vitamin-k-semiquinone-radical and Postthrombotic-Syndrome

Venous insufficiency following deep venous thrombosis is known as the post thrombotic syndrome. Whilst its presentation and symptoms can vary slightly between individuals, it can have a profound effect on quality of life. Symptoms range from mild limb swelling to severe intractable ulceration. A number of scoring systems have been developed to help monitor the disease progression, response to treatment as well as to classify patients for research purposes.Treatment involves a combination of therapies, including compression stockings, venous stenting for out flow obstruction and in some instances deep venous bypass. A considerable effort is made in preventing post thrombotic syndrome with a number of trials looking into the effect of prompt and stable anticoagulation, the effect of compression stockings, the effect of exercise and the outcomes following early thrombus removal strategies such as catheter directed and pharmacomechanical thrombolysis.

Topics: Anticoagulants; Disease Progression; Edema; Heparin, Low-Molecular-Weight; Humans; Leg Ulcer; Mechanical Thrombolysis; Postthrombotic Syndrome; Quality of Life; Severity of Illness Index; Stents; Stockings, Compression; Treatment Outcome; Venous Thrombosis; Vitamin K

The post-thrombotic syndrome (PTS) is a frequent, potentially disabling complication of deep vein thrombosis (DVT) that reduces quality of life and is costly. Clinical manifestations include symptoms and signs such as leg pain and heaviness, edema, redness, telangiectasia, new varicose veins, hyperpigmentation, skin thickening and in severe cases, leg ulcers. The best way to prevent PTS is to prevent DVT with pharmacologic or mechanical thromboprophylaxis used in high risk patients and settings. In patients whose DVT is treated with a vitamin K antagonist, subtherapeutic INRs should be avoided. We do not suggest routine use of elastic compression stockings (ECS) after DVT to prevent PTS, but in patients with acute DVT-related leg swelling that is bothersome, a trial of ECS is reasonable. We suggest that selecting patients for catheter-directed thrombolytic techniques be done on a case-by-case basis, with a focus on patients with extensive thrombosis, recent symptoms onset, and low bleeding risk, who are seen at experienced hospital centers. For patients with established PTS, we suggest prescribing 20-30 mm Hg knee-length ECS to be worn daily. If ineffective, a stronger pressure stocking can be tried. We suggest that intermittent compression devices or pneumatic compression sleeve units be tried in patients with moderate-to-severe PTS whose symptoms are inadequately controlled with ECS alone. We suggest that a supervised exercise training program for 6 months or more is reasonable for PTS patients who can tolerate it. We suggest that management of post-thrombotic ulcers should involve a multidisciplinary approach. We briefly discuss upper extremity PTS and PTS in children.

Topics: Anticoagulants; Humans; Postthrombotic Syndrome; Practice Guidelines as Topic; Vitamin K

Venous thrombosis typically involves the lower extremities. Rarely, it can occur in cerebral, splanchnic, or renal veins, with a frightening clinical impact. Other rare manifestations are upper-extremity deep vein thrombosis, that can complicate with pulmonary embolism and post-thrombotic syndrome, and retinal vein occlusion, significantly affecting the quality of life. This review is focused on venous thromboses at unusual extra-abdominal sites. Local infections or cancer are frequent in cerebral sinus-venous thrombosis. Upper-extremity deep vein thrombosis is mostly due to catheters or effort-related factors. Common risk factors are inherited thrombophilia and oral contraceptive use. Acute treatment is based on heparin; in cerebral sinus-venous thrombosis, local or systemic fibrinolysis should be considered in case of clinical deterioration. Vitamin-K antagonists are recommended for 3-6 months; indefinite anticoagulation is suggested for recurrent thrombosis or unprovoked thrombosis and permanent risk factors. However, such recommendations mainly derive from observational studies; there are no data about long-term treatment of retinal vein occlusion.

Topics: Anticoagulants; Catheters; Contraceptives, Oral; Heparin; Humans; Postthrombotic Syndrome; Pulmonary Embolism; Retinal Vein Occlusion; Risk Factors; Thrombophilia; Upper Extremity Deep Vein Thrombosis; Vitamin K; Warfarin

Venous thromboembolism, comprising deep vein thrombosis and pulmonary embolism, is a common disorder with at least 250 000 new events occurring each year in the United States alone. Treatment of venous thromboembolism includes anticoagulation, which is achieved initially with the use of a parenterally administered agent followed by a more prolonged course of treatment with an oral vitamin K antagonist. The duration of treatment depends on the clinical assessment of the benefit-to-risk ratio of prolonged anticoagulation versus the risk of recurrent events. In this review, we discuss some of the issues that we believe are among the most critical unanswered questions in the management of venous thromboembolism in the present era.

Topics: Anticoagulants; Humans; Postthrombotic Syndrome; Secondary Prevention; Venous Thrombosis; Vitamin K

The optimal anticoagulant following catheter-based therapy of acute iliofemoral deep vein thrombosis (IFDVT) is unknown.. From the Swiss Venous Stent registry, an ongoing prospective cohort study, we performed a subgroup analysis of patients with acute IFDVT who underwent catheter-based early thrombus removal followed by nitinol stent placement. Duplex ultrasound and Villalta scores were used to determine patency rates and incidence of the post-thrombotic syndrome (PTS) in patients treated with either rivaroxaban (n = 73) or a vitamin K-antagonist (VKA; n = 38) for a minimum duration of 3 months.. Mean follow-up duration was 24 ± 19 months (range 3 to 77 months). Anticoagulation therapy was time-limited (3 to 12 months) in 56% of patients (47% in the rivaroxaban group and 58% in the VKA group, p = 0.26), with shorter mean duration of anticoagulation in the rivaroxaban group (180 ± 98 days versus 284 ± 199 days, p = 0.01). Overall, primary and secondary patency rates at 24 months were 82% (95%CI, 71-89%) and 95% (95%CI, 87-98%), respectively, with no difference between the rivaroxaban (87% [95%CI, 76-94%] and 95% [95%CI, 85-98%]) and the VKA group (72% [95%CI, 52-86%] and 94% [95%CI, 78-99%]; p > 0.10 for both). Overall, 86 (86%) patients were free from PTS at latest follow-up, with no difference between the rivaroxaban and the VKA groups (57 [85%] versus 29 [88%]; p = 0.76). Two major bleeding complications (1 in each group) occurred in the peri-interventional period, without any major bleeding thereafter.. In patients with acute IFDVT treated with catheter-based early thrombus removal and venous stent placement, the effectiveness and safety of rivaroxaban and VKA appear to be similar.. The study is registered on the National Institutes of Health website (ClinicalTrials.gov; identifier NCT02433054).

Topics: Adult; Aged; Anticoagulants; Catheterization; Endovascular Procedures; Factor Xa Inhibitors; Female; Femoral Vein; Humans; Iliac Vein; Male; Middle Aged; Postthrombotic Syndrome; Prospective Studies; Rivaroxaban; Stents; Thrombolytic Therapy; Treatment Outcome; Vascular Patency; Venous Thrombosis; Vitamin K

Post-thrombotic syndrome (PTS) is a common complication of deep-vein thrombosis (DVT). Poor quality treatment with vitamin K antagonists (VKA) is a risk factor for PTS. We hypothesised that treatment with the direct oral anticoagulant (DOAC) rivaroxaban may lower PTS incidence as compared to enoxaparin/VKA, as DOACs have a more stable pharmacologic profile than VKA. We performed a post-hoc subgroup analysis of the Einstein DVT trial (n=3449). Kaplan-Meier survival analysis was performed to compare the cumulative incidence of PTS between the rivaroxaban and enoxaparin/VKA groups. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards models. We included 336 patients with a mean age of 58 ± 16 years and a median follow-up after index DVT of 57 months (interquartile range 48-64). Of these, 162 (48 %) had been treated with rivaroxaban and 174 (52 %) with enoxaparin/VKA. The cumulative PTS incidence at 60 months follow-up was 29 % in the rivaroxaban group and 40 % in the enoxaparin/VKA group. After adjusting for age, gender, body mass index, previous VTE, ipsilateral recurrent DVT, extent of DVT, idiopathic DVT, duration of anticoagulant treatment, compliance to assigned study medication, elastic compression stocking use and active malignancy, the HR of PTS development for rivaroxaban was 0.76 (95 % CI: 0.51-1.13). In conclusion, treatment of acute DVT with rivaroxaban was associated with a numerically lower but statistically non-significant risk of PTS compared to enoxaparin/VKA treatment. The potential effect on reducing PTS deserves evaluation in a large randomised trial.

Topics: Adult; Aged; Anticoagulants; Enoxaparin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Postthrombotic Syndrome; Recurrence; Rivaroxaban; Survival Analysis; Treatment Outcome; Venous Thrombosis; Vitamin K

The impact of residual vein thrombosis (RVT) on the long-term outcome of patients with deep vein thrombosis (DVT) is unknown. We assessed the incidence of recurrent venous thromboembolism (VTE), postthrombotic syndrome (PTS), arterial thrombotic events, and cancer in patients with DVT with and without RVT. For this purpose, we evaluated up to 3 years 869 consecutive patients with acute proximal DVT who had conventional anticoagulation. RVT, defined as ultrasound incompressibility of at least 4 mm in the common femoral and/or the popliteal vein after 3 months, was detected in 429 (49.4%) patients, and was more likely in males (adjusted odds ratio [OR], 1.82; 95% confidence interval [CI], 1.37-2.04), in patients with previous VTE (OR, 1.64; 95% CI, 1.06-2.54), and in those with extensive thrombosis (OR, 3.58; 95% CI, 2.19-5.86). During the 3-year follow-up, recurrent VTE developed in 84 (19.6%) patients with RVT and 43 (9.8%) patients without RVT (adjusted hazard ratio [HR], 2.03; 95% CI, 1.40-2.94); PTS in 225 (52.4%) and 118 (26.8%), respectively (HR, 2.34; 95% CI, 1.87-2.93); arterial thrombosis in 29 (6.7%) and 14 (3.2%), respectively (HR, 2.05; 95% CI, 1.08-3.88); and cancer in 21 (4.9%) and 8 (1.8%), respectively (HR, 3.09; 95% CI, 1.31-7.28). In conclusion, in patients treated with vitamin K antagonists for prevention of recurrent VTE, RVT doubles the risk of recurrent VTE, PTS, arterial thrombosis, and cancer. Males, patients with previous VTE, and those with extensive thrombosis are independent risk factors of RVT development. Studies addressing the impact of the novel direct anticoagulants on the development of RVT as well as the long-term complications of DVT are needed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Postthrombotic Syndrome; Recurrence; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Protein S is a vitamin K-dependent protein that acts as a break in secondary hemostasis by inactivating activated factor V and activated factor VIII. We report a case of a 40 years old male who had the first episode of deep vein thrombosis of the left lower limb 10 years back, which despite treatment, reoccurred 3 months later in the bilateral lower limb. Thrombophilic screening showed severe protein S deficiency. The patient then developed deep vein thrombosis of both upper limbs. The patient was advised to place an inferior vena cava filter, which he denied. The patient is now presenting with multiple episodes of post-thrombotic syndrome. Such attacks are treated with elastic compression stockings, rivaroxaban, and morphine. However, despite medication, the pain has not yet subsided. Hence, even though protein S deficiency is the rare cause of deep vein thrombosis when recurrent should be considered despite its rare occurrence.. deep vein thrombosis; protein S deficiency; rivaroxaban.

Topics: Adult; Humans; Male; Postthrombotic Syndrome; Protein S Deficiency; Rivaroxaban; Venous Thrombosis; Vitamin K

The novel direct oral anticoagulants (DOAC) have been shown to be at least as effective as and safer than conventional anticoagulants for the initial and long-term treatment of venous thromboembolic disorders. However, the rate of post-thrombotic syndrome (PTS) in patients with deep-vein thrombosis (DVT) treated with the DOACs is unknown. With the adoption of the Villalta scale, we assessed the rate of PTS at the end of the follow-up period in a consecutive series of 309 outpatients with acute proximal DVT who had received at least 3 months of treatment with a DOAC and had been followed-up for up to 3 years. The rate of PTS development was compared with that recorded in a historical cohort of 1036 consecutive patients who had been treated with vitamin K antagonists (VKA) and had received a similar follow-up examination. Logistic regression analysis, including propensity scoring to adjust for differing probabilities of undergoing VKA/DOAC, was used to identify predictors of PTS. PTS developed in 87 patients (28.2%) treated with the DOACs (severe in 12), and in 443 patients (42.8%) treated with VKAs (severe in 61). After adjusting for estimated propensity score, age, gender, concomitant symptoms of pulmonary embolism, duration of anticoagulation and development of residual vein thrombosis, the risk of PTS in the DOAC-treated patients was reduced by 54% in comparison to patients treated with conventional anticoagulation (odds ratio 0.46; 95% CI 0.33 to 0.63). We conclude that in comparison to VKAs, the use of the direct oral anticoagulants has the potential to offer a more favorable prognosis in terms of PTS development.

Topics: Adult; Factor Xa Inhibitors; Female; Humans; Logistic Models; Male; Middle Aged; Postthrombotic Syndrome; Risk Factors; Venous Thrombosis; Vitamin K

Defective clot contraction has been postulated to contribute to thrombosis. We aimed to evaluate the association of residual vein obstruction (RVO) with erythrocyte compression within the whole-blood clot. We studied 32 patients with venous thromboembolism (VTE) taking vitamin K antagonists (VKAs) for at least 3 months (median time in therapeutic range 60%), including 12 (37.5%) with RVO, and 32 age- and sex-matched controls. In all study participants we evaluated whole blood clot retraction, expressed as the erythrocyte compression index (ECI), defined as a ratio of mean polyhedrocyte area to mean native erythrocyte area, along with clot area covered by polyhedrocytes, plasma clot permeability (Ks), clot lysis time (CLT), and thrombin generation. In both groups higher ECI, indicating impaired clot contraction, increased with older age, higher body mass index, red blood cell distribution width, and lower platelet count (all p < 0.05), but not with red blood cell count. In VTE patients ECI was 15.8% higher than in controls (median 63.6 vs. 54.9%, p = 0.021). Subjects with RVO had 20% higher ECI and 155% lower clot area covered by polyhedrocytes. RVO patients had also prolonged CLT by 41%, but not Ks, and elevated peak thrombin generation by 33%, as compared to those without RVO (all p < 0.05). This study is the first to show impaired compression of erythrocytes in RVO patients despite VKA anticoagulation. Altered ECI coexisted with hypolysability and increased thrombin generation. ECI might be useful in the diagnostic process of RVO or post-thrombotic syndrome and can help optimize the anticoagulant therapy.

Topics: Adult; Anticoagulants; Case-Control Studies; Clot Retraction; Erythrocyte Indices; Female; Fibrin Clot Lysis Time; Humans; Male; Middle Aged; Postthrombotic Syndrome; Thrombin; Venous Thromboembolism; Vitamin K

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.. To assess whether the time-course of D-dimer, FVIII, and thrombotic burden are related to PTS development.. 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.. 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).. Thrombotic burden after 90days of VKA is correlated with PTS.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anticoagulants; Factor VIII; Female; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Leg; Male; Middle Aged; Postthrombotic Syndrome; Risk Factors; Ultrasonography; Venous Thrombosis; Vitamin K; Young Adult