Case Report: First Case of Cefotaxime-Sulbactam-Induced Acute Intravascular Hemolysis in a Newborn With ABO Blood Type Incompatibility by the Mechanism of Non-Immunologic Protein Adsorption

Abstract

Background: ABO blood type incompatibility hemolytic disease of newborn (ABO-HDN) and drug-induced immune hemolytic anemia (DIIHA) due to non-immunologic protein adsorption (NIPA) mainly cause extravascular hemolysis. All the reported severe DIIHA were caused by drug-induced antibodies, and rare report of acute intravascular hemolysis was caused by the NIPA mechanism or ABO-HDN.

Case presentation: We report the first case of acute intravascular hemolysis induced by cefotaxime sodium - sulbactam sodium (CTX - SBT) in a case of ABO-HDN which resulted in death at 55 h after birth. The mother's blood type was O and RhD-positive, and the newborn's blood type was B and RhD-positive. No irregular red blood cell (RBC) antibodies or drug-dependent antibodies related to CTX or SBT was detected in the mother's plasma and the plasma or the RBC acid eluent of the newborn. Before the newborn received CTX - SBT treatment, the result of direct antiglobulin test (DAT) was negative while anti-B was positive (2 +) in both plasma and acid eluent. After the newborn received CTX - SBT treatment, the results of DAT for anti-IgG and anti-C3d were both positive, while anti-B was not detected in plasma, but stronger anti-B (3 +) was detected in acid eluent. In vitro experiments confirmed that NIPA of SBT promoted the specific binding of maternal-derived IgG anti-B to B antigen on RBCs of the newborn, thereby inducing acute intravascular hemolysis.

Conclusion: The NIPA effect of SBT promoted the specific binding of mother-derived IgG anti-B in newborn's plasma to the newborn's RBC B antigens and formed an immune complex, and then activated complement, which led to acute intravascular hemolysis. Drugs such as SBT with NIPA effect should not be used for newborns with HDN.

Keywords: acute intravascular hemolysis; cefotaxime; drug-induced immune hemolytic anemia (DIIHA); hemolytic disease of newborn (HDN); non-immunologic protein adsorption (NIPA); sulbactam.

Figure 1

Timeline of the newborn disease process. ABO-HDN, ABO blood type incompatibility hemolytic disease of newborn; DAT, direct antiglobulin test; CTX-SBT, cefotaxime sodium - sulbactam sodium combination.

Figure 2

The mechanism of SBT’s NIPA induced acute intravascular hemolysis in the newborn with ABO-HDN. Before the newborn received CTX-SBT treatment, RBCs coated with less IgG anti-B were engulfed by macrophages to produce bilirubin (A). Since IgG anti-B were present in both plasma and RBCs (B), the anti-globulin method was used to detect IgG anti-B in plasma (C) and RBC acid eluent (D), the results were both positive (2+). Because the affinity between the newborn’s B antigen and IgG anti-B was low, and IgG anti-B bound to RBCs were less, it was not enough to activate complement, so the results of DAT for anti-IgG and anti-C3d were negative. After the newborn received CTX-SBT treatment, the NIPA of SBT promoted the combination of maternal IgG anti-B and the newborn’s RBC B antigen to form an immune complex, which activated complement, led to the RBCs coated with a large amount of IgG anti-B to dissolve in the blood vessel and produced hemoglobin (E). Since the NIPA promoted almost all maternal IgG anti-B in plasma to bind to the newborn’s RBCs (F), IgG anti-B cannot be detected in plasma (G), while stronger IgG anti-B were detected in acid eluent (H). Since enough IgG anti-B and C3d were bound to the newborn’s RBCs, the results of DAT for anti-IgG (3+) and anti-C3d (2+) were positive. FcγRn, Fc gamma receptor; SBT, sulbactam; CTX-SBT, cefotaxime sodium - sulbactam sodium combination; RBC, red blood cell; RBCs, red blood cells; NIPA, non-immunologic protein adsorption; DAT, direct antiglobulin test; ABO-HDN, ABO blood type incompatibility hemolytic disease of newborn.