S. Reitter

The impact of severe haemophilia on the social status and quality of life among Austrian haemophiliacs.

Summary.  Although many studies of the impact of haemophilia on the quality of life were conducted, there is hardly any data on the social status of haemophiliacs. It was the aim of our study to obtain data on the social status of Austrian haemophiliacs and to compare these with an age‐ and sex‐matched reference population. Furthermore, we collected data on the quality of life of haemophilia patients. We conducted a case–control study in two Austrian haemophilia centres with 53 patients (mean age 36.7 ± 10.6 years) and 104 male controls (mean age 36.7 ± 11.1 years). Socio‐demographic data were collected using a standardized questionnaire and quality‐of‐life data using the SF‐36. More patients (56.6%) than controls (37.5%) were married (P = 0.023), whereas more controls (17.3%) than patients (3.8%) had a partner with whom they were not married (P = 0.016). The percentage having children was equivalent in both groups (47% and 41% respectively), but controls had more children (mean number 1.5 in patients and 2.1 in controls, P < 0.007). A greater number of patients was unemployed (34% of patients, 9% of controls, P < 0.001) as well as retired (23% and 4% respectively; P < 0.001). Patients had worse scores regarding physical functioning, role‐physical, bodily pain and general health (P < 0.001), whereas vitality, social functioning, role‐emotional and mental health were similar in both groups. Despite their disability, most of the Austrian haemophiliacs share a sound family environment. This suggests that they are highly capable of coping with their chronic disease and is indicated by good scores for role‐emotional and mental health.

Survival in a cohort of patients with haemophilia at the haemophilia care center in Vienna, Austria, from 1983 to 2006.

Summary.  Survival of patients with haemophilia is still a relevant issue of great interest. A survival analysis was conducted among 226 patients with haemophilia A and B (128 severe haemophiliacs), who were treated at the haemophilia care centre in Vienna. Information on mortality in our patient cohort was obtained from the Austrian Central Death Register. Overall, 96 of a total of 226 patients (42.5%) died between 1983 and 2006; 37 patients (38.5%) died due to HIV‐infection, 15 due to HCV infection, 15 due to bleeding (15.6%, respectively) and 29 (30.2%) due to various other causes. The mortality of HIV‐positive patients was 74.3% (n = 55) and that of HCV‐positive patients was 40.4% (n = 55) in the analysed period. The patient mortality rates were compared with those of the general Austrian male population following adjustment for age and calendar period. We found that the cumulative relative survival of all patients was 0.694 (95% CI 0.614–0.767). The cumulative relative survival of patients with severe haemophilia (FVIII or IX level ≤1%) was 0.489 (0.394–0.579), but was normal (0.986; 95% CI 0.858–1.082) for patients with mild or moderate haemophilia (FVIII or IX level 2–50%). The survival rate was lowest in HIV‐positive patients (0.287; 95% CI 0.186–0.398), but was also decreased to 0.874 (0.776–0.951) in HIV‐negative patients. It can, therefore, be concluded that the survival of patients with severe haemophilia is still decreased compared to those with non‐severe haemophilia and the general male population, regardless of HIV‐infection.

Spectrum of causative mutations in patients with haemophilia A in Austria

In patients with haemophilia A knowledge of the pathogenetic mutation is important i) as basis for carrier diagnosis and ii) for risk estimation of inhibitor formation. The pathogenetic mutations were identified by testing inversions in intron 1 and 22 (IVS22 and IVS1) and sequencing part of the promoter, the coding region and the exon/intron boundaries in a cohort of Austrian haemophilia A patients. A total of 239 patients from nine participating centres, who had consented to genetic testing and of whom clinical information was available were included in the study. First, IVS22 and IVS1 were tested; in case of absence of either inversion patients were subjected to sequencing. Mutations within the FVIII gene were identified in 234 patients. Notably, 53 mutations had not previously been described in HAMSTeRS. Of our patient cohort, 72.5 % had either an IVS22 or a missense mutation. Interestingly, in three brothers with severe haemophilia, we found a double mutation in exon 14 (missense + small deletion). The spectrum of mutations in Austrian haemophilia A patients was comparable to that found in the German and Italian population; however, it differed from the spectrum reported in the UK. In conclusion, 53 not previously published mutations were identified in Austrian haemophilia A patients. The occurrence of double mutations in the factor VIII gene could be confirmed and their low frequency was corroborated. We speculate that the differences between mutations in Austria and other European countries are due to ethnic diversity. Detailed investigations of the association of ethnicity and the mutation spectrum are planned.

Long-term survival after venous thromboembolism: a retrospective selected cohort study among young women

Few data are available on long-term survival following venous thromboembolism. We performed a retrospective survival analysis covering the period January 1985 to December 2006 in 728 young women (median age 28.7 years; interquartile range 21.6–36.3 years) with a history of venous thromboembolism who visited our clinic between 1985 and 1998. Mortality information was obtained from the Austrian Central Death Register. Survival of our patients was compared to the general Austrian female population after adjustment for age and calendar period. Overall, 23 patients (3.2%) died, the cumulative relative survival was 1.03 (95% CI 0.99–1.04). Site of venous thromboembolism or triggering factors had no significant influence. Venous thromboembolism does not reduce long-term survival in young women considering our median follow up of 14 years. The risk of fatal bleeding and quality of life should be assessed versus that of fatal recurrent venous thromboembolism when deciding on long-term anticoagulation in young women.

Postoperative paraneoplastic factor VIII auto-antibodies in patients with solid tumours

Summary.  Paraneoplastic FVIII antibodies may occur concurrent with the diagnosis or at various times after diagnosis and treatment of cancer. Between 2002 and 2009, we observed two patients with acquired haemophilia A due to an FVIII auto‐antibody, which appeared 4 and 5 months after uncomplicated cancer surgery. We aimed to evaluate if such an association of cancer surgery and FVIII antibody formation has been observed previously. We retrieved all published case reports of cancer‐associated FVIII auto‐antibodies from PubMed for the period 1950–2010. The search in the literature revealed 13 patients in whom a FVIII inhibitor developed after uncomplicated surgery for cancer and a bleeding‐free time interval of up to 6 months; 11/15 patients had abdominal cancers (five colon cancer, four pancreatic cancer, gastric cancer and choledochus carcinoma one each). The median time period between surgery and antibody detection was 3 months (1 week–6 months). In most cases, the antibody titre was low (median: 14 BU mL−1, range: 1.7–64 BU mL−1). Immunosuppressive treatment was successful in most of the cases – nine of the treated patients reached a sustained CR of the antibody after a median time of 3 months. Postoperative paraneoplastic FVIII inhibitors may be regarded as a special, not yet recognized subgroup of acquired FVIII antibodies. They share some characteristics with postpartum FVIII inhibitors with regard to the latency period between the triggering event and the appearance of the antibody, and between the usually low antibody titres and their good response to immunosuppressive treatment.

Inhibition of tissue factor pathway inhibitor (TFPI) by ARC19499 improves clotting of hemophiliac blood

Background Hemophilia A and B are disorders resulting from a deficiency in factor VIII (FVIII), and factor IX (FIX), respectively. Tissue Factor (TF) is a key component of the extrinsic pathway and plays a role in the coagulation defect of hemophilic blood. Neutralizing the activity of TFPI represents a promising treatment concept in patients with hereditary or acquired hemophilia. ARC19499 is a polyethylene glycol (PEG)-conjugated aptamer that binds to TFPI and inhibits its function as a negative regulator of coagulation.