Activation of the Alternative Complement Pathway by Red Blood Cells from Patients with Sickle Cell Disease

Chudwin, David S.; Papierniak, Cynthia K.; Lint, Thomas F.; Korenblit, Allen D.

doi:10.1006/clin.1994.1072

Cited by 29 publications

(36 citation statements)

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“…Outside the context of RBC transfusions, various other diseases, such as thrombotic microangiopathy and sickle cell anemia, are characterized by hypercoagulability, 39 systemic complement activation, 40 and increased blood levels of microparticles. [41][42][43] Ståhl et al recently reported the presence of complement fragments on platelet and monocyte-derived microparticles in patients with shigatoxin-induced hemolytic uremic syndrome, a form of thrombotic microangiopathy, 42 suggesting a pathogenetic role of microvesicles in these conditions.…”

Section: Discussionmentioning

confidence: 99%

Erythrocyte-Derived Microvesicles Amplify Systemic Inflammation by Thrombin-Dependent Activation of Complement

Zecher

Čumpelik

Schifferli

2014

ATVB

111

100

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Objective-Transfusion of aged blood has been associated with increased morbidity and mortality in critically ill patients.During storage, erythrocytes release increasing numbers of microvesicles (red blood cell-derived microvesicles [RBC-MV]). We hypothesized that RBC-MV mediate some of the deleterious effects of aged blood transfusions. Approach and Results-We established a murine transfusion model using RBC-MV purified from aged mouse erythrocytes. Injection of RBC-MV into healthy mice had no effect. However, they aggravated pulmonary leukocyte sequestration and peripheral blood leukopenia induced by lipopolysaccharides. Lipopolysaccharide-induced proinflammatory cytokines were significantly increased in plasma after RBC-MV injection. These effects were not seen in C5aR-deficient mice. In vitro, RBC-MV bound C3 fragments after incubation with plasma but failed to bind immunoglobulins, C1q, or mannose-binding lectin. Preventing thrombin generation inhibited complement activation in vitro and in vivo and reversed the proinflammatory effects of RBC-MV in lipopolysaccharide-primed mice. Finally, the RBC-MV-induced phenotype was recapitulated using phosphatidylserineexpressing liposomes, suggesting that surface expression of phosphatidylserine by RBC-MV was mechanistically involved. Conclusions-These

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Section: Discussionmentioning

confidence: 99%

Erythrocyte-Derived Microvesicles Amplify Systemic Inflammation by Thrombin-Dependent Activation of Complement

Zecher

Čumpelik

Schifferli

2014

ATVB

111

100

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“…7,8 One prior case of ibrutinib-associated pneumonitis has been reported. 9 Herein, we report 4 cases of relapsed/refractory CLL patients who developed pneumonitis.…”

Section: To the Editormentioning

confidence: 99%

“…Complement activation may be involved in DHTR via the classic pathway when allo-or autoantibodies are detected, or by the alternative pathway. [7][8][9][10] Moreover, deleterious effects of free heme on endothelial cells through the alternative complement activation pathway have been demonstrated. [11][12][13] None of the patients presented C3 complement component consumption in the acute phase, but the final stage in complement activation was analyzed retrospectively and levels of sC5b9, reflecting membrane attack complex formation, were high in the plasma samples from the patients, suggesting that terminal pathway complement activation had occurred.…”

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confidence: 99%

Eculizumab salvage therapy for delayed hemolysis transfusion reaction in sickle cell disease patients

Dumas¹,

Habibi

Onimus

et al. 2016

Blood

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“…Eculizumab is an inhibitor of the C5 convertase inactivating the classical and alternative complement pathways. The results of some in vitro studies suggested the noxious effects of complement on endothelial cells exposed to free haem [22,23], the presence of C3 on transfused RBC in DHTR [24] and complement activation in sickle-cell red blood cells [25][26][27]. One SCD patient with anti-HI antibodies was treated with eculizumab and rituximab [20]; we also treated 3 patients with eculizumab during DHTR (manuscript in preparation), and it acted fast enough to reverse vasculopathy and slow DHTR-induced haemolysis.…”

Section: Innovative Therapiesmentioning

confidence: 99%

Management of hyperhaemolysis after a transfusion in sickle‐cell patients

Bartolucci

Pirenne

Habibi

2016

ISBT Science Series

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Transfusion is a corner stone treatment of sickle cell disease complications. However one of the serious complications of transfusions is represented by the delayed haemolytic transfusion reaction (DHTR) with a significant mortality. It is due to a massive intravascular haemolysis of both transfused and autologous red blood cells. It occurs between 5 to 20 days after a transfusion and is accompanied by a vaso‐occlusive crisis and haemoglobinuria in almost all cases. The evolution can be life‐threatening because of the appearance of a severe acute chest syndrome or a multi organ failure. About half patients are transferred in Intensive Care Unit. The biological diagnosis of DHTR is made by the rapid decline, or disappearance, of Hb A in sickle cell patients who were previously transfused. This event is associated with a significant increase of lactico‐dehydrogenase (LDH) and worsening of anemia due to haemolysis. Allo antibodies are not found in 30%. DHTR is under diagnosed because of the delay between the transfusion and the symptoms, which mimic sickle cell vaso occlusive crises. This can lead to further transfusions that worsen the evolution and are ineffective. Because of the severity of this manifestation many treatment have been tried to improve the outcome as steroids, immunoglobulins, rituximab or eculizumab, without consensual guidelines. Early diagnosis of DHTR should help to decide the appropriate treatment, and avoid reiteration of transfusions. Transfusion indications should be maximally restricted in patients with previous post‐transfusion haemolysis.

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Activation of the Alternative Complement Pathway by Red Blood Cells from Patients with Sickle Cell Disease

Cited by 29 publications

References 0 publications

Erythrocyte-Derived Microvesicles Amplify Systemic Inflammation by Thrombin-Dependent Activation of Complement

Erythrocyte-Derived Microvesicles Amplify Systemic Inflammation by Thrombin-Dependent Activation of Complement

Eculizumab salvage therapy for delayed hemolysis transfusion reaction in sickle cell disease patients

Management of hyperhaemolysis after a transfusion in sickle‐cell patients

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