Name: continuous manual exchange transfusion for patients with sickle cell disease: an efficient method to avoid iron overload
Uploaded: 2017-03-14T14:00:00
Description: Watch this Scientific Journal Video about Continuous Manual Exchange Transfusion for Patients with Sickle Cell Disease: An Efficient Method to Avoid Iron Overload at JoVE.com

We would like to thank the patients and parents for their continuous support; the caregivers for their dedication; Pr Bierling, director of the French Blood Bank in the Paris area, for his support of the collaborative work between our hospital and his team to develop the continuous manual exchange transfusion method; and the University Paris Diderot and the hospital Robert-Debr&#233; for their support.

The protocol follows the guidelines of the hospital ethics committee. There are 3 steps in the exchange sessions: patient preparation; initial isovolemic phlebotomy (if appropriate); and whole-blood exchange, consisting of several cycles, or continuous whole-blood phlebotomy, which is associated with the infusion of diluted PRBCs. Depending of the Hb level of the patient, a fourth step of intermediary isovolemic phlebotomy can be added midway through the exchange stage. At the start of the session, all of the necessary m...

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	<li>Stuart, M. J., Nagel, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sickle-cell+disease.">Sickle-cell disease.</a> Lancet. 364 (9442), 1343-1360 (2004).</li><li>Aygun, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+transfusion+practices+for+prevention+of+primary+stroke+in+children+with+sickle+cell+anemia+and+abnormal+TCD+velocities.">Chronic transfusion practices for prevention of primary stroke in children with sickle cell anemia and abnormal TCD velocities.</a> Am J Hematol. 87 (4), 428-430 (2012).</li><li>Ohene-Frempong, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebrovascular+accidents+in+sickle+cell+disease:+rates+and+risk+factors.">Cerebrovascular accidents in sickle cell disease: rates and risk factors.</a> Blood. 91 (1), 288-294 (1998).</li><li>Adams, R. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prevention+of+a+first+stroke+by+transfusions+in+children+with+sickle+cell+anemia+and+abnormal+results+on+transcranial+Doppler+ultrasonography.">Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography.</a> N Engl J Med. 339 (1), 5-11 (1998).</li><li>Scothorn, D. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Risk+of+recurrent+stroke+in+children+with+sickle+cell+disease+receiving+blood+transfusion+therapy+for+at+least+five+years+after+initial+stroke.">Risk of recurrent stroke in children with sickle cell disease receiving blood transfusion therapy for at least five years after initial stroke.</a> J Pediatr. 140 (3), 348-354 (2002).</li><li>Koehl, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+automated+erythrocytapheresis+versus+manual+exchange+transfusion+to+treat+cerebral+macrovasculopathy+in+sickle+cell+anemia.">Comparison of automated erythrocytapheresis versus manual exchange transfusion to treat cerebral macrovasculopathy in sickle cell anemia.</a> Transfusion. 56 (5), 1121-1128 (2016).</li><li>Kim, H. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Erythrocytapheresis+therapy+to+reduce+iron+overload+in+chronically+transfused+patients+with+sickle+cell+disease.">Erythrocytapheresis therapy to reduce iron overload in chronically transfused patients with sickle cell disease.</a> Blood. 83 (4), 1136-1142 (1994).</li><li>Adamkiewicz, T. V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Serum+ferritin+level+changes+in+children+with+sickle+cell+disease+on+chronic+blood+transfusion+are+nonlinear+and+are+associated+with+iron+load+and+liver+injury.">Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury.</a> Blood. 114 (21), 4632-4638 (2009).</li><li>Raghupathy, R., Manwani, D., Little, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Iron+overload+in+sickle+cell+disease.">Iron overload in sickle cell disease.</a> Adv Hematol. , (2010).</li><li>Porter, J. B., Evangeli, M., El-Beshlawy, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Challenges+of+adherence+and+persistence+with+iron+chelation+therapy.">Challenges of adherence and persistence with iron chelation therapy.</a> Int J Hematol. 94 (5), 453-460 (2011).</li></ol>

The risk associated with this procedure is an unexpected misbalance between the phlebotomy and the transfusion, which can have dangerous consequences. A rapid depletion will lead to hypovolemia and acute anemia, while an excess transfusion without bleeding will lead to a dangerous increase in blood viscosity. In both cases, SCA patients could suffer from vaso-occlusive complications, as well as strokes. For this reason, one nurse must be dedicated to each patient and stay at his bedside during the whole procedure. There ...

A single point mutation in the &#946;-globin gene is responsible for the production of abnormal hemoglobin (hemoglobin S, HbS). This causes sickle cell anemia (SCA), one of the most common diseases worldwide1. SCA patients&#39; acute symptoms and some chronic complications can be treated by the transfusion of packed red blood cells (PRBCs). Indeed, the transfusion of normal RBCs corrects the anemia while diluting the sickle RBCs. As a result, it can increase the oxygen transport capacity while decreasing hemolysis and vaso-occlusive events. To avoid chronic complications or to treat patients with acute complications, transfusion combined with the depletion of sickle RBCs, either by phlebotomy or by erythrapheresis, is an effective way to limit the dangerous increase in hemoglobin and blood viscosity while reducing the number of circulating SS RBCs2.
One of the main causes of psychomotor handicaps and neurocognitive deficiencies in children with SCA3 is cerebral vasculopathy, a devastating complication of this disease. In SCA children with abnormally high velocities on transcranial Doppler, chronic transfusions are effective in preventing the occurrence of the first stroke4. To reduce the risk of recurrence in patients that have already suffered from an ischemic stroke, transfusion therapy is the most adequate method5. In the case of chronic therapy, RBC exchange transfusion is better than simple RBC transfusion, as it removes sickle cells and adds normal cells while reducing blood viscosity and limiting iron overload. Nonetheless, simple RBC transfusion is still widely used as a treatment for cerebral macro-vasculopathy. While it rapidly leads to iron overload4, this choice is often made because it is technically simple and maximizes the number of patients in transfusion care. Indeed, even if erythrapheresis has been reported to be the most efficient method for the chronic transfusion of SCA patients, it cannot be implemented everywhere; it is not suitable for all patients, especially young children; and it necessitates specific and expensive equipment.
For more than 20 years now, we have been treating SCA children demonstrating cerebral vasculopathy and who were temporarily ineligible for erythrapheresis with a continuous manual exchange transfusion (MET) method. In 2016, our team published a follow-up of patients that had undergone continuous manual transfusion for several years, showing that our method is associated with a satisfactory HbS decrease, efficient stroke prevention, and a limitation of iron overload comparable to that of erythrapheresis6. A session of MET can be carried out in any hospital environment without specific apparatuses and by using the same volume needed for erythrapheresis. A notable advantage of this technique is that it could help prevent, or at least diminish, side effects (particularly iron overload) linked to repeated transfusions in patients who are not able to undergo erythrapheresis. The aim of this article is to describe, step by step, how to perform a session of continuous MET in order to allow the medical centers that do not have any apheresis machines, or that have patients who are not eligible for erythrapheresis, to use this method for their SCD patients, especially children.

<table border="0" cellpadding="0" cellspacing="0" width="569">
	<tbody>
		<tr height="20">
			<td height="20" style="height:20px;width:195px;">Precision scale</td>
			<td style="width:100px;"></td>
			<td style="width:117px;"></td>
			<td style="width:159px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Cannula (x2)</td>
			<td>Macopharma</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Transfusion tubing (x2)</td>
			<td>Macopharma</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Bleeding bag (x4)</td>
			<td>Macopharma</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">3 Way tap</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Syringe (x4)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="23">
			<td height="23" style="height:23px;">Hemoglobin test</td>
			<td>HemoCue</td>
			<td style="width:117px;">Hb 201+&#160;System</td>
			<td></td>
		</tr>
	</tbody>
</table>

continuous manual exchange transfusion for patients with sickle cell disease: an efficient method to avoid iron overload

Children with sickle cell anemia (SCA) may be at risk of cerebral vasculopathy and strokes, which can be prevented by chronic transfusion programs. Repeated transfusions of packed red blood cells (PRBCs) is currently the simplest and most used technique for chronic transfusion programs. However, iron overload is one of the major side effects of this therapy. More developed methods exist, notably the apheresis of RBC (erythrapheresis), which is currently the safest and most efficient method. However, it is costly, complicated, and cannot be implemented everywhere, nor is it suitable for all patients. Manual exchange transfusions combine one or more manual phlebotomies with a PRBC transfusion.
At the Reference Center of Sickle Cell Disease, we set up a continuous method of manual exchange transfusion that is feasible for all hospital settings, demands no specific equipment, and is widely applicable. In terms of HbS decrease, stroke prevention, and iron overload prevention, this method showed comparable efficiency to erythrapheresis. In cases where erythrapheresis is not available, this method can be a good alternative for patients and care centers.

Here, we will compare the safety, cost, and efficiency of the MET method with erythrapheresis6, which is the most effective method to decrease the percentage of HbS in SCD patients. To do so, we recorded 1,353 transfusion exchange sessions in the Reference Center of SCD, including 333 sessions of AET and 1,020 sessions of MET, all in SCD children suffering from cerebral vasculopathy and/or strokes. For patients, we chose MET in children with a body weight under 25 ...

Watch this Scientific Journal Video about Continuous Manual Exchange Transfusion for Patients with Sickle Cell Disease: An Efficient Method to Avoid Iron Overload at JoVE.com

Continuous Manual Exchange Transfusion for Patients with Sickle Cell Disease: An Efficient Method to Avoid Iron Overload

We have outlined a method of continuous manual exchange transfusion for the treatment of sickle cell disease in patients. This safe protocol was designed to effectively limit iron overload in patients in need of chronic transfusions and can be used extensively without any special equipment.

Children with sickle cell anemia (SCA) may be at risk of cerebral vasculopathy and strokes, which can be prevented by chronic transfusion programs. ...

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