TREATMENT of CRITICAL BLEEDS in PATIENTS with IMMUNE THROMBOCYTOPENIA: A SYSTEMATIC REVIEW

Document Type

Conference Proceeding

Publication Date

6-12-2024

Publication Title

HemaSphere

Keywords

corticosteroid, adult, adverse drug reaction, aged, autoimmune thrombocytopenia, bleeding, brain hemorrhage, case report, child, clinical article, clinical practice guideline, cohort analysis, compartment syndrome, conference abstract, disability, drug combination, drug therapy, female, gastrointestinal hemorrhage, GRADE approach, hemodynamics, hemoperitoneum, human, intraocular hemorrhage, male, observational study, pericardium, platelet count, randomized controlled trial, side effect, special situation for pharmacovigilance, splenectomy, systematic review, therapy, thrombocyte transfusion, treatment protocol

Abstract

Background: Intracranial hemorrhage and other critical bleeds in adults and children with immune thrombocytopenia (ITP) represent a medical emergency. However, evidence-based treatment protocols are lacking. Aims: To inform a clinical practice guideline addressing the issue, we undertook a systematic review of treatments for critical bleeding in patients with ITP. Methods: We conducted literature searches in four electronic databases from inception to October 2023: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. An ITP Critical Bleed was defined as (i) a bleed in a critical anatomical site including intracranial, 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 included randomized controlled trials, observational studies, case series, and single case reports that enrolled patients with ITP who received one or more interventions for the management of critical bleeding. Eligible studies reported any of the following outcomes: death, platelet count response, bleeding, and disability of patients and included any of the following interventions aimed to raise the platelet count: corticosteroids, intravenous immunoglobulin (IVIG), platelet transfusions, splenectomy, thrombopoietin receptor agonists (TPO-RAs) used alone or in combination. We used the GRADE approach to evaluate the certainty of the evidence. Results: We identified 47 eligible studies that reported on 94 ITP patients with critical bleeds, including 51 children (median age = 9.5 years), 32 adults (median age = 44 years), and 11 (11.7%) age unreported. The majority of critical bleeds were ICH (n=71). Others were gastrointestinal bleeds (n=5), ocular bleed (n= 1), and intraperitoneal bleed (n=1). Either alone or in combination with other treatments, patients received IVIG (n=49), corticosteroids (n=48), platelet transfusions (n=19), TPORAs (n=19), and splenectomy (n=7). Studies reported 38 unique treatment strategies, the most common of which were IVIG alone (n=18), corticosteroids + IVIG (n=11), corticosteroids + IVIG + TPO-RA (n=8), TPO-RAs alone (n=5), corticosteroids + platelet transfusion (n=4), and corticosteroids alone (n=4). Of patients with outcomes reported, 21.3% died and 24.3% developed disability; 71.4% achieved a platelet count >30 x109/L, 57.1% achieved a platelet count >50 x109/L, and 88.5% had bleeding resolution. Of the outcomes reported in Figure 1, the text below highlights the platelet count responses (>30 x109/L). Corticosteroids vs. no corticosteroids 16/20 (80.0%) patients who received corticosteroids achieved a platelet count >30 x109/L compared to 14/22 (63.6%) who did not receive corticosteroids. IVIG vs. no IVIG 18/22 (81.8%) patients who received IVIG achieved a platelet count >30 x109/L compared to 12/20 (60.0%) who did not receive IVIG. Platelet transfusion vs. no platelet transfusion 7/8 (87.5%) patients treated with platelet transfusion achieved a platelet count >30 x109/L compared to 23/34 (67.6%) patients not treated with platelet transfusion. Splenectomy vs. no splenectomy 3/4 (75.0%) patients treated with splenectomy achieved a platelet count >30 x109/L compared to 27/38 (71.1%) patients without splenectomy. TPO-RA vs. no TPO-RA 10/11 (90.9%) patients who received TPO-RAs achieved a platelet count >30 x109/L compared to 20/31 (64.5%) who did not receive TPO-RAs. Inferences on mortality, platelet count responses, bleeding resolution, and disability were highly uncertain due to the very low quality of evidence. Summary/Conclusion: Treatments for the management of critical bleeds in ITP patients are variable and the quality of evidence in support of specific treatments was very low. The most common treatments for ITP critical bleeds were IVIG, corticosteroids, TPO-RAs, and platelet transfusions alone or in combination. Given the rarity of ITP and the further rarity of critical bleeds among ITP patients, treatment decis ons will rely on a weak evidence base. (Table present).

Volume

8

First Page

6213

Last Page

6215

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