The rare but life-threatening disease Pulmonary Hypertension (PH) is characterized by high blood pressure in the lungs due to damage to the pulmonary arteries. These vessels are the ones used to transport blood from the right heart ventricle to the lungs, but as a result of the disease they become narrowed and blocked. Therefore, the heart needs to work under stress to properly pump the blood, which enlarges and weakens the organ, and may cause right heart failure.

The majority of the cases of pulmonary hypertension are associated with an underlying disease. Any condition that affects normal blood flow can cause PH, including Sickle Cell Disease (SCD). This term refers to a group of inherited red blood cell disorders, that causes abnormalities in the hemoglobin, the protein present in red blood cells that carries oxygen throughout the body.

Development of Pulmonary Hypertension and Sickle Cell Disease

Sickle cell disease is one of the most common genetic diseases among the African American population, but is also prevalent throughout the world in other populations as well. Due to the disease, the hemoglobin variant called hemoglobin S (Hb S) polymerizes upon deoxygenation. This reaction results in rigidity and “sickling” of the red blood cells, as well as consequent damage to the membranes and impairment of the red cells circulation, as explained in the study “Pulmonary Artery Hypertension in Sickle Cell Disease,” authored by Melissa E. Clarke, MD.

“The resulting microvascular occlusions injure major organ systems including the lungs, kidneys, liver, spleen, skeleton, skin, and central nervous system,” states the author. “Periods of stability in the disease are punctuated by vaso-occlusive crises (VOC), episodes of severe pain involving the back, chest, abdomen, and joints. Although VOC may sometimes be triggered by infection, dehydration, cold, stress, menses, and alcohol, its physiologic basis is largely unknown.” The damage caused to blood circulation can result in pulmonary hypertension.

Prevalence and Mortality of Pulmonary Hypertension and Sickle Cell Disease

The same research demonstrates that VOC typically occurs after two years of age, when fetal hemoglobin (Hb F) is replaced by Hb S. “Approximately one third of individuals with Hb S have only rare VOC, one third have 2-6 episodes a year, and one third have greater than six episodes a year.” Not all patients with sickle cell disease develop pulmonary hypertension, but it is a reality for about 32% of patients with the disease, as the prevalence of SCD-related PH is particularly high in patients with lower levels of fetal hemoglobin and lower systolic blood pressure. It also increases with age.

In addition to having to deal with the symptoms and burden of pulmonary hypertension associated with sickle cell disease, patients also face an increased risk for early death, renal failure, seizures, an elevated baseline white blood cell count higher than 15,000 cells/mm3, and a low level of fetal hemoglobin. The study reported a 40% mortality rate in SCD patients with pulmonary hypertension at 22 months post-diagnosis.

Treatment for Pulmonary Hypertension Caused by Sickle Cell Disease

There is currently no cure for pulmonary hypertension, but there are treatments that can help patients ease their symptoms and extend life expectancy. However, the coexistence of two or more conditions needs to be considered by physicians prior to defining the best treatment course. Treatment with hydroxyurea is able to increase the levels of Hb F, reducing Hb S polymerization and the burden of further complications associated with it, like pulmonary hypertension. New therapeutic approaches suggest the benefits of using nitroxic oxygen (NO) alone or in combination with arginine to treat the conditions.

“Some centers are now using inhaled NO experimentally in the treatment of acute complications of SCD. However, despite the promise on the horizon for investigational treatments, including NO, the standard therapy for SCD complicated by PAH remains to optimize disease treatment with hydroxyurea (with or without erythropoietin), and to use hydration and transfusions while employing standard PAH therapy (oxygen, anticoagulation, and pulmonary vasodilator therapy),” the study concludes.

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