Hematopoietic stem cell transplantation-associated thrombotic microangiopathy and the role of advanced practice providers and pharmacists

Abstract

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a severe and potentially life-threatening complication. HSCT-TMA is often underdiagnosed due to multifactorial pathophysiology and a historic lack of standard diagnostic criteria. Identification of the multi-hit hypothesis and the key role of the complement system, particularly the lectin pathway of complement, has led to development of treatments targeting the underlying pathogenesis of HSCT-TMA. Additional research is ongoing to investigate the efficacy and safety of these targeted therapies in patients with HSCT-TMA. Advanced practice providers (APPs; nurse practitioners and physician assistants) and pharmacists are critical members of the multidisciplinary HSCT team and ensure management of patients throughout the continuum of care. Additionally, pharmacists and APPs can improve patient care through medication management of complex regimens; transplant education for patients, staff, and trainees; evidence-based protocol and clinical guideline development; assessment and reporting of transplant-related outcomes; and quality improvement initiatives to improve outcomes. Understanding the presentation, prognosis, pathophysiology, and treatment options for HSCT-TMA can improve each of these efforts.

Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) and Growth Differentiation Factor-15 (GDF-15) Levels Are Significantly Associated with Endothelial Injury Indices in Adult Allogeneic Hematopoietic Cell Transplantation Recipients

“…This heightened complement activation ultimately results in the production of microthrombi, as indicated by hit 3. This well-established hyperactivation of the complement system is also supported by research studies which have shown mounting evidence that inhibiting the C5 level of the complement system with eculizumab—approved for use in aHUS—is effective in many HSCT-TMA patients, leading to better overall response and survival rates [ 23 , 24 ]. However, today, there is no approved targeted therapy available, and there are several ongoing trials investigating complement inhibitors [ 25 , 26 , 27 , 28 ] as potential treatments in both adult and pediatric patients with HSCT-TMA.…”

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

“…No treatment guidelines are available for the management of HSCT-TMA. Historically, several treatment approaches have been investigated for HSCT-TMA, including the discontinuation of CNIs, therapeutic plasma exchange, defibrotide, immunosuppressant agents, and rituximab, with various outcomes for patients [39]. Eculizumab (C5 complement inhibitor) has been shown to be efficient and safe in HSCT-TMA [40,41].…”

Thrombotic microangiopathy – the importance of a multidisciplinary approach

“…Various TA-TMA diagnostic criteria have been published [16], but use of the modified Jodele criteria is recommended -see ]. Excessive terminal complement activation can be measured using soluble C5b-9 levels (also known as 'soluble MAC') [17 & ].…”

“…Diagnosis of TA-TMA requires 1) biopsy proven disease (histologic diagnosis from affected tissue) OR 2) presence of 4/7 of the following clinical criteria. Elements suggestive for TA-TMA MODS by organ system and degree of involvement are listed below [16,20] (2a) TA-TMA Diagnostic Clinical Criteria: Defined as:…”