The ristocetin cofactor activity assay (VWF:RCo) is the reference method for assessing von Willebrand factor (VWF) activity but remains difficult to perform, and the coefficient of variation of the ...method is high (about 20-30%). This study evaluated and compared the performance for measuring the VWF activity of two newly commercialised assays VWF:Ac Innovance (VWF:Ac) and VWF:RCo Acustar (VWF:RCo Acu) with the reference VWF:RCo aggregation in 123 pathological plasma samples. The correlation and concordance between both new tests (VWF:RCo-Acu and VWF:Ac) and the reference VWF:RCo were good. The results of the VWF activity to VWF antigen ratio were also comparable whatever the method for the classification of VWF deficiency in all patients. Our results showed that both new tests could replace the "gold standard" VWF:RCo in aggregometry with several benefits: they are fully automated, easier and faster to perform, better adapted to emergency situations if necessary.
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.
Introduction
The rare coagulation disorders may present significant difficulties in diagnosis and management. In addition, considerable inter‐individual variation in bleeding phenotype is observed ...amongst affected individuals, making the bleeding risk difficult to assess in affected individuals. The last international recommendations on rare inherited bleeding disorders (RIBDs) were published by the United Kingdom Haemophilia Centre Doctors' Organisation in 2014. Since then, new drugs have been marketed, news studies on surgery management in patients with RIBD have been published, and new orphan diseases have been described.
Aim
Therefore, the two main objectives of this review, based on the recent recommendations published by the French Reference Centre on Haemophilia and Rare Bleeding Disorders, are: (i) to briefly describe RIBD (clinical presentation and diagnostic work‐up) to help physicians in patient screening for the early detection of such disorders; and (ii) to focus on the current management of acute haemorrhages and long term prophylaxis, surgical interventions, and pregnancy/delivery in patients with RIBD.
Background
Patients with symptomatic von Willebrand disease (VWD) should be offered long‐term prophylaxis (LTP) to prevent recurrent bleedings. Our objective was to evaluate the effectiveness and ...safety of Voncento®, a plasma‐derived FVIII/VWF concentrate (ratio 1:2.4), administrated in LTP.
Methods
We included patients from the OPALE study (May 2016 to April 2021), a French multicenter observational study following patients with inherited VWD, who received a Voncento® LTP during the study period.
Results
Among the 130 OPALE‐study patients, 23 patients (12 women) received a LTP and were therefore included. The median (range) age was 16 (1–85) years; 16 patients were type 3, 1 was type 2A, 6 were type 2B. Before inclusion, 19 (83%) were under LTP and 4 (17%) received on‐demand (OD) treatment. The indications for initiating prophylaxis in the overall population were joint bleeding (43%), ear, nose, and throat (ENT) bleeding including epistaxis or oral bleeding (39%), and recurrent muscle hematoma (22%). The medians (ranges) dose of Voncento® per infusion, frequency, and weekly dose were 45 (33–109) IU/kg, 2 infusions per week, and 96 (44–222) IU/kg/week, respectively. The median (range) annualized bleeding rate (ABR) was 0.8, 0.7 (0–3.5), and 0 (0–2.3) for type 2A, 2B, 3 patients, respectively. There was no difference regarding to the dose, frequency of infusion, or in terms of ABR in 9/19 patients who replaced previous concentrates with Voncento®. During the study period, no adverse event was reported.
Conclusion
These results suggest that Voncento® is effective to prevent recurrent bleedings in patients symptomatic VWD.
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.
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.
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).
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.
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.
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.
Background
Data are limited on prostate cancer (PC) management in patients with haemophilia (PWH).
Aim
To describe PC screening and diagnosis, treatment modalities and bleeding complications in a ...group of unselected PWH followed at French Haemophilia Treatment Centres (HTCs)
Patients and methods
PC screening, management and bleeding complications were retrospectively investigated at 14 French HTCs between 2003 and 2018.
Results
Among> 1549 > 50‐year‐old PWHs, 73 (4.7%) underwent PC screening (median age 71.1 years; 67/6 HA/HB, 17/56 severe‐moderate/mild). At diagnosis, haematuria was infrequent. Prophylaxis was administered during 76/86 (88%) prostate biopsies (PB) (n = 67 clotting factor concentrates, CFC; n = 9 desmopressin; n = 17 associated with tranexamic acid, TA). Bleeding (11/86, 12.8%) occurred mainly post‐prophylaxis (median delay: 7 days): haematuria (9/11, 81.8%), and rectal bleeding (2/11, 18.2%) including one major (1.2%). PC was confirmed in 50/86 PB and in two prostatectomy specimens (total n = 50 patients, n = 6 with only active surveillance). Surgery (n = 28/44 patients) was managed with CFC. Fifteen patients had radiotherapy/brachytherapy, 10 had hormone therapy; CFC‐based prophylaxis was only prescribed for brachytherapy (n = 2). Major bleedings occurred in 3/28 (10.7%) and 2/15 (13.3%) patients who underwent surgery and radio/brachytherapy, respectively. No bleeding risk factor was found.
Conclusion
Our data indicate that PB requires prophylaxis for atleast 7 days, using CFC, desmopressin or TA in function of haemophilia severity. PC surgery should be considered at high bleeding risk. Long‐term post‐procedural CFC or oral TA could be discussed. Radiotherapy/brachytherapy also should be managed with prophylaxis (CFC or TA).
Background The outbreak of coronavirus disease 2019 (COVID-19) exposes vulnerable patients to high risk of mortality. Patients with left ventricular assist device (LVAD) usually have symptoms such as ...cough, fever, and shortness of breath because of their cardiac condition and comorbidity, therefore these related symptoms challenge the correct diagnosis in time within the COVID-19 pandemic. Case summary We report two case studies of patients with LVAD in whom COVID-19 related symptoms were overlapped by their cardiac status and comorbidities. In the first case, the patient was admitted for suspicion of COVID-19 due to cough and shortness of breath for 1 month. The blood test evocated a high index of suspicion of COVID-19. The nasopharyngeal test for COVID-19 performed on admission and at Day 2 was inconclusive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the test obtained on Day 3 of admission was positive, whereas computed tomography confirmed the diagnosis of COVID-19. This patient developed acute respiratory distress syndrome (ARDS) and nasal epistaxis within 48 h during hospitalization. The ARDS was treated by non-invasive ventilation and probabilistic antibiotics for 3 days and resulted significant improvement. The nasal epistaxis due to international normalized ratio increase was treated by nasal packing and vitamin K antagonist was switched to parenteral heparin infusion. The patient was kept hospitalized for 1 month for further supportive treatment. In the second case, the patient was admitted for recurrent anaemia due to melaena, the patient was tested for COVID-19 because of new-onset symptoms of cough and rhinorrhoea. The first nasopharyngeal test was positive, and sudden increase of anticoagulation status was noted in the setting of gastrointestinal bleeding. The anticoagulation status was controlled by parenteral heparin infusion, and the melaena was disappeared at Day 3. The moderate dyspnoea of the patient was quickly improved with nasal oxygen delivery for 4 days. The patient was discharged at Day 5. Discussion COVID-19 specific symptoms are challenging to distinguish in patients with LVADs, although radiological evidence can be beneficial in the COVID-19 diagnosis. We also observed the need for precise anticoagulation control to avoid bleeding or thrombotic events in these patients. Keywords Case series * COVID-19 * Left ventricular assist device * LVAD
To evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline ...compliance.
This real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (ie, after guideline implementation).
We included 333 boys in the study cohort. The cumulative incidence of long-term prophylaxis use was 61.2% at 3 years of age vs 9.5% in a historical cohort of 39 boys born in 1996 (ie, before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. Long-term prophylaxis was delayed in 10.8% of patients. In the multivariate analysis, 2 variables were significantly associated with “timely long-term prophylaxis” as compared with “delayed long-term prophylaxis”: hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, P = .013 vs Paris area) and older age at long-term prophylaxis indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, P = .031). Long-term prophylaxis anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95% CI 0.3-0.8, P = .010 for birth years 2005-2009 vs 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95% CI 1.2-3.0, P = .005) were significantly associated with “long-term prophylaxis guideline compliance” vs “long-term prophylaxis anticipation.”
This study suggests that long-term prophylaxis guidelines are associated with increased long-term prophylaxis use. However, early initiation of long-term prophylaxis remains a challenge.
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