Recent insights into antiphospholipid antibody-mediated thrombosis

Field, Susan L.; Brighton, Timothy; McNeil, H. Patrick; Chesterman, Colin N.

doi:10.1053/beha.1999.0033

Cited by 41 publications

(19 citation statements)

References 100 publications

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“…However, platelet activation with exposure of membrane phospholipids could provide the antigenic stimulus for the disordered immune regulation [38]. Although the mechanism for antiphospholipid-associated thrombosis is far from resolved, an interference with the protein C system has been proposed [37]. If an association between MPD and the Factor V Leiden mutation is con®rmed, then the presence of antiphospholipid antibodies may further reduce the capacity of the protein C system to inactivate Factor Va and VIIIa.…”

Section: Discussionmentioning

confidence: 99%

Frequent occurrence of anticardiolipin antibodies, Factor V Leiden mutation, and perturbed endothelial function in chronic myeloproliferative disorders

et al. 2002

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Chronic myeloproliferative disorders (MPD) are characterized by a high incidence of thrombohaemorrhagic complications, possibly related to platelet abnormalities and disturbances of the coagulation system. In an attempt to de®ne abnormalities in coagulation and ®brinolysis, we investigated risk markers for venous thromboembolism, ®-brinolytic, and haemostatic system activation markers and antiphospholipid antibodies in blood samples from 50 MPD patients and 30 controls. Compared with controls median levels of protein S free and protein C were signi®cantly decreased in the patients (0.27 vs. 0.38 arbitrary units; P < 0.001 and 0.86 vs. 0.99 arbitrary units; P < 0.001, respectively), and activated partial thromboplastin time was signi®cantly prolonged in patients (33 vs. 27 sec; P < 0.001). No dierences were observed in levels of antithrombin, thrombin± antithrombin complex, and ®brin D-dimer. In patients the median value of thrombomodulin was signi®cantly increased indicating perturbed endothelial function. Anticardiolipin antibodies of IgM subtype (median 38 U/mL, 33±99) were detected in 11 patients (22%) and only in one control (3%) (P < 0.021; patients vs. controls). Seven patients were heterozygous for the Factor V Leiden, one patient was heterozygous for the prothrombin G20210A mutation, and one patient was homozygous for the Factor V Leiden mutation. Among controls, two were heterozygous for the Factor V Leiden mutation. Comparing the allele frequency of the Factor V Leiden mutation in patients with MPD and the background population disclosed a signi®cantly increased allele prevalence of the Factor V Leiden mutation in the patients (9% vs. 3.4%; P = 0.003). Alterations in the level of anticoagulant proteins, disturbances of endothelial cell function, and the presence of cardiolipin antibodies and Factor V Leiden mutation may increase the cumulative thrombotic risk in MPD besides the risk imposed by platelet activation. Am.

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Section: Discussionmentioning

confidence: 99%

Frequent occurrence of anticardiolipin antibodies, Factor V Leiden mutation, and perturbed endothelial function in chronic myeloproliferative disorders

et al. 2002

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“…By binding to antiphospholipid-binding proteins including β 2 -glycoprotein-1 and annexin V, aPL limit intrinsic anticoagulation. They also increase tissue factor, PAI-1, and vWF expression in endothelial cells; inhibit thrombomodulin, aPC, and antithrombin activity, and enforce platelet activation, all leading to a procoagulant environment [28,29]. Theoretically, thrombosis of the placental villous bed would lead to infarction on a micro or macro level and limit oxygen supply to the developing pregnancy, with the outcome depending on both the timing and extent of thrombosis.…”

Section: Pathophysiologymentioning

confidence: 99%

Obstetrical Considerations and Management of Antiphospholipid Syndrome

Gibbins¹,

Silver²

2015

TOUNJ

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Antiphospholipid syndrome is a pro-thrombotic, pro-inflammatory condition defined by at least one clinical criterion and one laboratory finding. Clinical criteria are met by history of thrombosis or obstetric morbidity, including recurrent early pregnancy loss, fetal death, or delivery prior to 34 weeks gestation due to pre-eclampsia or placental insufficiency. Laboratory criteria are evidence of lupus anticoagulant or high titers of anticardiolipin or anti-ß 2 -glycoprotein-I IgG or IgM. Treatment during pregnancy is primarily based on anticoagulant therapy, either at prophylactic or therapeutic doses depending on thrombosis history. This treatment certainly reduces thrombosis risk and may also improve obstetric outcome.

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“…14 Assuming causality, suggested pathogenic mechanism(s) by which APA-induce adverse pregnancy outcomes include APAmediated impairment of endothelial thrombomodulin and activated protein Cmediated anticoagulation, induction of endothelial tissue factor expression, impairment of fibrinolysis and AT activity, as well as augmented platelet activation and/or adhesion. Additional mechanisms may include impairment of the anticoagulant effects of the anionic phospholipid binding proteins b-2-glycoprotein-I and annexin V. 15,16 More recently, APA has been linked to placental and systemic vascular inflammation and complement activation potentially related to the induction of tissue factor. [17][18][19] As heparin is known to have antithrombotic, anti-inflammatory, and anticomplement properties, it is the ideal treatment strategy.…”

Section: Introductionmentioning

confidence: 99%

Thrombophilias and Stillbirth

Werner

Lockwood

2010

Clinical Obstetrics &Amp; Gynecology

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It is often postulated that both inherited and acquired thrombophilias increase the risk of stillbirth. In an attempt to reduce this theoretical risk, pregnant patients with prior fetal losses and thrombophilias are anticoagulated. However, there is no definitive proof that thrombophilias are causally linked to stillbirth. Prospective studies have failed to establish a definitive link between inherited thrombophilias and stillbirth. The extant literature suggests that only high concentrations of antiphospholipid antibodies are associated with stillbirth. Moreover, when pregnant women with prior fetal losses even in these cases are placed on anticoagulation, it is unclear that their recurrence risk of stillbirth decreases.

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Recent insights into antiphospholipid antibody-mediated thrombosis

Cited by 41 publications

References 100 publications

Frequent occurrence of anticardiolipin antibodies, Factor V Leiden mutation, and perturbed endothelial function in chronic myeloproliferative disorders

Frequent occurrence of anticardiolipin antibodies, Factor V Leiden mutation, and perturbed endothelial function in chronic myeloproliferative disorders

Obstetrical Considerations and Management of Antiphospholipid Syndrome

Thrombophilias and Stillbirth

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