Biomedical subjects

I Pabinger

Publications and source records attributed to I Pabinger.

At least 91 records · Page 5Linked to original sources

PubMed1994

The risk of thromboembolism in asymptomatic patients with protein C and protein S deficiency: a prospective cohort study.

BACKGROUND: Prospective studies on the incidence of thrombosis in asymptomatic individuals with hereditary protein C- or protein S deficiency have not been performed so far. OBJECTIVE: We have carried out a prospective cohort study in 44 asymptomatic protein C- and protein S deficient subjects and in 49 asymptomatic non-deficient relatives (age at study entry > 14 years) of symptomatic deficient patients. METHODS: 20 asymptomatic protein C deficient (median age 20 years) and 24 asymptomatic protein S deficient patients (median age 21.5 years) were prospectively followed and compared with 20 asymptomatic non-deficient relatives (median age 25 years) of protein C- and 29 (median age 27 years) of protein S deficient patients. The total observation period was 118.8 patient years for protein C deficient and 92.8 for protein S deficient patients. Patients were not on anticoagulants except for short duration in case of high risk situations. RESULTS: Eight thromboembolic events (1 pulmonary embolism, 1 deep vein thrombosis + pulmonary embolism, 3 deep vein thrombosis, 1 caval vein thrombosis and 2 superficial vein thrombosis) occurred in 6 deficient patients. The incidence of thromboembolism was 2.5% per patient year for protein C deficient and 3.5% per patient year for protein S deficient patients. 4 events occurred spontaneously, in 2 patients thromboembolic events were triggered by high risk situations (caesarean section, minor trauma). In the controls no thromboembolic events occurred. The probability for thromboembolism was significantly higher in protein C and protein S deficient patients compared to the control group (Wilcoxon test, p = 0.002, log rank test, p = 0.001). One major and 5 minor uneventful surgeries were carried out in the deficient patients using heparin prophylaxis. 1/8 pregnancies was complicated by superficial vein thrombosis during the second trimester despite prophylactic heparin administration. The same pregnancy was complicated by pulmonary embolism 5 weeks after delivery after discontinuation of heparin. CONCLUSIONS: Asymptomatic deficient relatives of symptomatic patients with protein C or protein S deficiency are at an increased risk of thrombosis compared to nondeficient individuals. Prophylactic treatment seems to be highly effective in high risk situations.

Adolescent↗

PubMed1994

Thrombotic risk of women with hereditary antithrombin III-, protein C- and protein S-deficiency taking oral contraceptive medication. The GTH Study Group on Natural Inhibitors.

The thrombotic risk of women with a heterozygous natural clotting inhibitor deficiency taking oral contraceptives (OC) has not been evaluated. Therefore, a retrospective collaborative controlled cohort-study was carried out in 8 coagulation laboratories and thrombosis units in Austria, Germany and Switzerland. The incidence of thromboembolism in 48 females heterozygous for hereditary type I deficiency of antithrombin III (n = 15), protein C (n = 16) or protein S (n = 17), who had taken OC at least once in their life were compared with that of 48 deficient women, who had never taken OC (controls). Diagnosis of the deficiency state was made in the participating centers. Data on the onset and duration of OC intake and the date and site of thrombotic events were obtained from a questionnaire filled in by the patient or a physician during a visit at a participating center. The observation period in the OC patients was started with onset of OC intake and was terminated when a thromboembolic event had occurred or when OC medication were discontinued. In the patients without OC, the observation period began at an age matched to that of the OC patient and ended when a thromboembolic event had occurred or was continued as long as the corresponding OC patient was on treatment. In AT III-deficient females the probability for thrombosis was significantly higher for patients taking OC compared to the non-OC-patients (Wilcoxon test p = 0.004, Log Rank test p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗

PubMed1993

Transient lupus anticoagulant associated with hypoprothrombinemia and factor XII deficiency following adenovirus infection.

A potent lupus anticoagulant (LA) was detected in four children, 1 week after the clinical onset of an adenovirus infection. The adenovirus infection was documented by direct virus detection in the stool of one patient and serologically in the others. None of the children had elevated titers of IgM- and only one of IgG-anticardiolipin antibodies (ACA). All patients had a marked reduction of prothrombin activity as well as antigen. Prothrombin-antibody complexes were demonstrated in the patients' plasma or mixtures of patient and normal plasma. Factor XII activity was moderately reduced in three of the patients. All coagulation abnormalities returned to normal within 4-12 weeks. Localized bleeding was observed in two cases, but there was no generalized bleeding tendency or evidence of thrombosis.

Adenoviridae Infections↗

PubMed1993

Identification of nine novel mutations in type I antithrombin deficiency by heteroduplex screening.

We have utilized DNA heteroduplex detection as a method for screening sequences of the antithrombin (AT) gene for the presence of mutations. Affected individuals from 41 kindreds with type Ia antithrombin deficiency were investigated. Heteroduplexes were detected in 12 cases; direct sequencing of the appropriate exons revealed nine cases with novel mutations, and two with previously described mutations. In addition, a new polymorphism in the 5' untranslated region was characterized. The defects included minor insertions and deletions which lead to the removal of intact codons or premature termination, and single base substitutions leading to premature termination or amino acid substitution. In all cases, the affected individuals were heterozygous for the defect and variant AT protein was not detected. In keeping with previous reports the defects associated with type Ia AT deficiency are extremely heterogeneous, the vast majority being point mutations. This study also demonstrates the efficiency of hydrolink gel electrophoresis as a method of screening for unknown mutations by heteroduplex detection.

Antithrombins↗

PubMed1993

Postpartum factor VIII inhibitors. Report of two cases with special reference to the efficacy of various treatments.

Two cases of postpartum inhibitors to F VIII are described. One patient had a severe bleeding tendency (iliopsoas bleeding, forearm bleeding). The maximum inhibitor titer was 800 BU/ml in case 1 and 120 BU/ml in case 2. Bleeding was controlled by treatment with human and porcine factor VIII concentrate and with activated prothrombin complex concentrate (FEIBA, Immuno AG, Vienna, Austria) in case 1, while no replacement therapy was given in case 2. Prednisone (given in both cases) and high-dose immunoglobulin (given in case 2) was without effect. Cyclophosphamide (100 mg per day), combined with small doses of prednisone led to complete disappearance of the inhibitor and normalization of factor VIII in case 1. In the other patient who refused treatment with cyclophosphamide the inhibitor titer remained high over a period of 13 months.

Adult↗

PubMed1992

Recurrent, isolated factor X deficiency in myeloma: repeated normalization of factor X levels after cytostatic chemotherapy followed by late treatment failure associated with the development of systemic amyloidosis.

We describe the case of a 64-year-old woman with isolated severe factor X deficiency associated with kappa light chain myeloma. At the time of diagnosis there was no evidence for amyloidosis. Complete remission (CR) of myeloma as well as normalization of factor X levels were achieved after cytostatic chemotherapy. Subsequently, factor X deficiency recurred twice without any evidence for relapse of myeloma. The first time factor X normalized again following cytostatic treatment, the second time, however, factor X deficiency was refractory to chemotherapy. Finally, relapse of myeloma became evident associated with rapidly progressing, systemic amyloidosis, which was fatal within a few months. Initially, factor X infusion studies showed a normal recovery, but when amyloidosis became overt the recovery decreased to 0%. We assume that factor X deficiency was due to a binding of factor X to kappa light chains associated with the proliferation of the malignant myeloma cell clone.

Amyloidosis↗

PubMed1992

Hereditary protein C-deficiency: laboratory values in transmitters and guidelines for the diagnostic procedure. Report on a study of the SSC Subcommittee on Protein C and Protein S. Protein C Transmitter Study Group.

A multicenter study on protein C-antigen and -activity values was carried out in transmitter patients with hereditary protein C deficiency (diagnosis established by pedigree analysis) and in normal controls in order to (1) establish the range of protein C levels in genetically determined heterozygotes and (2) to evaluate the usefulness of statistical procedures to discriminate between protein C deficient patients and controls. In transmitters absolute protein C activity values ranged from 19 to 82% and antigen values from 22 to 88.5%. Most transmitter patients could clearly be differentiated from the control group. However, in some transmitter patients values of protein C were within the range of the control group. The discrimination between transmitters and controls could be improved by statistical procedures. Using tolerance ellipses the overlapping area of the two groups was smallest when (factor II antigen+factor X antigen)/2 was plotted against protein C antigen. To specify the degree of uncertainty likelihood ratios were calculated to obtain the posterior probability for an individual for being deficient or not. In quadratic discriminant analysis the best discrimination between transmitters and controls was obtained using protein C activity versus factor X antigen and protein C antigen versus factor X antigen. Based on these analysis an equation was derived, which allows the calculation of the likelihood ratio favouring deficiency or non-deficiency in an individual.

Antigens↗

PubMed1992

Multicenter evaluation of three commercial methods for measuring protein S antigen.

This collaborative study was designed to assess the performance of commercial methods for protein S (PS) antigen measurement. Twenty-five different samples were distributed deep-frozen (24 plasmas) or lyophilized (one plasma) to five laboratories. They were analyzed blind in each laboratory by the method used locally and by three commercial methods which included two electroimmunoassays (EIA), Asseraplate-PS (Diagnostica Stago), Rellplate-S (American Diagnostica) and an ELISA system, Asserachrom-PS (Diagnostica Stago). 1. Reproducibility. Average between-laboratory coefficients of variation were 15.4%, 17.6% and 25.3% for Asserachrom-PS, Asseraplate-PS and Rellplate-S. 2. Specificity. Results of all methods showed that PS is underestimated when C4b binding protein is high. This influence was particularly evident for the ELISA Asserachrom-PS and disappeared when the antibody-antigen incubation period was prolonged to overnight. 3. Sensitivity. In all laboratories ELISA detected even the lowest PS concentration (4 U/dl), whereas the two EIAs were less sensitive (lower detection limit 14 U/dl). All methods and laboratories correctly diagnosed a plasma sample from a PS congenitally deficient patient. Conclusions. This study shows that better standardization of PS immunoassays is necessary to improve accuracy and reduce interlaboratory variability before a candidate plasma standard can be successfully calibrated in an international collaborative study.

Anticoagulants↗

PubMed1992

Cerebral sinus thrombosis in a patient with hereditary protein S deficiency: case report and review of the literature.

Hereditary protein S deficiency is an established risk factor for venous thrombosis. The common sites of thrombosis are the deep leg and pelvic veins. We report on a 38-year-old female patient with hereditary protein S deficiency and a previous history of deep leg vein thrombosis, who developed thrombosis of the cerebral straight and superior sagittal sinus while taking oral contraceptives. The diagnosis was established by computerized tomography and carotid angiography. Lysis of the thrombus occurred during heparin treatment. The hereditary nature of protein S deficiency was documented by family studies, since nine additional family members deficient in protein S were identified. Nineteen published cases of cerebral vein thrombosis and a deficiency of either anti-thrombin III, protein C, or protein S were reviewed. Compared with patients without a deficiency state, the clinical features of cerebral vein thrombosis were similar except for an earlier onset and a positive medical history of venous thromboembolic events in a considerable number of patients.

Adult↗

PubMed1992

Drug-testing in patients with pulmonary hypertension of unknown cause.

The acute haemodynamic effects of seven different drugs were serially evaluated in eight patients suffering from pulmonary hypertension of unknown cause. The following drugs were tested in randomized order: nifedipine, amrinone, isoproterenol, captopril, prostacyclin, dihydralazine and nitroglycerin. Only a reduction in pulmonary vascular resistance (PVR) of more than 30% of baseline was considered a satisfactory response. Overall, the decrease in PVR ranged from 9 +/- 12% (nitroglycerin) to 38 +/- 23% (prostacyclin). However, marked inter- and intra-individual variability in the efficacy of all drugs was observed, making cross reactivity totally unpredictable. The number of responders for each drug varied between five (prostacyclin) and zero (dihydralazine, nitroglycerin). Conversely, a maximum of three drugs was capable of eliciting a response in an individual patient, with only two out of eight patients being total non-responders. A reduction in PVR of more than 30% (n = 16) was associated with a significant decrease in mean pulmonary artery pressure (49.1 +/- 8.2 versus 39.4 +/- 6.4 mmHg) and a significant increase in cardiac index (2.5 +/- 0.6 versus 3.4 +/- 0.8l.min-1.m-2). Overall, none of the drugs tested proved to be clearly superior. However, because of marked inter- and intra-individual variability, the therapeutic approach must be based on trial and error and the evaluation of all drugs is indicated if one fails.

Adult↗

PubMed1992

Factor VIII concentrates in HIV-1-positive hemophiliacs--is pure better?

39 human immunodeficiency-virus-1 (HIV-1)-positive hemophiliacs who had been regularly treated with non-virus-inactivated intermediate-purity factor VIII concentrates were divided into two groups. Group A consisted of 21 patients with a CD4/CD8 cell ratio of less than 1.0 and group B of 18 patients with a CD4/CD8 cell ratio of greater than 1.0. All patients of group A were switched to a high-purity virus-inactivated factor VIII concentrate, whereas patients of group B continued to receive the intermediate-purity concentrate. There was no significant difference in the average decline of CD4 cells between the two groups during the observation period. 9 patients of group A and 4 patients of group B developed AIDS. 5 patients of group A but 11 patients of group B remained clinically asymptomatic. We conclude that the 15-fold increase in purity of the factor VIII concentrate had no apparent beneficial effect on the CD4 cell counts in this patient group.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Hereditary deficiency of antithrombin III, protein C and protein S: prevalence in patients with a history of venous thrombosis and criteria for rational patient screening.

Data in the literature on the prevalence of hereditary deficiency of the natural coagulation inhibitors are conflicting. We conducted a prospective study on 680 consecutive patients with a history of venous thrombosis to determine the prevalence of hereditary deficiency of antithrombin III (AT III), protein C(PC) and protein S(PS) and to establish selection criteria for rational patient screening. The mean age of the patients at investigation was 44.3 +/- 15.4 years, while that at the first thrombotic event was 38.5 +/- 14.8 years. The total prevalence of inhibitor deficiency states was 48/680 (7.1%). 19/680 patients (2.8%) had AT III-deficiency, 17 (2.5%) PC-deficiency, nine (1.3%) PS-deficiency and three (0.4%) a combined deficiency. In 37/48 deficient patients family studies were performed and the hereditary nature was established in 19 cases (2.8% of total patient population, six with AT III-deficiency, eight with PC-deficiency, four with PS-deficiency and one with a combined deficiency). Family studies in these 19 patients revealed 46 additional individual patients with a hereditary deficiency state. A positive family history was found in 15/19 (79%) with a proven hereditary deficiency state, in 153/619 (25%) of non-deficient patients and in 11/29 (38%) of deficient patients without established hereditary nature. The mean age at the first thrombotic event was significantly lower in patients with a hereditary deficiency state (26.8 years) compared with the other two groups (39.0 and 39.7 years, respectively). In all patients with a hereditary deficiency the first thrombotic event occurred before the age of 45 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

[Problems of long-term therapy with anticoagulants].

Oral anticoagulants are highly effective for the prevention of recurrence of venous thromboembolism and of thromboembolic complications in rheumatic and non-rheumatic atrial fibrillation, dilated cardiomyopathy and in patients with prosthetic heart valves, but less effective for prevention of arterial thrombosis. Bleeding is the main side effect, the risk of fatal bleeding is 0.2 to 0.4% per year, depending on the intensity of treatment. The problem of the standardization of the prothrombin time determination has been solved by the introduction of the international normalized ratio. Recent studies have shown that a lesser degree of anticoagulation (INR 2.0 to 3.0) is sufficient to prevent venous thromboembolism and cardiac emboli. The measurement of activation markers of coagulation will probably allow a more rational monitoring in the near future.

Administration, Oral↗

PubMed1991

Coincidence of acquired factor-X deficiency and disseminated intravascular coagulation in patients with acute nonlymphoblastic leukemia.

Systematic clotting studies were performed in 157 patients with de novo acute nonlymphoblastic leukemia (ANLL) prior to treatment. Sixteen patients had disseminated intravascular coagulation (DIC). Three of the patients with DIC (two with M3, one with M5 leukemia) had a marked isolated factor-X deficiency (factor X:C 21%, 33%, and 41%, respectively). Another four patients had a mild isolated factor-X deficiency (factor X:C 55%-68%). In these seven patients the remaining liver-synthesized clotting factors (factors II, VII, IX, V) as well as serum albumin and cholinesterase were within the normal range. Liver disease or vitamin-K deficiency could therefore be excluded. In none of the 141 patients without DIC was a marked isolated factor X deficiency observed; two patients had moderately reduced factor X:C levels but normal liver-synthesized proteins. Induction treatment led to the control of DIC with an almost parallel increase of fibrinogen and factor X up to normal in all patients with factor-X deficiency who achieved complete remission. In one patient, recurrence of leukemia was associated with reoccurrence of DIC and marked factor-X deficiency. We conclude that there is a coincidence of isolated factor-X deficiency and DIC in some patients with ANLL. In some patients, this factor-X deficiency may be severe enough to contribute to the bleeding tendency.

Adult↗

PubMed1991

Fertility, pregnancies and offspring complications after bone marrow transplantation.

Hormonal assessment including luteotropic hormone (LH), follicle stimulating hormone (FSH), testosterone (T), oestradiol and sex hormone binding globulin was performed 1-6 years after allogeneic, syngeneic and autologous bone marrow transplantation in nine patients with severe aplastic anaemia (SAA) and 14 patients with haematological malignancy (HM). Among nine allografted SAA patients, seven aged less than 26 years showed normal gonadal function while two women above 26 years had premature ovarian failure. All eight female patients transplanted for HM had premature ovarian failure. Among six male patients transplanted for HM, four have elevated FSH but normal LH and T levels, while two have normal LH, FSH and T levels or elevated LH and FSH levels but decreased T levels, respectively. Three patients transplanted for SAA (two female, one male), but none of those transplanted for HM, parented four healthy children. A high incidence of offspring complications was noticed, including (i) persistence of fetal circulation syndrome, (ii) erythroblastosis fetalis, and (iii) prolonged newborn icterus. One female patient transplanted for SAA had an abortion in the 25th week of gestation. These observations confirm previous reports on recovery of fertility, mainly in younger patients transplanted for SAA; there was, however, an unexpectedly high incidence of pre-, peri- and postpartum complications in the offspring of bone marrow graft recipients.

Adolescent↗

PubMed1990

Azidothymidine (AZT) in the treatment of symptomatic HIV-1-infected hemophiliacs.

Twenty-one immunodeficiency virus 1 (HIV 1)-positive hemophilic patients were treated with Azidothymidine (AZT) for symptomatic HIV infection. The median observation period was 20.5 months. At 25 months the probability of survival was 82%, the probability of progression of disease from CDC III or IV C2 to IV C1 (AIDS) was 20% in patients on continuous AZT treatment and 50% in patients with interruption of treatment. Three patients developed severe leukopenia and 3 patients severe anemia during AZT treatment. In 1 patient a dose-dependent striking increase of transaminases during AZT treatment was observed. In 7 patients treatment was interrupted, in 1 patient because of anemia, in 1 because of pruritus and in 5 patients because of non-compliance. No significant changes in the consumption of clotting factor concentrates and number of bleeding episodes before and during AZT treatment were noted. We conclude, that both hematological and non-hematological side effects of AZT in HIV 1-infected hemophilic patients are comparable to those seen in other risk groups. AZT does not increase the bleeding tendency in this patient group.

Adolescent↗

PubMed1990

Diagnosis of protein C deficiency in patients on oral anticoagulant treatment: comparison of three different functional protein C assays.

The efficacy of three different protein C activity assays and of protein C antigen determination for the diagnosis of protein C deficiency was studied in 13 protein C deficient patients (11 with type I, 2 with type II deficiency) and in 51 presumably non-deficient patients (control group), both groups being on oral anticoagulant (OAC) treatment. For protein C activity measurement (1) the assay according to Francis (slightly modified) with thrombin activation and measurement of activated protein C in the aPTT system, (2) an assay using Protac activation and chromogenic substrate (Protac-CS) and (3) an assay using Protac activation and the aPTT system (Protac-PTT) were used. Protein C antigen was determined by Laurell immunoelectrophoresis. The three activity assays gave different results, with the highest values obtained by the Protac-CS assay and the lowest values by the Protac-PTT assay. The Francis assay gave intermediate results. Protein C activity and antigen values were significantly lower in protein C deficient patients compared to the control group. Protein C activity tests had a higher discriminative power than the antigen determination. After taking into account the intensity of treatment, by the Francis assay all deficient and non-deficient patients were correctly classified, by the Protac-CS and the Protac-PTT assay 2 and 4 patients, respectively, were misclassified and by the antigen assay 8 patients were misclassified. Calculation of the ratios of protein C activity to factor II activity was of high discriminative power. We conclude that for diagnosis of protein C deficiency protein C activity tests are superior to antigen determination not only in type II but also in type I deficient patients.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Hydroxycoumarins↗

PubMed1990

Effect of conjugated estrogens on platelet function and prostacyclin generation in CRF.

In a double-blind, randomized, placebo-controlled cross-over study, we investigated in seven patients with chronic renal failure the effect of conjugated estrogens (0.6 mg/kg/day for 5 days) on template bleeding time and on thromboxane A2 (TxA2), beta-thromboglobulin (beta-TG) and prostacyclin (PGI2) concentrations in blood emerging from the template bleeding time incisions. Administration of conjugated estrogens resulted in a significant shortening of the bleeding time in six out of seven patients with a maximum effect 7 and/or 14 days following treatment. Both TxA2 (measured as thromboxane B2, TxB2) and beta-TG release in bleeding time blood were significantly higher following administration of conjugated estrogens as compared to placebo administration. No difference was seen in endothelial PGI2 (measured as 6-keto-prostaglandin F1 alpha) formation when patients were treated with conjugated estrogens as compared to placebo administration over the 28 day observation period. We conclude that in patients with chronic renal failure, infusion of conjugated estrogens results in a significant shortening of the bleeding time together with an increase in platelet reactivity, as indicated by an increase of TxA2 and beta-TG concentration in the microvasculature. No effect was seen on PGI2 production, thereby excluding a major effect on vascular prostaglandin metabolism.

6-Ketoprostaglandin F1 alpha↗