The CARMEN-France registry of adult patients with immune thrombocytopenia and autoimmune hemolytic anemia in France.

The CARMEN-France registry is a prospective, multicenter registry in France including adult patients with a new diagnosis of immune thrombocytopenia or of autoimmune immune hemolytic anemia (2402 patients included in December 31, 2023). The recording of clinical, biological and treatment data allows detailed epidemiological and pharmacoepidemiological real-world studies. This review summarizes the CARMEN-France registry protocol, gives examples of studies conducted in the registry, and indicates future directions such as inclusion of patient reported outcomes, linkage with the French national health insurance database and linkage with other registries in Europe.

Coombs-Negative Hemolytic Anemia in an Elderly COVID-19 Patient.

COVID-19 infections are known to cause multi-organ complications. Hematological complications like autoimmune hemolytic anemia with a positive direct antiglobulin test (DAT), are commonly encountered. However, Coombs-negative hemolytic anemia is extremely rare. We report an interesting case of an elderly female with moderate-severe acute respiratory distress syndrome in the setting of COVID-19 pneumonia-causing Coombs-negative hemolytic anemia. This patient initially presented with sudden onset abdominal pain and vomiting, found to have an incarcerated inguinal hernia with small bowel obstruction (SBO) on imaging. Additionally, labs revealed positive COVID-19 antigen test and normocytic anemia. The hospital course was complicated by worsening hemolytic anemia and thrombocytopenia requiring blood products. Extensive workup for hemolysis in this patient with no prior hematological abnormalities, was negative for DAT and other conditions associated with or causative of hemolysis. At discharge, hemolytic parameters improved and on follow-up, hemoglobin returned to baseline, and repeat hemolytic parameters were normal. This case emphasizes the importance of considering SARS-CoV-2 along with other viral infections as one of the differentials for Coombs-negative hemolytic anemia.

A Real-World Disproportionality Analysis of Drug-Induced Immune Hemolytic Anemia in the FDA Adverse Event Reporting System.

BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening pharmacogenic hematological adverse effect. Updating the risk of DIIHA among the currently available drugs based on spontaneously reported adverse event data is of great significance. OBJECTIVE: This study aimed to identify the top 50 drugs associated with immune hemolytic anemia in adults as well as common drugs that could cause immune hemolytic anemia in children based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: We extracted adverse events (AE) in the FAERS database from Q1 2004 to Q3 2022 using Open vigil2.1. We use the high-level term "anaemias haemolytic immune" according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary (version 24.0). The reported correlation between drugs and DIIHA risk was identified by reported odds ratio (ROR) and proportional reporting ratio (PRR). RESULTS: There were 10500309 AEs in FAERS from 2004Q1 to 2022Q3, of which 2326 (0.02%) were DIIHA cases. The incidence of DIIHA is comparable between males and females. The most common drugs associated with DIIHA in adults and children are summarized according to the number of AE reports. The top 3 categories in terms of quantity of drugs are antineoplastic agents, immunosuppressants, and antibiotics for systemic use. The top 5 drugs in terms of ROR and PRR are alemtuzumab, daclizumab, fludarabine, busulfan, and bendamustine in adults, with entecavir, treosulfan, vinorelbine, pegademase, and alemtuzumab for children. CONCLUSIONS: Our study identified the most common drugs that could induce DIIHA in adults and children, as well as the respective ROR and PRR value to discover new drug signals. This study provides references to clinicians for the management of rare DIIHA.

Tyrosine kinase inhibitor-induced immune hemolytic anemia; three different drugs in three separate cases.

INTRODUCTION: Molecular multitargeted small tyrosine kinase inhibitory (TKI) agents such as axitinib, sunitinib and pazopanib are commonly used in several types of solid tumors. Anemia is not a rare effect of these drugs which may occur at all grades. However, drug-induced immune hemolytic anemia (IHA), a very rare condition is distinctive from other types of anemia with its specific mechanism and management strategy. CASE REPORTS: We reported three different TKI-induced IHA cases that occurred due to axitinib, sunitinib, and pazopanib, respectively. The first two cases were diagnosed with renal cell carcinoma and the last one was diagnosed with soft tissue sarcoma. They all presented with the characteristic symptoms of anemia and hemolysis. All the cases were detected positive for the complement C3d direct antiglobulin (direct coombs) test. MANAGEMENT AND OUTCOMES: Discontinuation of the causative drug and 1 mg/kg/day dose of corticosteroid treatment were able to control IHA in all three cases. Excluding the other factors of IHA and an evident laboratory and clinical benefit after withholding the TKI led to the diagnosis of TKI-related IHA in each case. DISCUSSION: TKIs are relatively new in clinical practice and are being used for more indications and in more patients. To our knowledge#these three cases are unique in terms of axitinib#sunitinib#and pazopanib-related IHA.

Beyond the Norm: A Case of Multiorgan Injury Triggered by Ibuprofen.

We report the case of a 71-year-old African American male with a history of chronic obstructive pulmonary disease (COPD), heart failure, vitiligo, penicillin allergy, and cocaine use, who presented with respiratory symptoms and was diagnosed with sepsis, COVID-19 pneumonia, exacerbation of COPD, and acute kidney injury (AKI). Treatment included antibiotics and high-dose steroids. The patient developed thrombocytopenia, autoimmune hemolytic anemia, acute liver failure, and interstitial nephritis associated with prolonged ibuprofen use. High-dose steroids and ibuprofen discontinuation led to significant improvement. This case highlights the rare occurrence of multiorgan injury from ibuprofen use, possibly aggravated by COVID-19, emphasizing the need for cautious non-steroidal anti-inflammatory drug (NSAID) use and close patient monitoring.

Rare Loxoscelism-Associated IgG Coombs-Positive Hemolytic Anemia Treated Successfully With Systemic Corticosteroids.

Loxoscelism-associated hemolytic anemia is a rare but critical complication of brown recluse spider bites. It may lead to various systemic manifestations, including jaundice, dark urine, and anemia-related symptoms, in addition to general loxoscelism symptoms such as skin lesions, fever, myalgia, nausea, and vomiting. Prompt diagnosis is crucial and requires recognizing typical laboratory findings such as low hemoglobin, elevated lactate dehydrogenase, reduced haptoglobin levels, and possibly a positive direct antiglobulin test. There is no definitive guideline for the treatment of loxoscelism-associated hemolytic anemia. we report a case of a 32-year-old female who developed severe Coombs-positive autoimmune hemolytic anemia following a brown recluse spider bite, with an improvement in hemoglobin levels and hemolysis indices after the administration of systemic corticosteroids.

Metaxalone-induced Immune Hemolytic Anemia.

Drug-induced immune hemolytic anemia (DIIHA) is a relatively uncommon cause of anemia, and its diagnosis can be challenging. Although beta-lactam antimicrobial agents are often associated with DIIHA, any medication can potentially cause it. We describe a patient presenting with yellow skin discoloration and orange-colored urine after starting metaxalone for treatment of lumbosacral sprain. Laboratory studies were consistent with warm hemolytic anemia. Symptoms improved remarkably after discontinuation of metaxalone, coupled with initiation of glucocorticoids and rituximab.

A Rare Case of Cold Agglutinin Syndrome Associated With Legionella Pneumonia.

Cold agglutinin syndrome (CAS) is a rare subset of autoimmune hemolytic anemia (AIHA) and can be classified as either primary or secondary. Secondary cold agglutinin disease has been associated with both viral and bacterial pathogens with the most common bacterial pathogen being Mycoplasma pneumoniae. Legionella pneumonia is a well-known causative agent for community-acquired pneumonia that can lead to a severe disease requiring hospitalization that is rarely associated with AIHA. We highlight the importance of recognizing Legionella pneumonia as a causative pathogen for CAS.

Hemolytic Anemia in the Setting of Atypical Pneumonia: A Case of Cold Agglutinin Disease.

Cold agglutinin hemolytic anemia (cAHA) is a rare autoimmune disorder characterized by the production of cold agglutinins. We present a case of secondary cAHA in a 23-year-old female with severe anemia and unexplained hemolysis. The patient exhibited findings indicative of hemolysis and a positive direct antiglobulin test (DAT) with complement alone. Additional investigations revealed incidental lung infiltrates, negative serology for infections and autoimmune diseases, and a low cold agglutinin titer. The patient showed a favorable response to doxycycline and supportive therapy, including multiple packed red blood cell transfusions. At the two-week follow-up, the patient had a stable hemoglobin level with no evidence of ongoing hemolysis. This case highlights the importance of considering secondary cAHA in patients with cold symptoms or unexplained hemolysis. Primary cAHA patients may require more aggressive treatment, including rituximab and sutilumab.

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.

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 First-Reported Case of Drug-Induced Hemolytic Anemia by Piperacillin-Tazobactam in a Premature Neonate: A Case Report and Literature Review.

Drugs can have a wide array of effects on hematological cells, including red blood cells (RBCs), white blood cells (WBCs), and platelets. Drug-induced hemolytic anemia (DIHA) can be explained by three different pathophysiological mechanisms. We present a case of a premature neonate born at 34 weeks gestation who was admitted to the neonatal intensive care unit (NICU). He developed respiratory difficulty with mottled skin and was suspected to have bacterial sepsis due to necrotizing enterocolitis (NEC). The patient was eventually started on a broad-spectrum antibiotic, piperacillin-tazobactam. On day eight, the patient started developing jaundice and his hemoglobin level dropped from 12.1 to 8.2 mg/dL. His direct antiglobulin test (DAT) was strongly positive. The patient was suspected to have DIHA. Piperacillin-tazobactam is a commonly used antibiotic for neonatal sepsis, but its potential to cause DIHA in neonates is not well-established. Our case highlights the importance of considering piperacillin-tazobactam as an unrecognized contributor to neonatal jaundice and a potential cause of DIHA in neonates. Further research is needed to explore the extent of its involvement in this condition. Physicians should be cautious when administering this drug to neonates and be aware of the possibility of hemolysis and jaundice.

A RARE CAUSE OF RECURRENT HAEMOLYTIC ANAEMIA: CARBOPLATIN AND PACLITAXEL-INDUCED AUTOIMMUNE HAEMOLYTIC ANAEMIA.

Drug-induced immune haemolytic anaemia (DIIHA) is a rare but serious complication affecting approximately 1 in 1,000,000 patients, but its incidence might be underestimated due to misdiagnosis. Several factors should be considered to ensure an accurate diagnosis, including previous medical history, comorbidities, drug history, the temporal relationship between drug exposure and symptom onset, haemolytic features, and comorbidities in suspected cases. The authors report a case of DIIHA caused by combination chemotherapy with carboplatin and paclitaxel complicated with haeme pigment-induced acute kidney injury. LEARNING POINTS: Drug-induced immune haemolytic anaemia (DIIHA) should be suspected in patients with abrupt immune haemolytic anaemia with a temporal relationship between drug exposure and symptom onset.The main management of DIIHA consists of urgent discontinuation of the suspected drug and supportive treatment with close monitoring, resulting in a favourable outcome in most cases; the role of corticosteroids in DIIHA remains unclear.Haeme pigment-induced acute kidney injury is induced by intravascular haemolysis where urinalysis reveals elevated haemoglobin.

Attack of the Clones: A Patient With Untreated Aplastic Anemia Presenting With Classical Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired X-linked, clonal hematopoietic stem cell disease. Patients with PNH may complain of vague symptomatology that contributes to the challenge of its diagnosis. This is especially true in the clinical context of a coinciding hematologic disorder. Aplastic anemia (AA) is an additional immune-mediated illness that results in the destruction of hematopoietic precursors and pancytopenia. The authors encourage screening for PNH clones in patients initially diagnosed with AA, treating underlying hematologic disease to prevent clonal expansion, and further research to investigate the effectiveness of eculizumab in an unusual "classical" PNH secondary to AA with hypercellular bone marrow.

Progress in immune hemolytic anemia caused by drugs / 中国输血杂志

Drug-induced immune hemolytic anemia (DIIHA) is a rare cytopenia caused by damage to RBCs by drug-induced antibodies or non-immune protein adsorption (NIPA). The drugs associated with DIIHA and the mechanistic hypotheses that are thought to be involved have been controversial, with complex serological tests often required by specialized Immune Hematology laboratories for diagnosis. It is necessary to know the clinical manifestation and laboratory diagnosis of DIIHA in order to distinguish the immuno-hematological abnormality caused by drugs from other causes. How to improve the diagnostic ability of DIIHA and establish a scientific and reasonable idea of DIIHA serological examination is urgent to help clinical diagnosis and correct treatment.

How Should Complicated Cases of Thrombotic Thrombocytopenic Purpura With Positive Coombs Test Be Treated?

Thrombocytopenia with concomitant anemia is a serious condition with a high mortality risk. Destruction of platelets, i.e., thrombocytopenia, can be secondary to either auto-antibodies (immune-mediated) or mechanical destruction (non-immune-mediated). The Coombs test is a widespread tool to differentiate between the two categories, resulting in different specific treatment approaches for each diagnosis. A peripheral blood smear can also help make the diagnosis; for instance, in cases of mechanical destruction such as thrombotic thrombocytopenic purpura (TTP), the red blood cell (RBC) shape looks fragmented, forming schistocytes. In rare instances, TTP can present with both schistocytes and a positive Coombs test, challenging the diagnosis of TTP. TTP is a hematological emergency requiring appropriate anticipation and the initiation of treatment prior to the confirmatory ADAMTS-13 test results. Mild forms of TTP can be managed with glucocorticoids and therapeutic plasma exchange. Refractory cases need more aggressive additional treatment with caplacizumab and rituximab. Caplacizumab is an expensive medication that is usually reserved for use after confirmation of a TTP diagnosis. The advantage of caplacizumab lies in its targeted mechanism of action against the A1 domain of the von Willebrand multimers that are normally destructed by the ADAMTS-13 enzyme. Here, we present a young female patient with confirmed TTP, and the initial diagnosis was challenged by the presence of antibodies with the Coombs test. Very little research has studied this rare instance and the appropriate treatment. Our case will save many future lives, as clinicians should be more aggressive in treating refractory TTP with a positive Coombs test.

A Repeat Case of Cefotetan-Induced Hemolytic Anemia in a Surgical Patient.

Drug-induced hemolytic anemia is a rare hematologic condition in which the immune system creates antibodies against red blood cell antigens in response to a medication exposure. This condition is commonly triggered by antibiotics, nonsteroidal anti-inflammatory drugs, and certain chemotherapies. Here, we describe a patient who experienced a repeat episode of drug-induced hemolytic anemia related to prophylactic cefotetan given before surgery. This case is important for increasing awareness of cephalosporin-induced hemolytic anemia, illustrating the significance of early detection and treatment of the condition, and highlighting the need for careful review of medication history in the surgical setting.

Case report: First case of pemetrexed plus cisplatin-induced immune hemolytic anemia in a patient with lung adenocarcinoma.

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening drug-related complication. There are no previous reports of pemetrexed plus cisplatin as first-line chemotherapy for non-small cell lung cancer, resulting in DIIHA. Case presentation: In this report, a patient with advanced-stage lung adenocarcinoma developed severe immune hemolytic anemia 21 days after pemetrexed plus cisplatin chemotherapy. Laboratory findings showed severe hemolysis, including a rapid decrease in hemoglobin (HGB) and an elevated level of reticulocytes (Rets), indirect bilirubin (IBIL), and lactate dehydrogenase (LDH). A workup for the possibility of DIIHA was performed, including a direct antiglobulin test (DAT), a test in the presence of the soluble drug, and a drug-treated red blood cell (RBC) test. It showed a strongly positive (3+) result for anti-C3d but not for anti-immunoglobin G (IgG) in DAT. Enzyme-treated RBCs reacted weakly with the patient's serum and pemetrexed when complement was added. In addition, the patient's serum and normal sera were reactive with cisplatin-treated RBCs. However, eluates from the patient's RBCs and diluted normal sera were non-reactive with cisplatin-coated RBCs. Untreated and enzyme-treated RBCs reacted with the patient's serum in the presence of soluble cisplatin. In vitro serological tests suggested that complement-dependent pemetrexed antibodies and cisplatin-associated non-immunologic protein adsorption (NIPA) might combine to cause immune hemolytic anemia. The patient's anemia gradually recovered when pemetrexed and cisplatin were discontinued. Conclusion: This rare case demonstrated that complement-dependent pemetrexed antibodies and cisplatin-associated NIPA might occur simultaneously in a patient with DIIHA.

Isolated Respiratory Failure as a Presentation for Early Perinuclear Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune inflammatory disease that usually affects the small-sized vasculature, most notably of the lungs and kidneys. One of the challenges of suspecting and diagnosing the condition lies in the insidious and unclear symptoms of presentation. In this case report, we discuss the case of a patient who initially presented with solely unclear pulmonary symptoms, without other organ system dysfunction.

Non-immune Intravascular Hemolytic Anemia, an Unusual Presentation of Severe Vitamin B-12 Deficiency.

Vitamin B12 deficiency is a multifactorial condition, with a wide range of clinical presentations from mild to severe anemia and anemia-related neurological deficits. Hemolysis is a unique cause but has increasingly been recognized lately as a possible B12 deficiency presentation. Our patient presented with hemolytic anemia, for which extensive workup has excluded the common hemolysis etiologies. Therefore, it was attributed to B12 deficiency and improved significantly after treatment. Our case highlights the significance of this unusual presentation and its clinical implementation.

A Case Report of Autoimmune Phenomena With Underlying Breast Cancer: Occam's Razor Versus Hickam's Dictum.

The association between malignancies and autoimmunity had been well-established. The proposed pathophysiology and causality can be bidirectional. For example, a paraneoplastic syndrome can be triggered by an underlying malignancy or vice versa, where chronic inflammation of organs affected by autoimmunity can induce malignant transformation such as the case with inflammatory bowel disease and colorectal cancer or primary sclerosing cholangitis and hepatobiliary cancer. This report presents a case of autoimmune phenomena, namely, autoimmune hemolytic anemia, pernicious anemia, and Graves disease associated with newly diagnosed breast cancer. We also highlight the postulated pathophysiologic mechanisms in an attempt to answer the question of whether the occurrence of these autoimmune phenomena in our patient is a result of the law of parsimony (Occam's razor), where clinical variables are pathogenically related, or the counterargument, where random events and diseases can take place simultaneously (Hickam's dictum).