Immune Hemolysis and Aseptic Meningitis after Intravenous Immunoglobulin

INTRODUCTION

Human intravenous immunoglobulin (IVIG) products are generally considered safe and are used for the treatment of a variety of autoimmune and pro-inflammatory states. However, controlled trials involving IVIG have been of small size with limited power and described only the most common adverse effects [1]. IVIG related hemolysis is a rare adverse effect and is usually self-limited, rarely requiring blood transfusions. A few case reports have also described aseptic meningitis after IVIG use. We describe a patient who developed severe hemolytic anemia and aseptic meningitis after IVIG use.

CASE PRESENTATION

A 54 year old woman was admitted with severe head ache, dark colored urine and shortness of breath twenty four hours after receiving IVIG. She was diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) a month ago and was started on IVIG. Physical exam was unremarkable. Laboratory tests showed severe anemia with a hemoglobin of 6.1 g/dl (baseline 13 g/dl), indirect hyper-bilirubinemia, low haptoglobin, elevated LDH and hemoglobinuria confirming hemolysis. Hematological testing revealed a positive direct antiglobulin test (DAT), DAT IgG, DAT CD3 and eluate testing were also positive. A lumbar puncture showed neutrophil pleocytosis but no bacteria. A diagnosis of IVIG induced hemolysis and aseptic meningitis was made. O negative packed red blood cells were transfused for severe symptomatic anemia and non-steroidal anti-inflammatory drugs were given for headache. Steroids were deferred since the source of antibodies causing hemolysis was extrinsic. She improved clinically and blood counts returned to baseline in three weeks.

DISCUSSION

Pooled IVIG is extracted from at least 1000 individuals and contains highly purified polyvalent IgG [2]. Hemolysis after IVIG is thought to be secondary to donor antibodies against host red blood cell antigens and resolves once IVIG is stopped. Risk factors for hemolysis include non-O blood types and the use of high dose IVIG. The patient described was of AB Rh positive blood type but did not receive high dose IVIG. Aseptic meningitis is another rare adverse effect that has been postulated to be related to antibodies in the IVIG that mimic antineutophil cytoplasmic antibodies (ANCA) which activate neutrophils causing neutrophilic pleocytosis [3]. One must be aware of these two rare complications of a commonly used drug.

REFERENCES

[1] Risks associated with the use of intravenous immunoglobulin. Pierce LR et al. Transfus Med Rev. 2003 Oct;17(4):241-51.

[2] Appropriate uses of human immunoglobulin in clinical practice: memorandum from an IUIS/WHO meeting. Bull World Health Organ. 1982;60(1):43.

[3] Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNF alpha-dependent and Fc-receptor-independent way. Jarius et al. Blood. 2007;109(10):4376.