PB1290 - Investigation of bleeding phenotype and unmet needs in inherited RUNX1 familial platelet disorder, ANKRD26-related thrombocytopenia and germline DDX41 mutation

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

AA

Ahmad Alcheikh, MBBS FRACP FRCPA

PhD candidate
Kolling Institute, Royal North Shore Hospital, New South Wales, Australia

Co-Author(s)

MW

Mathilda Wilding

Consultant Clinical Geneticist
Familial Cancer Service, Royal North Shore Hospital, Sydney, NSW, Australia
Sydney, New South Wales, Australia
CW

Chris Ward

Consultant Haematologist
Northern Blood Research Centre, Kolling Institute, Royal North Shore Hospital, Sydney, NSW, Australia
Sydney, New South Wales, Australia
IK

Ian Kerridge

Consultant Haematologist
Department of Haematology, Royal North Shore Hospital, Sydney, NSW, Australia
Sydney, New South Wales, Australia
WS

William Stevenson

Head of Department, Haematologist
Haematology Department, Royal North Shore Hospital, Sydney, Australia
Sydney, New South Wales, Australia

Background: Some inherited thrombocytopenias (ITs) increase both bleeding and malignancy risk. There is little data on bleeding in familial platelet disorder (FPD), ANKRD26-related thrombocytopenia (ANKRD26-RT) and germline DDX41 mutation, an obstacle to tailored management.

Aims: To assess bleeding and unmet needs in these patients.

Methods: In initial recruitment, 14 patients completed a composite unmet needs questionnaire, and 13 the ISTH Bleeding Assessment Tool (BAT). Data was analysed using Fisher’s exact test and ANOVA.

Results: Mean BAT scores were highest in FPD (11.3) followed by ANKRD26-RT (9.0) and DDX41 (3.7) (p=0.21). BAT scores were abnormal in 7/7 FPD patients (range 4-24), 2/3 ANKRD26-RT patients (range 3-14), and 2/3 DDX41 patients (range 0-7) (p=0.19). The greatest bleeding included cutaneous (combined score 22), minor wounds (15), oral (12), and epistaxis (10). None reported haematuria, suggesting this may not be useful for assessing bleeding in IT. 3/5 females reported menorrhagia scores ≥ 3. FPD patients scored highest in cutaneous, minor wound and menorrhagia bleeding, ANKRD26-RT in cutaneous and gastrointestinal bleeding, and DDX41 in menorrhagia and oral bleeding. DDX41 patients had lower cutaneous bleeding. Regarding unmet needs, only 54% received genetic counselling. Surprisingly, there was no difference in perceived risk of cancer between the groups (p=0.43). ANKRD26-RT patients overestimated their lifetime cancer risk (mean 47%), suggesting unmet informational needs. The greatest unmet needs were deciding how to best manage cancer risk (43%), obtaining information about cancer risk (35%) and management (35%), and accessing expert specialists (43%). ANKRD26-RT patients reported the greatest PUGS uncertainty score from their genetic test (p=0.019) and highest PHQ-8 depression scores. ANKRD26-RT and FPD patients had higher GAD7 anxiety scores than DDX41.

Conclusion(s): Our preliminary data suggest differences in bleeding propensity between ITs, and a high unmet needs burden. Some similarities in FPD and ANKRD26-RT may reflect common pathogenic pathways. Ongoing recruitment should provide further insights.