Report of a recurrent cerebral venous thrombosis in a young athlete

BACKGROUND: Reports of occurrence of deep vein thrombosis during intensive sport are scarce. While a few cases have been described in the cerebral territory, these are only in the context of traumatism or anabolic agent consumption. Thus, causality with exercise remains uncertain and the mechanisms hypothetic. We present the case of a young athlete who experienced two episodes of severe cerebral venous thromboses (CVT), both during intensive training, in the absence of any other known thrombogenic factor. CASE PRESENTATION: A healthy 26-year-old man presented a thrombosis of the superior sagittal sinus during recent intensive training for a triathlon. Investigation at the time found no drug or anabolic steroid consumption, or any hematologic or coagulation disturbance. Anticoagulation therapy was initiated for 10 months with good outcome. One year later, soon after returning to intensive exercise, mainly running, the patient presented a thrombosis of the straight sinus complicated by bithalamic hyperintensities observed on T2 magnetic resonance imaging sequences. Anticoagulation treatment was reinitiated and led to repermeabilization of the cerebral vein and reversibility of thalamic abnormalities. Four months later, the patient was free of headache and had no cognitive impairment. He continues to practice intensive sport with vitamin K antagonist as preventive treatment. CONCLUSION: This is the first case report of recurrent CVT in a context of intensive sport, without any other thrombogenic features, suggesting a causal link. Intensive exercise should be considered as a potential promoting factor of CVT and investigated during routine examination

Usefulness of Flow Cytometric Mepacrine Uptake/Release Combined with CD63 Assay in Diagnosis of Patients with Suspected Platelet Dense Granule Disorder.

Dense granule disorder is one of the most common platelet abnormalities, resulting from dense granule deficiency or secretion defect. This study was aimed to evaluate the clinical usefulness of the flow cytometric combination of mepacrine uptake/release assay and CD63 expression detection in the management of patients with suspected dense granule disorder. Over a period of 5 years, patients with abnormal platelet aggregation and/or reduced adenosine triphosphate (ATP) secretion suggestive of dense granule disorder were consecutively enrolled. The flow cytometric assays were systematically performed to further investigate dense granule functionality. Among the 26 included patients, 18 cases showed impaired mepacrine uptake/release and reduced CD63 expression on activated platelets, consistent with δ-storage pool deficiency (SPD). Another seven patients showed decrease in mepacrine release and CD63 expression but mepacrine uptake was normal, indicating secretion defect rather than δ-SPD. Unfortunately, ATP secretion could not be measured in 7 out of the 26 patients due to insufficient sample and/or severe thrombocytopenia. This test combination provides a rapid and effective method to detect the heterogeneous abnormalities of platelet dense granule by distinguishing between storage and release defects. This combination is particularly advantageous for severely thrombocytopenic patients and pediatric patients in which only minimal sample is required

FranceCoag: a 22-year prospective follow-up of the national French cohort of patients with inherited bleeding disorders.

FranceCoag is an ongoing open prospective multicentre cohort project aimed at improving epidemiological knowledge about inherited bleeding disorders in France. The main objective of this article was to evaluate the project's progress as of the 30th December 2016. Between 1994 and this date, of the 10,047 patients included in the study, 384 (3.8%) were reported by clinicians to have died and 159 (1.6%) to be lost to follow-up. Among the remaining 9504 patients still being followed up, 5748 (60.5%) had haemophilia A, 1300 (13.7%) haemophilia B, 1980 (20.8%) von Willebrand Disease while 476 (5.0%) had another clotting factor deficiency (Factor I, II, V, combined V and VIII, VII, X, XI and XIII). The median age of the population was 32 years (Inter-quartile range (IQR) 18-50 years) at data extraction on December 30th, 2016. The subgroup of children (i.e., < 18 years old) with severe haemophilia and comprehensive information available since the first exposure to treatment was identified as the PUPs (Previously Untreated Patients) cohort. Data for the 643 children included in the PUPs' cohort had been collected since their birth. Follow-up data were collected by the clinicians in haemophilia treatment centres (HTC) every 12.9 months on median (IQR 11.4-21.3). In the PUPS cohort, data were updated every 6.2 months on median (IQR 3.7-11.7). A unique patient number assigned at study inclusion was kept at individual HTC by participating clinicians. The data collected included demographic, clinical, therapeutic and biological items on standard electronic forms. As of December 30th 2016, a plasma and serum samples was available for 2581 patients (27.1%)

Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?

International audienc

Relationship between plasma tissue Factor Pathway Inhibitor (TFPI) levels, thrombin generation and clinical risk of bleeding in patients with severe haemophilia A or B

International audienceAbstract Introduction Bleeding severity in severe haemophilic patients, with low thrombin generation (TG) capacity, can vary widely between patients, possibly reflecting differences in tissue factor pathway inhibitor (TFPI) level. Aim To compare free TFPI (fTFPI) levels in patients with severe haemophilia A (sHA) and severe haemophilia B (sHB) and to investigate in these patients as a whole the relationships between bleeding and TG potential, between TG potential and fTFPI level and between fTFPI level and bleeding tendency. Methods Data on bleeding episodes retrospectively recorded during follow‐up visits over 5–10 years were collected and used to calculate the annualised joint bleeding rate (AJBR). fTFPI levels and basal TG parameters were determined in platelet‐poor plasma (PPP) and platelet‐rich plasma (PRP) using calibrated automated tomography (CAT). Results Mean fTFPI levels did not differ significantly between sHA ( n = 34) and sHB ( n = 19) patients. Mean values of endogenous thrombin potential (ETP) and thrombin peak (peak) in PPP and PRP were two‐fold higher when fTFPI levels < 9.4 versus > 14.3 ng/mL. In patients treated on demand, ETP and peak in PRP were doubled when AJBR was , AJBR being halved in patients with a low fTFPI level (9.4 ng/mL). In patients on factor prophylaxis, no association was found between TG parameters and either fTFPI level or AJBR. Conclusion In patients treated on demand, bleeding tendency was influenced by fTFPI levels, which in turn affected basal TG potential. In patients on prophylaxis, bleeding tendency is probably determined primarily by the intensity of this treatment

Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?

We retrospectively analysed the data files of 171 adults and 87 children/adolescents with severe haemophilia, except for 14 patients (moderate; minor) (1), to develop a global population pharmacokinetic (PK) model for eight factors VIII (FVIII) that could estimate individual PK parameters for targeting the desired level of FVIII activity (FVIII:C); and (2) to compare half-life (HL) in patients switching from a standard half-life (SHL) to an extended half-life (EHL) and evaluate the relevance of the switch. One-stage clotting assay for the measurement of FVIII activity (FVIII:C, IU/mL) was used for population PK modelling. The software, Monolix version 2019R1, was used for non-linear mixed-effects modelling. A linear two-compartment model best described FVIII:C. The estimated PK parameters (between-subject variability) were: 2640 mL (23.2%) for volume of central compartment (V1), 339 mL (46.8%) for volume of peripheral compartment (V2), 135 mL/h for Q (fixed random effect), and 204 mL/h (34.9%) for clearance (Cl). Weight, age, and categorical covariate EHL were found to influence Cl and only weight for V1. This model can be used for all of the FVIII cited in the study. Moreover, we demonstrated, in accordance with previous studies, that Elocta had longer half-life (EHL) than SHL (mean ratio: 1.48) as compared to Advate, Factane, Kogenate, Novoeight, and Refacto.</jats:p