Piperacillin-tazobactam induced immune hemolytic anemia led to increased renal impairment and eventual death from multiple organ failure in a patient with hypertensive nephropathy: case report and literature review

Abstract

Background Piperacillin is one of the most common drugs that cause drug-induced immune hemolytic anemia, but a complete description of the serological features and course of the disease is rare. This study completely describes the serological characteristics and course of a patient with hypertensive nephropathy who developed drug-induced immune hemolytic anemia and worsened renal function during repeated administration of piperacillin-tazobactam. Case presentation A 79-year-old male patient with hypertensive nephropathy who developed severe hemolytic anemia and worsened renal function during intravenous piperacillin-tazobactam anti-infective treatment due to lung infection. Serological tests showed that the result of the direct antiglobulin test for anti-IgG was positive (4 +) and anti-C3d was negative, and the irregular red blood cell antibody screening test was negative. Plasma samples collected at different times from 2 days before to 12 days after the discontinuation of piperacillin-tazobactam administration were incubated with piperacillin solution and red blood cells of O-type healthy blood donors at 37 °C, IgG piperacillin-dependent antibodies were detected, and the highest titer was 128. However, no tazobactam-dependent antibody was detected in any plasma samples. Therefore, the patient was diagnosed with piperacillin-induced immune hemolytic anemia. Although blood transfusion and continuous renal replacement therapy were given, the patient died of multiple organ failure 15 days after the administration of piperacillin-tazobactam was stopped. Conclusion This is the first complete description of the disease course and serological changes of piperacillin-induced immune hemolytic anemia, which is bound to help deepen the understanding of drug-induced immune hemolytic anemia and draw profound lessons from it.

The Role of the Spleen and the Place of Splenectomy in Autoimmune Hemolytic Anemia—A Review of Current Knowledge

“…In drug-independent DIHA, IgG warm autoAbs can be detected in the absence of drugs [ 1 ]. Several drugs can modify the RBC membrane so that Ig (IgM or IgG), complement, albumin, and other plasma proteins adsorb nonimmunologically (non-immunologic protein adsorption(NIPA)), leading to a positive DAT result accompanied by slow and slight hemolysis [ 33 ].…”

Case report: Decreased hemoglobin and multiple organ failure caused by ceftizoxime-induced immune hemolytic anemia in a Chinese patient with malignant rectal cancer

“…These are antibodies that target red blood cells (RBCs) in the presence of the implemented drug. There are two subtypes of drug-dependent mechanisms ( 3 ); (a) antibodies that react to drug-coated RBCs (i.e., penicillin-type DIIHA) ( 4 ) and (b) antibodies that form immune complexes in the presence of soluble drugs and subsequently bind to and damage RBCs, such as those seen with quinine or ceftriaxone ( 5 ). The second mechanism is through drug-independent autoantibodies.…”

“…Historically, drugs like methyldopa and penicillin were frequently reported to induce DIIHA from the 1970s through the 1990s ( 6 , 9 ). More recent literature has also identified cases linked to antibodies reacting to erythrocytes induced by newer drugs such as piperacillin, ceftibuten, and ceftriaxone ( 4 – 6 ). To date, around 140 different drugs have been identified as potential DIIHA triggers ( 3 ).…”

“…Detection methods for DIIHA vary based on the antibody type. For drug-dependent cases, such as those related to penicillin, aggregation tests using patient serum, the drug, and RBCs are effective (4,9). Conversely, drug-independent autoantibodies, exemplified by those associated with methyldopa, react with untreated RBCs without the drug's presence (6), making them challenging to differentiate from warm-type autoantibodies.…”