| 1. |
- Holm, Elena, et al.
(author)
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Patients Referred for Bleeding Symptoms of Unknown Cause : Does Evaluation of Thrombin Generation Contribute to Diagnosis?
- 2016
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In: Mediterranean Journal of Hematology and Infectious Diseases. - 2035-3006. ; 8:1, s. 2016014-2016014
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Patients with mild to moderate bleeding symptoms referred for coagulation investigation sometimes never receive a definitive diagnosis. Bleed assessment tools have been developed and validated to assess the severity of symptoms. Global coagulation assays, e.g., the thrombin generation test (thrombogram) have a potential to identify hemostatic defects that are not detected in specific assays.MATERIAL AND METHODS: One hundred and eighty-five patients referred to our centre because of bleeding symptoms were evaluated using the bleeding assessment tool (BAT) described by Tosetto and colleagues in 2006. Blood samples were investigated for thrombin generation (TG) capacity (Technoclone), in platelet poor (PPP) plasma, and specific clotting factors, i.e., von Willebrand factor, factor VIII and IX, as well as INR, APTT, platelet count, and platelet adhesion.RESULTS: Of the 185 patients, five women were diagnosed with mild von Willebrand disease and one male with mild hemophilia A. The remaining 179 subjects (76% females and 24% males with average ages of 33 and 28 years, respectively) were evaluated further. In the total cohort and among women, peak TG, and lag time correlated with bleeding score (p=0.01 and p=0.04, respectively with correlation coefficients). No such correlations were found among males.DISCUSSION AND CONCLUSION: Although our study showed some correlation between TG and bleeding score, results are generally consistent with a previous report which failed to demonstrate the value of TG measurement in a similar setting. In conclusion, the complexity of the mechanisms underlying clinical bleeding complicates the ability to use TG tests as reliable predictors of bleeding. Mild congenital bleeding disorders, especially VWD, should be specifically screened for in patients with mild/moderate symptoms.
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| 2. |
- Labaf, Ashkan, et al.
(author)
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Thromboembolism, major bleeding and mortality in patients with mechanical heart valves : a population-based cohort study
- 2014
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In: Thrombosis Research. - : Elsevier. - 0049-3848 .- 1879-2472. ; 134:2, s. 354-359
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Journal article (peer-reviewed)abstract
- Introduction: Low incidences of thromboembolism (TE) and bleeding in patients with mechanical heart valves (MHV) have previously been reported. This study assesses the incidence of and clinical risk factors predicting TE, major bleeding and mortality in a clinical setting. Methods and results: All 546 patients undergoing anticoagulation treatment due to MHV replacement at hospitals in Malmo and Sundsvall in Sweden were monitored during 2008-2011 and the incidence of TE, major bleeding and mortality was prospectively followed. There were 398, 122 and 26 patients in the aortic group (AVR), mitral (MVR) group and the combined aortic/mitral valve group respectively. The incidence of TE was 1.8 and 2.2 per 100 patient-years in the AVR group MVR group respectively. The corresponding incidences of bleeding were 4.4 and 4.6, respectively. Independent predictor of thromboembolism was vascular disease (Odds ratio {OR}: 4.2; 95% CI: 1.0-17.4). Predictor of bleeding was previous bleeding (OR: 2.7; 95% CI: 1.4-5.3). Independent predictors of mortality was age (Hazard ratio {HR}: 1.03; 95% CI: 1.00-1.05), hypertension (HR: 2.4; 95% CI: 1.3-4.5), diabetes (HR: 2.4; 95% CI: 1.3-4.3) and alcohol overconsumption (HR: 5.2; 95% CI: 1.7-15.9). Standardized mortality/morbidity ratio for mortality and AMI was 0.99 (95% CI: 0.8-1.2) and 0.87 (95% CI: 0.5-1.2) respectively. Conclusion: The incidence of TE and major bleeding in this unselected clinical population exceeds that of previously reported retrospective and randomized trials. Despite this, mortality is equal to that of the general population.
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| 3. |
- Lövdahl, Susanna, et al.
(author)
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A longitudinal study of family structure in Swedish persons with haemophilia
- 2014
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In: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 20:4, s. 493-499
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Journal article (peer-reviewed)abstract
- Haemophilia is an X-linked inherited rare bleeding disorder affecting mainly men. The treatment consists of replacement therapy that has been associated with severe side effects, such as blood transmitted viral infections, but has markedly improved over the last decades. The aim of this study was to study family structure over time among Swedish persons with haemophilia (PWH), focusing on children, siblings and marital status. PWH A or B were identified from the haemophilia centres and the national Patient Registry. Each PWH was compared to five age- and gender-matched controls. The national Multi-Generation Registry was used to identify children and siblings. A total of 1365 children with a father suffering from haemophilia A or B and 1938 siblings of the PWH were identified. Having one or more children was significantly less common (P=0.003) for PWH than for controls. Significantly lower rates of having a child were also found for the subgroups of persons suffering from severe haemophilia and those infected with HIV (P<0.001). A higher proportion of PWH, with or without HIV and/or viral hepatitis had siblings compared to the controls (P<0.001). However, the mean number of siblings was significantly lower for persons with severe haemophilia (P=0.001). The number of marriages and divorces did not differ between PWH and controls. Our data indicate a negative impact of HIV and viral hepatitis on family structure for PWH despite the relatively good access to treatment in Sweden over the last few decades. This was particularly true for those with a severe form of haemophilia.
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| 4. |
- Lövdahl, Susanna
(author)
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Co-morbidity and mortality in Swedish patients with haemophilia - A register study
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Haemophilia is an X-linked inherited recessive disorder affecting males. The increased risk of hemorrhage is explained by the deficiency in either coagulation factor VIII (haemophilia A) or IX (haemophilia B). The severity of haemophilia A and B is characterized by the bleeding pattern. For severe haemophilia bleeding is often spontaneous, mainly in muscles and joints. Since the 1950s the manifestations and treatment of the disease have undergone dramatic changes with, formerly, a median survival of 10-15 years and today a survival comparable to the general population. However, development of the treatment was catastrophically affected by transmission of human immunodeficiency virus (HIV) and viral hepatitis through plasma-derived products until the 1980s. With an increased survival among the haemophilia population other age-related co-morbidities will inevitably become more prevalent. Studies of these co-morbidities are increasingly important, not least since their management may differ among patients with bleeding disorders. The present thesis focuses on incidence, mortality, first degree relatives, and co-morbidities over time, in Swedish persons with haemophilia compared to persons without haemophilia. This was performed by using Swedish national registries and local registries from the three haemophilia centers in Sweden: Malmö, Gothenburg and Stockholm. In Paper I the long-term outcome of haemophilia in terms of incidence, morbidity and mortality was studied. People with haemophilia in Sweden demonstrate higher mortality over time, independent of HIV and viral hepatitis, compared to the control cohort. In Paper II the family structure, focusing on children, siblings and marital status was studied. Having one or more children was less common for persons with haemophilia than the controls, especially for those infected with HIV. With respect to co-morbidities, a special focus was on malignancies and cardiovascular diseases. These were studied in Paper III and IV. Patients with haemophilia showed a higher incidence of malignancies than patients without haemophilia, again, regardless of infection with HIV or viral hepatitis. Hypertension was shown to be elevated, whereas deaths due to cardiovascular diseases were lower when compared to persons without haemophilia.
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| 5. |
- Lövdahl, Susanna, et al.
(author)
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Hypertension and cardiovascular diseases in Swedish persons with haemophilia - A longitudinal registry study
- 2019
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In: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 181, s. 106-111
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Journal article (peer-reviewed)abstract
- Introduction: Data on the prevalence of hypertension and cardiovascular diseases (CVD) among persons with haemophilia (PWH) vary. Sweden has a long tradition of maintaining population-based data registries, and there is extensive follow-up of haemophilia patients due to the use of prophylaxis over decades. We evaluated the prevalence of these diseases among Swedish PWH compared to matched controls using a longitudinal study design. Methods: Data were obtained from the National Patient Registry and linked to records of persons with haemophilia enrolled in the haemophilia centres. For each subject, five gender and age matched controls were identified. Results: We identified 193 (19.7%) diagnoses of hypertension in PWH born in 1978 or earlier over >= 30 years compared with 550 (11.2%) among controls. The median ages and interquartile ranges were 60.0 (42.8, 69.9) and 57.2 (42.6, 70.6) years. The hazard rate (HR) for hypertension, PWH vs. controls, was 2.1, 95% CI: [1.8; 2.5], p < 0.001. The findings were similar in subgroup analyses of patients with non-severe and severe haemophilia with or without HIV and/or viral hepatitis. Angina pectoris was diagnosed in 69 (4.8%) of patients censored at age 75 compared with 311 (4.3%) in controls, and myocardial ischemia in 84 (5.9%) compared with 442 (6.2%). As a cause of death, the HR for myocardial ischemia, comparing PWH and controls, was 0.58, 95% CI: [0.42, 0.80], p = 0.001. Conclusion: Our data support an increased prevalence of hypertension among persons with haemophilia. The prevalence of CVD seems to be similar to that of controls, but with lower mortality.
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| 6. |
- Lövdahl, Susanna, et al.
(author)
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Incidence, mortality rates and causes of deaths in haemophilia patients in Sweden.
- 2013
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In: Haemophilia. - : Wiley. - 1351-8216. ; 19:3, s. 362-369
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Journal article (peer-reviewed)abstract
- Sweden has been a pioneer in the treatment of haemophilia, with the first concentrate available in the 1950s. Treatment has improved over the years to its current state-of-the art. The aim of the current study was to evaluate the long-term outcome of haemophilia in terms of incidence, morbidity and mortality. Patients diagnosed with haemophilia A or B registered at the national haemophilia centres and/or the Patient Registry and born before 2009 and alive in 1968 were enrolled and linked to the Cause of Death-, Migration- and Medical Birth registries. Five age- and sex-matched controls were selected for each patient. A total of 1431 patients with haemophilia A or B were compared with 7150 controls. The 3-year moving average incidence rate per 100 000 population varied between 21 and 36. The hazard ratio for all-cause mortality compared with controls was 2.2, 95% CI: [1.8; 2.7], P < 0.001 for the entire group of patients and 1.7, 95% CI: [1.3; 2.2], P < 0.001 when patients with HIV and/or viral hepatitis were excluded. The corresponding figures for the severe haemophilia subgroup were 6.6, 95% CI: [4.5; 10.0], P < 0.001 and 8.2, 95% CI [3.2; 20.8], P < 0.001 respectively. The most common causes of death were related to malignancies and the haemostatic defect. People with haemophilia were 57% less likely to die from ischaemic heart disease than controls. People with haemophilia in Sweden demonstrate higher mortality over time, independent of HIV and viral hepatitis, despite relatively advantageous access to clotting factor concentrates.
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| 7. |
- Lövdahl, Susanna, et al.
(author)
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Malignancies in Swedish persons with haemophilia : a longitudinal registry study
- 2016
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In: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 27:6, s. 631-636
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Journal article (peer-reviewed)abstract
- The aim of the study was to investigate, over time, the incidence of and mortality due to malignant diseases among persons with haemophilia, compared to matched controls. Persons with haemophilia A or B were enrolled via registries at each haemophilia centre, as well as from the National Patient Registry, and were compared to five sex and age-matched controls per patient. Data from the national Cancer Registry were linked to the study participants. A total of 1431 persons with haemophilia and 7150 matched controls were enrolled. Between the years 1972 and 2008, 164 malignancies were reported. The most common type of cancer among patients was prostate cancer, followed by haematologic malignancies, including lymphoma and leukaemia, which were significantly more frequent in patients [ n=35 (2.4%) vs. n=60 (0.8%); P < 0.001]. Malignancies in bladder and other urinary organs were also significantly different [ n=21 (1.5%) vs. n=46 (0.6%); P < 0.01]. The overall incidence rate ratio of malignancies per 1000 person-years compared to the controls was 1.3 [95% confidence interval (CI) 1.1, 1.6]. In subgroup analysis, the corresponding incidence rate ratios per 1000 person-years for persons with severe haemophilia was 1.7 (95% CI 0.9, 3.1) and that for mild/moderate haemophilia 1.1 (95% CI 0.8, 1.5). Swedish persons with haemophilia had a significantly higher incidence of malignant diseases than controls. These were primarily haematologic malignancies and cancer in urinary organs, and the difference independent of any co-infections with HIV and/or viral hepatitis. The findings indicate the importance of further studies and close follow-up of malignancies in persons with haemophilia.
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| 8. |
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