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Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders. However, very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a worldwide, multicentric, retrospective study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted, and their efficacy in patients with inherited platelet disorders: the Surgery in Platelet disorders And Therapeutic Approach (SPATA) study. We rated the outcome of 829 surgical procedures carried out in 423 patients with well-defined forms of inherited platelet disorders: 238 inherited platelet function disorders and 185 inherited platelet number disorders. Frequency of surgical bleeding was high in patients with inherited platelet disorders (19.7%), with a significantly higher bleeding incidence in inherited platelet function disorders (24.8%) than in inherited platelet number disorders (13.4%). The frequency of bleeding varied according to the type of inherited platelet disorder, with biallelic Bernard Soulier syndrome having the highest occurrence (44.4%). Frequency of bleeding was predicted by a pre-operative World Health Organization bleeding score of 2 or higher. Some types of surgery were associated with a higher bleeding incidence, like cardiovascular and urological surgery. The use of pre-operative pro-hemostatic treatments was associated with a lower bleeding frequency in patients with inherited platelet function disorders but not in inherited platelet number disorders. Desmopressin, alone or with antifibrinolytic agents, was the preventive treatment associated with the lowest bleedings. Platelet transfusions were used more frequently in patients at higher bleeding risk. Surgical bleeding risk in inherited platelet disorders is substantial, especially in inherited platelet function disorders, and bleeding history, type of disorder, type of surgery and female sex are associated with higher bleeding frequency. Prophylactic pre-operative pro-hemostatic treatments appear to be required and are associated with a lower bleeding incidence.

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.

Summary Light transmission platelet aggregation (PA), adapted to measure platelet secretion (PS), is the reference test for diagnosing platelet functional disorders (PFD). Problems with these assays include lack of standardisation, unknown reproducibility and lack of universally accepted diagnostic criteria. We addressed these issues in patients with inherited mucocutaneous bleeding (MCB). Normal and abnormal PA tests in 213 patients were reproducible in 93·3% and 90·4% of the cases, respectively. Mean intra‐subject coefficient of variation for PA with strong agonists were <9% and mean intra‐class correlation coefficient for weak agonists were >0·86 (P < 0·0001). Concomitant impaired PA with 10 μmol/l‐adrenaline and 4 μmol/l‐ADP was observed in 13·7% of the controls. This combination was not considered per se a criterion for PFD. PA with adrenaline ≥42% or irreversible aggregation with 4 μmol/l ADP had 93% and 95% Negative Predictive Value for diagnosing PFD, respectively. PA defects were consistently associated with abnormal PS. In contrast, 14·3% of patients with MCB had isolated PS. Thus, standardized PA/PS assays are highly reproducible and concordant in normal and patient populations. Normal PA with adrenaline and low ADP concentration robustly predict a normal PA. Simultaneous PA/PS assays enable the diagnosis of isolated PS defects. This study confirmed that hereditary PA–PS defects are highly prevalent.

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