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American Family Physician Sep 2018Hemolytic anemia is defined by the premature destruction of red blood cells, and can be chronic or life-threatening. It should be part of the differential diagnosis for...
Hemolytic anemia is defined by the premature destruction of red blood cells, and can be chronic or life-threatening. It should be part of the differential diagnosis for any normocytic or macrocytic anemia. Hemolysis may occur intravascularly, extravascularly in the reticuloendothelial system, or both. Mechanisms include poor deformability leading to trapping and phagocytosis, antibody-mediated destruction through phagocytosis or direct complement activation, fragmentation due to microthrombi or direct mechanical trauma, oxidation, or direct cellular destruction. Patients with hemolysis may present with acute anemia, jaundice, hematuria, dyspnea, fatigue, tachycardia, and possibly hypotension. Laboratory test results that confirm hemolysis include reticulocytosis, as well as increased lactate dehydrogenase, increased unconjugated bilirubin, and decreased haptoglobin levels. The direct antiglobulin test further differentiates immune causes from nonimmune causes. A peripheral blood smear should be performed when hemolysis is present to identify abnormal red blood cell morphologies. Hemolytic diseases are classified into hemoglobinopathies, membranopathies, enzymopathies, immune-mediated anemias, and extrinsic nonimmune causes. Extrinsic nonimmune causes include the thrombotic microangiopathies, direct trauma, infections, systemic diseases, and oxidative insults. Medications can cause hemolytic anemia through several mechanisms. A rapid onset of anemia or significant hyperbilirubinemia in the neonatal period should prompt consideration of a hemolytic anemia.
Topics: Anemia, Hemolytic; Blood Cell Count; Diagnosis, Differential; Humans
PubMed: 30215915
DOI: No ID Found -
American Family Physician Jun 2004Hemolysis presents as acute or chronic anemia, reticulocytosis, or jaundice. The diagnosis is established by reticulocytosis, increased unconjugated bilirubin and... (Review)
Review
Hemolysis presents as acute or chronic anemia, reticulocytosis, or jaundice. The diagnosis is established by reticulocytosis, increased unconjugated bilirubin and lactate dehydrogenase, decreased haptoglobin, and peripheral blood smear findings. Premature destruction of erythrocytes occurs intravascularly or extravascularly. The etiologies of hemolysis often are categorized as acquired or hereditary. Common acquired causes of hemolytic anemia are autoimmunity, microangiopathy, and infection. Immune-mediated hemolysis, caused by antierythrocyte antibodies, can be secondary to malignancies, autoimmune disorders, drugs, and transfusion reactions. Microangiopathic hemolytic anemia occurs when the red cell membrane is damaged in circulation, leading to intravascular hemolysis and the appearance of schistocytes. Infectious agents such as malaria and babesiosis invade red blood cells. Disorders of red blood cell enzymes, membranes, and hemoglobin cause hereditary hemolytic anemias. Glucose-6-phosphate dehydrogenase deficiency leads to hemolysis in the presence of oxidative stress. Hereditary spherocytosis is characterized by spherocytes, a family history, and a negative direct antiglobulin test. Sickle cell anemia and thalassemia are hemoglobinopathies characterized by chronic hemolysis.
Topics: Algorithms; Anemia, Hemolytic; Autoimmune Diseases; Communicable Diseases; Hemoglobinopathies; Hemolysis; Humans; Physical Examination
PubMed: 15202694
DOI: No ID Found -
American Journal of Hematology Apr 2002Red blood cell (RBC) autoantibodies are a relatively uncommon cause of anemia. However, autoimmune hemolytic anemia (AIHA) must be considered in the differential... (Review)
Review
Red blood cell (RBC) autoantibodies are a relatively uncommon cause of anemia. However, autoimmune hemolytic anemia (AIHA) must be considered in the differential diagnosis of hemolytic anemias, especially if the patient has a concomitant lymphoproliferative disorder, autoimmune disease, or viral or mycoplasmal infection. Classifications of AIHA include warm AIHA, cold agglutinin syndrome, paroxysmal cold hemoglobinuria, mixed-type AIHA, and drug-induced AIHA. Characteristics of the autoantibodies are responsible for the various clinical entities. As a result, diagnosis is based on the clinical presentation and a serologic work-up. For each classification of AIHA, this review discusses the demographics, etiology, clinical presentation, laboratory evaluation, and treatment options.
Topics: Anemia, Hemolytic, Autoimmune; Autoantibodies; Cold Temperature; Erythrocytes; Hemoglobinuria, Paroxysmal; Hot Temperature; Humans
PubMed: 11921020
DOI: 10.1002/ajh.10062 -
Hematology/oncology Clinics of North... Apr 2022Cold agglutinin disease represents a form of immune-mediated hemolytic anemia whereby an IgM protein either monoclonal or polyclonal deposits complement on the surface... (Review)
Review
Cold agglutinin disease represents a form of immune-mediated hemolytic anemia whereby an IgM protein either monoclonal or polyclonal deposits complement on the surface of the red blood cell. Once complement is deposited, the 3rd component of complement is recognized by receptors in the mononuclear phagocyte system resulting in spherocytic extravascular hemolysis. This results in a Coombs positive hemolytic anemia with the peripheral blood film showing agglutination. In many instances, the source is a clonal population of lymphoplasmacytic cells in the bone marrow producing a monoclonal IgM protein. Traditional and emerging therapies directed against the production of the IgM may have a positive effect on hemolytic anemia. Success in the management of cold agglutinin disease with rituximab, fludarabine, bortezomib, and bendamustine has all been reported. Recent studies have demonstrated that the blockade of complement with sutimlimab can stop the hemolysis without the use of systemic chemotherapy.
Topics: Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Hemolysis; Humans; Immunoglobulin M; Rituximab
PubMed: 35282954
DOI: 10.1016/j.hoc.2021.11.001 -
Blood Sep 2020The mature red blood cell (RBC) lacks a nucleus and organelles characteristic of most cells, but it is elegantly structured to perform the essential function of... (Review)
Review
The mature red blood cell (RBC) lacks a nucleus and organelles characteristic of most cells, but it is elegantly structured to perform the essential function of delivering oxygen and removing carbon dioxide from all other cells while enduring the shear stress imposed by navigating small vessels and sinusoids. Over the past several decades, the efforts of biochemists, cell and molecular biologists, and hematologists have provided an appreciation of the complexity of RBC membrane structure, while studies of the RBC membrane disorders have offered valuable insights into structure-function relationships. Within the last decade, advances in genetic testing and its increased availability have made it possible to substantially build upon this foundational knowledge. Although disorders of the RBC membrane due to altered structural organization or altered transport function are heterogeneous, they often present with common clinical findings of hemolytic anemia. However, they may require substantially different management depending on the underlying pathophysiology. Accurate diagnosis is essential to avoid emergence of complications or inappropriate interventions. We propose an algorithm for laboratory evaluation of patients presenting with symptoms and signs of hemolytic anemia with a focus on RBC membrane disorders. Here, we review the genotypic and phenotypic variability of the RBC membrane disorders in order to raise the index of suspicion and highlight the need for correct and timely diagnosis.
Topics: Anemia, Hemolytic; Blood Proteins; Body Water; Cytoskeleton; Desiccation; Erythrocyte Membrane; Erythrocytes, Abnormal; Genetic Association Studies; Humans; Ion Channels; Models, Molecular; Mutation; Protein Conformation; Structure-Activity Relationship
PubMed: 32702754
DOI: 10.1182/blood.2019000946 -
American Journal of Hematology Jul 2012The direct antiglobulin test (DAT) is a laboratory test that detects immunoglobulin and/or complement on the surface of red blood cells. The utility of the DAT is to... (Review)
Review
The direct antiglobulin test (DAT) is a laboratory test that detects immunoglobulin and/or complement on the surface of red blood cells. The utility of the DAT is to sort hemolysis into an immune or nonimmune etiology. As with all tests, DAT results must be viewed in light of clinical and other laboratory data. This review highlights the most common clinical situations where the DAT can help classify causes of hemolysis, including autoimmune hemolytic anemia, transfusion-related hemolysis, hemolytic disease of the fetus/newborn, drug-induced hemolytic anemia, passenger lymphocyte syndrome, and DAT-negative hemolytic anemia. In addition, the pitfalls and limitations of the test are addressed. False reactions may occur with improper technique, including improper washing, centrifugation, and specimen agitation at the time of result interpretation. Patient factors, such as spontaneous red blood cell agglutination, may also contribute to false results.
Topics: Adult; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Anemia, Hemolytic, Congenital; Blood Group Incompatibility; Coombs Test; Hemolysis; Humans; Infant, Newborn
PubMed: 22566278
DOI: 10.1002/ajh.23218 -
Blood Mar 2021Microangiopathic hemolytic anemia (MAHA) with thrombocytopenia, suggests a thrombotic microangiopathy (TMA), linked with thrombus formation affecting small or larger... (Review)
Review
Microangiopathic hemolytic anemia (MAHA) with thrombocytopenia, suggests a thrombotic microangiopathy (TMA), linked with thrombus formation affecting small or larger vessels. In cancer patients, it may be directly related to the underlying malignancy (initial presentation or progressive disease), to its treatment, or a separate incidental diagnosis. It is vital to differentiate incidental thrombotic thrombocytopenia purpura or atypical hemolytic uremic syndrome in cancer patients presenting with a TMA, as they have different treatment strategies, and prompt initiation of treatment impacts outcome. In the oncology patient, widespread microvascular metastases or extensive bone marrow involvement can cause MAHA and thrombocytopenia. A disseminated intravascular coagulation (DIC) picture may be precipitated by sepsis or driven by the cancer itself. Cancer therapies may cause a TMA, either dose-dependent toxicity, or an idiosyncratic immune-mediated reaction due to drug-dependent antibodies. Many causes of TMA seen in the oncology patient do not respond to plasma exchange and, where feasible, treatment of the underlying malignancy is important in controlling both cancer-TMA or DIC driven disease. Drug-induced TMA should be considered and any putative causal agent stopped. We will discuss the differential diagnosis and treatment of MAHA in patients with cancer using clinical cases to highlight management principles.
Topics: Aged; Anemia, Hemolytic; Antineoplastic Agents; Disease Management; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Neoplasms; Organ Transplantation; Thrombotic Microangiopathies
PubMed: 33512445
DOI: 10.1182/blood.2019003810 -
British Journal of Haematology Feb 2017
Topics: Anemia, Hemolytic, Autoimmune; Guidelines as Topic; Humans
PubMed: 28005293
DOI: 10.1111/bjh.14478 -
Hematology. American Society of... Dec 2016Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease that affects 1 to 3/100 000 patients per year. AIHA caused by warm autoantibodies (w-AIHA), ie,... (Review)
Review
Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease that affects 1 to 3/100 000 patients per year. AIHA caused by warm autoantibodies (w-AIHA), ie, antibodies that react with their antigens on the red blood cell optimally at 37°C, is the most common type, comprising ∼70% to 80% of all adult cases and ∼50% of pediatric cases. About half of the w-AIHA cases are called primary because no specific etiology can be found, whereas the rest are secondary to other recognizable underlying disorders. This review will focus on the postulated immunopathogenetic mechanisms in idiopathic and secondary w-AIHA and report on the rare cases of direct antiglobulin test-negative AIHA, which are even more likely to be fatal because of inherent characteristics of the causative antibodies, as well as because of delays in diagnosis and initiation of appropriate treatment. Then, the characteristics of w-AIHA associated with genetically defined immune dysregulation disorders and special considerations on its management will be discussed. Finally, the standard treatment options and newer therapeutic approaches for this chronic autoimmune blood disorder will be reviewed.
Topics: Adult; Anemia, Hemolytic, Autoimmune; Female; Humans; Male
PubMed: 27913548
DOI: 10.1182/asheducation-2016.1.690 -
British Journal of Haematology Apr 2017
Topics: Humans; Anemia, Hemolytic, Autoimmune; Disease Management
PubMed: 28369704
DOI: 10.1111/bjh.14654