Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease: Cochrane systematic review
Assessed as up to date: 2016/05/16
Sickle cell disease is a genetic haemoglobin disorder, which can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Sickle cell disease is one of the most common severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality.
This is an update of a Cochrane review first published in 2011 and updated in 2014.Objectives
We wanted to determine whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with standard care, hydroxycarbamide (hydroxyurea) any other drug treatment show differences in the following: mortality associated with chronic chest complications; severity of established chronic chest complications; development and progression of chronic chest complications; serious adverse events.Search methods
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. Date of the last search: 25 April 2016.
We also searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 26 January 2016), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 26 January 2016.Selection criteria
We included randomised controlled trials of people of any age with one of four common sickle cell disease genotypes, i.e. Hb SS, Sβ0, SC, or Sβ+ that compared regular red blood cell transfusion regimens (either simple or exchange transfusions) to hydroxycarbamide, any other drug treatment, or to standard care that were aimed at reducing the development or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension).Data collection and analysis
We used the standard methodological procedures expected by Cochrane.Main results
No studies matching the selection criteria were found.Authors' conclusions
There is a need for randomised controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants repeatedly before and after the intervention.
Estcourt Lise J, Fortin Patricia M, Hopewell Sally, Trivella Marialena, Hambleton Ian R, Cho Gavin
The effect of long-term red blood cell transfusions on chronic chest complications of sickle cell disease
We reviewed the evidence to see if regular long-term red blood cell transfusions helped to reduce the occurrence or progression of chronic chest complications compared to hydroxycarbamide (hydroxyurea), any other treatment or standard care in people with sickle cell disease.
Oxygen is transported from our lungs to all parts of our body by haemoglobin, which is a major component of red blood cells. Sickle cell disease is an inherited disorder of haemoglobin. In people with sickle cell disease red blood cells become rigid once they have given up their oxygen and are often shaped like crescents. These rigid cells can block blood vessels, which causes problems throughout the body, including the lungs. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. Pulmonary hypertension is high blood pressure in the pulmonary arteries (the arteries that supply blood to the lungs). High blood pressure in these arteries are associated with an increased risk of death. Chronic sickle lung disease arises as a result of lung damage and loss of lung tissue.
Regular blood transfusions for people with sickle cell disease reduce the amount of the person's own sickled cells in their blood by replacing them with donated, non-sickled cells. Regular transfusions have already been shown to reduce the risk of strokes in people with sickle cell disease.The aim of this review was to find out if regular long-term blood transfusions in people with sickle cell disease lead to a reduction in new chronic chest complications or slowed the progression of any chronic chest complications that have already developed. It also aimed to consider death rates due to chronic chest complications and any adverse effects of the transfusion programme.
The evidence is current to March 2016. We found no studies in this update of the review.
There are no results because we found no relevant randomised controlled trials. We would need to design a study with at least 946 participants to be able to detect a decrease in the number of people who died from 12 in 100 to six in 100.
Quality of the evidence
There is no evidence from randomised controlled trials to answer our review questions.
Implications for practice
As no trials were found for inclusion in the review, it is not possible to comment on the evidence for or against the efficacy of long-term red blood cell transfusions for managing chronic chest complications in people with SCD.
Implications for research
There is a need for RCTs looking at the effect of long-term transfusion therapy on pulmonary hypertension and chronic sickle lung disease. The most likely starting point for any series of trials will be the effect of transfusion on existing pulmonary hypertension. The effect of transfusion on disease incidence and mortality would require trials with longer-term follow-on, making them more costly and conceptually more difficult. The definition of chronic sickle lung disease include is not agreed by consensus and this is a stumbling block for further studies in this area.
New trials could consider using a combination of objective and subjective outcome measures. Effectiveness could be measured objectively, for example, through echocardiogram or pulmonary function testing, or subjectively by measuring symptoms such as chest pain on a standardised scale. Such trials might provide useful information on the rate of deterioration in chronic chest complications. Given the chronic nature of the condition, trials could consider measuring pre-intervention 'severity' using an extended baseline 'steady state' period.
It should be remembered that transfusions may reduce symptoms such as breathlessness by increasing the haemoglobin level rather than having any beneficial effect per se on the chronic chest complication. Future RCTs in this area should have clear protocols for the aims of transfusion (such as a target haemoglobin level, or target sickle haemoglobin percentage) and how the long-term transfusion programme is to be carried out, for example, by simple or exchange transfusion.
Possible transfusion complications are a key concern, and it would be important to collect information on the complications arising from long-term transfusion therapy in trial participants.Get full text at The Cochrane Library
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