Successful treatment with eculizumab for posterior reversible encephalopathy syndrome due to underlying transplant‐associated thrombotic microangiopathy in patients transplanted for sickle cell disease

Abstract

Preexisting endothelial dysfunction and vascular injury sustained during allogeneic hematopoietic cell transplantation (HCT) increases risk for endothelial injury-related complications such as posterior reversible encephalopathy syndrome (PRES) and transplant-associated thrombotic microangiopathy (TA-TMA) in patients with sickle cell disease (SCD). We report two patients with SCD who developed PRES following allogeneic HCT. In both patients, PRES-related symptoms resolved only after a diagnosis of TA-TMA was established and eculizumab therapy was initiated. Renal manifestations at diagnosis included non-nephrotic range proteinuria and hypertension.This report highlights the importance of screening PRES-affected SCD HCT recipients for TA-TMA as usual treatment strategies may be inadequate. K E Y W O R D S eculizumab, hematopoietic cell transplant, posterior reversible encephalopathy syndrome, sickle cell disease, transplant-associated thrombotic microangiopathy

Transplant-associated thrombotic microangiopathy: theoretical considerations and a practical approach to an unrefined diagnosis

“…Symptoms include headache, seizures, confusion, and hallucinations. Posterior reversible encephalopathy syndrome has been described in pediatric patients due to uncontrolled TA-TMA associated hypertension [49,65]. CNS involvement is reported as a significant unfavorable predictor of mortality [5].…”

Acute Complications in Stem Cell Transplantation

“…Many factors predispose to development of PRES in any patient. Underlying disorders (hemoglobinopathies especially sickle cell > thalassemia) (Schmidt et al 2016;Gaziev et al 2017), hematological malignancies (Allo-SCT for myeloma) (Bartynski et al 2005), conditioning (MAC, TBI-containing regimens), unrelated donor transplant (Schmidt et al 2016), presence of concomitant acute GVHD/ steroid therapy, and CNI as GVHD prophylaxis (Bhunia et al 2019). Typical clinical features include headache with a surge in blood pressure, visual disturbance, seizures, focal neurodeficit with possible renal dysfunction.…”

“…Similar to its role in TA-TMA, Eculizumab has been shown to be useful in patients with PRES, refractory to conventional therapies (Bhunia et al 2019).…”

Etiologies, Cerebral Vasomotion, and Endothelial Dysfunction in the Pathophysiology of Posterior Reversible Encephalopathy Syndrome in Pediatric Patients

“…[260][261][262][263][264][265][266][267][268] In patients with sickle cell disease, missense mutations of the sixth codon of the hemoglobin β chain generate replacement of the acidic amino acid glutamate with the neutral amino acid valine, 208,[276][277][278] generating differential hemoglobin electrophoresis migration patterns and pathologic protein conformations augmenting the propensity of hemoglobin to polymerize under conditions of acidosis, hypoxia, and dehydration and thus effectively amplifying red blood cell microvascular aggregability and increases of the blood viscosity. [260][261][262][263][264][265][266][267][268] These events accelerate the rate of formation of thrombotic red blood cell aggregates within the cerebral microvasculature and generate decelerations of microvascular cerebral blood flow velocity. [279][280][281][282][283] Risk factors augmenting the propensity to a patient suffering from sickle cell disease to develop PRES include renal disease, hypertension, blood transfusions, HSCT, and direct perturbations of the microvasculature consequent to hemoglobin polymerization generating nondeformable red blood cells obstructing the cerebral capillaries.…”

“…HSCT generates an exquisitely risk-factor modifiable prevalence of PRES, varying from approximately 5% to a third of patients. 209,222,[256][257][258][259] Accordingly, the risk of developing PRES in patients undergoing HSCT is significantly increased in those patients with hemoglobinopathy, 22,202,209,[260][261][262][263][264][265][266][267][268] graft versus host disease, 232 and hypertension. 232 Thavamani and Umapathi 32 reported a significantly lower overall prevalence of developing PRES in pediatric patients receiving HSCT of 0.5%.…”