Antiphospholipid antibodies in patients with purported ‘chronic Lyme disease’

Lupus ◽  
2011 ◽  
Vol 20 (13) ◽  
pp. 1372-1377 ◽  
Author(s):  
TP Greco ◽  
AM Conti-Kelly ◽  
TP Greco
Keyword(s):  
Lyme Disease ◽  
Western Blot ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Anticardiolipin Antibodies ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antiphospholipid Antibody ◽  
Chronic Lyme Disease ◽  
Beta 2

Background: Antiphospholipid antibody (aPL) positive patients and patients with purported chronic Lyme disease (‘CLD’) share many clinical features. After identifying significant aPL in sera of several index patients with ‘CLD’, we performed aPL tests on all patients referred inwhom ‘CLD’ was suspected, diagnosed or treated. Methods: All patients with suspected, diagnosed or treated ‘CLD’ and reportedly ‘positive’ Lyme assays were studied. aPL testing included anticardiolipin antibodies (aCL), anti-beta-2-glycoprotein-1 antibodies (anti-β2GP1) and lupus anticoagulant (LAC). Patients were classified into four newly described categories of CLD and data was analyzed. Results: One hundred and six patients were evaluated, of whom 82% had neurologic symptoms and 51% rheumatologic symptoms. Eighty-eight of 106 (83%) patients had positive Lyme serologies (enzyme-linked immunosorbent assay [ELISA] 62/106, 58.4%; western blot [WB] 64/106, 60%), while 18/106 (16.9%) were negative or equivocal. aPL was found in all ‘CLD’ categories. aCL and/or anti-β2GP1 were positive in 85/106 (80%), with aCL present in 69/106 (65%) and anti-β2GP1 present in 69/106 (65%). For all assays, IgM isotypes predominated: WB 55/64 (85%), aCL 63/69 (91%), anti-β2GP1 52/69 (75%), aCL and/or anti-β2GP1 74/85 (87%). Anti-β2GP1 assays occurred in higher titer than aCL: 36/69 (52%) versus 63/69 (91%), p<0.001. Seventeen patients had aPL-related events. Only 12/106 (11.3%) had true post-Lyme syndromes (PLS), category IV, or late Lyme disease (LLD). Most patients had been treated for Lyme: 82/106 (79%). Conclusion: aPL occurs frequently in patients with ‘CLD’. IgM anti-β2GP1, IgM aCL and IgM WB were frequently found. Documented PLS or LLD was uncommon. The role of aPL in patients with ‘CLD’ needs further investigation. Lupus (2011) 20, 1372–1377.

The role of antiphospholipid antibodies in reproductive failure

1997 ◽  
Vol 6 (3) ◽  
pp. 133-143
Author(s):  
D Ware Branch ◽  
Harry H Hatasaka
Keyword(s):  
Pregnancy Outcome ◽  
Clinical Features ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Fetal Loss ◽  
Placental Insufficiency ◽  
Antiphospholipid Antibody ◽  
The Relationship

The relationship between antiphospholipid antibodies and the clinical features of placental insufficiency, pre-eclampsia, and fetal loss has emerged as one of the most exciting new observations in obstetrics in the last 15 years. Antiphospholipid syndrome is the only convincing ‘immunologic’ disturbance of pregnancy affecting the fetus other than anti-erythrocyte or antiplatelet alloimmunization disorders, and it is now routine to test patients with fetal loss for the two best characterized antiphospholipid antibodies, lupus anticoagulant and anticardiolipin. Although there is no proven mechanism for fetal loss, treatment of antiphospholipid antibody-positive mothers during pregnancy with heparin improves pregnancy outcome.

Is It Time To Reconfigure Lupus Anticoagulant Panels?.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2648-2648
Author(s):  
Zella Rose Zeigler ◽  
Andrea L. Cortese Hassett
Keyword(s):  
Risk Assessment ◽  
Venous Thromboembolism ◽  
Lupus Anticoagulant ◽  
Fetal Loss ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Clinical Events ◽  
Beta 2 ◽  
Record Review ◽  
Positive Results

Abstract Traditional lupus anticoagulant (LAC) panels are designed to test the presence/absence of antiphospholipid antibodies (APA). These usually include testing for a LAC with clot based assays (dRVV, Hex PL, aPTT) or with the tissue thromboplastin inhibition assay (TTI) and ELISA assays for anticardiolipin antibodies (ACA). It is now recognized that antibodies to a phospholipid binding protein, beta-2-GPI are important in the autoimmune form of the antiphospholipid syndrome (aPls). Moreover, some patients (pts.) may only be positive in this latter testing and have what is termed sero-negative aPls. The present study is a retrospective medical record review methodology to analyze the results of APA tests in 258 consecutive pts. referred to the PI at the Hemostasis & Thrombosis Clinic at the Institute For Transfusion Medicine. Inclusion criteria were any pt. who had a lupus panel and anti-beta-2-GPI (IgG, IgM and IgA) testing performed. Exclusion criteria were any pts. who did not have this testing or pts. with positive results which were not repeated > 2 months later. The cohort consisted of 258 pts (69M:189F) with a median age of 48 (range=13–85). Of these pts., 35 (13%) were referred for risk assessment, 133 (52%) for arterial or venous thrombosis, 62 (24%) for neurologic reasons, and 27 (11%) for other reasons. Patients on no anticoagulation (OAC) were considered to be LAC+, if any of the clot based assays was repeatedly positive, did not correct on a mix, and shortened with the additon of phospholipid. OAC pts. with positive ELISA assays were considered to have a LAC if the dRVV was positive on a mixing study and/or if the Hex PL test was positive. OAC pts. with only evidence for a LAC, were taken off OAC and then studied. ELISA assays were considered to be positive if low titer positive or higher, e.g. ≥ 3 STD above the mean. Positive results were found in 59/258 (22.8%) of these pts. The antibody results are listed in the table below in the pts. referred for risk assessment and in the pts. referred with events. The results are listed in categories of APA positivity. Antiphospholipid Antibody Results In Pts With Risk Assessment and Pts With Clinical Events Pt. Group LAC+beta-2-GPI LAC Only Beta-2-GPI Only ACA Only Total NOTE: 36% of the positive pts. would be missed by the traditional LAC panel. Risk Assessment 0/35 (0%) 0/35 (0%) 1/35 (3%) 0/35 (0%) 1/35 (3%) Pts. With Events 26/233 (11%) 12/233 (5%) 20/233 (9%) 0/35 (0%) 58/233 (25%) Total Positive Results 26/59 (44%) 12/59 (20%) 21/59 (36%) 0 59 These results indicate that one-third of the pts. with phospholipid antibodies were sero-negative, e.g. negative in the presently constructed panels but positive for anti-beta-2-GPI antibodies. Skeptism exists about the meaning of isolated anti-beta-2GPI positivity. Of the pts. with only + beta-2-GPI antibodies, one male was asymptomatic (5%). The remaining pts. in this group were females. Ten/twenty-one (48%) of the pts. with isolated beta-2-GPI positivity were referred for neurologic reasons. These consisted of TIA’s in 6, complex migraines with TIA’s and acral cyanosis (1), recurrent fetal loss and TIA’s in 3. Eight pts. (38%) had recurrent venous thromboembolism and 2 (9%) had both arterial and venous thromboembolism. We suggest that it may be time to consider constructing LAC screening panels containing tests for both LAC and anti-beta-2-GPI antibodies (all three isotypes) as sero-negative APls appear to be fairly common in females referred for thrombophilic testing.

High-Dose Intravenous Immunoglobulin Treatment of a Pregnant Patient with an Antiphospholipid Syndrome: Immunological Changes Associated with a Successful Outcome

1994 ◽  
Vol 71 (06) ◽  
pp. 741-747 ◽  
Author(s):  
J Arnout ◽  
B Spitz ◽  
C Wittevrongel ◽  
M Vanrusselt ◽  
A Van Assche ◽  
...  
Keyword(s):  
Platelet Count ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Interaction Analysis ◽  
High Titer ◽  
Anticardiolipin Antibodies ◽  
Successful Outcome ◽  
High Dose ◽  
Slight Reduction

SummaryA patient with a history of habitual abortion, deep venous thrombosis, thrombocytopenia, high titer IgG anticardiolipin antibodies and a clearly positive lupus anticoagulant, was treated during her seventh pregnancy with high-dose intravenous immunoglobulins (IVIg) from the third month onwards. Every month, a daily infusion of 400 mg immunoglobulins per kg body weight was given during five consecutive days. The patient’s pregnancy ended preterm with a live birth, delivered by caesarian section because of a placental abruption. The 1070 g (P20-P25) weighing girl was in good health, apart from a bradycardia, due to dysfunction of the atrioventricular conduction.Each treatment with IVIg resulted in a slight reduction of both anticardiolipin antibodies and lupus anticoagulant levels and in an increase in platelet count. During the six-month observation period, a gradual decline in antiphospholipid antibodies and an increase in platelet count was found. The potential role of anti-idiotypic antibodies, present in the IVIg used for treatment, was studied. In vitro, IVIg were able to reduce the binding of the patient’s anticardiolipin antibodies to cardiolipin coated microtiter plates. The presence of anti-idiotypic antibodies in IVIg was further documented by affinity chromatography and by realtime biospecific interaction analysis (BIA) on a BIA-core instrument. Affinity purified anticardiolipin antibodies were retarded on a column of insolubilized IVIg and a weak interaction was found between IVIg and affinity purified patient antiphospholipid antibodies, coupled to the BIA-core biosensor. In addition, the same technology revealed increased levels of anti-antiphospholipid antibodies in the patient’s plasma following IVIg therapy. The partial and transient reduction of anti-phospholipid antibody levels observed immediately following each treatment course seems compatible with low affinity complexation of idiotype-antiidiotypes, resulting in an accelerated clearance of the autoantibodies. Despite the low affinity for the patient’s idiotypes, the beneficial long term effects observed could be related to an immune regulatory role of these anti-idiotypic antibodies on the synthesis of antiphospholipid antibodies.

Antiphospholipid Antibody Syndrome

2011 ◽  
Vol 135 (9) ◽  
pp. 1092-1096 ◽  
Author(s):  
Nikhil A Sangle ◽  
Kristi J Smock
Keyword(s):  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Protein Complexes ◽  
Anticardiolipin Antibodies ◽  
Clinical Aspects ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Laboratory Results

Antiphospholipid antibodies are directed against phospholipid-protein complexes and include lupus anticoagulant, anticardiolipin antibodies, and anti–beta-2 glycoprotein I antibodies. Antiphospholipid antibody syndrome is a common cause of acquired thrombophilia and is characterized by venous or arterial thromboembolism or pregnancy morbidity and the presence of antiphospholipid antibodies. Antibodies should be demonstrable on at least 2 occasions separated by 12 weeks. Heterogeneity of the autoantibodies and absence of gold standard assays makes interpretation of laboratory results a challenge for both laboratorians and clinicians. This review discusses the key laboratory and clinical aspects of antiphospholipid antibody syndrome. Particular focus is given to lupus anticoagulant detection, in view of recently updated laboratory guidelines.

THE PREVELANCE OF ANTIPHOSPHOLIPID ANTIBODIES, BY ELISA TECHNIQUE, IN PATIENTS WITH THE LUPUS ANTICOAGULANT

1987 ◽  
Author(s):  
W Brien ◽  
G Denome ◽  
B O’Keefe
Keyword(s):  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Specific Binding ◽  
Normal Population ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Increased Risk ◽  
Elisa Technique ◽  
Tissue Thromboplastin ◽  
Positive Results

Patients with the Lupus Anticoagulant and/or anticardiolipin antibodies have been reported to be at increased risk of thrombosis and miscarriages. It has been proposed that the lupus anticoagulant is an antiphospholipid antibody.We evaluated 16 patients with the lupus anticoagulant for the presence of antiphospholipid antibodies. The lupus anticoagulant was documented by the presence of an abnormal APTT, abnormal mixing studies, positive tissue thromboplastin inhibition test and positive platelet neutralization test.Plasma from each patient was assessed for the presence of anticardiolipin, antiphosphatidylserine and antiphosphatidyl-glycerol antibodies by ELISAtechniques. As a control, a neutral phospholipid phosphatidylethanolamine was used. A positive result was established when a delta value of lipid minus control was greater than 3SD compared to a normal population (20 pt.).Using three different patient dilutions, positive results were obtained in 10/16 pt. for anticardiolipin, 11/16 pt. for antiphosphatidylserine and 5/16 pt. for antiphosphatidyl-glycerol antibodies. Three patients were negative for all lipids. If a neutral phospholipid was not used and a delta volume not obtained, 15/16 patients would have had positive results.Our results suggest 1) Not all patients with the Lupus Anticoagulant have antiphosphilipid antibodies by ELISA technique. In evaluating patients with thrombosis and/or miscarriages, both tests should be performed.2) Anticardiolipin antibodies are not present in all patients and with a panel of other negatively charged phospholipids more positive results are obtained. 3) A neutral lipid should be used as a control for non-specific binding of antibody and delta values obtained to see if the results obtained is truly against the negatively charged lipid.

scholarly journals Thromboelastography in the Characterization of Coagulation Status in Antiphospholipid Syndrome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4983-4983 ◽  
Author(s):  
Natalie H Wallace ◽  
Anne Dumont ◽  
Adrienne Burns ◽  
Tormey A Christopher ◽  
Henry M Rinder ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Conflicts Of Interest ◽  
Trauma Surgery ◽  
Anticardiolipin Antibodies ◽  
Bleeding Complications ◽  
Blood Collection ◽  
Transfusion Therapy ◽  
Beta 2

Abstract INTRODUCTION/ BACKGROUND Antiphospholipid syndrome (APS) is an immunologic disorder characterized by thrombotic or obstetrical complications and persistent positivity of anticardiolipin antibodies, lupus anticoagulant, or beta-2 glycoprotein-1 antibodies. Bleeding complications in APS may sometimes occur, in the form of adrenal hemorrhage, immune thrombocytopenia (ITP), or, rarely, the lupus anticoagulant-hypoprothrombinemia syndrome (LAHS). Traditional laboratory markers of coagulation are not reliable in evaluating thrombotic or hemorrhagic risk in APS due to baseline prolongation of the prothrombin time (PT) and/or partial thromboplastin time (PTT). Thromboelastography (TEG) is a global assay of hemostasis that has been utilized in trauma surgery, emergency medicine, and chronic liver disease to identify specific coagulation defects and guide transfusion therapy. We sought to explore the role of TEG in evaluation of APS. METHODS TEG was performed on whole blood obtained from 10 patients with APS (n = 6), catastrophic APS (CAPS; n = 3), or antiphospholipid antibodies without thrombosis (n = 1). Chronic aspirin (ASA) was used as monotherapy in 2 patients; 8 were on either warfarin or enoxaparin (some in combination with ASA). Immunomodulatory treatments included hydroxychloroquine, mycophenolate, azathioprine, monthly IVIG, rituximab, or eculizumab. Prior to blood collection, patients were instructed to hold ASA for 7 days, warfarin for 5 days, or enoxaparin for 2 days, as appropriate. For patients on enoxaparin in whom cessation of anticoagulation was not feasible, heparinase was added to samples for TEG measurements. The following data was compiled for each patient: baseline PTT; lupus anticoagulant, anticardiolipin IgG and IgM, and beta-2 glycoprotein-1 IgG and IgM titers; and thrombotic, hemorrhagic, and obstetrical events. RESULTS Baseline PTT was prolonged in most patients. TEG values were within or near the normal range in almost all cases, with no consistent differences among patients with thrombotic or obstetrical APS, CAPS, or antiphospholipid antibodies without thrombosis. R time (a measure of clot initiation) was mildly prolonged in 3 cases and minimally reduced in 1. One patient with lupus, ITP, arterial and venous thrombosis, and multiple miscarriages showed minor prolongation of K time (a measure of time to maximum clot amplification) and a slight decrease in ▢ angle (a measure of thrombin burst). LY30 (a measure of fibrinolysis) was normal in all cases. One patient with LAHS and severe hemorrhagic complications had marked prolongation of R and K times and marked reduction of ▢ angle and MA (a measure of clot tensile strength), consistent with a strong bleeding phenotype. CONCLUSIONS Despite abnormal baseline coagulation studies, APS patients generally do not demonstrate a major bleeding propensity in global hemostasis assays. TEG may have potential utility in identifying APS patients with bleeding due to LAHS. Disclosures No relevant conflicts of interest to declare.

scholarly journals Antiphospholipid Antibodies in Sickle Cell Disease: A Systematic Review and Exploratory Meta-Analysis

2021 ◽  
Vol 27 ◽  
pp. 107602962110029
Author(s):  
Mira Merashli ◽  
Alessia Arcaro ◽  
Maria Graf ◽  
Matilde Caruso ◽  
Paul R. J. Ames ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Antiphospholipid Antibodies ◽  
Meta Analysis ◽  
Age Groups ◽  
Anticardiolipin Antibodies ◽  
Cell Disease ◽  
Pooled Prevalence ◽  
The Relationship

The relationship between antiphospholipid antibodies (aPL) and sickle cell disease (SCD) has never been systematically addressed. Our aim was to evaluate potential links between SCD and aPL in all age groups. EMBASE/PubMed was screened from inception to May 2020 and Peto odds ratios for rare events were calculated. The pooled prevalence (PP) of IgG anticardiolipin antibodies (aCL) was higher in individuals with SCD than in controls (27.9% vs 8.7%, P < 0.0001), that of IgM aCL was similar in the two groups (2.9% vs 2.7%); only individuals with SCD were positive for lupus anticoagulant (LA) (7.7% vs 0%, P < 0.0001). The PP of leg ulcers was similar between aPL positive and negative individuals (44% vs 53%) and between patients in acute crisis and stable patients (5.6% vs 7.3%). Reporting of aPL as a binary outcome and not as a titer precluded further interpretation. The results indicate that a prospective case-control study with serial measurements of a panel of aPL in SCD patients might be warranted, in order to understand further the possible pathogenic role of aPL in SCD.

Variability in Anticardiolipin Antibody Detection: Role of Nonspecific IgG Binding and Different Microtiter Plates

2007 ◽  
Vol 13 (4) ◽  
pp. 404-409 ◽  
Author(s):  
Nelly M. Pellegrino ◽  
Domenico Caccavo
Keyword(s):  
Specific Binding ◽  
Anticardiolipin Antibody ◽  
Anticardiolipin Antibodies ◽  
Antibody Detection ◽  
Categorical Variables ◽  
Enzyme Linked Immunosorbent Assay ◽  
Microtiter Plates ◽  
Igg Binding ◽  
Coefficient Of Concordance

There are many studies that are available on the Internet that attempt to standardize the assay for anticardiolipin antibody evaluation because of the variability of results. The aim of this study was to evaluate simultaneously the role of different microplates and the importance of sample nonspecific binding in determining different results in anticardiolipin antibody detection. Sera from 8 patients with raised levels of IgG anticardiolipin antibodies and 10 control sera were assayed by enzyme-linked immunosorbent assay in the presence (specific binding) or in the absence of cardiolipin (sample blank) with four different microplates, that is, NUNC PolySorp, FALCON ProBIND, Greiner 655061 (high binding), and Greiner 655001 (medium binding). Results were expressed as optical densities or net-optical densities (following sample blank subtraction) as well as international IgG anticardiolipin units (GPL) or net-GPL. A wide interplate variability of optical densities was found. When results were expressed as GPL, significant differences were only found between Greiner 655061, FALCON ProBIND, and NUNC PolySorp ( P < .05 and P < .001, respectively) whereas differences were not statistically significant if interplate variability was analyzed as net-GPL. Results expressed as categorical variables (ie, positive/negative, according to a GPL cut-off and net-GPL cut-off, obtained with sera from 100 apparently healthy blood donors) showed a good or excellent Cohen's κ coefficient of concordance among plates when positivity was evaluated on net-GPL. Our data strongly suggest that quantification and subtraction of sample blank may improve both interlaboratory agreement and reliability of anticardiolipin assay and minimize false-positive results.

IgA Anticardiolipin Antibodies – Relation with other Antiphospholipid Antibodies and Clinical Significance

1998 ◽  
Vol 79 (02) ◽  
pp. 282-285 ◽  
Author(s):  
Josep Ordi-Ros ◽  
Francesc Monegal-Ferran ◽  
Nuria Martinez ◽  
Fina Cortes-Hernandez ◽  
Miquel Vilardell-Tarres ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Fetal Loss ◽  
Cross Sectional Study ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Serum Samples ◽  
Cross Sectional ◽  
Vein Thrombosis

SummaryObjective: To evaluate the usefulness of IgA antiphospholipid antibodies as markers of thrombosis and/or antiphospholipid antibody syndrome. Patients and Methods: A cross-sectional study design in a tertiary, university-based, autoimmune reference hospital. Seven-hundred ninety-five patients classified into five different groups – autoimmune diseases (255), deep vein thrombosis (153), transitory ischemic attacks (108), obstetric complications (196), infectious diseases (83) and controls (81) – were tested for IgA, IgG and IgM aPL, and lupus anticoagulant. Plasma and serum samples were drawn for detection of aPL using an internationally standardized ELISA method and LA was carried out using coagulometric assays. Results: True IgA aPL were found only in two patients with systemic lupus erythematosus; these patients were also positive to IgG aPL. Conclusion: The incidence of true positivity to IgA anticardiolipin antibodies is extremely low. Their determination was not helpful in diagnosing the antiphospholipid syndrome or in explaining thrombotic events or aPL related manifestations – fetal loss – in the groups studied.

scholarly journals Hemostasis system and immunomorphologic state of placenta under presence of antiphospholipid antibodies in plasma with consideration of their class and pregnancy outcome

2004 ◽  
Vol 53 (1) ◽  
pp. 22-26
Author(s):  
N. G. Kosheleva ◽  
L. В. Zubzhitskaia ◽  
О. N. Arzhanova ◽  
О. V. Tyshkevich ◽  
Y. Gromyko ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Recurrent Miscarriage ◽  
Anticardiolipin Antibodies ◽  
Research Groups ◽  
Hemostasis System ◽  
Autoimmune Antibodies ◽  
Glycoprotein I ◽  
Tissue Damages

The present study was undertaken to investigate hemostasis system of 197 women with recurrent miscarriage: Analysis placentas by immunomorphology are studied of 41 women and of 52 women with autoimmune antibodies to 2-glycoprotein-I (2-GPI) in placenta. There was exposed hyperactivation platelets blood of all women with antiphospholipid antibodies irrespective of groups with significantly was increased at the beginning of pregnancy and progressed with growing gestation. As result of investigation it is determined certain connection between outcome of pregnancy and activation degree platelets blood in vasculars. Was found absence influence anticardiolipin antibodies (aCL) on plasmocoagulative link hemostasis. The circulation of lupus anticoagulant (LA) was accompanied indication of hypercoagulation. In all research groups was determined significant oppression of fibrinolisis. Analysis placentas by immunomorphology was determined significantly tissue damages with LA and 2-GPI-dependent aCL.

Sign in / Sign up

Export Citation Format

Share Document