NIV Congres

Introduction: DIIHA is a rare, severe complication of a variety of different drugs, notably antibiotics, NSAIDs and chemotherapeutical agents. Three different pathophysiological mechanisms are recognized: drughapten, immune complex and autoantibody induction.[1] We report a case of acute DIIHA with an unusually severe clinical presentation caused by combined drughapten and immune complex mediated destruction of red blood cells.

Case report: 28-year old female patient with history of cystic fibrosis was admitted to hospital for recurrent pneumonia. Antibiotic treatment included piperacillin/tazobactam infusions. On day 7 clinical condition quickly deteriorated. She collapsed after loosing dark coloured stool and urine, became hypotensive and short-lasting cardiopulmonary resuscitation was performed. Severe anemia with Hb drop from 14 g/dl (8,4 mmol/L) on admission to 4 g/dl (2,4 mmol/l) was discovered. Acute gastro-intestinal blood loss from the upper tract was suspected. Intubation followed, an emergency gastroscopy was performed at the OR, which was without any signs of bleeding or recent blood loss. Meanwhile, immediate blood transfusion of uncrossmatched RBC units was ordered. From the transfusion laboratory came the observation of strong hemolytic serum, changing the probable diagnosis of acute blood loss to acute hemolysis as cause of the severe sudden anemia. Patient was transported to ICU, intubated and mechanically ventilated with inotropic support. Five ABO-Rhesus phenotype identical RBC concentrates were infused before immunohaematological work-up was finalized. Laboratory analysis showed LD 1098 U/L, total bilirubin 244 μmol/L, undetectable haptoglobin and free hemoglobinemia 135 μmol/L, indicating intravascular hemolysis. Direct antiglobulin test appeared positive with anti-IgM, anti-IgG and anti-complement. Transient autoantibodies were present in serum. However, no autoantibodies were detectable after acid elution of RBCs (negative eluate).

Results: A diagnosis of drug-induced immune hemolytic anemia (DIIHA) was made. In this unstable patient with overt signs of intravascular hemolysis, by warm IgM complement activating antibodies, the decision was taken to perform plasmapheresis with FFP as substitution fluid combined with prednisone 1 mg/kg. The procedure was repeated the day after and went without further complications, followed by full clinical recovery.

Additional immunohaematological work-up by Sanquin Diagnostics Amsterdam proved presence of piperacillin/tazobactam reactive antibodies; crossreactivity with cefalosporins, ciprofloxacin and meronem were excluded.

Conclusion: Piperacilin/tazobactam induced immune hemolytic anemia (PIIHA) caused a life-threatening intravascular hemolysis. In the literature a striking, yet unexplained, observation of PIIHA in cystic fibrosis patients is found.[2] Although selflimiting in nature, in severe DIIHA immediate plasmapheresis aiming at removal of the antibiotic agent and toxic agents such as free Hb and bilirubin appeared beneficial.