Role of complement in antiphospholipid antibody-mediated thrombosis

O’Neil, Kathleen M.

doi:10.1007/s11926-007-0033-y

Cited by 9 publications

(4 citation statements)

References 46 publications

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“…There is no convincing data that could explain a primary high level of DAF and MCP in the placentas of women with inherited thrombophilia, where the inflammatory reaction mediator is likely the thrombin [10,19]. LMWH mechanism of action known from APS related thrombophilia is not applicable there.…”

Section: Discussionmentioning

confidence: 99%

Complement inhibitory proteins expression in placentas of thrombophilic women

Wirstlein¹,

Jasiński²,

Rajewski³

et al. 2012

Folia Histochem Cytobiol.

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Abstract:Factors controlling complement activation appear to exert a protective effect on pregnancy. This is particularly important in women with thrombophilia. The aim of this study was to determine the transcript and protein levels of complement decay-accelerating factor (DAF) and membrane cofactor protein (MCP) in the placentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry staining of inhibitors of the complement cascade, DAF and MCP proteins, in the placentas of thrombophilic women. Placentas were collected from eight women with inherited thrombophilia and ten with acquired thrombophilia. The levels of DAF and MCP transcripts were evaluated by qPCR, the protein level was evaluated by Western blot. We observed a higher transcript (p < 0.05) and protein (p < 0.001) levels of DAF and MCP in the placentas of thrombophilic women than in the control group. DAF and MCP were localized on villous syncytiotrophoblast membranes, but the assessment of staining in all groups did not differ. The observed higher expression level of proteins that control activation of complement control proteins is only seemingly contradictory to the changes observed for example in the antiphospholipid syndrome. However, given the hitherto known biochemical changes associated with thrombophilia, a mechanism in which increased expression of DAF and MCP in the placentas is an effect of proinflammatory cytokines, which accompanies thrombophilia, is probable.

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Section: Discussionmentioning

confidence: 99%

Complement inhibitory proteins expression in placentas of thrombophilic women

Wirstlein¹,

Jasiński²,

Rajewski³

et al. 2012

Folia Histochem Cytobiol.

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“…Studies have shown that binding of aPL to endothelial cells induces their activation, expressed by upregulation of adhesion molecules and cytokines, as well as their procoagulant state expressed by upregulation of tissue factor [78]. In addition, recent studies have provided evidence that activation of complement cascade by pathogenic aPL has an important role in endothelial cell injury and aPL-associated thrombosis [79]. Other mechanisms more directly related to thrombosis, probably frequently overlapping, such as interference of aPL with coagulation cascade, as well as activation of thrombocytes, have been proposed to be also involved in APS [80].…”

Section: Pathology and Pathomorphogenesismentioning

confidence: 99%

Microthrombotic/Microangiopathic Manifestations of the Antiphospholipid Syndrome

Praprotnik

Ferluga

Vizjak

et al. 2008

Clinic Rev Allerg Immunol

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The paper presents an overview of clinical manifestations and histopathologic findings in different organs in microvascular thrombotic and microangiopathic antiphospholipid syndrome (MAPS). Subsets of antiphospholipid syndrome (APS) are presented and defined. Clinico-pathologic correlations seem insufficient so far, because of a lack of detailed systematic studies of the histopathology in different organs. Based on their own autopsy and biopsy studies, the authors propose a novel categorization of histopathologic lesions that occur in patients with classic and catastrophic APS. In addition to the already accepted category of a microvascular thrombotic type of lesions, microangiopathic lesions consistent with thrombotic microangiopathy are proposed to be included in new revised classification criteria for definite APS. Microvascular thrombotic and so far underestimated microangiopathic histopathologic lesions have been shown to appear in various combinations and of different ages in patients with both classic and catastrophic APS, which fits into the concept of MAPS. These preliminary findings of our studies are also in line with the most recent hypothesis of two main mechanisms in the pathogenesis of APS, emphasizing a key role of endothelial cell affection induced by aPL on the one hand and interference with coagulation cascade on the other side.

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“…Inflammation can also cause endothelial damage. Evidence is accumulating that complement activation-which, like the thrombosis system, is also a cascade of tightly-controlled serine proteases-is required for thrombosis due to aPL [20][21][22][23]. Thus, two of Virchow's principles are met, and disturbance of blood flow is very common in everyday life.…”

Section: Antiphospholipid Antibodies and Thrombogenesismentioning

confidence: 99%

Thrombolysis in antiphospholipid syndrome: Current hematologic perspectives

McNall-Knapp

2008

Curr Rheumatol Rep

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Antiphospholipid antibodies (aPL) can cause thromboembolic events, but the reason for the thrombogenesis has not been fully elucidated. Studies show that the true pathogenic targets of aPL are plasma proteins involved in hemostasis (eg, beta(2)-glycoprotein I and prothrombin). These plasma proteins in turn bind to phospholipids, leading to the misclassification as "antiphospholipid" antibodies. The hemostatic system has abundant checks and balances to avoid excess hemorrhage and thrombosis. Thus, thrombosis requires more than interrupting one protein in the complex system. This review examines host genetic factors important in predisposition to thrombosis associated with aPL and concentrates on how antibodies in antiphospholipid syndrome interact with our natural anticoagulants and lead to thrombosis.

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Role of complement in antiphospholipid antibody-mediated thrombosis

Cited by 9 publications

References 46 publications

Complement inhibitory proteins expression in placentas of thrombophilic women

Complement inhibitory proteins expression in placentas of thrombophilic women

Microthrombotic/Microangiopathic Manifestations of the Antiphospholipid Syndrome

Thrombolysis in antiphospholipid syndrome: Current hematologic perspectives

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