Low β<sub>2</sub>‐glycoprotein I levels in patients with disseminated intravascular coagulation

Matsuda, Juzo; Wakasugi, Kayoko; Saitoh, Noriko; Tsukamoto, Mitsuo; Miyajima, Yukari; Kazama, M; Asami, Katsuhisa; Hashimoto, Masakatsu

doi:10.1002/ajh.2830420224

Cited by 8 publications

(5 citation statements)

References 6 publications

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“…There is little published information on serum levels of B 2 GPI in disease states. Reduced serum levels of B 2 GPI have been reported in occasional patients with disseminated intravascular coagulation (DIC) (Schousboe, 1985;Matsuda et al, 1993). No correlation between B 2 GPI and other parameters of coagulation were presented in these studies.…”

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confidence: 60%

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Beta₂‐glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant

Brighton

et al. 1996

Br J Haematol

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Although the physiological role of beta2-glycoprotein (B2GPI) is unknown, in vitro evidence indicates that B2GPI may be a natural anticoagulant. In this study we have examined whether fluctuations of plasma B2GPI occur in in vivo coagulation. Serial measurements of B2GPI and other anticoagulant proteins were performed in 51 patients with thrombotic (group 1: six patients with disseminated intravascular coagulation (DIC), group 2: venous (n = 4) or arterial (n = 170 thrombosis) and non-thrombotic disease (group 3: 24 patients undergoing elective surgery). Reductions in plasma B2GPI levels were seen in most patients which were roughly proportional to the severity of their illness. Particularly striking reductions of B2GPI, protein C (PC) and antithrombin III (AT-III) (mean +/- 95% CI: 42.7 +/- 8.6%, 42.1 +/- 14.8%, 39.1 +/- 28.4% respectively) were seen in group 1. The reductions in plasma B2GPI were significantly greater in group 1 than in the other groups. Dilutional factors explain most of the reductions in B2GPI, PC and AT-III in groups 2 and 3, but contribute little to group 1. In conclusion, although B2GPI behaves as a 'negative acute phase reactant', the magnitude of reduction of plasma B2GPI levels, accompanied by reductions in other anticoagulant proteins in patients with DIC, suggests specific consumption of B2GPI in in vivo coagulation. This study provides further evidence that B2GPI is an anticoagulant of physiological importance.

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confidence: 60%

“…Reduced serum levels of B 2 GPI have been reported in occasional patients with disseminated intravascular coagulation (DIC) (Schousboe, 1985;Matsuda et al, 1993). Reduced serum levels of B 2 GPI have been reported in occasional patients with disseminated intravascular coagulation (DIC) (Schousboe, 1985;Matsuda et al, 1993).…”

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confidence: 99%

Beta₂‐glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant

Brighton

et al. 1996

Br J Haematol

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“…Recent reports support the possibility of such a regulatory role for ␤ 2 -glycoprotein I by identifying an association between low plasma levels of ␤ 2 -glycoprotein I and hypercoagulable states (63)(64)(65)(66)(67). Brighton et al (63) found a mean decrease in circulating ␤ 2 -glycoprotein I of 42.7 ± 8.6% in six patients with DIC, not accounted for by dilutional factors.…”

Section: Discussionmentioning

confidence: 96%

Enhancement of Protein S Anticoagulant Function by β2-glycoprotein I, a Major Target Antigen of Antiphospholipid Antibodies:

Merrill

Zhang²,

Shen³

et al. 1999

Thromb Haemost

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SummaryThrombosis in the antiphospholipid syndrome has been associated with acquired deficiency of the anticoagulant protein S. We sought evidence that β2-glycoprotein I, a major target antigen for antiphospholipid antibodies, is involved in regulation of protein S activity. Incubation of purified protein S or plasma with β2-glycoprotein I reversed functional modulation of protein S by its plasma inhibitor, the C4b-binding protein. In a plasma-free ELISA, β2-glycoprotein I prevented the binding of protein S and C4b-binding protein when pre-incubated with immobilized protein S but not when similarly preincu-bated with C4b-binding protein. β2-glycoprotein I in fluid phase interfered with precipitation of protein S by sepharose-bound C4b-binding protein. Effects of β2-glycoprotein I on protein S function were inhibited by one of four monoclonal anti-β2-glycoprotein I antibodies. These data suggest that β2-glycoprotein I helps maintain adequate plasma levels of circulating free, active protein S. Antiphospholipid (anti-β2-glycoprotein I) antibodies might cause sporadic thrombosis, at least in part, by impairing this novel regulatory mechanism.

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“…Reduced levels of β2GPI in patients with DIC has been assumed to reflect consumption, though whether β2GPI may be consumed in the context procoagulant or anticoagulant processes is unknown. 16,46 β2GPI has been reported to bind thrombin and prolong clotting times in fibrin generation assays by one group 17 , although others found only a modest effect on thrombin generation that occurred following preincubation of β2GPI with lipid at very low tissue factor concentrations. 19 β2GPI has also been reported to bind FXI and block FXI activation by thrombin or FXIIa 20 , suggesting an anticoagulant effect.…”

Section: Discussionmentioning

confidence: 99%

Protection of β2GPI Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation

Kulkarni,

Alluri,

Godwin

et al. 2023

Preprint

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Background: Antibodies to β2-glycoprotein I (?2GPI) cause thrombosis in antiphospholipid syndrome, however the role of β2GPI itself in regulation of coagulation pathways in vivo is not well understood. Methods: We developed β2GPI-deficient mice (Apoh-/-) by deleting exon 2 and 3 of Apoh using CRISPR/Cas9 and compared the propensity of wild-type (WT) and Apoh-/- mice to develop thrombosis using rose bengal and FeCl3-induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and assessed platelet activation in WT and Apoh-/- mice in the absence and presence of exogenous β2GPI. Results: Compared to WT littermates, Apoh-/- mice demonstrated a prolonged time to occlusion of the carotid artery after exposure to rose bengal or FeCl3, and reduced platelet and fibrin accumulation in cremasteric arterioles after laser injury. Similarly, significantly smaller thrombi were retrieved from the IVC of Apoh-/- mice 48 hours after IVC occlusion. The activated partial thromboplastin time (aPTT) and prothrombin time, as well as aPTT reagent- and tissue factor-induced thrombin generation times using plasma from Apoh-/- and WT mice revealed no differences. However, we observed significant prolongation of tail bleeding in Apoh-/- mice, and reduced P-selectin expression and binding of fibrinogen to the activated α2bβ3 integrin on platelets from these mice after stimulation with low thrombin concentrations; these changes were reversed by exogenous β2GPI. An antibody to PAR3 blocked thrombin-induced activation of WT, but not Apoh-/- platelets, as well as the ability of β2GPI to restore the activation response of Apoh-/- platelets to thrombin. β2GPI deficiency did not affect platelet activation by a PAR4-activator peptide, or ADP. Conclusions: In mice, β2GPI may mediate procoagulant activity by enhancing the ability of PAR3 to present thrombin to PAR4, promoting platelet activation at low thrombin concentrations.

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Low β₂‐glycoprotein I levels in patients with disseminated intravascular coagulation

Cited by 8 publications

References 6 publications

Beta₂‐glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant

Beta₂‐glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant

Enhancement of Protein S Anticoagulant Function by β2-glycoprotein I, a Major Target Antigen of Antiphospholipid Antibodies:

Protection of β2GPI Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation

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Low β2‐glycoprotein I levels in patients with disseminated intravascular coagulation

Cited by 8 publications

References 6 publications

Beta2‐glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant

Beta2‐glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant

Enhancement of Protein S Anticoagulant Function by β2-glycoprotein I, a Major Target Antigen of Antiphospholipid Antibodies:

Protection of β2GPI Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation

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Low β₂‐glycoprotein I levels in patients with disseminated intravascular coagulation

Beta₂‐glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant

Beta₂‐glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant