β-Lactam antibiotics promoting aging and clearance of RBCs would deteriorate the DIIHA / 中国输血杂志

【Objective】 To analyze the influence of β-lactam antibiotics on RBC aging and clearance by detecting various indicators of aging and clearance on RBCs, as well as the differences in phagocytosis for erythrocytes before and after drugs treated in vitro. 【Methods】 RBCs were treated by β-lactam antibiotics, including Penicillin, Cefepime, Cefoperazone and Ceftazidime, and the changing of phosphatidylserine (PS) and clearance related CD markers, including CD35, CD47, CD55 and CD59 on the surface of the RBCs, were detected by flow cytometry at 0h and 24h after drugs treatment. The proportion of acanthocytes by microscope also at 0h and 24h after drugs treatment was calculated. The phagocytosis of drug-treated RBC was detected by monocyte monolayer assay (MMA). Untreated RBCs were incubated in PBS by the same condition as a negative control.The influence of β-lactam antibiotics on RBC aging and clearance by all the results above was studied. 【Results】 Compare to the untreated RBCs, the drug treated RBCs showed a higher PS level on the cell surface. The results showed by percentage as following(0 h vs 24 h): Penicillin 9.42% vs 93.30%, Cefepime 3.88% vs 57.27%, Cefoperazone 4.71% vs 75.75% and Ceftazidime 3.05% vs 43.19%. The acanthocytes ratio was as following(0 h vs 24 h): Penicillin 7.33% vs 86%, Cefepime 2.67% vs 52.67%, Cefoperazone 3.33% vs 67.67% and Ceftazidime 3.33% vs 90.67%. On the opposite, the clearance related CD markers, showed an obviously lower level after drugs treated(0 h vs 24 h): CD35: Penicillin 7.36% vs 11.87%, Cefepime 0.14% vs 28.51%, Cefoperazone 11.85% vs 21.55% and Ceftazidime 7.63% vs 8.73%; CD47: Penicillin 1.22% vs 9.13%, Cefepime 1.80% vs 0.86%, Cefoperazone 0.08% vs 6.85% and Ceftazidime 1.54% vs 5.50%; CD55: Penicillin 14.46% vs 44.31%, Cefepime 17.27% vs 38.41%, Cefoperazone 19.28% vs 33.28% and Ceftazidime 14.62% vs 34.13%; CD59: Penicillin 4.71% vs 20.56%, Cefepime 4.03% vs 7.60%, Cefoperazone 5.91% vs 22.38% and Ceftazidime 5.93% vs 30.89%. Drug-treated RBCs attached more to monocytes than untreated RBCs. 【Conclusion】 The β-lactam antibiotics could induce the changing of PS and the clearance of related CD markers on surface of RBCs. They also could lead acanthocytes and make the RBCs more susceptible to phagocytosis by monocytes. The β-lactam antibiotics could promote the RBCs aging and clearance, which might deteriorate the DIIHA.

Ceftriaxone Induced Immune Hemolytic Anemia: Detection of Drug-dependent Antibody by Ex-vivo Antigen in Urine

There have been a few reported cases of immune hemolytic anemia induced by ceftriaxone. We encountered a patient with immune hemolytic anemia that seemed to be stimulated by a degradation product of ceftriaxone. The patient's direct antiglobulin test was positive only for C3d, and no ceftriaxone-dependent antibodies were detectable in the patient's serum. To demonstrate the presence of the ceftriaxone-induced antibodies, an ex-vivo antigen in urine was obtained from the patient. In addition, we prepared a 1 mg/mL suspension solution of ceftriaxone, and group AB serum as a complement source. Using several combinations of the above reactants, the indirect antiglobulin test was performed. Only the indirect antiglobulin test using the patient's serum with the ex-vivo urine antigen was found to be positive. Other combinations were not reactive. To our knowledge, this is the first reported case in Korea, in which the causative antibody appeared to be stimulated solely by a degradation product of ceftriaxone.

Ceftriaxone Induced Immune Hemolytic Anemia: Detection of Drug-dependent Antibody by Ex-vivo Antigen in Urine

There have been a few reported cases of immune hemolytic anemia induced by ceftriaxone. We encountered a patient with immune hemolytic anemia that seemed to be stimulated by a degradation product of ceftriaxone. The patient's direct antiglobulin test was positive only for C3d, and no ceftriaxone-dependent antibodies were detectable in the patient's serum. To demonstrate the presence of the ceftriaxone-induced antibodies, an ex-vivo antigen in urine was obtained from the patient. In addition, we prepared a 1 mg/mL suspension solution of ceftriaxone, and group AB serum as a complement source. Using several combinations of the above reactants, the indirect antiglobulin test was performed. Only the indirect antiglobulin test using the patient's serum with the ex-vivo urine antigen was found to be positive. Other combinations were not reactive. To our knowledge, this is the first reported case in Korea, in which the causative antibody appeared to be stimulated solely by a degradation product of ceftriaxone.

A Case of Rifampin-Induced Thrombocytopenia Associated with Specific Antibodies for Platelet Glycoprotein Ib/IX and IIb/IIIa / 대한혈액학회지

Rifampin is sometimes associated with hematologic complications such as hemolytic anemia or thrombocytopenia. Patients with drug-induced thrombocytopenia develop a drug- dependent antibody that binds to platelets in the presence of the drug causing platelet clearance. It has been previously proposed that the antibody binds the drug, resulting in an immune complex that is then adsorbed onto platelets. However, it has been recently known that drug-dependent antibodies bind to one or more of the platelet membrane glycoprotein Ib, IIb, IIIa, and IX. We, hereby, report a case of rifampin-induced thrombocytopenia in which drug-dependent antibody specific for platelet glycoprotein Ib/IX and IIb/IIIa was demonstrated by modified antigen capture ELISA method. The case was a 37 year-old female who had had pulmonary tuberculosis and taken antituberculous regimen including rifampin. Intermittent epistaxis appeared 10 days after treatment with rifampin. She was admitted to hospital due to gingival bleeding for 3 days and menorrhagia for 2 days. On admission, her platelet count was dropped to 7,000/microliter.