Gingival bleeding is a useful clinical feature in the diagnosis of hereditary bleeding disorders in children.

The search for hereditary bleeding disorders (HBD) prior to invasive procedures in children is primarily based on personal and family bleeding history. Although several scores are available, they have only been evaluated in specific situations or in adults. Our monocentric retrospective study aimed to analyze the association between clinical history and four scores (HEMSTOP, PBQ, ISTH-BAT, TOSETTO) and the diagnosis of MHC in children referred to the University Hospital of Montpellier for hemostasis investigations. A total of 117 children were retrospectively included in the study. Of these, 57 (49%) were diagnosed with HBD, with 30 having primary bleeding disorders and 27 having coagulation disorders. The diagnosis of HBD was significantly associated with gingival bleeding, which was present in 30% of HBD patients. In our population, only the HEMSTOP score showed an association with the diagnosis of HBD, but it was positive in only 48% of patients. By including gingival bleeding as a factor, we modified the HEMSTOP score, which increased its sensitivity from 0.45 to 0.53. When examining primary bleeding disorders, the modified HEMSTOP score, with the inclusion of gingival bleeding, enables us to diagnose 63% of patients (see Fig. 1).    Conclusion: Therefore, gingival bleeding should be considered a useful factor in bleeding history for HBD diagnosis. Adding this symptom to a screening score such as HEMSTOP improves its sensitivity. To confirm our findings, a prospective study is required.    Trial registration: Study registration number: NCT05214300. What is Known: • Screening for hereditary bleeding disorder diseases is a necessity and a challenge in children. • Minor disorders of primary hemostasis are the most common, but often escape standard coagulation tests. What is New: • Gingival bleeding is a frequent symptom that is easy to investigate and may point to a primary hemostasis disorder. • Adding the gingival bleeding item to a routine screening score such as HEMSTOP improves sensitivity.

Translational research: precision medicine, personalized medicine, targeted therapies: marketing or science?

Personalized medicine is based on: 1) improved clinical or non-clinical methods (including biomarkers) for a more discriminating and precise diagnosis of diseases; 2) targeted therapies of the choice or the best drug for each patient among those available; 3) dose adjustment methods to optimize the benefit-risk ratio of the drugs chosen; 4) biomarkers of efficacy, toxicity, treatment discontinuation, relapse, etc. Unfortunately, it is still too often a theoretical concept because of the lack of convenient diagnostic methods or treatments, particularly of drugs corresponding to each subtype of pathology, hence to each patient. Stratified medicine is a component of personalized medicine employing biomarkers and companion diagnostics to target the patients likely to present the best benefit-risk balance for a given active compound. The concept of targeted therapy, mostly used in cancer treatment, relies on the existence of a defined molecular target, involved or not in the pathological process, and/or on the existence of a biomarker able to identify the target population, which should logically be small as compared to the population presenting the disease considered. Targeted therapies and biomarkers represent important stakes for the pharmaceutical industry, in terms of market access, of return on investment and of image among the prescribers. At the same time, they probably represent only the first generation of products resulting from the combination of clinical, pathophysiological and molecular research, i.e. of translational research.

Translational research in immune and inflammatory diseases; what are the challenges, expected advances, and innovative therapies?

Despite very different aetiologies and clinical expressions, advancing knowledge in the physiopathology and treatment of immune and inflammatory diseases (IID) prompts us to consider them as a whole. These are chronic, often incapacitating and painful illnesses that progress and destroy organs. Management by discipline too often leads to erroneous diagnoses and sometimes inappropriate treatment. More integrated translational research would further understanding of the complex relationships between cytokines and organ damage, which vary with the conditions and patients, making it possible to develop new biomarkers and personalize treatment. The research in France has very many strengths but its organization is fragmented. Better coordinated research into IID, which could be based on creating a strategic valorization field (domaine de valorisation stratégique, DVS) and thematic multi-organization institute (Institut thématique multi-organismes ITMO), would advance patient management.

Multicenter evaluation of light transmission platelet aggregation reagents: communication from the ISTH SSC Subcommittee on Platelet Physiology.

BACKGROUND: Light transmission aggregation (LTA) is used widely by the clinical and research communities. Although it is a gold standard, there is a lack of interlaboratory harmonization. OBJECTIVES: The primary objective was to assess whether sources of activators (mainly adenosine diphosphate [ADP], collagen, arachidonic acid, epinephrine, and thrombin receptor activating peptide6) and ristocetin contribute to poor LTA reproducibility. The secondary objective was to evaluate interindividual variability of results to appreciate the distribution of normal values and consequently better interpret pathologic results. METHODS: An international multicenter study involving 28 laboratories in which we compared LTA results obtained with center-specific activators and a comparator that we supplied. RESULTS: We report variability in the potency (P) of activators in comparison with the comparator. Thrombin receptor activating peptide 6 (P, 1.32-2.68), arachidonic acid (P, 0.87-1.43), and epinephrine (P, 0.97-1.34) showed the greatest variability. ADP (P, 1.04-1.20) and ristocetin (P, 0.98-1.07) were the most consistent. The data highlighted clear interindividual variability, notably for ADP and epinephrine. Four profiles of responses were observed with ADP from high-responders, intermediate-responders, and low-responders. A fifth profile corresponding to nonresponders (5% of the individuals) was observed with epinephrine. CONCLUSION: Based on these data, the establishment and adoption of simple standardization principles should mitigate variability due to activator sources. The observation of huge interindividual variability for certain concentrations of activators should lead to a cautious interpretation before reporting a result as abnormal. Confidence can be taken from the fact that difference between sources is not exacerbated in patients treated with antiplatelet agents.

Idiopathic purpura fulminans associated with anti-protein S antibodies in children: a multicenter case series and systematic review.

Idiopathic purpura fulminans (IPF) is a rare but severe prothrombotic coagulation disorder that can occur after chickenpox or human herpesvirus 6 (HHV-6) infection. IPF leads to an autoantibody-mediated decrease in the plasma concentration of protein S. We conducted a retrospective multicenter study involving patients with IPF from 13 French pediatric centers and a systematic review of cases in published literature. Eighteen patients were included in our case series, and 34 patients were included as literature review cases. The median age was 4.9 years, and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 patients (94%) with typical lesions. In all, 41 patients (78%) had a recent history of varicella-zoster virus infection, and 7 patients (14%) had been infected by HHV-6. Most of the patients received heparin (n = 51; 98%) and fresh frozen plasma transfusions (n = 41; 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis seemed to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.