Introduction

The spleen is a unique lymphoid organ that plays important roles in innate and adaptive immunity and clearance of senescent, or abnormal, blood cells. It is also a part of the reticuloendothelial system and contributes to the recycling of iron. The spleen also hosts haematopoietic cells and participates in erythropoiesis when the capacity of bone marrow to meet erythroid demand is exhausted [1–3].

In haematological disorders, pathophysiology of splenomegaly is diverse, and it is mainly driven by the underlying disease process. For example, in hereditary spherocytosis, splenomegaly represents chronic congestion of splenic cords by rigid spherocytes and splenic hyperplasia [4]. In β-thalassaemia, in addition to the increased splenic hyperplasia due to extravascular haemolysis, ineffective erythropoiesis and elevated erythropoietin lead to extramedullary haematopoiesis in the spleen, further contributing to enlargement of the spleen. Ineffective erythropoiesis, in turn, further increases the metabolic demand, exacerbates the plasma volume expansion, and imposes greater load on the already-burdened myocardium [5]. Ineffective erythropoiesis also contributes to defective iron metabolism [6].

Splenomegaly is a common complication in patients with HbH disease (mainly the non-deletional forms) and the spleen is quite enlarged in patients with haemoglobin Bart’s hydrops foetalis (α-thalassaemia major) [7]. In HbH disease, most of erythrocyte destructions occur in the spleen, while the spleen also contributes to ineffective erythropoiesis, although to a lesser degree as compared to β-thalasssaemia [8–9].

Clinically, splenomegaly may be associated with a variety of complications, like sense of heaviness and discomfort, abdominal pain, early satiety, and features associated with hypersplenism, leading to worsening of anaemia, thrombocytopenia and leukopenia. A very large spleen poses the risk of acute rupture with abdominal trauma.

Splenectomy for HbH disease

Splenectomy is a treatment option for many benign haematological conditions, including immune thrombocytopenia (ITP) and heredity or acquired haemolytic anaemias like hereditary spherocytosis [10]. While improvements in surgical techniques have resulted in lower perioperative complications and mortality, there is increasing evidence of long-term complications due to the loss of spleen function.

Immune dysfunction and increased susceptibility to infection, particularly with encapsulated bacteria, are well-described complications of splenectomy. The risk of infection is highest within the first 2–3 years following splenectomy. Young children and older adults [11] and those with other underlying medical conditions (e.g., diabetes mellitus) may be at higher risk of infection. Effective vaccination against encapsulated bacteria prior to splenectomy is protective. Please refer to Chapter 7: Infections and haemoglobin H disease for further recommendations.

Other long-term complications of splenectomy are observed in a variety of haematological conditions. The rate of these complications vary according to the underlying condition. For example, splenectomized patients with β-thalassaemia are at particularly higher risk of venous thromboembolism or pulmonary hypertension [10]. While these complications have been observed in splenectomized patients with HbH disease [12–15], this risk is likely lower in patients with HbH disease as compared to splenectomized patients with β-thalassaemia. Furthermore, the risk of alloimmunization is likely higher in splenectomized patients [16].

In HbH disease, splenectomy is effective in increasing the haemoglobin levels, often by 20-30 g/L [17–19]. The actual clinical benefit of this increase in haemoglobin levels for patients with milder forms of HbH disease may be negligible; thus, splenectomy is not generally recommended for these patients [17]. Similarly, while in patients with very severe forms of HbH disease, who require early initiation of transfusion, or those with severe anaemia (functional Hb < 70 g/L), splenectomy may raise the haemoglobin level, it may not eliminate the need for transfusions and may be associated with a higher degree of complications. Thus, splenectomy is not ideal in this group of patients. For patients with an intermediate degree of anaemia (e.g., non-deletional HbH disease with moderate–severe anaemia and episodes of acute hemolysis requiring frequent transfusions), or those who have significant and symptomatic hepatosplenomegaly, splenectomy might be considered [17, 20]. Even in these patients, the decision to proceed with splenectomy (an irreversible procedure with long-term complications) is complicated. In addition to the severity of symptoms due to α-thalassaemia, existing risk factors that can increase or exacerbate complications (e.g., underlying risk of thrombosis, history of prior infection, presence of risk factors for pulmonary hypertension) and the availability or convenience of other therapeutic options (e.g., chronic transfusion programme and iron chelation) are important to be considered. Most importantly, a patient’s values and preference should be valued. Splenectomy is not recommended in very young children because of the higher risk of overwhelming sepsis in young children.

In patients with HbH disease, the effect of splenectomy on iron balance and distribution is not well-studied [21]. Thus, until further data becomes available, splenectomy is not recommended for iron management in patients who do not require regular or frequent transfusions and do not have other indications for splenectomy.

Splenectomy for haemoglobin Bart’s hydrops foetalis (α-thalassaemia major)

Patients with haemoglobin Bart’s hydrops foetalis (α-thalassaemia major) have significant splenomegaly, even when they are on an aggressive transfusion protocol. This is likely due to extravascular haemolysis and significantly increased erythropoiesis that cannot be fully abrogated by chronic transfusions in this severe haemolytic condition. In patients with haemoglobin Bart’s hydrops foetalis (α-thalassaemia major), removing the spleen would likely prolong the lifespan of endogenous cells that are exclusively made of non-functional haemoglobin H (see Chapter 5: Long-term management of α-thalassaemia major (haemoglobin Bart’s hydrops foetalis)). As such, although the total haemoglobin concentration may increase, this would not lead to any physiological improvement due to the higher proportion of nonfunctional haemoglobin H, and instead would make effective transfusion even more challenging [22]. In contrast, splenectomy may be associated with the development of a life-threatening thromboembolic complication [23]. Thus, currently, splenectomy is not recommended in patients with haemoglobin Bart’s hydrops foetalis [7].

Methods of splenectomy

Splenectomy can be performed via a laparotomy or a laparoscopic approach. Although there are no extensive data on the comparison of these two approaches in patients with HbH disease, in other conditions (including β-thalassaemias), laparoscopic splenectomy has been shown to be associated with a lower bleeding rate, earlier hospital discharge, less post-operative pain, and lower risk of infections. It is, however, associated with the possibility of conversion to open splenectomy [24, 25]. The choice of splenectomy approach should be individualized for the patient and the expertise of the surgical team.

Another approach to splenectomy is the complete removal of spleen tissue (total splenectomy), or partial removal of the spleen tissue (partial splenectomy) with the intent to preserve some of its desired function, mainly the immune function. While partial splenectomy may be considered in some patients with HbH disease, especially those who may be at higher risk of infection or other complication of asplenia (e.g., high risk of thrombosis), overall, the safety and effectiveness of partial splenectomy compared to total splenectomy in patients with HbH disease has not been studied.

Reduction of splenic tissue by embolization is a less invasive approach that has been used for other indications. One drawback is the risk of post-embolization syndrome (fever, nausea, significant pain) and the possible need for a subsequent total splenectomy. More significant complications include abscess formation, pleural effusion, portal vein thrombosis, and liver failure, especially with the larger areas of embolization [26, 27]. The effectiveness of splenic embolization has not been studied in α-thalassaemia.

Gallstones, including intrahepatic bile duct stones, are detected in over 30% of asymptomatic patients with HbH disease, which can cause abdominal discomfort and hepatobiliary infection [28]. It is thus reasonable to consider cholecystectomy, if splenectomy is being considered in patients with HbH disease.

Summary of recommendations

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