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Prothrombotic clot properties can predict venous ulcers in patients following deep vein thrombosis: a cohort study.

ABSTRACT: Venous ulcers are the most severe manifestation of post-thrombotic syndrome (PTS). We have previously demonstrated that formation of compact fibrin clots resistant to lysis is observed in patients following deep-vein thrombosis (DVT) who developed PTS. The current study investigated whether unfavourable fibrin clot properties can predict post-thrombotic venous ulcers. In a cohort study on 186 consecutive patients following DVT, we determined plasma fibrin clot characteristics, including clot permeability and lysability, inflammatory markers, thrombin generation, fibrinolysis proteins at 3 months since the index event. Occurrence of PTS and venous ulcers was recorded during follow-up (median, 53; range 24 to 76 months). Fifty-seven DVT patients (30.6%) developed PTS, including 12 subjects (6.45%) with a venous ulcer (4 individuals with recurrent ulcers). Patients who developed ulcers compared with the remainder had at enrolment 13.0% lower clot permeability (Ks), 17.4% longer clot lysis time (CLT), 13.1% longer lag phase of clot formation, and 5.0% higher maximum absorbance, with no difference in fibrinogen, C-reactive protein, and thrombin generation. The baseline prothrombotic fibrin clot phenotype (Ks???6.5?×?10-9 cm2 and CLT?>?100 min) was associated with a higher risk of ulcers [hazard ratio (HR), 5.37; 95% confidence interval (CI), 1.3-21.5]. A multivariate model adjusted for age, sex, and fibrinogen showed that independent predictors of the ulcer occurrence were body mass index (HR 1.53; 95% CI 1.30-1.86), CLT (HR 1.43; 95% CI 1.04-2.05), and ?2-antiplasmin (HR 0.95; 95% CI 0.90-0.99). This study suggests that formation of denser fibrin clots with impaired fibrinolysis predisposes to post-thrombotic venous ulcers.

SUBMITTER: Polak MW

PROVIDER: S-EPMC6800839 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Prothrombotic clot properties can predict venous ulcers in patients following deep vein thrombosis: a cohort study.

Polak Maciej Wiktor MW Siudut Jakub J Plens Krzysztof K Undas Anetta A

Journal of thrombosis and thrombolysis 20191101 4

Venous ulcers are the most severe manifestation of post-thrombotic syndrome (PTS). We have previously demonstrated that formation of compact fibrin clots resistant to lysis is observed in patients following deep-vein thrombosis (DVT) who developed PTS. The current study investigated whether unfavourable fibrin clot properties can predict post-thrombotic venous ulcers. In a cohort study on 186 consecutive patients following DVT, we determined plasma fibrin clot characteristics, including clot per ...[more]

PMID: 31432450

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Project description:UNLABELLED:Deep vein thrombosis (DVT) is a potentially catastrophic condition because thrombosis, left untreated, can result in detrimental pulmonary embolism. Yet in the absence of thrombosis, anticoagulation increases the risk of bleeding. In the existing literature, knowledge about the epidemiology of DVT is primarily based on investigations among Caucasian populations. There has been little information available about the epidemiology of DVT in Taiwan, and it is generally believed that DVT is less common in Asian patients than in Caucasian patients. However, DVT is a multifactorial disease that represents the interaction between genetic and environmental factors, and the majority of patients with incident DVT have either inherited thrombophilia or acquired risk factors. Furthermore, DVT is often overlooked. Although symptomatic DVT commonly presents with lower extremity pain, swelling and tenderness, diagnosing DVT is a clinical challenge for physicians. Such a diagnosis of DVT requires a timely systematic assessment, including the use of the Wells score and a D-dimer test to exclude low-risk patients, and imaging modalities to confirm DVT. Compression ultrasound with high sensitivity and specificity is the front-line imaging modality in the diagnostic process for patients with suspected DVT in addition to conventional invasive contrast venography. Most patients require anticoagulation therapy, which typically consists of parenteral heparin bridged to a vitamin K antagonist, with variable duration. The development of non-vitamin K oral anticoagulants has revolutionized the landscape of venous thromboembolism treatment, with 4 agents available,including rivaroxaban, dabigatran, apixaban, and edoxaban. Presently, all 4 drugs have finished their large phase III clinical trial programs and come to the clinical uses in North America and Europe. It is encouraging to note that the published data to date regarding Asian patients indicates that such new therapies are safe and efficacious. Ultimately, our efforts to improve outcomes in patients with DVT rely on the awareness in the scientific and medical community regarding the importance of DVT. KEY WORDS:Combination therapy; Hypertension; ?1-blocker.

Project description:BackgroundVenous leg ulceration is a widespread, debilitating pathology with high recurrence rates. Conservative treatment using graduated compression dressings may be associated with unacceptable ulcer recurrence rates. Early superficial venous ablation encourages ulcer healing and reduces recurrence. However, many of this cohort display concomitant ilio-caval stenosis, which further contributes to lower limb venous hypertension and ulceration. An approach that combines early superficial venous ablation with early treatment of ilio-caval stenotic disease may significantly improve ulcer healing and recurrence rates. We question whether early iliac vein interrogation with intravascular ultrasound (IVUS), stenting of significant occlusive disease plus superficial venous ablation, in patients with active venous leg ulceration, will produce superior ulcer healing to standard therapy.MethodsThis is a prospective, multi-centre, randomised controlled, feasibility trial recruiting patients with lower limb venous ulceration and saphenous venous incompetence. Patients will be randomised to undergo either truncal ablation and compression therapy or truncal ablation, simultaneous iliac interrogation with intravascular ultrasound and stenting of significant (>?50%) iliac vein lesions plus compression therapy. The primary feasibility outcome will be the rate of eligible patient participation while the primary clinical outcomes will be ulcer healing and procedural safety. Secondary outcomes include time to healing, quality of life and clinical scores, ulcer recurrence rates and rates of post-thrombotic syndrome. Follow-up will be over a 5-year period. This feasibility trial is designed to include 60 patients. Should it be practicable a total of 594 patients would be required to adequately power the trial to definitively address ulcer-healing rates.DiscussionThis trial will be the first randomised trial to examine the role iliac interrogation and intervention in conjunction with standard operative therapy in the management of venous ulceration related to superficial truncal venous incompetence.Ethical committee referenceC.A. 2111 Galway Clinical Research Ethics Committee REGISTRATION: Clinical Trials.gov registration NCT03640689 , Registered on 21 August 2018.

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Prothrombotic clot properties can predict venous ulcers in patients following deep vein thrombosis: a cohort study.

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Prothrombotic clot properties can predict venous ulcers in patients following deep vein thrombosis: a cohort study.

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