Critical Bleeding in Adults and Children with Immune Thrombocytopenia: A Multicentre Cohort Study

Introduction

Immune thrombocytopenia (ITP) is a rare autoimmune disease that causes low blood platelets and an increased risk of bleeding. Critical bleeds in patients with ITP such as intracranial hemorrhage (ICH) are life-threatening events that can cause death or life-long morbidity. Treatment of ITP bleeding emergencies requires a rapid, coordinated, multidisciplinary approach. The objective of this study was to describe critical ITP bleeds in adults and children, including the treatments they received and their outcomes. These data will be used to inform future guidelines on ITP bleeding emergencies.

Methods

We conducted a retrospective cohort study of ITP patients with critical bleeds across 7 centers in the United States and Canada from 2010 - 2020. Eligible patients were adults and children with an established diagnosis of ITP and a platelet count <20 x10⁹/L at presentation to the emergency room. A critical ITP bleed was defined using published criteria: (i) a bleed in a critical anatomical site including ICH, intraspinal, intraocular, retroperitoneal, pericardial, or intramuscular with compartment syndrome; or (ii) an ongoing bleed that results in hemodynamic instability or respiratory compromise (Sirotich et al., 2021). We summarized the data using descriptive statistics. None of the critical bleeds identified as intraocular were associated with vision loss, thus these were excluded post-hoc.

Results

We identified 1226 patients (n=296 adults; and n= 930 children) with ITP from 7 centers in North America who had a platelet count <20 x10⁹/L at presentation to the emergency room for evaluation. Of those, 1192 (97.2%) had any type of bleeding, and 28 (2.2%) had critical bleeding (n=15 adults; and n=13 children). Among the 28 patients with critical bleeding, 16 (57.1%) were female. Median (IQR) age for adults was 68 years (45-74); and median age for children was 11 years (5-16). Median lowest platelet count at the time of the critical bleed was 8 x10⁹/L (IQR 3-15) for adults and 3 x10⁹/L (IQR 1-6) for children.

Most critical bleeds were ICH (n=18; 64.3%), followed by epistaxis (n=4; 14.3%), gynecological (n=3; 10.7%), gastrointestinal (n=2; 7.1%), and pulmonary hemorrhage (n=1; 3.6%). Of the 28 ITP patients with a critical bleed, 14 (50%) were newly diagnosed (<3 months). Ten patients were admitted to the intensive care unit (n=4 adults; n=6 children).

Interventions used to treat critical bleeds were platelet transfusion (n=19), intravenous immune globulin (IVIG; n=18), methylprednisolone (n=13), prednisone (n=11), plasma transfusion (n=6), dexamethasone (n=5), and romiplostim (n=4). One patient (20 years old) underwent urgent splenectomy. Time to administration of first ITP treatment was 4.7 hours (median; IQR 3.2-9.5) for 21 evaluable patients; 6.9 hours (median; IQR 4.3-9.6) for adults (n=11) and 3.5 hours (median; IQR 2.7-7.8) for children (n=10). The most common treatment combination was corticosteroids, IVIG and platelet transfusion.

Overall, 10 patients died (35.7%), including 7 (46.7%) adults and 3 (23.1%) children. Causes of death were bleeding (ICH, n=7; gastrointestinal bleeding, n=1; pulmonary hemorrhage, n=1) and septic shock (n=1). Four patients developed neurological disability (14.3%, n=2 adults; and n=2 children).

Conclusion

Critical bleeds in ITP patients were rare, representing 2.2% of ITP patients in the emergency room with severe thrombocytopenia; yet, they were associated with a high risk of death (35.7%). ICH was the most common critical bleed. Common interventions included corticosteroids, IVIG and platelet transfusion; however, time to first treatment was approximately 5 hours, and longer for adults than children. A standardized approach to the management of ITP critical bleeds is needed.

Cuker:MingSight: Consultancy; UpToDate: Patents & Royalties: Authorship royalties; Synergy: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy. Grace:Novartis: Research Funding; Sobi: Consultancy, Research Funding; Sanofi: Consultancy; Agios: Consultancy, Research Funding. Pishko:Biomarin: Consultancy. Arnold:Amgen: Consultancy; Argenx: Consultancy; Medison: Consultancy; Principia: Consultancy; Rigel: Consultancy; Sanofi: Consultancy; Sobi: Consultancy; Novartis: Research Funding; Paradigm: Research Funding.