Pulmonary Hypertension: A Common Complication in Thalassemia.

Pulmonary hypertension (PHT) is a complication that is associated with high mortality rate. It is increasingly recognized in thalassemia intermedia (TI) as a leading factor in heart failure and death. Undetected PHT has been reported in 60–75% of patients. Data on PHT and thalassemia major is limited. However, these patients have many risk factors for PHT, including splenectomy, red cell phosphatidylserine exposure, coagulation abnormalities and iron overload. Since chronic hemolysis continues despite transfusion, these patients are also at risk for hemolysis-associated PHT. This is a recently described syndrome where free hemoglobin scavenges nitrous oxide and catalyzes the formation of reactive oxygen species. The purpose of this study is to determine the prevalence of PHT in transfused thalassemia patients and its risk factors. We compared the echocardiogram of 28 patients with their transfusion history, iron stores, chest x-ray, age, hemoglobin level, splenectomy status and cardiac function.

The prevalence of PHT in this population was 57%. Sixteen of the 28 patients had a tricuspid regurgitant jet velocity ≥2.5 m/s, indicating PHT. 5 patients had a jet velocity ≥ 2.9 m/s suggestive of moderate PHT. Patients with PHT were more likely to be older (29±10 vs. 24±7 years without PHT, r=0.52, p=0.01) and male (56%). 41% of the female patients undergoing echocardiogram exam had PHT, while 82% of the men screened had PHT (p=0.03). PHT was also inversely related to ferritin level (r=−0.46, p=0.02). A history of an abnormal CXR occurred more frequently in the PHT group (38% vs. 8%, p=0.08), but did not reach statistical significance. However, there was no difference in hemoglobin level, creatinine, splenectomy rate (63% vs. 58%) or abnormal cardiac function between patients with PHT vs. those without PHT.

Two of the 16 patients with PHT have initiated therapy with hypertransfusion or sildenafil. An intermittently transfused 25-year-old female patient lowered the tricuspid jet velocity from 3.2 to 2.4 m/s following hypertransfusion program. The second patient, a 44-year-old chronically transfused female, lowered her tricuspid jet velocity from 3 to 2.3 m/s within one month of sildenafil therapy.

In conclusion, PHT is a common complication in transfused thalassemia patients that is under recognized and under treated. In contrast to other complications, adequate chelation and low iron stores are not protective. Since secondary PHT is associated with a high mortality and morbidity, annual screening with echocardiogram for all thalassemia patients is recommended. Early identification of PHT and its risk factors may prevent the irreversible cardiomyopathy that may develop. Prospective studies evaluating therapies, including hypertransfusion, sildenafil and arginine are needed.