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The evaluation of patients with a bleeding tendency represents a challenge as the routinely available tests for evaluating bleeding disorders are limited, complicating the laboratory determination of the clinically observed bleeding tendency. As a result, some bleeding disorders remain undiagnosed. The aim of the study was to evaluate whether global coagulation tests would contribute to the laboratory analysis of patients with undiagnosed bleeding disorders. Patients were evaluated for coagulation and fibrinolysis activities by thrombin generation test and euglobulin lysis time. In addition, plasma activity of factor XIII, plasminogen, α-2 antiplasmin, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor was also obtained. Forty-five patients were included. Eight per cent presented a mild bleeding disorder and 20% a moderate bleeding disorder. The thrombin generation test results were similar between patients and controls. Euglobulin lysis time results, however, were lower in patients than in controls, both before (median 175 vs. 250 min, respectively; P = 0.003) and after (median 145 vs. 115 min, respectively; P ≤ 0.001) arm constriction, suggesting that they were experiencing hyperfibrinolysis. Interestingly, patients' median thrombin-activatable fibrinolysis inhibitor activity was higher than in controls (21.2 vs. 19.46 μg/ml; P = 0.016). However, plasminogen, α-2 antiplasmin, plasminogen activator inhibitor-1, and factor XIII activities did not differ between the groups. Global coagulation and fibrinolysis tests proved to be limited in detecting the hemostatic disorders in some patients with a relevant bleeding tendency and may not be adequate to address their bleeding risk. Bleeding scores are currently the available medical approach for the evaluation of these patients.

In rats with experimentally formed arterial hypertension, lipid peroxidation in the plasma, amplification of blood clotting mechanisms with a decrease in anticoagulation and fibrinolysis was noted. Regular forced jogging provided the experimental rats with a positive dynamics of all the indicators considered. Thus, with increased muscular activity, the level of acyl hydroperoxides of plasma decreased in rats with arterial hypertension formed due to the enhancement of its antioxidant activity. In addition, with the increase in muscle activity in experimental rats, normalization of clotting factor activity, indices of general coagulation tests, antithrombin III activity and protein C was achieved. This was accompanied by a normalization of the level of plasminogen, α2-antiplasmin and spontaneous euglobulin lysis time. In rats with formed arterial hypertension with standard physical activity, the initial violations of the measured parameters were completely preserved.

Fibrinolytic testing separates into three groups: (1) screening tests such as euglobulin lysis time and percent clot lysis on thromboelastometry, (2) routine tests such as fibrinogen and D-dimer, and (3) esoteric tests typically sent to reference laboratories such as tissue plasminogen activator (t-PA) activity and antigen, plasminogen activator inhibitor 1 (PAI-1) activity and antigen, plasminogen activity and antiplasmin activity. Screening assays are typically used to detect severe fibrinolysis associated with active bleeding (surgery, trauma). D-dimer is most often used to rule out venous thromboembolism, whereas t-PA, PAI-1, and antiplasmin assays are used to diagnose hereditary fibrinolytic bleeding disorders.

Type 2 diabetes mellitus (T2DM) is associated with a high incidence of vascular disease which can cause significant morbidity and mortality. The risk of cardiovascular mortality in T2DM patients is observed to be more compared to the age-matched subjects. This is attributed to depression of the fibrinolytic system which maintains patency of blood vessels. Endogenous inhibitors such as plasminogen activator inhibitor-1 (PAI-1) inhibit the activation of plasminogen and thus prevent the degradation of fibrinogen. In T2DM there is increased levels of PAI-1. Such a state of altered fibrinolysis is attributed to insulin resistance. A previous study done at our institute demonstrated higher euglobulin lysis time (ELT) in T2DM patients than controls, suggesting altered fibrinolytic activity in the former group. D-dimer is a degradation product of fibrin. Its presence indicates a state of hypercoagulability. In a study by Nwose et al rise in D-dimer levels were observed in diabetics, especially with cardiovascular complications as compared to controls indicating D-dimer could be a useful marker for predicting the complications in T2DM.

Introduction. Fibrinogen, like many proteins of hemostasis and fibrinolysis system, participates in many physiological processes, and its content may increase or decrease under various pathological conditions, and these modulations often serve as a diagnostic sign of the disease. Aim: to determine fibrinogen level and euglobulin lysis time as function of attraction degree to ethanol in rats. Materials and methods. The work was performed on male Wistar rats (n = 300) weighing 250–350 g. After 2 weeks of acclimatization the consumption of 10% ethanol and water in individual boxes was daily tested for 7 days. These fluids were available for 23 hours without access to food. Positions of 2 drinking pipettes of 50 ml volume randomly changed every 24 hours. Results. It was found that fibrinogen content was higher but fibrinolytic activity was lower in rats with more expressed initial degree of attraction to ethanol. Conclusion. The cases of increased fibrinogen content in initially refused rats that did not contact with ethanol indicate the possibility of genetically determined hyperfibrinogenemia that can become a source of prethrombotic conditions in case of predisposition to alcohol consumption as an energy self-correction. REFERENSES 1. Hillbom M., Numminen H. Alcohol and stroke: pathophysi- ologic mechanisms. Neuroepidemiology. 1998; 17 (6): 281–7. 2. Pichler M., Hutterer G.C., Stojakovic T. et al. High plasma fibrin- ogen level represents an independent negative prognostic factor regarding cancer-specific metastasis-free, as well as overall sur- vival in European cohort of non-metastatic renal cell carcino- ma patients. Br J Cancer. 2013; 3 (5): 1123–9. 3. Krzesinski P., Halas K., Gielerak G. et al. Cardiovascular risk and inflammatory markers in patients with hypertension. Pols- ki Merkurinsz Lekarski. 2015; 38 (224): 70–6. 4. Utrobicic I., Novak I., Marinovic-Terzic I. et al. 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Essentials Patients with bleeding disorders are at risk of operative bleeding, but screening for these disorders is challenging.Patients with and without bleeding symptoms on a guideline‐based screening questionnaire were included and hemostatically phenotyped.The questionnaire could not differentiate between patients with and without hemostatic abnormalities.The discriminative power of the PT, aPTT, TT, Euglobulin lysis time, PFA, and the ISTH‐BAT was also limited. Background Patients with mild bleeding disorders are at risk of perioperative bleeding, but screening for these disorders remains challenging. Objectives We aimed to assess the prevalence of hemostatic abnormalities in patients with and without reported bleeding symptoms on a preoperative questionnaire, consisting of guideline‐proposed questions, and appraised the diagnostic value of several screening modalities for the identification of patients with hemostatic abnormalities. Methods In this observational study, 240 patients with and 95 patients without bleeding symptoms on the preoperative questionnaire were included. Patients with known bleeding disorders, antithrombotic drugs, thrombocytopenia, and anemia were excluded. Preoperatively, all patients underwent elaborate hemostatic testing. Hemostatic abnormalities were defined as coagulation, vWF, or fibrinolysis factor levels below reference range and platelet function defects. Screening modalities included the ISTH Bleeding Assessment Tool (ISTH‐BAT), PT, aPTT, TT, Euglobulin Lysis Time (ELT), and Platelet Function Analyser (PFA). Results In 21 of 240 (8.8%) patients reporting bleeding symptoms, hemostatic abnormalities were found, including 7 reduced coagulation factor levels, 10 platelet function abnormalities, and 4 reduced vWF levels. In comparison, 10 of 95 (10.5%) patients not reporting bleeding symptoms had abnormalities. The ISTH‐BAT could not identify patients with abnormalities, while PT, aPTT, TT, ELT, and PFA had high specificity but low sensitivity to detect abnormalities. Conclusions The prevalence of hemostatic abnormalities in both patients with and without reported bleeding symptoms was 9%‐10%. This suggests that the guideline‐based questionnaire cannot differentiate between patients with and without abnormalities, while the discriminative power of the screening modalities is also limited.

Pathogenesis and clinical characteristics of the Budd-Chiari syndrome (BCS) in Asia are somewhat different from the ones observed in Western countries. Obstruction of the inferior vena cava (IVC) or of the hepatic veins is caused to a greater extent by membranous webs than by thrombosis. Impaired fibrinolysis has been found in European patients with BCS, but its status in Chinese patients with this condition is still unknown. To explore the characteristics of fibrinolysis in BCS patients in this country, we measured the euglobulin lysis time (ELT) for overall fibrinolysis and the plasma levels of five fibrinolytic components in 65 Chinese patients with BCS and 43 healthy controls. In patients, ELTs were slightly shorter than in controls (mean, 293 vs. 357 min, P0.02), tissue type plasminogen activator levels were higher than in controls (mean, 239 vs. 185 pg/ml, P0.01), and plasminogen activator inhibitor 1 levels were lower than in controls (mean, 1.43 vs. 1.73 ng/ml, P0.001). To explore BCS in more detail, we subgrouped the cases according to age, type of venous occlusion, Child-Pugh score, and thrombosis. As a result of this analysis, we found that young patients (age30 years) had a longer ELT (mean, 440 min) than the older patient groups (30 ≤ age ≤ 44, 45 ≤ age ≤ 54, age54 years; mean ELT = 242, 198, and 289 min, respectively, all P0.05). The independent hepatic vein occlusion subgroup showed a longer ELT (mean, 367 min) than the combined hepatic vein and IVC or the independent IVC occlusion subgroup (mean ELT = 233 and 260 min, both P0.05). ELT did not show significant differences between Child-Pugh class A and B subgroups (mean, 267 vs. 333 min, P0.05). ELT in the subgroup without thrombosis was shorter than in controls (mean, 288 vs. 358 min, P0.05), and in the subgroup with thrombosis, it was also slightly shorter than in controls, without reaching statistical significance (mean, 306 vs. 358 min, P0.05). By and large, overall fibrinolytic potential was slightly increased in Chinese patients with BCS in this study, but fibrinolysis differed according to its baseline characteristics. Compared with the one seen in BCS patients from Western countries, BCS in China exhibits certain special changes in fibrinolysis and we were able to explain some of these changes.

AIM To investigate the thrombolytic and antiplatelet effects of a novel plasminogen activator from the venom of the Gloydius brevicaudus viper (GBV-PA) in vitro and in vivo. METHODS Thrombolytic experiments were performed in rabbit models of ear vein thrombosis and carotid artery thrombosis and in dog model of acute cerebral infarction. Inhibition of thrombus formation was evaluated in rat inferior vena cava thrombosis model and ferric chloride-induced arterial thrombosis. In vitro, we assayed the antithrombotic effect of GBV-PA on rabbit blood clots, euglobulin lysis time (ELT) of rabbit plasma, and ADP-induced platelet aggregation. RESULTS GBV-PA intravenous administration significantly reduced vascular recanalization times of rabbit ear veins thrombosis and thrombus weight of rabbit carotid artery thrombosis. The arterial recanalization rates were dose- and time-dependently improved after the administration of GBV-PA in canine acute cerebral infarction model. Thrombus length and weight were significantly reduced by GBV-PA both in rat inferior vena cava and ferric chloride-induced arterial thrombosis models. Thrombus formation in the blood of rabbits that were administered of GBV-PA was also inhibited. GBV-PA radically reduced plasma ELT of the rabbit's blood clots. ADP-induced platelet aggregation was inhibited by GBV-PA in a dose-dependent manner with a half-maximal inhibitory concentration of 19.9 μg/mL. CONCLUSION This study demonstrates that GBV-PA is a thrombolytic and antiplatelet agent. It has significant antithrombotic effects on various in vitro and in vivo experimental models of thrombosis. The mechanisms that underline its antithrombotic effects were related to GBV-PA's capabilities of increasing fibrinolytic activity and inhibition of platelet aggregation.

Punica granatum is a shrub or tree, 8 to 10 m high from the Punicaceae family, and grows wild in Iran. Flowers are regular, solitary, or in fascicles at apices, with a size of 4 to 6 cm. Petals are lanceolate, wrinkled, and brilliant orange-red. Bleeding (hemorrhage) is the loss of blood or blood escape from the circulatory system. The aim of this study was to examine the effect of pomegranate flower extract on coagulation parameters in rats. Eighty-four Sprague–Dawley male rats, divided into twelve groups, each comprising seven rats, were used in the present study. Animals had free access to food but were deprived of drinking water for 24 h before warfarin injection. Hydroalcoholic extract of P. granatum flowers and tranexamic acid (various doses) were administered once daily for 7 days in warfarin-treated groups. Blood samples were obtained by inserting a needle into the heart, and their plasma was analyzed for prothrombin time (PT), partial thromboplastin time (PTT), platelet (PLT) count, fibrinogen, d-dimer, and euglobulin lysis time (ELT). The present study showed that administration of pomegranate flower extract led to a significant change in PTT, PLT count, and fibrinogen level and a significant decrease in PT level. There was no significant difference in d-dimer level between groups. In this study, animals showed no disseminated intravascular coagulation so no significant difference between control group and treatment in ELT test. It can be concluded that administration of pomegranate flower extract has negligible positive effects on the early stage of experimentally induced bleeding disorder in rats.

The plasminogen activator (PA) in snake venom, a serine protease, can convert plasminogen to active plasmin, indirectly causing the degradation of fibrin. It is difficult to purify sufficient snake venom PA (SV-PA) for clinical applications due to the low SV-PA content in venom. The gene encoding PA was obtained from the venom gland of Gloydius brevicaudus using RT-PCR with primers designed according to the N-terminal amino acids of G. brevicaudus venom PA (GBV-PA), was cloned into the prokaryotic expression vector pET-42a, and recombinant GBV-PA (rGBV-PA) was expressed via Isopropyl-β-d-1-Thiogalactopyranoside (IPTG) induction. Like human tissue PA, the purified renatured rGBV-PA could significantly reduce the rabbit plasma euglobulin lysis time (ELT) and prevent thrombus formation in the inferior vena cava of rats. Within the dosage range, the dosage and effects were positively correlated.

Lipoprotein (a) is a risk factor for adult cardiovascular events, in which the apolipoprotein (a) component is thought to promote atherogenesis and impair fibrinolysis. We investigated whether elevated plasma lipoprotein (a) concentration and small predominant apolipoprotein (a) isoform size (number of kringle-4 domains) are risk factors for childhood arterial ischemic stroke and correlate with plasma fibrinolytic function. Patients who had had an arterial ischemic stroke in childhood (29 days - 90th percentile of race-specific reference values and apolipoprotein (a)

Hyperfibrinolysis is observed during and immediately after major orthopedic surgery. The kinetics and duration of this phase should be defined to adjust the duration of antifibrinolytic treatment with tranexamic acid (TXA).We aimed to quantify the duration of postoperative fibrinolysis and to assess the biological impact of TXA administration.Fourteen patients undergoing total hip replacement (THR) and 10 patients undergoing total knee replacement (TKR) with tourniquet were included in an observational, prospective, single-center study. Among these patients, 7 THR patients and 5 TKR patients received TXA (15mg/kg IV intraoperatively, followed by continuous infusion of 15mg/kg/h until end of surgery, then every 4hours until 16±2hours after surgery). D-dimers, euglobulin lysis time (ELT), and thrombin generation time (TGT) were measured prior to surgery as well as 6, 18 and 24hours (H) after.No significant difference in ELT was observed between the groups. In contrast, D-dimers significantly increased postoperatively in patients not treated with TXA (p0.001), while such an increase was prevented in patients receiving TXA, as measured at H0, H6, H18 and H24 after THR, and at H6 and H18 after TKR (p0.001). No significant between-group change in TGT, was observed (peak thrombin and endogenous thrombin potential) all along the study.This study shows that fibrinolysis peaked 6hours after end of surgery and maintained about 18hours after surgery, as evidenced by an increase in D-dimers. When administered for up to 16±2hours after surgery, TXA reduced postoperative fibrinolysis.

Twenty-four patients with vascular disorders, randomly divided into 3 dosage groups of 8 patients, were treated with a single oral dose of sulodexide (50, 100 or 200mg) and placebo. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) activity and antigen, euglobulin lysis time, α2-antiplasmin, plasminogen, fibrinogen, blood and plasma viscosity, and whole blood filtration rate were determined before administration and over the following 24 hours. Sulodexide significantly increased t-PA activity linearly with the dose over the range of 50 to 200mg. At the same time, it also significantly decreased the concentration of PAI-1 linearly and proportionally with the dose. No clear effects were observed on the other monitored parameters, although euglobulin lysis time and plasma viscosity showed a tendency to decrease after the administration of sulodexide. These results justify the clinical activity of sulodexide. Indeed, the concomitant increase of t-PA and decrease of PAI-1 activity and antigen might increase the natural fibrinolytic activity with a physiological potentiation, without other adverse effects. The known activity of sulodexide in decreasing plasma viscosity during long term treatment is, however, not immediately explicable by the single-dose effects.

Improvement in blood fluidity leads to the prevention of various lifestyle-related diseases. A raw material for improving blood fluidity has been long desired in the research area of functional and supplemental foods. We successfully showed an improvement in blood fluidity by the Zingiberaceae plant, Kaempferia parviflora. The rhizome of the plant reduced the blood passage time through a micro slit using a disseminated intravascular coagulation model. The mechanism was attributed to the activation of fibrinolysis, as demonstrated by elongation of the euglobulin lysis time and an in-vitro fibrinolysis assay. The active principles were determined to be methoxyflavones. The results show that the rhizome of K. parviflora is a promising candidate preventive agent for treating lifestyle-related diseases.

1. Antithrombotic agents are effective in the treatment of ischaemic stroke. Timosaponin B-II (TB-II) is a major active component of Anemarrhena asphodeloides Bunge (Liliaceae; rhizome) that has protective effects against cerebral ischaemic damage. The present study examined the antiplatelet and antithrombotic actions of TB-II. 2. In in vitro experiments, TB-II (20, 40 and 80 mg/mL) potently and dose-dependently inhibited ADP-induced platelet aggregation. Furthermore, 1, 3 and 6 mg/kg TB-II prolonged activated partial thromboplastin time by 9.29, 16.86 and 25.50%, respectively, but had no effect on the prothrombin time. Furthermore, 1, 3 and 6 mg/kg TB-II significantly reduced the wet weight, dry weight and length of the thrombi (%inhibition (based on wet weight): 13.6, 19.8 and 24.7%, respectively). 3. In a rabbit arteriovenous shunt model, 1, 3 and 6 mg/kg, i.v., TB-II had no effect on thrombus formation. Plasma euglobulin lysis time and fibrin degradation product were not affected by 1, 3 and 6 mg/kg TB-II, but plasminogen levels were decreased significantly by 14.4, 18.3 and 29.0%, respectively. 4. The results of the present study demonstrate significant antiplatelet and anticoagulation effects of TB-II and suggest that these actions could contribute to its neuroprotective effect against damage following cerebral ischaemia damage.

Summary. Background: We found a high incidence of thrombotic deaths in COX-1+/−COX-2−/− mice and sought to define the mechanism of these events. The cyclooxygenase products thromboxane A2 and prostacyclin are important in the regulation of coagulation but their role in fibrinolysis is largely unexplored. PAI-1 blocks fibrinolysis by inhibiting plasminogen activator. Aim: Our objective was to explain the mechanism of increased thrombosis associated with the COX-1+/−COX-2−/− genotype. Methods: Carotid artery occlusion times were measured after photochemical injury. PAI-1 levels were measured in the plasma by ELISA. PAI-1 levels in the aorta were measured by RT-PCR and Western blotting. Urinary metabolites of Thromboxane A2 and prostacyclin were measured by ELISA. Results: The COX-1+/−COX-2−/− genotype is associated with a decreased time to occlusion in the carotid artery thrombosis model (30 ± 5 minutes vs 60 ± minutes in wild type, p

WOS: 000295613900002, PubMed: 20699259, Interferon (IFN) interacts with endothelial cells and modulates the functions of these cells. In our study, we aimed to determine the effects of treatment with pegylated IFN-alpha (peg-IFN-alpha) on fibrinolytic parameters in patients with chronic hepatitis C. Fifteen patients with chronic hepatitis C were treated with peg-IFN-a once per week plus daily oral ribavirin. Euglobulin lysis time (ELT), plasma levels of D-dimer, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI) were determined before treatment, 2 weeks, 1 month, and 3 months after the initiation of the treatment. Plasma levels of t-PA increased significantly 1 month and 3 months after the treatment (P < .05). The PAI-1 and TAFI levels in 2 weeks, 1 month and 3 months after treatment were not statistically different as compared with pretreatment levels (P > .05) No significant difference in plasma D-dimer levels was observed during peg-IFN-alpha treatment (P > .05). There was a significant decrease in ELT 1 month and 3 months after the treatment (P < .05). Our results indicated that treatment with peg-IFN-alpha may be associated with enhanced fibrinolysis

Background: Bleeding is an important complication of cirrhosis. Currently, there is no coagulation test that can reliably predict clinical hemorrhage. However, previous studies demonstrated significant correlations between hyperfibrinolysis and following bleeding in advanced cirrhotic patients. Objectives: Estimate the prevalence of hyperfibrinolysis in cirrhotic patients at stable conditions and to assess its role in predicting subsequent hemorrhage. Methods: The prospective cohort study included 58 consecutive cirrhotic patients at the Liver Clinic, Chulalongkorn Hospital. Assays for liver functions, PT, APTT, fibrinogen, fibrin degradation products (FDPs) and euglobulin lysis time (ELT) were performed at baseline. The subjects were followed-up for 10 months to observe clinical hemorrhage and survival. Results: The mean age was 56.4 years and 47% were male. The etiologies of liver diseases were virus (62.1%), alcohol (24.1%) or unknown (8.6%). Hyperfibrinolysis as reflected by ELT10 μg/mL was present in 32.8% and 74.1%, respectively. Fibrinolytic activity was significantly correlated with platelet counts and coagulation times, but not as much with liver function tests. By 10 months, 13 cases (22.4%) showed hemorrhagic episodes and 7 (12.1%) were expired, including 2 from bleeding. The significant predictors for death were Child class B or C, presence of ascites, hyperbilirubinemia, hypoalbuminemia, and prolonged APTT. However, none of the clinical, biochemical, or hemostatic factors was associated with clinical bleeding. Conclusion: Hyperfibrinolysis is common in cirrhotic outpatients. However, it cannot predict subsequent hemorrhage or survival. Novel hemostatic tests are required to assess the probability of bleeding in this disorder.

Fibrinolysis is a feature in the phylogeny of vertebrates. This review analyzes the fibrinolytic mechanism in different species compared to healthy adult humans. Additionally, it introduces the armadillo Chaetophractus villosus (Mammalia, Xenarthra, Dasypodidae) whose lytic process remains quite unknown until now. The analysis was conducted in a phylogenetic order: fish, amphibians, reptiles, birds, and mammals. It was designed to assess the fibrinolytic system in its various stages: global, specific, and degradation. The results are represented in tables grouped by test: fibrinogen, whole blood lysis time, whole blood diluted lysis time, euglobulin lysis time, plasminogen, fibrin/fibrinogen degradation products, D dimer, plasminogen activator inhibitor type 1, and alpha 2 antiplasmin activity. Global knowledge of the mechanism of fibrinolysis in vertebrates is a contribution of scientific interest not only in biology, but also for the development of experimental models applicable to the study of thrombotic and thrombolytic agents.

6 long distance runners from the Danish marathon elite and 6 non-runners completed test runs of 28 and 12 km, respectively. Distance runners and non-runners showed the same responses in platelet function. We found a significant decrease in ADP induced platelet aggregability, a decreased serotonin release induced by ADP and collagen and an increase in platelet factor 4 immediately following the run. The antithrombin III levels remained constant. Euglobulin lysis time was shortened (by approximately 50 %) and the plasminogen levels significantly increased. The last 2 findings indicate an equal increase in fibrinolytic activity during distance running in both groups. While short term, strenuous exercise induces platelet hyperaggregation, long term distance running induces a state of exhaustion of platelet aggregation capacity.

For the estimation of fibrinolytic activity in euglobulin precipitates after venous stasis, the euglobulin clot lysis time (ECLT) proved to be as reproducible and probably even more sensitive than the fibrin plate method (FP). Furthermore, when euglobulin precipitates from 55 healthy individuals and 36 patients with thromboembolic disease were examined, a good correlation between the two methods was observed. The present observations indicate that the ECLT is suitable for routine screening of fibrinolytic activity after venous stasis.

The effect of various concentrations of calcium on lysis of euglobulin clots was studied. If clot lysis times exceeded 200 minutes, 0.5 mM CaCl2 or less inhibited the process, whereas higher concentrations accelerated clot lysis. If clot lysis times were short, high calcium concentrations inhibited clot lysis. This happened if enhanced activity was obtained by removal of inhibitors or if it was obtained by a higher activator concentration. These effects of calcium were related to its procoagulant effect and disappeared on adsorbtion with BaSO4. Euglobulin from patients with severe coagulopathies revealed a reduced accelerating effect of calcium. The calcium effect on clot structure was probably of minor importance.

After clinical examination, 14 asymptomatic post-infarction male patients and 12 healthy control persons, aged 35-62 years, underwent two bicycle-ergometry tests. After a 20-min aerobic test of moderate intensity both groups had slight activation of the clotting system simultaneously with favorably increased fibrinolytic activity. After stepwise submaximal aerobic exercise, postinfarction patients had marked activation of the thrombocytic system; beta-thromboglobulin rose significantly from 36 to 102 ng/ml. But compared to the results in healthy persons, fibrinolytic activity was significantly reduced in the postinfarction patients (euglobulin lysis time 135 and 100 min, respectively). In three patients with unfavorable reactions of the hemostasis and fibrinolysis systems, ischemic changes or multifocal ventricular extrasystoles were recorded in the ECG after the second exercise test. These results indicate that intensive physical exercise in postinfarction patients can change the dynamic equilibrium between hemostasis and fibrinolysis in the direction of an increased clotting tendency. For this reason postinfarction patients and elderly untrained persons, especially those with an increased coronary risk factor, should avoid endurance training involving anaerobic exercise. On the other hand, moderate training at aerobic level favorably influences the hemostatic equilibrium in both healthy and postinfarction patients.

Autoprothrombin II-A anticoagulant was isolated from bovine prothrombin. Purified prothrombin was applied to DEAE-cellulose chromatography after incubation with thrombin. Four protein peaks were obtained where the third peak corresponded to the anti-coagulant effect. The fractions under the third peak were pooled together and the anticoagulant effect was evaluated with different methods. From 25,470 +/- 2,800 U of prothrombin, 5,800 +/- 1,400 U of inhibitor were obtained. The inhibitor was found to be most effective at pH 7.2--7.8. In vitro, the inhibitor inhibited the thrombin time and the plasma clotting time highly significantly but had no effect on euglobulin lysis time and fibrin plates. In vivo, when injected into rabbits, the inhibitor effect was also significant on the same tests. The autoprothombin II-A anticoagulant had a protective effect on DIC formation with rabbit brain thromboplastin administration. This protective effect was found to be statistically significant.

Objectives: To report on the changes in fibrinolytic activity in human immunodeficiency virus (HIV) infected pregnant women who are undergoing highly active antiretroviral therapy (HAART). Methods: Blood was collected from 50 HIV positive women on HAART (test subjects), and 50 HIV positive women not on HAART (controls). These women were attending the prevention of mother to child clinic (PMTCT) of the University of Benin Teaching Hospital, Benin City, Nigeria from January to June 2014. Standard manual techniques were used to estimate plasma fibrinogen concentration (PFC), euglobulin lysis time (ELT), packed cell volume (PCV), and plasma viscosity (PV). Results: The mean ± standard error of mean (SEM) of PFC was 4.02±0.13g/l and ELT from the test subjects was 378±15 mins was significantly higher (p0.05). There were differences in the various parameters investigated when the various trimesters were compared. These differences did not, however, follow a particular pattern. Conclusion: Highly active antiretroviral therapy can cause changes in fibrinolytic activity that may predispose pregnant women to hyperfibrinogenemia and anemia.

Trauma-induced coagulopathy (TIC) has been recognized as a potential preventable cause of mortality in 40% [1] of civilian deaths and 80% of military casualties [2]. Recent studies indicate that fibrinolysis may be a significant component of TIC in the most severely injured patients [3] and the CRASH2 study [4] has stimulated worldwide interest in this arena. Although treatment is available to prevent plasmin-induced hyperfibrinolysis in the forms of aminocaproic acid and tranexamic acid, it is important to confirm the diagnosis of systematic hyperfibrinolysis before subjecting a patient to a potentially thrombogenic agent. Raza et al. [5] have questioned the validity of thrombelastometry (ROTEM) to identify pathologic fibrinolysis in injured patients, but we respectfully caution that their conclusions may be misleading owing to a number of reasons. The gold standard, first developed in 1959, for evaluating fibrinolysis is the euglobulin lysis time (ELT) [6,7]. However, this time-consuming procedure is impractical for evaluation of the acutely injured patient. ROTEM and thrombelastography (TEG) have been used in elective cardiac surgical and liver transplant patients for decades for point-of-care detection of pathologic fibrinolysis [8,9]. Although present manufacturer recommendations for TEG and ROTEM assessment of fibrinolysis have been established in healthy individuals, these assays have not been validated in the trauma population. For example, Haemonetics has arbitrarily set their detection threshold for hyperfibrinolysis in their TEG instrument as a lysis of 3% lysis at 30 min by TEG was associated with an increase in mortality, 70 vs. 18.5%, P = 0.002, compared with lysis < 3% (Chapman MC, Moore EE, Ramos CR. Fibrinolysis above 3% is the critical value for initiation of anti-fibrinolytic therapy. J Trauma 2013 [In press]). Furthermore, we have documented a much lower TEG detection threshold for lysis with ELT (Ramos CR, Moore EE, Chapman MC. Defining post-injury hyperfibrinolysis with thrombelastography: technology in evolution. Shock Society 2013 [abst]). Presumably a similar issue exists for the ROTEM threshold for the detection of hyperfibrinolysis. Raza et al.[5] defined severe fibrinolysis based upon a ROTEM maximal lysis of > 15% compared with the moderate group with a maximal lysis 1500 μg L−1. The moderate and severe groups both had significant biomarkers of enzymatic fibrinolysis, including decreased antiplasmin and fibrinogen as well as increased D-dimer and TPA. A third group with elevated ROTEM lysis but normal levels of PAP complexes is noted to additionally differ from both the moderate and severe hyperfibrinolysis groups in having no changes in these biomarkers of hyperfibrinolysis. The TEM lysis only group did not differ from the normal group except in having lower D-dimer and prothrombin fragments 1+2, which are opposite to the expected direction of change. Furthermore, ROTEM has developed an assay in which aprotinin is added in vitro to the patient samples to inhibit the serine protease plasmin. This confirms plasmin-mediated clot dissociation by comparing the maximum lysis of a native sample (EXTEM) to the maximum lysis of a treated sample (APTEM). A potential explanation of the TEM lysis only group, using EXTEM, is (i) this small group (n = 8) did not have hyperfibrinolysis and (ii) the maximal lysis > 15% produced on ROTEM is alternatively reflecting platelet retraction or a non-enzymatic change in fibroelastic character of the formed clot, as has been previously reported in healthy individuals [11,12]. Such alternative causes for the observed ’hyperfibrinolysis‘ is also consistent with the low mean injury severity score for this group [2–9]. We expect that in patients with normal biomarkers of fibrinolysis, as in this TEM lysis only group, the EXTEM and APTEM maximal lysis would not be different. Thus, it would be interesting to determine if there was a correlation between elevated PAP levels and the difference in maximal lysis between EXTEM and APTEM in all groups. Finally, the massive elevations in PAP could be an artifact because the samples were not drawn into aprotinin and this has been previously described as a cause of falsely elevated PAP complexes [13–15]. Thus, an alternative explanation of the results of Raza et al. is (i) increased mortality occurs in patients with elevated fibrinolysis confirmed by plasma biomarkers and (ii) the group with negative biomarkers of proteolytic fibrinolysis are manifesting non-fibrinolytic changes in fibro-elastic clot characteristics. In summary, we agree further studies are required to determine both TEG and ROTEM thresholds for pathologic fibrinolysis in the trauma population, and this should be systematically validated by ELT.

Long-term metabolic changes in vein tissue of the limbs and feet have been reported in the course of chronic venous insufficiency (CVI). Low fibrinolytic potential was first demonstrated using fibrin-embedded vein rings (Todd's biopsy), then in blood via increased euglobulin lysis time. This defect is especially pronounced when blood is taken from foot veins of patients with grades 5 and 6 of CVI or skin lesions. Haemorrheological disorders such as increased blood viscosity and red cell aggregation, related mainly to high fibrinogen levels, have also been shown in patients with CVI. Such disorders, particularly observed in blood from foot veins, play an important role in the interaction between the blood cell components and the vessel wall. More recently, the margination and adhesion of white cells to the endothelium and the subsequent activation of white cells have been assumed. Adhesion molecules such as ICAM-1, VCAM-1 and P-selectin have been identified surrounding skin ulceration. There is also evidence that markers of neutrophil degranulation reach high levels in blood taken from foot veins after exposure to experimental venous hypertension. White cell activation results in elevated plasma levels of L-selectin, increased production of oxygen free radicals, pseudopods, CD11b integrin, platelet-monocyte aggregates and abnormal lymphocyte L-selectin. Increased nitric oxide, presumably due to monocyte activation, as well as increased urine haemosiderin related to skin microvessel leakage have also been reported. VCAM-1 and metalloproteinase MMP9 activity have been stated as sensitive markers in relation to endothelium activation and white cell trapping, which follows hypoxia and/or alterations in wall shear stress, mainly in skin venulae and in the region of valves.

The thienopyridine drugs, ticlopidine, and clopidogrel are used extensively as antiplatelet agents. Clopidogrel is used in the treatment of myocardial infarction, stroke, and peripheral vascular disease [1--3]. Clopidogrel’s beneficial effects are derived from its antiplatelet effect, mediated by the inhibition of adenosine diphosphate (ADP) receptors on platelets [4]. Recent studies have suggested that thienopyridines have fibrinolytic properties and propose that a thrombolytic role may be an important mechanism in their efficacy [5]. Oral ticlopidine reduced the euglobulin lysis time (ELT) in human subjects, and experimental infusions of clopidogrel and ticlopidine were shown to reduce the thrombus burden in rats [6]. An associated increase in prostacyclin (PGI 2) was considered as a possible initiator for tissue plasminogen activator (tPA) release.

Extraction of nattokinase, a fibrinolytic enzyme in natto bacillus, was attempted by the following 4 methods: 1) extraction with saline, 2) treatment with the organic solvents acetone, toluene and hexane prior to extraction, 3) alkaline treatment at pH 11.0 and, 4) autolysis in the presence of 0.1% NaN3 at 4\\xa1 C. Each fraction showed not only a strong fibrinolytic activity, but also H-D-Val-Leu-Lys-pNA and Suc-Ala-Ala-Pro-Phe-pNA amidolytic activities. Doses of 50–200 mg/kg natto bacillus (11011 active cells/g) were orally administered for rat experimental pulmonary thrombosis and to healthy human volunteers. A decrease in thrombus count and plasma euglobulin lysis time (ELT), as well as an increase in tissue plasminogen activator (t-PA), indicate that natto bacillus serves to activate plasma fibrinolysis in vivo.

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a fibrinolytic inhibitor. Studies in coronary artery disease have reported increased TAFI activity (TAFI Act) and low TAFI antigen (TAFI Ag) levels. This controversy might be explained by the polymorphisms of its gene. Only the Thr325Ile polymorphism modulates both TAFI Ag and Act levels in vitro. This study assessed TAFI Ag and Act levels, TAFI Thr325Ile polymorphism, the fibrinolytic and protein C systems and some prothrombotic mutations in a young patient group (n = 127, aged < 51 years, with myocardial infarction) and a control group (n = 99) with similar characteristics. Patients exhibited hypofibrinolysis and higher plasminogen activator inhibitor-1 (PAI-1) levels. Although TAFI Ag was lower, TAFI Act level was significantly higher in patients and positively correlated with PAI-1, protein C inhibitor and the euglobulin lysis time. No differences between groups were found according to the Thr325Ile polymorphism. Irrespective of the genotype, patients had higher TAFI Act levels. The Ile-325 variant exhibited lower TAFI Ag levels. We suggest that the hypofibrinolysis observed in these patients results from an increase in both PAI-1 and TAFI Act, which is not related to the Thr325Ile polymorphism. Patients have high TAFI Act with low TAFI Ag levels, probably because of an increased stability of TAFI related to a fibrinolytic hypofunction.

Background: In vitro studies have shown that nonionic radiographic contrast material may induce the generation of thrombin in blood, whereas ionic contrast agents, such as iohexol, do not. However, knowledge of the effects of contrast material on coagulation and fibrinolytic systems in vivo is limited. Objective: This study was designed to assess the effects of the nonionic radiographic contrast material iopamidol on hemostasis in patients undergoing coronary angiography or cardiac catheterization. Methods: Patients aged ?18 years with chest pain and/or dyspnea who underwent coronary angiography or cardiac catheterization with intra-arterial contrast material were assessed for hemostasis. Blood samples were drawn before and 3 minutes after injection of iopamidol. Complete blood count and coagulation profile (bleeding time, clotting time, clot retraction time, euglobulin lysis time [ELT], prothrombin and partial thromboplastin times, coagulation factor I [CFI] level, and platelet factor 3 [PF-3] availability) were assessed. The natural coagulation inhibitors protein C, protein S, and antithrombin III (AT-III) also were measured. Results: Thirty patients (7 males, 23 females; mean [SD] age, 51.3 [20.2] years; range, 17-79 years) were included in this single-center study. All hematologic variables (hemoglobin, white blood cell count, and platelet count) decreased significantly (P < 0.001, P < 0.001, and P < 0.05, respectively) after administration of iopamidol but remained within normal limits. Mean levels of protein C, protein S, and AT-III did not change significantly after administration of iopamidol. Bleeding time was not changed significantly, and PF-3 availability was prolonged in both groups, but the changes were not statistically significant. Conclusions: In this study population, although hemostasis remained grossly intact after injection of nonionic contrast material, the coagulation system may have been affected by the accelerated consumption of CFI and platelets. The affected variables were platelets, clot retraction time, ELT, and natural coagulation inhibitors (protein C, protein S, and AT-III). Although the natural coagulation inhibitors remained within the normal range, the correlations were found significant. These changes in hemostasis affected the vascular phase. If the vascular compartment, especially the endothelium, remained intact, the infusion of nonionic agents in low concentrations might be safe for angiography and other procedures; however, more studies are needed. Copyright © 2003 Excerpta Medica, Inc.

Background. Cardiovascular disease is the most common cause of death among renal transplant recipients (RTRs). Impaired fibrinolytic capacity caused by an increase in plasminogen activator inhibitor type 1 (PAI-1) levels is involved in the onset of atherosclerosis and thrombotic complications. Long-term steroid treatment may induce arterial hypertension and metabolic and prothrombotic changes (including up-regulation of PAI-1 synthesis), which increase the cardiovascular risk. We evaluated plasma fibrinolytic behavior in two groups of RTRs treated with different immunosuppressive regimens. Methods. Twenty-seven RTRs were randomized to receive long-term (17 patients) or perioperative short-term (10 patients) steroids in addition to immunosuppression with cyclosporine A plus everolimus (Certican; Novartis, Basel, Switzerland) (7 patients) or FK506 plus mycophenolate mofetil (20 patients). In each patient, fibrinolytic capacity was studied with the 20-min venous occlusion test 1 and 6 months after transplantation. The following were assayed: euglobulin lysis time, tissue-type plasminogen activator antigen, and PAI-1 antigen and activity. Results. One month after transplantation, a severe impairment of fibrinolytic capacity, mainly caused by an increase in PAI-1 antigen and activity levels, was seen in patients with and without steroid treatment. Six months after transplantation, an improvement in fibrinolytic potential as the result of a decrease in PAI-1 levels was observed only in patients without steroid therapy. None of the steroid-treated patients demonstrated PAI-1 values correlating with body mass index, blood pressure, and metabolic parameters, thus confirming the effect of exogenous factors on PAI-1 expression. Moreover, all patients revealed a slight impairment of stimulated endothelial tissue-type plasminogen activator release, regardless of any steroid treatment, which was probably attributable to calcineurin inhibitor-induced endothelial dysfunction. Conclusions. Our study suggests that steroid-free immunosuppression is associated with a better fibrinolytic capacity in RTRs. This finding may contribute toward reducing the risk of cardiovascular events.

Background. Thromboembolic complications are frequent in advanced Chagas’ disease. Objective. This study was designed to explore the presence of a prothrombotic state in the early stages of chronic Chagas’ disease by evaluating serum markers of thrombosis and fibrinolysis. Patients and method. Forty-two patients with chronic Chagas’ disease (12 men and 30 women, 32.5 ± 6.7 years) were compared with 21 healthy volunteers (10 men and 11 women, 24.2 ± 5.6 years). The markers of thrombotic activation used were fragment 1 + 2, ATM complex, PDF/pdf, D-dimer, and β-thromboglobulin. Fibrinolysis was evaluated before and after venous occlusion, together with euglobulin lysis time, t-PA, and PAI-1 titers. Results. The markers of thrombotic state were significantly higher in patients with chronic Chagas’ disease than in controls: F1 + 2 (p < 0.0001), ATM (p < 0.0001), PDF/pdf (p < 0.05), and D dimer (p < 0.05). There was no significant difference in β-thromboglobulin (p = 0.06). Euglobulin lysis time, a global fibrinolytic marker, differed significantly (p < 0.0001) between patients with Chagas’ disease and healthy volunteers. However, the more specific fibrinolytic markers t-PA and PAI-1 did not differ significantly between the two study groups. Conclusions. Although there were no significant differences in fibrinolytic markers between patients with chronic Chagas’ disease and healthy volunteers, the significant increase in thrombosis markers (F1 + 2, ATM complex, PDF/pdf, and D dimer) suggests the presence of a prothrombotic state in the early stages of chronic Chagas’ disease.

Background: Decreased fibrinolytic activity results in longer fibrinolysis time of blood and an increased propensity for hypercoagulable states of blood. Subjects with less fibrinolytic activity are prone to coronary artery disease, stroke and thromboembolic phenomena. Aim: The study aims to identify the impact of gender, dietary habits, body mass index, physical activity level and menstrual cycle on fibrinolytic activity in healthy subjects. Settings and Design: Cross-sectional study on randomly selected 206 healthy medical students aged 17 to 23 years. Materials and Methods: Anthropometric measurements, dietary habits, physical activity level and menstrual history were obtained. Fibrinolysis time of fasting venous blood sample was determined by Euglobulin Lysis Time (ELT) method. Results: Highly significant gender difference was noted in mean fibrinolytic activity (p=0.002). Mean fibrinolytic activity also showed a significant relationship with BMI (p=0.001) and with different phases of menstrual cycle in females (p=0.004). However, such relationship was not observed with diet and physical activity (p>0.05) in boys and girls. Conclusion: Gender difference, body mass index and menstrual cycle phases have influences on the fibrinolytic activity of blood. This might be due to cyclical changes in the sex hormones levels, endometrium-derived plasmin and plasminogen activators and excess production of plasminogen activator inhibitor type-1 (PAI-I) in visceral adipocytes.

The measurement of D-dimer in serum samples (s-DD) after standardized coagulation has been reported as a possible single global test for fibrinolysis in unstimulated conditions in healthy subjects and in patients with ischemic heart disease and with different metabolic disorders. No study has been performed on the use of this test in pregnancy, a condition characterized by physiological changes both in coagulation and in fibrinolysis. In this preliminary study, we have evaluated in 28 women with physiological pregnancy and in 23 comparable controls s-DD and a number of markers of coagulation and fibrinolysis. In nonpregnant women s-DD showed a good correlation with fibrinolytic parameters [euglobulin lysis time (ELT) and type 1 inhibitor of tissue plasminogen activator (PAI-1) act: P

The fibrinolytic system is known to play an important role in the protection of lung architecture and function. This study investigated the effects on lungs of inhibiting the fibrinolytic system using tranexamic acid (TXA). Thirty cats were used, 15 experimental and 15 control. TXA was administered intravenously to the experimental animals for 3 h at 200 mg/kg (acute) and 7 days at 100 mg/kg (chronic). Blood samples were obtained from the carotid artery. The acute dose cats were sacrificed at 3 h and 24 h and the chronic dose cats at 8 days. Samples of inflated and fixed lung were examined morphologically and their collagen contents were determined. Fibrinolytic activity in blood samples was determined by fibrinogen degradation products levels, fibrin plate lytic area diameter, and the euglobulin lysis time. Hyperemia, lung interstitial oedema, haemorrhaging, inflammatory cell infiltration, pneumocyte type II cell proliferation, thrombosis and emphysema-related changes, characterized by enlargement of air spaces accompanied by destruction of alveolar walls, were observed in experimental cats group. None of these alterations except hyperemia and lung interstitial oedema were observed in two control animals. Electron microscopy results revealed oedema fluid in the interstitium, proliferation of pneumocyte type II cells, thickening of the alveolar septa and presence of marked amounts of collagen. Vacuoles were seen in the capillary endothelial cells. Elastic tissue was observed as elastic masses and partly disrupted, although elastic fibers were not prominent in all parts of the interstitium. Collagen content in the chronic dose experimental group was significantly higher than in all control and acute dose experimental groups. The inhibition of fibrinolytic system appears to have caused the emphysematous alterations, alveolar wall destruction and collagen accumulation possibly by causing microthromboses leading to mechanical blockage-ischemic changes, or by causing secondary fibrinolysis as a result of fibrin degradation products affecting local plasminogen activators and proteases. An injury-repair process also appears to have occurred.

FUNDAMENTOS: A aprotinina, um antifibrinolítico de natureza protéica, tem sido proposta pela literatura, no intuito de minimizar os efeitos adversos da circulação extracorpórea ao sistema fibrinolítico, permitindo assim uma hemostasia mais adequada. OBJETIVO: Estudar comparativamente o efeito da utilização profilática de baixas doses de aprotinina em pacientes submetidos à circulação extracorpórea. MÉTODO: Dezessete pacientes portadores de valvopatia mitral submetidos a correção cirúrgica utilizando-se circulação extracorpórea foram aleatoriamente divididos em dois grupos: I (controle) -- 9 pacientes nos quais foi administrado placebo no perfusato e a cada hora de CEC; II (aprotinina) -- 8 pacientes nos quais foram administrados 30000 KIU/kg e 7500 KIU/kg de aprotinina adicionados ao volume do perfusato a cada hora de CEC. O volume total de sangramento pós-operatório nas primeiras 24 horas foi monitorado, assim como amostras sangüíneas foram colhidas após indução anestésica e após a neutralização da heparina com sulfato de protamina para que os seguintes parâmetros fossem avaliados: atividade de protrombina (AP), tempo de tromboplastina parcial ativado (TTPA), tempo de trombina (TT), dosagem de fibrinogênio, concentração de antitrombina III (ATIII), tempo de lise da euglobulina (TLE) e dosagem do dímero --D (DDi). RESULTADOS: O volume médio total de sangramento nas primeiras 24 horas no grupo controle foi 690,67 ± 377,12, enquanto que no grupo da aprotinina em baixas doses foi de 248,75 ± 103,13 (p=0,0017). No quadro abaixo estão apresentados os resultados obtidos a partir das análises das amostras sangüíneas pré e pós-operatórias comparativas dos grupos controle (I) e aprotinina (II). CONCLUSÃO: A utilização da aprotinina, em baixa dose, foi eficaz na redução do sangramento, assim na diminuição da fibrinólise. BACKGROUND: The use of aprotinin, a antifibrinolytic agent, has been shown to decrease damaging effects on cardiopulmonary bypass in fibrinolytic system, which may improve hemostasis. OBJECTIVE: To study the effect of low dose aprotinin in patients undergoing extracorporeal circulation. METHOD: Seventeen patients, underwent cardiopulmonary bypass to mitral valve replacement, was ramdomized in two groups: I (control) -- 9 patients received placebo after anesthesia induction and each hour in the priming; II (aprotinin) -- 8 patients received after anesthesia induction 30,000 KIU/kg and 7.500 KIU/kg each hour in the priming during the perfusion. The blood loss was observed through the first 24 hours postoperatively. Arterial blood samples were taken after anesthesia induction and after administration of protamina in order to analyse: prothrombin activity (PA), partial thomboplastin time (PTT), thrombin time (TT), euglobulin lysis time (ELT) and to measure levels of fibrinogen (F), d-dimer (dD) and antithrombin III (ATIII). RESULTS: Mean postoperative bleeding at the 24th hours was 690.67±377 in the control group and 248,.75±105 in the aprotinin group (p=0.0017). The results taken from the blood samples were shown above. CONCLUSION: It follows that aprotinin, in low dose, was able to inhibit fibrinolysis and reduced bleeding after cardiopulmonary bypass.

A 26-year-old woman presented to our institute for a routine check-up. Nothing was abnormal excepted a prolonged Thrombin Time and a low fibrinogen concentration determined by the Clauss method. Fibrinogen concentration was then measured by PT-derived method, and revealed normal levels. This was therefore suggestive for a dysfibrinogenemia. The patient had no history of haemostatic problems and was under no medication. Her family history revealed nothing relevant, but death of her father from a cerebrovascular accident.Complementary tests were performed: Platelet Function Assay, Factor VIII coagulant activity, von Willebrand antigen quantification, Ristocetin Cofactor activity, thromboelastogram and euglobulin lysis time were all within normal ranges. Finally, thrombin time and Clauss fibrinogen using a human thrombin instead of a bovine thrombine revealed normal results. DNA was then extracted for sequencing the genes coding for fibrinogen. This revealed the presence of a substitution ArgCys in position 275 of the γ-chain of the fibrinogen.This mutation has already been reported in the literature with four cases of thrombosis, three cases of haemorrhage and eight had no clinical signs. The gamma chain is implicated in several crucial interactions such as the primary polymerization 'a', the binding to calcium, the factor XIIIa-induced cross-linking, the binding to plasminogen and to tissue plasminogen activator. Results of the literature show that this mutation has several impacts on in vitro tests, and we proved that those can be corrected by the use of human thrombin.

Introduction Cydonia oblonga Miller (COM) is traditionally used in Uyghur medicine for the prevention of cardiovascular disease. The present study is designed to explore the effects of COM extracts on models and markers of thrombosis and related biomarkers. Materials and methods 20, 40, 80 mg/kg/day COM aqueous extracts and 5 mg/kg/day aspirin, orally for 14 days were compared to untreated controls in mice on bleeding and clotting times, using the tail cutting and glass slide methods and for death rates in collagen–epinephrine pulmonary thrombosis, thrombolysis in vitro and euglobulin lysis time (ELT). In rats, common carotid artery FeCl 3 -induced thrombus and inferior vena cava thrombosis occlusion time, plasma concentrations of thromboxane B 2 (TXB 2 ) and 6-keto-prostaglandine F 1 α (6-keto-PGF1α) were measured. Results and conclusion Compared to controls, COM extracts dose-dependently prolonged bleeding by 2.17, 2.78 and 3.63 times, vs. aspirin 2.58, and the clotting time by 1.44, 2.47 and 2.48 times, vs. aspirin 1.91. COM reduced pulmonary embolus mortality by 27, 40 and 53%, vs. 47% for aspirin. COM dose-dependently increased thrombolysis by 45, 55 and 63%, vs. 56% for aspirin, and shortened ELT to 71, 61 and 43%, vs. 43% for aspirin. In rats, venous occlusion time was prolonged. Arterial and venous thrombus weights were dose-dependently reduced in COM groups. TXB 2 decreased and 6-keto-PGF1α increased with COM and aspirin, with an association between 6-keto-PGF1α/TXB2 and arterial or venous thrombus weight for all products, and for occlusion time with COM but not for aspirin. Conclusion We confirm the experimental effects of COM on hemostasis and thrombosis. Further exploration of putative clinical effects appear justified.

PURPOSE. To evaluate perioperative changes in fibrinolysis in patients undergoing retinal detachment surgery under general or local anesthesia. PATIENTS. Prospective study of 81 patients (43 male, 38 female), aged from 15 to 82 (mean 50.7 SD = 17.8) years, undergoing retinal detachment surgery (encirclement with scleral buckling) under general anesthesia (group A), and 14 patients (6 male, 8 female) aged from 15 to 78 (mean 52.9, SD =19.8) years, operated under local anesthesia (group B). Excluded were patients with venous or arterial disease or other factors that could change the parameters investigated. METHODS. Blood was sampled from a cubital vein one day before surgery, immediately after induction of anesthesia but before surgery, immediately after completion of the operation but before the termination of anesthesia and after the operation (on days 1 and 4). In patients' citrated plasma, tissue plasminogen activator antigen (t-PA-Ag), plasminogen activator inhibitor type 1 antigen (PAI-1 Ag) and activity (PAI-1), fibrin-fibrinogen degradation products (FDP) and euglobulin lysis time (ELT) were measured. RESULTS. The pattern of changes in perioperative fibrinolytic activity was similar in both groups. Intraoperative levels of FDP were significantly higher and ELT shorter than preoperatively. In both groups t-PA Ag concentration was significantly increased on the first postoperative day. There were no changes in PAI-1 in both groups. Postoperatively, the FDP concentration was reduced and ELT prolonged. CONCLUSIONS. Retinal detachment surgery induces intraoperative activation of fibrinolysis in the systemic circulation regardless of the type of anesthesia.