Risk Factors for Pulmonary Hypertension In Patients with Thalassemia Intermedia

Mechanisms leading to pulmonary hypertension (PHT) in patients with thalassemia intermedia (TI) are still controversial. Moreover, clinical and laboratory characteristics of patients who eventually develop PHT have not been identified. Our aim was to identify factors that characterize TI patients who develop PHT.

Data was retrospectively retrieved from the Thalassemia Intermedia Registry, a database of 584 TI patients currently registered at six comprehensive care centers in Lebanon, Italy, Iran, Egypt, United Arab Emirates, and Oman. Institutional review boards at each center approved the study protocol. Two Groups of patients were identified: Group I, TI patients with documented PHT (n=64; mean age 37.3 ± 10.6; 44% males); and Group II, age- and sex-matched TI patients without PHT (n=64; mean age 37.9 ± 11.4; 44% males). Collected data included demographics, laboratory parameters, disease-complications, and received treatments that may influence PHT development and reflected the period prior to PHT occurrence.

There were no statistically significant differences in mean platelet counts, total or fetal hemoglobin levels between the two Groups. However, mean serum ferritin level was higher in Group I compared to Group II (1233.2 ± 499.2 vs. 654.7 ± 234.5 ng/ml; P=0.01). Moreover, mean nucleated red blood cell (NRBC) count was higher in Group I compared to Group II (354.2 ± 199.2 vs. 214.7 ± 94.5 ×10^⋀6/l; P=0.03). A higher proportion of patients were splenectomized (84.4% vs. 46.9%; P<0.001) or had a previous history of thromboembolic events (40.6% vs. 7.8%; P<0.001) in Group I compared to Group II. Conversely, a higher proportion of patients received transfusion (78.1% vs. 56.2%; P<0.001), iron chelation (62.5% vs. 37.5%; P<0.001), or hydroxycarbamide (34.4% vs. 17.2%; P<0.001) therapy in Group II compared to Group I. There were no statistically significant differences in the proportion of patients with heart failure, prothrombotic mutations, or receiving antiplatelet or anticoagulant therapy between the two Groups. Multivariate logistic regression analysis revealed that patients in Group I are more likely to be splenectomized (OR:4.9, 95%CI:1.9-8.5); transfusion-naive (OR:3.5, 95%CI:2.1-6.25); on no hydroxycarbamide (OR:2.6, 95%CI:1.1-5.25) or iron chelation therapy (OR:2.3, 95%CI:1.2-4.25); and have NRBC count >300 ×10^⋀6/l (OR:2.59, 95%CI:1.69-6.05) or a previous history of thromboembolism (OR:3.69, 95%CI:2.38-7.05).

Splenectomy, previous history of thromboembolism, and a high NRBC count characterize TI patients who develop PHT. Transfusion, iron chelation, and hydroxycarbamide therapy deserve evaluation for a protective role against PHT in TI.

No relevant conflicts of interest to declare.