Fundamentals for a Systematic Approach to Mild and Moderate Inherited Bleeding Disorders: An EHA Consensus Report

Abstract

Healthy subjects frequently report minor bleedings that are frequently ‘background noise’ of normality rather than a true disorder. Nevertheless, unexpected or unusual bleeding may be alarming. Thus, the distinction between normal and pathologic bleeding is critical. Understanding the underlying pathologic mechanism in patients with an excessive bleeding is essential for their counseling and treatment. Most of these patients with significant bleeding will result affected by non-severe inherited bleeding disorders (BD), collectively denominated mild or moderate BD for their relatively benign course. Unfortunately, practical recommendations for the management of these disorders are still lacking due to the current state of fragmented knowledge of pathophysiology and lack of a systematic diagnostic approach. To address this gap, an International Working Group (IWG) was established by the European Hematology Association (EHA) to develop consensus-based guidelines on these disorders. The IWG agreed that grouping these disorders by their clinical phenotype under the single category of mild-to-moderate bleeding disorders (MBD) reflects current clinical practice and will facilitate a systematic diagnostic approach. Based on standardized and harmonized definitions a conceptual unified framework is proposed to distinguish normal subjects from affected patients. The IWG proposes a provisional comprehensive patient-centered initial diagnostic approach that will result in classification of MBD into distinct clinical-pathological entities under the overarching principle of clinical utility for the individual patient. While we will present here a general overview of the global management of patients with MBD, this conceptual framework will be adopted and validated in the evidence-based, disease-specific guidelines under development by the IWG.

Validation of the ISTH/SSC bleeding assessment tool for inherited platelet disorders: A communication from the Platelet Physiology SSC

“…Despite the preponderance of patients with GT among IPFD and with MYH9 ‐RD among IT, the enrolled population was representative of a wide range of disorders and included also very rare forms, thus providing information on the whole spectrum of these heterogeneous diseases …”

“…Strengths of our study are the large study population, very stringent inclusion criteria, the enrollment of pediatric cases, the systematic comparison with another BS and the worldwide representation. Limitations are (1) the lack of a population of subjects with mucocutaneous bleeding symptoms but without a definite diagnosis, thus the sensitivity of the ISTH‐BAT in differentiating IPFD from HC in bleeding of unknown cause will require a prospective validation in a large international collaborative study; (2) the enrollment of subjects in specialized hemostasis centers, which may have led to a selection of the more symptomatic cases—however, VWD‐1 and HC were enrolled by the same centers making the comparison between groups reliable; (3) the inability to provide information on the predictive value of an increased BS for subsequent bleeding—however a prospective arm of the study is ongoing to assess its prognostic capability; (4) the lack of correlative data between altered BS and the presence of a defect at diagnostic laboratory tests—however, an ad hoc designed substudy (BAT‐LAB) is ongoing and will provide this information.…”

“…24 Four previous studies have shown that the ISTH-BAT is useful to discriminate IPFD from HC, Despite the preponderance of patients with GT among IPFD and with MYH9-RD among IT, the enrolled population was representative of a wide range of disorders and included also very rare forms, thus providing information on the whole spectrum of these heterogeneous diseases. 2,11,[22][23][24][25][26] The BS was more severely altered in some specific conditions, like the CalDAG-GEFI-related disorder, GPS, and GT among IPFD, and the TAR and X-linked thrombocytopenia among IT, although for some of these the observation requires confirmation given the low number of cases.…”

“…The ISTH‐BAT combines a standardized questionnaire designed to capture also recurrent minor but not trivial bleeds, and a well‐defined interpretation grid allowing the computation of a final BS. It was developed as a consensus tool to record bleeding symptoms in patients with any suspected bleeding disorder and it has been recently proposed by an International Working Group as the main tool to discriminate bleedings deserving investigation from not relevant hemorrhages …”

“…It was developed as a consensus tool to record bleeding symptoms in patients with any suspected bleeding disorder 10 and it has been recently proposed by an International Working Group as the main tool to discriminate bleedings deserving investigation from not relevant hemorrhages. 11 Inherited platelet disorders are a heterogeneous group of bleeding diseases of variable clinical severity associated with a reduction of platelet number (inherited thrombocytopenias, IT) and/or function (inherited platelet function disorders, IPFDs).…”