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Biomedical subjects

U Harbrecht

Publications and source records attributed to U Harbrecht.

17 recordsLinked to original sources
PubMed2005

Heparin-induced thrombocytopenia in neurologic patients treated with low-molecular-weight heparin.

The authors prospectively studied the risk for immune-mediated heparin-induced thrombocytopenia (HIT) in neurologic patients during administration of low-molecular-weight heparin (LMWH) vs unfractionated heparin (UFH). None of 111 neurologic patients receiving LMWH developed HIT, whereas HIT occurred in 2.5% of 200 patients treated with UFH (p = 0.17). The rate of heparin-induced antibodies in patients treated with LMWH was lower than in patients treated with UFH (1.8 vs 20.5%; p < 0.001).

Adult↗
PubMed2005

Common genetic variants of homocysteine metabolism in ischemic stroke: a case-control study.

Hyperhomocysteinemia is a risk factor for ischemic stroke. We investigated five functional polymorphisms involved in homocysteine metabolism in each 159 stroke patients and controls. The folate-sensitive polymorphism methylenetetrahydrofolate reductase (MTHFR) c. 677 C > T (A222V) referred a non-significant risk of ischemic stroke (odds ratio: 1.20) in all patients, and homozygosity for MTHFR c. 677 C > T was associated with an earlier onset of stroke selectively in patients younger than 60 years (38 +/- 3 years vs. 45 +/- 1 years; P = 0.043). This study suggests that the investigated polymorphisms are no major risk factors for stroke, although MTHFR c. 677 C > T could be a minor factor of vulnerability especially in young patients (TT genotype), which might be helpful for the clinical work-up of stroke cases and for preventive dietary strategies.

Adult↗
PubMed2004

Polymorphisms in glutathione S-transferase omega-1 and AD, vascular dementia, and stroke.

BACKGROUND: Glutathione S-transferase omega-1 (GSTO1) protects from oxidative stress, a risk factor for Alzheimer disease (AD), vascular dementia (VaD), and stroke. Polymorphisms in GSTO1 might influence the function of the protein and thus the risk of AD, VaD, and stroke. METHODS: The GSTO1 gene was screened for variations. The effect of the detected polymorphisms on the risk of AD, VaD, and stroke was evaluated. CSF levels of cholesterol and plasma homocysteine levels were compared according to the GSTO1 genotype. RESULTS: Two missense polymorphisms in exon 4 of GSTO1 (Ala140Asp and Glu155DeltaGlu) were detected and tested for their association with AD, VaD, and stroke. The Asp/Asp and Ala/Asp genotypes increased the risk of stroke (p = 0.003, OR = 2.1), and the Asp/Asp genotype increased the risk of VaD (p = 0.02, OR = 2.2). GSTO1 polymorphisms did not influence the risk of AD, but the Asp allele influenced the age at onset (p = 0.05). In nondemented probands CSF levels of cholesterol were increased in carriers of the Asp/Asp genotype (p = 0.004); however, in patients with manifest dementia the authors found decreased CSF levels of cholesterol in carriers of the Asp/Asp genotype (p = 0.028). Serum homocysteine levels in stroke patients were higher in carriers of at least one Asp allele (p = 0.011). CONCLUSION: The GSTO1 Asp allele may be a genetic risk factor for cerebrovascular diseases, and might influence the course of Alzheimer disease, even though effects vary in different studies.

Adult↗
PubMed2004

Heparin-induced thrombocytopenia in neurologic disease treated with unfractionated heparin.

The risk for immune-mediated heparin-induced thrombocytopenia (HIT) in neurologic patients receiving unfractionated heparin (UFH) is not known. In a prospective study of 200 patients, the authors found a 2.5% rate of HIT and a 2% rate of HIT-associated thromboses, suggesting that neurologic patients treated with UFH are at considerable risk for development of HIT and its complications. Prevalence of heparin-induced antibodies was 20.5% and was dependent on heparin dose. It was higher in cerebrovascular than in noncerebrovascular (29.4% versus 11.2%, p < 0.01) patients.

Adult↗
PubMed2002

[Massive pulmonary capillary occlusion by microthrombi. Unexpected cause of fatal right heart failure during liver transplantation].

We report the case of a 46-year old man who developed an unexpected fatal cardiac failure during liver transplantation. Attempts at resuscitation were unsuccessful. At necropsy the lungs showed numerous microthrombi occluding small lung vessels and pulmonary capillaries. Thrombi were not found in other organs. The source of this extensive thrombus formation is not known. The thrombi could have been developed within the liver, the venous blood stream between liver and lungs or the pulmonary capillaries. In our experience, this complication is very rare, and a risk profile is not known.

Capillaries↗
PubMed2000

Neurologic complications in immune-mediated heparin-induced thrombocytopenia.

OBJECTIVE: To evaluate neurologic complications in patients with immune-mediated heparin-induced thrombocytopenia (HIT) with respect to incidence, clinical characteristics, outcome, and therapy. METHODS: One hundred and twenty consecutive patients with immune-mediated HIT were recruited over a period of 11 years and studied retrospectively for the occurrence of neurologic complications. Diagnosis of HIT was based on established clinical criteria and confirmed by detection of heparin-induced antibodies using functional and immunologic tests. RESULTS: Eleven of the 120 patients (9.2%) presented with neurologic complications; 7 suffered from ischemic cerebrovascular events, 3 from cerebral venous thrombosis, and 1 had a transient confusional state during high-dose heparin administration. Primary intracerebral hemorrhage was not observed. The relative mortality was much higher (Chi-square test, p < 0.01) in HIT patients with neurologic complications (55%) as compared to patients without neurologic complications (11%). The mean platelet count nadir in neurologic patients was 38 +/- 25 x 10(9)/l on average, and was lower in patients with fatal outcome compared to those who survived (21 +/- 13 x 10(9)/l versus 58 +/- 21 x 10(9)/l; p < 0.05, Wilcoxon test). In three patients neurologic complications preceded thrombocytopenia. There was a high coincidence of HIT-associated neurologic complications with other HIT-associated arterial or venous thrombotic manifestations. CONCLUSION: Neurologic complications in HIT are relatively rare, but associated with a high comorbidity and mortality. HIT-associated neurologic complications include cerebrovascular ischemia and cerebral venous thrombosis. They may occur at a normal platelet count.

Adult↗
PubMed2000

Segmental hepatic vein thrombosis associated with heparin-induced thrombocytopenia II.

We report the case of a 55-year-old man who developed heparin-induced thrombocytopenia II after a vertebral fracture. Autopsy revealed segmental hepatic vein thrombosis of the right lobe with subacute congestion and an activation of hepatic stellate cells. This case shows that heparin-induced thrombocytopenia II is a possible cause of the Budd-Chiari syndrome.

Anticoagulants↗
PubMed2000

Congenital deficiency of vitamin K dependent coagulation factors in two families presents as a genetic defect of the vitamin K-epoxide-reductase-complex.

Hereditary combined deficiency of the vitamin K dependent coagulation factors is a rare bleeding disorder. To date, only eleven families have been reported in the literature. The phenotype varies considerably with respect to bleeding tendency, response to vitamin K substitution and the presence of skeletal abnormalities, suggesting genetic heterogeneity. In only two of the reported families the cause of the disease has been elucidated as either a defect in the gamma-carboxylase enzyme (1) or in a protein of the vitamin K 2,3-epoxide reductase (VKOR) complex (2). Here we present a detailed phenotypic description of two new families with an autosomal recessive deficiency of all vitamin K dependent coagulation factors. In both families offspring had experienced severe or even fatal perinatal intracerebral haemorrhage. The affected children exhibit a mild deficiency of the vitamin K dependent coagulation factors that could be completely corrected by oral substitution of vitamin K. Sequencing and haplotype analysis excluded a defect within the gamma-carboxylase gene. The finding of highly increased amounts of vitamin K epoxide in all affected members of both families indicated a defect in a protein of the VKOR-multienzyme-complex. Further genetic analysis of such families will provide the basis for a more detailed understanding of the structure-function relation of the enzymes involved in vitamin K metabolism.

Blood Coagulation Factors↗
PubMed1998

Increased sensitivity of factor IX to phenprocoumon as a cause of bleeding in a patient with antiphospholipid antibody associated thrombosis.

We report one patient who presented with a spontaneous bleeding complication under phenprocoumon therapy. Oral anticoagulation was initiated due to deep-vein thrombosis which was attributed to an antiphospholipid antibody syndrome. Coagulation analysis revealed a strong and selective reduction of factor IX (F IX) activity to 1%, whereas the other vitamin K-dependent factors (II, VII, X), the prothrombin time and International Normalized Ratio (INR) were within the therapeutic range. After withdrawal of phenprocoumon, all vitamin K-dependent factors including F IX normalized. Because the patient suffered from a recurrence of thrombotic events, he was re-exposed to phenprocoumon and the disproportionate decline of F IX was observed again. These findings indicate an increased sensitivity of F IX to vitamin K antagonists, representing an uncommon mechanism associated with bleeding complications under oral anticoagulant treatment.

Adult↗
PubMed1997

Missense mutations at ALA-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy.

Bleeding complications are the most common and unwanted side-effect of oral anticoagulant therapy. We report three patients in whom mutations in the factor IX (FIX) propeptide were found to cause severe bleeding during coumarin therapy. Strikingly, the bleeding occurred within the therapeutic ranges of the prothrombin time (PT) and international normalized ratio (INR). In all three patients coumarin therapy caused an unusually selective decrease of FIX activity (FIX:C) to levels below 1-3%. Upon withdrawal of coumarin, FIX:C increased to subnormal or normal values of 55%, 85% and 125%, respectively. Analysis of the FIX gene revealed two different missense mutations affecting the Ala-10 residue in the propeptide coding region: Ala[GCC] to Val[GTC] in two patients and Ala[GCC] to Thr[ACC] in one patient. No further mutation was detected by screening 195 random blood donors for mutations at Ala-10, thus excluding a frequent polymorphism at this position. The mutation in the FIX propeptide at a position which is essential for the carboxylase recognition site causes a reduced affinity of the carboxylase enzyme to the propeptide. This effect leads to an impaired carboxylase epoxidase reaction which is decisively triggered by the vitamin K concentration. Determination of FIX and APTT in addition to PT and INR is therefore recommended in coumarin-treated patients with an uncommon bleeding pattern.

Administration, Oral↗
PubMed1992

Platelet cAMP and cGMP in essential hypertension.

Vasodilator substances released in the blood vessel wall, such as the endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2), may participate in the regulation of arterial blood pressure. However, their role in the pathogenesis of human essential hypertension to date remains unclear. For some of these factors affecting vascular smooth muscle cells, blood platelets represent a second target tissue. Thus, EDRF and PGI2 inactivate platelets by stimulation of cyclic guanosine-5'-monophosphate (cGMP) and cyclic adenosine-5'-monophosphate (cAMP) synthesis, respectively. In the present study, platelet cAMP (n = 68) and cGMP (n = 60) were determined in a control group of healthy subjects (C) and in 12 patients with untreated essential hypertension (EH). In the control group, platelet cAMP and cGMP content averaged 13.52 +/- 0.38 and 1.48 +/- 0.06 pmol/10(9) platelets and no dependence of either variable on sex or age could be established. Furthermore, cGMP levels were similar in EH as compared to the control group (1.38 +/- 0.11 pmol/10(9) platelets). However, intracellular concentrations of cAMP were significantly lower in EH as compared to C (11.22 +/- 1.37 pmol/10(9) platelets; P < .01). In addition, we investigated the stimulatory effect on cAMP of the stable PGI2 analog iloprost (10(-9), 5 x 10(-9), 10(-8), 5 x 10(-8) mol/L) in the platelets of 12 control subjects (C12) and EH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

[DTIC: effect on fibrinolysis and thrombocyte function].

Pathogenesis of Budd-Chiari-syndrome, under treatment e.g. of malignant melanoma with DTIC (dacarbacin) is still unknown. In our investigations we could not find any hint for the hypothesis that Budd-Chiari-syndrome under DTIC is caused by hemostaseological impairment.

Blood Coagulation Tests↗
PubMedDate not supplied

[Incidence of thrombophilic factor V Leiden and prothrombin G20210A mutation in Perthes disease--a pilot study].

AIM: Thrombophilic mutations may play a role in the pathogenesis of the juvenile osteonecrosis of the femoral head, Perthes' disease. We investigated whether children with Perthes' disease have an increased incidence of mutations of factor V (Leiden) and prothrombin (G2O210A), which predispose to thrombosis. METHODS: For this pilot study, we analysed the data of twenty consecutive children (16 boys, 4 girls, mean age at diagnosis 6.4 years). According to Catterall's classification of severity, 2 children were in group 1, 7 in group 2, 8 in group 3, and 3 were in the most severe group 4. Mutations of factor V and prothrombin were identified in EDTA-blood by PCR amplification, digestion with restriction enzymes, and gel electrophoresis. RESULTS: Heterozygoty for the factor V mutation was detected in two children, for the prothrombin mutation in one child. Both results did not differ significantly from the incidence in Germany, which is 0.05 for factor V mutations and 0.04 for prothrombin mutations. CONCLUSIONS: For the presented group of children with Perthes' disease, we did not find an increased rate of factor V or prothrombin mutations compared to the natural incidence. In accordance to other recent studies, our results do not support a link between inherited thrombophilic mutations and Perthes' disease.

Alleles↗
PubMedDate not supplied

[Hereditary heterozygote factor VII deficiency].

Hereditary Factor VII deficiency is one of the rare congenital coagulopathies. Prolonged prothrombin time (PT) with normal partial prothrombin time (PTT) may be an indicator for Factor VII deficiency. A family with hereditary heterozygous Factor VII deficiency is presented in whom no symptoms of a bleeding disorder were clinically detectable. A discussion of the therapeutic options follows.

Blood Coagulation Tests↗