Lupus Anticoagulant, Recurrent Abortion, and Prostacyclin Production by Cultured Smooth Muscle Cells

Castellarnau, Conxita de; Vilá, Luis M.; Sancho, María J.; Borrell, Montserrat; Fontcuberta, Jordi; Rutllant, M.L.

doi:10.1016/s0140-6736(83)90646-3

Cited by 45 publications

(8 citation statements)

References 10 publications

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“…Overall, the present data seem difficult to reconcile with our own (2-4), or with those of others (5)(6)(7)(8) concerning the inhibitory effect of IgGs on the formation of prostacyclin "in vitro". However, the effect of aPL antibodies on endothelial PGI2 generation "in vitro" may be influenced by the experimental conditions (1).…”

Section: Discussioncontrasting

confidence: 99%

“…Indeed, we provided the first evidence that the IgG fraction with LA activity from a patient with thrombosis and repeated intrauterine death interfered with PGI2 formation in rat aortic rings and human pregnant myometrium, and in cultured bovine aortic endothelial cells (2). Similar results have since been reported on the interference of plasma (5,6) or the IgG fraction from other patients (7,8) with the production of vascular prostacyclin. This point remains controversial and contradictory findings have been published on the enhancement of prostacyclin production by human umbilical vein endothelial cells (HUVEC) incubated with sera or immunoglobulin fractions containing LA or aPL antibodies (9)(10)(11)(12).…”

Section: Introductionsupporting

confidence: 79%

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Increased Expression of Inducible Cyclooxygenase-2 in Human Endothelial Cells by Antiphospholipid Antibodies

et al. 1995

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SummaryThe effect of IgGs from 4 patients with antiphospholipid antibodies and elevated excretion of urinary 11-dehydro-thromboxane B2 was evaluated on the production of prostacyclin by human endothelial cells in culture. After 6 h incubation, there was no change in 6-keto-prosta-glandin F1α in the supernatant. However patients’ IgGs induced a marked increase in cyclooxygenase (Cox) activity compared to IgGs from 2 normal individuals or a commercial pool of IgGs from normal donors, tested by adding exogenous arachidonic acid. Western blot analysis of the cellular Cox content using antibodies specific for the different forms of the enzymes revealed that patients’ IgGs stimulated the synthesis of the newly described inducible Cox-2 without affecting the constitutive Cox-1. This effect was partially neutralized by preincubating the IgGs with phospholipids. The induction was dependent on the amount of IgGs; it was visible at 2 h and persisted up to 24 h. Analysis of mRNA levels showed a pattern of variation in good agreement with the results obtained for protein. The protein kinase inhibitor H-7 or long-term incubation of cells with PMA strongly reduced the induction. These results suggest that antiphospholipid antibodies may not prevent the potential of the vascular cells from generating higher amounts of prostacyclin in response to acute episodes of thrombosis.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionsupporting

confidence: 79%

Increased Expression of Inducible Cyclooxygenase-2 in Human Endothelial Cells by Antiphospholipid Antibodies

et al. 1995

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“…It has been proposed that there is an interaction altering prostaglandin release. There may be activation of platelets and changes in prostaglandin metabolism, or the antibodies block protein C or alter phospholipid interactions with activated Factor V. 112 It has also been proposed that there may be hyperactivity of the fibrinolytic system and increased levels of plasminogen activation inhibitor. 113 To date there remains no consensus on the mechanism of action.…”

Section: Lupus Anticoagulantmentioning

confidence: 99%

Antiphospholipid and Thrombosis Syndromes

Bick

Baker²

1994

Semin Thromb Hemost

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ACAs and the lupus anticoagulant are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism or mechanisms whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories, as previously discussed, have been advanced. The most common thrombotic events associated with ACAs are DVT and PE (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome), cerebrovascular or retinal vessel thrombosis (type III syndrome), and occasionally patients present with mixtures (type IV syndrome). The relative frequency of ACAs in association with arterial and venous thrombosis strongly suggests that these should be looked for in any patient with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I through IV) should be defined, if possible, because this may dictate both type and duration of both immediate and long-term anticoagulant therapy. Unlike those with ACAs, patients with primary lupus anticoagulant thrombosis syndrome usually have venous thrombosis. Since the aPTT is unreliable in patients with lupus anticoagulant and is not usually prolonged in patients with ACAs, definitive tests (ELISA for ACA and the dRVVT for lupus anticoagulant) should be immediately ordered when suspecting antiphospholipid syndrome or in patients with otherwise unexplained thrombotic or thromboembolic events.

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“…It has been proposed that there might be an interaction with the vasculature, thereby altering prostaglandin release. There may be activation of platelets and changes in prostaglandin metabolism, or the antibodies either block protein C or the activated protein C pathway or alter phospholipid interactions with activated factor V. 39 It has also been proposed that there may be hypoactivity of the fibrinolytic system and increased levels of plasminogen activation inhibitor. 40 Despite many proposed mechanisms, to date there remains no consensus on the precise mechanism(s) of action of lupus anticoagulants.…”

Section: Lupus Anticoagulants and Thrombosismentioning

confidence: 99%

Antiphospholipid Syndrome and Thrombosis

Bick¹,

Baker²

1999

Semin Thromb Hemost

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Antiphospholipid antibodies [such as anticardiolipin antibodies (ACLA)] are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. The most common thrombotic events associated with ACLA are deep vein thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome) or cerebrovascular/retinal vessel thrombosis (type III syndrome), and occasionally patients present with mixtures (type IV syndrome). Type V patients are those with antiphospholipid antibodies and fetal wastage syndrome. It is as yet unclear how many seemingly normal individuals who may never develop manifestations of antiphospholipid syndrome (type VI) harbor asymptomatic antiphospholipid antibodies. The relative frequency of ACLA in association with arterial and venous thrombosis strongly suggests that these should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I through VI) should be defined, if possible, as this may dictate both type and duration of both immediate and long-term anticoagulant therapy. Unlike those with ACLA, patients with primary lupus anticoagulant thrombosis syndrome usually suffer venous thrombosis. Because the activated partial thromboplastin time (aPTT) is unreliable in patients with lupus anticoagulant (prolonged in only about 40 to 50% of patients) and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests including ELISA for ACLA, the dRVVT for lupus anticoagulant, hexagonal phospholipid neutralization procedure, and B-2-GP-I (IgG, IgA, and IgM) should be immediately ordered when suspecting antiphospholipid syndrome or in individuals with otherwise unexplained thrombotic or thromboembolic events. If these are negative, in the appropriate clinical setting, subgroups should also be assessed. Finally, most patients with antiphospholipid thrombosis syndrome will fail warfarin therapy and, except for retinal vascular thrombosis, most will fail antiplatelet therapy, thus it is of major importance to make this diagnosis in order that patients can be treated with the most effective therapy for secondary prevention, low-molecular weight heparin (LMWH) or unfractionated heparin (UHF) in most instances.

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Lupus Anticoagulant, Recurrent Abortion, and Prostacyclin Production by Cultured Smooth Muscle Cells

Cited by 45 publications

References 10 publications

Increased Expression of Inducible Cyclooxygenase-2 in Human Endothelial Cells by Antiphospholipid Antibodies

Increased Expression of Inducible Cyclooxygenase-2 in Human Endothelial Cells by Antiphospholipid Antibodies

Antiphospholipid and Thrombosis Syndromes

Antiphospholipid Syndrome and Thrombosis

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