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E Lechler

Publications and source records attributed to E Lechler.

At least 19 recordsLinked to original sources

Pregnancy-associated risk for venous thromboembolism and pregnancy outcome in women homozygous for factor V Leiden.

INTRODUCTION: To evaluate the pregnancy-associated risk of venous thromboembolism and the risk of stillbirth and miscarriage a multicenter, retrospective and controlled study was conducted in women carrying the homozygous factor V Leiden mutation and in an agematched control group of women from the normal population. PATIENTS AND METHODS: In 64 homozygous (median age 44 years, range 21-75 years) and in 52 control women from five different centers data on venous thromboembolism and pregnancy outcome were obtained. RESULTS: The 64 homozygous women had in total 212 pregnancies, the 52 control women had 118 pregnancies. In homozygous women 65% of pregnancies ended with delivery of a viable infant, 15% with fetal loss (3.3% stillbirth, 12% miscarriage) and 20% by pregnancy termination. In the control women 75% of pregnancies ended with delivery of a viable infant, 12% with fetal loss (1.7% stillbirth, 10% miscarriage) and 13% by pregnancy termination. The differences were statistically not significant. Venous thromboembolism occurred significantly more often in the homozygous women, in 4.2% (9/212) during pregnancy and in 4.7% (10/212) after delivery or pregnancy termination. None of the control women had a thromboembolic episode. CONCLUSION: Our data indicate that women with homozygous factor V Leiden have a high probability for a favorable pregnancy outcome. The increased risk for venous thromboembolism during pregnancy and after delivery would favor heparin prophylaxis during and after pregnancy in women homozygous for factor V Leiden.

Adult↗

Thromboembolic complications associated with the use of prothrombin complex and factor IX concentrates.

In 1994, shortly after a heat-treated prothrombin complex concentrate (PCC) had been withdrawn from the German market due to transmission of hepatitis B, the license of another brand was withdrawn, due to 3 acute fatalities associated with the use of this product. We report on the clinical data of altogether 5 patients, who died during a 3 month period in Germany after having received this brand of PCC. All patients had surgery, acquired deficiencies of coagulation factors, and underlying diseases predisposing for thrombosis or disseminated intravascular coagulation. PCC was administered for the prevention of bleeding. In three patients, a drug interaction of PCC with aprotinin may also have played a role. Several points, however, are suspicious of a major causative effect of the respective product, (a) the close temporal correlation between administration of the drug and the subsequent clinical as well as laboratory deterioration, (b) the accumulation of these adverse events in a short period of time, when the use and market share of this brand increased due to the shortage of other products, and (c) laboratory abnormalities of this brand which have been consistently observed in several in vitro studies.

Adult↗

The venous thrombotic risk in non-surgical patients: epidemiological data and efficacy/safety profile of a low-molecular-weight heparin (enoxaparin). The Prime Study Group.

In a multicentre, randomized, double-blind controlled trial comparing the low-molecular-weight heparin enoxaparin (40 mg) with a standard unfractionated heparin (Ca-heparin, 3 x 5,000 U) in deep-vein thrombosis prophylaxis in a high-risk group of 959 hospitalized medical patients, enoxaparin was at least as efficacious as standard heparin, with fewer adverse events.

Aged↗

Results of a screening for von Willebrand disease type 2N in patients with suspected haemophilia A or von Willebrand disease type 1.

A screening program for the detection of patients with von Willebrand disease type 2N (VWD 2N) was carried out in 177 unrelated patients previously diagnosed with haemophilia A and in 199 unrelated patients with VWD type 1 in comparison. By measuring the factor VIII (FVIII) binding capacity of von Willebrand factor (VWF), we detected 13 patients with VWD 2N within 8 unrelated families. The former diagnosis has been haemophilia A in 5 index patients, and VWD in the remaining 3. Included in this study were 14 patients with suspected haemophilia A, whose molecular analysis for mutations in the FVIII gene was unsuccessful. Five of them had VWD 2N. In all patients with the VWD 2N phenotype we were able to identify specific molecular defects in the corresponding DNA sequence of the FVIII binding domain of VWF. The most common defect was R91Q. Four patients from 4 families were homozygous for R91Q, six patients from 3 families were compound heterozygous for R91Q and a silent yet unidentified allele. The VWD 2N phenotype of father, daughter, and son in one family, was based on 2 different genotypes, compound heterozygosity for R91Q and VWD type 1 in the father and the daughter, and homozygosity for R91Q in the son. Two patients from one family were compound heterozygous for T28M and delta C2680-2685 in exon 18, and one patient was compound heterozygous for a novel candidate missense mutation in exon 18(E24K) and delta C2680-2685 in exon 18 which is regarded the most common defect causing severe VWD type 3. FVIII:C values of 0.07 and 0.14 IU/ml were observed in patients with the genotype T28M/delta C2680-2685 whereas in patients being homozygous or compound heterozygous for R91Q, FVIII:C was 0.19 +/- 0.071 IU/ml. In contrast to the other genotypes, E24K/delta C2680-2685 is correlated with a more severe haemophilic phenotype with a FVIII residual activity of only 0.01-0.02 IU/ml. This emphasizes the need for inclusion of the factor VIII binding assay in the diagnostic workup of suspected haemophilia A.

Adult↗

High rate of false positives in blood donor screening for antibodies to hepatitis C virus. Cause of underestimation of virus transmission rate?

Anti-hepatitis C virus antibody screening of blood donors in different countries revealed prevalences ranging from 0.4-1.4%. These results were obtained with an enzyme immunoassay based on a recombinant hepatitis C virus antigen. We applied a specific inhibition assay (neutralization assay) and a recombinant immunoblot assay to determine the specificity of positive reactions in the enzyme immunoassay. Of 2836 blood donor sera tested, 10 (0.35%) were reactive in the enzyme immunoassay, however, only 3 sera (0.1%) proved to be specifically anti-HCV positive in the inhibition assay. The recombinant immunoblot assay gave similar results. The prevalence of anti-hepatitis C virus antibodies among blood donors has been overestimated in recent publications. Furthermore the high rate of false positives in the enzyme immunoassay may explain reports claiming that only a minor part of EIA positive blood units transmitted the hepatitis C virus to recipients. The inhibition assay was also applied to sera of haemophiliacs and of patients with hepatopathy which had reacted positively in the anti-hepatitis C virus antibody enzyme immunoassay. The anti-hepatitis C virus specificity was confirmed for all sera from the haemophiliacs group (100%) and for 77% of the hepatopathy patients group. Thus, the anti-hepatitis C virus enzyme immunoassay has a high predictive value when it is used to screen groups with high risks of parenteral hepatitis C virus infection, however, its predictive value is very low when it is used for blood donor screening.

Antigens, Viral↗

[Treatment of arterial occlusions of the lower extremities using 2-stage local application of urokinase].

We report the results of a 2-phase urokinase protocol for treatment of 28 arterial occlusions of the lower extremities. 26 patients, aged 43-86, with up to 6 weeks old occlusions were treated. In Phase I (average duration 2.7 h) the urokinase solution was injected in intervals directly into the occlusion-material via a F-5 catheter (120,000 U/h). In the following phase II (average duration 26.1 h) 100,000 U/h were given as a continuous arterial infusion and a full heparin regimen was started. In 86% of the treatments there was an improvement as shown by angiography. 75% of the patients could be released from the hospital without a further surgical revascularisation. Alterations of the systemic coagulation-system and bleeding-complications at the puncture site must be expected.

Aged↗

Plasminogen hemizygosity. Detection of a silent allele in 7 members of a family by determination of plasminogen phenotypes, antigenic levels, and functional activity.

The accumulation of the homozygous plasminogen (PLG) variant A3 in 4 siblings of a family led to the detection of 5 cases of apparent inverse homozygosity of PLG phenotypes which seemed to exclude paternity. Determination of 22 blood group markers and HLA typing, but under exclusion of PLG phenotypes, confirmed paternity in all cases (biostatistical probability of paternity greater than 99.9985%). Comparing the results of 'Western blots' with functional-caseinolytic phenotyping, the existence of inactive plasmin, as described earlier, could be excluded. Besides inverse homozygosity the assumption of a silent allele was confirmed by reduction of PLG antigenic levels and functional activities to approximately 50% of normal range. The PLG phenotype A in 1 individual with anamnestic thrombosis, reduced values of PLG antigen, and reduced functional activity, although in accordance with Mendelian inheritance, was also considered as indicative for PLG hemizygosity.

Alleles↗

[Hemophilia and HTLV-III infection].

The recognition of AIDS in several hemophiliacs in the U.S.A. in 1982 has contributed to the understanding that this disease may be transmitted by blood and blood products and that it is of infectious nature. American factor VIII and factor IX concentrates as well as the high portion of American plasma used in the production of further concentrates in Germany led to the rapid spread of this infection in German hemophiliacs. More than 50% of the patients suffering from severe hemophilia proved positive to anti-HTLV III. About 1% of these patients developed AIDS, and some of them already died. The absence of Kaposi's sarcomas in hemophiliacs remains unexplained. Virus inactivation by means of heat treatment of the concentrates by now most probably prevent further infections with the AIDS virus. probably prevent further infections with the AIDS virus.

Acquired Immunodeficiency Syndrome↗

Prevalence of antibodies to human T-lymphotropic virus-III (HTLV-III) in hemophiliacs and other patients chronically substituted with blood products.

The prevalence of antibodies to human T-lymphotropic virus III (HTLV-III) was determined in a total of 140 hemophiliacs and 36 polytransfused patients from three medical centers by an enzyme linked immunosorbent assay (ELISA) and confirmatory tests. 58 hemophiliacs (41.4%) were seropositive. In all instances where the origin of the coagulation factors given to these patients could be determined, blood products came from the United States. In addition, 2 of 36 polytransfused patients, mostly with acute leukemias, who were transfused with blood products from local donors were positive for HTLV-III antibodies. No HTLV-III antibodies were detected in 237 blood donors selected in part from the donor pool of the polytransfused patients.

Antibodies, Viral↗

Prevalence of antibodies to HTLV-III in AIDS risk groups in West Germany.

The prevalence of antibodies to human T-lymphotropic virus III was determined in acquired immunodeficiency syndrome (AIDS) risk groups by an enzyme linked immunosorbent assay and confirmatory tests in four different areas in West Germany. Twenty-four of 28 homosexual AIDS patients (86%), 24 of 33 homosexual patients with lymphadenopathy syndrome or AIDS related complex (73%), and 44 of 113 asymptomatic homosexuals at risk for AIDS (39%) were seropositive. In three groups of hemophiliacs, 8 of 35 in 1983 (23%), 25 of 65 in early 1984 (39%), and 19 of 23 in late 1984 (83%) showed positive results. Two sera from 36 polytransfused patients were also positive, whereas 36 selected blood donors, and 32 healthy laboratory and clinical personnel were all negative. Also no human T-lymphotropic virus III antibodies were detected in sera of 187 prostitutes in the Munich area.

Acquired Immunodeficiency Syndrome↗