Thromboembolism in Beta-Thalassemia Disease

*Rungrote Natesirinilkul*

#### **Abstract**

Thalassemia disease is a common inherited hemolytic anemia frequently found in several parts of the world, especially in the Mediterranean and some Asian countries. Besides the complications of secondary hemochromatosis from regular red blood cell (RBC) transfusion and increased gastrointestinal absorption of iron, thromboembolism (TE) is one of the common long-term complications of beta-thalassemia disease, particularly in patients with non-transfusion-dependent thalassemia (NTDT), which is commonly seen after the second decade of life. The risk factors of TE in beta-thalassemia disease including exposure of phosphatidylserine of abnormal RBCs, increase of platelet activation and aggregation, elevation of endothelial microparticles and increased endothelial activation, decreased nitric oxide (NO) secondary to hemolysis, rise of platelet count and nucleated RBCs after splenectomy, organ dysfunction caused by hemochromatosis, and thrombophilia such as natural anticoagulant deficiencies leading to hypercoagulable state. The understanding of the pathophysiology would result in effective prevention of this complication of beta-thalassemia disease.

**Keywords:** thromboembolism, beta-thalassemia, NTDT

#### **1. Introduction**

Beta-thalassemia disease is one of the most common congenital hemolytic anemia commonly found in the malarial belt areas including the Mediterranean, the Middle East, Transcaucasus, Africa, South and Southeast Asian countries, and China [1]. It is inherited by autosomal recessive manner [1, 2]. Beta-thalassemia disease is the result from the mutation of beta-globin genes causing decrease of beta-globin leading to imbalance of alpha-globin and beta-globin and subsequently causing ineffective erythropoiesis. According to the Thalassemia International Federation (TIF), patients with thalassemia disease can be categorized into two groups, transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT), based on their phenotypes and genotypes [1–3]. The major long-term complication of TDT is hemochromatosis-induced organ failures secondary to red blood cell (RBC) transfusion [1, 2], while the complications of NTDT are hemochromatosis secondary to increased iron absorption from gastrointestinal tract, pulmonary hypertension, leg ulcer, and thromboembolism (TE) [3–5].

The incidence of thromboembolism is between 0.8 and 2.7 per 1000 population [6] which has been increasing over the decades in both adult and pediatric population [6, 7] patients with thalassemia disease are at risk of hypercoagulable state and thromboembolism [8, 9]. The studies of thromboembolism in thalassemia disease

have been increasingly published recently. Understanding the pathophysiology of thromboembolism in thalassemia diseases is the key for the management to prevent this complication.
