Summary
This FranceCoag network study assessed 33 patients with congenital factor XIII (FXIII) deficiency presenting FXIII levels <10 iu/dl. Diagnosis was based on abnormal bleeding in 29 patients, a ...positive family history in 2, recurrent miscarriages in 1 and was fortuitous in 1. Eighteen patients (62·1%) presented life‐threatening umbilical or intracranial haemorrhages (ICH). Seven of the 15 patients who experienced ICH were diagnosed but untreated, including 3 with secondary neurological sequelae. All pregnancies without prophylaxis (26/26) led to miscarriages versus 3/16 with prophylaxis. In patients exhibiting FXIII levels <10 iu/dl, prophylaxis could be discussed at diagnosis and at pregnancy. Further controlled prospective studies are needed.
rVIII-SingleChain is a recombinant factor VIII (FVIII) with increased binding affinity to von Willebrand factor compared with other FVIII products. rVIII-SingleChain is indicated for the treatment ...and prevention of bleeding episodes in patients with hemophilia A.
To collect real-world evidence data from patients treated with rVIII-SingleChain to confirm the efficacy and safety established in the clinical trial program and carry out a population pharmacokinetic (PK) analysis.
This interim analysis includes data, collected between January 2018 - September 2021, from patients treated with rVIII-SingleChain prophylaxis at French Hemophilia Treatment centers. Data on annualized bleeding rates, dosing frequency, and consumption before and after switching to rVIII-SingleChain were recorded. A population PK analysis was also conducted to estimate PK parameters.
Overall, 43 patients switched to prophylaxis with rVIII-SingleChain either from a previous prophylaxis regimen or from on-demand treatment. Following the switch to rVIII-SingleChain, patients maintained excellent bleed control. After switching to rVIII-SingleChain, most patients maintained or reduced their regimen. Interestingly, a majority of patients treated >2 ×/weekly with a standard half-life FVIII reduced both injection frequency and FVIII consumption with rVIII-SingleChain. A PK analysis revealed a lower clearance of rVIII-SingleChain (1.9 vs. 2.1 dL/h) and a longer half-life both in adolescents/adults (
= 28) and pediatric (
= 6) patients (15.5 and 11.9 hours, respectively vs. 14.5 and 10.3 hours) than previously reported.
Patients who switched to rVIII-SingleChain prophylaxis demonstrated excellent bleed control and a reduction in infusion frequency. A population PK analysis revealed improved PK parameters compared with those reported in the clinical trial.
Several studies have shown the benefits of delayed cord clamping (DCC) in preterm and in healthy newborns at short and long term. Our objective was to evaluate the potentials benefits and risks of ...DCC in red cell alloimmunization.
This was a comparative before/after study of all living born neonates followed after fetal anemia requiring in utero transfusion. DCC was defined as cord clamping 30 seconds after birth.
We included a continuous series of 72 neonates: 36 without DDC (group 1) and 36 with DDC (group 2). Hemoglobin at birth was lower in group 1 (10.2 vs 13.4 g/dL, P = .0003); 7 (25%) neonates in group 1 vs 24 (70.6%) in group 2 had no anemia at birth (P = .004). The rate of transfusion was similar between the 2 groups. Postnatal exchange transfusions were more likely performed in the group without DCC than in the group with DCC (47.2% vs 19.4%, P = .0124). Delay between birth and first transfusion was higher in group 2 (0 0-13 vs 1 0-21, P = .0274). The maximum level of bilirubin, the rate of intensive phototherapy, and the total duration of phototherapy were similar in the 2 groups.
This study highlights a significant benefit of DCC in anemia secondary to red blood cell alloimmunization with a resulting decreased postnatal exchange transfusion needs, an improvement in the hemoglobin level at birth and longer delay between birth and first transfusion with no severe hyperbilirubinemia.
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.
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).
Defining hemostatic profile for preterm infants is a challenge when severe bleedings are frequent.
The aim was to define the hemostatic profile at birth of infants with spontaneous prematurity and to ...evaluate whether characteristic profiles can predict the development of intraventricular hemorrhage (IVH) in prematures.
We included 122 newborns with a median age of 31
gestational age (GA) 29
;34
and median weight of 1145 g 785;1490. Levels of fibrinogen, factor II (FII) and factor V (FV) rose with GA (p = 0.017,p = 0.009, p = 0.001). In the group of 23
- 28
GA, the 5th percentile was defined as 0.6 g/L for fibrinogen, 15 IU/dL for FII and 16 IU/dL for factor V (n = 30). In the group of 29
-32
GA, the 5th percentile was defined as 1.0 g/L for fibrinogen, 24 IU/dL for FII and 41 IU/dL for factor V (n = 46). In the group of 33
-36
GA, the 5th percentile was defined as 1.0 g/L for fibrinogen, 24 IU/dL for FII and 30 IU/dL for factor V (n = 46). Level of fibrinogen was higher in case of vaginal delivery and lower in case of IUGR. Only lower level of FV at birth was significantly associated with IVH (63.5 46.0; 76.5 vs 74.0 58.0; 89.0, p = 0.026) with an unadjusted OR per SD increase in FV of 0.57 (95%CI, 0.34 to 0.96). After adjustment for age, the association between FV level and IVH was slightly attenuated (adjusted OR, 0.70; 95%CI, 0.40 to 1.23) but remained not significant (p = 0.22).There was no correlation with FII and fibrinogen.
We can define hemostastic profile of prematures and corroborate references ranges for studied parameters. Further large studies are still called for, to correlate the grade of hemorrhage and the factor V level at birth.
Introduction
Antihaemophilic factor (recombinant) (rAHF; ADVATE®) is approved for prophylaxis and treatment of bleeding in children and adults with haemophilia A. Reconstitution in 2 mL sterile water ...for injection instead of 5 mL allows for a 60% reduction in infusion volume and administration time, but could increase the likelihood of hypersensitivity and infusion‐related reactions, especially in children.
Aim
To assess local tolerability, safety and effectiveness of rAHF 2 mL during routine clinical practice factor VIII (FVIII) replacement (on‐demand and prophylaxis) in children with severe (FVIII < 1%) or moderately severe (FVIII 1%‐2%) haemophilia A.
Methods
This was a prospective, non‐interventional, postauthorization safety surveillance study (NCT02093741). Eligible patients were previously treated with rAHF and had a negative inhibitor test result during ≤10 exposure days prior to study entry.
Results
Of 65 patients enrolled (0‐11 years of age), 54 and 11 had severe and moderately severe haemophilia A, respectively; 56 patients received prophylaxis, and 11 had ≤50 exposure days, of which 4 had ≤4 exposure days. No patients reported local hypersensitivity reactions, treatment‐related adverse events or developed inhibitors. Investigators rated overall effectiveness of rAHF 2 mL prophylaxis as excellent or good. Ninety‐four bleeding events in 34 patients were treated. Haemostatic effectiveness was rated as excellent or good for 75.8% of bleeds; 86.2% of bleeds required 1 or 2 infusions.
Conclusion
In children with severe/moderately severe haemophilia A, no hypersensitivity reactions were reported with rAHF 2 mL treatment, and the safety and effectiveness are consistent with data previously reported for rAHF 5 mL.
IntroductionSevere haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to ...avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life.Methods and analysisWe present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14–17 years) with those from a group of young adults (aged 20–29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants’ views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag.Ethics and disseminationThe study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public.Trial registration number NCT02866526; Pre-results.
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