Heparin-induced thrombocytopenia leading to a diagnosis of essential thrombocythemia

International audienceEssential thrombocythemia (ET) belongs to the “BCR-ABL-negative” subcategory of myeloproliferative neoplasms (MPN) along with polycythemia vera (PV) and primary myelofibrosis (PM). Various recurrent molecular alterations have been described in classical MPN, such as JAK2 V617F, MPL W515L/K mutations, and deletion or insertions in the calreticulin (CALR) gene.1 MPN are known for high incidence of thrombotic complications, with a predominance of arterial rather than venous events (16.2% vs 6.2%). Indeed, the prevalence of overall thrombosis has been described in 28.6%, 20.7%, and 9.5% of patients with PV, ET, and PM, respectively.2 In addition to the traditional risk factors of thrombosis, blood cells count, mutational profile, chronic inflammation, and abnormal cell adhesion appear to be specific risk factors of thrombosis in MPN-patients.3 The classical initial treatment of these thrombotic complications includes unfractionated heparin (UFH)

Management of a High-Risk Surgery with Emicizumab and Factor VIII in a Child with a Severe Hemophilia A and Inhibitor

International audienceThe recent development of a humanized, bi-specific, and monoclonal antibody mimicking the function of activated factor VIII was a revolution in the management of patients suffering from severe hemophilia A with inhibitors. The phase III randomized studies have shown a more efficient prophylaxis of this subcutaneous administered drug in these patients compared with recombinant FVIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC). Nonetheless, there are “real life” matters that need to be explored in this new era of managing hemophilia patients, such as surgery management under emicizumab, especially in children. Here, we report the first case, to our knowledge, of major orthopedic surgery managed with factor VIII infusions in a child with inhibitor receiving emicizumab

Factors Influencing anti-Xa assays: A Multicenter Prospective Study in Critically Ill and Noncritically Ill Patients Receiving Unfractionated Heparin

International audienceBackground: The presence of dextran sulfate (DS) in reagents and the type of blood collection tube (citrate/citrated-theophylline-adenosine-dipyridamole [CTAD]) can lead to discrepancies between unfractionated heparin (UFH) anti-Xa levels.Objectives: To evaluate the extent of the effect (1) of different reagents containing or not containing DS and (2) of the blood collection tubes, on UFH anti-Xa levels, in various clinical situations (NCT04700670).Methods: We prospectively included patients from eight centers: group (G)1, cardiopulmonary bypass (CPB) after heparin neutralization (n = 39); G2, cardiothoracic intensive care unit (ICU) after CPB (n = 35); G3, medical ICU (n = 53); G4, other medical inpatients (n = 38). Blood was collected into citrated and CTAD tubes. Chromogenic anti-Xa assays were centrally performed, using seven reagent/analyzer combinations including two without DS. The association between anti-Xa levels and covariates was tested using a linear mixed-effects model.Results: We analyzed 4,546 anti-Xa values from 165 patients. Median anti-Xa levels were systematically higher with reagents containing DS, whatever the patient group, with the greatest effect observed in G1 (0.32 vs. 0.05 IU/mL). Anti-Xa levels were slightly higher in CTAD than in citrate samples, irrespective of the assay. The model showed: (1) a significant dextran-patient group interaction (p < 0.0001), the effect of DS on anti-Xa levels varying from 30.9% in G4 to 296% in G1, and (2) a significant effect of CTAD, varying between patient groups (p = 0.0302).Conclusion: The variability of anti-Xa levels with a great overestimation of the values, using a reagent containing DS, can lead to different treatment decisions, especially after heparin neutralization by protamine. Clinical consequences of these differences remain to be demonstrated

Comparative Analysis of a French Prospective Series of 144 Patients with Heparin-Induced Thrombocytopenia (FRIGTIH) and the Literature

International audienceBACKGROUND: 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