Cerebrovascular disease associated with sickle cell pulmonary hypertension

Gregory J. Kato, Matthew Hsieh, Roberto Machado, James Taylor VI, Jane Little, John A. Butman, Tanya Lehky, John Tisdale, Mark T. Gladwin

Research output: Contribution to journalReview articlepeer-review

75 Scopus citations


In patients with sickle cell disease, anemia is a recognized risk factor for stroke, death, and the development of pulmonary hypertension. We have proposed that hemolytic anemia results in endothelial dysfunction and vascular instability and can ultimately lead to a proliferative vasculopathy leading to pulmonary hypertension. Consistent with this mechanism of disease, we now report a case series of six patients with obliterative central nervous system vasculopathy who also have pulmonary hypertension and high hemolytic rate. These patients, identified in the course of a prospective screening study for pulmonary hypertension, presented with neurological symptoms prompting neuroimaging studies. Compared to 164 other patients of similar age in the screened population, those with newly diagnosed or clinically active cerebrovascular disease have significantly lower hemoglobin levels and higher levels of lactate dehydrogenase. A review of the literature suggests that many clinical, epidemiological, and physiological features of the arteriopathy of pulmonary hypertension closely overlap with those of stroke in sickle cell disease, both known to involve proliferative vascular intimal and smooth muscle hypertrophy and thrombosis. These cases suggest that cerebrovascular disease and pulmonary hypertension in sickle cell disease share common mechanisms, in particular, reduced nitric oxide bioactivity associated with particularly high-grade hemolysis. Clinicians should suspect occult cerebrovascular disease in sickle cell patients with pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)503-510
Number of pages8
JournalAmerican journal of hematology
Issue number7
StatePublished - Jul 2006
Externally publishedYes


  • Hemolysis
  • Nitric oxide
  • Sickle cell disease
  • Stroke
  • Vascular disease

ASJC Scopus subject areas

  • Hematology


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