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Biomedical subjects

H Pollmann

Publications and source records attributed to H Pollmann.

At least 19 recordsLinked to original sources
PubMed2007

Von Willebrand disease within the collective of haemophilic patients as reason for unexpected bleeding episodes.

In the treatment of haemophilia A and B, recombinant coagulation factors are increasingly replacing plasma-derived factor VIII and IX concentrates. Although provided with replacement therapy, individual patients may exhibit bleeding episodes, which are difficult to control. These bleeds may be caused by von Willebrand disease (VWD) as an additional underlying coagulation disorder. We report in the present study our experience that in the collective of haemophilic patients, VWD must be anticipated at least with the same order of magnitude as it appears in a normal healthy population. Among the patients at our treatment centre, two patients (1.5%) were identified as suffering from VWD in addition to haemophilia A. In the collective of haemophilia B patients at our centre, three patients (10%) with VWD were found. Two of these patients exhibited unexpected severe bleeding episodes, which could only satisfactorily be controlled by the administration of Haemate-P or DDAVP supplementary to the recombinant coagulation factor concentrate.

Blood Coagulation Tests↗
PubMed2006

Neurophysiological abnormalities in HIV-infected long term survivors.

BACKGROUND: HIV is a neurotropic virus causing neuronal damage independent of opportunistic infections. A subgroup of patients suffer from long-term infection without developing significant disease symptoms requiring antiretroviral therapy (long-term survivors, LTS). We investigated the prevalence and severity of neurophysiological abnormalities in LTS. METHODS: The outpatient database of the Dept. of Neurology, University of Münster, was searched for HIV-infection LTS (infection for more than 9 years, no antiretroviral therapy since infection, stable CD4-positive lymphocyte count of more than 400/ul). Their neurophysiological test results (nerve conduction studies, event-related potentials, EEG) were compared to a control group of patients with similar disease duration not fulfilling the criteria for LTS. RESULTS: Sixteen LTS patients and 22 control patients were investigated. Median age at examination was 35 years. There were no significant differences between the groups regarding age, sex, duration of the disease and way of infection. By definition, CD4+-lymphocyte counts differed between LTS and both control groups. Standard nerve conduction studies of the peroneal or the sural nerve were abnormal in 1 LTS patient and 3 control patients. Sural nerve paired stimulation amplitude showed abnormal findings in 4 LTS patients and 4 control patients. P300 latency was prolonged in 4 LTS patients and 4 control patients. EEG background frequency was normal in all but one patient (LTS). There were no differences between groups regarding any of the parameters. CONCLUSION: Sensitive methods showed subtle affection of the nervous system in HIV-infected outpatients infected for more than 9 years. However, there was no difference between patients fulfilling accepted criteria of LTS, and those who did not. LTS most likely form the extreme end of a continuum of disease severity.

Adult↗
PubMed2006

Factor X deficiency: clinical manifestation of 102 subjects from Europe and Latin America with mutations in the factor 10 gene.

Inherited factor X deficiency (FXD) is a rare (1:1,000,000) recessive bleeding disorder. The clinical and laboratory phenotypes of FXD are poorly correlated and few regional studies on the genotype and the clinical manifestations of FXD are known. To understand the association between clinical manifestations and causative genotype, detailed evaluation of bleeding pattern in a high number of patients is needed. This international study analysed the phenotype and genotype of 102 subjects from Central Europe (Germany, Poland and Slovakia) and Latin America (Costa Rica and Venezuela) with causative mutations in the F10 gene, via sequencing. Twenty-eight homozygous, seven compound-heterozygous and 67 heterozygous FXD subjects were characterized. Twenty-nine different causative mutations, including 15 novel mutations, were analysed. Spontaneous bleeding symptoms in 42 symptomatic individuals (26 homozygous, seven compound heterozygous and nine heterozygous) comprised easy bruising (55%), haematoma (43%), epistaxis (36%), haemarthrosis (33%), intracranial haemorrhage (ICH; 21%), and gastrointestinal (GI) haemorrhage (12%). The manifestation of bleeding symptoms in 9 of 67 (13%) symptomatic heterozygous subjects is described. The bleeding patterns of the enrolled patients showed differences that are associated with the types of F10 mutation, and the corresponding genotypes. The homozygous patients were evaluated for genotype-phenotype correlation. The results suggested that ICH seems to be associated with the F10 mutation Gly380Arg, and possibly with the mutations IVS7-1G>A and Tyr163delAT. A tentative association of other mutations to severe symptoms such as haemarthrosis and GI haemorrhage is reported. The severity of FXD, the genotype-phenotype association, and the results of regional studies are discussed.

Adolescent↗
PubMed2003

Haemophilia and thrombophilia. What do we learn about combined inheritance of both genetic variations?

UNLABELLED: For the study presented here 135 pediatric PUP patients with haemophilia consecutively admitted to German pediatric haemophilia treatment centers were investigated. In addition to factor VIII activity, the factor V (FV) G1691A mutation, the factor II (FII) G20210A variant, methylenetetrahydrofolate reductase (MTHFR) T677T genotype, elevated lipoprotein a (Lp a), antithrombin, protein C, and protein S were investigated. 103 out of 122 HA patients (FVIII activity <1%) were suffering from severe HA. The prevalence of prothrombotic risk factors in children with severe haemophilia A (HA) did not differ from previously reported data: FV GA 5.8%, FII GA 3.9%, MTHFR TT 10%, elevated Lp a 7%, protein C type I deficiency 1.1%. The first symptomatic bleeding leading to diagnosis of severe haemophilia occurred with a median age of 1.6 years (range: 0.5-7.1 years) in children carrying prothrombotic risk factors compared to non-carriers (0.9 years (0.1-4.0; p = 0.01). Two patients presenting with neonatal stroke due to elevated Lp a and the FII GA variant showed haemorrhagic stroke transformation triggered by severe haemophilia. In addition, when haemophilia A was corrected by administration of factor VIII concentrates eight out of 25 children with central lines in place developed catheter-related thrombosis. CONCLUSION: The data of this multicentre cohort study demonstrate that the clinical phenotype of severe haemophilia A in childhood is clearly influenced by the coinheritance of prothrombotic risk factors.

Blood Proteins↗
PubMed2001

Seven novel and four recurrent point mutations in the factor VIII (F8C) gene.

Haemophilia A is a X-linked bleeding disorder, caused by deficiency in the activity of coagulation factor VIII due to mutations in the corresponding gene. The most common defect in patients is an inversion of the factor VIII gene that accounts for nearly 45% of individuals with severe hemophilia A. Point mutations and small deletions/insertions are responsible for the majority of cases with moderate to mild clinical course and for half of the severe hemophilia A occurrences. The majority of these mutations are "private", because of the high mutation rate for this particular gene. We report on eleven pathological changes in the factor VIII sequence detected in male patients with haemophilia A or in female obligate carriers. Seven of these mutations are novel [E204N, E265X, M320T, F436C, S535C, N2129M and R2307P] and four have been previously identified [V162M, R527W, R1966X, and R2159C]. Genotype-phenotype correlations and computer prediction analysis on the effect of missense mutations on the secondary structure of the factor VIII protein are performed and the relationships evaluated.

DNA↗
PubMed2001

Symptomatic onset of severe hemophilia A in childhood is dependent on the presence of prothrombotic risk factors.

It has been recently suggested that the clinical phenotype of severe hemophilia A (HA) is influenced by co-inheritance with the factor V G1691A mutation. We therefore investigated 124 pediatric PUP patients with hemophilia (A: n = 111) consecutively admitted to German pediatric hemophilia treatment centers. In addition to factor VIII activity, the factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, antithrombin, protein C, protein S and antithrombin were investigated. 92 out of 111 HA patients (F VIII activity < 1%) were suffering from severe HA. The prevalence of prothrombotic risk factors in children with severe HA was no different from previously reported data: FV G1691A 6.5%, PT G20201A 3.2%, and protein C type I deficiency 1.1%. No deficiency states of antithrombin or protein S were found in this cohort of hemophilic patients. The first symptomatic bleeding leading to diagnosis of severe hemophilia (< 1%) occurred with a median (range) age of 1.6 years (0.5-7.1) in children carrying defects within the protein C pathway or the PT gene mutation compared with non-carriers of prothrombotic risk factors (0.9 years (0.1-4.0; p = 0.01). The cumulative event-free bleeding survival was significantly prolonged in children carrying additionally prothrombotic defects (log-rank/Mantel-Cox: p = 0.0098). In conclusion, data of this multicenter cohort study clearly demonstrate that the first symptomatic bleeding onset in children with severe HA carrying prothrombotic risk factors is significantly later in life than in non-carriers.

Actuarial Analysis↗
PubMed2000

Molecular biology and clinical manifestation of hereditary factor VII deficiency.

Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder. Mutations and polymorphisms of the FVII gene were characterized in more than 40 unrelated patients with FVII deficiency. Among the 29 different mutations, the most frequent were Ala294 Val, Ala294Val;404delC, IVS7+7, and Val281 Phe. Four novel mutations (IVS2+1G>C, Arg247 Cys, Glu265 Lys, Asp343 His) were detected. The relationships between genotypes of mutations and polymorphisms of the FVII gene, FVII deficiency, and clinical phenotype were investigated. Homozygosity of the Phe4 Leu, IVS4+1G>A, Cys135 Arg, Ala244 Val, and Ala294 Val;404delC and the double heterozygosity of Tyr68 Cys / IVS3-1G>A, Val252 Met / IVS2+5G>T, Val281 Phe / Cys135 Arg, Ala294 Val / Val281 Phe, Ala294 Val;404delC / Val281Phe, Ala294 Val;404delC / Arg152 stop, Ala294Val;404delC / Gln(-35) stop, Ala294 Val / Val252 Met, Ala294 Val / Gly156 Asp, and Thr359 Met / Asp242 His were related to clinical symptoms. Double heterozygotes for Arg247 Cys / IVS2+1G>C, Ala206 Thr / Pro303 Arg, Leu(-20) Pro / Val252 Met as well as IVS7+7 /Ala294 Val, IVS7+7 /Ala206 Thr, and IVS7+7 / Met298 Ile were asymptomatic. The clinical symptomatology is rather poor in correlation with the FVII activity. Concerning the clinical phanotype, a correlation seems to exist between specific mutations and clinical symptoms.

Factor VII↗
PubMed1999

Mutational-screening in the factor VIII gene resulting in the identification of three novel mutations, one of which is a donor splice mutation. Mutations in brief no. 245. Online.

Hemophilia A is an X-linked bleeding disease caused by mutations in the coagulation factor VIII gene. The identification and characterization of pathogenic mutations allows the recognition of new mechanisms of functional disturbances of factor VIII. To screen for mutations exons 1-26 of the factor VIII gene have been amplified genomically and analyzed by SSCP followed by direct sequencing of respective exons showing abnormal electrophoretic mobility on SSCP analysis. In the present study we report the detection of four mutations in the factor VIII gene, of which three are novel. The mutational analysis of a patient with severe hemophilia A has revealed that the ac transversion at position 3 of the donor-splice-site of intron 23 results in the skipping of exon 23. A novel nonsense mutation Q1778X in exon 16 of factor VIII gene has been identified in a second hemophilia A case. Furthermore two missense mutations have been ascertained: a novel, S183R, causing a mild phenotype of hemophilia A and R282H, previously described in association with severe hemophilia A.

Exons↗
PubMed1999

When are children diagnosed as having severe haemophilia and when do they start to bleed? A 10-year single-centre PUP study.

UNLABELLED: The aim of this single-centre study was to obtain data prospectively on when children are diagnosed as having severe haemophilia and when they start to bleed. Results of this 10-year PUP study suggest that severe haemophilia is nowadays diagnosed much earlier than in the Sixties. Patients with severe haemophilia (n = 37: FV III <0.01 U/ml) start to bleed at very different ages. While 44% of patients have their first bleeding episode within the first year of life, others do not bleed before the age of four. The onset of joint bleedings generally occurs about half a year later than other types of bleeding. While half our patients developed their first bleeding by the age of 1.22 years, the mean age for the first joint bleeding was 1.91 years. CONCLUSION: Early-onset prophylactic therapy can prevent damage to the joints, but for rational therapy the age at onset of bleeding must also be taken into account. A non-bleeding child does not benefit from prophylactic treatment.

Age of Onset↗
PubMed1998

Molecular diagnostics of 15 hemophilia A patients: characterization of eight novel mutations in the factor VIII gene, two of which result in exon skipping.

The X-linked bleeding disorder hemophilia A is caused by mutations in the coagulation factor VIII gene. A high frequency of de novo mutations and the large size of this gene complicate the molecular diagnostic of hemophilia A. Characterization of mutations, however, may help identify amino acids or regions with essential functional or structural properties and thereby clarify the mechanism of pathogenesis. In the present study, we describe the identification of 15 mutations in the factor VIII gene, of which eight are novel. Among the patients with severe hemophilia A, two splice mutations (IVS5-3 and IVS19-2), a 4-bp deletion ((TACA) at codon 1215, and a missense mutation G1850V have been characterized. The missense mutations G479R, R531C, V537D, N2129S and I2190N were found for five patients with a moderate course of hemophilia A disease. A silent mutation resulting in activation of a cryptic acceptor splice site within exon 11 and four other missense mutations Y114C, R1689H, R2150H (2x), M2164V have been identified for six patients with mild hemophilia A.

Animals↗
PubMed1997

Mutational analysis of ectopic factor VIII transcripts from hemophilia A patients: identification of cryptic splice site, exon skipping and novel point mutations.

Mutational analysis of the gene for clotting factor VIII is complicated by its large size, the high frequency of de novo mutations and its tissue-specific expression. In order to facilitate the search for mutations, we have used a combination of reverse transcription-polymerase chain reaction (RT-PCR) of ectopic factor VIII transcripts, PCR of genomic DNA, single-strand conformation polymorphism analysis and direct sequencing. Here we describe the characterization of seven potentially pathogenic mutations: five of them are novel and the reason for the pathogenicity of the sixth could be determined. Here cDNA analysis revealed the absence of the first 47 bp of exon 16 in approximately 80% of the processed factor VIII mRNA, likely due to activation of a cryptic acceptor splice site within exon 16. The other novel mutations reported here include the skipping of exon 19, which predicts the removal of the corresponding 39 amino acids from the A3 domain, and four missense mutations: W14G, Y620C, W1889L, and Q2087R.

DNA Mutational Analysis↗
PubMed1997

Lipoprotein (a): its role in childhood thromboembolism.

PURPOSE: Elevated lipoprotein (a) [LP (a)] concentrations are independent risk factors of coronary heart disease or stroke in young adults. To clarify its role in childhood thromboembolism, Lp (a) was measured in 72 children with thromboembolism. METHODS: In addition to Lp (a), defects of the protein C anticoagulant system, antithrombin, and antiphospholipid antibodies were investigated in children with arterial (n = 36) or venous (n = 36) thrombosis. RESULTS: Enhanced Lp (a) >50 mg/dL was diagnosed in 8 out of 36 children with arterial and 5 out of 36 patients with venous thrombosis. Of the 72 children, 25 showed the factor V Leiden mutation, 10 showed protein C deficiency, 2 showed antithrombin deficiency, and 4 showed primary antiphospholipid syndrome. Three children with increased Lp (a) were heterozygous for the factor V Leiden mutation, and 1 girl showed additional protein C deficiency. CONCLUSIONS: Data of this study indicate that increased concentrations of Lp (a) play an important role in childhood thrombosis.

Adolescent↗
PubMed1996

Effect of a reduced vitamin K supplementation on prothrombin time in prematures and high-risk neonates.

Recommendations for vitamin K supplementation were recently changed to 3 x 1 mg orally in healthy term neonates and 0.2 mg parenterally in prematures and high-risk neonates. Prothrombin times (PT) at reduced vitamin K doses (120 patients, 170 samples) during the first 6 weeks of life were below 40% in 6 patients only; all low PTs were unrelated to vitamin K. In the remaining patients, median PT was 100%; 79% of patients had values above 70%. PT was related to birthweight, gestational age and age. There was no decrease over the observation period. Following reduced oral and parenteral vitamin K regimens PTs were well within published reference values for neonates given larger amounts of vitamin K.

Administration, Oral↗