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APS - Hematology & Rheumatology Related


Mechanisms of Disease: antiphospholipid antibodies—from clinical association to pathologic mechanism

Nature Clinical Practice Rheumatology. Published online: 19 February 2008. doi:10.1038/ncprheum0740 Received 6 September 2007. Accepted 4 December 2007. Conclusion and future directions: APS is still seen as a rather obscure disease despite extensive research; this view is mainly the result of the unreliability of the current assays for detecting the presence of antiphospholipid antibodies. The consequences are a poor correlation between serological markers and clinical manifestations, and a lack of clarity about the pathogenetic mechanism causing the syndrome. As mentioned above, we found that the presence of LA-inducing anti-beta2 GPI antibodies (with an affinity for domain I) correlates almost uniformly with the occurrence of thrombosis.21, 23 Our next aim is to investigate whether the presence of anti-domain I antibodies correlates with recurrent fetal loss. Research focused specifically on anti-domain I antibodies will hopefully provide information about the mechanism that causes APS. We have found that these antibodies cause increased (factor V Leiden-independent) APC resistance, increased resistance against the anticoagulant properties of annexin A5 and increased levels of activated von Willebrand factor (Figure 3).39, 42, 46 It is anticipated that this population is also involved in disease-causing mechanisms other than thrombosis in APS. It seems strange that new roles for a protein with no previous clear function come to light in the presence of an autoantibody. Perhaps native beta2 GPI already possesses these functions, but requires activation (such as a conformational change) before it can perform them. Native beta2 GPI could potentially already exhibit these actions at sites of cellular damage.47 Under apoptotic conditions, the antigen would be concentrated on the anionic phospholipids of the exposed cellular membranes and inhibit the unwanted consequences of the exposure of negatively-charged surfaces to components of the circulating bloodstream. In the presence of anti-beta2 GPI antibodies, the active conformation of the beta2 GPI protein is stabilized and its function is no longer limited to sites of damage. The consequence would be an imbalance in the hemostatic system, resulting in thrombosis at any vascular site in the body. In the future, more insight is needed into whether there are more antibody subpopulations that can cause the (specific) clinical manifestations that are observed in APS. Future investigations into the pathology should be performed with antibody populations with precisely defined epitopes.

Monitoring Warfarin Therapy in Patients with Lupus Anticoagulants

Recommended therapeutic international normalized ratios (INRs) for oral anticoagulation in patients with lupus anticoagulants who sustain a thromboembolic event are controversial. Patients with lupus anticoagulants often have a prolonged prothrombin time, which may complicate management of anticoagulant therapy.

Antibody Resource Page


Antiphospholipid antibodies and venous thromboembolism

Volume 86, Issue 10, pp. 3685-3691, 11/15/1995 Copyright © 1995 by The American Society of Hematology

RATIONAL LABORATORY DIAGNOSTICS OF ANTIPHOSPHOLIPID ANTIBODIES: ANTI-CARDIOLIPIN, ANTI-β2-GLYCOPROTEIN I, ANTI-PROTHROMBIN AND ANTI-ANNEXIN V ANTIBODIES

A possible co-appearance of anticardiolipin (aCL), anti-β2-glycoprotein I (anti-β2-GPI), anti-prothrombin (aPT) and anti-annexin V (aANXV) antibodies of IgG, IgM and IgA class were studied in 58 patients with SLE alone and 32 patients APS in the view of rational laboratory diagnostics. The presence of anti-phospholipid antibodies (aPL) were defined by our in-house ELISA methods. Out of 17 aCL negative SLE patients 6 had other antigenically defined aPL antibodies. In 13 patients only IgA but not IgG and IgM anti-β2GPI were detected. Different combinations of aPL subsets were equally distributed in APS and SLE groups. The prevalence of aANXV were similar in APS and SLE patients which was not the case with other aPL. Our findings support the idea of measuring additional subsets of aPL (aPT and aANXV) in unclear cases. IgA (either aCL or anti-β2-GPI) improved neither the diagnostic specificity nor diagnostic sensitivity, but only increased the frequency of the total anti-β2-GPI.

Diagnosis and Treatment of Livedo Reticularis on the Legs

The term livedo reticularis refers to a reddish-violet reticular discoloration of the skin that mainly affects the limbs. It is caused by an interruption of blood flow in the dermal arteries, either due to spasm, inflammation, or vascular obstruction, and is associated with diseases of varying etiology and severity. To establish the cause of livedo reticularis, it is essential to determine its course (chronic, acute, or fulminant), the presence of other cutaneous signs such as nodules, retiform purpura or necrosis, and the possible association of general symptoms or laboratory findings that suggest a particular systemic process. The aim of this review is to describe the diagnosis and treatment of the disease. Key words: livedo reticularis, retiform purpura, livedo racemosa, vasculitis, cholesterol emboli, calciphylaxis, antiphospholipid antibodies.

Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression

American Journal of Obstetrics & Gynecology Volume 205, Issue 6 , Pages 576.e7-576.e14, December 2011. Conclusion: These results provide the first morphologic evidence for this effect of hydroxychloroquine on human placental syncytiotrophoblasts and support the possibility of novel treatments that target antiphospholipid antibody binding.

Antiphospholipid Antibody Testing Update

From: The Rheumatologist, January 2012. The field of aPL antibody testing has evolved tremendously since the first aCL test was described by Harris and colleagues in 1983. 43 Controversies and uncertainties still exist despite the significant efforts to standardize the aPL antibody tests. However, the scientific community is aware of these difficulties, and important initiatives are underway to hopefully enhance the performance of tests that are critical for the diagnosis of APS. Even with major laboratory research, the most important question a clinician faces today has remained almost the same since the discovery of aCL: What test(s) should I order to diagnose APS in a patient with thrombosis and/or pregnancy loss? In the diagnosis and treatment of patients with APS, we believe strongly that clinicians should understand the scientific evidence supporting the use of a particular test and that laboratories should provide interpretative information and consultation to the physicians ordering the test. Such an approach would represent an important advance and hopefully improve the care of patients with these complicated, confusing, and often debilitating conditions.

Antiphospholipid Syndrome Challenges in the Laboratory Diagnosis and Treatment


Diagnosis and management of the antiphospholipid syndrome

Antiphospholipid syndrome is recurrent venous and arterial thrombosis with foetal loss. Trigger mechanism and therapeutics principles are yet to be completely ascertained. Novel ideas of recognition are activation of beta – 2 – glycoprotein 1 antibodies, complement activation. Although there are no racial dominance of primary antiphospholipid syndrome Female dominance are elicited the heterogeneity of its presentation allows us to think about multiple pathophysiology involved. Currently there are no biomarkers to predict the prognosis (1).Patients with lupus anticoagulant, high titre ACL IgG, LA or ACL with anti-B2 GPI antibodies have the highest thrombotic risk. Most common venous presentation is the deep vein thrombosis and arterial thrombosis is the stroke. Pregnancy related complication involves pre-eclampsia, premature birth, early and late foetal loss (2). Non thrombotic manifestations involve neurologic manifestations like cognitive dysfunction and emylination.Pulmonary capillaritis leads to diffuse alveolar haemorrhage. In case of life threatening APS the early therapies are – plasma exchange ,intravenous immunoglobulin and parenteral steroids .An interesting group is the one with all classical features of APS but negative blood test.But , they also need anticoagulation (3). Treatment in respect to venous thrombosis is to keep INR 2.0 – 3.0 (4) and in arterial thrombosis > 3.0 (5).More data is necessary to translate the changes in understanding mechanism and management.


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