A Pilot Study of Chronic Red Blood Cell Transfusion in Sickle Cell Disease-Associated Pulmonary Hypertension

As patients with sickle cell disease (SCD) age, recurrent vaso-occlusive episodes lead to
progressive end-organ damage. Pulmonary hypertension (PHT) represents an example of such
end-organ damage. Pulmonary hypertension, a common complication in patients with sickle cell
disease (SCD), results in a shortened survival. The high mortality reported in SCD patients
with PHT appears to occur particularly in those patients with moderate and severe elevations
in their pulmonary artery pressure. The overall objective of this proposal is to evaluate
the effect of chronic red blood cell transfusion on PHT in SCD. We hypothesize that by
increasing the hemoglobin concentration and decreasing the amount of HbS, these patients
would experience improvements in their PHT.

Thus, the specific aim of this clinical trial is to evaluate the effects of RBC transfusion
on pulmonary hypertension in SCD, as well as the effect of chronic RBC transfusion on plasma
markers of thrombin generation, platelet activation, and nitric oxide metabolites.

Study subjects will be transfused monthly for 6 months to investigate the safety and
efficacy of RBC transfusion in SCD patients with PHT. All packed red blood cells will have
extended antigen matching for C, D, E and Kell to minimize the risk of alloimmunization.
Subjects will receive other routine treatments for SCD. Specific outcome variables will be
evaluated at 1 month, 3 months, and 6 months. All study subjects will receive simple
transfusion of packed red blood cell to achieve a post-transfusion hemoglobin (Hb) not
greater than 10 g/dL. For those subjects who may have baseline hemoglobins in whom a post
transfusion Hb would exceed 10 g/dL, they will require a limited exchange transfusion, i.e.
phlebotomy of 1 unit of blood, followed by transfusion of 2 units of packed RBC. All study
subjects will return for assessment of safety and/or efficacy measures every two weeks for
the first month, and subsequently every four weeks till the completion of the study. Study
subjects who experience a documented worsening of their disease (decreased SaO2, worsening
6-minute walk) on at least two consecutive follow up visits will be taken off the study. At
the end of the study, subjects will have the option of continuing on chronic RBC
transfusion.