Fibrin Clot Properties In Patients Research Articles

Changes in fibrin clot properties in patients after Roux-en-Y gastric bypass surgery

BackgroundObesity is a complex condition associated with prothrombotic fibrin networks that are resistant to fibrinolysis. Altered fibrin clot properties enhance cardiovascular risk and associate with a poorer prognosis following acute ischemic events. Bariatric surgery is commonly employed to improve cardiometabolic outcomes in individuals with obesity. However, the effects of this surgical intervention on fibrin clot properties have not been comprehensively studied. ObjectivesTo examine fibrin clot and lysis parameters in Roux-en-Y gastric bypass (RYGB) patients before and after surgery. MethodsThe fibrin clot properties of 32 individuals living with obesity before and 9 months after RYGB surgery were determined using turbidimetric analysis. Correlation and regression analyses were used to identify relationships between clot properties and anthropomorphic and clinical measures. ResultsRYGB surgery resulted in a significant reduction in adiposity-associated anthropometric measures as well as improvements in glycemia and lipid profile. Clot maximum absorbance was reduced from 0.43 ± 0.11 at baseline to 0.29 ± 0.10 at 9 months postsurgery (P < .0001), while fibrin clot lysis time failed to show a difference. The change in maximum absorbance was not caused by alterations in fibrinogen levels, while plasminogen activator inhibitor-1 concentration was significantly increased after surgery from 10,560 ± 6681 pg/mL to 15,290 ± 6559 pg/mL (P = .009). Correlation and regression analyses indicated that maximum absorbance was influenced by markers of adiposity as well as glycated hemoglobin and high-sensitivity C-reactive protein concentrations. ConclusionRYGB surgery led to a decrease in the maximum absorbance of the fibrin clot. Values of maximum absorbance were associated with measures of glycemic control and inflammation. In contrast to previous reports, fibrin clot lysis time was not affected after surgery.

PB0016 Plasma Protein Carbonylation is Associated with Unfavorably Altered Fibrin Clot Properties in Patients with Atrial Fibrillation: A Novel Risk Factor of Ischemic Cerebrovascular Events

PB0016 Plasma Protein Carbonylation is Associated with Unfavorably Altered Fibrin Clot Properties in Patients with Atrial Fibrillation: A Novel Risk Factor of Ischemic Cerebrovascular Events

PB0010 Neutrophil-Activating Peptide 2 as a Novel Modulator of Fibrin Clot Properties in Patients with Atrial Fibrillation on Anticoagulation

PB0010 Neutrophil-Activating Peptide 2 as a Novel Modulator of Fibrin Clot Properties in Patients with Atrial Fibrillation on Anticoagulation

Increased factor XI but not factor XII is associated with enhanced inflammation and impaired fibrin clot properties in patients with eosinophilic granulomatosis with polyangiitis.

In eosinophilic granulomatosis with polyangiitis (EGPA) a prothrombotic state, including formation of denser fibrin networks with reduced lysability has been observed. Little is known about the intrinsic pathway in EGPA. We investigated whether coagulation factors (F)XI and FXII are associated with eosinophil-driven prothrombotic state. In 34 consecutive EGPA patients with remission we assessed FXI and FXII levels along with plasma fibrin clot permeability (Ks), fibrin clot morphology using scanning electron microscopy, and efficiency of fibrinolysis, expressed as lysis time (t50%) and maximum rate of increase in D-dimer levels (D-Drate). Increased FXI level (>130%, the upper reference limit) was found in 8 (23.5%) patients. Compared to patients with FXI levels ≤130%, those with increased FXI had higher eosinophil count (+365%) and reduced percentage of neutrophils (-20.4%), along with reduced Ks (-20.5%). In patients with FXI>130% clots were composed of thinner fibrin fibers (-17.5%). FXI was not associated with C-reactive protein and fibrinogen levels or anti-neutrophil cytoplasmic antibodies titers. There were no correlations between FXI and FXII levels as well as between FXII and eosinophil count (all p>0.05). To our knowledge, this study is the first to show association between FXI and a prothrombotic state in EGPA. Given clinical trials on FXI inhibition as an antithrombotic option, our findings suggest that this therapeutic approach could be useful in diseases with hypereosinophilia.

Neutrophil-activating Peptide 2 as a Novel Modulator of Fibrin Clot Properties in Patients with Atrial Fibrillation.

Neutrophil-activating peptide 2 (NAP-2, CXCL7), a platelet-derived neutrophil chemoattractant, is involved in inflammation. We investigated associations between NAP-2 levels, neutrophil extracellular traps (NETs) formation, and fibrin clot properties in atrial fibrillation (AF).We recruited 237 consecutive patients with AF (mean age, 68 ± 11years; median CHA2DS2VASc score of 3 [2-4]) and 30 apparently healthy controls. Plasma NAP-2 concentrations were measured, along with plasma fibrin clot permeability (Ks) and clot lysis time (CLT), thrombin generation, citrullinated histone H3 (citH3), as a marker of NETs formation, and 3-nitrotyrosine reflecting oxidative stress.NAP-2 levels were 89% higher in AF patients than in controls (626 [448-796] vs. 331 [226-430] ng/ml; p < 0.0001). NAP-2 levels were not associated with demographics, CHA2DS2-VASc score, or the AF manifestation. Patients with NAP-2 in the top quartile (> 796ng/ml) were characterized by higher neutrophil count (+ 31.7%), fibrinogen (+ 20.8%), citH3 (+ 86%), and 3-nitrotyrosine (+ 111%) levels, along with 20.2% reduced Ks and 8.4% prolonged CLT as compared to the remaining subjects (all p < 0.05). NAP-2 levels were positively associated with fibrinogen in AF patients (r = 0.41, p = 0.0006) and controls (r = 0.65, p < 0.01), along with citH3 (r = 0.36, p < 0.0001) and 3-nitrotyrosine (r = 0.51, p < 0.0001) in the former group. After adjustment for fibrinogen, higher citH3 (per 1ng/ml β = -0.046, 95% CI -0.029; -0.064) and NAP-2 (per 100ng/ml β = -0.21, 95% CI -0.14; -0.28) levels were independently associated with reduced Ks.Elevated NAP-2, associated with increased oxidative stress, has been identified as a novel modulator of prothrombotic plasma fibrin clot properties in patients with AF.

P-selectin as a modulator of fibrin clot properties in patients treated with high-dose statins

Background and Aims : It has been reported that P-selectin, a marker of platelet activation, is associated with denser fibrin networks in coronary artery disease (CAD). It is unclear whether high-intensity statin therapy reduces P-selectin levels and such changes can affect the fibrin clot phenotype in CAD patients.

Apolipoproteins and lipoprotein(a) as factors modulating fibrin clot properties in patients with severe aortic stenosis

Background and aimsLarge amounts of clot-bound lipoproteins were reported in proteomic analysis of plasma clot but their impact on fibrin clot properties is unknown. We investigated a contribution of lipid profile and apolipoproteins (apo) to the prothrombotic plasma fibrin clot phenotype in patients with aortic stenosis (AS). MethodsIn 138 patients with isolated severe AS, we determined serum apoA-I, A-II, B, C-II, C-III, E, oxidized low-density lipoprotein (OxLDL) and lipoprotein(a) concentrations. Plasma fibrin clot permeability (Ks), maximal absorbance (MaxAbsCLT2018 and MaxAbsLys50), and fibrinolytic capacity were studied using 3 plasma-based lysis assays (CLT2018, CLT, and Lys50), and compared with well-matched patients without AS (control group). ResultsAfter adjustment for confounding factors, including statin use, only low-density lipoprotein cholesterol (LDL-C) and apoB levels were inversely associated with Ks. Triglycerides, apoC-II, and C-III were associated with MaxAbsCLT2018 and MaxAbsLys50, explaining 56–64% of their variability. CLT2018 and CLT showed associations with total cholesterol, LDL-C, triglycerides, and OxLDL as well as with apoB, C-II, C-III, and E. ApoA-I, C-II, and C-III but not serum lipids were associated with Lys50. Only CLT2018 was associated with lipoprotein(a). ApoC-III, B, A-I, and E along with estimated glomerular filtration rate and OxLDL predicted hypofibrinolysis in multiple regression analysis. AS patients had higher lipoprotein(a) (+34.9%) and apoA-I (+25.9%) levels and less compact fibrin clots (−13.3% lower MaxAbsCLT2018, -53.2% lower MaxAbsLys50, and +28.3% higher Ks) displaying higher susceptibility to lysis (−17.9% lower Lys50) in comparison with control group. ConclusionsApolipoproteins and OxLDL contribute to prothrombotic fibrin clot phenotype in severe AS. Moreover, apolipoproteins better than serum lipids predicted hypofibrinolysis, which provides additional argument for a role of elevated lipoproteins in the prothrombotic state.

Fibrinogen β chain and FXIII polymorphisms affect fibrin clot properties in acute pulmonary embolism.

Prothrombotic fibrin clot properties, including increased clot density, are in part genetically determined. We investigated whether fibrinogen alpha-chain gene (FGA) c.991A>G (rs6050), fibrinogen beta chain gene (FGB) -455G>A (rs1800790) and factor XIII gene (F13) c.103G>T (rs5985) polymorphisms affect plasma fibrin clot properties in patients with acute pulmonary embolism (PE). As many as 126 normotensive patients with PE, free of cancer, were genotyped by TaqMan assay. Fibrin clot permeability (Ks ), clot lysis time (CLT) and endogenous thrombin potential (ETP) were assessed on admission. The minor allele frequencies were as follows: FGA rs6050 (n=62, 0.31), FGB rs1800790 (n=40, 0.17) and F13 rs5985 (n=49, 0.23). There were no differences related to any of the polymorphisms with regard to demographic, clinical and laboratory data, except for fibrinogen concentration, which was higher in carriers of F13 rs5985 polymorphism (p=.024), and PE combined with deep-vein thrombosis, which was less prevalent in FGB rs1800790 polymorphism carriers (p=.004). Carriers of FGB rs1800790 A allele and F13 rs5985T allele had lower Ks , prolonged CLT and higher ETP compared with major homozygotes (all p<.05). After adjustment for fibrinogen, all differences remained significant (all p<.01). There were no associations between the FGA rs6050 polymorphism and Ks , CLT or ETP. Our study showed that FGB rs1800790 and F13 rs5985 polymorphisms contribute to the prothrombotic fibrin clot phenotype and these effects are strong enough to be observed in the acute phase of PE.

Fibrin clot properties in coronary artery disease: new determinants and prognostic markers.

Despite improved diagnosis and treatment options, coronary artery disease (CAD) is still the leading cause of mortality and morbidity worldwide. Established risk factors such as smoking, hypercholesterolemia, and hypertension only partly explain the pathophysiology of CAD. Besides the well-known role of platelets in atherosclerosis and arterial thrombus formation, reduced endogenous fibrinolytic activity may play a key role in CAD formation and progression. Thus, biomarkers of fibrinolysis may be future CAD risk markers. In this review, we provide an overview of regulators of fibrinolysis and the main factors of importance to fibrin clot formation including coagulation factor XIII, thrombin, and fibrinogen. We summarize markers of altered fibrinolysis and current laboratory methods applied in clinical practice and research. We present today’s evidence on fibrin clot properties in patients with stable CAD or acute coronary syndrome compared with healthy individuals and the significance of altered fibrinolysis as a risk for coronary thrombotic disease. In conclusion, we found evidence that altered fibrin clot properties and impaired fibrinolysis appear to contribute significantly to the thromboembolic risk in CAD patients. Therefore, more research is crucial in order to clarify whether modulation of the fibrinolytic system may pave the way for improved treatment of CAD.

Plasma fibrin clots of pulmonary embolism patients present increased amounts of factor XIII and alpha2-antiplasmin at 3 months' anticoagulation since the acute phase.

Fibrin cross-linking by coagulation factor (F)XIII leads to clot stabilization. Reduced plasma FXIII levels have been reported in acute pulmonary embolism (PE) patients. We investigated the impact of anticoagulant therapy on clot-bound amounts of FXIII and α2-antiplasmin and their associations with fibrin clot properties in patients with PE. Clots generated from plasma of 18 acute symptomatic patients on admission and after a 3-month treatment with rivaroxaban were assessed off anticoagulation using mass spectrometry. Plasma FXIII and α2-antiplasmin activity were determined at the 2 time points along with thrombin generation markers, plasma fibrin clot permeability (Ks), and clot lysis time (CLT). Following anticoagulant therapy, clot-bound FXIII increased from 2.97 (interquartile range, 1.98 - 4.08) to 4.66 (3.5 - 6.9) mg/g protein and α2-antiplasmin from 9.4 (7.2 - 10.6) to 11 (9.5 - 14) mg/g protein (both p < 0.0001). The two parameters showed positive correlation at baseline only (r = 0.63, p = 0.0056). Similarly to clot-bound amounts, plasma FXIII (+25.8%) and α2-antiplasmin activity (+12%) increased at 3 months. Plasma FXIII activity on admission, but not after 3 months since the index PE, was associated with amounts of clot-bound FXIII (r = 0.35, p = 0.043) and α2-antiplasmin (r = 0.47, p = 0.048). At baseline, clot-bound FXIII correlated with plasma F1+2 prothrombin fragments levels (r = 0.51, p = 0.03), while clot-bound α2-antiplasmin correlated with CLT (r = 0.43, p = 0.036). At 3 months associations of clot-bound FXIII and α2-antiplasmin were abolished. This study assessed for the first time changes in the fibrin clot composition following acute PE, suggesting an increase of clot-bound and plasma FXIII and α2-antiplasmin levels after 3 months.

Effects of direct oral anticoagulants on thromboelastographic parameters and fibrin clot properties in patients with venous thromboembolism.

Data concerning the impact of direct oral anticoagulants (DOACs) on the thromboelastography (TEG) indices in venousthromboembolism (VTE) patients are limited. The goal of this study was to compare the impact of DOACs on clot properties measured in whole blood using TEG kaolin test and in plasma obtained from real-life VTE patients. We assessed 53 patients, including 20 on rivaroxaban, 20 on apixaban, and 13 on dabigatran. Using the TEG® 5000, coagulation status was evaluated in whole blood samples, while plasma fibrin clot permeability (Ks) and its susceptibility to lysis (CLT) were assessed in citrated plasma. Plasma concentrations of rivaroxaban (99 [48 - 311] ng/ml) and apixaban (85 [40 - 105] ng/ml) were positively associated with Ks and inversely with CLT, while dabigatran concentrations (71 [39 - 98] ng/ml) correlated positively with Ks. Moreover, Ks was associated with clot formation times (R and K), time to maximum clot strength (TMA), coagulation index (CI) reflecting the overall coagulation status, and whole blood clot lysis time (TEG-CLT). Blood clot lysis index (CL30) was associated with plasma CLT in all patients on DOACs, while TMA correlated with CLT only in patients on apixaban. Higher DOAC concentrations were associated with longer retardation of whole blood clot formation and longer time needed to reach maximum level of its strength as well as with more permeable clots. We concluded that plasma fibrin clot properties correlate with corresponding TEG indices suggesting that TEG might be helpful in providing prognostic information about DOAC influence in VTE patients.

Antiphosphatidylserine/prothrombin complex antibodies as a determinant of prothrombotic plasma fibrin clot properties in patients with antiphospholipid syndrome

BackgroundAntiphosphatidylserine/prothrombin complex (aPS/PT) antibodies are recognized as a marker for antiphospholipid syndrome (APS). Dense and poorly lysable fibrin clots occur in thrombotic APS. Compact clots predict thromboembolism, but determinants of the unfavorable clot phenotype remain unknown in APS. We hypothesized that elevated aPS/PT antibodies determine unfavorable clot features. MethodsIn a cohort study involving 124 consecutive patients with thrombotic APS, we measured at baseline plasma fibrin clot permeability (Ks), efficiency of fibrinolysis (clot lysis time, CLT), and turbidity (off anticoagulation) along with immunoglobulin (Ig)G/IgM aPS/PT. During follow‐up, symptomatic thromboembolic events were recorded. ResultsElevated IgG and IgM aPS/PT antibodies >30 international enzyme units (UI) were detected in 54.8% and 42.7% of APS patients, including 76.2% and 54% of lupus anticoagulant‐ (LA, n = 63) positive patients, respectively. Elevated IgG and IgM aPS/PT antibodies predicted low Ks (lower quartile, <6 × 10−9 cm2; odds ratio [OR] = 5.93, 95% confidence interval [CI] 2.09‐16.82 and OR = 11.79, 95% CI 4.10‐33.92) and prolonged CLT (top quartile, ≥116 min; OR = 4.85, 95% CI 2.42‐25.07 and OR = 6.04, 95% CI 2.42‐15.07). No such associations were observed for anticardiolipin or β2‐glycoprotein I antibodies or LA presence. During follow‐up (median 72.5, range 66‐83 months), thromboembolic events observed in 32 (26.7%, 4.6%/year) patients were independently predicted by IgG aPS/PT antibodies >30 UI (hazard ratio [HR] = 3.04, 95% CI 1.20‐8.88) and low Ks (HR = 3.00, 95% CI 1.41‐6.50). ConclusionsWe identified aPS/PT antibodies as a determinant of denser and poorly lysable plasma fibrin clot formation in APS patients. The association of elevated aPS/PT antibodies with thromboembolism in APS could be at least in part mediated by prothrombotic clot properties.

Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban.

We sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (Ks) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2-6 hours (h) after and 20-25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (Ks -12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for Ks and CLT before rivaroxaban intake. At 2-6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (Ks +38 %, and +37 %, CLT -25 % and -25 %, CLT-TAFI -20 % and -24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (Ks -12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20-25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.

Unfavorably Altered Fibrin Clot Properties in Patients with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Association with Thrombin Generation and Eosinophilia.

ObjectivesGiven reports on the increased prevalence of thromboembolic incidents in patients with eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome), we investigated whether fibrin clot properties are unfavorably altered in EGPA.MethodsEx vivo plasma fibrin clot characteristics, including clot permeability, turbidimetry and efficiency of fibrinolysis using two assays, were investigated in 34 consecutive patients with remission in EGPA according to the Birmingham Vasculitis Activity Score version 3 (23 female, 11 male), aged 48 (range, 21–80) years. The control group comprised 34 age- and sex- matched volunteers.ResultsCompared with controls, patients with EGPA were characterized by denser fiber clots (estimated pore size, Ks, 7.30±0.93 vs 10.14±1.07 10−9 cm2), faster fibrin polymerization (lag phase in a turbidimetric curve, 41.8±3.6 vs 47.4±2.9 s), thicker fibrin fibers (maximum absorbance, ΔAbs, 0.87±0.09 vs 0.72±0.07), higher maximum levels of D-dimer released from clots (DDmax 4.10±0.46 vs 3.54±0.35 mg/L), and prolonged clot lysis time (t50%; 9.50±1.45 vs 7.56±0.87 min); all p<0.0001. Scanning electron microscopy images confirmed denser plasma fibrin networks composed of thinner fibers formed in EGPA. Antineutrophil cytoplasmic antibody status and C-reactive protein did not affect clot variables. Multivariate analysis adjusted for fibrinogen showed that Ks was predicted by eosinophil count, peak thrombin generation, factor VIII, and soluble CD40 ligand, whereas eosinophil count, peak thrombin generation and antiplasmin predicted t50%.ConclusionThis study is the first to show that EGPA is associated with prothrombotic plasma fibrin clot phenotype, which may contribute to thromboembolic manifestations reported in this disease.

Vitamin K antagonists favourably modulate fibrin clot properties in patients with atrial fibrillation as early as after 3 days of treatment: Relation to coagulation factors and thrombin generation

IntroductionAtrial fibrillation (AF) increases the risk of thromboembolism that is reduced by vitamin K antagonists (VKAs). We sought to investigate changes in plasma fibrin clot phenotype at the onset of oral anticoagulation. Materials and methodsForty consecutive AF patients (aged 45–83 years, CHA2DS2-VASc score 3.0±1.5) who started therapy with warfarin or acenocoumarol were studied. Plasma fibrin clot permeability (Ks), clot lysis time (CLT), along with clotting factors (F), thrombin generation (TG) profiles and protein C (PC) levels were determined on days 3, 5, 7, 28 and 56±1 since the first dose. ResultsAF patients had 16% higher median of Ks and 15% lower median of CLT as early as on day 3 of VKA therapy compared with the baseline (both p<0.001), reaching the plateau values on day 7 and 5, respectively. Higher Ks values on days 1 and 3 were found in AF patients with further stable anticoagulation (both p<0.05). Moreover, FIX explained 32% of the total variability in Ks. Multivariate analysis adjusted for potential confounders including time as a predictor showed that vitamin K-dependent (VKD) factors, PC and TG parameters were the predictors of Ks (all p<0.0001), while only the lag phase of TG and thrombin peak predicted CLT (both p<0.05) in AF patients. Regression analysis of time-series showed however, that CLT was also predicted by VKD factors and PC (all p<0.05). ConclusionsPlasma fibrin clot properties in AF patients are favourably modified as early as after 3days of VKA administration, which might contribute to antithrombotic effectiveness.

Altered Fibrin Clot Properties in Patients With Cerebral Venous Sinus Thrombosis: Association With the Risk of Recurrence.

Venous thromboembolism and ischemic stroke are associated with unfavorable fibrin clot structure and function. We hypothesized that denser fibrin networks displaying impaired lysability characterize patients with cerebral venous sinus thrombosis (CVST). We assessed plasma fibrin clot properties in 50 patients (aged 38.9±9.8 years, 36 women) after the first CVST unrelated to trauma or malignancy after anticoagulation withdrawal and 50 well-matched controls. Recurrences were recorded during follow-up (18-46; median, 36 months). Clot permeability was lower in patients with CVST than in controls (Ks, 6.43±0.97 versus 7.3±1.2 10(-9) cm(2); P<0.001) and was associated with prolonged clot lysis time (103.0±16.8 versus 92.4±16.2 minutes; P<0.001), lower maximum rate of D-dimer release from clots (0.068 [0.064-0.071] versus 0.072 [0.067-0.078] mg/L per minute; P<0.001) and higher maximum D-dimer levels in the lysis assay (4.39±0.56 versus 4.19±0.46 mg/L, respectively; P=0.03). Patients with CVST had a slightly shorter lag phase (P=0.02) and higher maximum absorbance of fibrin gels on turbidimetry (P<0.001) compared with controls. Deficiencies in natural anticoagulants or antiphospholipid syndrome, and factor V Leiden occurred more often in the patients (P<0.05). CVST recurred in 6 patients (12%) and was associated with 21% higher baseline fibrinogen (P=0.007), 20% lower Ks (P=0.04) and 17% greater D-Dmax (P=0.01). Multiple logistic regression showed that only elevated D-Dmax (>4.83 mg/L) predicted CVST recurrence (odds ratio, 5.1; 95% confidence interval, 1.63-16.19) after adjustment for fibrinogen. CVST is associated with the formation of more compact plasma fibrin clots and resistance to fibrinolysis, which may predispose to the recurrence.

Fibrin clot properties and haemostatic function in men and women with type 1 diabetes.

The increased risk of vascular complications in type 1 diabetes may in part be explained by changes in haemostatic function. In the present study, we investigated the fibrin clot properties in patients with type 1 diabetes in relation to sex and microvascular complications. The study included 236 patients (107 women) aged between 20-70 years and without any history of cardiovascular disease. Fibrin clot properties, assessed by determination of the permeability coefficient (Ks) and turbidimetric clotting and lysis assays, did not differ between men and women. Compared with men, women had worse glycaemic control as well as higher levels of prothrombin fragment 1+2 and peak thrombin generation in vitro, indicating increased thrombin generation both in vivo and in vitro. Subgroup analyses of patients younger than 30 years revealed less permeable fibrin clots and prolonged lysis time in females compared with age-matched men. Patients with microvascular complications had higher fibrinogen concentrations and denser and less permeable fibrin clots. Thus, we conclude that in vitro fibrin clot properties in patients with type 1 diabetes without cardiovascular disease are not different between the sexes, but associate with prevalence of microvascular complications. Tighter fibrin clot formation in younger women, as suggested by our results, may affect their future cardiovascular risk and should be investigated in a larger population.

Increased Oxidation as an Additional Mechanism Underlying Reduced Clot Permeability and Impaired Fibrinolysis in Type 2 Diabetes.

Aims. We sought to investigate whether enhanced oxidation contributes to unfavorable fibrin clot properties in patients with diabetes. Methods. We assessed plasma fibrin clot permeation (K s, a measure of the pore size in fibrin networks) and clot lysis time induced by recombinant tissue plasminogen activator (CLT) in 163 consecutive type 2 diabetic patients (92 men and 71 women) aged 65 ± 8.8 years with a mean glycated hemoglobin (HbA1c) of 6.8%. We also measured oxidative stress markers, including nitrotyrosine, the soluble form of receptor for advanced glycation end products (sRAGE), 8-iso-prostaglandin F2α (8-iso-PGF2α), oxidized low-density lipoprotein (oxLDL), and advanced glycation end products (AGE). Results. There were inverse correlations between K s and nitrotyrosine, sRAGE, 8-iso-PGF2α, and oxLDL. CLT showed a positive correlation with oxLDL and nitrotyrosine but not with other oxidation markers. All these associations remained significant for K s after adjustment for fibrinogen, disease duration, and HbA1c (all P < 0.05), while oxLDL was the only independent predictor of CLT. Conclusions. Our study shows that enhanced oxidative stress adversely affects plasma fibrin clot properties in type 2 diabetic patients, regardless of disease duration and glycemia control.

RETRACTED: Correlation between the number and origin of circulating microparticles and fibrin clot properties in patients with coronary artery disease

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted after the journal was approached by its authors bringing important matters to our attention. It has been retracted due to the fact that following this publication there appeared concerns about provenance of the data presented and the authorship of this paper.

The influence of type 2 diabetes on fibrin clot properties in patients with coronary artery disease.

Type 2 diabetes mellitus (T2DM) increases the risk of coronary thrombosis and both conditions are associated with altered fibrin clot properties. However, the influence of T2DM on fibrin clot properties in patients with coronary artery disease (CAD) remains unclear. We aimed to investigate the influence of T2DM on fibrin clot properties in patients with CAD. Fibrin clot structure and fibrinolysis were investigated in 581 CAD patients (148 with T2DM) using turbidimetric assays, confocal and scanning electron microscopy. Clots made from plasma and plasma-purified fibrinogen were studied, and plasma levels of inflammatory markers were analysed. T2DM patients had increased clot maximum absorbance compared with non-diabetic patients (0.36 ± 0.1 vs 0.33 ± 0.1 au; p=0.01), displayed longer lysis time (804 [618;1002] vs 750 [624;906] seconds; p=0.03) and showed more compact fibrin structure assessed by confocal and electron microscopy. Fibrinogen levels were elevated in T2DM (p< 0.001), but clots made from purified fibrinogen showed no differences in fibrin properties in the two populations. Adjusting for fibrinogen levels, T2DM was associated with C-reactive protein and complement C3 plasma levels, with the former correlating with clot maximum absorbance (r=0.24, p< 0.0001) and the latter with lysis time (r=0.30, p< 0.0001). Independent of fibrinogen levels, females had more compact clots with prolonged lysis time compared with males (all p-values< 0.001). In conclusion, T2DM is associated with prothrombotic changes in fibrin clot properties in patients with CAD. This is related to quantitative rather than qualitative changes in fibrinogen with a possible role for inflammatory proteins.