Summary
The prognosis of patients with myocardial infarction (MI) and normal coronary arteries (NCA) in the presence of an inherited coagulation disorder is unknown. The purpose of this study was to ...compare the clinical thrombosis outcome of patients with (GpI) or without (GpII), inherited coagulation disorders, who suffered from an acute MI with NCA. Eighty two consecutive patients (mean age 49 ± 15 years; 29 females) with MI, but NCA, were recruited. Twelve patients (15%) had an inherited coagulation disorder. GpI and GpII were statistically similar regarding age (45 ± 11 vs 50 ± 16 years-old), gender (33 vs. 36% female), tobacco consumption (50 vs. 53%), diabetes mellitus (8 vs. 10%), hypertension (25 vs. 17%), obesity (8.3 vs. 14%), family history of coronary heart disease (33 vs. 19%), hypercholesterolemia (50 vs. 21%; p = . 08), left ventricular ejection fraction (58 ± 13 vs. 61 ± 13%) and spasm (8.3% vs. 17%). All patients were initially treated with antiplatelet agents with the exception of one (8%) in GpI, and 6 (9%) in GpII who were taking oral anticoagulant therapy (ns). The mean follow-up was 57 ± 26 (range from 2-91 months). During the outcome, 12/78 (15.4%) thrombosis events occurred, including venous thrombosis or pulmonary embolism (1/12 vs. 1/66), reinfarction (2/12 vs. 4/66), and stroke (2/12 vs. 2/66), with two events in one patient (GpI). Kaplan-Meier event-free survival, with combined end-point, defined as venous thrombo-embolic event, reinfarction, or stroke differed between the two groups: 4/12 (33.3%) in GpI and 7/66 (10.6%) in Gp II (p <. 02). Patients with MI, NCA and congenital coagulation disorder present a high risk of thrombosis recurrence under antiplatelet agent.
Presented in part at the 52nd Annual Scientific Session of the American College of Cardiology; March 30-April 2, Chicago USA 2003, Abstract.
Abstract Background Calibrated Automated Thrombography (CAT) has been widely used to assess in vitro thrombin generation as an informative intermediary phenotype of coagulation. Interlaboratory ...exercises have documented a worrisome poor reproducibility. There are some data on the normalisation with an appropriate external reference plasma (RP). This multicentre study of the French-speaking CAT Club aimed at providing further evidence for the usefulness of such a normalisation. Materials and Methods Lyophilised aliquots of a RP along with 3 plasmas (P1 = normal; P2 = hypo-; P3 = hypercoagulable) were sent to 34 laboratories (corresponding to 38 instruments). CAT was studied using 1 and 5 pM tissue factor and other dedicated reagents. Normalisation with the local RP in use in the laboratory could also be performed. Interlaboratory CVs were calculated for each plasma before and after normalisation. Results Regarding endogenous thrombin potential, a good discrimination between the 3 plasmas was achieved in all laboratories but there was no overlap after normalisation only. CVs were generally not reduced with the use of local RP but were generally improved with normalisation using the external RP, often becoming lower than 10%. Regarding P2 however, the benefit of normalisation was poor, and there were analytical difficulties as well, some laboratories being unable to get a useable signal. Conclusions We confirm that normalisation of CAT results with a suitable external RP is useful in “real life” practice as it often permits an acceptable level of interlaboratory variability. In case of frank hypocoagulability, further improvements are required to get reliable, potentially clinically relevant results.
Introduction
Health of people with severe haemophilia (PwSH) improves thanks to the advancements in haemophilia care, giving them more opportunities in occupational integration. However, there is ...little literature on the occupational integration of PwSH.
Objectives
The main objective of our study was to assess the occupational integration of PwSH and to compare it with that of the general population. The secondary objective was to study the association between individual characteristics (sociodemographic, clinical and psycho‐behavioural) and occupational integration of PwSH.
Methods
A multicentre, non‐interventional, cross‐sectional study was conducted in 2018–2020 on PwSH, aged over 18 and under 65 years and included in the FranceCoag registry. Measurements included indicators of occupational integration, sociodemographic, clinical and psycho‐behavioural characteristics. The indicators of occupational integration were compared with those of the general population, using indirect standardization. The data of the general population were available from the National Institute of Statistics and Economic Studies (INSEE). Determinants of occupational integration were explored using structural equation modelling.
Results
Of 1262 eligible people, 588 were included. PwSH had a lower employment rate than the general population (standardized ratio, .85; 95% CI, .77–.94). There were more PwSH at tertiary education level than expected (standardized ratio, 1.38; 95% CI, 1.17–1.61). HIV infection, poor physical health and mental health concerns were associated with a higher risk of unemployment in PwSH.
Conclusion
Employment rate of PwSH is lower than that of the general population despite their higher education level. Target interventions focusing on determinants of difficult occupational integration could be helpful for PwSH.
Argatroban is a direct anti-IIa (thrombin) anticoagulant, administered as a continuous intravenous infusion; it has been approved in many countries for the anticoagulant management of heparin-induced ...thrombocytopaenia (HIT). Argatroban was recently proposed as the non-heparin anticoagulant of choice for the management of patients diagnosed with Vaccine-induced Immune Thrombotic Thrombocytopaenia (VITT). Immunoglobulins are also promptly intravenously administered in order to rapidly improve platelet count; concomitant therapy with steroids is also often considered. An ad hoc committee of the French Working Group on Haemostasis and Thrombosis members has worked on updated and detailed proposals regarding the management of anticoagulation with argatroban, based on previously released guidance for HIT, and adapted for VITT. In case of VITT, the initial dose to be preferred is 1.0 µg × kg−1 × min−1, with further dose-adjustments based on iterative and frequent clinical and laboratory assessments. It is strongly advised to involve a health practitioner experienced in the management of difficult cases in haemostasis. The first laboratory assessment should be performed 4 h after the initiation of argatroban infusion, with further controls at 2–4-h intervals until steady state, and at least once daily thereafter. Importantly, full anticoagulation should be rapidly achieved in case of widespread thrombosis. Cerebral vein thrombosis (which is typical of VITT) should not call for an overly cautious anticoagulation scheme. Argatroban administration requires baseline laboratory assessment and should rely on an anti-IIa assay to derive argatroban plasma levels using a dedicated calibration, with a target range between 0.5 and 1.5 µg/mL. Target argatroban plasma levels can be refined based on meticulous appraisal of risk factors for bleeding and thrombosis, on frequent reassessments of clinical status with appropriate vascular imaging, and on the changes in daily platelet counts. Regarding the use of aPTT, baseline value and possible causes for alterations of the clotting time must be taken into account. Specifically, in case of VITT, an aPTT ratio (patient’s/mean normal clotting time) between 1.5 and 2.5 is suggested, to be refined according to the sensitivity of the reagent to the effect of a direct thrombin inhibitor. The sole use of aPTT is discouraged: one has to resort to a periodical check with an anti-IIa assay at least, with the help of a specialised laboratory if necessary. Dose modifications should proceed in a stepwise manner with 0.1 to 0.2 µg × kg−1 × min−1 up- or downward changes, taking into account the initial dose, laboratory results, and the whole individual setting. Nomograms are available to adjust the infusion rate. Haemoglobin level, platelet count, fibrinogen plasma level and liver tests should be periodically checked, depending on the clinical status, the more so when unstable.
Introduction
There is a lack of joint recommendations by healthcare professionals (HCP) and patient organizations when a partnership between high and low‐income countries in the field of haemophilia ...is planned.
Aim
To draft recommendations to clarify the methodology when a partnership between low‐ and high‐income countries is planned with the objective of a long‐term implication. This methodology is to be implemented for fulfilling both medical and associative aims.
Methods
Based on the available literature, a first document was written, then diffused to AFATH (Alliance Franco‐Africaine pour le Traitement de l’Hémophilie) members, and after a one‐day meeting and further amendments, a second draft was approved by all members before submission for publication.
Results
Based on 6 years experience, several recommendations regarding the joint and separate roles of patient association and HCP for a first mission in French‐speaking sub‐Saharan African countries have been established. The proposed methodology for establishing preliminary contacts, the first visit and the key points for diagnostic action, medical follow‐up, patient education and advocacy strategy outlines a model of partnership between patients and HCP.
Conclusion
This paper written jointly by patients and physicians underlines the importance of reciprocal expert guidance and a partnership based on complementary inputs.
Summary
Factor VIII inhibitor bypass activity (FEIBA) is a recommended first‐line bypassing agent for bleeding episodes in patients with acquired haemophilia A (AHA). Due to the low incidence of AHA, ...available clinical data on FEIBA treatment are limited. The study aim was to delineate practice patterns in FEIBA treatment of AHA patients, the haemostatic efficacy of FEIBA, including criteria for its assessment, and safety. A prospective registry was established of AHA patients receiving FEIBA for bleeding episodes or prophylaxis at the time of invasive procedures. Data were collected at 16 participating centres in France. Patients were followed up for 3 months. Haemostatic efficacy, FEIBA regimen and FEIBA‐related adverse events were documented. Thirty‐four patients averaging 81.8 years old with standard deviation (SD) 8.1 years were included in the study: 33 for acute bleeding and one for haematoma evacuation. The mean initial dose of FEIBA for acute bleeding was 75.4 U kg−1 (SD, 7.7 U kg−1), most often administered twice daily, and the median duration of FEIBA treatment was 4.0 days (interquartile range, 2.2–8.0 days). FEIBA was effective in managing 88.0% of bleeding episodes (95% confidence interval, 75.8–94.5%). No baseline variables influencing treatment response could be identified. The sensitivity and specificity of an objective haemostatic efficacy scale in predicting sequential investigator assessments of haemostatic efficacy were 45.3% and 84.1% respectively. Four patients experienced a total of six serious adverse events possibly related to FEIBA. In the first prospective study specifically focused on FEIBA treatment of patients with AHA, 88.0% of bleeding episodes were effectively managed.
Abstract
Background
Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin treatments, and only a few large patient cohorts have been reported. In this study, biological and ...clinical data from 144 French patients with HIT were analyzed in comparison with the literature.
Methods
The diagnosis of HIT was confirmed in all patients by an immunoassay combined with serotonin release assay. In the literature, only cohorts of at least 20 HIT patients published from 1992 were selected for a comparative analysis.
Results
Two-thirds of patients were hospitalized in surgery and most were treated with unfractionated heparin (83.2% vs. 16.8% with low molecular weight heparin only). Thrombotic events in 54 patients (39.7%) were mainly venous (41/54). However, arterial thrombosis was more frequent after cardiac surgery (13.2% vs. 2.4% in other surgeries,
p
= 0.042) with a shorter recovery time (median = 3 vs. 5 days,
p
< 0.001). The mortality rate was lower in our series than in the 22 selected published studies (median = 6.3% vs. 15.9%). Three genetic polymorphisms were also studied and homozygous subjects FcγRIIA RR were more frequent in patients with thrombosis (37.8 vs. 18.2% in those without thrombosis,
p
= 0.03).
Conclusion
This study shows that the mortality rate due to HIT has recently decreased in France, possibly due to earlier diagnosis and improved medical care. It also confirms the strong association between polymorphism FcγRIIA H131R and thrombosis in HIT.
Abstract Objectives Many questions remain regarding the mechanism of perinatal stroke. Methods In a series of 100 prospectively enrolled term neonates with symptomatic arterial ischemic stroke, we ...explored family antecedents, pregnancy and delivery conditions and clinical presenting features and distinguished features of the 50 larger infants with the remainder. Cardiac and cervical arterial imaging were performed in 70 and 51 cases. Results Previous fetal loss, first pregnancy, primiparity, twin-gestation, cesarean and traumatic delivery, neonatal distress, male sex and premature rupture of membranes were statistically more common than in the general population. Normal pregnancy proportion and mean birthweight were in the normal range, arguing against a vasculo-placental origin in the majority. Furthermore, there was an excess of large babies. The larger infants were more subject to suffer from acute perinatal events, with a trend for an excess of neonatal distress ( p = 0.065) and for more severe presenting features ( p = 0.027), while the lighter were more likely to have experienced longstanding obstetrical risk factors such as complicated pregnancy ( p = 0.047) and tobacco exposure ( p = 0.028). Cervical MR angiography showed an internal carotid occlusion in two babies, whereas echo-Doppler was always normal; in one case the two methods were discordant. Echocardiography was non-informative. Interpretation The data from this prospective cohort of neonates with stroke confirm that many obstetrical and perinatal factors are risk determinants. They also suggest that birthweight and gender may be biomarkers of two populations of neonates with different pathological mechanisms. MR angiography appears more sensitive than echo-Doppler for the exploration of the neonatal cervical vasculature.
The Innovance VWF:Ac test (Siemens) has the particularity to assess the binding capacity of von Willebrand factor (VWF) to recombinant platelet GPIb mutated in the absence of ristocetin. Our study ...aimed to evaluate and validate according to standard NF EN ISO 15189 the original protocol adaptation on STA-R Evolution series analyser (Diagnostica Stago). We evaluated the performance in terms of imprecision and we validate additional parameters necessary in range B as recommended by the SH GTA 04 (Cofrac). We compared the new assay with the reference assay: ristocetin cofactor activity (VWF:RCo) performed on the BCS-XP analyser by testing retrospectively samples from 82 healthy normal subjects and 61 patients with von Willebrand disease (VWD). This new assay is consistent with objectives set in terms of imprecision with CV around 4%. Excepted limit of quantification higher, additional parameters evaluated in range B have been validated. The Innovance VWF: Ac assay allowed the detection of all deficits of VWF already detected by the VWF:RCo test on the BCS-XP. This adjustment on STA-R analyser therefore has satisfactory analytical performance criteria. Apart from the limit of quantification, this reagent can be used according to the recommendations specified in the original protocol adaptation. Its performance and compatibility with the spot measurement allow the diagnosis and therapeutic monitoring of VWD according to current requirements and guidelines.
Blood coagulation represents one of the most studied processes in biomedical modelling. However, clinical applications of this modelling remain limited because of the complexity of this process and ...because of large inter-patient variation of the concentrations of blood factors, kinetic constants and physiological conditions. Determination of some of these patients-specific parameters is experimentally possible, but it would be related to excessive time and material costs impossible in clinical practice. We propose in this work a methodological approach to patient-specific modelling of blood coagulation. It begins with conventional thrombin generation tests allowing the determination of parameters of a reduced kinetic model. Next, this model is used to study spatial distributions of blood factors and blood coagulation in flow, and to evaluate the results of medical treatment of blood coagulation disorders.
PDF
