Antiphospholipid-protein Antibodies Research Articles

Investigation of Antiphosphatidyl‐Serine Antibody and Antiphosphatidyl‐Inositol Antibody in Ischemic Stroke Patients

Antiphospholipid syndrome is characterized by arterial or venous thrombosis and the presence of antiphospholipid antibodies (aPL). We measured β2-GPI aCL, IgGaCL, LA, antiphosphatidyl-serine antibody (PS), and antiphosphatidyl-inositol antibody (PI) in each patient at one month after the onset of stroke. In addition, carotid artery echography was performed in patients positive for PI or PS. Among the 250 patients, 13.6% (34/250) were positive for either PI or PS, and 6.8% (17/250) were positive for both. Carotid artery echography performed on these 34 patients showed that the frequencies of increased intimal-medial thickness (IMT) of 1.1 mm or more, plaque, and carotid artery stenosis of 50% or more were all significantly higher in patients positive for antinuclear antibody than those negative for the antibody (P < .05). PI and PS are associated with antinuclear antibody and precipitation of atherosclerosis. Ischemic stroke patients with SLE frequently showed a variety of antiphospholipid-protein antibodies.

1103 Clinical diversity of Antiphospholipid protein antibodies in ischemic stroke

1103 Clinical diversity of Antiphospholipid protein antibodies in ischemic stroke

A Cross Sectional Study of Antiphospholipid-protein Antibodies in Patients with Venous Thromboembolism

To look for an association between venous thromboembolism (VTE) and antiphospholipid antibodies (aPL) in patients without Systemic Lupus Erythematosus (SLE) when implementing, beside conventional assays, new tests for aPL screening directed towards purified proteic targets. We conducted a cross-sectional, hospital-based study of consecutive unselected outpatients. We compared VTE+ patients to VTE- among 398 consecutive unselected outpatients referred for clinical suspicion of VTE. To detect aPL, the following ELISAs were performed: 1) a conventional standardized ELISA 2) an improved APA assay, 3) an anti-Beta2GPI ELISA, 4) an anti-Annexin V ELISA, 5) an anti-Prothrombin ELISA. We sought an association between VTE and aPL through a quantitative (t-test) and a qualitative comparison (chi-square test, according to the cut-off values set as the 95th percentile of aPL distribution). First we conducted an analysis of all patients. Then we stratified them into 2 subgroups, with or without a wellknown risk factor for VTE (prolonged immobilization >72h, surgery or trauma within the past three months, current malignancy). 61% of patients were classified as VTE-positive. Before stratification, we did not find any significant association between the VTE status and aPL. However, after stratification, in the subgroup without risk factors for VTE, the frequency of positive values as regards the anti Prothrombin antibodies detection was significantly higher in VTE+ patients (p = 0,04). The presence of anti Prothrombin antibodies might be an independent risk factor of VTE. However systematic screening for aPL in non SLE patients referred for VTE suspicion at the time of the thrombo-embolic event has little clinical relevance.

Recent insights into antiphospholipid antibody-mediated thrombosis

The clinically relevant antiphospholipid antibodies (APA) include anticardiolipin antibodies and lupus anticoagulant. Most autoimmune APA require the presence of a cofactor for phospholipid binding, and the growing list of candidate cofactors has prompted redefinition of APA to ‘antiphospholipid protein antibodies’. Current evidence favours β2-glycoprotein I (β2GPI) and prothrombin as the primary antigens for anticardiolipin antibodies and lupus anticoagulant respectively. Patients with APA show a predisposition for venous and arterial thromboembolism, recurrent fetal loss, thrombocytopenia and a number of neurological syndromes and miscellaneous conditions. The association between APA and thrombosis has been well documented, but a definite mechanism remains to be clarified. Proposed mechanisms have included disruption of endothelial regulatory processes, impairment of fibrinolysis, augmented platelet activation and/or adhesion, inhibition of antithrombin activity and negation of the anticoagulant effects of β2GPI and annexin V. In this review we describe recent insights into the role of β2GPI as a natural anticoagulant, the procoagulant effects of APA on the Protein C system, the interactions between APA and prothrombin resulting in augmentation of thrombin generation, and cellular expression of Tissue Factor in patients with APA. Cellular immunity to β2GPI is also discussed. Elucidation of these pathophysiological mechanisms may shed further light on the association between APA and thrombosis.

Antiphospholipid-Protein Antibodies

Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which recognize a number of plasma proteins that bind to activated phospholipid membranes. Among these plasma proteins are: β2 Glycoprotein I (β2 GPI), prothrombin, Annexin V, and other vitamin K dependent proteins (e.g., factor X). APA have been associated with venous and arterial events as well as recurrent spontaneous abortion (RSA). It is estimated that 8 to 14% of venous thrombosis is secondary to the presence of APA. APA are the most common cause of acquired thrombophilia. The concept of antibody-mediated thrombosis is now widely accepted.The laboratory diagnosis of APA requires the use of coagulation-based tests to identify lupus anticoagulants (LA) and ELISA assays to identify anticardiolipin antibodies (ACA). The importance of testing for antibodies to β2 GPI is now well recognized. Antibodies to β2 GPI are more specific in identification of patients at risk for thrombosis.

Evans's Syndrome with Positive Lupus Anticoagulant and Antiphospholipid-Protein Antibodies

We report a case of a 34-year-old Caucasian man with Evans's syndrome, first manifested in childhood as autoimmune thrombocytopenia. Besides anti-erythrocyte antibodies and platelet-associated immunoglobulins, this patient's serum showed also the presence of antiphospholipid-protein antibodies detected by coagulometric (lupus anticoagulant) as well as immunoenzymatic methods (anticardiolipin, antiprothrombin, and anti-β2-glycoprotein I antibodies). Over 25 years of clinical observation the patient never experienced any thromboembolic events. We suggest that in the pathogenesis of Evans's syndrome and related disorders a major role is played by an autoimmune reaction with a predilection to various cell phospholipid-containing membrane structures, possibly damaged by a yet unknown primary insult. The significance of these various antiphospholipid-protein antibodies as predictors of thromboembolic complications in such patients remains, however, to be established. Key Words: Evans's syndrome-Lupus anticoagulant-Antiphospholipid-protein antibodies.

Thrombin Generation Measured Ex Vivo Following Microvasculor Injury Is Increased in SLE Patients with Antiphospholipid-protein Antibodies

Antiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and beta2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. However, the pathogenic mechanism leading to thrombosis in patients with APA remains unclear. We studied 32 patients with systemic lupus erythematosus (SLE) who were divided into two groups depending on the presence (n = 19) or absence (n = 13) of APA. Healthy volunteers (n = 12) matched by age and sex served as controls. In all subjects LA and IgG class anticardiolipin antibodies (ACA) were determined. Thrombin generation was monitored ex vivo measuring fibrinopeptide A (FPA) and prothrombin fragment F1 + 2 (F1 + 2) in blood emerging from a skin microvasculature injury, collected at 30 second intervals. In subjects with antiphospholipid antibodies mean FPA and F1 + 2 concentrations were significantly higher at most blood sampling times than in controls. In some SLE patients with APA the process of thrombin generation was clearly disturbed and very high concentrations of fibrinopeptide A were detected already in the first samples collected. Two minutes after skin incision SLE patients without APA produced slightly more FPA, but not F1 + 2, as compared to healthy subjects. Mathematical model applied to analyze the thrombin generation kinetics revealed that APA patients generated significantly greater amounts of thrombin than healthy controls (p = 0.02 for either marker). In contrast, in the same patients generation of thrombin in recalcified plasma in vitro was delayed pointing to the role of endothelium in the phenomenon studied. In summary, these data show for the first time that in SLE patients with antiphospholipid-protein antibodies thrombin generation after small blood vessel injury is markedly increased. Enhanced thrombin generation might explain thrombotic tendency observed in these patients.

Lupus Anticoagulants/Antiphospholipid-Protein Antibodies: The Great Imposters

Antiphospholipid-protein antibodies (APA) represent a family of immunoglobulins which recognize protein-phospholipid complexes. A variety of proteins have been implicated including: prothrombin, annexin V, beta 2-Glycoprotein I, and protein S. APA are detected utilizing either coagulation-based tests to identify lupus anticoagulants (LA) or solid phase ELISA assays to identify anticardiolipin antibodies (ACA). APA may be seen in a variety of different clinical settings including convalescence from infections, resulting from exposure to certain drugs, or in association with autoimmune diseases. Autoimmune APA have been linked to a variety of thromboembolic complications involving both arterial and venous sites. In addition, recurrent fetal loss has been linked to a APA. The underlying pathophysiology of the thromboembolic events remains controversial. Given the diversity of anatomic sites, more than one thromboembolic mechanism(s) is likely. Abnormalities of the protein C system most likely account for the venous thromboembolic events. Because of the spectrum of clinical complications, virtually any clinician may encounter patients with the APA syndrome (thrombosis, thrombocytopenia, recurrent fetal loss coupled with positive LA or ACA testing).

ANTIPHOSPHOLIPID-PROTEIN ANTIBODIES ARE NOT AN UNCOMMON FEATURE IN RETINAL VENOUS OCCLUSIONS

The Primary Antiphospholipid Protein Syndrome (PAPS) is characterised by venous and/or arterial thromboses and recurrent foetal loss, in the presence of the Lupus Anticoagulant (LA), elevated antibodies to cardiolipin (ACA) or both. This investigation evaluates the relation between the PAPS and Retinal Vein Occlusion (RVO). Forty-eight consecutive patients with RVO were screened for ACA and LA. PAPS was present in 16 (33%) of the patients. Our results suggest that testing Antiphospholipid-Protein Antibodies (APA) may be useful in these patients, together with the assessment of other vascular risk factors.

Antiphospholipid-protein antibodies: clinical use of laboratory test results (identification, predictive value, treatment).

Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which recognize protein-phospholipid complexes. Among the proteins implicated are: beta 2 Glycoprotein I, prothrombin, Annexin V, protein C, and protein S. Laboratory tests are used to identify, predict potential clinical complications, and manage patients with the antiphospholipid-protein syndrome (APS). Emerging evidence suggests laboratory tests can be used to stratify relative risk of patients with APA.

Antiphospholipid-protein antibodies: Laboratory detection and clinical relevance

Antiphospholipid-protein antibodies: Laboratory detection and clinical relevance

Protean Clinical Presentation of Antiphospholipid-Protein Antibodies (APA)

Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which have been defined by varying laboratory test systems. Lupus anticoagulants (LA) and anticardiolipin antibodies (ACA) are the two most prominent members of this family of antibodies. LA are detected utilizing various phospholipid (PL) dependent tests of coagulation (e.g., activated partial thromboplastin time [APTT], Kaolin Clotting Time [KCT], dilute Russell Viper Venom Time [dRVVT]). Originally, LA were thought to be a laboratory nuisance since the vast majority of individuals with LA did not bleed. Paradoxically, patients with LA were found to have an increased incidence of thromboembolic events and also recurrent spontaneous abortions (RSA). Thus, the laboratory detection of LA has become part of the work up of patients with thromboembolic disorders and RSA. ACA are detected using solid phase assay systems (radioimmunoassay or ELISA). The presence of ACA has the same clinical implications as that of LA. Although originally it was suggested ACA and LA were the same antibody, it is now well accepted that they, in many instances, are different antibodies. Therefore, it is critical for laboratories to evaluate patient samples for both LA and ACA. In approximately 60% of circumstances, both antibodies will be found. In the remaining cases, there will be discordance between the two test systems. The question of whether APA are causative, coincidental, or a consequence of the clinical complications of RSA and thrombosis remains controversial. Recent evidence based on prospective clinical studies and analysis of markers of in vivo coagulation suggests APA are causative.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent Advances in Blood Coagulation

Regulation of Coagulation By Tissue Factor Pathway Inhibitor. Developments in Antiphospholipid Protein Antibodies. The Relationships of Platelets to Arterial Thrombosis and Atherosclerosis. Inherited Resistance to Activated Protein C as a Pathogenic Risk Factor for Venous Thrombosis. Haemostatic Risk Factors for Arterial and Venous Thrombosis. Thromboembolism in Pregnancy and Its Prevention. Plasma Factor Viia. Lipids and Coagulation. Changing Indications for Warfarin Therapy. Progress in Clinical Fibrinolysis. New Antithrombotic Agents. Von Willebrand Disease and Its Diagnosis. Treatment of Von Willebrand Disease. Treatment of Haemophilia. Gene Therapy for Haemophilia