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Lupus anticoagulant (LA) is composed of heterogeneous autoantibodies, which have a close association with thrombotic events. Due to its heterogeneity, two methods for increasing sensitivity are recommended for LA. An investigation of the thrombotic risk and anticardiolipin (aCL) and anti-β2-glycoprotein I (aB2GPI) antibody profiles was conducted based on the results of using two parallel methods (dilute Russell viper venom time (dRVVT), silica clotting time (SCT)) in a real world clinical laboratory. Of 5120 patients, 684 patients (13%) were LA positive, and 422 patients (8%) experienced thrombotic events including pregnancy complication. Development of thrombotic events was more likely to occur in patients who were positive for both dRVVT and SCT compared with those who were positive for dRVVT or SCT only. In addition, significantly higher positive rates of aCL and aB2GPI and the persistently positive rate of LA at intervals of 12 weeks or longer were observed in patients who were positive for both dRVVT and SCT compared with those who were positive for dRVVT or SCT only. Considering three laboratory tests (LA, aCL, and aB2GPI), high thrombotic risk was observed for patients with both dRVVT and SCT positive LA results. A report on LA results that divides LA positive into two types (LA-single positive and LA-both positive) may be beneficial to clinicians in detection of high-risk thrombotic patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The contact system activation can play a role in microthrombus formation of disseminated intravascular coagulation (DIC). This study investigated whether the activity of prekallikrein and high-molecular-weight kininogen (HMWK) correlated DIC progression. Contact system factors (prekallikrein, HMWK, activated factor XII), coagulation factors (IX, XI, XII) and tissue factor were measured in 140 patients who clinically suspected of having DIC. Prekallikrein and HMWK activity levels showed significant linear relationships with DIC score and antithrombin level, whereas prekallikrein and HMWK antigen levels did not. The activated factor XII, factor XII, factor XI and tissue factor were significant risk factors of overt-DIC. This finding suggests that consumption of prekallikrein and HMWK contributes to microvascular thrombosis in DIC. Measurements of prekallikrein and HMWK activity could be used as potential diagnostic markers for overt-DIC., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Although a few antiphospholipid syndrome (APS) occurs with acquired thrombotic thrombocytopenic purpura (TTP), the relationship between antiphospholipid antibodies (aPL) and anti-ADAMTS13 (anti-a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) antibody remains uncertain. We investigated the relationship between high-risk thrombotic aPL and anti-ADAMTS13 antibody. Two hundred and thirty-seven patients with positive lupus anticoagulant and/or anticardiolipin antibody were included. Anti-β 2 GPI (anti-β 2 -glycoprotein I), anti-β 2 GPIdI (anti-β2-glycoprotein I domain I), anti-PS/PT (anti-phosphatidylserine and prothrombin), ADAMTS13 activity, and anti-ADAMTS13 antibody were measured. Double positivity of anti-β 2 GPI and anti-PS/PT increased thrombotic risk more than three-fold and showed increased positivity of anti-ADAMTS13 antibody in comparison with the double negative group. Double positivity of anti-β 2 GPIdI and anti-PS/PT presented both effects even more. In the linear regression analysis, double positivity of anti-β 2 GPI and anti-PS/PT independently affected the anti-ADAMTS13 antibody level (β = 1.982, P = 0.042). Our results revealed that double positivity of anti-β 2 GPI or anti-β 2 GPIdI and anti-PS/PT increased not only thrombotic risk but also the positivity of anti-ADAMTS13 antibody, especially indicating anti-β 2 GPIdI showed a higher synergistic effect with anti-PS/PT. We suggest a possible association of anti-ADAMTS13 antibody with a high thrombotic risk of APS. Double positivity of anti-β 2 GPI (anti-β 2 -glycoprotein I) and anti-PS/PT (anti-phosphatidylserine and prothrombin) antibodies enhanced not only thrombotic risk but also positivity of anti-ADAMTS13 (anti-a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) antibody. Furthermore, double positivity of anti-β 2 GPIdI (anti-β2-glycoprotein I domain I) combined with anti-PS/PT even more elevated both thrombosis and positivity of anti-ADAMTS13 antibody. Double positivity of β 2 GPI and anti-PS/PT was found as an independently significant contributing factor to anti-ADAMTS13 antibody level. We suggest the association between anti-ADAMTS13 antibody and the pathophysiology of antiphospholipid syndrome, which should be further evaluated., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Increasing interest has focused on the development of new assays more specific for APS and application of multiple combinations of anti-phospholipid antibodies (aPLs). This study explored the thrombotic risk of non-criteria aPLs measured by a new line immunoassay (LIA) and the benefit of additional non-criteria aPLs results to the APS diagnosis., Methods: LIA were performed to detect 9 aPLs in 180 patients requested for lupus anticoagulant (LA) measurement. Antibodies against anti-cardiolipin (CL), β2 glycoprotein I (GPI), and β2GPI domain I were measured by ELISA., Results: The agreement percentages for IgG/IgM anti-CL and anti-β2GPI between ELISA and LIA (anti-CL 68.2% and 82.6%; anti-β2GPI 71.7% and 93.2%, respectively). Among 9 aPLs measured by LIA, single presence IgG of anti-phosphatidylserine (odds ratio (OR) 16.477) and anti-phosphatidic acid (OR 9.625) predicted higher thrombotic risk than anti-β2GPI (OR 5.538). Other aPLs measured by LIA (anti-prothrombin, anti-annexin V, anti-phosphatidylinositol, phosphatidylethanolamine, and anti-phosphatidylglycerol) did not show any significant thrombotic risk. Addition of the 2 non-criteria aPLs (anti-phosphatidylserine and anti-phosphatidic acid) to the established APS criteria increased the diagnostic specificity and accuracy for thrombosis. The positive rates of anti-β2GPI and anti-phosphatidylserine measured by LIA were quite high in patients with positive anti-β2GPI domain I., Conclusions: The anti-phosphatidylserine and anti-phosphatidic acid among non-criteria aPLs have a high likeli-hood as new markers for thrombotic prediction.

Background: Highly specific assays for measuring antiphospholipid antibodies (aPLs) are required for accurate assessment of thrombotic risk. aPLs against β2-glycoprotein I domain I (anti-β2GPIdI) and against prothrombin complexed with phosphatidylserine (anti-PS/PT) have been recently identified as being associated with a hypercoagulable state. This study evaluated the synergism between anti-β2GPIdI and anti-PS/PT for predicting thrombotic events., Methods: A total of 180 patients with clinical suspicion of hypercoagulability were evaluated. The plasma levels of lupus anticoagulant (LA) and antibodies against anticardiolipin (anti-CL) (IgG and IgM), β2GPI (IgG and IgM), PS/PT (IgG and IgM), and β2GPI dI (IgG) were measured., Results: IgG anti-β2GPIdI and LA were highly associated with thrombosis. Mean values and positivity rates of IgG anti-β2GPI dI and IgG anti-PS/PT were significantly higher in the triple-positive group (LA+, IgG anti-CL+, IgG anti-β2GPI+) than in the other groups. Interestingly, the thrombotic risk [odds ratio (OR) 24.400, 95% confidence interval (CI) 1.976-63.273, p<0.001] of the newly defined triple positive group (LA+, IgG anti-CL+, IgG anti-β2GPIdI+; OR 11.182, 95% CI 1.976-63.273, p=0.006) was more than twice that of the triple-positive group (LA+, IgG anti-CL+, IgG anti-β2GPI+). Double positivity for IgG anti-PS/PT and IgG anti-β2GPI also indicated significant thrombotic risk (OR 7.467, 95% CI 2.350-23.729, p=0.001). Furthermore, the thrombotic risk associated with double positivity for IgG anti-PS/PT and IgG anti-β2GPIdI was markedly elevated (OR 33.654, 95% CI 6.322-179.141, p<0.001)., Conclusions: Our data suggest that simultaneous measurement of IgG anti-β2GPIdI and IgG anti-PS/PT may improve clinical decision-making for aPL-positive patients.

Background: Coagulation and anticoagulation systems are good targets of antiphospholipid antibodies. We assessed the contribution of the antiphospholipid antibodies to the thrombotic risk., Methods: Enzyme-linked immunosorbent assays on antibodies against phosphatidylserine and prothrombin (PS/PT), protein C, protein S, protein Z, and thrombomodulin were performed in 164 patients who showed positive results for lupus anticoagulant or anticardiolipin antibody., Results: Anti-β-2-glycoprotein I (β2GPI) and anti-PS/PT were significant risk factors for thrombotic events (P < .001, P = .049). However, there was no association between antiprotein C, antiprotein S, antiprotein Z, or antithrombomodulin and thrombosis. Coexistence of anti-β2GPI and anti-PS/PT antibodies was significantly associated with thrombotic events (P = .001). Interestingly, the absence of both anti-β2GPI and anti-PS/PT antibodies was a significant preventive factor for thrombosis (P = .003)., Conclusion: Our data show a lack of association of antiprotein C, antiprotein S, antiprotein Z, and antithrombomodulin antibodies with thrombosis. However, the combination of conventional anti-β2GPI with anti-PS/PT antibody is expected to enhance the predicting power of thrombotic risk.

Introduction: Patients with end-stage renal disease (ESRD) on maintenance haemodialysis are predisposed to bleeding and thrombotic events. Recently thrombin generation assay (TGA) has been introduced as a laboratory assessment of global haemostatic potential. We investigated the global haemostatic potential assessed by TGA in ESRD patients on haemodialysis and patients who developed vascular access thrombosis., Materials and Methods: A total of 69 ESRD patients who underwent haemodialysis (58 stable patients and 11 vascular access thrombosis patients) were included and 33 healthy controls were included. TGA was performed on the calibrated automated thrombogram using tissue factor with/without addition of thrombomodulin or activated protein C, producing three parameters including lag time, endogenous thrombin potential (ETP) and peak thrombin., Results: Haemodialysis patients showed low ETP values measured by thrombin generation assay compared with the healthy controls. Interestingly, patients with vascular access thrombosis exhibited short PT and aPTT and increased resistance of coagulation inhibition to APC anticoagulant protein, reflecting hyper-coagulability. Haemodialysis patients who are taking anti-platelet agents showed decreased thrombin inhibition rate, representing antithrombotic effect of anti-platelet agents., Conclusion: Whereas the haemodialysis patients showed hypo-coagulability, the patients with vascular access thrombosis exhibited hyper-coagulability. Further study is required to investigate how this haemostatic potential may be utilized to guide the physician to more effective management of haemostatic complication., (© 2013.)

The mixing test is used to determine the presence of inhibitors in laboratory diagnoses of lupus anticoagulant. Updated international guidelines state that an integrated lupus anticoagulant test system does not require the mixing test; an appraisal of the mixing tests in integrated lupus anticoagulant test systems is, therefore, required. We investigated the clinical relevance of mixing tests by using the best cutoff value of the mixing test through thrombotic risk analysis. A retrospective analysis was performed on 525 specimens with positive screening tests by using two integrated lupus anticoagulant tests: diluted Russell's Viper venom (dRVVT) and silica clotting time. The diagnostic performance of two interpretation formulas (percentage correction, Rosner index) was assessed, and the thrombotic risk of a subgroup based on the mixing results was investigated. Finally, the thrombotic risk of lupus anticoagulant positivity based on the integrated lupus anticoagulant test system procedures was assessed for the appraisal of mixing test exclusion in integrated lupus anticoagulant test systems. The best cutoff values of mixing test interpretation methods based on dRVVT were as follows: 60.1% for percentage correction and 15.7 for Rosner index. There was no substantial difference in the thrombotic risk between percentage correction and the Rosner index. The mixing-positive group showed a higher lupus anticoagulant titer and higher thrombotic risk than the mixing-negative group. However, even the mixing-negative group carried a significant risk of thrombosis. Finally, lupus anticoagulant positivity determined by the updated two-step procedure (screening and confirmation tests) showed higher thrombotic risk than that determined by the traditional three-step procedure (screening, mixing, and confirmation tests). Although a positive mixing result can predict a high risk of thrombosis, negative mixing results are also associated with a substantial thrombotic risk. The updated two-step procedure without the mixing test is relevant for lupus anticoagulant detection in the context of thrombotic risk estimation.

Background: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction caused by antibodies to the heparin/platelet factor 4 (PF4) complex, resulting in thrombocytopenia and prothrombotic state. HIT diagnosis is challenging and depends on clinical presentation and laboratory tests. We investigated the usefulness of clinical scores and heparin/PF4 ELISA optical density (OD) as a diagnostic marker and thrombosis predictor in HIT., Methods: We analyzed 92 patients with suspected HIT. The heparin/PF4 antibody was measured using a commercial ELISA kit (GTI, USA). For each patient, the 4 T's score and Chong's score were calculated., Results: Of the 92 patients, 28 were anti-heparin/PF4-seropositive. The 4 T's score and Chong's score showed good correlation (r=0.874). The 4 T's score and OD values showed good performance for diagnosis of the definite and unlikely HIT groups; however, OD levels showed better sensitivity (93.8%) than the 4 T's score used alone (62.5%). Of the 92 patients, 26 developed thrombosis. The OD values were significantly higher in patients with thrombosis than in those without thrombosis (0.52 vs. 0.22, P<0.001). Patients with high OD values (OD>0.4) had an increased risk of thrombosis (adjusted odds ratio 9.44 [3.35-26.6], P<0.001) and a shorter 250-day thrombosis-free survival (32.1% vs. 54.7%, P=0.012)., Conclusions: ELISA OD values in combination with clinical scoring can improve the diagnosis of and thrombosis prediction in HIT. More attention should be paid to the use of clinical scores and OD values as thrombosis predictors in HIT.

Recently, a semiquantitative enzyme-linked immunoassay for detecting IgG or IgM class autoantibody to beta2-GPI for use as an aid in the diagnosis of certain autoimmune or thrombotic disorders. We evaluated the prevalence of anti-beta2-GPI antibody and its relation to plasma beta2-GPI levels and occurrence of thrombosis in 69 patients with liver cirrhosis. As expected, plasma beta2-GPI levels were lower in the patients with liver cirrhosis and correlated with Child classification. Anti-beta2-GPI antibodies were positive in 11 (15.9%) patients. However, there were no differences in beta2-GPI levels, platelet counts, and thrombosis between positive and negative groups for anti-beta2-GPI antibodies.

Although a few antiphospholipid syndrome (APS) occurs with acquired thrombotic thrombocytopenic purpura (TTP), the relationship between antiphospholipid antibodies (aPL) and anti-ADAMTS13 (anti-a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) antibody remains uncertain. We investigated the relationship between high-risk thrombotic aPL and anti-ADAMTS13 antibody. Two hundred and thirty-seven patients with positive lupus anticoagulant and/or anticardiolipin antibody were included. Anti-β2GPI (anti-β2-glycoprotein I), anti-β2GPIdI (anti-β2-glycoprotein I domain I), anti-PS/PT (anti-phosphatidylserine and prothrombin), ADAMTS13 activity, and anti-ADAMTS13 antibody were measured. Double positivity of anti-β2GPI and anti-PS/PT increased thrombotic risk more than three-fold and showed increased positivity of anti-ADAMTS13 antibody in comparison with the double negative group. Double positivity of anti-β2GPIdI and anti-PS/PT presented both effects even more. In the linear regression analysis, double positivity of anti-β2GPI and anti-PS/PT independently affected the anti-ADAMTS13 antibody level (β = 1.982, P = 0.042). Our results revealed that double positivity of anti-β2GPI or anti-β2GPIdI and anti-PS/PT increased not only thrombotic risk but also the positivity of anti-ADAMTS13 antibody, especially indicating anti-β2GPIdI showed a higher synergistic effect with anti-PS/PT. We suggest a possible association of anti-ADAMTS13 antibody with a high thrombotic risk of APS. Double positivity of anti-β2GPI (anti-β2-glycoprotein I) and anti-PS/PT (anti-phosphatidylserine and prothrombin) antibodies enhanced not only thrombotic risk but also positivity of anti-ADAMTS13 (anti-a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) antibody. Furthermore, double positivity of anti-β2GPIdI (anti-β2-glycoprotein I domain I) combined with anti-PS/PT even more elevated both thrombosis and positivity of anti-ADAMTS13 antibody. Double positivity of β2GPI and anti-PS/PT was found as an independently significant contributing factor to anti-ADAMTS13 antibody level. We suggest the association between anti-ADAMTS13 antibody and the pathophysiology of antiphospholipid syndrome, which should be further evaluated. [ABSTRACT FROM AUTHOR]