The James Blundell Award Lecture 2007: Do we really understand immune red cell destruction?

Garratty, George

doi:10.1111/j.1365-3148.2008.00891.x

Cited by 68 publications

(66 citation statements)

References 87 publications

(84 reference statements)

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“…In SCD, the process has been attributed to macrophage activation, bystander hemolysis, reactive hemolysis, and possible continuation of hemolysis of autologous RBCs during painful VOC. 74,82 Incubation of stored donor RBCs in the pretransfusion plasma from SCD patients encountering DHTR without detectable antibodies caused the stored RBCs to undergo eryptosis, 80 an antibody-independent phenomenon characterized by erythrocyte shrinkage, membrane blebbing, and PS exposure, all classic features of apoptotic death of nucleated cells and observed in aging or damaged erythrocytes. 83 52 suggesting a role for FY protein in hyperhemolytic reactions without detectable antibodies.…”

Section: Main Features and Hypothesized Mechanisms In Scdmentioning

confidence: 99%

Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management

Yazdanbakhsh

Ware

Noizat‐Pirenne

2012

Blood

338

350

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Red blood cell transfusions have reduced morbidity and mortality for patients with sickle cell disease. Transfusions can lead to erythrocyte alloimmunization, however, with serious complications for the patient including life-threatening delayed hemolytic transfusion reactions and difficulty in finding compatible units, which can cause transfusion delays. In this review, we discuss the risk factors associated with alloimmunization with emphasis on possible mechanisms that can trigger delayed hemolytic transfusion reactions in sickle cell disease, and we describe the challenges in transfusion management of these patients, including opportunities and emerging approaches for minimizing this life-threatening complication. (Blood. 2012;120(3):528-537) IntroductionBlood transfusion remains a cornerstone of treatment of patients with sickle cell disease (SCD). Despite improved patient outcomes with hydroxyurea administration, indications for chronic transfusions have increased in the last 10 years and are associated with considerable reduction in morbidity and mortality, most notably in preventing first stroke in children. [1][2][3] However, transfusions can lead to erythrocyte alloimmunization with serious complications for the patient. These antibodies are often directed against antigens expressed on RBCs of white persons, which represent the majority of donors in Western countries. 4 Finding compatible units lacking those antigens can sometimes be difficult, and identifying and characterizing the antibodies can be timeconsuming and laborious, causing transfusion delays. Genetic as well as acquired patient-related factors are likely to influence the process of alloimmunization.The most serious consequence of alloimmunization in SCD patients is the risk of developing a delayed hemolytic transfusion reaction (DHTR), which can be life-threatening. In many cases of DHTR in SCD, the patient's hemoglobin level falls below the pretransfusion level, suggesting that, in addition to hemolysis of the transfused RBCs, the patient's own RBCs are lysed, a condition known as hyperhemolysis. Additional transfusions may exacerbate the hemolysis and further worsen the degree of anemia. The destruction of the patient's own RBCs in DHTR of SCD is partly explained by the presence of autoantibodies 5 because alloimmunization is known to trigger autoantibody production. However, DHTR/hyperhemolysis cases have also been reported in the absence of detectable alloantibodies or autoantibodies.In this review, we discuss the known risk factors associated with alloimmunization, then emphasize possible mechanisms that can trigger autoimmunization and DHTR in SCD, and finally describe the challenges in transfusion management of these patients. We emphasize opportunities and emerging approaches for minimizing this life-threatening complication. RBC alloimmunization pathobiologyAlloimmunization to erythrocytes involves multiple steps, including RBC antigen recognition, processing, and presentation of antigen by HLA class II to TCR, activation of CD4 ...

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Section: Main Features and Hypothesized Mechanisms In Scdmentioning

confidence: 99%

Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management

Yazdanbakhsh

Ware

Noizat‐Pirenne

2012

Blood

338

350

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“…However, progress in treatment has been much slower. [3][4][5][6][7][8] Therapy has been reviewed by several investigators, [8][9][10][11][12][13][14][15] but no treatment guidelines have yet been published. …”

mentioning

confidence: 99%

How I treat autoimmune hemolytic anemias in adults

Lechner

Jäger

2010

Blood

279

246

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Autoimmune hemolytic anemia is a heterogeneous disease with respect to the type of the antibody involved and the absence or presence of an underlying condition. Treatment decisions should be based on careful diagnostic evaluation. Primary warm antibody autoimmune hemolytic anemias respond well to steroids, but most patients remain steroid-dependent, and many require second-line treatment. Currently, splenectomy can be regarded as the most effective and best-evaluated second-line therapy, but there are still only limited data on longterm efficacy and adverse effects. The monoclonal anti-CD20 antibody rituximab is another second-line therapy with documented short-term efficacy, but there is limited information on long-term efficacy and side effects. The efficacy of immunosuppressants is poorly evaluated. Primary cold antibody autoimmune hemolytic anemias respond well to rituximab but are resistant to steroids and splenectomy. The most common causes of secondary autoimmune hemolytic anemias are malignancies, immune diseases, or drugs. They may be treated in a way similar to primary autoimmune hemolytic anemias, by immunosuppressants or by treatment of the underlying disease. IntroductionAutoimmune hemolytic anemia (AIHA) is a rare disease. In a recent population-based study 1 the incidence was 0.8/100 000/year, but the prevalence is 17/100 000. 2 Primary (idiopathic) AIHA is less frequent than secondary AIHA. Secondary cases are often challenging because not only AIHA but also the underlying disease(s) must be diagnosed and treated. AIHA is essentially diagnosed in the laboratory, and considerable improvement has been made in this field. However, progress in treatment has been much slower. [3][4][5][6][7][8] Therapy has been reviewed by several investigators, [8][9][10][11][12][13][14][15] but no treatment guidelines have yet been published. DiagnosisThe diagnosis of AIHA is usually straightforward and made on the basis of the following laboratory findings: normocytic or macrocytic anemia, reticulocytosis, low serum haptoglobin levels, elevated lactate dehydrogenase (LDH) level, increased indirect bilirubin level, and a positive direct antiglobulin test with a broad-spectrum antibody against immunoglobulin and complement ( Figure 1). However, there are pitfalls, particularly in secondary cases, because not always are all of the typical laboratory findings of AIHA present. 15 Two pieces of information are of utmost importance for the clinician to make an appropriate treatment decision: (1) What type of the antibody is involved? (2) Is the AIHA primary or secondary? The type of antibody can be identified with the use of monospecific antibodies to immunoglobulin G (IgG) and C3d. When the red cells are coated with IgG or IgG plus C3d, the antibody is usually a warm antibody (warm antibody AIHA [WAIHA]). When the red cells are coated with C3d only, the antibody is often but not always a cold antibody. For definite diagnosis of a cold antibody AIHA (CAIHA), the cold agglutinin titer should be markedly elevated (Ͼ 1:512)...

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“…Authors considered that the loss of CD47 can lead to the removal of cells from the circulation because CD47-deficient mice showed accelerated clearance of erythrocytes comparing to wild-type (WT) mice. Also, CD47-deficient RBCs transfused to WT mice had a shortened life span, which was interpreted as a lack of ability to inhibit macrophage activation and phagocytosis [6,13].…”

Section: Discussionmentioning

confidence: 99%

“…It is suggested that senescent cell neoantigens appear among proteins: Rh, band 3 and glycophorin A (GPA) on the erythrocyte surface and initiate the binding of the natural autoantibody [1,[6][7][8]. CD47 is a transmembrane glycoprotein, named also integrin-associated protein, which is closely related to the Rh macrocomplex.…”

Section: Introductionmentioning

confidence: 99%

Experimental immunology Expression levels of CD47 on red blood cells during their storage in blood bank

Gmerek¹,

Stachurska²,

Fabijańska-Mitek³

2013

cejoi

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The James Blundell Award Lecture 2007: Do we really understand immune red cell destruction?

Cited by 68 publications

References 87 publications

Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management

Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management

How I treat autoimmune hemolytic anemias in adults

Experimental immunology Expression levels of CD47 on red blood cells during their storage in blood bank

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