Current recommendations on thromboprophylaxis for foot and ankle (FA) surgery are often inconsistent and generally based on weak evidence. The aim of this survey study was to evaluate the current... Show moreCurrent recommendations on thromboprophylaxis for foot and ankle (FA) surgery are often inconsistent and generally based on weak evidence. The aim of this survey study was to evaluate the current practice among ortho-pedic surgeons regarding venous thromboembolism (VTE) prophylaxis following FA surgery. From February 2019 to March 2020, an online questionnaire was sent by e-mail to orthopedic societies across the world. The question-naire was hosted by the International Society of Thrombosis and Haemostais RedCAP platform. Topics of interest were VTE rates following FA surgery, duration and type of thromboprophylaxis, bleeding complications, VTE risk factors for prophylaxis and use of risk assessment. A total of 693 FA orthopedic surgeons from all continents completed the survey of whom 392 (57%) performed more than 200 FA procedures per year. A total of 669/693 (97%) respondents stated that thromboprophylaxis is necessary in FA surgeries. When thromboprophylaxis was prescribed, half of surgeons prescribed it for the duration of immobilization. Acetylsalicylic acid, low molecular weight heparin and direct-oral anticoagulants were, in this order, the preferred choice. Acetylsalicylic acid and low molecular weight heparin were predominantly prescribed in North America and Europe, respectively. Previous deep vein thrombosis, immobility, obesity and inherited thrombophilia were considered the main risk factors indicative of thromboprophylaxis use. In this survey, most surgeons agree that thromboprophylaxis is indicated for FA surgery, but the prescription, type and duration of prophylaxis differs greatly with a large intercontinental discrepancy. These survey results could be a foundation for developing uniform guidelines to optimize thromboprophylactic strategies in FA procedures around the world. (c) 2023 by the American College of Foot and Ankle Surgeons. All rights reserved. Show less
Background: The mortality rate of Brazilian people with haemophilia (PwH) is decreasing, but the relative incidence of deaths associated with cardiovascular disease (CVD) is increasing.Objectives:... Show moreBackground: The mortality rate of Brazilian people with haemophilia (PwH) is decreasing, but the relative incidence of deaths associated with cardiovascular disease (CVD) is increasing.Objectives: We aimed to describe the CVD risk score of PwH according to Pooled Cohort Equations Risk (PCER) Calculator tool and its treatment recommendations. We also compared the PCER estimates with the respective Framingham Risk Score (FRS).Methods: This cross-sectional study included male PwH = 40 years treated at the Comprehensive Haemophilia Treatment Centre of Pernambuco (Recife/Brasil). PwH with a previous CVD event or a low-density lipid cholesterol = 5.0 mmol/L were excluded. Interviews, medical file reviews, and blood tests were performed. The PCER tool was used to estimate the CVD risk and compare it with the respective FRS. A p-value < 0.05 was accepted as statistically significant.Results: Thirty PwH were included. Median age was 51.5 [interquartile range-IQR; 46.0-59.5] years. The prevalence of obesity, systemic arterial hypertension, diabetes mellitus, hypertriglyceridaemia, hypercholesterolaemia, and hypoHDLaemia were 20%, 67%, 24%, 14%, 47%, and 23%, respectively. The median PCER score was 6.9% [IQR; 3.1-13.2], with 50% having a high risk (PCER = 7.5%). Statin use was suggested for 54% of PwH. Blood pressure was poorly controlled in 47% of PwH. The agreement between PCER and FRS was 80% (? = 0.60; p = 0.001).Conclusions: Half of the male people with haemophilia aged 40 years or older had a 10-year high risk of developing CVD with strong recommendations to improve control of dyslipidaemia and blood pressure. Show less
Background Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and... Show moreBackground Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and high-responding inhibitor (PwHA-HRi). The association between ITI outcome and time elapsed between inhibitor detection and start of ITI ( increment t(inhi-ITI)) is debatable. Objective The aim of this study was to evaluate this association among a large cohort of severe PwHA-HRi. Methods Severe (factor VIII activity level <1%) PwHA-HRi on ITI (n = 142) were enrolled in 15 hemophilia treatment centers. PwHA-HRi were treated according to the Brazilian ITI Protocol. ITI outcomes were defined as success (i.e., recovered responsiveness to exogenous FVIII) and failure (i.e., no responsiveness to exogenous FVIII and requirement of bypassing agents to control bleeding). Results Median ages at inhibitor detection and at ITI start were 3.2 years (interquartile range [IQR], 1.6-8.1) and 6.9 years [IQR, 2.6-20.1), respectively. PwHA-HRi were stratified according to increment t(inhi-ITI) quartiles: first (0.0-0.6 year), second (>0.6-1.7 year), third (>1.7-9.2 years), and fourth quartile (>9.2-24.5 years). The overall success rate was 65.5% (93/142), with no difference among first, second, third, and fourth quartiles (62.9%, 69.4%, 58.3%, and 71.4%, respectively) even after adjusting the analyses for potential confounders. Conclusion In conclusion, delayed ITI start is not associated with failure of ITI in PwHA-HRi. Therefore, ITI should be offered for these patients, regardless of the time elapsed between the detection of inhibitor and the ITI start. Show less
The risk of recurrence after discontinuation of anticoagulation for a combined oral contraceptive (COC)-associated venous thromboembolism (VTE) is unclear. Therefore, we conducted a systematic... Show moreThe risk of recurrence after discontinuation of anticoagulation for a combined oral contraceptive (COC)-associated venous thromboembolism (VTE) is unclear. Therefore, we conducted a systematic review and meta-analysis to estimate the incidence of recurrent VTE among women with COC-associated VTE, unprovoked VTE and to compare the incidence of recurrent VTE between the two groups. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase Classic +Embase and Medline ALL to July 2020 and citations from included studies were searched. Randomized controlled trials, prospective cohort studies and meta-analyses of these study types were selected. The analysis was conducted by random-effects model. Nineteen studies were identified including 1537 women [5828 person-years (PY)] with COC-associated VTE and 1974 women (7798 PY) with unprovoked VTE. Studies were at low risk of bias. The incidence rate of VTE recurrence was 1.22/100 PY [95% confidence interval (CI) 0.92-1.62, I-2 = 6%] in women with COC-associated VTE, 3.89/100 PY (95% CI 2.93-5.17, I-2 = 74%) in women with unprovoked VTE and the unadjusted incidence rate ratio was 0.34 (95% CI 0.26-0.46, I-2 = 3%). The recurrence risk in women after COC-associated VTE is low and lower than after an unprovoked VTE. Show less
Jardim, L.L.; Santana, M.P.; Chaves, D.G.; Bom, J. van der; Rezende, S.M. 2021
Up to 35% of patients with hemophilia A and 5% with hemophilia B develop neutralizing antibodies which can inhibit the therapeutic activity of factor replacement (inhibitors). Despite the clinical... Show moreUp to 35% of patients with hemophilia A and 5% with hemophilia B develop neutralizing antibodies which can inhibit the therapeutic activity of factor replacement (inhibitors). Despite the clinical relevance of antifactor VIII and IX neutralizing antibodies, there is still a major gap on the knowledge of risk factors for their development. Furthermore, most of the studies on risk factors for inhibitor development come from Caucasian and Afro-American populations. The HEMFIL is a Brazilian prospective cohort study of previously untreated children with hemophilia, which primary aim is to identify new risk factors related to inhibitor development. This manuscript aims at describing the study design and its methodology. After the diagnosis, children are followed up to 75 exposure days or to inhibitor development. Standardized forms and blood samples are collected to describe clinical characteristics and to perform the measurement of immunological and genetic biomarkers at three time points; Inclusion time (T0), at inhibitor development or at 75 exposure days without inhibitors (T1) and after immune tolerance induction for patients in whom it is indicated and performed (T2). Currently, 120 children have been included, of whom, 95 have completed the follow-up. For severe/moderately severe hemophilia A, the cumulative incidence of inhibitors at 75 exposure days was 35% (95% confidence interval, 26-46%). The inclusion of additional patients and a longer follow-up will allow the analysis of risk factors for inhibitor development. Show less
Camelo, R.M.; Caram-Deelder, C.; Duarte, B.P.; Moura, M.C.B. de; Costa, N.C.D.; Costa, I.M.; ... ; Bom, J. van der 2021
Since the introduction of episodic and prophylactic treatments with safer factor concentrates, the life expectancy of people with haemophilia (PwH) has improved considerably. Ageing-related... Show moreSince the introduction of episodic and prophylactic treatments with safer factor concentrates, the life expectancy of people with haemophilia (PwH) has improved considerably. Ageing-related diseases such as cardiovascular disease (CVD) have also become more prevalent in PwH. This cross-sectional study aimed to evaluate CVD risk factors and estimate 10-year risk for CVD events among PwH. Male patients >= 30 years were interviewed and examined. Blood tests were performed at the local laboratory. Eighty-two patients were included, of whom 83% had haemophilia A and half had severe disease. Median age at study entry was 43.0 years (interquartile range [IQR], 36.0-51.3). Prevalence of obesity, systemic arterial hypertension (SAH) and diabetes mellitus were 16%, 60% and 16%, respectively. Hypertriglyceridaemia, hypercholesterolaemia and low HDL blood levels were present in 18%, 41% and 30% of patients, respectively. Metabolic syndrome was found in 37%. The Framingham Risk Score showed that 39% of PwH had a high risk of developing cardiovascular events in the following 10 years. We conclude that, in this cohort, PwH have a higher prevalence of SAH when compared with Brazilian men without haemophilia and about two-fifths have a high risk of developing a CVD event in the following 10 years. Show less
Objective This study aimed at evaluating the effect of thrombophilia on the risk of venous thromboembolism (VTE) in patients undergoing any type of orthopedic surgery.Background Patients undergoing... Show moreObjective This study aimed at evaluating the effect of thrombophilia on the risk of venous thromboembolism (VTE) in patients undergoing any type of orthopedic surgery.Background Patients undergoing orthopedic surgery are at high risk for VTE. Although patients with thrombophilia have an increased risk of VTE, it is currently unclear whether there is a synergetic effect in patients with thrombophilia who undergo orthopedic surgery.Methods Data from a large population-based case-control study (the Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis study) were used. Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for age, sex, and body mass index (BMI) (ORadj) were calculated for patients undergoing any orthopedic intervention.Results Of 4721 cases and 5638 controls, 263 cases and 94 controls underwent orthopedic surgery. Patients who had any orthopedic intervention in the year before the index date were at higher risk of VTE (ORadj 3.7; 95% CI, 2.9-4.8) than those who did not undergo any orthopedic surgery. There was an additionally increased risk in patients with factor V Leiden (OR 17.5, 95% CI, 4.1-73.6), non-O blood group (OR 11.2; 95% CI, 3.4-34.0), or elevated plasma levels of factor VIII (OR 18.6; 95% CI, 7.4-46.9) all relative to patients without these defects, not undergoing orthopedic surgery.Conclusions Patients with factor V Leiden, high levels of factor VIII, or blood group non-O were found to have a high risk of VTE after orthopedic surgery. Identification of these patients may enable individualized thromboprophylactic treatment to efficiently reduce VTE risk. Show less
Venous thromboembolism (VTE) is a chronic disease. Strategies to assess groups at a high risk of recurrence are needed. We reported that patients without prior risk situation for VTE had an... Show moreVenous thromboembolism (VTE) is a chronic disease. Strategies to assess groups at a high risk of recurrence are needed. We reported that patients without prior risk situation for VTE had an incidence rate ratio (IRR) three times higher when compared with those with this history. The aim of this study was to re-evaluate the cohort, with a longer follow-up and evaluated the association between the absence of a prior risk situation for VTE with an increased risk for recurrence. A total of 289 patients with a previous VTE were followed for 116 months. Patients were advised to attend the outpatients' clinic in case of suspected VTE recurrence. Incidence rates of recurrent thrombotic events were calculated as the number of events over the accumulated observation time. Recurrent VTE occurred in 52 (18%) patients. Patients with a provoked first event and positive prior risk situations for VTE had an incidence rate for recurrence of 1.2 [95% confidence interval (95% CI), 0.7-1.9] per 100 patient-years. The IRR of this subgroup compared with patients with a provoked event without prior risk situations for VTE was 0.9 (95% CI 0.4-2.4). IRR was 2.5 (95% CI, 1.3-4.9) in patients with an unprovoked event and positive prior risk situations and 5.9 (95% CI, 32.8-12.5) in patients with an unprovoked event and no prior risk situations compared with patients with a provoked event without other prior risk situations for VTE. Exposure to prior risk situations for VTE was a protective factor among those patients whose first VTE event was unprovoked. Show less
This illustrated review focuses on the development of inhibitors in patients with congenital hemophilia, which is the most serious treatment-related complication in these patients. Hemophilia A (HA... Show moreThis illustrated review focuses on the development of inhibitors in patients with congenital hemophilia, which is the most serious treatment-related complication in these patients. Hemophilia A (HA) is an inherited X-linked bleeding disorder affecting 1:5000-10 000 newborn males worldwide. It results from the deficiency of coagulation factor VIII (FVIII), due to mutation(s) in its coding gene (F8). Treatment requires administration of FVIII-containing products either on demand or as prophylaxis, which can induce inhibitor development in 20%-35% of patients. Inhibitors are alloantibodies that neutralize the procoagulant activity of exogenous FVIII. During the initial administration of FVIII-containing products, patients with HA can develop a proinflammatory immune response with synthesis of anti-FVIII IgG1, which has no FVIII inhibitory activity. However, in patients with inhibitors, immune response shifts toward an anti-inflammatory/regulatory pattern favoring the synthesis of anti- FVIII IgG4 antibodies. Patients with inhibitors present with bleeding episodes that are difficult to control, and they have reduced response to FVIII replacement. Currently, immune tolerance induction is the available treatment for eradication of persistent high-titer inhibitors. Despite the clinical relevance, the immunological mechanisms for inhibitor development in patients with HA remains unexplained. Show less
Introduction Brazil has the fourth largest world population of patients with haemophilia. However, mortality rates in this population are unknown. Aim To analyse mortality and its causes in... Show moreIntroduction Brazil has the fourth largest world population of patients with haemophilia. However, mortality rates in this population are unknown. Aim To analyse mortality and its causes in Brazilian patients with haemophilia from 2000 to 2014. Methods The number of deceased patients with haemophilia and causes of death were obtained from the Brazilian National Mortality Information System (SIM), according to the 10th International Classification of Diseases (ICD-10). Standardized mortality ratios (SMR) were calculated to estimate the rate of overall death of patients with haemophilia relative to that of the Brazilian general male population. Results A total of 784 deaths were identified in the period of 15 years. Mortality of patients with haemophilia was 13% higher when compared with the general male population (SMR 1.13, 95% CI: 1.01-1.16). Haemorrhage was the main cause of death (n = 254; 32.4%) of which 137 (54%) was intracranial haemorrhage. The total number of deaths due to HIV decreased over the years, and an increase in deaths due to cancer and cardiovascular disease was observed. A total of 129 deaths (16.5%) were related to hepatitis infection, of whom, 109 (86.5%) patients also presented with cirrhosis and hepatocellular carcinoma or other liver diseases. Conclusion Mortality rate of Brazilian patients with haemophilia decreased over the evaluated period. Intracranial haemorrhage is still an important cause of death in these patients, which requires major effort for prevention. Death due to age-related cardiovascular disease and cancer has increased over the years, following the same tendency observed in developed countries. Show less
