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

Abstract

Background Careful assessment of bleeding history is the first step in the evaluation of patients with mild/moderate bleeding disorders, and the use of a bleeding assessment tool (BAT) is strongly encouraged. Although a few studies have assessed the utility of the ISTH‐BAT in patients with inherited platelet function disorders (IPFD) none of them was sufficiently large to draw conclusions and/or included appropriate control groups. Objectives The aim of the present study was to test the utility of the ISTH‐BAT in a large cohort of patients with a well‐defined diagnosis of inherited platelets disorder in comparison with two parallel cohorts, one of patients with type‐1 von Willebrand disease (VWD‐1) and one of healthy controls (HC). Patients/Methods We enrolled 1098 subjects, 482 of whom had inherited platelet disorders (196 IPFD and 286 inherited platelet number disorders [IT]) from 17 countries. Results IPFD patients had significantly higher bleeding score (BS; median 9) than VWD‐1 patients (median 5), a higher number of hemorrhagic symptoms (4 versus 3), and higher percentage of patients with clinically relevant symptoms (score > 2). The ISTH‐BAT showed excellent discrimination power between IPFD and HC (0.9 < area under the curve [AUC] < 1), moderate (0.7 < AUC < 0.9) between IPFD and VWD‐1 and between IPFD and inherited thrombocytopenia (IT), while it was inaccurate (AUC ≤ 0.7) in discriminating IT from HC. Conclusions The ISTH‐BAT allows to efficiently discriminate IPFD from HC, while it has lower accuracy in distinguishing IPFD from VWD‐1. Therefore, the ISTH‐BAT appears useful for identifying subjects requiring laboratory evaluation for a suspected IPFD once VWD is preliminarily excluded.

Bleeding phenotype and diagnostic characterization of patients with congenital platelet defects

“…CPDs showed that epistaxis and cutaneous bleeds most frequently occurred, and that epistaxis and oral cavity bleeding were the most severe bleeding symptoms. 6 Glanzmann thrombasthenia was widely represented in their study population (40%) and their study population had fewer women included (57%) as compared to ours (64%).…”

“…Since the ISTH-BAT documents large variety of bleeding symptoms, it is also used for the phenotyping of patients. 4,5 Very few studies have reported the bleeding phenotype in adult patients with CPDs 6 and most studies focused on a few specific types of CPD 7,8 or a specific mutation. 9,10 Phenotypic characterization of the whole spectrum of CPDs is necessary, since this could help physicians recognize CPD subtypes and inform new patients on prognostic implications regarding their bleeding phenotype.…”

Diagnosis of Inherited Platelet Disorders on a Blood Smear

“…Most affected individuals do not have a spontaneous hemorrhage, but may develop bleeding complications in case of hemostatic challenges such as traumas or surgery. When present, spontaneous bleedings are prevalently muco-cutaneous (e.g., easy bruising, epistaxis, gum bleeding, menorrhagia, gastrointestinal bleeding) and rarely serious [23]. When a hemorrhagic phenotype is overt, the kind of symptoms may help to differentiate "IPD-" from "non-IPD-bleeding-subjects" (e.g., having coagulopathies).…”

“…When a hemorrhagic phenotype is overt, the kind of symptoms may help to differentiate "IPD-" from "non-IPD-bleeding-subjects" (e.g., having coagulopathies). In contrast, this criterion is fairly useless in distinguishing among diverse IPDs as symptomatic patients commonly share prevalently mucocutaneous hemorrhages [23].…”

“…Besides clinical evaluation, including the documentation of hemorrhagic history using a validated assessment tool, such as the ISTH Bleeding Assessment Tool (ISTH-BAT) [23,60], the first diagnostic step for IPDs requires an estimation of platelet size [61], light-transmission aggregometry (along with the evaluation of dense granule release by lumiaggregometry), and flow cytometry. Generally, only selected patients undergo, in the first instance, further sophisticated investigations like western blotting, electron microscopy, or the measurement of certain enzyme activity [62].…”