| 1. |
- Lanke, E., et al.
(författare)
-
Co-segregation of the PROS1 locus and protein S deficiency in families having no detectable mutations in PROS1
- 2004
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Wiley-Blackwell. - 1538-7933 .- 1538-7836. ; 2:11, s. 1918-1923
-
Tidskriftsartikel (refereegranskat)abstract
- Inherited deficiency of protein S constitutes an important risk factor of venous thrombosis. Many reports have demonstrated that causative mutations in the protein S gene are found only in approximately 50% of the cases with protein S deficiency. It is uncertain whether the protein S gene is causative in all cases of protein S deficiency or if other genes are involved in cases where no mutation is identified. The aim of the current study was to determine whether haplotypes of the protein S gene cosegregate with the disease phenotype in cases where no mutations have been found. Eight protein S-deficient families comprising 115 individuals where previous DNA sequencing had failed to detect any causative mutations were analyzed using four microsatellite markers in the protein S gene region. Co-segregation between microsatellite haplotypes and protein S deficiency was found in seven of the investigated families, one family being uninformative. This suggests that the causative genetic defects are located in or close to the protein S gene in a majority of such cases where no mutations have been found.
|
|
| 2. |
- Lanke, E., et al.
(författare)
-
Genetic analysis of 31 Swedish type 1 von Willebrand disease families reveals incomplete linkage to the von Willebrand factor gene and a high frequency of a certain disease haplotype
- 2005
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Wiley-Blackwell. - 1538-7933 .- 1538-7836. ; 3:12, s. 2656-2663
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The most common type of von Willebrand disease (VWD), type 1, has in only a few cases been explained by an identified causative mutation in the von Willebrand factor (VWF) gene. The ABO blood group and other modifier loci outside the VWF gene may contribute to the development of type 1 VWD. OBJECTIVES AND METHODS: Our aim was to determine whether there was genetic linkage to the VWF gene in 31 Swedish type 1 VWD families. Stringent diagnostic criteria in accordance with ISTH guidelines were used. Genetic linkage was investigated by using two highly informative dinucleotide microsatellite markers, which we have recently identified, located in introns six and 15 of the VWF gene. We also investigated the existence of common disease haplotypes and the relation between type 1 VWD and ABO blood group. RESULTS: We found genetic linkage to the VWF gene in 27 (87%) of the families. However, in four (13%) of the families, there was clearly no genetic linkage. We found the 4751A>G (Tyr1584Cys) sequence variation in exon 28, which is a common mutation in the Canadian VWD population (14.3%), in only one of the 31 families (3.2%). A possible common mutation was identified in six of the 27 (22%) families with genetic linkage. Blood group O was over-represented among type 1 VWD patients. CONCLUSION: We conclude that there is linkage between the VWF gene and hereditary type 1 VWD in a majority of families.
|
|
| 3. |
- Lethagen, Stefan, et al.
(författare)
-
Clinical spectrum of hepatitis C-related liver disease and response to treatment with interferon and ribavirin in haemophilia or von Willebrand disease
- 2001
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 113:1, s. 87-93
-
Tidskriftsartikel (refereegranskat)abstract
- Our aim was to evaluate the severity of liver disease resulting from chronic hepatitis C in haemophilia or von Willebrand disease and the efficacy of 6 months treatment with interferon alpha and ribavirin. Fifty-five liver biopsies were performed in 43 patients without any bleeding complications, as seen with ultrasound immediately after the biopsy and 48 h thereafter. Histological changes were mild, with low scores for both inflammation and fibrosis, in spite of long exposure to blood products (mean 27 years). Two patients had compensated cirrhosis. Thirty-five out of 39 included patients completed study treatment. Hepatitis C virus (HCV)-RNA was negative in 77% (30/39) of patients at the end of treatment, and 36% (14/39) achieved a complete sustained response at follow-up 6 months after treatment. Treatment failure was more frequent in patients with virus genotype 1 compared with non-1 (P = 0.0003). The response rate correlated well with that of non-haemophilic patients. In summary: (1) liver biopsy was safe with our regimen; (2) liver disease in our patients was usually mild and had a slow progress; (3) only HCV genotype 1 predicted treatment failure; (4) our treatment results agreed with those from non-haemophilic patients.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Astermark, Jan, et al.
(författare)
-
Low recurrence rate after deep calf-vein thrombosis with 6 weeks of oral anticoagulation
- 1998
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 244:1, s. 79-82
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the recurrence rate after deep calf-vein thrombosis treated with 6 weeks of oral anticoagulation. DESIGN AND SUBJECTS: A 2 year follow-up of 126 consecutive patients admitted to the Department of Internal Medicine with venographically verified deep calf-vein thrombosis. RESULTS: One hundred and twenty-six patients were treated with warfarin for 6 weeks, 18 of them having had a previous episode of venous thrombosis (DVT). Eleven patients (8.7%) suffered a recurrent thromboembolic episode within 2 years, four of which were within the first 3 months. Eight of those without a history of DVT had a recurrence (7.4%). Three of these were activated protein C (APC)-resistant, one was protein C-deficient and one had malignant melanoma. Eight patients (6.3%) reported minor haemorrhagic complications, but no major bleeding was seen. CONCLUSION: Our data support the use of a 6 week regimen of secondary oral prophylaxis after a first episode of deep calf-vein thrombosis in patients without a permanent risk factor. Whether individuals with inherited thrombophilia require prolonged treatment remains to be evaluated.
|
|
| 7. |
- Astermark, Jan, et al.
(författare)
-
Major surgery seems not to influence HIV disease progression in haemophilia patients
- 1998
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 103:1, s. 10-14
-
Tidskriftsartikel (refereegranskat)abstract
- The influence of major surgery on HIV disease progression and decline in CD4+ cell count was evaluated in 23 seropositive haemophilia patients. 24 HIV-infected patients served as non-operated controls. In addition, 32 age-matched seronegative subjects were included. The follow-up time was up to 5 years. During the course of the study, eight of the operated (35%) and 11 of the non-operated (48%) subjects developed HIV-related symptoms (P=0.267). The relative risk for developing HIV-related symptoms after surgery was 0.60 (95% CI 0.25; 1.48). A significant decline in CD4+ cell counts was observed in both the surgery (4.0 x 10(6)/l/month, 95% CI 2.0; 6.0 x 10(6), P=0.001) and the non-surgery (4.0 x 10(6)/l/month, 95% CI 2.0; 6.0 x 10(6), P=0.004) seropositive subgroup, but no difference between the two subgroups was seen (P=0.793). HIV (6.0 x 10(6)/l/month, 95% CI 2.1; 9.9 x 10(6), P=0.0005) but not surgery (-1.0 x 10(6)/l/ month, 95% CI -3.0; 0.96 x 10(6), P=0.647) was an independent predictor for the decline in CD34+ cell count. No interaction effect was observed between HIV infection and surgery (P=0.361). The annual amount of factor concentrate used for regular replacement therapy did not influence the decline in CD4+ cell count (P=0.492). We conclude that major surgery may be considered in symptom-free HIV-seropositive haemophilia patients, with CD4+ cell counts > or = 0.20 x 10(9)/l under similar premises as for seronegative subjects.
|
|
| 8. |
- Astermark, Jan, et al.
(författare)
-
The B-Natural study—The outcome of immune tolerance induction therapy in patients with severe haemophilia B
- 2021
-
Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 27:5, s. 802-813
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Inhibitors develop less frequently in haemophilia B (HB) than haemophilia A (HA). However, when present, the success of tolerization by immune tolerance induction (ITI) therapy is lower and the risk of complications higher. Aim: To evaluate the use and outcome of ITI in patients with HB and inhibitors. Methods: Subjects include singletons or siblings with a current/history of inhibitors enrolled in B-Natural—an observational study designed to increase understanding of clinical management of patients with HB. Patients were followed for 6 months and information on demographics, medical and social history, and treatment were recorded. Results: Twenty-nine patients with severe HB and inhibitors were enrolled in 24 centres. Twenty-two underwent one or more courses of ITI with or without immune suppression. Eight patients (36.4%) were successfully tolerized after the first course of ITI. One of these successes (12.5%) experienced allergic manifestations, whereas the corresponding number for the 10 treatment failures was five (50%). One of seven (14.2%) patients with large deletions and three of eight (37.5%) with nonsense mutations were tolerized at the first attempt, and all patients experiencing nephrosis either failed or were on-going. At study end, 11 (50%) were considered successfully tolerized after one or more ITI courses, three were unsuccessful, and eight were still undergoing treatment. Conclusion: Our data underscore the possibilities and difficulties of achieving tolerization in patients with HB with inhibitors. The type of mutation and complications appear to correlate with ITI outcome, but more accurate definitions of successful ITI are warranted.
|
|
| 9. |
- Berntorp, Erik, et al.
(författare)
-
A systematic overview of the first pasteurised VWF/FVIII medicinal product, Haemate P/ Humate -P: history and clinical performance.
- 2008
-
Ingår i: European Journal of Haematology. Supplementum. - : Wiley. - 0902-4506 .- 0902-4441 .- 1600-0609. ; 80:s70, s. 3-35
-
Forskningsöversikt (refereegranskat)abstract
- Patients with von Willebrand disease (VWD) and haemophilia A (HA) lack, to varying degrees, the von Willebrand factor (VWF) and coagulation factor VIII (FVIII) that are critical for normal haemostasis. These conditions in turn make patients prone to uncontrolled bleeding. Historically, patients with severe forms of VWD or HA were crippled before adulthood and their life expectancy was significantly reduced. Over the past decades, specific coagulation factor replacement therapies including Haemate P, have been developed to help patients achieve and maintain normal haemostasis. Haemate P is a human, plasma-derived VWF/FVIII medicinal product, which was first licensed in Germany in 1981 for the treatment of HA-associated bleeding. It has since then come to be accepted as the gold standard for both the treatment and prophylaxis of bleeding in VWD, especially in cases where desmopressin [1-deamino-8-D-arginine vasopressin (DDAVP)] has been ineffective. Haemate P was the first effectively virus-inactivated (pasteurisation: 60 degrees C for 10 h in aqueous solution) FVIII product, whereby the risk of potentially threatening infective complications of plasma-derived products was reduced. Haemate P was also shown to have a VWF multimer profile remarkably close to that of normal plasma. This bibliographic review presents previously unpublished clinical data of Haemate P, based upon internal clinical study reports of the proprietor, CSL Behring, in addition to data already presented in other publications. The data demonstrate a predictable and well-characterised pharmacokinetic profile, and a proven record of short- and long-term safety, while effectively correcting the haemostatic defects in VWD and HA. Recently available data have also shown Haemate P to be of haemostatic value in exceptional clinical circumstances including surgical interventions. By virtue of its plasma-derived combination of VWF and FVIII, in addition to its high VWF:FVIII content ratio (2.4:1), Haemate P is also associated with successful immune tolerance induction in those patients developing inhibitor antibodies. Although the theoretical risk of thromboembolic complications does exist while receiving Haemate P, as it does with any FVIII replacement therapy, the incidence of such complications has remained notably low. Given the robust data that have accumulated for the use of Haemate P, dosing recommendations are also described in this review; the recommendations are tailored to patient-specific contexts including baseline VWF and FVIII levels in plasma and the type of surgical intervention being undertaken. A wide variety of studies have also provided data on paediatric and geriatric populations, all of which have suggested that Haemate P can be safely and effectively used in a wide variety of clinical circumstances.
|
|
| 10. |
- Berntorp, Erik, et al.
(författare)
-
Centraliserad vård grundläggande i vårdprogram för blödarsjuka
- 1999
-
Ingår i: Läkartidningen. - 0023-7205. ; 96:15, s. 1849-1852
-
Tidskriftsartikel (refereegranskat)abstract
- Haemophilia is a rare and potentially life-threatening disease. In Sweden, with a population of approximately 8.5 million, about 350 people suffer from the more severe forms of haemophilia or von Willebrand disease. Meticulous management is important if the patients are to be spared chronic disability and serious treatment complications. The disease is lifelong and affects psychosocial aspects of life among patients and their families. With the help of a grant from the Swedish Board of Halth and Welfare, a care programme has been designed to guarantee Swedish haemophiliacs comparable and optimal care. The programme has been drawn up by representatives of the three haemophilia centres in Sweden (at University Hospital, Malmo, Sahlgrenska University Hospital, Gothenburg, and Karolinska Hospital, Stockholm) in co-operation with the World Federation of National Haemophilia Organisations. To ensure optimal individual application of the programme, individualised management strategies and patient information leaflets have been prepared.
|
|
