Clinical Manifestations of Patients with Highly Elevated Anticardiolipin Antibodies

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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Possible Association of Etanercept, Venous Thrombosis, and Induction of Antiphospholipid Syndrome

Case Reports in Rheumatology ◽

10.1155/2014/801072 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Shanti Virupannavar ◽

Anthony Brandau ◽

Carla Guggenheim ◽

Heather Laird-Fick

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Manifestations ◽

Case Series ◽

Anticardiolipin Antibodies ◽

Limited Data ◽

Autoantibody Production ◽

Glycoprotein I ◽

Criteria For Diagnosis ◽

Dsdna Antibodies ◽

Necrosis Factor

Tumor necrosis factorα(TNFα) inhibitors are commonly used for treatment of aggressive rheumatoid arthritis and other rheumatic diseases. Etanercept is one of the medications approved for treatment of rheumatoid arthritis. Though many studies have documented the safety and efficacy of these medications, evidence for adverse effects is emerging including cancer, infections, and cardiovascular disease. There have been studies showing that these medications induce autoantibody production, including antinuclear antibodies and anti-dsDNA antibodies. Limited data exists, however, regarding induction of antiphospholipid antibodies (APLs) by TNFαinhibitors, including anticardiolipin antibodies (ACLs), lupus anticoagulant (LAC), and anti-β2-glycoprotein I (anti-β2GPI), or an association between antibody development and clinical manifestations. In this case series, we describe five patients who developed venous thromboembolism (VTE) and APLs while receiving etanercept therapy. All five of our patients met the criteria for diagnosis of APS after receiving etanercept. Our case series supports the association between etanercept, APLs, and VTE. We believe that testing for APLs prior to initiation of anti-TNF therapy is reasonable, given this relationship and the risks associated with VTE.

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Management of antiphospholipid syndrome

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-213846 ◽

2018 ◽

Vol 78 (2) ◽

pp. 155-161 ◽

Cited By ~ 32

Author(s):

Imad Uthman ◽

Mohammad Hassan A Noureldine ◽

Guillermo Ruiz-Irastorza ◽

Munther Khamashta

Keyword(s):

Antiphospholipid Syndrome ◽

Recurrent Pregnancy Loss ◽

De Novo ◽

Clinical Manifestations ◽

Transverse Myelitis ◽

Anticardiolipin Antibodies ◽

New Drugs ◽

Ischaemic Attack ◽

Cardiac Valve Disease ◽

Almost All

Antiphospholipid syndrome, also known as ‘Hughes Syndrome’, is an autoimmune disease characterised by a set of clinical manifestations, almost all of which are direct or indirect sequelae of a hypercoagulable state involving the venous, and to a lesser extent the arterial vasculature. The incidence and prevalence of antiphospholipid syndrome are estimated at approximately 5 de novo cases per 100 000 per year and 40–50 cases per 100 000 individuals, respectively. The clinical spectrum of antiphospholipid syndrome involves haematological (thrombocytopaenia, venous thrombosis), obstetrical (recurrent pregnancy loss), neurological (stroke, transient ischaemic attack, migraine, seizures, cognitive dysfunction, chorea, transverse myelitis, multiple sclerosis), cardiovascular (cardiac valve disease), dermatological (livedo reticularis and racemosa, skin ulceration and necrosis), renal (glomerulonephritis, renal thrombotic microangiopathy) and orthopaedic (avascular necrosis of bones, non-traumatic fractures) manifestations, among others. In addition to the classical antiphospholipid antibodies, namely anticardiolipin antibodies and lupus anticoagulant, new autoantibodies and antibody complexes of different immunoglobulin subtypes (IgA, IgG, IgM) are now recognised as significant contributors to the pathogenesis of antiphospholipid syndrome. Anticoagulation remains the cornerstone in the management of antiphospholipid syndrome; nevertheless, new drugs and therapeutic strategies are being tested, and some have been found effective for the primary and secondary thromboprophylaxis in antiphospholipid syndrome.

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ANTIPHOSPHOLIPID ANTIBODIES IN PAEDIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS, JUVENILE CHRONIC ARTHRITIS AND OVERLAP SYNDROMES: SLE PATIENTS WITH BOTH LUPUS ANTICOAGULANT AND HIGH-TITRE ANTICARDIOLIPIN ANTIBODIES ARE AT RISK FOR CLINICAL MANIFESTATIONS RELATED TO THE ANTIPHOSPHOLIPID SYNDROME

Rheumatology ◽

10.1093/rheumatology/34.9.873 ◽

1995 ◽

Vol 34 (9) ◽

pp. 873-881 ◽

Cited By ~ 46

Author(s):

M. GATTORNO ◽

A. BUONCOMPAGNI ◽

A. C. MOLINARI ◽

G. C. BARBANO ◽

G. MORREALE ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Clinical Manifestations ◽

Juvenile Chronic Arthritis ◽

High Titre ◽

Chronic Arthritis ◽

Anticardiolipin Antibodies ◽

Systemic Lupus ◽

Overlap Syndromes

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Antigenic Specificities of Antiphospholipid Autoantibodies: Implications for Clinical Laboratory Testing and Diagnosis of the Antiphospholipid Syndrome

Lupus ◽

10.1177/096120339600500518 ◽

1996 ◽

Vol 5 (5) ◽

pp. 425-430 ◽

Cited By ~ 26

Author(s):

RAS Roubey

Keyword(s):

Clinical Studies ◽

Lupus Anticoagulant ◽

Laboratory Testing ◽

Clinical Laboratory ◽

Clinical Manifestations ◽

Anticardiolipin Antibodies ◽

Protein Antigens ◽

Advantages And Disadvantages ◽

Glycoprotein I ◽

Clinical Laboratory Testing

Most autoantibodies associated with the antiphospholipid (aPL) syndrome and detected in standard anticardiolipin and/or lupus anticoagulant assays are directed against β2-glycoprotein I (β2-GPI) or prothrombin. Recent data indicate that these antibodies can also be detected in immunoassays utilizing purified protein antigens, in the absence of phospholipids. Initial clinical studies suggest that positivity in anti-β2-GPI immunoassays is more closely associated with the clinical manifestations of the aPL syndrome than is positivity in conventional anticardiolipin ELISAs. Anti-β2-GPI immunoassays may detect certain anti-β2-GPI antibodies that are not detectable in conventional anticardiolipin assays, but do not detect authentic (β2-GPI-independent) anticardiolipin antibodies. It appears that the former, but not the latter, antibodies are associated with the clinical manifestations of the aPL syndrome. The potential advantages and disadvantages of these new immunoassays in the clinical evaluation of the aPL syndrome are discussed.

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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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Gastrointestinal symptoms as the first manifestation of antiphospholipid syndrome

BMC Gastroenterology ◽

10.1186/s12876-021-01736-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiaojuan Zou ◽

Zhongqi Fan ◽

Ling Zhao ◽

Weiling Xu ◽

Jin Zhang ◽

...

Keyword(s):

Abdominal Pain ◽

Antiphospholipid Syndrome ◽

Clinical Manifestation ◽

High Titer ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Recurrent Abdominal Pain ◽

Anticardiolipin Antibodies ◽

Glycoprotein I ◽

Gastrointestinal Lesions

Abstract Background Antiphospholipid syndrome (APS) is an acquired pre-thrombotic autoimmune condition, which produces autoantibodies called antiphospholipid antibodies (APL) against phospholipid-binding plasma proteins. The diagnosis of APS requires at least one of Sapporo standard clinical manifestations and one laboratory criteria (persistently medium/high titer anticardiolipin antibodies, and/or medium/high titer anti-β2-glycoprotein I antibodies, and/or a positive lupus anticoagulant test). Gastrointestinal lesions are rarely reported in APS patients. APS cases with recurrent abdominal pain as the first clinical manifestation are even rarer. Case presentation This report describes an APS case with recurrent abdominal pain as the first clinical manifestation of antiphospholipid syndrome. The patient has a history of two miscarriages. Computed tomography of the abdomen confirmed mesenteric thrombosis and intestinal obstruction while laboratory tests for serum antiphospholipid and anti-β2-glycoprotein I antibodies were positive. This led to the diagnosis of APS. Conclusions This paper provides useful information on gastrointestinal manifestations and APS, also including a brief literature review about possible gastrointestinal symptoms of APS.

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A subgroup of multiple sclerosis patients with anticardiolipin antibodies and unusual clinical manifestations: Do they represent a new nosological entity?

Annals of Neurology ◽

10.1002/ana.410440408 ◽

1998 ◽

Vol 44 (4) ◽

pp. 629-634 ◽

Cited By ~ 83

Author(s):

Dimitrios Karussis ◽

Ronen R. Leker ◽

Avi Ashekenazi ◽

Oded Abramsky

Keyword(s):

Multiple Sclerosis ◽

Clinical Manifestations ◽

Anticardiolipin Antibodies ◽

Nosological Entity ◽

Multiple Sclerosis Patients

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Spectrum of juvenile antiphospholipid syndrome in two siblings: Case reports and review of literature

10.21203/rs.3.rs-80942/v1 ◽

2020 ◽

Author(s):

Basil Fathalla ◽

Khulood W Khawaja ◽

Samina Afzal

Keyword(s):

Lupus Erythematosus ◽

Case Reports ◽

Clinical Manifestations ◽

Human Leukocyte ◽

Anticardiolipin Antibodies ◽

Leukocyte Antigen ◽

Hla Dr ◽

Whole Exome ◽

High Index Of Suspicion ◽

Diagnosis Criteria

Abstract BackgroundAntiphospholipid syndrome (APS) in children together with familial APS is extremely rare, differs from adult APS, and has no validated diagnosis criteria. Use of adult APS classification criteria for the diagnosis of pediatric APS may result in missed or delayed diagnoses in children as non-thrombotic clinical manifestations may precede thrombotic manifestations for prolonged periods. We report rare triple positivity of antiphospholipid antibodies (aPL) in two siblings presenting with a variable spectrum of juvenile primary APS manifestations and a review of literature.Case reportTwo siblings presented with a variable spectrum of juvenile primary APS manifestations at 13 years of age. Both patients had high triple aPL positivity on multiple occasions at least 12 weeks apart including positive anticardiolipin antibodies, anti-β2-glycoprotein 1 antibodies, and lupus anticoagulant tests. The older brother, currently 16 years of age, had a spectrum of clinical manifestations during his disease course including cutaneous thrombotic microangiopathy, arthralgia, and pulmonary embolism. His sister is currently 14 years of age and she presented with non-thrombotic clinical manifestations, was immediately screened, and diagnosed with triple aPL positivity at 13 years of age. A seven years old healthy brother was screened once and had negative aPL test results. Systemic investigations including work up for systemic lupus erythematosus in both symptomatic siblings were unremarkable and whole exome sequencing was inconclusive. Human leukocyte antigen (HLA) screen revealed positive HLA-DR4 and DQB1*0302 tests for both symptomatic siblings but not for the healthy brother.ConclusionWe conclude that non-thrombotic clinical manifestations may precede thrombotic manifestations in primary APS in children, and this may cause significant delays in the diagnosis. Familial primary APS is very rare but may occur and high index of suspicion is required to test relatives with subtle clinical manifestations. Our case reports further support possible HLA-DR and -DQ associations with aPL antibodies.

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