Fibrin Clot Structure and Properties are Altered in Systemic Lupus Erythematosus

Набиуллина, Р М; Shakurova, Mileusha A.; Maksudova, A. N.; Zubairova, L. D.; Litvinov, Rustem I.

doi:10.1007/s12668-016-0234-9

Cited by 2 publications

(2 citation statements)

References 6 publications

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“…aPL are observed in up to 10% of patients with deep vein thrombosis (DVT) with or without pulmonary embolism (PE) 2 . Multiple prothrombotic mechanisms associated with the presence of aPL have been demonstrated including enhanced blood coagulation and impaired fibrinolysis 3 . Looking for new prothrombotic mechanisms underlying thrombotic APS, in 2014 we demonstrated in APS patients the so-called prothrombotic clot phenotype involving faster formation of denser fiber networks with the subsequent lower clot permeability and lysability 4 , which has been confirmed by Vikerfors et al .…”

Section: Introductionmentioning

confidence: 99%

Differences in plasma fibrin clot composition in patients with thrombotic antiphospholipid syndrome compared with venous thromboembolism

Stachowicz

Ząbczyk

Natorska

et al. 2018

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The prothrombotic fibrin clot phenotype has been reported in patients with thrombotic antiphospholipid syndrome (APS) and venous thromboembolism (VTE). Protein composition of plasma fibrin clots in APS has not been studied. We evaluated 23 patients with thrombotic APS, 19 with VTE alone, and 20 well-matched controls. A proteomic analysis of fibrin clots generated from citrated plasma was based on liquid chromatography-mass spectrometry. Plasma levels of thrombospondin-1 (TSP1), apolipoprotein(a), A-I, and B-100, complement components (C)3a, C5b-C9, histidine-rich glycoprotein (HRG), and prothrombin were evaluated using immunoenzymatic tests. In plasma fibrin clots of APS patients, compared with VTE subjects and controls, we identified decreased amounts of (pro)thrombin, antithrombin-III, apolipoprotein A-I, and HRG with no differences in plasma levels of antithrombin, prothrombin, along with lower plasma HRG and apolipoprotein A-I. In APS patients, plasma HRG positively correlated with amounts of clot-bound HRG, while apolipoprotein A-I was inversely associated with clot-bound levels of this protein. The most predominant proteins within the clots of APS patients were bone marrow proteoglycan, C5-C9, immunoglobulins, apolipoprotein B-100, platelet-derived proteins, and TSP1. Our study is the first to demonstrate differences in the protein composition of fibrin clots generated from plasma of thrombotic APS patients versus those with VTE alone.

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Section: Introductionmentioning

confidence: 99%

Differences in plasma fibrin clot composition in patients with thrombotic antiphospholipid syndrome compared with venous thromboembolism

Stachowicz

Ząbczyk

Natorska

et al. 2018

Sci Rep

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“…A high concentration of fibrinogen in the blood of SLE patients might be an additional cause of reduced clot contraction due to an increased elasticity of a dense fibrin network, comprising the mechanical scaffold of clots and thrombi [19,20]. Moreover, recent studies have revealed an alteration in the ultrastructure of fibrin network in the blood of SLE patients [30] which, in combination with hyperfibrinogenemia and fibrinogen phosphorylation [10,12], might also contribute to the increased elasticity and reduced deformability of the fibrin network, resulting in the impaired clot contraction. It is likely that rigidity and decreased deformability of the erythrocyte membrane resulting from lipid peroxidation associated with SLE also reduces the extent of clot contraction [31].…”

Section: Discussionmentioning

confidence: 99%

Impaired contraction of blood clots as a novel prothrombotic mechanism in systemic lupus erythematosus

et al. 2018

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The aim of this work was to examine a possible role of clot contraction/retraction in thrombotic complications of systemic lupus erythematosus (SLE). Using a novel automated method, we investigated kinetics of clot contraction in the blood of 51 SLE patients and 60 healthy donors. The functionality of platelets in the SLE patients was assessed using flow cytometry by expression of P-selectin and fibrinogen-binding capacity. The rate and degree of clot contraction were significantly reduced in SLE patients compared with healthy subjects, especially in the patients with higher blood levels of anti-dsDNA antibodies. The reduced platelet contractility correlated with partial refractoriness of platelets isolated from the blood of SLE patients to stimulation induced by the thrombin receptor activating peptide. To test if the anti-dsDNA autoantibodies cause continuous platelet activation, followed by exhaustion and dysfunction of the cells, we added purified exogenous anti-dsDNA autoantibodies from SLE patients to normal blood before clotting. In support of this hypothesis, the antibodies first enhanced clot contraction and then suppressed it in a time-dependent manner. Importantly, a direct correlation of clot contraction parameters with the disease severity suggests that the reduced compactness of intravascular clots and thrombi could be a pathogenic factor in SLE that may exaggerate the impaired blood flow at the site of thrombosis. In conclusion, autoantibodies in SLE can affect platelet contractility, resulting in reduced ability of clots and thrombi to shrink in volume, which increases vessel obstruction and may aggravate the course and outcomes of thrombotic complications in SLE.

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Fibrin Clot Structure and Properties are Altered in Systemic Lupus Erythematosus

Cited by 2 publications

References 6 publications

Differences in plasma fibrin clot composition in patients with thrombotic antiphospholipid syndrome compared with venous thromboembolism

Differences in plasma fibrin clot composition in patients with thrombotic antiphospholipid syndrome compared with venous thromboembolism

Impaired contraction of blood clots as a novel prothrombotic mechanism in systemic lupus erythematosus

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