In normal blood, hemolytic reactions do not occur in the absence of antigen-antibody reactions, but the hemolytic reactions in patients with PNH are independent of antigen-antibody reactions. In patients with PNH, RBCs are destroyed by an activated complement system due to the deficit of membrane proteins DAF and CD59, which inhibit the formation of the MAC.
Transfusions in patients with PNH used to be performed with saline washed RBCs to reduce the risk of leukocyte sensitization, antibody production against human leukocyte antigens, and reactions which may activate complement system [3]. However, a review on the subject concluded that the use of washed RBCs is not necessary and group-specific fresh blood and blood products should be used instead [2, 4]. For our patient, we prepared 6 units of packed RBCs and an autologous blood salvage device because of the positive irregular antibody screening result. Autologous blood transfusion can avoid risks or side effects associated with blood transfusions. Moreover, the autologous blood salvage device can eliminate over 90% of plasma components [5] presumably including complement factors, which (in theory) would be an added advantage for patients with PNH, although the RBCs themselves are still vulnerable. In the past, over 90% of the K+ in salvaged blood was shown to be removed by the wash process [the washed RBCs were left with 1–2 mmol/L of (K+)] [6], but in our case, the K+ concentration in the transfer bag was > 6 mmol/L. This fact indicates that the salvaged blood of patients with PNH continued to be lysed even after the wash process. Physical stresses, such as infections and surgery, can cause complement activation [7]. In addition, the unwashed salvaged blood contains increased levels of proinflammatory cytokines, such as interleukin-1β, 6, and 8, and activated complement components compared to the circulatory blood [8, 9]. We suspect the hemolysis in our patient was caused by surgical stress or surgical inflammation as the K+ concentration increased gradually during the operation. The attack to the RBCs by the activated complement may have proceeded also in the reservoir of blood salvage device. The level of activated proinflammatory cytokines and activated complement in the salvaged blood is reduced by the wash [8]; however, once the complement in the patients with PNH becomes activated and starts forming MAC on the RBCs during the processes of the operation and blood salvage, the hemolytic reaction may not be stopped even with the washing procedure. That is, the MAC on the membrane of RBCs does not get washed off. Recently, eculizumab, a monoclonal antibody to the complement component 5 (C5), is widely used in PNH therapy. However, not all the patients with PNH are administered eculizumab because of several reasons such as indication, insurance, and patients’ choice. Eculizumab inhibits C5, resulting in the inhibition of MAC formation and the effect of eculizumab is remarkable [1, 10, 11]. Although further reports are needed, if eculizumab had been used in the present case, the results might have been different.
Based on our experience, packed RBCs using a potassium adsorption filter, if available, should be preferred to autologous blood in case of perioperative transfusion in patients with PNH. Kathirvel S et al. has mentioned that in general unwashed RBCs can be used without problems, but for large blood transfusion volumes, the RBCs may need to be washed [12]. Some anesthesiologists may consider the use of washed autologous RBCs under some situations, such as massive hemorrhage or existence of irregular antibodies; however, a pitfall lurks in the autologous RBCs of the patients with PNH. The washed autologous RBCs may transiently guarantee oxygen transport to the tissues, but the salvaged RBCs in patients with PNH will become the target of the complement and will get lysed again after the transfusion.
Conclusively, packed RBCs instead of salvaged autologous RBCs should be used for transfusions in patients with PNH. The use of salvaged autologous RBCs in patients with PNH should be limited to critical situations such as massive bleeding and physicians should keep in mind that the hemolytic reaction may be present inside the transfer bag even after the wash process.