Manifestations of the Antiphospholipid Syndrome in Patients with Malignancies.

Abstract The presence of antiphospholipid antibodies has been reported in a large variety of malignancies. It is not clear, however, if the antiphospholipid antibodies are related to thrombotic associations of the antiphospholipid syndrome (APS) in these patients. We investigated the frequency of thrombotic manifestations in 58 patients with the presence of antiphospholipid antibodies and a history of neoplasia, including haematologic and lymphoproliferative malignancies. Methods Antiphospholipid antibodies were detected by clotting assay (lupus anticoagulant, LA) or by enzyme-linked immunosorbent assay (anticardiolipin antibodies). LA were tested by more than 2 different methods according to the proposed criteria of the SSC of the ISTH. Results 39/58 patients suffered from solid tumours mostly from carcinoma of the breast, prostate, and colon and 19/58 patients from malignant haematologic or lymphoproliferative diseases mostly from Non-Hodgkin lymphoma. One patient was suffering simultaneously from two carcinomas of the prostate and the testicle and a Non-Hodgkin’s lymphoma. Among the patients with solid tumours 18/39 (46 %) patients had thromboembolic complications of the antiphospholipid syndrome. Among the patients with haematologic and lymphoproliferative malignancies only 6/19 (32 %) suffered from thromboembolic complications. Thrombotic manifestations were more common on the arterial than the venous site. There was no relation between the titres of aCL antibodies and the rate of clinical manifestations. In two patients aPL disappeared after the effective treatment of the tumor. Especially patients with very high titres did not present any thromboembolic manifestation. Conclusion The presence of antiphospholipid antibodies may identify a subset of cancer patients with high risk of developing thrombotic complications but the frequency of thrombosis is lower in aPL positive patients with lymphoproliferative and haematological malignancies. Especially in these patients very high titres of aCL antibodies do not seem to be associated with clinical manifestations of the APS.

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Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations

Journal of Ophthalmic Inflammation and Infection ◽

10.1186/s12348-021-00240-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Gunay Uludag ◽

Neil Onghanseng ◽

Anh N. T. Tran ◽

Muhammad Hassan ◽

Muhammad Sohail Halim ◽

...

Keyword(s):

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Clinical Manifestations ◽

Autoimmune Disorder ◽

Ocular Involvement ◽

Ocular Manifestations ◽

Different Types ◽

Thrombotic Complications ◽

Specific Factors ◽

Arteries And Veins

AbstractAntiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.

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Antiphospholipid syndrome accompanying systemic lupus erythematosus

Medicinski pregled ◽

10.2298/mpns0204089m ◽

2002 ◽

Vol 55 (3-4) ◽

pp. 89-96 ◽

Cited By ~ 2

Author(s):

Gorana Mitic

Keyword(s):

Systemic Lupus Erythematosus ◽

Antiphospholipid Syndrome ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Lupus Anticoagulant ◽

Clinical Manifestations ◽

Spontaneous Abortions ◽

Systemic Lupus ◽

Recurrent Spontaneous Abortions ◽

Thrombotic Complications

The aim of the study was the assessment of the prevalence of antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE). 72 patients with SLE had been investigated, 66 females and six males, aged 17 to 70 years, average 37,03. The presence of APA was determined using both ELISA assay for antiphospholipid antibodies ASSERACHROM APA by Diagnostica Stago and clotting tests for lupus anticoagulant: activated partial thromboplastin time (aPTT), tissue thromboplastin inhibition test (TTI) and dilute Russell viper venom time (dRVVT). Antiphospholipid antibodies have been found in 24 patients (33.44%), 10 of them were. with positive lupus anticoagulant tests, 6 of them were with positive ELISA test, while 8 of them had positive coagulation and immunological tests. Clinical manifestations that could be related to antiphospholipid syndrome were present in 22 patients (30.5%). The most common were thrombotic complications in 16 patients (22.25), recurrent spontaneous abortions in 7 patients (9.7%) and thrombocytopenia in 1 patient (1.39%). Presence of antiphospholipid syndrome was determined in 15 patients (20.83%). We can conclude that there is a significant correlation between presence of antiphospholipid antibodies and both thrombotic events and recurrent spontaneous abortions in SLE patients. Occurrence of thrombotic complications is in direct correlation with the level of antiphospholipid antibodies.

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The Coinicidence of Venous and Arterial Thrombosis in Patients with Antiphospholipid Syndrome - Correlation with Laboratory Findings.

Blood ◽

10.1182/blood.v104.11.4045.4045 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4045-4045

Author(s):

Wolfgang A. Miesbach ◽

Robert Hudeck ◽

Martina Boehm ◽

Inge Scharrer

Keyword(s):

Venous Thrombosis ◽

Antiphospholipid Syndrome ◽

Arterial Thrombosis ◽

Clinical Manifestations ◽

Anticardiolipin Antibodies ◽

Enzyme Linked Immunosorbent Assay ◽

Normal Range ◽

Laboratory Findings ◽

Lupus Anticoagulants ◽

Vein Thrombosis

Abstract The antiphospholipid syndrome (APS) is one of the most common acquired causes of thrombosis on the venous or arterial site. The initial type of the thrombosis appears to be the most likely type of event to recur. In general, APS patients present more common venous thrombosis, especially deep vein thrombosis of the legs. Arterial thromboses are less common and mostly manifest with ischemia or infarction. It is not clear whether a combination of phospholipid antibodies or the additional presence of lupus anticoagulants in patients with anticardiolipin antibodies increase the risk of manifestation of APS. Methods: We investigated retrospectively 300 patients with elevated aCL antibodies. IgG and IgM aCL antibodies were tested by enzyme-linked immunosorbent assay (ELISA). LA were tested by more than 2 different methods according to the proposed criteria of the SSC of the ISTH. Results: Of these patients, 61 % suffered from manifestations of APS, 35 % from venous and 28 % from arterial thrombosis, 7 % of the patients had abortions. In 39 % no thromboembolic disease was found. The coincidence of venous and arterial thrombosis was found in 25/300 (8 %) of the patients. An increased titer of IgG aCL was found in 135 of 300 patients (45 %, median 49 GPL-U/ml, normal range: - 11,3 GPL-U/ml), and an increased titer of IgM aCL in 260 patients (87 %, median 13 MPL-U/ml, normal range: 5,6 MPL-U/ml). Lupus anticoagulants were additionally detected in 130/300 patients (43 %). The rate of clinical manifestations did not differ between LA-positive patients (78 of 130 patients, 60 %) and LA-negative patients (105 of 170, 62 %) patients with elevated aCL antibodies. Regarding the patients with the coincidence of venous and arterial thrombosis, we found a significantly higher rate of positive lupus anticoagulants than in the patients with APS manifestation of one site only (17/25 vs. 113/275, p < 0.05, OR 3.04; 95 % CI 1.31 – 7.06). An elevation of IgG-aCL titres were more frequently found, too. Table 1: Characteristics of the patients with a coincidence of venous and arterial thrombosis compared to patients with thrombosis of one site only Conclusion: The additional presence of lupus anticoagulants in patients with anticardiolipin antibodies identifies a group of patients with high risk of recurrent manifestations of the antiphospholipid syndrome. Particularly the risk of manifestation of both, arterial and venous thrombosis in these patients should be early recognized to initiate a careful follow-up and antithrombotic therapy in these patients. Venous and Arterial Thrombosis Thrombosis of One Site No APS Manifestation n 25/300 (8 %) 157/300 (59 %) 118/300 (39 %) Age (yrs) median 48.5 50 46 Sex (F/M) 17/8 (2.1) 62/157 (2.1) 51/118 (2.3) LA 17/25 (68 %) 62/157 (39 %) 51/118 (43 %) IgG-aCL 15/25 (60 %) 73/157 (46 %) 47/118 (40 %) median titre 108 GPL 87 GPL 37 GPL IgM-aCL 24/25 (96 %) 129/157 (82 %) 104/118 (88 %) median titre 13 MPL 14 MPL 14 MPL

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Functional Analyses of Patient-derived IgG Monoclonal Anticardiolipin Antibodies Using In Vivo Thrombosis and In Vivo Microcirculation Models

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614033 ◽

2000 ◽

Vol 84 (09) ◽

pp. 388-395

Author(s):

Xiaowei Liu ◽

Ricardo Espinola ◽

Tsawei Olee ◽

Min Zhu ◽

Nigel Harris ◽

...

Keyword(s):

Endothelial Cells ◽

Antiphospholipid Syndrome ◽

Adhesion Molecule ◽

Antiphospholipid Antibodies ◽

Cell Function ◽

Leukocyte Adhesion ◽

Anticardiolipin Antibodies ◽

Intercellular Adhesion Molecule ◽

Enzyme Linked Immunosorbent Assay

SummaryAntiphospholipid antibodies (aPL) have been associated with thrombosis and pregnancy losses in patients diagnosed with antiphospholipid syndrome (APS) and enhance thrombus formation in vivo in mice, but the mechanism of thrombosis by aPL is not completely understood. It has been proposed that aPL may affect endothelial cell (EC) function and/or induce their activation, transforming their anticoagulant surface into procoagulant, thus predisposing to thrombosis. It has been proposed that aPL may affect EC cell function and/or induce their activation, transforming their anticoagulant surface into procoagulant, thus predisposing to thrombosis. This study proposes to test the hypotheses that some IgG anticardiolipins (IgG aCL) with thrombogenic properties in mice, exert their effects through activation of endothelium. We studied seven patient-derived monoclonal aCL for their thrombogenic properties in an in vivo pinch-induced thrombosis model, and their functional activities in activating EC by analyzing in vivo leukocyte adhesion to endothelium in microcirculation in venules in exposed murine cremaster muscle and in vitro adhesion molecule expression in cultured EC. The binding of the monoclonal aCL to EC was also tested. In addition to the previous identified thrombogenic IS2, four of the five new more IgG monoclonal aCL (from two patients) were found to be thrombogenic. Of these five thrombogenic aCL, three caused more in vivo leukocyte adhesion to EC in microcirculation, as compared to that induced by the H2 control human monoclonal IgG, and enhanced expression of adhesion molecules (particularly VCAM-1) on cultured EC. These data show that about 2/3 patientderived IgG monoclonal aCL are thrombogenic and suggest that some thrombogenic IgG aCL exert their effects through activating EC. Abbreviations: aCL, anticardiolipin antibodies; aPL, antiphospholipid antibodies; APS, antiphospholipid syndrome; CL, cardiolipin; dRVVT, dilute Russell’s viper venom time; EC, endothelial cells; ELISA, enzyme-linked immunosorbent assay; GP, glycoprotein; h, hour; HUVEC, human umbilicalvein endothelial cells; ICAM, intercellular adhesion molecule; KCT, kaolin clotting time; LA, lupus anticoagulant; PBS, phosphate-buffered saline; PL, phospholipid; sq, square; TBS, Tris-buffered saline; VCAM, vascular cell adhesion molecule; PMBC, peripheral mononuclear blood cells

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Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study

Blood ◽

10.1182/blood-2007-01-066043 ◽

2007 ◽

Vol 110 (4) ◽

pp. 1178-1183 ◽

Cited By ~ 117

Author(s):

Monica Galli ◽

Giovanna Borrelli ◽

Eva Marie Jacobsen ◽

Rosa Maria Marfisi ◽

Guido Finazzi ◽

...

Keyword(s):

At Risk ◽

Clinical Significance ◽

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Protein S ◽

Anticardiolipin Antibodies ◽

Antibody Detection ◽

Enzyme Linked Immunosorbent Assay ◽

Igm Antibodies ◽

Glycoprotein I

Abstract To assess the clinical significance of lupus anticoagulants (LAs) and antiphospholipid antibodies (aPLs) toward thrombosis and abortions, we measured them in 112 patients whose samples were available at enrollment in the warfarin in the antiphospholipid syndrome (WAPS) study. Enzyme-linked immunosorbent assay (ELISA) and coagulation test values in the highest and lowest tertiles were compared. When considered separately, IgG antibodies to β2-glycoprotein I (aβ2GPI) and prothrombin (aPT) were associated with anamnestic arterial and venous thrombosis, respectively, and those to annexin AV (aAnAV) with abortions. IgM antibodies to protein S and the lupus ratio of the dilute prothrombin time were associated with prospective thrombosis. No other association for IgM antibodies was seen. LA-positive patients who carried aβ2GPI antibodies were at risk of anamnestic arterial and total thrombosis and aPT antibodies to that of anamnestic venous and total thrombosis. LA-positive patients who carried IgG aβ2GPI and aAnAV antibodies were at risk for both anamnestic abortion and prospective thrombosis. Overall, these data support the inclusion of aβ2GPI antibodies in and suggest the removal of anticardiolipin antibodies from the laboratory criteria of the antiphospholipid syndrome. They also suggest that the measurement of aPT and aAnAV antibodies is useful in some selected situations and that there is little role for IgM antibody detection.

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Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome

Blood ◽

10.1182/blood-2005-07-2636 ◽

2006 ◽

Vol 107 (11) ◽

pp. 4375-4382 ◽

Cited By ~ 122

Author(s):

Gabriela Cesarman-Maus ◽

Nina P. Ríos-Luna ◽

Arunkumar B. Deora ◽

Bihui Huang ◽

Rosario Villa ◽

...

Keyword(s):

Endothelial Cells ◽

Cell Surface ◽

Antiphospholipid Syndrome ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Cell Surface Receptor ◽

Enzyme Linked Immunosorbent Assay ◽

Target Antigen ◽

Healthy Individuals ◽

Annexin 2

AbstractThe association of thrombosis and gestational morbidity with antiphospholipid antibodies is termed antiphospholipid syndrome (APS). Annexin 2 (A2) is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and β2-glycoprotein I (β2GPI), the main antigen for antiphospholipid antibodies. Here, we evaluate A2 as a target antigen in APS. Serum samples from 434 individuals (206 patients with systemic lupus erythematosus without thrombosis, 62 with APS, 21 with nonautoimmune thrombosis, and 145 healthy individuals) were analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoblot for antiphospholipid and A2 antibodies. Anti-A2 antibodies (titer > 3 SDs) were significantly more prevalent in patients with APS (22.6%; venous, 17.5%; arterial, 34.3%; and mixed thrombosis, 40.4%) than in healthy individuals (2.1%, P < .001), patients with nonautoimmune thrombosis (0%, P = .017), or patients with lupus without thrombosis (6.3%, P < .001). Anti–A2 IgG enhanced the expression of tissue factor on endothelial cells (6.4-fold ± 0.13-fold SE), blocked A2-supported plasmin generation in a tPAdependent generation assay (19%-71%) independently of β2GPI, and inhibited cell surface plasmin generation on human umbilical vein endothelial cells (HUVECs) by 34% to 83%. We propose that anti-A2 antibodies contribute to the prothrombotic diathesis in antiphospholipid syndrome.

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Atherosclerosis and the antiphospholipid syndrome: A link unravelled?

Lupus ◽

10.1177/096120339800700231 ◽

1998 ◽

Vol 7 (2_suppl) ◽

pp. 140-143 ◽

Cited By ~ 46

Author(s):

Y Shoenfeld ◽

D Harats ◽

J George

Keyword(s):

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Dominant Role ◽

Clinical Manifestations ◽

Humoral Response ◽

Arterial System ◽

Glycoprotein I ◽

Shock Proteins ◽

Modified Forms ◽

Progression Of Atherosclerosis

Atherosclerosis is a multifactorial disease that involves the arterial system. Recent data suggest that immune and autoimmune factors play a dominant role in mediating the progression of atherosclerosis. Among these factors, humoral response to modified forms of LDL and heat-shock proteins has been shown to be influential. The antiphospholipid syndrome (APS) entails clinical manifestations that result from a hypercoagulable state. Antibodies to phospholipids and to β2-glycoprotein I have been suggested to confer the tendency to thrombosis. In a set of recent studies, we have been able to show that generation of antiphospholipid antibodies in mice is associated with enhanced atherosclerosis. These findings imply that APS and atherosclerosis may share a common etiologic background, which may have direct implications for the management of both conditions.

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Antiphospholipid Syndrome

REVISTA CIÊNCIAS EM SAÚDE ◽

10.21876/rcshci.v9i4.892 ◽

2019 ◽

Vol 9 (4) ◽

pp. 37-42

Author(s):

Thaís da Silva Santos ◽

Izabel Galhardo Demarchi ◽

Tatiane França Perles Mello ◽

Jorge Juarez Vieira Teixeira ◽

Maria Valdrinez Campana Lonardoni

Keyword(s):

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Binding Proteins ◽

Clinical Manifestations ◽

Cellular Activation ◽

Pathophysiological Mechanisms ◽

Individual Character ◽

History Of ◽

Autoimmune Condition ◽

In Pregnancy

Antiphospholipid syndrome (APS) was characterized as an autoimmune condition with the production of antiphospholipid antibodies (aPL) associated with thrombosis and morbidity in pregnancy. The prevalence of aPL in the population ranges from 1% to 5% in patients with APS. The hypotheses regarding pathophysiological mechanisms are strongly related to binding proteins and antiphospholipid antibodies. The exact mechanisms by which they lead to clinical manifestations appear to be heterogeneous, but it is believed which aPL contribute to the cellular activation/coagulation, and so cause the thrombotic events. The treatment of APS should be an individual character and several factors should be taken into accounts, such as a number of antibodies, the age of the patient and the history of thrombotic events.

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Antiphospholipid Antibodies and Fertility: No Impact on Ovarian Reserve in Premenopausal Women

Journal of Clinical Rheumatology and Immunology ◽

10.1142/s2661341720500017 ◽

2020 ◽

Vol 20 (01) ◽

pp. 4-8

Author(s):

Sciascia Savino ◽

Radin Massimo ◽

Menegatti Elisa ◽

Barinotti Alice ◽

Sini Federica ◽

...

Keyword(s):

Risk Assessment ◽

Antiphospholipid Syndrome ◽

Immunosorbent Assay ◽

Ovarian Reserve ◽

Antiphospholipid Antibodies ◽

Premenopausal Women ◽

Classification Criteria ◽

Enzyme Linked Immunosorbent Assay ◽

Asymptomatic Carriers ◽

Healthy Donors

Objective: To investigate possible differences in levels of ovarian reserve between antiphospholipid antibodies (aPL) asymptomatic carriers and antiphospholipid syndrome (APS) patients, by measuring the levels of anti-Müllerian hormone (AMH). Methods: We enrolled 69 premenopausal women divided in 2 groups: a) patients with APS, either primary (PAPS) or secondary (SAPS), according to the Sydney classification criteria; b) asymptomatic aPL carriers. Aged-matched premenopausal healthy donors (HDs) were also recruited. Complete aPL testing was performed and AMH levels were measured using enzyme-linked immunosorbent assay. Results: Among the 69 patients included in the study, 22 were diagnosed with PAPS, 13 with SAPS, and 14 patients were asymptomatic aPL carriers. No differences in AMH levels were observed among the three groups [mean AMH: PAPS 3.09 ng/ml ± 1.9 (range 1.02 − 7.1); SAPS 3.1 ng/ml ± 2.2 (range 1.1 − 7.6); aPL carriers 2.2 ng/ml ± 5.4 (range 1 − 6.3)] and between patients/aPL carriers and HDs [mean AMH 2.82 ng/ml ± 2.9 (range 1 − 6.9)]. Any correlation between the global APS score (GAPSS) and AMH levels failed to be found (rho = 0.31; p = 0.073). Conclusion: With the limitations of the current study, as observed in women with APS, we confirm that ovarian reserve, assessed with AMH levels, is not reduced in premenopausal women with isolated aPL positivity. Moreover, when granulating the aPL profile in terms of risk assessment, using the GAPSS, no impact on fertility was observed.

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Antiphospholipid Syndrome: A Review

Haematology Journal of Bangladesh ◽

10.37545/haematoljbd201824 ◽

2018 ◽

Vol 2 (02) ◽

pp. 51-58

Author(s):

Md. Motahar Hossain ◽

Md. Akhter Hossain ◽

Yasmin Rahman ◽

Md. Kamrul Hasan

Keyword(s):

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Arterial Thrombosis ◽

Anticardiolipin Antibodies ◽

Vitamin K Antagonist ◽

Classification Criteria ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Pregnancy Morbidity ◽

Pregnancy And Postpartum

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by venous thromboembolism, arterial thrombosis, and obstetric morbidities in the setting of persistently positive levels of antiphospholipid antibodies. It may be primary or secondary. The latest classification criteria (Sydney 2006) recognize just three tests to define this syndrome- lupus anticoagulant, anticardiolipin antibodies and anti-?2-glycoprotein-1 antibodies. Treatment of thrombotic events involves lifelong anticoagulation with vitamin K antagonist warfarin. Antiphospholipid antibody syndrome (APS) with only pregnancy morbidity is treated with thromboprophylaxis with heparin during pregnancy and postpartum for 6 weeks. In this review we discuss the pathogenesis, diagnosis, treatment and prognosis of the APS.

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