New method to differentiate between lupus anticoagulants, progressive coagulation inhibitors and coagulation factor deficiencies in the mixing tests.

Introduction: Mixing tests in activated partial thromboplastin time (APTT) are used for the differentiation between lupus anticoagulants (LA), coagulation inhibitors, and factor deficient samples with APTT prolongation. However, the indexes for the differentiation have not been established. The present study aimed to develop new mixing test indexes for the differentiation.

Comparison of results obtained using clot-fibrinolysis waveform analysis and global fibrinolysis capacity assay with rotational thromboelastography.

Global fibrinolysis assays detect the fibrinolysis time of clot dissolution using tissue-type plasminogen activator (tPA). Two such assays, clot-fibrinolysis waveform analysis (CFWA) and global fibrinolysis capacity (GFC) assay, were recently developed. These were compared with rotational thromboelastography (ROTEM).

Age-related variation in coagulation factors in non-valvular atrial fibrillation patients receiving direct oral anticoagulants.

Age is a significant risk factor for ischemic stroke. However, the influence of aging on coagulation parameters in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOACs) remains unclear. A total of 775 samples were collected from 224 NVAF patients receiving apixaban, edoxaban or rivaroxaban.

Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study.

Background: Unfractionated heparin (UFH) is primarily monitored using activated partial thromboplastin time (APTT). However, the recent introduction of anti-activated factor X (anti-Xa) activity testing has provided a direct evaluation of Xa inhibition by anticoagulants. This study aimed to investigate discrepancies between APTT and anti-Xa activity during UFH monitoring in critically ill patients and explore their underlying causes.

Characterization and Usefulness of Clot-Fibrinolysis Waveform Analysis in Critical Care Patients with Enhanced or Suppressed Fibrinolysis.

Introduction:  Recently, clot-fibrinolysis waveform analysis (CFWA), which is a coagulation and fibrinolysis global assay based on assessing the activated partial thromboplastin time with tissue-type plasminogen activator, was developed. This study aimed to investigate the characteristics of CFWA using plasma samples from patients in the critical care unit.

Materials And Methods:  The fibrinolysis times using CFWA were measured in 298 plasma samples.

Evaluation of newly-developed modified diluted prothrombin time reagent in non-valvular atrial fibrillation patients with direct oral anticoagulants: A comparative study with conventional reagents.

Introduction: A single assay to assess the effect of the direct FXa inhibitor is needed clinically because prothrombin (PT) assay is not yet sensitive enough for accurate evaluation. We developed modified diluted prothrombin time (mdPT) assay showing a high reactivity to direct FXa inhibitors based on prothrombin time (PT) reagent. The purpose of this study was to evaluate the reactivity of mdPT to direct FXa inhibitors comparing to that of commercial PT reagents and diluted prothrombin time (dPT).

Thrombin generation capacity is enhanced by low antithrombin activity and depends on the activity of the related coagulation factors.

Background: Supplementation with antithrombin (AT) concentrates is now common in the treatment of congenital and acquired AT deficiency. However, there is no established consensus on the target and timing of supplementation. We aimed to elucidate the effects of AT deficiency on the balance between coagulation activation and inhibition using a thrombin generation assay as in vitro global assay.

Applying index of circulating anticoagulant to mixing tests with lupus anticoagulant screen and confirm reagents can distinguish with high specificity between lupus anticoagulants and direct factor Xa inhibitors.

Background: Lupus anticoagulants (LA) are detected by prolongation of clotting times for dilute Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT) screening tests. Direct oral anticoagulants (DOACs) can interfere with both screening and confirmatory tests. The present study aimed to investigate the influence of direct factor Xa inhibitors (DiXaIs) on screen, confirm and mixing tests and establish a method for differentiation from other sample types.

Updates on Anticoagulation and Laboratory Tools for Therapy Monitoring of Heparin, Vitamin K Antagonists and Direct Oral Anticoagulants.

Anticoagulant drugs have been used to prevent and treat thrombosis. However, they are associated with risk of hemorrhage. Therefore, prior to their clinical use, it is important to assess the risk of bleeding and thrombosis.

Characterization of fibrin/fibrinogen degradation products reagents and their utility in critical care patients with enhanced fibrinolysis.

Introduction: Fibrin/fibrinogen degradation products (FDP) values reflect coagulation and fibrinolysis status, and FDP levels are helpful for diagnosis and classification of disseminated intravascular coagulation (DIC). FDP measurement has always played a key role in diagnosing DIC, a phenomenon that has recently gained renewed attention because of its occurrence in coronavirus disease 2019 (COVID-19) patients. Although the evaluation of FDP is crucial for the management of critical care, the variability among FDP reagents is unclear.

Expert consensus regarding standardization of sample preparation for clotting time assays.

Accurate clotting time assay results are vital, as the test is employed to indicate the amount of oral anticoagulant to be prescribed, while it is also used for screening the hemorrhagic and thrombotic diseases. The procedure chosen for preparation of a patient blood sample including centrifugation can contribute to significant differences in the results obtained. Thus, for the purpose of proposing a standardized method to appropriately prepare blood samples prior to assay, the Japanese Society of Laboratory Hematology organized the Working Group for Standardization of Sample Preparation for Clotting Time Assays (WG).

Lupus anticoagulant assay cut-offs vary between reagents even when derived from a common set of normal donor plasmas.

Background: Multicenter studies reveal that diagnostic efficacy of lupus anticoagulant (LA) assays is enhanced if cut-offs are locally generated. However, a potential confounder is the inevitable use of separate normal donor populations.

Objectives: Generate cut-offs for multiple LA reagents with the same analyzer and normal donor plasmas.

Ruling out lupus anticoagulants with mixing test-specific cutoff assessment and the index of circulating anticoagulant.

Background: Lupus anticoagulant (LA) is classified in the antibody family that is recognized in antiphospholipid syndrome. Mixing tests are recommended for LA detection, and either a mixing test-specific cutoff (MTC) or index of circulating anticoagulant (ICA) is used for the interpretation. Although we previously showed MTC had higher sensitivity for LA than ICA, there are few studies investigating specificity.

Paired APTTs of low and high lupus anticoagulant sensitivity permit distinction from other abnormalities and achieve good lupus anticoagulant detection rates in conjunction with dRVVT.

Introduction: A prolonged activated partial thromboplastin time (APTT) may be indicative of a specific or multiple factor deficiency, therapeutic anticoagulation, presence of a nonspecific factor inhibitor, or lupus anticoagulant (LA). Recently, pairing of the LA-sensitive APTT and standard APTT reagents, Cephen LS and Cephen, respectively, has been shown to be effective in LA detection. The present study aimed to evaluate the usefulness of this reagent pair for discriminating between causes of APTT elevation and the detection of LA in conjunction with dilute Russell's viper venom time (dRVVT).

Lupus anticoagulant mixing tests for multiple reagents are more sensitive if interpreted with a mixing test-specific cut-off than index of circulating anticoagulant.

Background: Lupus anticoagulant (LA) is classified in the antibody family that is recognized as antiphospholipid antibodies. Guidelines for LA detection recommend mixing test interpretation with either a mixing test specific cut-off (MTC) or index of circulating anticoagulant (ICA). We previously evidenced that MTC was superior to ICA in detecting the in vitro inhibition of LA with a single dilute APTT (activated partial thromboplastin time) and dRVVT (diluted Russell's viper venom time) pairing.

Sarcolipin expression is repressed by endoplasmic reticulum stress in C2C12 myotubes.

Sarcolipin is a transmembrane protein expressed in the sarco/endoplasmic reticulum of skeletal and atrial muscles in large animals. Sarcolipin plays crucial roles in heat production through modifying the function of sarco/endoplasmic reticulum Ca ATPase, thereby being involved in thermogenesis and systemic metabolism. In skeletal muscle, endoplasmic reticulum (ER) stress has been implicated in several conditions, such as insulin resistance, muscle diseases, and hypo/hyper-contraction.

New formulas for mixing test to discriminate between lupus anticoagulant and acquired hemophilia A.

Introduction: Lupus anticoagulant (LA) is an antibody that interferes with in vitro coagulation reactions. The mixing test is considered useful for LA diagnosis and is also recommended to differentiate between acquired hemophilia A (AHA) and factor deficiency. However, there has been little study to differentiate between LA and AHA.

Mixing test specific cut-off is more sensitive at detecting lupus anticoagulants than index of circulating anticoagulant.

Introduction: Recent guidelines for lupus anticoagulant (LA) detection recommend mixing test interpretation with either a mixing test-specific cut-off (MTC) or index of circulating anticoagulant (ICA). Few studies directly compare efficacy of these approaches. We retrospectively applied MTC and ICA assessment to raw data of 350 LA-positive plasmas from non-anticoagulated patients to compare detection rates of inhibition.

Verification of the guidelines for lupus anticoagulant detection: usefulness of index for circulating anticoagulant in APTT mixing test.

Introduction: Lupus anticoagulant (LA) is an antibody that interferes with one or more in vitro coagulation reactions, which are dependent on interactions with protein-phospholipid complexes. For LA diagnosis, a mixing test is considered useful for differentiating the inhibitor from a factor deficiency. However, the usefulness and the index of circulating anticoagulant (ICA) in a mixing test with activated partial thromboplastin time (APTT) has not been adequately investigated, and there is scant information regarding the effects of warfarin, heparin, and hemophilia plasma on ICA.