Iron deficiency anemia and bleeding management in pediatric patients with Bernard‐Soulier syndrome and Glanzmann Thrombasthenia: A single‐institution analysis

Abstract

Introduction:Frequent and severe bleeding events (SBE) in patients with inherited qualitative platelet disorders Bernard-Soulier Syndrome (BSS) and Glanzmann Thrombasthenia (GT) can lead to secondary iron deficiency anemia (IDA). SBE are primarily treated with platelet transfusions or recombinant activated factor VII (rFVIIa) infusions. The impact of IDA on bleeding management and disease outcomes is understudied.Aim: To evaluate bleeding management, outcomes, and any association with IDA in pediatric patients with BSS and GT.Methods: Retrospective chart-review of pediatric patients with BSS or GT followed at a single hemophilia treatment center between 2007 and 2019. Results:We identified 14 patients with BSS (n = 2) or GT (n = 12). Patients received rFVIIa (7%), platelet transfusions (7%), or a combination of both (57%) for SBE.Eleven patients (79%) had IDA requiring oral and/or intravenous iron replacement and 50% required red blood cell transfusions. Due to recurrent SBE and refractory IDA, three patients (21%) received rFVIIa prophylaxis at 90 μg/kilogram 2-3 times/week for ≥15 months. Patients initiated on rFVIIa prophylaxis had a median baseline hemoglobin of 9.8 g/dL (min-max: 8.0-10.7 g/dL) compared to 11.7 g/dL (8.4-13.8 g/dL) for patients treated on-demand. Following initiation of rFVIIa prophylaxis, median hemoglobin and ferritin increased by 1.3 g/dL (0.7-2.5 g/dL) and 14.6 ng/mL (0.2-42.9 ng/mL), respectively, and bleeding rates were reduced by 7-78%. Conclusion:IDA is a known complication of recurrent bleeding events in individuals with inherited bleeding disorders. Routine monitoring for IDA may help improve bleeding management and reduce bleed burden in BSS/GT.

Rare bleeding disorders: Advances in management

“…22 The optimal platelet transfusion strategy for severe IPFD (i.e., numbers of units and duration of treatment) is uncertain, as dysfunctional autologous platelets may competitively inhibit the localization of transfused platelets to bleeding sites. 25 Considerable data has emerged on the usefulness (and low thrombotic risks) of recombinant activated factor VIIa (rFVIIa) as a platelet-sparing treatment for GT 26 and an ancillary treatment for BSS bleeding 27 and more studies are needed on its role (and cost effectiveness as a treatment) for other IPFD, including storage pool disorders. 28 Thrombopoietin receptor agonist drugs have been used to temporarily increase platelet counts in some IT (e.g., for surgery, during chemotherapy etc.…”

Treatment of Inherited Platelet Disorders: Current Status and Future Options

“…11 Testing for iron-deficiency anemia in patients with frequent bleedings should be performed on a regular basis. 12 Adequate treatment is provided by oral and/or intravenous iron supplementation. 12 A good dental hygiene is essential to prevent gum bleeding and tooth loss.…”

Immune gene polymorphisms associated with poor response to platelet transfusion and recombinant factor VII administration in Glanzmann thrombasthenia

“…9,10 Recombinant factor VIIa (rFVIIa) is effective and can be used as an early treatment for bleeding episodes, particularly with a history of alloantibody or transfusion resistance. [11][12][13] According to Bagheri et al, while the prophylactic Tranexamic Acid has no effect on the frequency of platelet transfusions in GT patients, it can reduce the number of bleeding episodes. 14 In some cases, patients respond poorly to platelet transfusion due to the presence of inhibitor alloantibodies, which block platelet aggregation, resulting in rapid removal of the transfused platelets.…”

“…Most GT patients receive platelets or red blood cells (RBCs), regardless of the severity or the frequency of their bleeding 9,10 . Recombinant factor VIIa (rFVIIa) is effective and can be used as an early treatment for bleeding episodes, particularly with a history of alloantibody or transfusion resistance 11–13 . According to Bagheri et al., while the prophylactic Tranexamic Acid has no effect on the frequency of platelet transfusions in GT patients, it can reduce the number of bleeding episodes 14 …”