Ultrasound Characteristics of Calf Deep Vein Thrombosis and Residual Vein Obstruction After Low Molecular Weight Heparin Treatment.

OBJECTIVE/BACKGROUND: Calf deep vein thrombosis (CDVT) is frequently found in symptomatic outpatients, but CDVT ultrasound diagnostic criteria are still debated. It has been proposed that only clots with ≥5 mm maximum diameter can be considered as CDVT. AIMS: To assess clot diameters and characteristics of CDVT, and to assess the recanalization rate of CDVT after anticoagulant treatment. METHODS: In a prospective, multicenter cohort study symptomatic outpatients in whom CDVT was diagnosed by ultrasound were enrolled. Posterior tibial, fibular, medial and lateral gastrocnemius, and soleal veins were compressed transversally over their entire length. Clot diameter was measured during maximum compression and ultrasound was repeated after 6 weeks of low molecular weight heparin treatment. RESULTS: In 172 patients (age 70 ± 1 y, male 32%) CDVT was detected in 132 (76.7%) muscle veins only, and in 24 (14%) axial veins only, while 16 (9.3%) patients had both muscular and axial CDVT. A total of 212 clots were found with a diameter of 5.8 ± 1.8 mm (IQR 4.5-6.8 mm) with the 10th percentile being ≥3.5 mm. A cut off value of ≥5 mm had a sensitivity of 0.76 (95% CI 0.69-0.82), whereas a value of ≥3.5 mm had a sensitivity of 0.94 (95% CI 0.89-0.97). Recanalization (i.e. residual vein obstruction ≤2 mm) was found in 51% of patients and the recanalization rate was not correlated with clot diameter at enrolment (rho -0.128 p = 0.93) or with type of CDVT (axial vs. muscular thrombosis). Patients with significantly reduced mobility had lower probability of CDVT recanalization. CONCLUSION: A clot diameter ≥5 mm is found in only 76% of CDVT patients and a clot diameter ≥3.5 mm may be more appropriate as a threshold for CDVT. After 6 weeks of anticoagulant treatment, half of CDVT patients had recanalization and recanalization was not correlated with clot characteristics at enrolment, but with mobility of the patients.

Translational insights into mechanisms underlying residual venous obstruction and the role of factor XI, P-selectin and GPVI in recurrent venous thromboembolism.

BACKGROUND: Residual venous obstruction (RVO) after deep vein thrombosis (DVT) is considered a risk factor of recurrent venous thromboembolism (VTE), arterial events and post-thrombotic syndrome (PTS). We hypothesized thrombo-inflammatory markers might be associated with RVO and clinical outcomes. MATERIALS AND METHODS: In a DVT cohort with routine RVO-assessment and 5-year follow-up, patients were invited for blood withdrawal after stopping anticoagulants. Thrombin generation potential, coagulation enzyme:inhibitor complexes, soluble platelet markers and clinical markers were measured in platelet-poor plasma. Associations were represented as odds ratio (OR) or hazard ratio (HR) per standard deviation. RESULTS: Patients with RVO (102/306, 33 %) had higher rates of PTS (24 vs. 12 %, p = 0.008), but similar rates of recurrence (16 vs. 15 %, p = 0.91) and arterial events (7 vs. 4 %, p = 0.26). RVO was associated with thrombin peak height (OR 1.40 [1.04-1.88]), endogenous thrombin potential (ETP, OR 1.35 [1.02-1.79]), and CRP (OR 1.74 [1.10-2.75]). Recurrent VTE was associated with ETP (HR 1.36 [1.03-1.81]), FXIa:C1-inhibitor (HR 1.34 [1.04-1.72]), thrombin:antithrombin (HR 1.36 [1.16-1.59]), soluble P-selectin (HR 2.30 [1.69-3.11]), soluble glycoprotein VI (sGPVI, HR 1.30 [1.01-1.69]), D-dimer (HR 1.56 [1.31-1.86]), and factor VIII (HR 1.44 [1.15-1.82]). Arterial events were associated with sGPVI (HR 1.80 [1.25-2.59]). PTS was not associated with any marker. CONCLUSIONS: Our findings indicate RVO was associated with thrombo-inflammation, but this did not predict clinical outcomes in this setting. Importantly, we found recurrent VTE was associated with ongoing coagulation and platelet activation in patients well beyond the acute phase of DVT. Furthermore, sGPVI indicated an increased risk of arterial events, highlighting the role of platelets in arterial thrombosis following DVT.

D-dimer, FVIII and thrombotic burden in the acute phase of deep vein thrombosis in relation to the risk of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is the most common complication of deep vein thrombosis (DVT), but few data are available on the risk factors for PTS. AIMS: To assess whether the time-course of D-dimer, FVIII, and thrombotic burden are related to PTS development. METHODS: Patients (n=59) with proximal DVT of the lower limbs (age 64; range:20-88years; male 56%) were enrolled on the day of diagnosis (D0) and all received heparin for 5-7days, overlapped and followed by vitamin K antagonists (VKA) for 3months. Whole-leg compression ultrasound examination was conducted on D0 and 7 (D7), 30 (D30), and 90 (D90) days afterwards, when blood samples were also taken for D-dimer (STA Liatest) and FVIII (chromogenic assay) testing. Thrombotic burden was defined at each time point according to a score, which considered thrombosis extent and occlusion degree. Villalta score was evaluated at D30, D90, and D180. RESULTS: At D90, 12 patients developed PTS (Villalta score ≥5) and the median Villalta score was 1 (IQR 0.3-3.0) and was not correlated with either D-dimer or FVIIII time course. At D180, 13 patients had PTS and they had similar thrombotic score at D0, D30 to those without PTS, but higher at D90 (7.6±5.1 vs. 3.2±3.6; p=0.011). Thrombotic score at D90 was correlated with Villalta score at D90 (rho=0.374, p=0.009) and at D180 (rho=0.436, p=0.006). CONCLUSIONS: Thrombotic burden after 90days of VKA is correlated with PTS.

Prognostic significance of residual venous obstruction in patients with treated unprovoked deep vein thrombosis: a patient-level meta-analysis.

Residual venous obstruction (RVO) could improve the stratification of the risk of recurrence after unprovoked deep vein thrombosis (DVT), but results from clinical studies and study-level meta-analyses are conflicting. It was the objective of this analysis to determine if RVO is a valid predictor of recurrent venous thromboembolism (VTE) in patients with a first unprovoked DVT who had received at least three months of anticoagulant therapy. Individual patient data were obtained from the datasets of original studies, after a systematic search of electronic databases (Medline, Embase, Cochrane Library), supplemented by manual reviewing of the reference lists and contacting content experts. A multivariate, shared-frailty Cox model was used to calculate hazard ratios (HRs) for recurrent VTE, including, as covariates: RVO; age; sex; anticoagulation duration before RVO assessment; and anticoagulation continuation after RVO assessment. A total of 2,527 patients from 10 prospective studies were included. RVO was found in 1,380 patients (55.1%) after a median of six months from a first unprovoked DVT. Recurrent VTE occurred in 399 patients (15.8%) during a median follow-up of 23.3 months. After multivariate Cox analysis, RVO was independently associated with recurrent VTE (HR = 1.32, 95% confidence interval [CI]: 1.06-1.65). The association was stronger if RVO was detected early, i.e. at three months after DVT (HR = 2.17; 95% CI: 1.11-4.25), but non-significant if detected later, i.e. >6 months (HR = 1.19; 95% CI: 0.87-1.61). In conclusion, after a first unprovoked DVT, RVO is a weak overall predictor of recurrent VTE. The association is stronger if RVO is detected at an earlier time (3 months) after thrombosis.