Pulmonary Hypertension and Associated Risk Factors in a High Burden Sickle Cell Disease Population

Introduction: Chronic pulmonary complications in sickle cell disease (SCD) are major causes of morbidity and mortality, particularly among those with sickle cell anemia (SCA), and accounts for 20-30% of all sickle cell deaths (Gray et. al. J Clin Pathol 1991; Thomas et. al. BMJ 1982).

These complications include abnormalities in pulmonary function, interstitial lung disease and pulmonary hypertension (PH) in its severest form. An elevated tricuspid regurgitant jet velocity (TRV) obtained via doppler echocardiography, is a validated non-invasive screening tool for possible PH and an independent risk factor for early death among patients with SCD (Gladwin et. al. N Engl J Med 2004; Mehari et. al. JAMA 2012). It has been shown that measured TRV ≥ 2.5m/s is associated with decreased survival, estimated to be 40% at 40 months (Castro et. al. Blood 2003). The prevalence of PH determined by echocardiography is between 25-30% in SCA patients (Aliyu et. al. Am J Hematol 2008).

Though the burden of SCD in Sub-Saharan Africa is high, there is paucity of research into chronic lung complications, particularly pulmonary hypertension in this special population. Ghana, a West African country, has a high burden of SCD with over 16,000 babies born annually with the disease. This study therefore determined the prevalence of pulmonary hypertension and its associated risk factors.

Methods

This was a cross-sectional study involving 76 clinically stable SCA patients aged 18 years and above. A structured and pre-tested questionnaire was used to obtain socio-demographic and clinical information. The cardiopulmonary system of participants was thoroughly examined and a modified version of St George's questionnaire was used to screen and exclude those with chronic lung disease. Doppler echocardiography was used to measure TRV. The participants underwent spirometry testing, pulse oximetry measurement, and laboratory investigations including a complete blood count, free plasma hemoglobin, blood urea and creatinine.

Results

Twenty-five (32.9%) of the SCA participants had elevated TRV (≥ 2.5m/s), which was suggestive of pulmonary hypertension. Nineteen (76%) had values between 2.5m/s - 2.9m/s, representing mild pulmonary hypertension and Six (24%) had values ≥ 3.0m/s suggestive of moderate-severe pulmonary hypertension.

A negative correlation between TRV and steady-state haemoglobin (Hb) was observed (R= - 0.456, p < 0.001). Those with elevated TRV had a mean Hb of 6.9g/dl compared to 8.6g/dl in those with TRV < 2.5m/s. Further analysis showed that 6 of the SCA participants with TRV ≥ 3.0m/s had a much lower mean Hb (5.8g/dl). There was also an association between TRV and blood urea level (p = 0.030), but not with serum creatinine (p < 0.088). Oxygen saturation was significantly associated with measured TRV (p < 0.001) values. The proportion of SCA with abnormal spirometry (restrictive, obstructive and mixed defects) was 70.4% but this was however not significantly associated with measured TRV values.

Conclusion

Pulmonary hypertension occurred in about a third of the SCA participants, the presence of which was significantly associated with steady state hemoglobin, oxygen saturation and blood urea level. Early screening and identification of risk factors for PH is therefore recommended to reduce morbidity and mortality.