Successful Treatment of Acute Thrombotic Microangiopathy by Eculizumab After Combined Lung and Kidney Transplantation

Commereuc, Morgane; Karras, Alexandre; Amrein, C.; Boussaud, Véronique; Sberro-Soussan, Rébecca; Guillemain, R.; Bacchi, Veronique Frémeaux; Thervet, Éric

doi:10.1097/tp.0b013e3182a7fccd

Cited by 13 publications

(18 citation statements)

References 3 publications

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“…Therefore through inhibition of glucuronidation of MPA and uninterrupted enterohepatic recirculation, tacrolimus can result in higher MPA levels which can lead to marrow toxicity [ 169 ]. Calcineurin inhibitors may also indirectly cause thrombocytopenia through thrombotic microangiopathy [ 83 – 87 ].…”

Section: Insight Into Etiology Of Hematological Cytopenia and Subsmentioning

confidence: 99%

“…Keeping these studies in mind, many studies conducted in Asian renal transplant recipients, including a randomized controlled trial, suggested the need for MMF dose reduction in patients with tacrolimus to minimize the side effects of MMF including myelotoxicity [ 171 – 173 ]. If calcineurin inhibitor induced thrombotic microangiopathy occurred, everolimus, belatacept, or eculizumab can be considered as alternative options [ 84 , 86 , 87 ].…”

Section: Insight Into Etiology Of Hematological Cytopenia and Subsmentioning

confidence: 99%

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Drug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant Physicians

Khalil

Khan

et al. 2018

Journal of Transplantation

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Drug-induced hematological cytopenia is common in kidney transplantation. Various cytopenia including leucopenia (neutropenia), thrombocytopenia, and anemia can occur in kidney transplant recipients. Persistent severe leucopenia or neutropenia can lead to opportunistic infections of various etiologies. On the contrary, reducing or stopping immunosuppressive medications in these events can provoke a rejection. Transplant clinicians are often faced with the delicate dilemma of balancing cytopenia and rejection from adjustments of immunosuppressive regimen. Differentials of drug-induced cytopenia are wide. Identification of culprit medication and subsequent modification is also challenging. In this review, we will discuss individual drug implicated in causing cytopenia and correlate it with corresponding literature evidence.

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Section: Insight Into Etiology Of Hematological Cytopenia and Subsmentioning

confidence: 99%

Section: Insight Into Etiology Of Hematological Cytopenia and Subsmentioning

confidence: 99%

Drug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant Physicians

Khalil

Khan

et al. 2018

Journal of Transplantation

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“…Eculizumab treatment was reported in four patients with de novo TMA, developed after combined (lung-kidney or pancreas kidney transplantation) or ABO-incompatible kidney transplantation. [133][134][135] Administration of eculizumab led to a prompt hematologic and renal recovery (►Table 2).…”

Section: De Novo Thrombotic Microangiopathy After Renal Transplantationmentioning

confidence: 99%

Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches

Riedl

Fakhouri

Quintrec

et al. 2014

Semin Thromb Hemost

125

116

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Thrombotic microangiopathy (TMA) is a rare but severe disorder characterized by endothelial cell activation and thrombus formation. It manifests with the triad of hemolytic anemia, thrombocytopenia, and organ failure. Prompt diagnosis and treatment initiation are crucial for long-term outcome. TMA often manifests subsequent to infectious events, of which (enterohemorrhagic) Escherichia coli is the most frequently reported. TMA also occurs on the background of genetic/autoimmune defects in the complement system (atypical hemolytic uremic syndrome [aHUS]) and underlying conditions, such as pregnancy, transplantation, drugs, other glomerulopathies, vasculitides, or metabolic defects. Complement activation or defects in its regulation have now been described in an increasing number of acquired diseases with TMA. Coinciding with this expanding spectrum of complement-mediated diseases, the question arises which patients might benefit from a complement-targeted therapy. Success of therapy depends on the individual contribution of complement activation in disease pathogenesis. The advent of eculizumab, a monoclonal antibody that blocks terminal complement activation, has markedly improved outcome and quality of life in patients with aHUS. This review discusses the contribution of complement and highlights its complex interaction with inflammation, coagulation, and the endothelium. Treatment experiences focusing on eculizumab therapy are discussed in detail across the emerging spectrum of complement-mediated thrombotic microangiopathies.

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“…13 A review of published reports 65 demonstrates the use of eculizumab in a total of 26 cases of TA-TMA following HSCT or solid organ transplant. 9,13,[66][67][68][69][70][71][72][73][74][75] The cases were initially treated with discontinuation or dose reduction in CNI with or without plasma exchange. Of these patients, 24 (92%) were alive at 1-year follow-up, 65 and the remaining 2 (8%) pediatric patients did not achieve therapeutic levels even after dose escalation and died.…”

Section: Managementmentioning

confidence: 99%

Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy

Elsallabi

Bhatt

Dhakal

et al. 2015

Clin Appl Thromb Hemost

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Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal, multifactorial disorder, which may present with thrombocytopenia, hemolysis, acute renal failure, mental status changes and involvement of other organs. The pathogenesis of TA-TMA is complex and includes multiple risk factors such as certain conditioning regimens, calcineurin inhibitors (CNIs), graft-versus-host disease (GVHD), human leukocyte antigen mismatch, and opportunistic infections. The end result of these insults is endothelial injury in the kidney and other organs. Recent studies also indicate a role of complement activation in tissue damage. The lack of sensitive and specific diagnostic tests for TA-TMA often results in delayed diagnosis. Biopsy is not always possible for diagnosis because of the risk of complications such as bleeding. Recently, an emerging role of renal-centered screening approach has been demonstrated, which utilize the monitoring of blood pressure, urine protein, serum lactate dehydrogenase and hemogram for early detection. Therapeutic options are limited, and plasma exchange plays a minor role. Withdrawal of offending agent such as CNIs and the use of rituximab can be effective in some patients. However, the current treatment strategy is suboptimal and associated with high mortality rate. Recently, eculizumab has been utilized in a few patients with good outcomes. Patients, who develop TA-TMA, are also at an increased risk of GVHD, infection, renal, cardiovascular, and other complications, which can contribute to high mortality. Better understanding of molecular pathogenesis, improvement in posttransplant management, leading to early diagnosis, and management of TA-TMA are required to improve outcomes of this fatal entity.

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Successful Treatment of Acute Thrombotic Microangiopathy by Eculizumab After Combined Lung and Kidney Transplantation

Cited by 13 publications

References 3 publications

Drug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant Physicians

Drug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant Physicians

Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches

Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy

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