H Lenk

University of Leipzig, Leipzig, Saxony, Germany

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Publications (16)48.7 Total impact

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    ABSTRACT: An adequate number of qualified haemophilia centres is an essential requirement for effective and cost-efficient haemophilia care. During a reassessment of the delivery of haemophilia care in Germany a broad range of criteria relating to structure and quality of the centres were defined and a questionnaire was developed. Results: Of 137 doctors who received the questionnaire, 113 (82%) replied. Based on data related to diagnostic and treatment services, together with voluntary information from PEI forms (Paul Ehrlich Institut, Germany), 72 haemophilia centres were established. Three levels of haemophilia care were defined by the Medical Advisory Council of the German Haemophilia Society. This is in accordance with criteria defined by European working parties. 17 haemophilia centres were designated CCC (Comprehensive Care Centre), 24 were designated HTC (Haemophilia Treatment Centre) and 31 smallest centres were allocated the status HTR (Haemophilia Treatment Regional). In comparison to the survey in 2007, there was only slight variance in the CCC centres (+ 2 centres/-1 centre). From the previous HTC centres, 7 have withdrawn from this treatment level: 4 maintain treatment on the lower level HTR, and 3 centres had ceased treatment. On the HTR level of treatment, 6 of 29 (21%) had ceased to offer treatment. 9 had been able to increase the number of patients and were designated HTC. 5404 patients with haemophilia and 3047 with the severe form of haemophilia were reported. 67% were treated in CCC, 25% in haemophilia treatment centres and 8% in the 31 smallest centres. 13 of the adult CCC are situated in the department of internal medicine and 4 in the section of transfusion medicine. Conclusions: The survey and analysis of the haemophilia treatment centres in Germany show that the delivery of haemophilia care through 17 CCC, 24 HCT and 31 HTR appears to be adequately structured. But it is noticeable and alarming, however, that on both HTC and HTR levels of treatment, 32% and 21%, respectively, have left their treatment level. 9 centres (12.5%) have finished working in haemophilia care in the last four years. On the strength of these results, endeavours to maintain haemophilia centres must be intensified. A high level of effective care can be guaranteed only through continued existence of the centres.
    Hamostaseologie 01/2012; 32 Suppl 1:S12-9. · 1.59 Impact Factor
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    ABSTRACT: An open-label, multicentre, postmarketing surveillance study conducted in Germany and Austria with recombinant factor VIII (REFACTO) has enrolled 217 patients (mean age 26.3 years) from 38 haemophilia centres during the first 4.8 years. Most patients (188/217; 86.6%) had severe to moderately severe haemophilia A, of whom 153 completed sufficient diary information for the main efficacy analysis. These 153 patients experienced a median of 6.6 (interquartile range 1.4-18.6) bleeding episodes per year. Patients treated with prophylaxis experienced a median of 4.4 (1.1-9.3) bleeds per year, while patients treated on-demand experienced a median of 22.8 (11.3-29.0) bleeds per year. Overall, most physicians (41/43 [95.3%]) were 'very satisfied' or 'satisfied' with the efficacy of REFACTO in the treatment of bleeding episodes. A total of 137 non-serious adverse events have been reported in 52/217 patients (24.0%) to date. In addition, 129 serious adverse events in 87 patients (40%) were reported, including 41 cases of 'less than expected therapeutic effect' (LETE). Of these, 39 LETE cases were reported in one centre; however, patients in this centre experienced considerably fewer bleeding episodes per year than patients outside this centre. Overall, six patients (2.8%) have developed de novo inhibitors, three of which were considered high titre. Four of these patients were at high risk (0-50 exposure days [ED]) of inhibitor formation, one was at intermediate risk (51-100 ED) and one was at low risk (>100 ED). These results emphasize the benefit of postmarketing surveillance and, overall, this study confirms the efficacy, safety and tolerability of REFACTO in the treatment of patients with haemophilia A.
    Haemophilia 04/2007; 13(2):131-43. · 3.17 Impact Factor
  • 12/2005: pages 34-37;
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    ABSTRACT: Continuous infusion (CI) of coagulation factor concentrates has been used since the early 1990s. Recent reports of the occurrence of an inhibitor after CI have raised concerns about this method of treatment. We conducted a retrospective study to investigate the development of inhibitors after CI of Factor VIII concentrates in Germany. So far, 13 hemophilia centers have been contacted, and data have been collected by a questionnaire. Of the 13 centers, CI had never been performed in three, no inhibitors had been detected in five, and inhibitor development after CI was recorded in 10 patients in the remaining five centers. Of these 10 patients (ages 7 months to 57 years), five were suffering from severe, one from moderate, and four from mild hemophilia. Indications for treatment were major bleeds and surgical procedures. Plasma-derived (6 cases) and recombinant (4 cases) factor concentrates were given in various infusion sets. Data concerning amount infused (4300 to > 100,000 IU), number of days of exposure to factor concentrates (1 to > 100), and inhibitor characteristics (alloantibodies, 3 LR, 7 HR) were collected. Regarding hemophilia genotype, we found missense mutations in four patients, intron-22 inversions in two, and one small deletion in one; the genotype in three was unknown. In conclusion, only 3 out of 10 patients who developed an inhibitor after CI showed the typical risk profile for inhibitor formation, which is severe hemophilia A with a severe gene defect and less than 50 days of exposure to coagulation factor concentrates. Especially striking was the finding that 50% of the patients who developed inhibitors had mild to moderate hemophilia A. Our data point to the existence of a so-far unknown factor, related to CI, that might lead to inhibitor formation.
    Annals of the New York Academy of Sciences 06/2005; 1051:498-505. · 4.38 Impact Factor
  • 12/2004: pages 368-368;
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    ABSTRACT: To evaluate current treatment patterns and resource utilization as well as related cost in the management of severe haemophilia patients with inhibitors in Germany, a cost-of-illness study was conducted. Generally, data were generated by structured literature search. Missing data were collected by expert interviews. All data were validated by a panel of German experts in haemophilia care. In Germany, immune tolerance therapy (ITT) is first-line therapy in inhibitor management for children in the initial year after inhibitor development, particularly for high responders (HR). In adult HR patients ITT is applied but to a remarkably lower extent than in children. To treat bleeding episodes, factor VIII (FVIII) is first-line therapy in low responders (LR). For paediatric HR patients, bleeds are mainly treated with recombinant FVIIa (rFVIIa). In adult HR patients, activated prothrombin complex concentrate (aPCC) and rFVIIa are more equally distributed as treatment options. Treatment costs were calculated for paediatric patients (15 kg) and adult patients (75 kg) from third party payers' perspective. Cost for ITT ranges from Euro 70,290 (2 months; LR) to Euro 3 812,400 (24 months; with aPCC; HR) in a paediatric patient. For an adult patient ITT cost ranges from Euro 287,500 (6 months; LR) to Euro 17,253,000 (36 months; HR). For on average 12.5 acute bleeds, average annual treatment costs amount to Euro 77,000 for a child and Euro 354,000 for an adult. Assessing the results it has been taken into consideration that ITT can last longer and annual number of bleeds can be extremely higher than on average 12.5 episodes. This indicates more health care resource consumption in some patients.
    Haemophilia 10/2004; 10(5):499-508. · 3.17 Impact Factor
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    ABSTRACT: A multicentre, international, cross-sectional study was carried out in the frame of field testing of the first haemophilia-specific quality-of-life (QoL) questionnaire (Haemo-QoL). The aim of this paper is to describe health status and health care and their impact on QoL in haemophilic children in Western Europe. Children aged 4-16 years with severe haemophilia without inhibitors were enrolled by 20 centres in France, Germany, Italy, the Netherlands, Spain and the United Kingdom. Clinical information was collected by the physicians with a medical documentation form. Health-related QoL (HRQoL) of children was assessed with Haemo-QoL, available for three age groups. Clinical data were available in 318 patients, 85.5% with haemophilia A. The mean age at first bleeding was 11 months, at first joint bleed 25 months. Functional joint impairments were found in 11.3%. Prophylaxis treatment was given to 66.7% of children in whom breakthrough bleeds occurred 0.4 times a month compared to 1.1 bleeds in children receiving on-demand treatment. A significantly higher factor consumption was found only in the two younger age groups of prophylaxis patients compared to on-demand patients. HRQoL was satisfactory in this cohort: young children were impaired mainly in the dimension 'family' and 'treatment', whereas older children had higher impairments in the so-called 'social' dimensions, such as 'perceived support' and 'friends'. Health care of children in Western Europe is progressively improving with a large diffusion of home treatment and prophylaxis. This provides a high level of health status and HRQoL, being better in haemophilic adolescents on prophylaxis.
    Haemophilia 04/2004; 10 Suppl 1:26-33. · 3.17 Impact Factor
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    ABSTRACT: The inhibitory capacity of plasma samples from 24 patients with severe haemophilia A and high-responding inhibitors were evaluated in a concentrate-based assay using two plasma-derived (Haemate and Monoclate-P) and three recombinant (Helixate, Recombinate and ReFacto) factor VIII concentrates and correlated with the corresponding epitope profile. In most, but not all, inhibitor plasmas with a relatively low reactivity against the von Willebrand-containing product Haemate, the main epitopes were located in the FVIII light chain. The reactivities within the group of recombinant products varied in that the reactivity against the B-domain deleted ReFacto was in general higher than that against Recombinate and Helixate. This difference did not correlate with any particular epitope profile and indicates that the B-domain, type of formulation and/or purification procedures may have an impact on the inhibitor reactivity in vitro. The ratio between the inhibitor titres in the concentrate-based assay and the Bethesda assay was dependent on the inhibitor plasma and concentrate used. Taken together, our results show that the reactivity of inhibitor plasmas varies considerably between different FVIII concentrates and that it does not fully correlate with the epitope profile. Potential clinical implications of the observed differences in inhibitor reactivity are discussed.
    Haemophilia 10/2003; 9(5):567-72. · 3.17 Impact Factor
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    ABSTRACT: Plasmas from 40 haemophilia A patients enrolled in a study by the paediatric group of the German Society on Thrombosis and Hemostasis were tested by the Bethesda assay for inhibitor antibodies and by a more sensitive immunoprecipitation assay (IP) for all antifactor VIII antibodies. Of the 26 severe, 11 moderate and three mild haemophiliacs, 18, two, and none, respectively, had positive Bethesda titres after several factor VIII infusions. In 275 plasmas with Bethesda titres of 0, 0.6--1.0, > 1--5, and > 5--655, the IP responses were 0-238, 0--61, 0--786, and 43--6141, respectively, and a reliable positive IP titre was > 4.2. The overlapping ranges of IP titres indicated large differences in the ratio of inhibitory to noninhibitory antibodies in individual plasmas. In five of seven patients with Bethesda titres of 0.6--1, the IP titres were < 4.2, suggesting a lack of precision of Bethesda titres < or = 1. Detection of the primary immune response was found in only three patients by IP assay before a positive Bethesda assay. This precludes early, reliable testing of which patients will be immunologically responsive. In four patients undergoing immune tolerance therapy, antifactor VIII antibodies were still detectable by the IP assay in the absence of a Bethesda titre, which indicates that antibodies were completely eradicated in none of the patients. Our results show that the use of both the Bethesda and IP assays can provide more accurate detection of antifactor VIII antibodies in all patients.
    Haemophilia 02/2001; 7(1):26-32. · 3.17 Impact Factor
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    ABSTRACT: 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.
    Seminars in Thrombosis and Hemostasis 02/2000; 26(4):393-400. · 4.22 Impact Factor
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    ABSTRACT: Besides the investigation of coagulation factor VIII:c and von Willebrand factor in plasma. vWF antigen and vWF collagen-binding activity in platelets of 24 patients with various forms of von Willebrand disease were analysed. No platelet vWF:Ag or vWF:CBA was detectable in type 3 patients (n = 4). In contrast 6 out of 7 patients with type 2 vWD had normal or increased vWF levels. Two type I patients (out of n = 13) with low von Willebrand factor in platelets had no increased bleeding tendency. In two other individuals with normal amounts of von Willebrand factor in platelets and low plasmatic vWF and factor VIII:c, more frequent bleeding episodes reflecting the low plasmatic levels were observed in a long-term follow-up. CONCLUSION: In our patients, bleeding history corresponded to plasmatic levels of FVIII:c and vWF.
    European Journal of Pediatrics 01/2000; 158 Suppl 3:S177-9. · 1.98 Impact Factor
  • Blood 01/2000; 96(11):3817-. · 9.78 Impact Factor
  • European Journal of Pediatrics 01/2000; 158 Suppl 3:S209-10. · 1.98 Impact Factor
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    ABSTRACT: Haemophilia A is the most common X-chromosomal-linked congenital bleeding disorder and is caused by decreased activity of blood coagulation factor VIII. Affected individuals develop a variable phenotype of haemorrhages, mainly into joints and muscles depending on the amount of the residual factor VIII. The exogenous factor VIII-substitution by plasma-derived or recombinant products are the only treatments either on demand or prophylactically. The most important complication of treatment is the development of inhibitors that affect about 20%-50% of the severe cases. These antibodies neutralize the therapeutic effect of factor VIII-concentrates, leading to recurrent bleeding episodes, progredient joint damages and sometimes life-threatening situations. The only chance for a complete and permanent eradication of the inhibitors in these patients is the induction of Immune-Tolerance (ITT) to substituted factor VIII by the application of high-doses of factor VIII. The treatment demands a strict compliance of the patient and a much higher effort of the physician, to non-compared inhibitor patients. Requirements for a consistent realization of the ITT to increase the successful outcome was carried out by German Haemophilia Center Directors.
    Haemophilia 06/1999; 5(3):203-6. · 3.17 Impact Factor
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    ABSTRACT: To reduce the risk of transmission of hepatitis A virus, an Octapharma produced factor VIII (fVIII) concentrate treated with solvent detergent (FVIII-SD) was further pasteurized after purification. This product, Octavi SDPlus (FVIII-SDP), was marketed in Europe in 1993 to 1995. Inhibitors appeared from September to October, 1995, in 12 of 109 previously treated German hemophilia A patients. A study of similarly treated Belgian patients, who also developed inhibitors, had shown antibodies to the fVIII light chain (domains A3-C1-C2) only. In the present study, the epitope specificity of 8 German inhibitor plasmas was also found to be restricted to the light chain. In radioimmunoprecipitation assays to localize the light chain epitope(s), antibody binding to heavy chain (domains A1-A2-B) was 11-148 fold lower than to the C2 domain, and binding to recombinant A3-C1 was barely detectable. These results were supported by >95% neutralization of a high responder inhibitor titer by the C2 domain.
    Thrombosis and Haemostasis 02/1999; 81(1):39-44. · 5.76 Impact Factor
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    ABSTRACT: Our findings suggest that among women with recurrent miscarriages and recurrent IVF failures anti-annexin V antibody positivity is less prevalent than APC-resistance, lupus anticoagulant or elevated levels of antibodies against cardiolipin or β2-glycoprotein-1 and that the IVF-result in women with APC-resistance, lupus anticoagulants or elevated levels of antibodies against annexin V, cardiolipin or β2-glycoprotein-1 might be positively influenced by low molecular weight heparin.