Abstract Introduction Bronchoalveolar fibrin deposition is a characteristic of various lung disorders including acute lung injury, acute respiratory distress syndrome and sepsis. It is secondary to ...the activation of coagulation and inhibition of fibrinolysis in the alveolar space, and can be stimulated by lipopolysaccharide (LPS) inhalation. The aim of this study was to determine the relation between compartmental stress in the lung and systemic response after LPS inhalation by measuring haemostatic parameters. Patients and methods 12 healthy subjects underwent a bronchial challenge test with LPS; sequential dosages were performed for 5 biological markers (Interleukin-6 (IL-6), C-Reactive Protein (CRP), Prothrombin Fragments 1 and 2 (F 1+2), cortisol and Plasminogen Activator Inhibitor 1 (PAI-1) before endotoxin inhalation and 2, 4, 6, 8 and 24 hours afterwards. Results IL-6 and CRP levels in the peripheral blood were higher after LPS inhalation; there was no activation of coagulation and no increase in PAI-1 level. Conclusion This study confirms that despite systemic release of proinflammatory cytokines, LPS inhalation does not induce systemic haemostatic response to LPS challenge.
Abstract 3493
Poster Board III-430
Antibodies (Abs) directed against Factor VIII (FVIII) remain the main iatrogenic complication in haemophilia A (HA) patients. Anti-FVIII Abs neutralize procoagulant ...activity of FVIII. They are called inhibitors. Non-neutralizing antibodies (NNA) have also been described in hemophiliacs treated by FVIII concentrates. Their role and prevalence are still under debate. NNA could form immune complexes with FVIII and be responsible of an increased FVIII clearance inducing a shortened half-life. The aim of this retrospective study was to evaluate the prevalence of NNA in a large cohort of HA patients without inhibitors and to determine their epitope specificity against the two chains of FVIII or the B domain, using a x-MAP technology. Indeed, this approach has many advantages: it is fast, requires small volumes of plasma, and is suitable for multiplexing immuno-assay.
Samples of 187 patients (mean age 29 years, range 1-86) with severe (n= 133), moderate (n= 31) or mild (n= 23) HA from three haemophilia centers were studied. All patients have been previously treated and were inhibitor-free at the time of the test (<0.6 Bethesda Units/mL). Among them 33% (n=61) were treated by plasma-derived FVIII while 67% (n=126) had received recombinant FVIII (rFVIII). Two assays based on x-MAP technology were used: (i) the first determined the NNA reactivity with the heavy chain (HC) or the light chain (LC) of FVIII (Lavigne-Lissalde et al. 2008); (ii) the second identified the NNA directed towards the B-domain, by differential binding to full-length rFVIII or B-domain deleted rFVIII.
The observed NNA prevalence in the 187 patients under study was 24% (n=45): 13.3% (n=6) of NNA were directed against the LC, 62.2% (n= 28) were directed against the HC and 24.5% (n=11) against both chains. In the NNA positive population, the proportion of NNA directed toward the B-domain was of 9% (n=4). No difference was observed in the prevalence between the 3 centers. The prevalence of NNA in patients grouped into four categories of age 1-15 yrs (n=51, NNA prevalence: 27%), 16-30 yrs (n=65; 20%), 31-45 yrs (n=35; 20%) and >45 yrs (n=33; 27%) was not statistically different.
This retrospective study, using the x-MAP technology, found a prevalence of 24% NNA in HA patients, comparable to other reports in the literature. Most of the NNA were directed against the HC of FVIII. In 9% of the cases, NNA recognized the B domain. Further prospective studies will allow to better explain the role of NNA, overall on the FVIII pharmacokinetics and particularly those binding to the B domain. Other prospective studies could highlight a difference according to the type of treatment.
Lavigne-Lissalde G. et al. (2008). “Simultaneous detection and epitope mapping of anti-factor VIII antibodies.” Thromb Haemost99(6): 1090-6
No relevant conflicts of interest to declare.
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.
Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) appears effective and relatively safe for the treatment of bleeding and for surgical prophylaxis in patients with ...Glanzmann thrombasthenia as reported to the International Registry on rFVIIa and Congenital Platelet Disorders. One of the shortcomings of the Registry data is the heterogeneity of treatment protocol, including dosage, number of doses used, duration of treatment before declaration of failure, and mode of rFVIIa administration (bolus v continuous infusion). The data are not yet sufficient to define optimal regimens for various indications such as the type of bleeding or the type of procedures. The place of this drug compared to platelet transfusion in the overall management of patients with Glanzmann thrombasthenia will need to be determined in relationship to a number of challenges and unresolved issues in the clinical care of these patients. These issues include: how to improve local measures for patients with mucosal bleeds, optimal management of young women during menarche, optimal platelet transfusion regimens for various indications, the relationship between antiplatelet antibodies detected by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and effectiveness of platelet transfusion, whether there are other biological tests that may correlate with effectiveness of platelet transfusion, and management of pregnancy and delivery regarding antiplatelet immunization.
Antibodies (inhibitors and non-neutralising antibodies NNA) directed against factor VIII (FVIII) remain the main iatrogenic complication in haemophilia A (HA) patients. Inhibitors reduce FVIII ...pro-coagulant properties, whereas NNA are directed against non-functional epitopes. NNA are poorly studied and their prevalence, epitope specificity and physiopathology inadequately defined. The aim of this study was first to evaluate NNA prevalence in a French retrospective multicentric series of 210 patients without inhibitors, then to determine their epitope specificity (against the heavy chain HC or the light chain LC of FVIII) and particularly to assess the prevalence of anti-B domain NNA using specifically designed x-MAP assays. NNA occurred in 18.1% of patients (38/210) and their prevalence was not influenced by the severity of the disease. Among the 38 patients with NNA, 73.7% had anti-FVIII Abs against the HC, 13.2% against the LC and 13.2% had anti-FVIII Abs against both chains. There is thus a clear immuno-dominance of the HC of FVIII in the epitope profile of NNA, whatever the severity of HA. The proportion of NNA that recognised the B domain was 18.4% (n=7/38). A multivariate analysis did not highlight differences in NNA occurrence between patients treated with recombinant FVIII or with plasma- derived FVIII (19.6% vs. 14.9%, p=0.53).
Abstract Introduction The value and challenges of long-term prophylaxis (LTP) in adolescents and young adults need further characterisation. Aim To determine the proportions of adolescents and young ...adults with severe or moderately severe haemophilia in France under LTP and treatment on demand (OD). Methods Patients 15 to 25 years old with haemophilia A or B, factor VIII/IX ≤ 2% and no current inhibitor could be included if they had been under factor VIII/IX treatment at least 12 months and kept a treatment and bleeding diary. Results LTP was administered to 169/212 patients (79.7%) and OD treatment to 40/212 patients (18.9%). The most frequent reasons for initiating LTP were joint bleeding, target joints and frequent bleeds; whereas OD treatment was most often selected on the basis of mild bleeding phenotype or because of constraints on LTP. The mean annual bleed rate (ABR) in the OD group (6.33) was higher than in the LTP group (3.07, p < 0.001). Mean ABR did not differ significantly between age strata (15
–
18, > 18
–
21 and > 21
–
25 years), but was significantly higher for patients with severe haemophilia (4.02) as compared to those with moderate haemophilia (1.97, p = 0.002). No significant difference was observed in mean ABR for joint bleeds between the LTP and OD groups. Physician reported LTP compliance was good or excellent in 97.0% of patients. Conclusion LTP is the predominant factor VIII/IX treatment among adolescents and young adults with severe or moderately severe haemophilia in France. LTP was associated with low ABR and high compliance.
The few cases of antiphospholipid syndrome that have been reported in neonates are believed to have resulted from a transplacental transfer of antiphospholipid antibodies. Here we report on a boy ...with a neonatal stroke revealing a de novo primary antiphospholipid, the mother being free of antiphospholipid antibodies. Other thrombosis risk factors included primiparity, gestational diabetes, macrosomia, polyglobulia, and lipoprotein(a) >30 mg/dL. Anti-cardiolipin and anti-β2-glycoprotein I persisted more than 2 years. Under aspirin therapy, the child did not exhibit recurrence of thrombotic events or symptoms of autoimmunity after a follow-up of 3 years. Our case indicates that clinicians should consider a second retesting for anticardiolipin antibodies and anti-β2-glycoprotein I antibodies, even when children and mother neonatal tests are negative.
Factor V inhibitor: case report and literature review Dubois-Galopin, Frédérique; Lebreton, Aurélien; Marques-Verdier, Alain ...
Annales de biologie clinique (Paris),
2011 Mar-Apr, Letnik:
69, Številka:
2
Journal Article
Recenzirano
Acquired inhibitors to factor V are considered rare events and the cause is often unknown. Diagnostic haemostasis assays to correctly assess this phenomenon are not always perfect and reproducible. ...Various treatments have been attempted but a standardised management of patients is still lacking. We report the case of a patient who developed a factor V inhibitor and we take the opportunity to make an inventory of the latest data.
A 17-year-old girl presented with Neisseria meningitidis sepsis, with evidence of disseminated intravascular coagulation. Substitution therapy with both antithrombin and protein C concentrates was ...initiated, leading to clinical and biological improvement. Sequential dosages were performed for biological markers including thrombin-activatable fibrinolysis inhibitor (TAFI). Substitution therapy with both antithrombin and protein C concentrates led to a clinical and biological improvement. Biological markers showed a decrease in thrombin generation and in plasminogen activator inhibitor 1 (PAI-1) and a return of TAFI to a normal value. Discontinuation of substitutive treatment was marked by a clinical relapse at 24 h, with thrombin generation and increase in PAI-1, while TAFI remained unchanged. This report shows the evolution of hemostasis markers during septic shock and provides new data concerning the effects of a substitutive therapy.
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