Ethanol Gelation Test Research Articles

Peculiarities of blood coagulation disorders in patients with COVID-19

To study the relationship of hemostatic disorders with inflammation and estimate their role in the course and outcomes of COVID-19. We examined 215 consecutive patients with moderate and severe forms of acute COVID-19. The patients were on anticoagulants and immunosuppressive drugs. Hemostasis was assessed using the thrombodynamics assay, thromboelastography, fibrinogen and D-dimer levels, prothrombin time, and soluble fibrin-monomer complexes (ethanol gelation test). The hemostatic parameters were correlated with hematological and biochemical tests, including markers of inflammation (C-reactive protein, interleukins 6 and 8), as well as with the disease severity and outcomes. Laboratory signs of coagulopathy were revealed in the vast majority of the cases. Despite the use of low-molecular-weight heparins in the prophylactic and therapeutic doses, coagulopathy in COVID-19 manifested predominantly as hypercoagulability that correlated directly with the systemic inflammation and metabolic changes due to liver and kidney dysfunction. A direct relationship was found between the grade of coagulopathy and the severity of COVID-19, including comorbidities and the mortality. The chronometric hypocoagulability observed in about 1/4 cases was associated with a high level of C-reactive protein, which may decelerate coagulation in vitro and thereby mask the true inflammatory thrombophilia. Persistent hyperfibrinogenemia and high D-dimer in the absence of consumption coagulopathy suggest the predominance of local and/or regional microthrombosis over disseminated intravascular coagulation. The results obtained substantiate the need for laboratory monitoring of hemostasis and active prophylaxis and treatment of thrombotic complications in COVID-19.

Successful Management of Heparin-Induced Thrombocytopenia Using Argatroban in a Very Old Woman: A Case Report

Thrombosis due to heparin-induced thrombocytopenia (HIT) is rare but has a severe prognosis. Its management is not always easy, particularly in old patients with renal insufficiency. A 95-year-old woman was hospitalized for dyspnea. Curative treatment with unfractionated heparin was started because pulmonary embolism was suspected. Disseminated intravascular coagulation was then suspected because of thrombocytopenia, hypoprothrombinemia, hypofibrinogenemia, and a positive ethanol gelation test. The first immunoassay for HIT was negative. On the 12th day of hospitalization, bilateral cyanosis of the toes occurred associated with recent deep bilateral venous and arterial thrombosis at duplex ultrasound. New biological tests confirmed HIT and led us to stop heparin and to start argatroban with a positive clinical and biological evolution. Venous and arterial thrombosis associated with thrombocytopenia during heparin treatment must be considered HIT whatever the biological test results are. Argatroban is a good alternative treatment in the elderly.

Activated factor VII: my story

My story starts in the early 1970s when I was appointeda resident in the Hemophilia Clinic at the Malmo¨University Hospital, University of Lund, in Sweden,which at that time was headed by Professor Inga MarieNilsson. This Haemophilia Clinic was very special incombining the clinical investigation and care of haemo-philia patients from all over Sweden together with aresearch programme at the forefront of haemostasis,covering both bleeding and thrombotic disorders. Myown research was focused on fibrinolysis, and Ipresented my dissertation in early 1974. However, inparallel, I was, as the only physician along with IngaMarie in the clinic, deeply involved with the clinicalcare of haemophilic patients. This involved being onduty most of the time dealing with both inpatient andoutpatient care.In the early 1970s, the most serious problem was totreat haemophilia patients who had developed inhibi-tors against factor VIII (FVIII) or factor IX (FIX).Various treatment modalities such as exchange trans-fusions combined with substitution therapy were tried[1–3]. In 1971, David Green described a combination ofsimultaneous administration of large amounts of FVIII/FIX and cyclophosphamide. This regimen was used tocover extensive dental surgery in two haemophilia Bpatients during 1971 [4]. The same treatment modalitywas successfully used in four haemophilia A patientsduring 1972 [5], and later in another five patients [6]. Inthose patients who had an inhibitor titre too high to besuppressed by the administration of large amounts ofFVIII/FIX concentrates, the addition of an extracor-poral adsorption of the inhibitory gamma globulin asdescribed by Edson et al. [7] was considered.However, in association with the very high doses ofFIX-concentrate (PCC) required in some of the haemo-philia B patients, to achieve a neutralization of theinhibitors as well as a haemostatic plasma level ofFIX:C, there were signs of thrombin activation with asystemic activation of the coagulation system (highlevels of fibrinogen degradation products, decrease offibrinogen, decreased platelet counts, positive ethanolgelation test, decreased alfa-2-macroglobulin). Theaddition of antithrombin concentrate did not entirelyneutralize these changes [8]. Increasing numbers ofreports with similar findings following the use ofvarious PCCs were being published [9,10]. As no pureFIX concentrates were commercially available at thetime, this presented a problem for the treatment ofhaemophilia B patients, especially those with high titreinhibitors, who required large doses of the PCCs forhaemostasis.However, reports appeared in the early 1970s on theuse of PCCs in the treatment of mild to moderatebleeding episodes in inhibitor patients. Thus, Feketeet al. [11] reported a haemostatic effect with an‘activated prothrombin complex concentrate’. Thisconcentrate was claimed to include certain amounts ofactivated FIX, FX, FVII as well as traces of thrombin.A high in vitro clotting activity was demonstrated, andthis was called ‘auto-activated FIX’ [12].In Malmo¨, we were not very satisfied with theseconcentrates when used in the treatment of haemophiliaB patients, as we saw changes in the plasma coagulationpattern, indicating activation of systemic coagulation[8], which could cause thrombo-embolic side-effectsincluding disseminated intravascular coagulation (DIC).Furthermore, we did not see any significant clinicaleffect in patients with inhibitors. At this time, it wassuggested that the clot promoting effect in PCCs wascaused by the presence of activated coagulation factors,especially FIXa and FXa [10,13,14].

Endothelial Dysfunction In Preeclampsia

Preeclampsia is a complication of pregnancy characterized by hypertension, edema, and proteinuria. Based on these signs, it is suggested that endothelial dysfunction plays a role in the pathogenesis of preeclampsia. The aims of this study were to know whether endothelial dysfunction occur in preeclampsia by measuring the level of sVCAM-1, von Willebrand factor, and fibrin monomer. The relationship between markers of endothelial dysfunction and blood pressure would also be sought. In this cross-sectional study, 30 women at the 24–42 weeks of pregnancy with preeklampsia, were enrolled and control group comprised of fullterm pregnant women. The level of sVCAM-1 was determined by ELISA method using reagents from R&D system, while vWF level was measured by enzyme linked fluorescent assay (ELFA) using reagent from VIDAS bioMerieux, and fibrin monomer was detected by ethanol gelation test. The mean of sVCAM-1 level in the preeklampsia group and in the control group were 576.4 ng/mL, and 375.7 ng/mL, respectively while the standard deviation were 58.3 ng/mL, and 43 ng/mL, respectively. The mean of vWF level in the preeklampsia group and in the control group were 305.3% and 162.4%, respectively while the standard deviation were 107.4% and 33%, respectively. Moderate correlation were found between sVCAM-1 as well as vWF level with both systolic and diastolic pressure. Fibrin monomer was found in 28 out of 30 subjects of preeclampsia group, but only 1 out of 31 subjects in the control group. The results of this study indicated that endothelial dysfunction occurred in preeclampsia.

Plasma markers of hypercoagulability in patients with serious infections and risk of septic shock.

Hyperthrombinogenesis due to bacterial septicemia may aggravate the risk of irreversible septic shock. In 22 patients with septicemia complicating urinary or alimentary infections, daily assessment of hemostasis was performed throughout 1 week. Standard screening of hemostasis revealed significantly increased mean values of prothrombin time, fibrinogen, and fibrinogen degradation product (FDP) concentration. However, platelet counts, activated partial thromboplastin times (APTT), thrombin times, ethanol gelation tests, and antithrombin activity remained within the normal range. By contrast, except for insignificant changes in protein C activity and activated factor VII content, specific markers of plasma hypercoagulability, that is, thrombin-antithrombin (TAT) complexes, prothrombin activating factor F 1+2, activated factor XII (XIIa), and dimer D were all markedly increased. Pathologic levels of TAT and Xlla were found in 82% and 73% of all plasma samples, respectively. The augmentation of TAT correlated with prolongation of thrombin time and increases in F 1+2 levels. The increase in XIIa correlated with thrombocytopenia, prolongation of APTT, exhaustion of antithrombin, and accumulation of F 1+2 and FDP in the plasma. Moreover, a significant increase in XIIa, stronger positivity of the ethanol gelation test, a greater increase in FDP, and a more pronounced decrease in protein C activity were observed in 8 patients with fatal septic shock. This study suggests the usefulness of TAT and XIIa measurements in the early recognition of plasma hypercoagulation in serious infections.

Hemodynamic Changes and Systemic Activation of Coagulation and Fibrinolysis During Controlled Endotoxemia in Pigs

In this study, we have established a pig model that can combine extensive hemodynamic monitoring with simultaneous repetitive (serial) blood sampling for the study of multiple variables related to the hemostatic system. Sixteen healthy young pigs were studied to evaluate the influence of continuous endotoxin infusion on hemodynamic patterns and activation of coagulation and fibrinolysis. The chief aim of the study was to investigate the applicability of analytical methods primarily developed for use with human plasma samples in quantification of factors and reaction products of the porcine coagulation and fibrinolytic systems, and further, to use these methods to study the longitudinal changes in the plasma levels of these hemostatic variables as a consequence of endotoxin infusion. We found that acute, controlled endotoxemia induced a hemodynamic state of shock and reduced pulmonary gas exchange. Simultaneously, a gradual increase in peripheral blood mononuclear cell tissue factor activity was demonstrated, and increased maximally 5.5-fold 4 hours after onset of endotoxin infusion. Thrombin-antithrombin complexes increased in plasma to maximum levels after 3 hours, accompanied by an ethanol gelation test that was regularly positive after 1 to 2 hours, and fibrin monomer levels that gradually increased maximally 3.8-fold after 6 hours. These changes were followed by gradual decreases of both fibrinogen and factor VII levels, mainly due to consumption. Plasma levels of tissue type plasminogen activator activity peaked at 1.5 hours (11.3-fold increase), whereas the peak of plasminogen activator inhibitor-1 activity (14-fold increase at 4.5 hours) was delayed compared to tissue plasminogen activator and completely extinguished plasma tissue plasminogen activator activity. The sequential activation of coagulation and fibrinolysis established a procoagulant state favoring disseminated intravascular coagulation and microthrombus formation, potentially leading to multiple organ dysfunction.

Demonstration of Platelet-Derived Microvesicles in Blood from Patients with Activated Coagulation and Fibrinolysis Using a Filtration Technique and Western Blotting

Platelet vesiculation in vitro is correlated to platelet activation. It was therefore considered of interest to see if microvesicles (MV) are present in blood in clinical situations associated with platelet activation in vivo. Patients with both activated coagulation and fibrinolysis, implying that thrombin has been generated, suit such a purpose. Thus, the aim of this study was to investigate whether microvesicles could be detected in patients with activated coagulation and fibrinolysis, as diagnosed by the presence of soluble fibrin (positive ethanol gelation tests) and positive tests for fibrin degradation products (FDP). Platelet-rich plasma was prepared from citrated blood from patients (n = 22) and healthy controls (n = 32) matched as to age and sex. The intact platelets were removed from plasma by centrifugation. Any MV present were isolated from the platelet-free plasma by a filtration procedure, washed, solubilized in Triton X-100 and subjected to SDS-PAGE with Western blotting using a MAb against GPIIb alpha as an indicator of the presence of microvesicles. All of the 22 patients showed the presence of microvesicles detectable by the content of GPIIb alpha, whereas this could be observed in only 4 out of the 32 normal controls and then in small or trace amounts only. The presence of microvesicles among cell-derived material in the plasma of two of the patients was also confirmed by electron microscopy. To the best of our knowledge this is the first report on the presence of microvesicles in plasma from patients with both activated coagulation and fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Disseminated intravascular coagulation and decrease in fibrinogen levels induced by vincristine/prednisolone therapy of lymphoid blast crisis of chronic myeloid leukemia

Therapy with vincristine (2 mg i.v. weekly) and prednisolone (100 mg p.o. daily) caused a decrease in fibrinogen levels in nine patients treated for lymphoid blast crisis LBC) of chronic myeloid leukemia (CML). During the first days of treatment disseminated intravascular coagulation (DIC), evidence by a positive ethanol gelation test, markedly increased thrombin-antithrombin III complex and fibrin-split product D-dimer levels, and a rapid fall in fibrinogen levels was observed in two patients. The induction of DIC in these two patients caused profuse bleeding in one and necessitated substitution therapy with fibrinogen and platelet concentrates. The remaining seven patients revealed no signs of DIC; nevertheless, four of them showed a moderate increase in D-dimer levels after initiation of therapy. In these patients a well-known side effect of long-term steroid therapy, namely a decrease of fibrinogen levels, was observed within the first week of treatment. Fibrinogen levels did not fall below 150 mg/dl and increased after dose reduction from 100 mg/day to 50 mg/day. We conclude from our results that two types of disturbances in fibrinogen metabolism can be observed during vincristine/prednisolone therapy of LBC of CML: (a) a decrease of fibrinogen levels due to a steroid-mediated impairment of liver synthesis, and (b) a rapid fall in fibrinogen levels in the course of DIC, most likely induced by the release of procoagulants from deteriorating blast cells, leading to severe bleeding in selected cases.

Comparison of methods for detecting soluble fibrin in plasma. An in vitro study

The ability of the COA-SET Fibrin monomer (COA-SET FM) test to detect soluble fibrin was evaluated by comparing the results of the COA-SET FM test with fibrino-peptide A (FPA) determinations following thrombin incubation of plasma or whole blood. In addition, two semiquantitative tests (erytrocytes-agglutination test (FM-test) and ethanol gelation test (EGT)) were included in the study. Under the experimental conditions used, the COA-SET FM test proved less sensitive than the FPA-assay. There was a strong correlation between the results obtained by the two tests (r=0.86, p=0.0001). When solely regarding low levels of soluble fibrin, however, the correlation was weaker (r=0.59, p=0.0003). The FM-test was less sensitive than the COA-SET FM test, but more sensitive than EGT at normal and low fibrinogen concentrations. At high fibrinogen concentrations, however, EGT proved more sensitive than the FM-test. Knowing that 1–2 moles of FPA are released per mole of fibrin monomers formed, a discrepancy was observed between the FPA concentrations and the fibrin monomer concentrations as determined by the COA-SET FM test, the FPA levels being 2–25 times higher than the fibrin monomer levels. The discrepancy was greatest at incipient fibrinogen-fibrin transformation and at high plasma fibrinogen levels. This may suggest that fibrinogen in some way interfered with the stimulating effect of fibrin on the t-PA catalyzed activation of plasminogen, the principle upon which the COA-SET FM test is based. In addition, the way of preparing fibrin monomers might influence their properties as plasminogen activators and contribute to the discrepancy. Further studies are in progress to clarify these matters.

83 Diagnostic value of D-dimer, fibrinogen degradation products, ethanol gel test and transfer test in deep venous thrombosis and pulmonary embolism

83 Diagnostic value of D-dimer, fibrinogen degradation products, ethanol gel test and transfer test in deep venous thrombosis and pulmonary embolism

Epsilon-aminocaproic Acid for Treatment of Fibrinolysis during Liver Transplantation

In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; aPTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F less than 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with epsilon-aminocaproic acid (0.09%) and an untreated sample. Blood treated with epsilon-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of epsilon-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, epsilon-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with epsilon-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 +/- 29.5% to 94.8 +/- 7.4% (mean +/- SD, P less than 0.001). None of the treated patients had hemorrhagic or thrombotic complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulatory effect of the gastrointestinal tract (gut) on fibrinolysis and fibrinogen derivatives.

We have investigated some components of the fibrinolytic system and fibrinogen derivatives in blood samples taken simultaneously from the human portal and cubital veins. In the first series the blood was drawn during laparotomy from 12 cholecystectomized, otherwise healthy patients. The mean value of euglobulin lysis time was significantly lower in the portal than in the cubital vein. The values of the fibrinogen, plasminogen, serial dilution protamine sulfate, and ethanol gelation tests in both samples were quite similar. In the second series blood was taken from eight patients with cancer of the gut and from six cholecystectomized patients. The staphylococcal clumping test (SCT) in serum was performed for fibrin degradation products (FDP) in samples from both veins. In patients with cancer the mean FDP level was significantly higher in the portal than in the cubital vein. In cholecystectomized patients the SCT was negative in samples from both veins. We conclude that fibrinogen pathway metabolism does not differ in the portal and cubital veins under normal conditions, whereas in neoplastic disease fibrinogen degradation is greater in the portal vein. We also suggest that the gut probably modulates fibrinolytic activity in normal conditions.

Hypercoagulation and fibrinolysis in oral sub-mucous fibrosis.

In seven out of seven patients suffering from oral submucous fibrosis (OSMF), we detected circulating molecules that are immunologically similar to fibrinogen (MISFI), as suggested by the hemagglutination inhibition studies using the FDP Kit (Wellcome) and by paracoagulation tests such as serial dilution protamine tests. The ethanol gelation test was positive in three of the seven patients. Cryofibrinogen developed in six of the seven patients within three to six days of incubation of plasma samples at 4 degrees C. Plasma kept at 37 degrees C did not develop any fibrous or amorphous precipitate. In OSMF, fibrinogen, fibrinogen intermediates, and fibrin degradation products deserve further scrutiny, as this may help define the etiology of OSMF which is, so far, obscure.

肝がんに対する肝切除前後の凝血学的検討

In order to investigate the influence of hepatic resection on hemostasis, coagulation studies were carried out in patients with hepatocellular carcinoma. Twenty-nine patients were divided into 2 groups designed as group A which underwent 2 segmentectomy or more (13 patients) and group B which underwent 1 or less than a segmentectomy (16 patients).Preoperative studies of both groups revealed almost normal coagulation studies except for minor degree of thrombocytopenia, but liver function tests were slightly impaired. Postoperative studies revealed thrombocytopenia, prolonged PT, decreased levels of factor II, V, VII, IX, X, fibrinogen, plasminogen, AT-III and α2-M and increase of FDP. Seven out of the 29 patients showed positive ethanol gelation test in their postoperative course. These findings were more prominent in group A compared with group B and recovery of the levels of factor II, V, VII, IX, X, plasminogen and AT-III to the preoperative levels were significantly delayed in group A.Increased FDP and positive ethanol gelation test which generally indicate presence of hypercoagulability improved proportionally to the recovery of coagulation abnormalities. DIC was confirmed only in one out of 29 patients by the clinical and laboratory findings.Consequently coagulation disorders seen in the postoperative period of liver resection are mostly due to impaired liver functions which include impaired synthesis and RES clearance.

Soluble fibrin (ethanol gelation test) and fibrin(ogen) degradation products in suspected thrombosis with reference to the 125I‐fibrinogen uptake test for detection of thrombus formation

When symptoms of deep vein thrombosis is confirmed by venography (established DVT), the 125I‐fibrinogen uptake test (FUT) will discriminate between thrombi which incorporate the isotope (FUT+) and those who do not (FUT−). These are probably forming and non‐forming thrombi, respectively. The aim of the present study was to compare the occurrence of fibrinaemia, using the ethanol gelation test (EGT), in patients with FUT+ and FUT− thrombi. Fibrin(ogen) degradation products (FDP) were also analysed.The study included 64 medical patients with suspected DVT, confirmed by venography in 43 and precluded in 21 patients. Isotope studies included 12 patients with FUT+ and 13 with FUT− thrombi.Significant concordance between hemostatic parameters and venography was found only for FDP. The sensitivity of FDP on admission was 53%, but also patients without DVT had increased values (5%, P < 0,001).Among patients with documented DVT, a positive EGT was specific for those with FUT+ thrombi which incorporated the isotope in at least 4 recording positions, whereas the sensitivity on admission was 89% (P < 0,005). A positive EGT was not associated with other variables, including disorders other than DVT. The strong association between abnormal isotope findings and a positive EGT suggests that FUT+ thrombi may induce fibrinaemia.

Heparin precipitable fraction of plasma (HPF) is not influenced by the presence of fibrin monomers

The heparin precipitable fraction of plasma consists mainly of fibrinogen and fibronectin. In our work with HPF in patients with acute myocardial infarction we observed variations in the amount of precipitate that could not be accounted for by corresponding variations in the plasma content of fibrinogen and fibronectin. To see whether the presence/absence of fibrin monomers in plasma could be of importance for this variation in HPF, we have: added fibrin des‐AA monomers to normal and patient plasmas incubated normal and patient plasmas with insolubilized reptilase until a strongly positive ethanol gelation test could be demonstrated examined a potential correlation between a positive ethanol gelation test and HPF in a patient material. From the results of the above investigations, we could conclude that the presence of fibrin monomers (presence of soluble fibrin) is of no importance for the variations observed in the HPF‐phenomenon.

The Value of Variables of Disseminated Intravascular Coagulation in the Diagnosis of Adult Respiratory Distress Syndrome

In an investigation on 19 patients with traumatic (n = 11) and septic (n = 8) shock, at risk of developing adult respiratory distress syndrome (ARDS), various coagulation and fibrinolysis variables and also blood gases and chest x-ray were monitored. Eight patients developed ARDS - two after traumatic shock and six following septic shock. the conventional disseminated intravascular coagulation variables (fibrinogen, platelet counts, activated partial thromboplastin time, ethanol gelation test, thrombotest, normotest and fibrin degradation products) could not discriminate between ARDS and non-ARDS patients, but showed an essentially similar reaction pattern in these two groups. Antithrombin-III and plasminogen levels were significantly lower in patients with ARDS, while factor VIII-related antigen levels were significantly higher in ARDS than in non-ARDS patients. patients with septic shock run a significantly greater risk of developing ARDS (6 of 8) than those with traumatic shock (2 of 11; P less than 0.02). Furthermore, the onset of ARDS after septic shock seems to occur in a more rapid way, while ARDS following traumatic shock develops more gradually. Early ventilator treatment with positive end expiratory pressure counteracts the classical radiographic picture of ARDS with bilateral alveolar densities.

Liquoid-Induced Disseminated Intravascular Coagulation in the Blue Fox

The present experiments were performed to study the effects of a single high intravenous dose of Liquoid (10 mg/kg body weight) upon platelets, coagulation activities and hematocrit in blue foxes, and their correlation with the survival time. Both “short-living” (< 9 h) and “long-living” (24 h or more) blue foxes showed a marked consumption of coagulation factors, initial fall in fibrinogen, positive ethanol gel test and a gradual decrease in platelet counts. In addition “short-living” animals developed a marked rise in hematocrit, reflecting a considerable increase in vascular permeability. We conclude that activation of plasma proteases has as one of its effects increased permeability in microvasculatory vessels and that this may play a central role for the course and outcome of Liquoid-induced disseminated intravascular coagulation.

Fibrinopeptide A after strenuous physical exercise at high altitude.

To examine hemostasis after physical exercise at altitudes easily accessible to tourists by public transport, 20 young male volunteers were exposed to 3,457 m above sea level. Ten of them were subjected to an exhaustive exercise for about 8 min on a bicycle ergometer. The preexercise samples (n = 20) taken 1 h after arrival showed no significant alteration of coagulation compared with control values at 600 m. After the exercise the clotting times (P less than 0.001) and euglobulin lysis times (P less than 0.001) were shortened, whereas factor VIII activity (P less than 0.001) was elevated. There was, however, no significant difference in fibrinopeptide A levels between the exercise and the control group. Ethanol gelation test remained negative. We found no rise in fibrin(ogen) degradation products and fibrin(ogen) fragment E and thus conclude that there is no evidence for clinically relevant intravascular coagulation after short-term strenuous physical exercise at altitude.

Influence of brinase on fibrinogen: fibrin transition in vitro and in vivo studies. II. Induction of fibrin deposits by brinase in the kidneys of rats with inhibited fibrinolysis.

The influence of brinase on fibrinogen levels, ethanol gelation test (EGT), fibrin content of lungs and kidneys (125I-fibrinogen) and brinase inhibitor capacity was investigated in the rat. The animals were either treated with i.v. infusions of brinase (4 mg/kg), tranexamic acid (AMCA) + brinase or heparin + AMCA + brinase. A control group was given i.v. saline, a reference group AMCA + thrombin. Brinase caused a decrease in fibrinogen levels and an increase in the incidence of positive EGT, deposition of fibrin was not observed. Infusion of brinase into rats with inhibition fibrinolytic system (AMCA), caused a more pronounced decrease in fibrinogen levels, a further increase in the incidence of positive EGT and also fibrin deposition in the kidneys. In rats treated with AMCA + thrombin a similar decrease in fibrinogen levels was recorded, the EGT was positive in all animals, and extensive fibrin deposits were observed in the kidneys and lungs of the animals. Heparinization before infusion of AMCA + brinase antagonized the lowering in fibrinogen levels and the increase in incidence of positive EGT and, moreover, fibrin deposits were no longer observed.