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Use of erythropoiesis stimulating agents for the treatment of anaemia and related fatigue in a pregnant woman with HbH disease

2009; Wiley; Volume: 146; Issue: 3 Linguagem: Inglês

10.1111/j.1365-2141.2009.07755.x

1365-2141

Antonio Macciò, Clelia Madeddu, Paola Chessa, Giovanni Mantovani, Renzo Galanello,

Erythropoietin and Anemia Treatment

Physiological changes in pregnancy affect haemoglobin (Hb) and a relative or absolute reduction in Hb concentration without symptoms of anaemia can occur. During pregnancy, anaemia should only be diagnosed when Hb levels are ≤110 g/l at the end of the first trimester and ≤105 g/l in the second and third trimesters (Sifakis & Pharmakides, 2000). Prematurity, spontaneous abortions, low birth weight and foetal deaths may be complications of maternal anaemia. However, fatigue is the most evident symptom of anaemia that profoundly affects the evolution of pregnancy as well as patient quality of life (QoL). Interestingly, the majority of studies on anaemia in pregnancy do not seem to have assessed fatigue and so, QoL questionnaires assessing fatigue should not be neglected in the overall evaluation of pregnant women. Notwithstanding, the most common true anaemias during pregnancy are iron and/or folate deficiency anaemia; in particular regions of the world congenital anaemias, such as thalassaemias, may be the most frequent causes of pregnancy anaemia. HbH disease, which is the intermediate clinical form of alpha thalassaemia, is usually associated with an increased severity of anaemia during pregnancy (Chui et al, 2003). Haemoglobin level may sometimes fall to 70 g/l, or even less, necessitating blood transfusions to preserve the health of the mother and the developing foetus (Origa et al, 2007). Pre-eclampsia, congestive heart failure, miscarriage, perinatal death and premature births are the main obstetrical complication described in pregnant women with HbH disease (Galanello et al, 1992). Recently an increasing number of studies have demonstrated that treatment with Erythropoietic Stimulating Agents (ESA) can avoid the use of blood transfusion, which has traditionally been the only available treatment for severe pregnancy-related anaemia not responding to conventional therapy. ESA have been employed in the treatment of pregnancy-related anaemia associated with chronic renal failure, iron-deficiency resistant to supplementary therapy (Breymann et al, 1995, 2001; Sifakis et al, 2001) as well as congenital haemoglobinopathies (Krafft & Breymann, 2004). These studies demonstrated recombinant human erythropoietin (rHuEPO) therapy was effective in correcting anaemia but highlighted the need of appropriate modulation throughout the pregnancy. Darbopetin alpha has also been safely and successfully used in anaemic pregnant women with chronic renal failure (Sobiło-Jarek et al, 2006). This article provides the first case report of a pregnant woman affected by HbH disease treated with ESA. A 27-year-old pregnant woman affected by HbH disease (due to the deletional type −−/−alpha3·7 genotype) presented with severe anaemia at the 15th week of gestation. Laboratory investigations revealed Hb 70 g/l, hematocrit 23%, serum ferritin 26 μg/l and serum iron 157 μg/dl (Table I). In accordance with our patient’s wishes ESA treatment rather than haemotransfusion was initiated for the correction of severe anaemia. RHuEPO-β 30 000 IU subcutaneously was administered twice in the first week as induction therapy, followed by darbopoetin 500 IU every 3 weeks, until delivery, without intravenous iron therapy, in order to keep the patient’s Hb at the same level as before pregnancy or higher. She also received folic acid 20–25 mg/d, vitamin D 0·25 μg/every other day, and calcium carbonate 1–2 mg/day. The two different type of ESAs were chosen accordingly the following rationale: induction with rHuEPO to obtain a rapid response in terms of Hb values and fatigue symptoms and then maintenance with 3-weekly darbopoetin for better patient compliance and QoL (Glaspy et al, 2006). As the patient was not iron deficient, iron supplement was not indicated (Chui et al, 2003). Haematological variables were assessed once a week, whilst liver and renal function parameters and obstetric evaluation (including monitoring of foetal activity and growth, placental maturity and umbilical artery perfusion) were determined every 3 weeks. The patient was also invited to complete the Numerical Rating Scale for Fatigue (NRS-F) questionnaire at baseline, after 1 week of treatment and then every 3 weeks. NRS-F provides a single rating of patient fatigue-related problem on a 0–100 scale according to the severity of fatigue: 0 score indicates no fatigue and 100 score indicates the worst fatigue possible. After the first week of treatment, the reticulocyte count rapidly increased, Hb reached 80 g/l and then progressively rose to 95 g/l. Moreover, from the first week of ESA treatment the patient reported a significant and continuous improvement of her fatigue (Table I). The patient had no signs of renal or hepatic impairment and her blood pressure was in the normal pregnancy range. Serial ultrasonography revealed normal foetal growth. After hospital admission at the 38th week for elective labour induction, the patient developed a spontaneous labour followed by pathological foetal heart rate trace consequent to the umbilical cord wrapped around the foetus’ neck. An emergency caesarean section was performed, with delivery of a 3·13 kg male infant. Apgar scores were 8 and 10 at 1 and 5 min, respectively. Neonatal evaluation revealed no abnormalities. The patient had an uneventful postpartum course with Hb values stable at 85 g/l until hospital dismissal. In conclusion, we have successfully used ESA to treat pregnancy-induced anaemia in a patient with HbH disease without detrimental effect to either the patient, pregnancy or the foetus, at the same time avoiding transfusion and measurably improving the patient’s QoL. Indeed, ESA treatment gives several advantages over transfusion: reduced risk of infection or transfusion reaction, less transient effect and benefit for patient, increased acceptability to patients, in particular those with religious objections to transfusion, i.e. Jehovah’s witnesses, as well as decreased blood product utilization and no need for hospitalization. Notably, we have shown, for the first time in the literature, the effectiveness of ESA treatment to rapidly and significantly relieve severe fatigue symptoms. Our results suggest that ESA should be considered as a viable alternative treatment in similar cases of pregnancy-induced anaemia in HbH disease although further studies are warranted. Moreover, it is to be hoped that fatigue associated with anaemia in pregnancy will be carefully assessed and addressed in forthcoming studies.