Altered fibrin clot structure/function in patients with idiopathic venous thromboembolism and in their relatives

Abstract

We tested the hypothesis that fibrin structure/function is unfavorably altered in patients after idiopathic venous thromboembolism (VTE) and their relatives. Ex vivo plasma fibrin clot permeability, turbidimetry, and efficiency of fibrinolysis were investigated in 100 patients with first-ever VTE, including 34 with pulmonary embolism (PE), 100 first-degree relatives, and 100 asymptomatic controls with no history of thrombotic events. Known thrombophilia, cancer, trauma, and surgery were exclusion criteria. VTE patients and their relatives were characterized by lower clot permeability (P < .001), lower compaction (P < .001), higher maximum clot absorbancy (P < .001), and prolonged clot lysis time (P < .001) than controls, with more pronounced abnormalities, except maximum clot absorbance, in the patients versus relatives (all P < .01). Fibrin clots obtained for PE patients were more permeable, less compact, and were lysed more efficiently compared with deep-vein thrombosis patients (all P < .05) with no differences in their relatives. Being VTE relative, fibrinogen, and C-reactive protein were independent predictors of clot permeability and fibrinolysis time in combined analysis of controls and relatives.

Altered Fibrin Clot Properties in Patients With Cerebral Venous Sinus Thrombosis

“…Demographic and clinical data were recorded on the day of blood sampling. 5,6,8 Follow-up started at the time of discontinuation of anticoagulant therapy and was carried out on the 6-month basis (a visit at the center or telephone contact). We recorded the objectively documented recurrence of CVST.…”

“…1 The risk of recurrent CVST is 3% and remains higher in the first year after discontinuation of anticoagulant therapy, with no association with mild thrombophilias. 4 Unfavorable fibrin characteristics including faster formation of denser fibrin clots resistant to lysis represent a novel risk factor for both venous thromboembolism 5 and ischemic stroke. [6][7][8] We hypothesized that CVST is also associated with altered fibrin clot phenotype.…”

A new structural biomarker that quantifies and predicts changes in clot strength and quality in a model of progressive haemodilution

“…[3][4][5][6] Previous studies have highlighted the importance of clot microstructure and how it affects the rate of clot lysis, where densely organised clots have been linked to thromboembolic disease. [7][8][9][10] This study investigates the in-vitro effect of dilution with saline on the organization and arrangement of clot microstructure and how this affects the mechanical properties of the developing clot. The aim is to determine whether quantifying the changes in clot microstructure provides an improved clinical biomarker of haemostasis and clot quality, particularly in the setting of surgery, trauma and critical illness where the administration of resuscitation fluids and the associated effect on coagulation and clot quality still poses a significant clinical issue.…”

Plasma fibrin clot structure and thromboembolism: clinical implications

“…Less compact fibrin structure associated with faster clot lysis seems to characterize patients who experienced PE, regardless of the presence of concomitant DVT. 61 It might be speculated that higher K s combined with shorter lysis time, found in patients with PE compared with DVT, contributes to clot fragmentation and the subsequent embolization. 61 Recently published computational model simulations describing interactions between main clot components under shear flow suggest that blood clots with higher clot shell permeability are more prone to embolization under increasing shear rate.…”

“…61 It might be speculated that higher K s combined with shorter lysis time, found in patients with PE compared with DVT, contributes to clot fragmentation and the subsequent embolization. 61 Recently published computational model simulations describing interactions between main clot components under shear flow suggest that blood clots with higher clot shell permeability are more prone to embolization under increasing shear rate. 62 It has been reported that some environmental factors affect fibrin clot structure in patients with DVT.…”