism - still a challenging issue.

As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

Management and outcomes of calf deep vein thrombosis in patients with contraindication to full anticoagulation due to bleeding.

BACKGROUND: This prospective observational study was aimed at assessing early outcomes of inpatients with isolated distal deep vein thrombosis (IDDVT) and coexisting bleeding. METHODS: Patients received enoxaparin 4000 units daily or intermediate doses, and ultrasound surveillance (US). Primary outcomes were extension to the popliteal vein (PDVT) or symptomatic pulmonary embolism (PE), bleeding complications during the treatment and the composite of PDVT and bleeding complications. Secondary outcomes were recurrent IDDVTs and death. RESULTS: 90/95 patients completed the study period (30 days). PDVT occurred in 2/41 (4.9%) and in 3/45 (6.7%) subjects receiving enoxaparin 4000 units and intermediate doses respectively (OR 1.39; 95% CI: 0.22-11; P=0.72). PE occurred in only one of the 4 untreated subjects (25% vs. 0 patients taking enoxaparin 4000 units or intermediate doses; P=1.0). Recurrent IDDVTs occurred in 29 subjects (32.2%), more frequently during enoxaparin 4000 (19/29, 65.5%). Four patients died (4.4%). Bleeding complications occurred in 8 subjects (8.9%), all treated with intermediate doses (0 vs. 17.8%; P=1.0). Enoxaparin 4000 units significantly reduced the risk of the composite outcome compared with higher doses (4.9% vs. 24.4%; OR 6.31; 95% CI: 1.56-42.65; P=0.02). Major trauma significantly increased the risk of PDVT (OR 20.92; 95% CI: 2.82-427.51, P=0.01; logistic regression P=0.01). Patients with major trauma are also at increased bleeding risk (OR 5; 95% CI: 1.06-23.76, P=0.04; logistic regression P=0.03). CONCLUSIONS: Enoxaparin 4000 units daily, supported by US, may be an option for selected patients.

Calf deep vein thrombosis: frequency, therapeutic management, early outcomes and all-causes mortality in a cohort of hospitalized patients.

BACKGROUND: Isolated distal deep vein thromboses (IDDVT) are frequent; however, their optimal management is still controversial. METHODS: We performed a retrospective study on inpatients undergoing ultrasound for suspected deep vein thrombosis (DVT) or with a particular risk profile, during 2016. This study aimed to assess the frequency of proximal deep vein thromboses (PDVT) and IDDVT; to evaluate therapeutic management and identify variables associated with early outcomes and mortality among IDDVT patients; to compare all-causes mortality between subjects with PDVT and IDDVT. RESULTS: Among 21594 patients hospitalized in the study period 251 IDDVT and 149 PDVT were diagnosed; the frequency was 1.2% and 0.7% respectively. 19% of IDDVT patients died compared to 25.5% of PDVT subjects (OR=0.72; 95% CI=0.44-1.17; P=0.19). In IDDVT patients, age ≥80, cancer and intracranial bleeding increased the risk of death (OR=2; 95% CI=1.07-3.75, P=0.001; OR=8.47; 95% CI=3.28-21.88, P=0.0000003; OR=2.33; 95% CI=1.18-4.58, P=0.0003). A significant association between intracranial hemorrhage and both proximal extension by using the Fisher's exact test (P=0.031; OR=16.11; 95% CI=0.80-321.2), and composite of propagation to popliteal or to other calf veins (OR=8.28, 95% CI=2.07-33 P=0.001) was observed. Standard anticoagulation significantly reduced the composite of propagation to popliteal or to other calf veins (OR=0.07; 95% CI=0.009-0.61, P=0.007), and all-causes mortality (OR=0.37; 95% CI=0.17-0.8; P=0.02), without a significant increase of bleeding. CONCLUSIONS: Among inpatients, IDDVT exceeded 60% of DVT. Mortality was not significantly different between IDDVT and PDVT subjects. Intracranial bleeding significantly increased the risk of propagation and death. Although standard anticoagulation decreased both these complications, further targeted studies are needed.