**1. Introduction**

## **1.1 Thalassemia syndrome**

Beta (β)-thalassemia disease is one of the common hereditary hemolytic anemias with high prevalence in the malarial belt areas including the Mediterranean, the Middle East, Transcaucasia, Africa, South and Southeast Asia, and China. It results from mutations on chromosomes 11 and 16 for cases of β-thalassemia and alpha (α)-thalassemia, respectively, with more than 150 different mutations [1, 2]. It describes all the inherited genetic abnormalities that affect the synthesis of α- or β-globin chains and consequently normal erythropoiesis and oxygen-carrying capacity of blood.

Thalassemia is an autosomal recessive disorder classified into two main categories: α- and β-thalassemia. It commonly presents as chronic hemolytic anemia [2]. β-Thalassemia major results from homozygous or compound heterozygous mutations. It involves early presentation, multi-organ complications, frequent hospitalization, and lifelong management. Its treatment depends mainly on blood transfusion. The severe form of β-thalassemia results from defects in two globulin genes and severely reduced production of β-globulin genes [1]. β-Thalassemia minor is an asymptomatic condition due to heterozygous mutations, whereas β-thalassemia intermedia involves two defective genes and is characterized by mild-to-moderate reduction in β globulin production. It is associated with absence of regular blood transfusion and iron chelation therapy, and it may lead to serious specific complications like gall and renal stones, leg ulcer, thrombophilia, and right heart failure [1].

#### **1.2 Pathophysiology**

α-Thalassemia occurs when one or more of the four α-globin genes are missing, damaged, or changed. β-Thalassemia occurs when both β-globin genes are affected [2, 3].

β-Thalassemia is characterized by the reduced synthesis or absence of the β-globin chains in the hemoglobin molecule, resulting in accumulation of unbound α-globin chains that precipitate in erythroid precursors within bone marrow and mature erythrocytes, ultimately resulting in ineffective erythropoiesis and peripheral hemolysis [3].

Anemia stimulates the production of erythropoietin with consequent intensive but ineffective expansion of the bone marrow (up to 25–30 times more than normal), which in turn may cause the typical bone deformities. Prolonged, severe anemia and increased erythropoietic drive result in hepatosplenomegaly and extramedullary erythropoiesis [3].

The molecular and pathophysiological mechanisms underlying the disease process in patients with thalassemia have substantially increased over the past decade. There are many factors that highlight the pathophysiology of β-thalassemia. These include ineffective erythropoiesis, chronic anemia/hemolysis, and iron overload, which is secondary to increased intestinal absorption in thalassemia intermedia and excessive blood transfusion in β-thalassemia major. Thromboembolic events are common in β-thalassemia intermediate in comparison to β-thalassemia major [3], as shown in **Figure 1**.

#### **1.3 Iron toxicity**

One unit of transfused blood contains 200–250 mg of elemental iron. The body has no ability to excrete such quantities of iron. Therefore, the development of iron overload in patients receiving chronic blood transfusion is inevitable. The free or unbound iron accumulates in various organs, such as the liver, heart, pancreas, pituitary, and gonads, and causes the catalysis of injurious compounds, such as free radicals, which will begin to damage cells, leading to fibrosis or organ dysfunction [3]. Iron is highly reactive and easily alternates between two states-iron III and iron II-in a method that results in loss and gain of electrons and the generation of unsafe free radicals. This can damage lipid membranes, organelles, and DNA, ultimately causing cell death and fibrosis [1]. In a healthy individual, iron is kept safe by binding to transferrin, whereas in patients with iron overload, the transferrin capacity to bind iron is exceeded within the cells and in the plasma. This results in the production of free iron within cells or plasma, damaging many tissues in the body, which can be fatal unless treated by iron chelation therapy [4], as shown in **Figure 2**.

*Portal Vein Thrombosis in Patients with β-Thalassemia DOI: http://dx.doi.org/10.5772/intechopen.106564*

#### **Figure 1.** *Pathophysiology of patients with thalassemia.*

The most common complication of β-thalassemia is iron overload, caused either by recurrent blood transfusion in β-thalassemia major or excessive iron absorption in β-thalassemia intermedia. Iron overload results in multiple organ damage [5]. Cardiac complications include cardiomyopathy, arrhythmia, and pericarditis. Liver complications include liver fibrosis and cirrhosis. Endocrine complications include hypothyroidism, pituitary failure, hypoparathyrodism, growth hormone deficiency and sex organ failure. There is also risk of embolism resulting in portal vein thrombosis and portal vein hypertension.

### **1.4 Treatment**

Treatment involves early and regular transfusion to maintain hemoglobin (Hb) levels greater than 9–10 gm/dl. This helps to improve growth and development, reduce hepatosplenomegaly and bone deformity, improve survival, and decrease severity of disease and hemolysis (because chronic transfusion may ameliorate ineffective erythropoiesis) [1].

Chelation therapy is used to maintain safe levels of body iron at all times [5].

Dosing of the drugs involved in chelation therapy (desferrioxamine, deferasirox, jadenu, and deferiprone) and treatment require careful monitoring by serum ferritin and MRI techniques.

**Figure 2.** *Summary of mechanism of iron toxicity.*
