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Electronic letters published:
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Reply to Dr. Logtenberg's Letter
Blood Products for Spanish Influenza: A future H5N1 treatment?
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Thomas C Luke, MD, MTMH, MA. Department of Population Health, US Navy Bureau of Medicine and Surgery, Stephen L Hoffman, MD, DTMH.
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tcluke{at}us.med.navy.mil Thomas C Luke, et al.
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We agree with Dr. Logtenberg that the possible benefit of convalescent blood products, including plasma, for the treatment of Spanish influenza-pneumonia may not have been entirely due to the presence of neutralizing antibodies. Plasma is a complex mixture of immunoglobulins, coagulation factors, cytokines and other immunologically and physiologically active molecules. It is sometimes used to treat patients with circulatory collapse - presumably because it expands volume while raising oncotic pressure as theorized by Dr. Logtenberg. Furthermore, it is likely that both adaptive and innate immune responses contribute to the control of influenza infections. It is possible that products of the innate immune system in plasma may have contributed to controlling the infection in Dr. Logtenberg's patient and in the patients reported in our paper. However, the therapeutic effect of passively delivered neutralizing antibodies cannot be dismissed. Multiple strains of H3N2 influenza have circulated globally since it first arose in 1968, and many if not most plasma donors have been exposed to multiple wild-type H3N2 strains and seasonal influenza vaccines or both. It is likely that the fresh frozen plasma units transfused into Dr. Logtenberg's patient contained neutralizing H3 antibodies. We believe that Dr. Logtenberg's experience suggests that patients suffering from serious seasonal H1 or H3 influenza infections may benefit from receiving transfusions with plasma with an unknown titer of neutralizing antibodies or preferably with plasma or purified immunoglobulin specifically selected for a high titer of H1 and H3 antibodies. Conflict of Interest:None declared |
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Susan J Logtenberg, MD Department of Internal Medicine, Isala Clinics, The Netherlands, Henk J Bilo, MD, PhD, FRCP
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s.j.j.logtenberg{at}isala.nl Susan J Logtenberg, et al.
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To the Editor: To add to the discussion of Luke and colleagues (1) in their meta- analysis of historic literature concerning the possible beneficial effect of transfusion on the clinical outcome of patients with Spanish influenza, we would like to suggest that this effect might not be due to the specific neutralizing effects of anti-influenza antibodies in the blood product, but to the transfusion of whole blood per se, including immunoglobulins (and – thus – the provision of plasma oncotic pressure). Recently, we reported on a previously healthy man who experienced a severe shock requiring ICU-admission, apparently associated with a virtually complete disappearance of circulating immunoglobulins (2). Immunoglobulin levels were 0.23 g/L (IgA), 0.12 g/L (IgM) and 1.0 g/L (IgG). With supportive treatment, including administration of fresh frozen plasma, the condition of the patient improved rapidly. After some days, immunoglobulin levels had returned to normal. Only influenza A virus (H3N2) could be isolated, suggesting a causal relationship. The acute onset and nearly fatal course resembled that of patients during the Spanish flu pandemic. We were able to retrieve a plasma sample of this patient obtained two weeks before the acute onset of disease. Pre-disease immunoglobulin levels proved to be normal, as opposed to the almost total disappearance of the immunoglobulins in the acute stage of the illness. Therefore, keeping limitations of this single observation in mind, we would like to suggest that the possible beneficial effect that Luke and colleagues claim, might be caused by the administration of protein, including immunoglobulins, that occurs in whole blood transfusion. 1. Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006;145:599-609. 2. Logtenberg SJ, Pasma FH, Wolfhagen MJ, Dikkeschei LD, Bilo HJ. Disappearance of immunoglobulins in acute phase of influenza A infection. Lancet. 2006;368:1546. Conflict of Interest:None declared |
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