Immune-Mediated Cytopenias After Hematopoietic Cell Transplantation: Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment Strategies

Michniacki, Thomas F.; Ebens, Christen L.; Choi, Sung Won

doi:10.1007/s11912-019-0838-7

Cited by 23 publications

(14 citation statements)

References 43 publications

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“…In approximately 50% of cases, the primary form of AIHA is diagnosed, while in other cases the autoantibodies are related to autoimmune diseases, lymphoproliferative diseases, infections (also SARS-CoV-2 infection), solid tumors or solid organ transplantation (Table 1) [3,5,12,13]. The condition is also seen in patients after allogeneic stem cell transplantation (HSCT) with increasing incidence (reaching 2-6%), severe course and a high mortality rate [14][15][16][17]. Hemolysis which occurs after drugs is known as drug-induced immune hemolytic anemia (DIIHA), and is currently classified as a secondary form of AIHA [3].…”

Section: Introductionmentioning

confidence: 99%

Autoimmune hemolytic anemia: current knowledge and perspectives

et al. 2020

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Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases which includes warm AIHA, cold agglutinin disease (CAD), mixed AIHA, paroxysmal cold hemoglobinuria and atypical AIHA. Currently CAD is defined as a chronic, clonal lymphoproliferative disorder, while the presence of cold agglutinins underlying other diseases is known as cold agglutinin syndrome. AIHA is mediated by autoantibodies directed against red blood cells (RBCs) causing premature erythrocyte destruction. The pathogenesis of AIHA is complex and still not fully understood. Recent studies indicate the involvement of T and B cell dysregulation, reduced CD4+ and CD25+ Tregs, increased clonal expansions of CD8 + T cells, imbalance of Th17/Tregs and Tfh/Tfr, and impaired lymphocyte apoptosis. Changes in some RBC membrane structures, under the influence of mechanical stimuli or oxidative stress, may promote autohemolysis. The clinical presentation and treatment of AIHA are influenced by many factors, including the type of AIHA, degree of hemolysis, underlying diseases, presence of concomitant comorbidities, bone marrow compensatory abilities and the presence of fibrosis and dyserthropoiesis. The main treatment for AIHA is based on the inhibition of autoantibody production by mono- or combination therapy using GKS and/or rituximab and, rarely, immunosuppressive drugs or immunomodulators. Reduction of erythrocyte destruction via splenectomy is currently the third line of treatment for warm AIHA. Supportive treatment including vitamin supplementation, recombinant erythropoietin, thrombosis prophylaxis and the prevention and treatment of infections is essential. New groups of drugs that inhibit immune responses at various levels are being developed intensively, including inhibition of antibody-mediated RBCs phagocytosis, inhibition of B cell and plasma cell frequency and activity, inhibition of IgG recycling, immunomodulation of T lymphocytes function, and complement cascade inhibition. Recent studies have brought about changes in classification and progress in understanding the pathogenesis and treatment of AIHA, although there are still many issues to be resolved, particularly concerning the impact of age-associated changes to immunity.

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Section: Introductionmentioning

confidence: 99%

Autoimmune hemolytic anemia: current knowledge and perspectives

et al. 2020

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“…Multiple causes contribute to post-HSCT secondary thrombocytopenia, after engraftment of megakaryocytes and achievement of an adequate platelet count, including decreased production and increased destruction, which may coexist. [154][155][156] Decreased production may be due to myelotoxicity of the conditioning regimen, poor graft function, rejection, graft versus marrow immunologic dysregulation (as a pattern of graft-versus-host disease), stromal damage, and viral reactivation. Increased platelet destruction is most often due to transplant-related microangiopathy, belonging to the umbrella of endothelial inflammatory diseases, which coincide to cause posttransplant thrombocytopenia.…”

Section: Posttransplantmentioning

confidence: 99%

A Review of Romiplostim Mechanism of Action and Clinical Applicability

Bussel¹,

Soff²,

Balduzzi³

et al. 2021

DDDT

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Thrombocytopenia results from a variety of conditions, including radiation, chemotherapy, autoimmune disease, bone marrow disorders, pathologic conditions associated with surgical procedures, hematopoietic stem cell transplant (HSCT), and hematologic disorders associated with severe aplastic anemia. Immune thrombocytopenia (ITP) is caused by immune reactions that accelerate destruction and reduce production of platelets. Thrombopoietin (TPO) is a critical component of platelet production pathways, and TPO receptor agonists (TPO-RAs) are important for the management of ITP by increasing platelet production and reducing the need for other treatments. Romiplostim is a TPO-RA approved for use in patients with ITP in the United States, European Union, Australia, and several countries in Africa and Asia, as well as for use in patients with refractory aplastic anemia in Japan and Korea. Romiplostim binds to and activates the TPO receptor on megakaryocyte precursors, thus promoting cell proliferation and viability, resulting in increased platelet production. Through this mechanism, romiplostim reduces the need for other treatments and decreases bleeding events in patients with thrombocytopenia. In addition to its efficacy in ITP, studies have shown that romiplostim is effective in improving platelet counts in various settings, thereby highlighting the versatility of romiplostim. The efficacy of romiplostim in such disorders is currently under investigation. Here, we review the structure, mechanism, pharmacokinetics, and pharmacodynamics of romiplostim. We also summarize the clinical evidence supporting its use in ITP and other disorders that involve thrombocytopenia, including chemotherapy-induced thrombocytopenia, aplastic anemia, acute radiation syndrome, perisurgical thrombocytopenia, post-HSCT thrombocytopenia, and liver disease.

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“…7 This condition is more common in children with innate or acquired immune dysregulation (e.g., autoimmune lymphoproliferative syndrome, post-HSCT), in whom the management is frequently challenging. 8 Moreover, AIHA can be combined with thrombocytopenia (Evans syndrome). 7 Since the beginning of the pandemic, AIHA has seldom been described in adults with COVID-19 9,10 and appears to be even rarer in children.…”

Section: E T T E R T O T H E E D I T O R Autoimmune Hemolytic Anemia In Children With Covid-19mentioning

confidence: 99%