Pulmonary arterial hypertension in pediatric patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy

Pulmonary arterial hypertension (PAH) is rarely included in the differential diagnosis of cardiorespiratory failure after pediatric hematopoietic stem cell transplant (HSCT) as the clinical presentation is nonspecific and may mimic other etiologies. The pathogenesis of PAH in HSCT is poorly understood and the diagnosis requires a high degree of suspicion. We describe 5 children diagnosed with PAH after allogeneic HSCT. All 5 patients had prolonged clinical signs of transplantation-associated thrombotic microangiopathy (TA-TMA) when they presented with hypoxemic respiratory failure and evidence of PAH. Four of the 5 patients had echocardiographic evidence of PAH, and 1 patient was diagnosed with PAH only on autopsy. PAH was diagnosed a median of 76 days (range, 56-101 days) after a diagnosis of TA-TMA. Despite aggressive medical management, including inhaled nitric oxide, 4 of the 5 patients died. One patient recovered from PAH after 11 months of sildenafil therapy. Three of the 4 deceased patients had an autopsy performed, demonstrating severe pulmonary vascular disease consistent with TA-TMA and severe PAH. We conclude that TA-TMA can be associated with significant pulmonary vascular injury presenting as hypoxemic respiratory failure with PAH after HSCT. Pediatric patients with unexplained hypoxemia after HSCT should be evaluated for both transplantation complications, TA-TMA and PAH, accordingly.