Impact of inherited bleeding disorders on maternal bleeding and other pregnancy outcomes: A population-based cohort study.

INTRODUCTION: Increasing rate of postpartum haemorrhage (PPH) has been observed between 2003 and 2010 in Canada. Inherited bleeding disorders contribute to the risk of PPH. AIM: To identify the trend in PPH in the last decade, assess the impact of bleeding disorders on pregnancy outcomes and evaluate their coagulation workup during pregnancy. METHODS: We conducted a population-based retrospective cohort study using the Alberta Pregnancy Birth Cohort from 2010 to 2018. We included women with von Willebrand disease (VWD) and haemophilia, identified by previously validated algorithm and matched with controls. Logistic regression was used to compute odds of PPH and other pregnancy outcomes. RESULTS: We identified 311,330 women with a total of 454,400 pregnancies with live births. The rate of PPH did not change significantly from 10.13 per 100 deliveries (95% CI 10.10-10.16) in 2010-10.72 (95% CI 10.69-10.75) in 2018 (p for trend = .35). Women with bleeding disorders were significantly more likely to experience PPH (odds ratio [OR] 2.3; 95% CI 1.5-3.6), antepartum haemorrhage (OR 2.9; 95% CI 1.5-5.9) and red cell transfusion (OR 2.8; 95% CI 1.1-7.0). We observed a nonsignificant rise in the rate of PPH in women with VWD and haemophilia. Only 49.5% pregnancies with bleeding disorders had third trimester coagulation factor levels checked. Higher odds of PPH and antepartum haemorrhage were observed even with factor levels ≥0.50 IU/mL in third trimester. CONCLUSION: Despite comprehensive care in women with bleeding disorders, they are still at higher risk of adverse pregnancy outcomes compared to population controls.

Increased acute care utilisation, comorbidities and mortality in adults with haemophilia: A population-based cohort study from 2012 to 2019.

INTRODUCTION: Improvements in treatment strategies have led to increased life expectancy of persons with haemophilia (PWH). Consequently, age-related comorbidities become increasingly relevant. AIM: To evaluate the prevalence of age-related comorbidities, mortality, health service utilisation and predictors of hospitalisation in PWH compared to the general population. METHODS: We conducted a population-based retrospective cohort study using linked administrative data. Men with haemophilia were identified in Alberta, Canada (2012-2019) with a validated case definition and were age-matched with male population controls. We calculated the prevalence of major comorbidities, all-cause mortality, and examined health service utilisation including Emergency Department visits and hospitalisations. Logistic regression was applied to identify predictors of hospitalisation. RESULTS: We identified 198 and 329 persons with moderately severe haemophilia and mild/moderate, respectively. Moderately severe haemophilia had a higher risk of death (standardised mortality ratio 3.2, 95% confidence interval [CI] 1.4-6.3) compared to the general population. PWH had a significantly higher prevalence of hypertension, liver diseases and malignancies than controls. Moderately severe haemophilia was associated with significantly higher rates of hospitalisations (52.5% vs. 14.5%), Emergency Department visits (89.1% vs. 62.7%) and intensive care admissions (8.9% vs. 2.3%). Age > 65 years (adjusted odds ratio [aOR] 6.8) and presence of multiple comorbidities (aOR 3.9) were significant predictors of hospitalisations among PWH. CONCLUSION: Despite advanced care, haemophilia is associated with higher acute care utilisation than the general population, highlighting the substantial burden of illness on patients and the health care system.

All-cause mortality and causes of death in persons with haemophilia: A systematic review and meta-analysis.

INTRODUCTION: Improvements in haemophilia treatment over the last decades resulted in increased life expectancy in persons with haemophilia (PWH). AIM: We conducted a systematic review and meta-analysis to examine all-cause mortality and causes of death among PWH. METHODS: We systematically searched EMBASE, MEDLINE, Web of Science, CINAHL and Cochrane central register of controlled trials from inception through March 15, 2021. Studies that reported a mortality estimate of PWH compared with the general population and/or reported causes of death were included. Random-effects meta-analysis with inverse variance method was used to obtain pooled estimates. We stratified the analysis by the year of cohort entry (before 2000 vs after 2000). RESULT: Of the 4769 studies identified, 52 met the eligibility criteria. The pooled all-cause standardized mortality ratio (SMR) from 9 studies in PWH was 1.93 (95% CI 1.38-2.70; I2 = 97%). The pooled SMRs before and after the year 2000 were 2.40 (95% CI 1.92-3.00; I2 = 87%) and 1.20 (95% CI 1.03-1.40; I2 = 62%), respectively. Before the year 2000, 31.2% deaths occurred due to HIV followed by haemorrhage (26.0%), cardiovascular disease (18.2%), liver disease (9.0%), and cancer (8.9%). Fewer (13.9%) deaths were attributable to HIV after the year 2000 with the proportion of deaths due to haemorrhage remaining unchanged. CONCLUSION: With treatment advances, mortality in PWH has declined over the last few decades approaching that of the general population. However, haemorrhage remains a leading cause of death requiring further attention.

Development and validation of a case definition to identify hemophilia in administrative data.

INTRODUCTION: Administrative data is useful in population-based studies in hemophilia, but few studies validated the coding accuracy. AIM: We validated the accuracy of a case definition using a combination of International Classification of Diseases diagnostic codes and coagulation factor level for identifying hemophilia in administrative data. METHODS: This is a retrospective population-based study of all residents of Alberta, Canada, who underwent testing for coagulation factor VIII (FVIII) or factor IX (FIX) activity between 2009 and 2017 using linked administrative data. Our predefined algorithm was a combination of the relevant ICD codes and FVIII/FIX activity <0.4 IU/ml. Medical charts of 2114 randomly selected patients tested for FVIII and 528 patients tested for FIX were reviewed to identify physician diagnoses of hemophilia. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were calculated. RESULTS: With our algorithm, 72 (3.4%) patients tested for FVIII and 21 (4.0%) tested for FIX met the combined ICD code and laboratory criteria for hemophilia A and hemophilia B, respectively, whereas 63 (3.0%) and 22 (4.2%) had confirmed hemophilia A and hemophilia B upon chart review. Our algorithm had a sensitivity of 93.7% and specificity of 99.4% for identifying hemophilia A, and a sensitivity of 90.9% and specificity of 99.8% for identifying hemophilia B. CONCLUSION: This study showed that using a case definition of ICD codes and coagulation factor activities can identify hemophilia in administrative data with very high accuracy and can be used for future research.

Survival patterns among venous thromboembolism patients with hematologic malignancies in Alberta, Canada from 2003 to 2015.

BACKGROUND: Hematologic malignancies are at increased risk of developing venous thromboembolism (VTE). OBJECTIVES: We aimed to identify the prevalence of hematologic malignancy in VTE patients and compare the survival with or without VTE. METHODS: Using linked administrative data and a validated algorithm we identified VTE cases in Alberta, Canada from 2003 to 2015. Subjects having International Classification of Diseases code for hematologic malignancies, solid tumors and both cancers within 1 year before and after the VTE index event were defined as cancer associated VTE cases. We also identified patients with no VTE. Cox proportional hazards model was applied to estimate the hazard ratio (HR) of death. Kaplan Meier analysis was performed to compare survival rate between different groups. RESULTS: We identified 5157 cancer associated VTE patients and 24,932 cancer patients with no VTE. Among the cancer associated VTE patients 697 (13.5%), 4376 (84.9%) and 84 (1.6%) had hematologic malignancies, solid tumors and both cancers, respectively. The median survival (in months) was significantly shorter in myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN) and plasma cell dyscrasia patients with VTE than those without (16.6 vs 27.1, p = 0.004; 70.6 vs 99.2, p = 0.023 and 32.9 vs 55.5, p = 0.007 respectively). Occurrence of pulmonary embolism in MDS and MPN patients and deep vein thrombosis in plasma cell dyscrasia patients were significantly associated with increased risk of death (adjusted HR: 3.0, 95% CI: 1. 46-6.16; adjusted HR 1.60, 95% CI:1.01-2.51 and adjusted HR: 1.40, 95% CI: 1.03-1.89 respectively). CONCLUSIONS: VTE adversely affects the survival among patients with hematologic malignancies.