Fibrin clot susceptibility to lysis is impaired after on-pump coronary artery by-pass grafting with tranexamic acid: clinical implications.

Coronary artery bypass grafting (CABG) done on-pump may cause a significant blood loss. Low fibrinogen is associated with perioperative bleeding. The influence of cardiopulmonary bypass on fibrin clot properties is poorly investigated. We studied 55 patients with isolated coronary artery disease on aspirin undergoing on-pump CABG with tranexamic acid. Fibrinogen levels, fibrinolytic capacity expressed as clot lysis time (CLT), thrombin generation potential and platelet count were assessed before and after the surgery (prior to admission to the intensive care unit). A postoperative drop in haemoglobin (-30% from baseline), haematocrit (-31% from baseline) and platelet count (-42% from baseline) was observed (all, P < 0.0001). Postoperative fibrinogen level was lower by 57%, compared with preoperative value (1.5 [1.3-1.8] vs. 3.5 [2.8-3.9] g/l, P < 0.0001). Postoperative CLT was longer by 48 min, compared with preoperative (182 [170-218] vs. 134 [122-165] min, P < 0.0001). Thrombin generation was impaired postoperatively: both lag time and time to peak thrombin were prolonged by 44 and 45%, respectively, whereas endogenous thrombin potential and peak thrombin generation decreased by 45 and 78%, respectively (all P < 0.0001). Median postoperative drainage at 12 h was 400 [290-570] ml. Predictors of blood loss at 12 h identified in multivariable linear regression model adjusted for sex and preoperative fibrinogen level were: BMI (b = -23.4, P = 0.048) and postoperative CLT (b = -2.4, P = 0.042). Despite decreased fibrinogen levels after on-pump CABG with tranexamic acid, fibrin clot susceptibility to lysis is impaired, as reflected by prolonged CLT. Postoperative CLT is associated with mediastinal drainage at 12 h.

[Decreased retraction of blood clots in patients with venous thromboembolic complications]. / Umen'shenie retraktsii sgustkov krovi u bol'nykh s venoznymi tromboémbolicheskimi oslozhneniiami.

Haemostatic disorders play an important role in the pathogenesis of acute venous thrombosis. One of the least studied reactions of blood coagulation and thrombogenesis is spontaneous contraction of blood clots, which takes place at the expense of the contractility apparatus of activated blood platelets adhered to fibrin fibres. The work was aimed at studying the parameters of contraction of blood clots, formed in vitro, in blood of 41 patients with acute venous thromboses as compared with the same parameters in apparently healthy donors. We used a new instrumental method making it possible to determine the time from initiation to the beginning of contraction, as well as the degree and velocity of clot contraction. It was revealed that in patients with venous thrombosis the ability of clots to shrink was significantly reduced as compared with the control. We detected a statistically significant retardation of and decrease in of blood clot concentration in patients with venous thrombosis complicated by pulmonary artery thromboembolism as compared with contraction in patients with isolated deep vein thrombosis, witch may be important for early diagnosis and determination of the risk of thromboembolism. Besides, we revealed a statistically significant retardation of contraction in patients with proximal thrombosis as compared with contraction in patients with distal thrombosis, with similar values of the degree of contraction. Contraction was statistically significantly reduced in acute thrombosis (less than 21 days), whereas in subacute thrombosis (more than 21 days) the parameters of contraction were closer to normal values. The obtained findings suggest that reduction of blood clot contraction may be a new, hitherto unstudied pathogenetic mechanism deteriorating the course and outcome of venous thrombosis. The clinical significance of contraction and its impairments, as well as the diagnostic and prognostic value of the laboratory test for blood clot contraction would merit further study.

Simultaneous presence of hypercoagulation and increased clot lysis time due to IL-1ß, IL-6 and IL-8.

Circulating cytokines, and particularly the interleukin (IL)-family are known to play an important role in inflammation. These molecules circulate in the blood and therefore have a direct effect on the plasma molecules and the formed elements like the erythrocytes and platelets. Aberrant coagulation (hypercoagulation or blood clots that form too easily) and clot lyses (hypofibrinolysis, where clots do not dissolve properly, with an abnormally low rate of clot lysis time), are usually the hallmarks of many inflammatory conditions. However, the mechanism by which cross-linking augments clot stiffness remains undetermined. IL-1ß; IL-6 and IL-8 has been found to be involved in most chronic and acute inflammatory diseases. In the present study, we investigate clot structure of healthy blood, with the addition of these 3 interleukins, to determine the individual effects at concentrations that mimic low-grade, chronic inflammation. Previous studies showed that clot rheological behavior is regulated by at least the following three factors, fibrinogen concentration, fibrin network architecture and FXIIIa-induced ligation. We investigated clot formation and lysis using thromboelastography (TEG), before and after exposure, and created clots by adding thrombin to whole blood. This allowed us to look at extensive fibrin fiber formation and their interactions with particularly the erythrocytes, using scanning electron microscopy (SEM). Our results showed that IL-1ß; IL-6 and IL-8 causes hypercoagulation and results in a disheveled fibrin clot, with trapped RBCs. IL-8 showed eryptosis (a type of apoptosis in erythrocytes). Our lysis results showed that both clot lysis time and maximum rate of lysis are decreased, with the addition of the interleukins. This is a novel finding and the observations reported in this paper, therefore points to the importance of looking at the effects of individual circulating inflammagens, to better understand the role that each play in the expression of disease. These methods can be used for an individualized patient-orientated approach in healthcare to track blood viscosity in conditions with acute and chronic inflammation.

Bacterial proteases and haemostasis dysregulation in the CF lung.

BACKGROUND: Pathogenic bacteria which chronically colonise the cystic fibrosis (CF) lung produce a number of virulence determinants, including distinct proteolytic activities. The potential role bacterial proteases play on haemostatic dysregulation within the CF lung is, however, poorly defined, despite haemoptysis being a common complication in CF. METHODS: The potential impact of known CF pathogens (Pseudomonas aeruginosa and Burkholderia cepacia complex spp.) on haemostasis was examined for their ability to degrade fibrinogen and dysregulate fibrin clot formation and platelet aggregation. RESULTS: Results demonstrate that key CF pathogens growing as a biofilm on mucin exhibit considerable fibrinogenolytic activity, resulting in fibrinogen breakdown, impaired clot formation, and modulation of platelet aggregation. Human neutrophil elastase may also contribute to fibrinogen breakdown and dysregulated clot formation at high concentration. CONCLUSION: Bacterial-derived proteases may play an important role in the dysregulation of airway haemostasis, and potentially contribute to episodes of haemoptysis within the CF lung.

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

OBJECTIVES: Given 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. METHODS: Ex 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. RESULTS: Compared 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%. CONCLUSION: This 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.

[Evaluation of fibrinolysis with streptokinase in ST-elevation myocardial infarction admitted to emergency department]. / Evaluation de la fibrinolyse par la streptokinase dans l'infarctus du myocarde avec sus décalage du segment ST admis aux urgences.

BACKGROUND: Fibrinolysis during ST elevation myocardial infarction (STEMI) is feasible in the emergency departments (ED), and this reduces the delay from first medical contact to coronary reperfusion. The aim of the study is to: 1) Evaluate fibrinolysis with streptokinase (SK) in STEMI admitted to the ED. 2) identify clinical criteria predictive of fibrinolysis success. METHODS: prospective study (July 2008-March 2012). Inclusion of STEMI thrombolysed by SK. Fibrinolysis success was defined according to clinical and Electrocardiogram criteria. Multivariate study is used to identify the factors associated with thrombolysis success. RESULTS: Out of the 329 STEMI enrolled during the study period, 224 (68%) were thrombolysed. Mean age = 57 ± 11 years (20-86 years) sex ratio = 6. The average time chest pain - emergency admission was 195 ± 177 min (15 min to 12 hours). The 2/3 of patients had consulted during the first 3 hours. The average success rate of thrombolysis was 59% and reached 83% the first hour, 66% the second hour and 58.7% the third hour. In multivariate analysis, the three independent predictors factors of a fibrinolysis success were: active smoking, current treatment with beta blockers and the delay from onset chest pain to the ED visit less than 180 min. Conversely, diabetes was associated with fibrinolysis failure. Fibrinolysis got complicated by two intracerebral hemorrhages. Three patients had died in the ED. CONCLUSION: Two thirds of patients with STEMI have consulted 3 h after onset of chest pain. Fibrinolysis with streptokinase was effective in 59% of cases.