DRB, IS, and JP were supported by a grant from Grifols.
Acute hemolysis after intravenous immunoglobulin amid host factors of ABO-mismatched bone marrow transplantation, inflammation, and activated mononuclear phagocytes
Article first published online: 5 JUL 2013
© 2013 American Association of Blood Banks
Volume 54, Issue 3, pages 681–690, March 2014
How to Cite
Michelis, F. V., Branch, D. R., Scovell, I., Bloch, E., Pendergrast, J., Lipton, J. H. and Cserti-Gazdewich, C. M. (2014), Acute hemolysis after intravenous immunoglobulin amid host factors of ABO-mismatched bone marrow transplantation, inflammation, and activated mononuclear phagocytes. Transfusion, 54: 681–690. doi: 10.1111/trf.12329
This work was presented in part at the 2012 American Association of Blood Bank (AABB) Annual Conference in Boston, MA, USA (Red Blood Cells—Alloimmunization Risk Factors, Rates, and Hemolytic Reactions, #SP219, Abstract Control # 1401283), Transfusion 2012;52S:136A.
- Issue published online: 11 MAR 2014
- Article first published online: 5 JUL 2013
- Manuscript Accepted: 22 MAY 2013
- Manuscript Revised: 3 MAY 2013
- Manuscript Received: 20 MAR 2013
Hemolysis may follow intravenous immunoglobulin (IVIG), with product, dosing, and host factors contributing. The importance of recipient features remains unclear.
A 52-year-old obese woman, 10 years after ABO-mismatched (recipient O, donor A) marrow transplantation, presented with immune thrombocytopenia (ITP). IVIG at 100 g/day × 2 days was followed by hemoglobinuria and angina and dyspnea, with frank hemoglobinemia and anemia (hemoglobin 12.9 to 8.4 over 24 hr, to a nadir of 6.9 g/dL).
Study Design and Methods
Serologic methods established ABO, A1, Lewis, and Secretor type, while monocyte monolayer assay (MMA) examined erythrophagocytosis with control or patient monocytes, and the implicated IVIG lot to opsonize control (group A1, A2, B, O) or patient red blood cells (RBCs). Baseline, hemolytic, and convalescent markers (including cytokines) were assessed.
Passive anti-A was identified on reverse type and eluted from sensitized RBCs (immunoglobulin G 1+, C3d–). Le(a–b+) typing and saliva confirmed H Secretor status. MMA revealed significant activity between patient RBCs, monocytes, and IVIG. However, normal A1 cells opsonized with IVIG were not significantly phagocytosed by either normal or patient monocytes. Proinflammatory markers were significantly elevated before and after IVIG.
Synergizing host factors (including obesity-unadjusted dosing and existing inflammation) marked this severe post-IVIG hemolytic crisis. Group A antigen restriction to myeloid tissues, with H Secretor phenotype, may have contributed, rendering this bone marrow transplant chimera vulnerable to anti-A in a manner analogous to the idiosyncratic effect of therapeutic anti-D in certain D+ ITP recipients. However, MMA suggested a macrophage activation state as contributory, perhaps precipitated by existing inflammation.