Lupus Anticoagulant In Patients Research Articles

Myocardial fibrosis associates with lupus anticoagulant in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that carries increased risk of cardiovascular disease; however, the underlying pathophysiological mechanisms remain poorly understood. We aimed to investigate the prevalence and degree of myocardial fibrosis in SLE patients and associated disease characteristics. Forty-nine SLE patients (89% female, mean age 52 ± 13 years, median disease duration 19 (11–25) years) and 79 sex-and age-matched healthy controls were included. CMR with T1 mapping was performed on SLE patients and healthy controls. Fifty-one SLE patients received gadolinium contrast for the evaluation of late gadolinium enhancement (LGE) and extra cellular volume (ECV). Multiple linear regression analyses were performed to investigate the association between markers of myocardial fibrosis on CMR (LGE, T1, ECV) and SLE-related variables [clinical disease activity, lupus nephritis, chronic kidney disease, anti-cardiolipin and/or anti-beta-2 glycoprotein I antibodies, and lupus anticoagulant (LAC)] with adjustment for traditional risk factors. T1 values were elevated in SLE patients compared to healthy controls (1031 ± 36 ms vs. 1019 ± 25 ms, p = 0.01). LGE was present in 20% of SLE patients who received gadolinium contrast. On multivariable analysis, LAC was associated with LGE in SLE patients (β = 3.87, p = 0.02). Neither T1 nor ECV associated with SLE disease characteristics; however, there was a trend towards an association between LAC and T1 (β = 16.9, p = 0.08). SLE patients displayed signs of myocardial fibrosis on CMR that were associated with the presence of LAC. These findings support the pathophysiological understanding of LAC as a mediator of microvascular and subsequent myocardial dysfunction.Graphical abstract

Prevalence and Impact of Lupus Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation.

Monitoring of blood coagulation is essential in ECMO patients. We investigated the prevalence of lupus anticoagulant (LA) and its association with coagulation testing and hemostaseologic complications in patients treated with ECMO. This is a retrospective analysis including adult patients who received ECMO at a medical intensive care unit at the Medical University of Vienna. The primary outcome was the prevalence of LA. Secondary outcomes included conditions associated with LA positivity, rates of bleeding and thromboembolic events, as well as the proportions of aPTT and antiXa measurements within the target range. Between 2013 and 2021 193 patients received ECMO, in 62 (32%) of whom LA diagnostics were performed. Twenty-two (35%) patients tested positive. LA positive patients had more frequently received VV ECMO (77.3% vs 34.3%; p = 0.002), were more frequently diagnosed with viral respiratory infections (SARS-CoV2: 45.5% vs 20%; p = 0.041, influenza virus: 22.7% vs 0%; p = 0.003), had a longer ECMO treatment duration (25 vs 10 days; p = 0.011) and a longer ICU stay (48 vs 25 days; p = 0.022), but similar rates of bleeding and thromboembolic events.

Progress of lupus anticoagulant detection in venous thromboembolism

Lupus anticoagulant is one of the risk factors for venous thromboembolism, and the detection of lupus anticoagulant in patients with venous thromboembolism is important for the choice of treatment options and prognosis of treatment. There was no relevant literature to analyze and summarize the application progress of lupus anticoagulant detection in venous thromboembolism. In order to deepen the understanding of such patients, and help clinicians to conduct reasonable diagnosis, treatment and management of these patients, we reviewed the relevant epidemiology, test precautions, and the value of test results in venous thromboembolism and related treatments.

Lupus anticoagulant in patients with systemic lupus erythematosus is associated with lower E/A ratio and progressive left ventricular dilatation: a five-year follow-up study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Copenhagen University Hospital Background Systemic lupus erythematosus (SLE) is an autoimmune disease with increased risk of cardiovascular complications such as coronary artery disease, myocarditis, pericarditis and valvular dysfunction. The pathophysiological mechanisms are poorly understood and clinical, biochemical and/or imaging markers to identify high risk patients are warranted. Purpose We aimed to identify SLE-characteristics that are associated with progressive cardiac dysfunction during a five-year follow-up period in patients with SLE. Methods A total of 147 patients with SLE were included from 2013 to 2014. All patients underwent standard echocardiography at baseline as well as a collection of blood samples, including a selection of biomarkers. Patients were invited to a five-year follow-up with a total of 108 patients (90 % female, mean age 46 ± 13 years, median disease duration of 14 (7-21) years) completing a full echocardiographic, laboratory, and clinical examination. Multivariate regression analyses with eight independent baseline variables of interest (age, sex, disease activity (SLEDAI-2K), lupus nephritis, ischemic heart disease (IHD), antiphospholipid antibodies (IgM and IgG), and lupus anticoagulant(LAC)) were performed as for the association with baseline echocardiographic parameters as well as for changes during follow-up. Only echocardiographic measurements that changed significantly (p < 0.01) during follow-up were selected for the regression analyses. Left ventricular end-diastolic volume index (LVEDVI) and E/A ratio were log-transformed at baseline in the regression analyses due to non-normality. Results During a five-year follow-up period, LVEDVI increased from 43.5 ± 13.9 to 52.5 ± 15.7 ml/m2 (p <0.001), and left ventricular diastolic measures declined (E/A ratio 1.4 ± 0.5 vs. 1.3 ± 0.5, p = 0.002; e’ velocity 12.8 ± 3.8 vs. 12.0 ± 3.7 ms, p = 0.02; mitral valve deceleration time 227.9 vs. 200.8 ms, p < 0.001), except for E/e’ (7.5 ± 3.8 vs. 6.8 ± 3.4, p = 0.02). Left ventricular ejection fraction remained stationary (59.5 ± 6.8 vs. 59.6 ± 6.4 %, p = 0.81). In multivariate regression analyses, presence of LAC was significantly associated with progressive left ventricular dilation during the follow-up period (p = 0.003) but not with higher baseline levels (p = 0.64) (Fig. A1 & A2). LAC was associated with lower E/A ratio at baseline (p = 0.005) but did not predict a decrease of E/A ratio during follow-up (p = 0.24) (Fig. B1 & B2). IHD was associated with higher LVEDVI at baseline (p = 0.004), but not with further progression of dilation (p = 0.07). Conclusion Presence of LAC was associated with lower E/A ratio at baseline as well as progressive left ventricular dilation during a five-year follow-up period. Hence, LAC might be a predictor of progressive cardiac dysfunction in patients with SLE. LAC is known to have implications for the microvascular circulation, but the clinical significance of the present findings is yet to be elucidated. Abstract Figure A Abstract Figure B

Warfarin monitoring and interference by lupus anticoagulant in patients with antiphospholipid syndrome

IntroductionPatients with antiphospholipid syndrome (APS) receive vitamin K antagonists, which warrants international normalized ratio (INR) monitoring. Research has indicated that presence of lupus anticoagulant (LA) can interfere with INR results obtained by point-of-care testing (POCT) devices. We aimed to investigate whether a systematic difference exists between POCT-INR and plasma-INR in patients with APS. Materials and methodsWe compared 291 paired POCT- and plasma-INR results from 52 LA-positive APS patients receiving warfarin with each patient having a minimum of three paired measurements of paired POCT-INR (CoaguChek, Roche Diagnostics) and plasma-INR. Agreement limits were considered satisfactory if differences were within ±0.4 INR for plasma-INR < 2.0, within ±20% for plasma-INR 2.0 to 3.5, within ±20% for plasma-INR > 3.5 to 4.5, within ±25% for plasma-INR > 4.5 to 6.0 and within ±30% for plasma-INR > 6.0. ResultsA strong positive correlation was found between POCT- and plasma-INR, Spearman's rho (95% CI) = 0.72 (0.65–0.78), p < 0.001. The average bias was 0.1 INR (3.7%), p < 0.001. 79% of paired INR results met the agreement limits with 67% of the diverging POCT-INRs being from a subset of five patients, who had consistently higher POCT- than plasma-INR. ConclusionsThe majority of LA-positive APS patients had no clinically significant difference between POCT-INR and plasma-INR. However, in a subset of patients, clinically significant systematic differences were found. Consequently, systematic comparison of a minimum three paired POCT- and plasma-INR results is recommended before implementing POCT-INR monitoring in LA-positive APS patients.

Direct oral anticoagulants‐Remove versus Taipan snake venom time for detection of a lupus anticoagulant in patients taking oral direct factor Xa inhibitors

BackgroundThe optimal method of detecting a lupus anticoagulant (LA) for patients taking direct factor Xa inhibitor (DFXaI) direct oral anticoagulants (DOACs) remains controversial. Methods include charcoal adsorption of the DOACs to allow testing with the activated partial thromboplastin time (APTT) and dilute Russell viper venom time (dRVVT), or use of the DFXaI‐insensitive Taipan snake venom time (TSVT) and Ecarin time (ET) assays on neat plasma. ObjectivesThe objective was to compare the utility of APTT and dRVVT analysis following DOAC Remove against TSVT/ET on untreated plasma for LA detection in spiked plasmas and routine clinical samples for patients on DFXaIs. Patients/methodsVarious LA‐negative and LA‐positive samples were assayed by APTT, dRVVT, and TSVT/ET, and then separately spiked with rivaroxaban, apixaban, and edoxaban calibrators to a concentration of ~190 ng/ml and the assays repeated on spiked plasma before and after DOAC Remove treatment. Testing of 284 consecutive samples from DFXaI‐anticoagulated patients by APTT/dRVVT and TSVT/ET before and after DOAC Remove treatment was undertaken. ResultsIn the spiking model, we found that both TSVT/ET and DOAC Remove strategies generally distinguished LA‐negative and LA‐positive samples, but some false‐positive LA results occurred. In the investigation of 284 consecutive patient samples on DFXaIs, the percentage agreement for LA detection in neat samples tested by TSVT/ET versus APTT and dRVVT after DOAC Remove treatment was 90% (Cohen kappa 0.12). ConclusionOur data highlight uncertainty and disagreement for testing LA in patients on DFXaI. Further studies are required.

Lupus anticoagulant in patients with COVID-19: A review

Introduction: Coronavirus disease 2019 (COVID-19) is characterized by a pro-coagulant state that can lead to fatal thromboembolic events. A high prevalence of lupus anticoagulant has been shown in several studies that may at least partially explain the pro-coagulant profile of COVID-19. However, the relation between COVID-19 and lupus anticoagulant is arguable, and no study has clearly evaluated the concussion of lupus anticoagulant on mortality. Methods: We searched the articles that related to lupus anticoagulant and patients with COVID-19. Two authors independently reviewed the search results to select English language articles discussing lupus anticoagulant in patients with COVID-19. Results: Recent studies found conflicting results about the association between lupus anticoagulant and thromboembolic complications of COVID-19. Studies documented a high prevalence of lupus anticoagulants as well as several other studies. Patients with lupus anticoagulants were older, and their C-reactive protein, high-sensitivity troponin, and activated partial thromboplastin time (aPTT) were significantly higher than patients without lupus anticoagulants. Conclusion: Those started on therapeutic anticoagulation showed more severe and complicated involvements and a higher risk of death. According to our results, lupus anticoagulant is highly prevalent among hospitalized COVID-19 patients. Whether these antibodies promote a hypercoagulable state or they are merely a coincidence, epiphenomenon needs further evaluation.

Mixing Studies in Patients With Prolonged Activated Partial Thromboplastin Time or Prothrombin Time.

Patients presenting for surgery may have isolated or combined prolonged activated partial thromboplastin time (aPTT) and/or prothrombin time (PT). In patients not receiving anticoagulants or with no identifiable cause for abnormal clot formation, a mixing study is performed. The index of circulating anticoagulant (ICA) has been used to predict the presence of an inhibitor, usually a lupus anticoagulant. We retrospectively reviewed the results of mixing studies performed at Northwestern Memorial Hospital, between January 1, 2010 and February 29, 2012. We determined the number of samples that normalized or remained prolonged, the clotting factors associated with prolonged test results, and the presence of coagulation inhibitors. We calculated the ICA in the samples with prolonged aPTT and PT to determine its ability to predict a lupus anticoagulant. The primary comparison of interest was the diagnostic utility of the ICA at cutoff values of 11% for predicting the presence of lupus anticoagulant. There were 269 mixing studies performed: 131 samples with prolonged aPTT; 95 with prolonged PT; and 43 with both prolonged aPTT and prolonged PT. Of the samples with a prolonged aPTT, 55 of 131 (42%) normalized, 36 of 131 (27%) partially corrected, and 40 of 131 (31%) remained prolonged. Thirty-three of 95 samples (35%) with prolonged PT normalized, while 62 of 95 (65%) remained prolonged. Eight of 43 (19%) mixing studies of patients with prolonged PT and aPTT normalized; the aPTT normalized, but the PT remained prolonged in 17 of 43 (39%); the PT normalized, but the aPTT remained prolonged in 7 of 43 (16%); and both tests remained prolonged in 11 of 43 (26%) samples. Prolongations in the aPTT were primarily associated with low activities of CF XII, while the majority of the prolongations in PT were secondary to low activities in CF VII. Combined prolongations were secondary to deficiencies in both the intrinsic and extrinsic as well as the common pathways. An ICA >11% had 100% (95% CI, 59%-100%) sensitivity, 53% (95% CI, 35%-70%) specificity, and 77% (95% CI, 62%-92%) accuracy in predicting the presence of lupus anticoagulant in patients with prolonged aPTT. Normalization of the aPTT and PT in a mixing study was associated with low clotting factor activity. The ICA may be helpful in predicting the presence of a lupus anticoagulant. As anesthesiologists take ownership of the perioperative surgical home, we need to understand the clinical implications of the results of mixing studies.

Modern metods for laboratory detection of lupus anticoagulant in patients with antiphospholipid syndrome

Modern metods for laboratory detection of lupus anticoagulant in patients with antiphospholipid syndrome

Screening for lupus anticoagulants in patients treated with vitamin K antagonists.

The dRVVT test for detecting lupus anticoagulants (LA) is difficult to interpret when patients are treated with vitamin K antagonists (VKA). We performed LA testing in 33 VKA-treated patients with definite antiphospholipid syndrome (APS) and compared the results with 100 controls subjects not receiving VKA and 110 APL-negative patients anticoagulated for reasons other than APS. Compared with the dRVVT ratio before the initiation of VKA therapy, a higher cutoff value, defined as the 99th percentile, was established for VKA-treated patients with INR values between 2.0 and 3.5. A dRVVT ratio of >1.7 yielded a sensitivity of 81.3%, specificity of 99.1%, and positive and negative predictive values of 98.7% and 85.8%, respectively, for detecting LA. Cohen's kappa coefficient indicated good agreement for the dRVVT ratio obtained from testing with and without VKA treatment (κ = 0.813; 95% CI: 0.773-0.853), which was higher (κ = 0.941; 95% CI: 0.917-0.965) when the LA diagnosis was based on the results of both the dRVVT and a second test system (i.e., Mixcon-LA assay). Lupus anticoagulants testing in VKA-treated patients with APS according to current guidelines appears to be possible for the majority of patients without discontinuing anticoagulant therapy.

False-positive lupus anticoagulant in patients receiving rivaroxaban: 24 h since the last dose are needed to exclude antiphospholipid syndrome.

Rivaroxaban, a direct factor Xa inhibitor, affects laboratory clotting tests. We report here 10 venous thromboembolism patients with false-positive lupus anticoagulant during rivaroxaban therapy. Two dilute Russell Viper Venom time (dRVVT)-based integrated assays, HemosIL dRVVT Screen/HemosIL dRVVT Confirm (Instrumentation Laboratory, LA1/LA2 (Siemens, Germany) and LA1/LA2 (Siemens, Marburg, Germany), showed that the patients were lupus anticoagulant-positive. Antiphospholipid antibodies were negative except for one patient. Screening activated partial thromboplastin time-based assay PTT lupus anticoagulant was lupus anticoagulant-positive, whereas the confirmatory Staclot lupus anticoagulant (both Diagnostica Stago, France) was lupus anticoagulant-negative. Re-examination after discontinuation of rivaroxaban (>24 h) ruled out the presence of lupus anticoagulant. Our data indicate that to reliably evaluate lupus anticoagulant in patients on rivaroxaban, blood should be drawn 24 h after the last dose.

Abstract T P188: High Prevalence Of Igm Anti-phosphatidylserine-prothrombin Complex Antibodies And Lupus Anticoagulant In Patients With Non-lacunar Ischemic Stroke Without A Determined Cause

Background and Purpose: The cause of ischemic stroke remains undetermined in about 25% of patients even after appropriate studies. Antiphospholipid syndrome (APS) is an autoimmune disease in which vascular thrombosis occurs in patients with antiphospholipid (aPL) antibodies. Anti-phosphatidylserine-prothrombin complex (aPS/PT) antibodies are reported to be associated with symptoms of APS and lupus anticoagulant (LAC) activity. Correlations between ischemic stroke and IgM aPS/PT antibodies have not been well investigated. We tried to explore possible correlations between non-lacunar ischemic stroke without a determined cause and aPL antibodies. Methods: Diagnostic studies consisted of brain MRI/CT, extracranial and intracranial MRA, carotid ultrasonography, 12-lead ECG, 24-hour ECG, transthoracic echo cardiography, transesophageal echo cardiography and venous ultrasonography. After excluding lacunar stroke, proximal arterial stenosis and caridoembolic sources with all these diagnositc studies, we selected 22 non-lacunalr ischemic stroke patients without a determined cause (age 48.5 +/- 14.4 years; 9 woman). We preliminarily measured IgG and IgM anticardiolipin (aCL) antibodies, IgG and IgM aPS/PT antibodies, anti-beta2-glycoprotein I-dependent cardiolipin (anti-beta2 GPI/CL) antibodies and LAC. aCL, aPS/PT, and anti-beta2 GPI/CL antibodies were measured by enzyme-linked immunosorbent assay. LAC was determined according to the Subcommittee on Lupus Anticoagulant/Phospholipid Dependent Antibody guidelines. Results: IgM aPS/PT antibodies, LAC, and both of them were detected in 10, 7, and 3 patients, respectively. Neither aCL nor anti-beta2 GPI/CL antibodies were identified in all patients. Conclusion: Our data demonstrate a high prevalence of IgM aPS/PT antibodies and LAC in patients with non-lacunar ischemic stroke without a determined cause. IgM aPS/PT antibodies and LAC might play some role in the development of ischemic stroke of these patients.

Factor X and factor II activity levels do not always agree in warfarin-treated lupus anticoagulant patients

Warfarin therapy is used in lupus anticoagulant patients with thrombosis and yet the prothrombin time (PT)/international normalized ratio (INR) in these patients can sometimes be falsely elevated. Both a PT-based factor II (FII) assay and a chromogenic, enzymatic factor X (CFX) assay have been used for monitoring when the INR may be artifactual. This study compared FII and CFX assays in lupus anticoagulant-positive and lupus anticoagulant-negative warfarin-treated patients in a cross-sectional study of samples from 21 lupus anticoagulant-positive and 19 lupus anticoagulant-negative outpatients. Plasma samples were simultaneously measured for FII and CFX and the ratio of FII/CFX was used to measure concordance. Compared with lupus anticoagulant-negative patients 14 of the 21 lupus anticoagulant-positive patients had lower FII/CFX ratios (P < 0.01). Three of the patients had ratios less than 0.6 indicating strong disagreement (P < 0.0001). The patient with the lowest FII/CFX ratio had evidence suggesting a specific antibody to FII. Another patient showed that the discordance between FII and CFX varied over time. The CFX assay in the laboratory was technically superior, more precise, and less costly. The CFX assay is preferred for warfarin therapy monitoring in lupus anticoagulant patients when INR artifacts are suspected.

The utility of the Taipan snake venom assay in assessing lupus anticoagulant status in individuals receiving or not receiving an oral vitamin K antagonist

The objective of the present study was to evaluate the Taipan snake venom time (TSVT) assay in the detection of lupus anticoagulant in patients receiving or not receiving oral vitamin K antagonists. Blood samples were collected from individuals requiring investigation for the presence of a lupus anticoagulant. The TSVT test was run in parallel with the dilute Russell viper venom time (dRVVT) assay and anticardiolipin antibody assays. Results were assessed by Bayesian statistics. Two thousand and five plasma samples were obtained from 1335 individuals. One thousand, one hundred and eleven individuals were not receiving oral vitamin K antagonists; of these, 451 had a lupus anticoagulant by conventional testing, and the TSVT showed a sensitivity of 22%, specificity of 98%, positive predictive value of 80%, negative predictive value of 78%, positive likelihood ratio of 12.3 and a negative likelihood ratio of 0.790. Two hundred and ten of the 224 patients receiving oral vitamin K antagonists were known to have a persistent lupus anticoagulant prior to oral anticoagulation. In this setting, TSVT had a sensitivity of 39% and specificity of 93%, but the dRVVT had a 50% false-positive rate, which meant that despite having a higher sensitivity at 61% than the TSVT, its specificity was only 53%. TSVT is a specific but insensitive assay for the lupus anticoagulant in individuals not receiving oral vitamin K antagonists, when assessed against the dRVVT as the gold standard. It can be argued that despite the TSVT's poor sensitivity in patients taking oral vitamin K antagonists, its high specificity and positive predictive value make it a preferable assay to the dRVVT to diagnose lupus anticoagulant in this group.

Lupus Anticoagulant in Patients with Livedo Reticularis and Leg Ulcers

Lupus Anticoagulant in Patients with Livedo Reticularis and Leg Ulcers

Performance of Platelin LS and dilute Russell's viper venom for the screening of lupus anticoagulant in patients with venous thromboembolism

Lupus anticoagulant is associated with thrombosis and pregnancy morbidity, and its detection is of major clinical importance. The nature and concentration of phospholipids strongly influence the sensitivity of activated partial thromboplastin time (aPTT) reagents to lupus anticoagulant. We investigated the ability of Platelin LS, an aPTT reagent, to screen lupus anticoagulant among 94 patients with venous thromboembolism by comparing its performance with the dilute Russell viper venom time (dRVVT). Twenty-four patients had an abnormal aPTT and dRVVT, whereas 37 only had a prolonged dRVVT. In users of oral anticoagulants (n = 56), the dRVVT prolonged more frequently than the aPTT (98.2 vs 39.3%, P < 0.0001). After the mixing study, seven patients maintained abnormal aPTT and dRVVT ratios, five of whom had prolonged mixture with both tests. The agreement in the mixing study between aPTT and dRVVT was substantial (kappa = 0.78, 95% confidence interval = 0.48-1.00). Except for one patient, the aPTT screened all cases that demonstrated phospholipid dependency of their inhibitor during the confirmatory procedure with the dRVVT. In conclusion, the aPTT using Platelin LS was highly associated with the presence of lupus anticoagulant detected by the dRVVT among patients with venous thromboembolism, and could be reliably employed as a screening assay for lupus anticoagulant.

The risk for thromboembolic disease in lupus anticoagulant patients due to pathways involving P-selectin and CD154

Individuals with lupus anticoagulants (LA) are at risk for thromboembolism (TE). Chronic inflammation is an important characteristic in LA patients which may dispose for TE. Platelets play a key role in inflammation and TE. We therefore investigated gene polymorphisms as well as plasma levels of platelet receptors as predictors of TE in 107 LA patients. We compared 74 patients with a history of thromboembolic disease (TE+), 56 with venous thrombosis (VT), 12 with arterial thrombosis (AT), and six patients who had both, with 33 LA patients without previous thrombosis (TE-). The P-selectin Pro715 allele was slightly more frequent in VT (OR = 3.167,95% CI 0.955-10.503; p = 0.0594), but no patient with AT had this allele (OR = 0.099, 95 % CI 0.001-0.790; p = 0.0238) which therefore may protect from AT. Plasma levels of P-selectin, collected a median of 35 months (range 2-329 months) after the last thrombotic event, were higher in patients withVT (p = 0.0096) than in TE-, but not with AT (p = 0.4713). These high P-selectin levels were not explained by the P-selectin polymorphism. The CA repeat polymorphism in the 3'-noncoding region of CD154 was significantly associated with the development of AT (OR = 4.035,95 % CI 1.329-12.249; p = 0.0138). Plasma levels of CD154 were not significantly different among the subgroups. Thus, the Thr715Pro polymorphism of P-selectin and CA repeats of CD154 are differentiating between the risk for VT and AT. Further, soluble P-selectin is elevated in LA patients with previous VT, but its role to predict VT needs to be evaluated in prospective studies.

Specificities of Platelet Autoantibodies and Platelet Activation in Lupus Anticoagulant Patients: A Relation to their History of Thromboembolic Disease

Lupus anticoagulants (LA) prolong in vitro phospholipid-dependent coagulation tests, but are associated with thromboembolic disease (TE). However, a subgroup of individuals with LA has no TE, and it is therefore desirable to distinguish those at risk for TE from those without. Whether platelets have a primary role in the development of TE is not clear yet. We determined platelet autoantibodies to identify a specific platelet target which is associated with platelet activation in 97 patients with a long history of detectable LA, 65 patients with TE (LA/TE+), and 32 individuals without TE (LA/TE-). Thrombocytopenia was more common in the LA/TE- than in the LA/TE+ group (P < 0.05). Both groups had platelet antibodies, but the frequency of antibodies was lower in LA/TE+ than LA/TE- patients (P < 0.01), who had higher antibody titres against glycoprotein IIb/IIIa and glycoprotein Ib/IX (P < 0.05). Also, their platelets were more activated, as determined by PAC-1 binding (P < 0.01). These differences were also noted if patients with arterial thrombosis were evaluated separately. These findings in LA/TE- individuals were similar to those in patients with chronic autoimmune thrombocytopenia. However, there was no autoantibody target identifiable to distinguish between LA/TE- from LA-TE+ individuals. We therefore conclude that the presence of platelet antibodies, even if associated with platelet activation, is not sufficient to dispose LA patients to thromboembolic disease.

A functional coagulation test to identify anti-β 2-glycoprotein I dependent lupus anticoagulants

Introduction Lupus Anticoagulants (LAC) activity due to β 2-glycoprotein I (β 2GPI) antibodies shows a high correlation with thrombotic events. Since the binding of β 2GPI antibodies to phospholipids may be influenced by the final calcium chloride (CaCl 2) concentration a discrimination between β 2GPI dependent LAC and β 2GPI independent LAC could be possible using clotting tests with various CaCl 2 concentrations and making them this way more sensitive to the presence of β 2GPI antibodies. Materials and methods I evaluated the effect of 5 mM, 8.3 mM, 10.3 mM and 17.9 mM final CaCl 2 concentration in a commonly used screening test for LAC, the PTT-LA, on LAC positive patients with and without β 2GPI antibodies. Results Mean coagulation times of LAC patients negative for β 2GPI antibodies were significant shorter with 5 mM CaCl 2 in comparison with 8.3 mM and 10 mM ( P < 0.05 and P < 0.01, respectively). In the LAC patients with positive β 2GPI antibodies no significant difference at 5 mM CaCl 2, 8.3 mM or 10 mM was observed. Mean coagulation times at 5 mM CaCl 2 were significant higher ( P = 0.003) in patients positive for β 2GPI antibodies than in patients negative for β 2GPI antibodies. Conclusion The most remarkable observation was that the coagulation time, measured by PTT-LA at low final CaCl 2 concentration, is much more prolonged in the LAC positive β 2GPI antibody positive patients than in the LAC positive β 2GPI antibody negative patients. Thus, the competition with clotting factors for binding on phospholipids is stronger for β 2GPI antibodies than for other antibodies and explains the longer coagulation times in the presence of β 2GPI antibodies.

The laboratory diagnosis of lupus anticoagulant in patients on oral anticoagulation

Laboratory-specific cut-off lupus ratios (LR), above which a plasma is judged positive for lupus anticoagulant (LA), were established for both activated partial thromboplastin time-based and dilute Russell viper venom time-based methods. The validity of using these cut-off values to determine the presence of LA in patients on oral anticoagulation (OAC) was assessed. A cohort of 40 patients (23 male and 17 female), aged 22-84 years (mean 52 years) were tested for LA at the time of a thrombotic event. Repeated testing was performed after the same patients were treated with OAC (international normalized ratio 2.0-3.5). For 36 patients (90%), LA status was unchanged pre- and on-OAC. Thirteen of the 40 patients (32.5%) were positive for LA both pre- and on-OAC. Of the 27 patients negative for LA pre-OAC, 23 remained negative on-OAC. The four discordant results were interesting in that LA positivity was demonstrated only after the patient was stable on-OAC. In our cohort of 40 patients, there was a trend for LRs to decrease on-OAC, but this did not reach statistical significance. The subset (4) went against this trend and became positive after the thrombotic event.