Altered plasma clot properties increase the risk of recurrent deep vein thrombosis: a cohort study

Abstract

It has been demonstrated that fibrin clots generated from plasma samples obtained from patients with prior thromboembolic events are denser and less susceptible to lysis. Such a prothrombotic fibrin clot phenotype has been suggested as a new risk factor for venous thromboembolism, but its prognostic value is unclear. To assess whether abnormal clot properties can predict recurrent deep vein thrombosis (DVT), we studied 320 consecutive patients aged 18 to 70 years following the first-ever DVT. Plasma clot properties were evaluated after 3 months of anticoagulant treatment since the index event. A mean duration of anticoagulation was 10 months (range, 4-20). Recurrent DVT was observed in 77 patients (25%; 6.6%/year) during a median follow-up of 44 months. Recurrences of DVT were associated with faster formation (-9% lag phase) of denser fibrin networks (-12% fibrin clot permeability [K]) and 4% higher maximum absorbance of plasma clots that displayed impaired fibrinolytic degradation (+25% prolonged clot lysis time [CLT]) and a 5% slower rate of increase in D-dimer levels during clot degradation (D-D; all < .05). Proximal DVT alone, higher C-reactive protein, D-dimer, peak thrombin, lower K shorter lag phase, decreased D-D, and prolonged CLT were independent predictors of recurrences (all < .05). Individuals characterized by low K (≤7.3 × 10 cm) and prolonged CLT (>96 min) were at the highest risk of recurrent DVT (odds ratio, 15.8; 95% confidence interval, 7.5-33.5). Kaplan-Meier curves showed that reduced K and prolonged CLT predicted recurrent DVT. We demonstrate that unfavorably altered clot properties may predict recurrent DVT after anticoagulation withdrawal.

Prothrombotic fibrin clot properties associated with increased endogenous thrombin potential and soluble P‐selectin predict occult cancer after unprovoked venous thromboembolism

“…In our study patients diagnosed with malignancy were older, and advanced age is reported to be associated with prothrombotic fibrin clot properties . We observed longer CLT in men; however, the impact of sex on fibrin properties is uncertain . In our previous study we did not observe differences in fibrin clot properties between men and women .…”

“…The so‐called prothrombotic clot phenotype,that is, a combination of increased density of fibrin clot networks, reflected by low permeability coefficient (K s ) and reduced overall efficiency of fibrinolysis (CLT), has been demonstrated to predispose to VTE and its recurrences . Similar prothrombotic clot characteristics have been found in patients with gastrointestinal cancers and lung cancer…”

Recurrent venous thromboembolism patients form clots with lower elastic modulus than those formed by patients with non‐recurrent disease

“…Interestingly, previous work has shown that clot structures for samples from patients with recurrent and nonrecurrent PE were different, with recurrent PE clots being more densely packed and less porous than non-recurrent PE clots, although these clots were made with purified fibrinogen [24]. Similarly, it was shown that recurrent DVT was associated with less permeable clots than non-recurrent DVT, suggesting that these clots are less porous [25]. In the current study, turbidity experiments showed that there was a higher maximum absorbance for nrVTE plasma samples.…”

Fibrinogen and factor XIII: newly recognized roles in venous thrombus formation and composition

“…(20) Moreover, following discontinuation of anticoagulation after first DVT, faster formation of less permeable fibrin networks and prolonged clot lysis time is associated with increased risk of DVT recurrence (odds ratio 15.8; confidence interval 7.5–33.5). (21) Abnormal clot properties, including reduced plasma clot permeability and susceptibility to fibrinolysis are also associated with increased risk of developing long-term sequelae, including chronic thromboembolic pulmonary hypertension, post-thrombotic syndrome, and persistent venous obstruction. (22–24) Notably, although these observations are of platelet-poor plasma clots formed ex vivo, their association with VTE risk suggests these clot properties recapitulate aspects of venous thrombus (dys)function in vivo.…”