HbH disease

It is clear from the preceding chapters that the clinically significant forms of α-thalassaemia present a wide spectrum of severity. Nevertheless, in all cases age brings with it morbidities that cannot be explained by iron overload alone since hypoxemia and haemolysis may play an equal if not greater role. Even though these complications may be less common in HbH disease compared to β-thalassaemia [see Table 1], they are still to be expected. Even more frequent or severe complications are to be expected in non-deletional forms. In one study from Thailand, comparing the deletional and non-deletional HbH, patients with the non-deletional type of HbH disease had more symptoms at a younger age, more severe haemolytic anaemia, more growth deficiency, more dysmorphic facial features, larger spleens, larger livers, and higher serum ferritin levels, and they required more transfusions than patients with deletional HbH disease [1]. Similar observations were described in Middle Eastern populations [2]. The clinical severity is highly variable even among patients with an identical genotype in HbH disease [3].

Table 1

Reproduced from Lee YC et al 2022: Differences between HbH and β-thalassaemia intermedia [5].

For all these reasons HbH disease requires careful follow up from childhood, irrespective of the initial clinical picture and irrespective of the genotype; only the frequency of clinic visits may vary, especially in childhood, between those with mild anaemia and those with more severe anaemia. Patients who are in a steady state have haemoglobin levels around 90 to 100 g/L, and they may be seen once a year. Patients with non-deletional HbH disease may be more anaemic with significant splenomegaly, and they may require regular blood transfusions, thus requiring more frequent visits [4]. As patients grow, however, the need for vigilance concerning iron overload and other complications will necessitate more frequent monitoring and a more strict protocol of investigations.

Like β-thalassaemia, HbH disease becomes, over time, a multi-organ pathology with considerable variation in severity and frequency of complications. An individualized programme of clinical monitoring and management by various specialists is therefore inevitable. It is noted that although most clinical studies describing the clinical features are based on small numbers of patients and are retrospective, a pattern of clinical evolution emerges:

Box

A history of blood transfusion is described in more than double the patients with non-deletional types of HbH disease compared to deletional. Iron overload, as reflected by serum ferritin measurements, increased with age in a study from Hong Kong [6], (more...)

Blood transfusion is usually a response to haemolytic episodes which are triggered usually by infections. If, however, there is declining baseline Hb, rapid enlargement of the spleen, failure of growth or secondary sexual development, signs of bone changes, poor quality of life, and frequent haemolytic crises, then regular blood transfusions should be considered [9]. During haemolytic episodes, red cell transfusion, at a volume of 5 to 10 ml/kg (or 1–2 units in adults) depending on levels of anaemia, should be provided to restore Hb to 80 to 90 g/L.

Role of nutrition: Patients with HbH disease may have excessive iron absorption triggered by ineffective erythropoiesis and haemolysis. In general, all patients with HbH should receive folic acid supplementation at a dose of 1–5 mg/day, as this is required to increase erythropoietic activity. Biannual monitoring of vitamin D levels and supplementation of vitamin D and calcium as needed is recommended, even though data on vitamin deficiency or bone disease are limited.

The care of patients with HbH disease should also include complete immunization of vaccine-preventable diseases, prompt treatment of fever and infections, and alertness to acute anaemic symptoms. Psychosocial support may be required as in all chronic conditions, and physicians and nurses should be alert to such needs. At the same time more studies on the quality of life of these patients are needed, especially in cases where there is a more severe clinical burden.

Conclusion

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From all published clinical observations, there is concern of underdiagnosed end-organ damage. The management of HbH disease, according to these observations, should be based on inter-professional teams that consist of primary care providers, haematologists, (more...)

Hb Bart’s hydrops foetalis

Management of this condition is inter-professional from the moment a pregnancy is recognized as being a possible case of Hb Bart’s hydrops foetalis. The parents require careful counselling on the genetic aspects, the possible clinical course for both the mother and baby, and the postnatal course and needs of the affected parents. The first dilemma that parents have to face is whether to terminate the pregnancy because of concerns about foetal prognosis, including survival and the risk of obstetric complications for the mother. Indeed maternal complications such as preeclampsia may be life threatening. This is a process that demands the attention of competent genetic counsellors to ensure informed choice in the options offered, an experienced obstetric team, including an ultrasonographer, and an expert haematologist. This can be a traumatic period for the parents and psychosocial support should not be neglected [11].

The pregnancy will be complicated by polyhydramnios, preeclampsia, abruptio placenta, and possible intrauterine infections. Such a high-risk pregnancy should be cared for in a competent centre that is able to perform prenatal diagnoses and has the expertise to perform intrauterine transfusions if the parents choose to have this treatment for their unborn child. Intrauterine transfusions have been shown to reverse hydrops foetalis by improving anaemia and oxygenation, enabling the pregnancy to be carried to term or near term and avoiding the consequences of the condition to both the foetus and the mother [12]. Nevertheless, the outcomes of the surviving newborn are not always as hoped for.

Experience of surviving neonates is increasing and an international registry has been created to collect this experience [13]. Prematurity is prevalent in around 70% of pregnancies and perinatal respiratory depression are frequent, and as a consequence resuscitation, intubation, and mechanical ventilation are needed [14]. This means that along with expertise from the obstetric service, expert neonatal paediatric services and intensive care will also be required to ensure the best possible outcomes. During the neonatal period several interventions may be needed to correct anaemia (blood transfusions), jaundice (exchange transfusions), and respiratory distress syndrome and pulmonary hypertension. Added to this are several congenital abnormalities such as urogenital abnormalities in males (hypospadias and undescended testes), skeletal malformations, congenital heart defects (mainly atrial septal defect), jejunal atresia, and neonatal hepatitis. All these require specialist interventions from paediatric surgery and heart surgery.

Cerebral palsy in the form of spastic diplegia has been described in the post-neonatal period, along with developmental delay. All patients will require regular blood transfusions [15]. As a consequence, all the multi-organ complications arising from iron overload as experienced in β-thalassaemia are to be expected while iron overload is manifest earlier in life as their transfusions had started in utero [16].

Conclusion

Box

Overall management of Hb Bart’s hydrops foetalis is a complex process which starts from the moment prospective at-risk parents select to initiate or continue a pregnancy which will lead to the production of foetal anaemia and heart failure due (more...)

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