ro13-9904 and Anemia--Hemolytic--Autoimmune

Drug-induced immune hemolytic anemia (DIIHA) is a rare cytopenia; about 130 drugs have been incriminated. The antibodies causing DIIHA can be i) drug-independent (drug not needed to be present to detect antibodies in vitro)-DIIHA caused by this type of antibody presents clinically and serologically as an autoimmune hemolytic anemia (AIHA) with red cell (RBC) autoantibodies in patients' sera and in eluates from their RBCs; or (2) drug-dependent (antibodies react in vitro with RBCs only in the presence of drug, on the RBC membrane or when added to the patient's plasma and RBCs).. Literature is reviewed regarding pathophysiology of DIIHA (mechanisms; incidence of drugs involved; the clinical, hematological, and serological characteristics of the most common antibodies causing DIIHA).. DIIHA is often poorly investigated and many reports do not provide data to support the diagnosis (i.e., no serology to support an immune etiology). The three most common drugs currently causing DIIHA are piperacillin, cefotetan, and ceftriaxone. All three (especially piperacillin) can cause in vitro and in vivo effects mimicking AIHA, and in transfused patients, hemolytic transfusion reactions. It is important to exclude DIIHA in such patients as the only treatment needed is to discontinue the drug.

Topics: Anemia, Hemolytic, Autoimmune; Cefotetan; Ceftriaxone; Coombs Test; Humans; Piperacillin

We report the case of an 82-year old male patient admitted in our medical intensive care unit for diffuse skin lesions, 3 days after the onset of ceftriaxone for bilateral pneumonia without microbiological documentation. The patient concomitantly exhibited diffuse skin lesions compatible with livedo and neurological and haemodynamic failure. Biological analysis revealed acute haemolytic anaemia. Warming of patient, red blood-cells transfusion and high-doses corticosteroids were initiated and ceftriaxone was stopped. Despite these therapeutics, the patient exhibited multiple organ failure and died. The main suspected triggering factor of this acute and fatal haemolytic anaemia was ceftriaxone administration considering: (i) the delay between cephalosporin administration and symptoms; (ii) the worsening of livedo and acrocyanosis a few hours after meningeal ceftriaxone doses; and (iii) fatal evolution. Cephalosporin-induced autoimmune haemolytic anaemia is a rare and serious cause of livedo that should be suspected in patients exhibiting livedo and acute haemolytic anaemia within hours/days following cephalosporin administration.

Topics: Aged, 80 and over; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Ceftriaxone; Cephalosporins; Hemolysis; Humans; Male

Acute splenic sequestration crisis is a complication of sickle cell disease (SCD) occurring when intrasplenic red blood cell (RBC) sickling prevents blood from leaving the spleen, causing acute splenic enlargement. Although typically seen in young children, it has been reported in older children with hemoglobin (Hb)SC disease, eventually resulting in functional asplenia. Ceftriaxone is a frequently used antibiotic of choice for children with SCD, because of its efficacy against invasive pneumococcal disease.. We report a case of a 9-year-old female with HbSC disease, who had a fatal reaction after receiving a dose of ceftriaxone in the outpatient clinic for fever. Her Hb level decreased abruptly from 9.3 to 2.3 mg/dL. RBC clumps with no visible hemolysis were observed in the postreaction sample. Autopsy examination revealed marked splenomegaly with acute congestion and sickled cells in the spleen and liver. Serologic testing revealed a positive direct antiglobulin test with polyspecific antibody, anti-C3, and anti-C3d, but negative with anti-immunoglobulin G. Ceftriaxone-dependent RBC antibodies were detected in her serum and RBC eluate when tested in the presence of the drug.. We report a new presentation of ceftriaxone-induced drug reaction in a patient with SCD mimicking an acute splenic sequestration crisis. Review of the literature for cases of ceftriaxone-induced drug reactions in pediatric patients revealed nine previously reported cases of ceftriaxone-induced immune hemolytic anemia in children with SCD since 1995, but none with an initial presentation suggestive of acute splenic sequestration crisis.

Topics: Anemia, Hemolytic, Autoimmune; Autoantibodies; Ceftriaxone; Child; Erythrocytes; Fatal Outcome; Female; Hemoglobin SC Disease; Humans; Liver; Spleen; Splenomegaly

'Chronic Lyme disease' is a controversial condition. As any hard evidence is lacking that unresolved systemic symptoms, following an appropriately diagnosed and treated Lyme disease, are related to a chronic infection with the tick-borne spirochaetes of the Borrelia genus, the term 'chronic Lyme disease' should be avoided and replaced by the term 'post-treatment Lyme disease syndrome.' The improper prescription of prolonged antibiotic treatments for these patients can have an impact on the community antimicrobial resistance and on the consumption of health care resources. Moreover, these treatments can be accompanied by severe complications. In this case report, we describe a life-threatening ceftriaxone-induced immune hemolytic anemia with an acute kidney injury (RIFLE-stadium F) due to a pigment-induced nephropathy in a 76-year-old woman, who was diagnosed with a so-called 'chronic Lyme disease.'

Topics: Aged; Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; Ceftriaxone; Chronic Disease; Female; Humans; Lyme Disease

Ceftriaxone-induced immune hemolytic anemia (CIHA) is the second most common cause of drug-induced hemolytic anemia. Prompt recognition of this drug reaction is essential because brisk hemolysis can be deadly. The extent to which ceftriaxone antibodies persist after CIHA is unknown; rechallenging patients who have experienced CIHA is not recommended. We report a case of CIHA in a neurooncology patient, which is the first to show anticeftriaxone antibodies with Rh specificity and persisted for 8 months after the drug reaction. These findings have implications for understanding the mechanism of CIHA.

Topics: Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; Antibodies; Brain Neoplasms; Ceftriaxone; Child, Preschool; Female; Glioma; Humans

Drug-induced hemolytic anemia is an immune-mediated phenomenon that leads to the destruction of red blood cells. Here, we present a case of life-threatening ceftriaxone-induced hemolytic anemia (CIHA) in a previously healthy 3-year-old girl. We also reviewed the literature to summarize the clinical features and treatment of hemolytic anemia. Acute hemolysis is a rare side effect of ceftriaxone therapy associated with high mortality. Our patient had a sudden loss of consciousness with macroscopic hematuria and her hemoglobin dropped from 10.2 to 2.2 g/dl over 4 hours, indicating that the patient had life-threatening hemolysis after an intravascular dose of ceftriaxone who had previously been treated with ceftriaxone in intramuscular form for six days. CIHA is associated with a positive direct antiglobulin test, revealing the presence of IgG in all cases and C3d in most cases. Our patient's direct antiglobulin test was positive for IgG (3+) and for C3d (4+). The case was managed successfully with supportive measures and intravenous immunoglobulin therapy. Ceftriaxone is used very frequently in children; an early diagnosis and proper treatment of hemolytic anemia are essential to improve the patient outcome. The pathophysiological mechanism is the same as for non-drug autoimmune hemolytic anemia. However, there is still no consensus treatment for CIHA. Intravenous immunoglobulin can be used in clinical emergencies, such as our case, or in refractory cases.

Topics: Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; Ceftriaxone; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Erythrocytes; Female; Humans; Immunoglobulins, Intravenous

To describe a case of ceftriaxone-induced immune hemolytic anemia (CIIHA) in a 6 year-old boy with sickle cell disease (SCD) and perform a systematic literature review to delineate the clinical and laboratory features of this condition.. EMBASE (1947-January 2014), MEDLINE (1946-January 2014), and databases from the US Food and Drug Administration and Health Canada were searched, using anemia, hemolytic anemia, hemolysis, and ceftriaxone as search terms. Additional references were identified from a review of literature citations.. All case reports and observational studies describing clinical and laboratory features of CIIHA were included.. A total of 37 eligible reports of CIIHA were identified, including our index case, and 70% were children. Mortality was 30% in all age groups and 64% in children. The majority of patients had underlying conditions (70%), of which SCD was most commonly reported. Previous ceftriaxone exposure was reported in 65%. Common features included elevated lactate dehydrogenase (70%); early, new-onset hemoglobinuria (59%); acute renal failure (46%); positive direct antibody testing (70%); and anticeftriaxone antibodies (68%). Also, 32% had a preceding, unrecognized, hemolytic episode associated with ceftriaxone.. Given the common use of ceftriaxone worldwide, knowledge of CIIHA, which often goes undiagnosed until late in the course, is essential for clinicians. Based on the findings of this review, we suggest obtaining past history of ceftriaxone exposures and screening for new-onset hemoglobinuria during ceftriaxone therapy in selected patients as potential methods for early diagnosis of this rare but potentially fatal condition.

Topics: Anemia, Hemolytic, Autoimmune; Anemia, Sickle Cell; Anti-Bacterial Agents; Autoantibodies; Ceftriaxone; Child; Humans; Male; Respiratory Tract Infections

Ceftriaxone, a third-generation cephalosporin, is commonly used to prevent and treat infections. Since 1987, it has been the second most common cause of drug-induced immune hemolytic anemia (DIIHA) investigated in our laboratory.. Samples from 79 patients (1987-2010), suspected of having DIIHA caused by ceftriaxone, were studied for the presence of ceftriaxone antibodies. Direct antiglobulin tests (DATs) and tests with ceftriaxone-treated red blood cells (RBCs) or untreated and enzyme-treated RBCs in the presence of ceftriaxone were performed.. Twenty-five (32%) of the 79 patients had antibodies to ceftriaxone detected. Seventeen (68%) of the 25 patients were children; reactions in children were usually dramatic and severe. Nine (36%) of the 25 patients had fatal DIIHA. Nineteen of the 25 samples had DATs performed by our laboratory; 100% of samples were reactive with anti-C3 and 47% were reactive with anti-IgG. All 25 sera had ceftriaxone antibodies detected when testing untreated or ficin-treated RBCs in the presence of ceftriaxone (resulting in agglutination, hemolysis or sensitization of test RBCs). These antibodies were primarily IgM and reactivity was enhanced by testing ficin-treated RBCs. Sixteen (64%) of the 25 sera reacted with test RBCs when no ceftriaxone was added in vitro; this was most likely due to the transient presence of drug or drug-immune complexes in the patient's circulation at the time that the blood samples were drawn.. Ceftriaxone antibodies can cause severe intravascular hemolysis. Complement can usually be detected on the patient's RBCs and IgM antibodies are usually detected in the patient's serum.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; Autoantibodies; Ceftriaxone; Child; Child, Preschool; Complement C3; Cross Reactions; Erythrocytes; Humans; Immunoglobulin G; Infant; Middle Aged; Serologic Tests

To describe the first case of ceftriaxone-related haemolysis in a patient with congenital nephrotic syndrome (CNS).. Severe haemolysis caused by an immune reaction to ceftriaxone has mostly been described in patients with underlying haematological or immune dysfunction.. The authors present a 20-month-old boy with CNS of the Finnish type with several previous severe infections treated with ceftriaxone, admitted for suspected sepsis. Following ceftriaxone administration he developed shock secondary to an acute haemolytic reaction, with severe anaemia. Hypersensitivity to ceftriaxone was documented through positive agglutination tests.. Onset of haemolysis following ceftriaxone administration, particularly in a patient previously exposed to the drug, must raise the suspicion of a possible immune reaction.

Topics: Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; Ceftriaxone; Humans; Infant; Male; Nephrotic Syndrome; Sepsis

Topics: Adverse Drug Reaction Reporting Systems; Aged; Anemia, Hemolytic, Autoimmune; Anti-Infective Agents; Anticoagulants; Benzodiazepines; Caffeine; Canada; Ceftriaxone; Central Nervous System Stimulants; Child; Drug Interactions; Female; Humans; Ketolides; Middle Aged; Olanzapine; Peripheral Nervous System Diseases; Phytotherapy; Pulmonary Embolism; Rhabdomyolysis; Selective Serotonin Reuptake Inhibitors; Warfarin; Weight Loss

An immune complex mechanism for ceftriaxone sodium- induced severe autoimmune hemolytic anemia has previously been demonstrated using routine blood bank techniques. We describe herein a patient with severe hemolysis that subsided once the drug was discontinued. Serologic techniques demonstrated immune complex-mediated ceftriaxone-dependent red cell antibodies. These findings were further supported by the results of flow cytometry, in which a change in basal red cell autofluorescence was seen in the presence of the antibody and the drug. Our case illustrates the adjunctive value of flow cytometry in the diagnosis of ceftriaxone-dependent red cell antibody.

Topics: Anemia, Hemolytic, Autoimmune; Anemia, Sickle Cell; Antigen-Antibody Complex; Blood Transfusion; Ceftriaxone; Child; Drug Hypersensitivity; Epilepsy, Generalized; Erythrocytes; Flow Cytometry; Fluorescence; Humans; Male; Oxidative Stress; Pneumonia, Bacterial; Respiratory Insufficiency

Topics: Adult; Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; Ceftriaxone; Child; Hemolysis; Humans

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.

Topics: Anemia, Hemolytic, Autoimmune; Antigens; Ceftriaxone; Cephalosporins; Coombs Test; Humans; Male; Middle Aged

Topics: Aged; Anemia, Hemolytic, Autoimmune; Antibodies; Ceftriaxone; Female; Humans

A 16-year-old girl who was treated with ceftriaxone developed two intravascular haemolytic attacks that led to acute renal failure and death. The direct antiglobulin test was positive only for C3d, and no ceftriaxone-dependent antibodies were detectable. Her serum reacted strongly positive with red blood cells in the presence of ex vivo antigen related to ceftriaxone (urine samples from patients receiving the drug). This is the first reported case in which the causative antibodies appeared to be stimulated solely by a degradation product of ceftriaxone.

Topics: Adolescent; Anemia, Hemolytic, Autoimmune; Antibodies; Ceftriaxone; Cephalosporins; Fatal Outcome; Female; Humans

An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.

Topics: Acute Disease; Aged; Aged, 80 and over; Anemia; Anemia, Hemolytic, Autoimmune; Ceftriaxone; Cephalosporins; Chemical and Drug Induced Liver Injury; Erythroblasts; Hematopoiesis; Humans; Male

A 2-year-old boy with sickle cell anemia had a massive, fatal hemolytic reaction after administration of an intravenous dose of ceftriaxone. Laboratory studies demonstrated the presence of an IgM antibody against ceftriaxone, binding to and destroying the patient's erythrocytes by an immune complex mechanism. This rare complication should be considered in the differential diagnosis when hemoglobinuria develops in a child after administration of ceftriaxone or a similar agent.

Topics: Anemia, Hemolytic, Autoimmune; Anemia, Sickle Cell; Ceftriaxone; Child, Preschool; Fatal Outcome; Hemoglobinuria; Hemolysis; Humans; Immunoglobulin M; Male