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Biomedical subjects

M Barthels

Publications and source records attributed to M Barthels.

At least 37 records · Page 2Linked to original sources
PubMed1991

The use of high dose aprotinin in liver transplantation: the influence on fibrinolysis and blood loss.

Orthotopic liver transplantation (OLT) is frequently associated with systemic fibrinogenolysis and diffuse bleeding. At present antifibrinolytic treatment has not been initiated routinely in OLT. Therefore the influence of high dose aprotinin in OLT (2 million kallikrein inactivator units (KIU) given after induction of anesthesia followed by a 500,000 KIU/h infusion throughout the operation) on intraoperative blood loss and fibrinolysis was studied in 25 patients compared to 25 patients without aprotinin. The incidence of fibrinolysis shown in thrombelastography was 72% in the control group versus 16% in the aprotinin group. Oozing after reperfusion of the graft caused by severe fibrinolysis defined as a clot lysis index below 15% was only observed in the control group (42.8%). In contrast no significant difference was found between the groups in the course of fibrin and fibrinogen degradation product levels (FbDP, FgDP) although the mean concentrations of both parameters were evidently lower in the aprotinin treated patients. Levels of tissue-type plasminogen activator (t-PA) activity were initially high in both groups and peaked during and after the anhepatic period. After aprotinin there was a trend of lower t-PA levels which reached significance at the time of reperfusion (p less than 0.02). In both groups the course of thrombin antithrombin complex was in line with the variations of FbDP and FgDP. No correlation between thrombin formation and t-PA activity was found. Mean homologous blood requirement was reduced by 50% (5.6 +/- 4.0 vs. 11.2 +/- 8.6 units, p less than 0.005). The blood saving effect was more pronounced in the postanhepatic period (p less than 0.000001). In conclusion high dose aprotinin inhibits hyperfibrinolysis and reduces intraoperative homologous blood requirement. Therefore its routine use in OLT is recommended.

Adult↗
PubMed1991

Hemostatic studies of ex situ hepatic surgery.

Ex situ hepatic surgery, in which a diseased liver is resected from outside the body, was first reported in 1988. This study investigates the hemostatic changes occurring during such surgery in two cases. During the anhepatic period of more than 5 hours, veno-venous bypass without heparin was performed. The tests included platelet count, prothrombin activity (PT), partial thromboplastin time (PTT), fibrinogen (Fbg), factor II (F.II), factor V (F.V), and thromboelastography (TEG). Three to 4 hours after entering the anhepatic phase, marked fibrinolysis and a fall in the values of PT, Fbg and F.V. were observed. Every parameter temporarily deteriorated immediately after revascularization of the graft, however, all returned to almost normal values within 1-2 hours after hepatic reperfusion except for F.V and platelets. In conclusion, the coagulopathy during ex situ hepatic surgery is caused by the marked fibrinolysis and depletion of hemostatic factors which develop 3-4 hours after the onset of the anhepatic phase.

Adult↗
PubMed1991

Coagulation disorder during liver transplantation.

Detailed haemostatic changes were investigated during eight liver transplantations. The patients were divided into two groups; group 1 had minor operative bleeding (four cases) and group 2 had major bleeding (four cases). Group 2 had lower levels of platelets, fibrinogen, factor V (FV), and alpha 2-antiplasmin than group 1, and the thromboelastography showed fibrinolysis. In both groups, plasma tissue-plasminogen activator levels rose slightly. After revascularization of the graft liver, reductions in the values of PT, fibrinogen, FV and FVII were noted, along with a prolongation of the PTT and an increase in thrombin-antithrombin III complex levels. Plasma levels of protein C, protein S, antithrombin III, and plasminogen remained relatively stable throughout the operation. These results show that the preceding fibrinolysis and subsequent superimposed activation of the clotting system are the main causes of coagulopathy during liver transplantation, which correlate with the amount of operative haemorrhage and the abnormalities found in haemostatic tests.

Adult↗
PubMed1991

Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Relevance for the success of therapy.

BACKGROUND: It has been suggested that thrombolysis in a feedback reaction may generate pro-coagulant activities. METHODS AND RESULTS: Fifty-five patients were treated with urokinase-preactivated prourokinase (n = 35) or tissue-type plasminogen activator (n = 20) for acute myocardial infarction and underwent coronary angiography at 90 minutes and at 24-36 hours into thrombolysis, and fibrinogen (Ratnoff-Menzie), D-dimer (ELISA) and thrombin-antithrombin III complex levels (ELISA) were measured. Primary patency was achieved in 39 patients (70.9%), 13 of whom (33.3%) suffered early reocclusion. Nonsignificant decreases in fibrinogen levels were observed while D-dimer levels increased +3,008 +/- 4,047 micrograms/l (p less than 0.01), differences not being significant in respect to the thrombolytic agents or to the clinical course. In contrast, while thrombin-antithrombin III complex levels decreased -4.4 +/- 13.0 micrograms/l in patients with persistent patency, they increased +7.5 +/- 13.6 micrograms/l in case of nonsuccessful thrombolysis (p less than 0.02) and +11.9 +/- 23.8 micrograms/l in case of early reocclusion (p less than 0.001). For patients with thrombin-antithrombin III complex levels greater than 6 ng/l 120 minutes into thrombolysis, the unfavorable clinical course was predicted with 96.2% sensitivity and 93.1% specificity. CONCLUSION: Generation of thrombin, occurring during thrombolysis, is a major determinant for the success of therapy and thrombin-antithrombin III levels may serve as predictors for the short-term prognosis.

Antithrombin III↗
PubMed1990

Role of thrombolysis and thrombin in patients with acute coronary occlusion during percutaneous transluminal coronary angioplasty.

In a series of 447 patients with single vessel angioplasty, 27 (6.0%) had acute thrombotic occlusion early after the procedure. They were treated with combined intracoronary (20 mg)/intravenous (50 mg) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and repeat mild balloon inflations. Reopening of the vessel was achieved in 22 patients (81.5%). Follow-up coronary angiography 24 to 36 h later revealed reocclusion in 12 patients (54.5%). Thrombin levels measured as thrombin-antithrombin-III complex in patients with successful thrombolysis and persistent patency decreased from 8.5 +/- 11.4 micrograms/liter at baseline to 3.5 +/- 1.4 micrograms/liter 120 min after the start of thrombolysis; these levels increased from 9.4 +/- 15.0 micrograms/liter at baseline to 15.7 +/- 13.5 micrograms/liter 120 min after the start of thrombolysis in the patients with unsuccessful thrombolysis or early reocclusion (p less than 0.05). When a borderline value for thrombin-antithrombin-III complex level of 6 micrograms/liter was selected to separate the two groups of patients, patients with an unfavorable clinical course were identified 120 min after the start of thrombolysis by levels greater than 6 micrograms/liter (sensitivity 100%, specificity 92.8%). Thus, after abrupt thrombotic vessel closure during coronary angioplasty, the short-term results of thrombolysis seem to be governed by the release of thrombin. In two thirds of patients, however, the thrombin release cannot be suppressed by concomitant aspirin and heparin therapy. Even after successful reopening of the vessel these patients should therefore undergo immediate aortocoronary bypass grafting.

Angioplasty, Balloon, Coronary↗
PubMed1989

Low dose urokinase preactivated natural prourokinase for thrombolysis in acute myocardial infarction.

By inducing minimal free-fibrinolytic activity with low dose urokinase, the lag phase of prourokinase can be overcome, and the rate of thrombolysis with this substance can be strongly enhanced. The thrombolytic potency of a combination of 250,000 IU of urokinase and 2 doses of prourokinase (4.5 or 6.5 megaunits) was evaluated in an open-label, nonrandomized dose-finding study. Thirty-one patients participated. With 4.5 megaunits of prourokinase (group 1, 15 patients) patency was demonstrated angiographically at 60 minutes in 33% while with 6.5 megaunits (group II, 16 patients) 75% patency was achieved (p less than 0.01). A second angiogram recorded 24 to 36 hours after thrombolysis revealed reocclusion in 60 versus 8% of primarily patent coronary arteries (p less than 0.05). Hemostatic monitoring in both groups revealed only slight to moderate consumption of fibrinogen (-9 vs -13%), plasminogen (-29 vs -34%) and alpha 2-antiplasmin (-59 vs -63%), and an increase in D-dimers, the split products of cross-linked fibrin, to a maximum of 1.008 +/- 1.211 vs 0.547 +/- 0.684 micrograms/liter. None of these differences was significant. Bleeding complications were more frequently observed in group II (13 vs 37%) (difference not significant), but were mild and related to puncture sites, except in 1 patient with mild oozing from the gum. No major hemorrhage was observed. These results suggest that low dose urokinase preactivation enhances the thrombolytic potency of prourokinase, without affecting its high fibrin specificity. Compared to previous studies using only prourokinase, low dose urokinase preactivation reduces by 50% the prourokinase dose as required for effective thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

[Prevention of thromboembolism in surgery].

Thromboembolic complications are one of the most common complications in patients undergoing major surgery or conservative treatment in cast. The incidence of thromboembolic complications is the highest in orthopedic and trauma surgery. Stasis in the deep veins of the lower extremity, intimal damage and disorders in blood coagulation are important factors in the pathogenesis of deep vein thrombosis. The most important predisposing risk factors are age, previous thrombosis, varices and the combination of oral contraceptives and smoking. 50% of thrombosis begins intraoperatively and 80-90% in the first 3-4 days after operation. The incidence of thromboembolic complications was significantly reduced after introduction of low-dose heparin and heparin with dihydroergotamine in the perioperative regimen. Recently various investigations demonstrated that low-molecular-weight heparin (LMWH) is equally as effective as a low-dose heparin regimen in preventing postoperative thromboembolic complications. Our own management of prophylaxis of thromboembolic complications is presented. In a prospective pilot study 100 trauma patients were evaluated. 84 patients received LMWH plus dihydroergotamine (DHE), 12 patients heparin alone because of contraindications for DHE and 4 patients received a low dose continuous intravenous heparin prophylaxis because of high risk. Two deep vein thrombosis occurred, one in a patient with high risk prophylaxis and one in a patient with a subcutaneously heparin prophylaxis. No thromboembolic complications occurred in patients with LMWH + DHE prophylaxis.

Heparin, Low-Molecular-Weight↗
PubMed1987

Multicenter evaluation of a chromogenic substrate method for photometric determination of prothrombin time.

A multicenter study of a chromogenic substrate method for photometric determination of prothrombin time was conducted in order to evaluate its clinical application. Seven laboratories participated in the study using a total of 742 plasma samples from 417 patients on oral anticoagulant therapy, 261 healthy subjects and 64 patients with different diseases especially of the liver as well as 30 patients with hereditary deficiency of coagulation factors II, V, VII, X. The chromogenic PT method was compared to a standardized coagulometric PT assay which uses the same sensitive human placenta thromboplastin calibrated against international reference preparations. A high correlation of the prothrombin ratio values of the chromogenic and the coagulometric assay was obtained in 402 plasma samples (r = 0.940; y = 1.02x - 0.1). The study showed that the chromogenic PT reagent is sensitive to deficiency of the coagulation factors of the extrinsic pathway but not affected by heparin up to 1 IU/ml because of the heparin antagonist added. The precision (coefficient of variation) of the photometric method ranged between 0.6 and 3% (intraassay CV) and between 1.4 and 5.8 (interassay CV). The International Sensitivity Index (ISI) obtained for the used lot was 1.09. The therapeutical range in percentage activity for patients in a stable phase of an anticoagulant therapy was found to be from 15 to 27 percent of normal. The results of the clinical evaluation proved the good comparability of the new chromogenic PT test with coagulometric methods, its high factor sensitivity, good reproducibility and easy performance.

Anticoagulants↗
PubMed1987

[Determination of thromboplastin time with a new standardized thromboplastin from human placenta: results of a cooperative study].

In five centres a new sensitive standardized thromboplastin from human placenta (Thromborel S) for determination of prothrombin time (PT) was evaluated on plasmas from healthy subjects, from patients on oral anticoagulant therapy and from patients with different diseases, especially of the liver. The standardization of the human placenta thromboplastin (HPT) for prothrombin time determination was performed by comparison with a lot of the Reference Preparation British Comparative Thromboplastin (BCT). The obtained International Sensitivity Index (ISI) for 14 differents lots of the new thromboplastin varied between 1.04 and 1.29 (mean value: 1.16). The reagent is highly sensitive to the factors of the extrinsic coagulation pathway and is not affected by heparin at least up to 0.6 IU/ml. From the comparison with the British Comparative Thromboplastin lot No. 235, a therapeutical range for the stable phase of the oral anticoagulation of 2.4-4.0 prothrombin ratio or 15-27% of normal, respectively, was obtained. Comparison of prothrombin time determination using the Human Placental Thromboplastin and the British Comparative Thromboplastin lot No. 235 in 330 patients on oral anticoagulation showed good correlations either in "percent normal" or in prothrombin ratio.

Anticoagulants↗
PubMed1986

Thromboembolic complications in children with nephrotic syndrome. Risk and incidence.

Coagulation studies were performed in 16 children with steroid responsive minimal change nephrotic syndrome in order to elucidate the incidence of thromboembolic complications. Fibrinogen and alpha 2-macroglobulin concentrations were inversely correlated with serum albumin concentrations, antithrombin III correlated positively (p less than 0.001). Factor VIII:R:AG concentration was elevated. Coagulation disturbances in children are not less severe than in adults with nephrotic syndrome. Combined scintigraphic pulmonary ventilation and perfusion studies were employed in 26 children to detect noninvasively events of pulmonary embolism, respectively their residual changes. The lung scintigraphic investigation demonstrated a pattern consistent with pulmonary embolism in 7 patients (27.9%), residual changes in 10 (38.5%) and normal findings in 9 (34.9%). The incidence of thromboembolic complications in children with severe nephrotic syndrome is as high as reported for adults. Pulmonary symptoms may well be due to pulmonary embolism.

Antithrombin III↗
PubMed1986

Distribution of alpha-polymers and residual alpha-chains in in vitro and in vivo formed fibrin clots.

In vitro and in vivo formed fibrin clots were investigated by SDS-PAA gel electrophoresis in regard to the amount and distribution of fibrin subunits. It was found that with decreasing factor XIII levels fewer and shorter alpha-polymers were formed in vitro and more so in the exterior than in the core of a clot. Inversely the concentrations of residual alpha-chains rose. These structural changes already began at factor XIII levels of 50%. gamma-dimer formation was not influenced. Nearly all in vivo thrombi, either arterial or venous, consisted of a normal distribution of subunits, but alpha-polymerization was more extensive in the core than in the exterior parts. A significant impairment of alpha polymerization was found in extravasal clots, but not in thrombi formed during anticoagulant therapy.

Blood Coagulation↗
PubMed1986

[Cavernous hemangioma and disseminated intravascular coagulation (Kasabach-Merritt syndrome) in a newborn infant with a large ventricular septal defect].

In a 3170 g newborn with a large cavernous hemangioma at the left thigh, heart failure was evident. Echo- and angiographically a large perimembranous ventricular septal defect was found. An important a-v shunt within the hemangioma could be excluded by hemodynamic investigation and selective arteriographic examination of the vascular tumor. Thrombocytopenia present from the first day of life was only temporarily overcome by corticosteroid therapy but nevertheless consumption coagulopathy (Kasabach-Merritt-Syndrome) developed and additional therapy with heparin was necessary in order to normalize the coagulation factors. However, no regression in size of the tumor occurred over the first 8 weeks of life and a total exstirpation of the hemangioma was performed. Postoperatively no further cortison or heparin therapy was necessary. Despite vigorous medical treatment the congestive heart failure persisted. After surgical closure of the ventricular septal defect at the age of three months the infant thrived and could be discharged without pathological symptoms.

Cardiac Catheterization↗
PubMed1985

Acquired thrombin inhibitor in a patient with liver cirrhosis.

An unusual thrombin inhibitor is described in a patient suffering from liver cirrhosis, associated with a polyclonal gammopathy. In all screening tests that are based on thrombin action, the plasma clotting time was prolonged; in contrast, a test using the thrombin-like enzyme thrombin coagulase was not influenced. A specific thrombin inhibitor, present in the patient's plasma, was assumed. Fractionation experiments showed that the inhibitor was associated with the patient's IgG fraction. The IgG fraction dose-dependently inhibited the action of thrombin on fibrinogen and the inhibition of thrombin by antithrombin III, but the amidolytic activity of thrombin was only little affected.

Aged↗