Blood transfusion policies for sickle cell disease in pregnancy

What is the issue?

Sickle cell disease is an inherited disorder of haemoglobin, the protein in red blood cells that carries oxygen. In this condition, an abnormal haemoglobin S from one parent is combined with another abnormal haemoglobin from the other parent. Haemoglobin S inherited from both parents (genotype HbSS), described as sickle cell anaemia is the most common form.

Why is this important?

When oxygen tension is low, haemoglobin S crystallises and makes the red blood cells sickle-shaped. Sickling reduces red blood cell capacity to manoeuvre through very small blood vessels causing vascular blockage and early destruction of red cells. The breakdown of red blood cells and massive pooling of damaged red blood cells in the liver and spleen cause anaemia. Acute illnesses include painful crises, pulmonary embolism, acute chest syndrome and congestive cardiac failure. Therefore, pregnant women with sickle cell disease require careful management.

Depending on the institutional policy, blood transfusion can be given at intervals to a pregnant woman with HbSS with relatively few or no symptoms to improve the oxygen carrying capacity of blood by increasing haemoglobin blood concentration and lowering haemoglobin S levels; or only when indicated by the development of medical or pregnancy complications. Giving blood at frequent intervals carries the risks of blood-borne infections and excessive levels of iron.

This review set out to determine whether giving blood at intervals before serious complications occur compared with giving blood only when medically indicated makes a difference to the health of the mother and her baby.

What evidence did we find?

We searched for evidence on 30 May 2016 and identified one controlled trial, with an unclear risk of bias, that randomised 72 women with sickle cell anaemia (haemoglobin SS) before 28 weeks of gestation to one of the two blood transfusion policies. The trial indicated no difference in severe ill health and death of the mother or newborn. There was no difference in the risk of delayed blood transfusion reaction. The trial suggested giving blood at frequent intervals reduced the risk of pain crisis, with a large degree of uncertainty about the size of the effect, compared with giving blood only when medically indicated. Blood transfusion was delivered at a ratio of four to one for prophylactic versus selective blood transfusion, respectively. Overall, the quality of evidence for outcomes that are important to the woman is very low.

What does this mean?

The available evidence on this subject is insufficient to advocate for a change in clinical practice and policy. More research needs to be conducted.

Authors' conclusions: 

Evidence from one small trial of very low quality suggests that prophylactic blood transfusion to pregnant women with sickle cell anaemia (HbSS) confers no clear clinical benefits when compared with selective transfusion. Currently, there is no evidence from randomised or quasi-randomised trials to provide reliable advice on the optimal blood transfusion policy for women with other variants of sickle cell disease (i.e. HbSC and HbSβThal). The available data and quality of evidence on this subject are insufficient to advocate for a change in existing clinical practice and policy.

Read the full abstract...
Background: 

Pregnant women with sickle cell disease (HbSS, HbSC and HbSβThal) may require blood transfusion to prevent severe anaemia or to manage potential medical complications. Preventive blood transfusion in the absence of complications starting from the early weeks of pregnancy or blood transfusion only for medical or obstetric indications have been used as management policies. There is currently no consensus on the blood transfusion policy that guarantees optimal clinical benefits with minimal risks for such women and their babies. This is an update of a Cochrane review that was published in 2013.

Objectives: 

To assess the benefits and harms of a policy of prophylactic versus selective blood transfusion in pregnant women with sickle cell disease.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 May 2016) and reference lists of retrieved studies. We did not apply any language or date restrictions.

Selection criteria: 

Randomised controlled trials evaluating the effects of prophylactic versus selective (emergency) blood transfusion in pregnant women with sickle cell disease (SCD). Quasi-randomised trials and trials using a cluster-randomised design were eligible for inclusion but none were identified.

Data collection and analysis: 

Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two review authors independently assessed the quality of the evidence using the GRADE approach.

Main results: 

Out of six relevant reports identified by the search strategy, one trial involving 72 women with sickle cell anaemia (HbSS) met our inclusion criteria. The trial was at unclear risk of bias. Overall, there were few events for most of the reported outcomes and the results were generally imprecise. The included trial reported no maternal mortality occurring in women who received either prophylactic or selective blood transfusion. Very low-quality evidence indicated no clear differences in maternal mortality, perinatal mortality (risk ratio (RR) 2.85, 95% confidence interval (CI) 0.61 to 13.22; very low-quality evidence) or markers of severe maternal morbidity (pulmonary embolism (no events); congestive cardiac failure (RR 1.00, 95% CI 0.07 to 15.38; very low-quality evidence); acute chest syndrome (RR 0.67, 95% CI 0.12 to 3.75)) between the treatment groups (prophylactic blood transfusion versus selective blood transfusion). Low-quality evidence indicated that prophylactic blood transfusion reduced the risk of pain crisis compared with selective blood transfusion (RR 0.28, 95% CI 0.12 to 0.67, one trial, 72 women; low-quality evidence), and no differences in the occurrence of acute splenic sequestration (RR 0.33, 95% CI 0.01 to 7.92; low-quality evidence), haemolytic crises (RR 0.33, 95% CI 0.04 to 3.06) or delayed blood transfusion reaction (RR 2.00, 95% CI 0.54 to 7.39; very low-quality evidence) between the comparison groups.

Other relevant maternal outcomes pre-specified for this review such as cumulative duration of hospital stay, postpartum haemorrhage and iron overload, and infant outcomes, admission to neonatal intensive care unit (NICU) and haemolytic disease of the newborn, were not reported by the trial.

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