The Effects of Indirect- and Direct-Acting Anticoagulants on Lupus Anticoagulant Assays

Seheult, Jansen N.; Meyer, Michael; Bontempo, Franklin A.; Chibisov, Irina

doi:10.1093/ajcp/aqx035

Cited by 27 publications

(32 citation statements)

References 26 publications

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“…This effect of emicizumab on DRVVT is much smaller than the effect of direct oral anticoagulants on this assay. 7 The mechanism of DRVVT prolongation is likely due to a weak steric interference with coagulation reactions in which FXa is generated, due to the binding of FX by emicizumab. 8 The lack of effect of emicizumab on TVT was expected, as emicizumab acts further upstream in the coagulation cascade.…”

Section: Dear Editorsmentioning

confidence: 99%

Effects and interferences of emicizumab, a humanized bispecific antibody mimicking activated factor VIII cofactor function, on lupus anticoagulant assays

Adamkewicz¹,

Kiialainen

Paz‐Priel³

2019

Int J Lab Hematology

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Section: Dear Editorsmentioning

confidence: 99%

Effects and interferences of emicizumab, a humanized bispecific antibody mimicking activated factor VIII cofactor function, on lupus anticoagulant assays

Adamkewicz¹,

Kiialainen

Paz‐Priel³

2019

Int J Lab Hematology

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“…Tests for LA detection should include screening, mixing and confirmation steps performed with at least two different methodologies, with only one result required to be positive [19,35]. Many studies have reported DOAC interference with tests for LA, leading to false-positive and unreliable results [36][37][38][39]. Dabigatran and apixaban interfere with both activated partial thromboplastin time (aPTT) based and dilute Russell viper venom time (dRVVT) based tests [40][41][42][43].…”

Section: Laboratory Monitoring Of Anticoagulation In Patients Receivimentioning

confidence: 99%

Use of direct oral anticoagulants in antiphospholipid syndrome

Cohen

Efthymiou

Isenberg

2018

Journal of Thrombosis and Haemostasis

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The direct oral anticoagulants (DOACs) are therapeutic alternatives to warfarin and other vitamin K antagonists (VKAs), and constitute the standard of care for many indications. VKAs constitute the conventional therapy for the treatment and secondary thromboprophylaxis of thrombotic antiphospholipid syndrome (APS), but are often problematic, owing to the variable sensitivity of thromboplastins to lupus anticoagulant. Thus, the International Normalized Ratio may not accurately reflect anticoagulation intensity, or be clinically effective. Definition of the current role of DOACs in the treatment of APS is based on limited clinical trial data and information from other sources, including manufacturers' data, case series or cohort studies, and expert consensus. The Rivaroxaban in Antiphospholipid Syndrome (RAPS) randomized controlled trial (RCT), which had a laboratory surrogate primary outcome measure, suggests that rivaroxaban has the potential to be an effective and convenient alternative to warfarin in thrombotic APS patients with a single venous thromboembolism event requiring standard-intensity anticoagulation. However, further studies, in particular to provide better long-term efficacy and safety data, are needed before it can be widely recommended. APS patients are clinically heterogeneous, with the risk of recurrent thrombosis and the intensity of anticoagulation being influenced by their clinical phenotype and risk profile. DOAC trials involving homogeneous thrombotic APS populations, with the antiphospholipid antibody status well defined, will help to optimize the appropriate treatment in APS patient subgroups. Ongoing and emerging DOAC RCTs should provide further information to guide the use of DOACs in APS patients. Optimal identification of APS patients is a key step in working towards improved therapeutic strategies in these individuals.

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“…This highly selected patient population explains the high incidence of thrombophilic factors reported in the 50 patients finally included in this study (e.g., 76% lupus anticoagulant in the study group (n = 50) compared to 25.2% in the patient population screened (n = 151) and listed for liver transplantation at Menoufia University). We are aware that oral anticoagulants - vitamin K antagonists as well as direct oral anticoagulants (DOACs) - and heparin can interfere with lupus anticoagulant assays [32,33]. This was one reason to exclude liver transplant recipients with oral anticoagulation from the study.…”

Section: Discussionmentioning

confidence: 99%

Perioperative Thromboelastometry for Adult Living Donor Liver Transplant Recipients with a Tendency to Hypercoagulability: A Prospective Observational Cohort Study

Kamel

Hassanin

Ahmed

et al. 2018

Transfus Med Hemother

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Background: Hypercoagulability can lead to serious thromboembolic events. The aim of this study was to assess the perioperative coagulation status in liver transplant recipients with a tendency to hypercoagulability. Methods: In a prospective observational study (South African Cochrane Registry 201405000814129), 151 potential liver transplant recipients were screened for thrombophilic factors from October 2014 to June 2017, and 57 potential recipients fulfilled the inclusion criterion of presenting two or more of the following thrombophilic factors: low protein C, low protein S, low anti-thrombin, increased homocystein, increased antiphospholipid IgG/IgM antibodies, increased lupus anticoagulant, and positive Factor V Leiden mutation. Seven patients were excluded from the study because they fulfilled the exclusion criteria of cancelling the liver transplantation, oral anticoagulation, or intraoperative treatment with rFVIIa. Accordingly, 50 patients were included in the final analysis. Thromboelastometry (ROTEM) (EXTEM, INTEM and FIBTEM) and conventional coagulation tests (CCT) were performed preoperatively, during the anhepatic phase, post reperfusion, and on postoperative days (POD) 1, 3 and 7. ROTEM was used to guide blood product transfusion. Heparin was infused (60-180 U/kg/day) postoperatively for 3 days and then was replaced by low-molecular-weight heparin (20 mg/12 h). Results: FIBTEM MCF significantly increased postoperatively above reference range on POD 7 despite normal fibrinogen plasma concentrations (p < 0.05). Both EXTEM and INTEM demonstrated significant changes with the phases of transplantation (p < 0.05), but with no intra- or postoperative hypercoagulability observed. INTEM CT (reference range, 100-240 s) normalized on POD 3 and 7 (196.1 ± 69.0 and 182.7 ± 63.8 s, respectively), despite prolonged aPTT (59.7 ± 18.7 and 46.4 ± 15.7 s, respectively; reference range, 20-40 s). Hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) were reported in 12.0% and 2.0%, respectively, mainly after critical care discharge and with high FIBTEM MCF values in 57% on POD 3 and 86% on POD 7. Receiver operating characteristics curve analyses of FIBTEM MCF were significant predictors for thromboembolic events with optimum cut-off, area under the curve and standard error on POD 3 (>23 mm, 0.779 and 0.097; p = 0.004) and POD 7 (>28 mm, 0.706 and 0.089; p = 0.020). Red blood cells (mean ± SD, 8.68 ± 5.81 units) were transfused in 76%, fresh frozen plasma (8.26 ± 4.14 units) in 62%, and cryoprecipitate (12.0 ± 3.68 units) in 28% of recipients. None of the recipients received intraoperative platelet transfusion or any postoperative transfusion. Main transplant indication was hepatitis C infection in 82%. 76% of recipients included in this highly selected patient population showed increased lupus anticoagulant, 2% increased antiphospholipid IgG/IgM antibodies, 20% increased homocysteine, 74% decreased anti-thrombin, 78% decreased protein C, 34% decreased protein S, and 24% a positive Factor V Leiden mutation....

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The Effects of Indirect- and Direct-Acting Anticoagulants on Lupus Anticoagulant Assays

Abstract: Results of LAC testing performed while patients are receiving anticoagulant therapies should be interpreted with caution to avoid misdiagnosing patients with the antiphospholipid syndrome and potentially committing them to long-term anticoagulation therapy.

Cited by 27 publications

References 26 publications

Effects and interferences of emicizumab, a humanized bispecific antibody mimicking activated factor VIII cofactor function, on lupus anticoagulant assays

Effects and interferences of emicizumab, a humanized bispecific antibody mimicking activated factor VIII cofactor function, on lupus anticoagulant assays

Use of direct oral anticoagulants in antiphospholipid syndrome

Perioperative Thromboelastometry for Adult Living Donor Liver Transplant Recipients with a Tendency to Hypercoagulability: A Prospective Observational Cohort Study

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