Sickle Cell Anemia and Pulmonary Hypertension

Sickle cell anemia is a debilitating disease affecting 70,000 persons in the U.S.  A like number of patients may be affected in Europe and the Middle East.  Misshapen red blood cells in patients with sickle cell anemia cause numerous secondary health problems.  It now appears that pulmonary hypertension is one such secondary manifestation of sickle cell anemia.

 At the 2000 American Thoracic Society Dr. Salah Aboubakr of Wayne State University reported that 152 of his institution’s 414 sickle cell patients over a nine year period had one or more echocardiograms.  Of these patients, pulmonary hypertension was detected in 32.9%, based on right ventricle dilation, paradoxical motion of the ventricular septum and a peak tricuspid valve regugitant jet velocity in excess of 2.5 m/s.  Furthermore, mortality among the sickle cell patients with suspected pulmonary hypertension (44%) was significantly (p = 0.0003) higher than among the others (17%).  There were no other significant differences between the two groups other than the indications of pulmonary hypertension.

Dr. Aboubakr’s research lends strong credence to the view that many patients die of undiagnosed pulmonary hypertension.  There is a remarkable divergence between autopsy-based estimates of the prevalence of pulmonary hypertension and those based on patient presentation.  For example, Sean Gaine has reported that “necropsy studies have shown a prevalence of 1300 per million” for pulmonary hypertension.  The Lancet, 1998, 352:719-24.  On the other hand, International Registry of Primary Pulmonary Hypertension gives the prevalence as 6-8 per million.  If, in fact, 12% of sickle cell anemia patients have undiagnosed pulmonary hypertension, as Dr. Aboubakr’s research implies, these 8,400 patients would translate into a prevalence of 33 per million.  In other words, there may be 4-5 times as many people walking around with undiagnosed pulmonary hypertension secondary to sickle cell anemia as there are people with primary pulmonary hypertension.

It is reasonable to expect that the sickle cell anemia population is almost wholly unaccounted for in current statistical estimates of pulmonary hypertension.  This editor has found never found sickle cell anemia included in any description of secondary forms of pulmonary hypertension.  The recently concluded World Health Organization Symposium on Primary Pulmonary Hypertension made no mention of sickle cell anemia in its reconceptualization of primary and secondary pulmonary hypertension into pulmonary arterial hypertension.  In addition, descriptions of morbidity and mortality associated with sickle cell anemia do not generally make mention of pulmonary hypertension.  Consequently, Dr. Aboubakr’s research was worthy of publication.

The association of sickle cell anemia with pulmonary hypertension is especially troubling given the high mortality discovered by Dr. Aboubakr.  Continuous prostacyclin has been shown to extend life significantly for patients with pulmonary hypertension.  It is reasonable to expect that continuous prostacyclin will be similarly effective in the sickle cell subset.  While sickle cell anemia is associated with a heightened susceptibility to infectious morbidity, continuous prostacyclin has been safely administered to HIV positive patients.  In addition, new subcutaneous forms of prostacyclin offer the promise of a much reduced risk of iatrogenic infection.

In conclusion, it appears worthwhile to screen sickle cell anemia patients for pulmonary hypertension.  For those patients diagnosed with pulmonary hypertension, strong consideration should be given to managing the condition with currently available pharmacologic agents.