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Blood Jun 2022Immune checkpoint inhibitors are a class of antineoplastic therapies that unleash immune cells to kill malignant cells. There are currently 7 medications that have been... (Review)
Review
Immune checkpoint inhibitors are a class of antineoplastic therapies that unleash immune cells to kill malignant cells. There are currently 7 medications that have been approved by the US Food and Drug Administration for the treatment of 14 solid tumors and 2 hematologic malignancies. These medications commonly cause immune-related adverse effects as a result of overactive T lymphocytes, autoantibody production, and/or cytokine dysregulation. Hematologic toxicities are rare and of uncertain mechanism, and therefore management is often based on experiences with familiar conditions involving these perturbed immune responses, such as autoimmune hemolytic anemia, immune thrombocytopenia, and idiopathic aplastic anemia. Management is challenging because one must attend to the hematologic toxicity while simultaneously attending to the malignancy, with the imperative that effective cancer therapy be maintained or minimally interrupted if possible. The purpose of this review is to help clinicians by providing a clinical and pathophysiological framework in which to view these problems.
Topics: Anemia, Hemolytic, Autoimmune; Antineoplastic Agents; Hematologic Neoplasms; Humans; Immune Checkpoint Inhibitors; Neoplasms
PubMed: 34610113
DOI: 10.1182/blood.2020009016 -
Blood Mar 2021The last decades have seen great progress in the treatment of cold agglutinin disease (CAD). Comparative trials are lacking, and recommendations must be based mainly on... (Review)
Review
The last decades have seen great progress in the treatment of cold agglutinin disease (CAD). Comparative trials are lacking, and recommendations must be based mainly on nonrandomized trials and will be influenced by personal experience. Herein, current treatment options are reviewed and linked to 3 cases, each addressing specific aspects of therapy. Two major steps in CAD pathogenesis are identified, clonal B-cell lymphoproliferation and complement-mediated hemolysis, each of which constitutes a target of therapy. Although drug treatment is not always indicated, patients with symptomatic anemia or other bothersome symptoms should be treated. The importance of avoiding ineffective therapies is underscored. Corticosteroids should not be used to treat CAD. Studies on safety and efficacy of relevant drugs and combinations are briefly described. The author recommends that B cell-directed approaches remain the first choice in most patients requiring treatment. The 4-cycle bendamustine plus rituximab combination is highly efficacious and sufficiently safe and induces durable responses in most patients, but the time to response can be many months. Rituximab monotherapy should be preferred in frail patients. The complement C1s inhibitor sutimlimab is an emerging option in the second line and may also find its place in the first line in specific situations.
Topics: Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bendamustine Hydrochloride; Complement Inactivating Agents; Disease Management; Female; Humans; Middle Aged; Rituximab; Thrombosis
PubMed: 33512410
DOI: 10.1182/blood.2019003809 -
Disease Markers 2015Several hemolytic markers are available to guide the differential diagnosis and to monitor treatment of hemolytic conditions. They include increased reticulocytes, an... (Review)
Review
Several hemolytic markers are available to guide the differential diagnosis and to monitor treatment of hemolytic conditions. They include increased reticulocytes, an indicator of marrow compensatory response, elevated lactate dehydrogenase, a marker of intravascular hemolysis, reduced haptoglobin, and unconjugated hyperbilirubinemia. The direct antiglobulin test is the cornerstone of autoimmune forms, and blood smear examination is fundamental in the diagnosis of congenital membrane defects and thrombotic microangiopathies. Marked increase of lactate dehydrogenase and hemosiderinuria are typical of intravascular hemolysis, as observed in paroxysmal nocturnal hemoglobinuria, and hyperferritinemia is associated with chronic hemolysis. Prosthetic valve replacement and stenting are also associated with intravascular and chronic hemolysis. Compensatory reticulocytosis may be inadequate/absent in case of marrow involvement, iron/vitamin deficiency, infections, or autoimmune reaction against bone marrow-precursors. Reticulocytopenia occurs in 20-40% of autoimmune hemolytic anemia cases and is a poor prognostic factor. Increased reticulocytes, lactate dehydrogenase, and bilirubin, as well as reduced haptoglobin, are observed in conditions other than hemolysis that may confound the clinical picture. Hemoglobin defines the clinical severity of hemolysis, and thrombocytopenia suggests a possible thrombotic microangiopathy or Evans' syndrome. A comprehensive clinical and laboratory evaluation is advisable for a correct diagnostic and therapeutic workup of the different hemolytic conditions.
Topics: Anemia, Hemolytic, Autoimmune; Biomarkers; Diagnosis, Differential; Erythrocyte Count; Hemolysis; Humans
PubMed: 26819490
DOI: 10.1155/2015/635670 -
Journal of Veterinary Internal Medicine Jul 2022Current reports about the use of splenectomy for the management of immune-mediated hemolytic anemia (IMHA) or immune-mediated thrombocytopenia (ITP) or both in dogs are...
BACKGROUND
Current reports about the use of splenectomy for the management of immune-mediated hemolytic anemia (IMHA) or immune-mediated thrombocytopenia (ITP) or both in dogs are limited.
OBJECTIVES
To retrospectively describe the use of splenectomy as part of the management for IMHA, ITP, and concurrent IMHA and severe thrombocytopenia (CIST) in dogs. It was hypothesized that splenectomy would be beneficial in allowing for reduction of dose of immunosuppressive drugs or discontinuation in 1 or more of these groups.
ANIMALS
Seventeen client-owned dogs (7 with IMHA, 7 with ITP, and 3 with CIST) were identified across 7 UK-based referral hospitals from a study period of 2005 to 2016.
METHODS
Data were collected retrospectively via questionnaires and included information about diagnosis, management and treatment response before and after splenectomy. Based on clinical outcome, treatment with splenectomy as part of the management protocol was classified as either successful or unsuccessful.
RESULTS
Six of 7 dogs with ITP were managed successfully with splenectomy as part of their management protocol (3 complete and 3 partial responses), although 1 subsequently developed suspected IMHA. Of the 7 dogs with IMHA, splenectomy was part of a successful management protocol in 4 dogs (2 complete and 2 partial responses). In the CIST group, 1 case (1/3) responded completely to management with splenectomy as part of the management protocol.
CONCLUSIONS AND CLINICAL IMPORTANCE
Splenectomy was considered successful and well tolerated in most cases of isolated ITP. Whether there is a benefit of splenectomy in cases of IMHA and CIST could not be determined in the current study.
Topics: Anemia, Hemolytic, Autoimmune; Animals; Dog Diseases; Dogs; Retrospective Studies; Splenectomy; Thrombocytopenia
PubMed: 35801263
DOI: 10.1111/jvim.16469 -
Current Opinion in Hematology Nov 2023Warm autoimmune hemolytic anemia (wAIHA) is the most common of the immune hemolytic anemias. Although there are numerous case reports and reviews regarding this... (Review)
Review
PURPOSE OF REVIEW
Warm autoimmune hemolytic anemia (wAIHA) is the most common of the immune hemolytic anemias. Although there are numerous case reports and reviews regarding this condition, some of the unusual and more recent findings have not been fully defined and may be contentious. This review will provide insight into the common specificity of the warm autoantibodies and hypothesize a novel mechanism of wAIHA, that is proposed to be linked to the controversial subject of red blood cell senescence.
RECENT FINDINGS AND HYPOTHESES
It is now well established that band 3 on the red blood cell is the main target of autoantibodies in wAIHA. wAIHA targets the older red blood cells (RBCs) in about 80% of cases and, recently, it has been shown that the RBCs in these patients are aging faster than normal. It has been proposed that in these 80% of patients, that the autoantibody recognizes the senescent red blood cell antigen on band 3. It is further hypothesized that this autoantibody's production and potency has been exacerbated by hypersensitization to the RBC senescent antigen, which is processed through the adaptive immune system to create the pathogenic autoantibody. Recent publications have supported previous data that the senescent RBC antigen is exposed via a dynamic process, wherein oscillation of a band 3 internal loop flipping to the cell surface, creates a conformational neoantigen that is the RBC senescent antigen. It has also recently been shown that the cytokine profile in patients with wAIHA favors production of inflammatory cytokines/chemokines that includes interleukin-8 which can activate neutrophils to increase the oxidative stress on circulating RBCs to induce novel antigens, as has been postulated to favour exposure of the senescent RBC antigen.
SUMMARY
This manuscript reviews new findings and hypotheses regarding wAIHA and proposes a novel mechanism active in most wAIHA patients that is due to an exacerbation of normal RBC senescence.
Topics: Humans; Anemia, Hemolytic, Autoimmune; Immunoglobulin G; Erythrocytes; Autoantibodies
PubMed: 37497853
DOI: 10.1097/MOH.0000000000000779 -
Blood Apr 2023Relapsing or occurring de novo autoimmune hemolytic anemia (AIHA) during pregnancy or puerperium is a poorly described condition. Here, we report 45 pregnancies in 33...
Relapsing or occurring de novo autoimmune hemolytic anemia (AIHA) during pregnancy or puerperium is a poorly described condition. Here, we report 45 pregnancies in 33 women evaluated at 12 centers from 1997 to 2022. Among the 20 women diagnosed with AIHA before pregnancy, 10 had a relapse. An additional 13 patients developed de novo AIHA during gestation/puerperium (2 patients had AIHA relapse during a second pregnancy). Among 24 hemolytic events, anemia was uniformly severe (median Hb, 6.4 g/dL; range, 3.1-8.7) and required treatment in all cases (96% steroids ± intravenous immunoglobulin, IVIG, 58% transfusions). Response was achieved in all patients and was complete in 65% of the cases. Antithrombotic prophylaxis was administered to 8 patients (33%). After delivery, rituximab was administered to 4 patients, and cyclosporine was added to 1 patient. The rate of maternal complications, including premature rupture of membranes, placental detachment, and preeclampsia, was 15%. Early miscarriages occurred in 13% of the pregnancies. Fetal adverse events (22% of cases) included respiratory distress, fetal growth restriction, preterm birth, AIHA of the newborn, and 2 perinatal deaths. In conclusion, the occurrence of AIHA does not preclude the ability to carry out a healthy pregnancy, provided close monitoring, prompt therapy, and awareness of potential maternal and fetal complications.
Topics: Humans; Female; Infant, Newborn; Pregnancy; Anemia, Hemolytic, Autoimmune; Placenta; Premature Birth; Rituximab; Immunoglobulins, Intravenous; Postpartum Period
PubMed: 36706358
DOI: 10.1182/blood.2022018890 -
Archives of Pathology & Laboratory... Nov 2015Autoimmune hemolytic anemia is a rare disorder caused by autoreactive red blood cell (RBC) antibodies that destroy RBCs. Although autoimmune hemolytic anemia is rare,... (Review)
Review
Autoimmune hemolytic anemia is a rare disorder caused by autoreactive red blood cell (RBC) antibodies that destroy RBCs. Although autoimmune hemolytic anemia is rare, RBC autoantibodies are encountered frequently and can complicate transfusion workups, impede RBC alloantibody identification, delay distribution of compatible units, have variable clinical significance that ranges from benign to life-threatening, and may signal an underlying disease or disorder. In this review, we discuss the common presenting features of RBC autoantibodies, laboratory findings, ancillary studies that help the pathologist investigate the clinical significance of autoantibodies, and how to provide appropriate patient care and consultation for clinical colleagues. Pathologists must be mindful of, and knowledgeable about, this entity because it not only allows for direct clinical management but also can afford an opportunity to preemptively treat an otherwise silent malignancy or disorder.
Topics: Anemia, Hemolytic, Autoimmune; Autoantibodies; Clinical Laboratory Techniques; Diagnosis, Differential; Erythrocytes; Hematology; Humans; Pathology, Clinical
PubMed: 26516943
DOI: 10.5858/arpa.2014-0337-RS -
Journal of Veterinary Internal Medicine 2006Immune-mediated hemolytic anemia (IMHA) occurs less frequently in cats than in dogs. The value of the Coombs' test (CT) has been questioned, but detailed surveys of its...
Immune-mediated hemolytic anemia (IMHA) occurs less frequently in cats than in dogs. The value of the Coombs' test (CT) has been questioned, but detailed surveys of its use are lacking. The objective of this study was to describe 19 cats with primary IMHA (pIMHA) and to examine the diagnostic value of the direct CT. The CT was performed in 92 cats; it was negative in 5 healthy, in 9 sick nonanemic, and in 55 cats with different types of anemia. The CT was positive in 18 anemic cats (2 feline leukemia virus (FeLV) positive, 1 with cholangiohepatitis, 15 with no underlying disease). Moreover, agglutination persisted after saline washing in 5 anemic cats (1 lymphoma, 4 pIMHA). Inclusion criteria for pIMHA were a positive CT (15) or persistent agglutination (4), and the exclusion of other diseases. The age of the 19 cats ranged from 0.5 to 9 years (median, 2 years); male cats were overrepresented. The PCV on admission was 6-22% (median, 12%). The anemia was nonregenerative in 11 cats. Additional abnormal laboratory results were leukocytosis (2), lymphocytosis (6), hyperbilirubinemia (13), hyperglobulimemia (10), and increased liver enzyme activities (10). Initial treatment consisted of blood transfusions (10), crystalloids (11), prednisolone (19), antibiotics (19), and H2-blockers (11). Four of 17 cats were euthanized 9, 63, 240 and 2,160 days after initial presentation (mortality rate, 23.5%). Relapses were reported in 5 of 16 cases (31%). Thus, pIMHA appears to occur more frequently than recognized previously, with a more favorable prognosis in cats than in dogs. The CT was useful in identifying immune-mediated pathogenesis.
Topics: Anemia, Hemolytic, Autoimmune; Animals; Anti-Bacterial Agents; Blood Transfusion; Cat Diseases; Cats; Female; Histamine H2 Antagonists; Immunosuppressive Agents; Male; Prednisolone; Treatment Outcome
PubMed: 16496936
DOI: 10.1892/0891-6640(2006)20[159:pihaic]2.0.co;2 -
Hematology. American Society of... Dec 2022Warm autoimmune hemolytic anemia (wAIHA) is characterized by evidence of red blood cell (RBC) hemolysis and a direct antiglobulin test positive for IgG and sometimes...
Warm autoimmune hemolytic anemia (wAIHA) is characterized by evidence of red blood cell (RBC) hemolysis and a direct antiglobulin test positive for IgG and sometimes complement. While varying with the extent of the compensatory increase in RBC production, symptoms of anemia predominate, as does jaundice, the latter often exacerbated by concurrent Gilbert's syndrome. Initial treatment with corticosteroids is highly effective, with over 85% of patients responding but with less than one-third maintaining that response upon weaning. Subsequent rituximab administration in those failing corticosteroids provides complete remission in over 75% of patients and may be long-lasting. Over 50% of patients failing rituximab respond to erythropoiesis-stimulating agents or immunosuppressive agents. Splenectomy is best deferred if possible but does offer long-term remission in over two-thirds of patients. A number of new treatments for wAIHA (fostamatinib, rilzabrutinib, and FcRn inhibitors) show promise. A treatment algorithm for wAIHA is proposed to avoid the excessive use of corticosteroids.
Topics: Humans; Anemia, Hemolytic, Autoimmune; Rituximab; Erythrocytes; Immunosuppressive Agents; Splenectomy; Adrenal Cortex Hormones
PubMed: 36485114
DOI: 10.1182/hematology.2022000405 -
Pediatric Blood & Cancer Jan 2022Autoimmune hemolytic anemia (AIHA) after allogeneic hematopoietic stem cell transplant (HSCT) is a rare but complex and serious complication. Detailed descriptions of...
BACKGROUND
Autoimmune hemolytic anemia (AIHA) after allogeneic hematopoietic stem cell transplant (HSCT) is a rare but complex and serious complication. Detailed descriptions of cases and management strategies are needed due to lack of prospective trials.
OBJECTIVES
Describe the incidence, clinical characteristics, and management of AIHA after HSCT in a pediatric cohort.
METHODS
This is a retrospective cohort study of 33 pediatric patients with AIHA after HSCT at an academic tertiary care center from 2003 to 2019.
RESULTS
The overall incidence of AIHA after allogeneic HSCT was 3.8% (33/868). AIHA was significantly more common after transplant for nonmalignant versus malignant diagnoses (7.0% [26/370] vs. 1.4% [7/498], p < .0001). AIHA developed at a median of 4.7 months (range 1.0-29.7) after transplant. Sixteen of 33 patients (48.5%) required new AIHA-directed pharmacologic therapy; 17 (51.5%) were managed on their current immunosuppression and supportive care. Patients managed without additional therapy were significantly older, more likely to have a malignant diagnosis, and tended to develop AIHA at an earlier time point after transplant. Patients received a median of two red blood cell transfusions within the first 2 weeks of diagnosis and a median of one AIHA-directed medication (range one to four), most commonly corticosteroids and rituximab.
CONCLUSIONS
AIHA after HSCT is rare but occurs more commonly in patients transplanted for nonmalignant diagnoses. While some pediatric patients who develop AIHA after transplant can be managed on current immunosuppression and supportive care, many require AIHA-directed therapy including second-line medications.
Topics: Anemia, Hemolytic, Autoimmune; Child; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Retrospective Studies; Transplantation, Homologous
PubMed: 34709706
DOI: 10.1002/pbc.29410