scholarly journals 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

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanjun Wu ◽  
Yong Wu ◽  
Yong Yang ◽  
Baochan Chen ◽  
Jianqun Li ◽  
...  
Keyword(s):  
Protein Adsorption ◽  
Specific Binding ◽  
Blood Type ◽  
Intravascular Hemolysis ◽  
Drug Induced ◽  
First Case ◽  
Immune Hemolytic Anemia ◽  
Abo Blood Type ◽  
Drug Dependent

BackgroundABO 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 presentationWe 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.ConclusionThe 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.

scholarly journals On the mechanisms of sensitization and attachment of antibodies to RBC in drug-induced immune hemolytic anemia

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1006-1010 ◽  
Author(s):  
A Salama ◽  
C Mueller-Eckhardt
Keyword(s):  
Specific Binding ◽  
Drug Induced ◽  
Cell Complexes ◽  
Large Panels ◽  
Plot Analysis ◽  
Number Of Patients ◽  
Immune Hemolytic Anemia ◽  
Drug Dependent ◽  
Reaction Patterns

Abstract The mechanisms of sensitization and attachment of drug-dependent antibodies to RBC in drug-induced immune hemolytic anemias are largely speculative. Nomifensine has been incriminated in causing immune hemolysis in a large number of patients. The hemolysis was usually of the so-called immune complex type, less commonly of the autoimmune type, and more surprisingly, few patients had developed both types of hemolysis. To determine whether nomifensine (metabolite)-dependent antibodies (ndab) exhibit specificity for antigenic structures of RBC membranes, 30 ndab were tested against large panels of RBC with common and rare antigens. We found that only 14 out of 30 ndab were invariably reactive with all cells tested. Nine antibodies were, similar to the majority of idiopathic or drug-induced autoantibodies, not or only weakly reactive with Rhnull RBC. Three antibodies did not react with cord RBC and could be inhibited by soluble I antigen. The remaining four antibodies gave inhomogeneous reaction patterns or were even negative with selected RBC; their specificity could not be identified. On a Scatchard plot analysis of one ndab, a maximum of 173,000 drug- dependent antibodies of the IgG class can specifically bind per RBC in the presence of the drug. Although nomifensine and its metabolites do not attach tightly onto RBC, our results clearly indicate that RBC do not act as “innocent bystanders,” but rather serve as a surface for a loose attachment of drugs that possibly cause a subtle structural change in the cell antigens and, by this means, allow in vivo sensitization; and a specific binding of the resultant antibodies. This concept would explain why these antibodies can be directed against drug- cell complexes, against cell antigens alone (autoantibodies), or against both in the same patient.

scholarly journals Drug-induced immune hemolytic anemia

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 73-79 ◽  
Author(s):  
George Garratty
Keyword(s):  
Membrane Proteins ◽  
Hemolytic Anemia ◽  
Drug Induced ◽  
Serological Tests ◽  
Laboratory Findings ◽  
Rbc Membrane ◽  
Immune Hemolytic Anemia ◽  
Drug Dependent

Abstract Drug-induced immune hemolytic anemia (DIIHA) is rare, and a specialized laboratory is often required to provide the optimal serological tests to confirm the diagnosis. The most common drugs associated with DIIHA and the hypotheses for the mechanisms thought to be involved have changed during the last few decades. The drugs most frequently associated with DIIHA at this time are cefotetan, ceftriaxone, and piperacillin. DIIHA is attributed most commonly to drug-dependent antibodies that can only be detected in the presence of drug (eg, cephalosporin antibodies). DIIHA can also be associated with drug-independent antibodies; such antibodies do not need drug to be present to obtain in vitro reactions (eg, fludarabine). In these latter cases, the drug affects the immune system, causing production of red cell (RBC) autoantibodies; the clinical and laboratory findings are identical to autoimmune hemolytic anemia (AIHA), other than the remission associated with discontinuing the drug. Some of the mechanisms involved in DIIHA are controversial. The most acceptable one involves drugs, like penicillin, that covalently bind to proteins (eg, RBC membrane proteins); RBCs become coated with drug in vivo and, a drug antibody (usually IgG) attaches to the drug-coated RBCs that are subsequently cleared by macrophages. The most controversial is the so-called immune complex mechanism, which has been revised to suggest that most drugs are capable of binding to RBC membrane proteins, but not covalently like penicillins. The combined membrane plus drug can create an immunogen; the antibodies formed can be IgM or IgG and often activate complement, leading to acute intravascular lysis and sometimes renal failure; fatalities are more common in this group. It is still unknown why and how some drugs induce RBC autoantibodies, sometimes causing AIHA.

scholarly journals On the mechanisms of sensitization and attachment of antibodies to RBC in drug-induced immune hemolytic anemia

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1006-1010 ◽  
Author(s):  
A Salama ◽  
C Mueller-Eckhardt
Keyword(s):  
Specific Binding ◽  
Drug Induced ◽  
Cell Complexes ◽  
Large Panels ◽  
Plot Analysis ◽  
Number Of Patients ◽  
Immune Hemolytic Anemia ◽  
Drug Dependent ◽  
Reaction Patterns

The mechanisms of sensitization and attachment of drug-dependent antibodies to RBC in drug-induced immune hemolytic anemias are largely speculative. Nomifensine has been incriminated in causing immune hemolysis in a large number of patients. The hemolysis was usually of the so-called immune complex type, less commonly of the autoimmune type, and more surprisingly, few patients had developed both types of hemolysis. To determine whether nomifensine (metabolite)-dependent antibodies (ndab) exhibit specificity for antigenic structures of RBC membranes, 30 ndab were tested against large panels of RBC with common and rare antigens. We found that only 14 out of 30 ndab were invariably reactive with all cells tested. Nine antibodies were, similar to the majority of idiopathic or drug-induced autoantibodies, not or only weakly reactive with Rhnull RBC. Three antibodies did not react with cord RBC and could be inhibited by soluble I antigen. The remaining four antibodies gave inhomogeneous reaction patterns or were even negative with selected RBC; their specificity could not be identified. On a Scatchard plot analysis of one ndab, a maximum of 173,000 drug- dependent antibodies of the IgG class can specifically bind per RBC in the presence of the drug. Although nomifensine and its metabolites do not attach tightly onto RBC, our results clearly indicate that RBC do not act as “innocent bystanders,” but rather serve as a surface for a loose attachment of drugs that possibly cause a subtle structural change in the cell antigens and, by this means, allow in vivo sensitization; and a specific binding of the resultant antibodies. This concept would explain why these antibodies can be directed against drug- cell complexes, against cell antigens alone (autoantibodies), or against both in the same patient.

scholarly journals Drug-induced agranulocytosis: in vitro evidence for immune suppression of granulopoiesis and a cross-reacting lymphocyte antibody

Blood ◽  
1979 ◽  
Vol 54 (2) ◽  
pp. 501-512 ◽  
Author(s):  
R Taetle ◽  
TA Lane ◽  
J Mendelsohn
Keyword(s):  
Bone Marrow ◽  
Inhibitory Activity ◽  
Polymorphonuclear Leukocytes ◽  
Population Distribution ◽  
Thymidine Uptake ◽  
Allogeneic Bone ◽  
Drug Induced ◽  
Culture Techniques ◽  
Drug Dependent

Two patients with agranulocytosis associated with diphenylhydantoin (DPH) therapy and clinical data suggesting suppression of granulopoiesis were investigated using in vitro culture techniques for committed granulocyte/macrophage precursors. Addition of DPH to cultures containing the patients' sera resulted in significant suppression of colony growth. Extensive studies on the acute serum from one patient revealed the drug-dependent inhibitory activity to be nondialyzable, resistant to chloroform extraction, heat stable, active in the presence of heat-inactivated fetal bovine serum, active against autologous as well as allogeneic cells, and absent from convalescent sera. Drug-dependent bone marrow colony-suppressing activity was removed by absorption on an antiimmunoglobulin-Sepharose column but not by IgG-Sepharose. The serum show non-drug dependent suppression of oxygen consumption by normal polymorphonuclear leukocytes engaged in phagocytosis and also showed evidence of ability to opsonize these cells. When the serum was incubated with mitogen-stimulated lymphocytes, suppression of 3H-thymidine uptake by autologous but not allogeneic cells was noted. Similarly, the serum suppressed short-term 3H-thymidine uptake by autologous but not allogeneic bone marrow. Absorption of the patients' sera with allogeneic polymorphonuclear leukocytes, autologous polymorphonuclear leukocytes, or autologous lymphocytes removed the drug-dependent inhibitory activity, but absorption with allogeneic lymphocytes did not. These data are most consistent with the presence of a noncomplement dependent antibody capable of suppressing granulopoiesis, mediating peripheral destruction of polymorphonuclear leukocytes, and cross-reacting with a lymphocyte antigen of limited population distribution.

scholarly journals Serologic Characterization of Antibodies in Patients Experiencing Piperacillin-Induced Immune Thrombocytopenia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1078-1078
Author(s):  
Mark Rasmussen ◽  
Daniel W. Bougie ◽  
Gregory H. Denomme ◽  
Richard H. Aster
Keyword(s):  
Conflicts Of Interest ◽  
Normal Subjects ◽  
Normal Serum ◽  
Beta Lactam ◽  
Drug Induced ◽  
Beta Lactam Antibiotics ◽  
Immune Hemolytic Anemia ◽  
Drug Dependent ◽  
High Concentrations ◽  
Optimized Conditions

Beta lactam antibiotics (penicillins, cephalosporins, etc) are relatively common triggers for immune hemolytic anemia, neutropenia and drug-induced thrombocytopenia (DITP) but the mechanism(s) responsible for this side effect are not well understood. The ureidopenicillin, piperacillin, is one of the beta lactam drugs implicated most often as a trigger for immune cytopenia. We characterized drug-dependent reactions of antibodies (abs) identified in 18 patients with piperacillin-associated thrombocytopenia. Each of the 18 patients had an ab that reacted strongly (flow cytometry) with normal platelets but not RBC when soluble piperacillin was present. These reactions were not inhibited by the highest drug concentration that could be achieved in the reaction mixture and similar antibodies were not found in normal serum. These reactions are similar to those obtained with drug-dependent antibodies (DDAbs) found in patients sensitive to quinine, vancomycin, and many other drugs known to cause DITP. Evidence suggests that such drugs promote binding of DDAbs to their targets by reacting with antibody CDR3 and modifying its specificity (Blood 2015;126:2138). Beta-lactam drugs differ from most other medications in their ability to spontaneously link covalently to free amino groups on membrane proteins to produce potentially immunogenic haptens that could induce abs theoretically capable of contributing to thrombocytopenia in piperacillin-treated patients. We optimized conditions for "haptenization" of platelets and RBCs with piperacillin and tested patient and normal sera for abs that recognize piperacillin-coated cells. Complete inhibition of binding by excess soluble drug was a criterion for a "positive" reaction. As shown in Table 1, IgG and IgM abs reactive with piperacillin-coated RBCs were found in each of 18 patient and 20 normal sera tested; IgM abs reactive with piperacillin-coated platelets were found in nearly all of both groups and similar IgG abs were found in about half. Reaction strength of IgM abs against piperacillin-coated RBCs correlated closely with that against piperacillin-coated platelets The findings demonstrate two distinctly different types of piperacillin-specific abs in patients experiencing piperacillin-induced thrombocytopenia. The first is usually IgG, binds to platelets but not RBCs only when soluble drug is present, is not inhibited by excess drug, even at high concentrations, correlates with exposure to piperacillin and development of thrombocytopenia and is not found in normal persons. This behavior is similar to that of DDAbs induced by quinine, vancomycin and many other drugs. The second is commonly IgM and less often IgG, binds to piperacillin-coated platelets and RBCs, is inhibited by soluble drug and, as the IgM isoform, is found in nearly all normal subjects. Failure of abs that recognize piperacillin-coated cells to distinguish between platelets and RBCs in any consistent way argues against the possibility that they play a role in the pathogenesis of piperacillin-induced DITP. "Naturally-occurring" IgM abs that recognize piperacillin-coated RBC were previously described by Garratty et al (Transfusion 2008;48:2429) and could reflect widespread environmental exposure to beta-lactam antibiotics. Disclosures No relevant conflicts of interest to declare.

The first case of drug-induced immune hemolytic anemia due to hydrocortisone

Transfusion ◽  
2008 ◽  
Vol 48 (9) ◽  
pp. 1925-1929 ◽  
Author(s):  
Marina Martinengo ◽  
Diego Fabio Ardenghi ◽  
Gino Tripodi ◽  
Giorgio Reali
Keyword(s):  
Hemolytic Anemia ◽  
Drug Induced ◽  
First Case ◽  
Immune Hemolytic Anemia

scholarly journals Drug-Induced Thrombocytopenia following a Transvaginal Oocyte Retrieval for In Vitro Fertilization

2015 ◽  
Vol 2015 ◽  
pp. 1-3
Author(s):  
Ioanna A. Comstock ◽  
Michelle Longmire ◽  
Richard H. Aster ◽  
Amin A. Milki
Keyword(s):  
In Vitro Fertilization ◽  
Immune Thrombocytopenia ◽  
Oocyte Retrieval ◽  
Blood Products ◽  
Drug Induced ◽  
Vitro Fertilization ◽  
Platelet Antibodies ◽  
Drug Dependent ◽  
Transvaginal Oocyte Retrieval

Drug-induced immune thrombocytopenia has been associated with hundreds of medications and can lead to devastating consequences for the patient. We present a case of a healthy 33-year-old female undergoing in vitro fertilization who developed a severe drug-induced thrombocytopenia, petechiae, and a large hemoperitoneum after receiving Cefazolin antibiotic prophylaxis for a transvaginal oocyte retrieval. The patient was admitted to the intensive care unit for resuscitation with blood products. The presence of drug-dependent platelet antibodies to Cefazolin was confirmed serologically.

Quinine-induced thrombocytopenia: drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro

Blood ◽  
2011 ◽  
Vol 117 (22) ◽  
pp. 5975-5986 ◽  
Author(s):  
José Perdomo ◽  
Feng Yan ◽  
Zohra Ahmadi ◽  
Xing-Mai Jiang ◽  
Roland Stocker ◽  
...  
Keyword(s):  
Cell Size ◽  
Production Capacity ◽  
Drug Induced ◽  
Average Cell Size ◽  
Average Cell ◽  
Human Cd34 ◽  
Cd34 Cells ◽  
Life Threatening ◽  
Drug Dependent

Abstract The development of immune cytopenias is a well-recognized side effect of many drugs. Quinine- and quinidine-dependent antibodies are classic examples of drug-induced effects that cause severe, life-threatening thrombocytopenia. Whereas the effects of drug-dependent antibodies on platelets have been well documented, their effects on megakaryocyte (Mk) biology are still unclear. We analyzed sera from several quinine-induced thrombocytopenia (QITP) patients on highly pure Mks (98% glycoprotein IIb-positive [GPIIb+]; 92% GPIX+) derived from human CD34+ cells cultured with human thrombopoietin. We demonstrate by flow cytometry and confocal microscopy that QITP IgGs bind Mks efficiently in the presence of quinine. Incubation of day-4 Mks with QITP sera or purified IgG resulted in induction of apoptosis, a significant decrease in cell viability, and an increase in cell death. Furthermore, QITP sera preferentially reduced the number of late GPIX+/GPIbα+ Mks and the number of receptors per cell in the surviving population. Ploidy distribution, lobularity, and average cell size of Mks remained unchanged after treatment. In addition, treated Mks showed a marked decrease in their proplatelet production capacity, suggesting that drug-dependent antibodies hinder platelet production. Therefore, QITP antibodies considerably reduce the proplatelet production capabilities of Mks despite undetectable effects on DNA content, morphology, and cell size.

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