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Review
. 2015 Jul;13(3):363-9.
doi: 10.2450/2015.0249-14. Epub 2015 Feb 2.

Complement-mediated haemolysis and the role of blood transfusion in paroxysmal nocturnal haemoglobinuria

Tolulase Olutogun  1   2 , Ilaria Cutini  3 , Rosario Notaro  1 , Lucio Luzzatto  4
Affiliations
Review

Complement-mediated haemolysis and the role of blood transfusion in paroxysmal nocturnal haemoglobinuria

Tolulase Olutogun et al. Blood Transfus. 2015 Jul.
No abstract available

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Figures

Figure 1
Figure 1
Blood transfusion in the management of PNH: illustrative cases. (A) This 35-year old male businessman with long-standing haemolytic PNH is subjectively well, is leading an active life, and has not yet needed a single blood transfusion. His intravascular haemolysis of considerable degree (see LDH levels) produces continued iron loss through the urine, necessitating periodic treatment with oral iron, without which his anaemia would be much more severe (whereby the patient would need blood transfusion eventually). (B) This 48-year female office worker had a very high degree of intravascular haemolysis (see LDH levels) and was transfusion-dependent (average 2 units/month). On eculizumab her LDH dropped dramatically, the percentage of her GPI(−) red cells increased and, most importantly, she no longer needs blood transfusion. (C) This 42-year old housewife has moderate to severe anaemia from a combination of haemolysis and probably inadequate bone marrow response (see reticulocytes). She was transfusion-dependent, requiring an average of 2–3 units/month. Unfortunately on eculizumab she remains transfusion-dependent, although she requires fewer units of red cells. The continued administration of eculizumab is justified by this, as well as by the full relief of subjective symptoms which, before she was on eculizumab, included frequent abdominal pain and dysphagia. Note that the increase in GPI(−) red cells appears spuriously poor, because these cells are diluted by the GPI(+) transfused red cells. PNH: paroxysmal nocturnal haemoglobinuria; Hb: haemoglobin (g/dL); LDH: lactate dehydrogenase (×UNL: upper normal levels); Retics: reticulocytes (×105/μL). ↓ 2 units of packed red blood cells; GPI: glycosyl phosphatidyl inositol; GPI-RBC: GPI-negative red blood cells (%); ■: iron therapy.
Figure 2
Figure 2
The role of complement in intravascular and extravascular haemolysis in PNH. (Modified from Luzzatto L, Risitano AM, Notaro R. Paroxysmal nocturnal hemoglobinuria and eculizumab. Haematologica 2010; 95: 523–6). (A) Normal red cells are protected from complement activation and subsequent haemolysis by CD55 and CD59. PNH red cells, lacking CD55 and CD59, suffer from complement and will be lysed sooner or later by activated complement through formation of the MAC with consequent intravascular haemolysis. (B) PNH red cells, in the presence of eculizumab, are protected from intravascular haemolysis because the inhibition of C5 prevents the formation of the MAC, but once opsonised by C3 they will become prey to macrophage with consequent extravascular haemolysis. PNH: paroxysmal nocturnal haemoglobinuria; MAC: membrane attack complex; RES: reticuloendothelial system.
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References

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    1. Rosse WF, Dacie JV. Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. I. The sensitivity of PNH red cells to lysis by complement and specific antibody. J Clin Invest. 1966;45:736–48. - PMC - PubMed

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