Treatment of thrombotic cardiovascular diseases in people with haemophilia: A Japanese consensus study.

Introduction: Cardiovascular diseases (CVD) that require long-term anticoagulant and antiplatelet therapy presents a problem in people with haemophilia (PWH) who receive factor replacement therapy to reduce bleeding risk. Currently, there are no Japanese guidelines for the management of PWH with CVD.

Aim: To develop expert guidance on managing CVD in PWH in Japan.

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.

[Suspected autoimmune coagulation factor IX deficiency difficult to diagnose due to concurrent lupus anticoagulant].

A woman in her 70s who was undergoing treatment for an overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis developed persistent genital bleeding. Coagulation tests revealed a longer activated partial thromboplastin time, a 7% decrease in coagulation factor IX activity (FIX:C) and a FIX inhibitor (of 3 BU/ml). Lupus anticoagulant (LA), anticardiolipin antibody, and anti-β2 glycoprotein I antibody were positive, and the activated partial thromboplastin time cross-mixing test suggested the presence of LA.

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).

Bleeding After Gastric Endoscopic Submucosal Dissection Focused on Management of Xa Inhibitors.

Purpose: The use of direct oral Xa inhibitors (DXaIs) to prevent venothrombotic events is increasing. However, gastrointestinal bleeding, including that related to endoscopic resection, is a concern. In this study, we evaluated bleeding and coagulation times during the perioperative period of gastric endoscopic submucosal dissection (ESD).

Determination of diagnostic threshold in harmonization and comparison of clinical utility for five major antiphospholipid antibody assays used in Japan.

Background: Anticardiolipin antibodies (aCL) and anti-β -glycoprotein I antibodies (aβ GPI) are essential in diagnosing antiphospholipid syndrome (APS) according to the international APS guideline. Five commercial assays for aCL and aβ GPI are available in Japan, but their test results are quite discordant. For harmonization of diagnosing APS, upper reference limit (URL) and diagnostic accuracy of each assay were evaluated and compared by testing common sets of specimens across all assays.

Measurement of coagulation factor antibody levels is useful for diagnosis and determining therapeutic efficacy in hemorrhagic patients with autoantibodies to coagulation factor VIII and factor V: results from a single center in Japan.

Coagulation factor inhibitors (CFIs) sometimes cause fatal bleeding conditions. Determination of an inhibitor titer (INH-titer) using the Bethesda method is essential for diagnosing diseases associated with CFIs and examining the effects of immunosuppressive therapy. We reviewed 17 cases with CFIs (acquired hemophilia A, n = 11; FV inhibitor, n = 6) to examine the usefulness of determining quantities of an autoantibody to a coagulation factor (CF-IgG) by ELISA for diagnosis and therapeutic efficacy, as compared with INH-titer.

[Antiphospholipid syndrome: diagnosis and management].

Antiphospholipid syndrome (APS) is an acquired thrombophilia associated with autoimmunity and is a syndrome that should always be considered when examining patients with thrombosis and pregnancy complications. As per the Sydney criteria, a diagnosis can be established with at least one clinical finding, such as arteriovenous thrombosis and the presence of at least one of the antiphospholipid antibodies (aPL), such as anticardiolipin antibodies (aCL). Moreover, phosphatidylserine-dependent anti-prothrombin antibody and anti-b2GPI-domain 1 antibody are correlated with APS manifestations and enable APS diagnosis.

International Council for Standardization in Haematology (ICSH) laboratory guidance for the verification of haemostasis analyser-reagent test systems. Part 2: Specialist tests and calibrated assays.

Before a new method is used for clinical testing, it is essential that it is evaluated for suitability for its intended purpose. This document gives guidance for the performance, verification and implementation processes required by regulatory and accreditation bodies. It covers the planning and verification of specialist haemostatic tests, including factor assays, D-dimers, direct anticoagulants and thrombophilia testing.

Lupus anticoagulant hypoprothrombinemia syndrome associated with bilateral adrenal haemorrhage in a child: early diagnosis and intervention.

Background: Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is characterized by bleeding and thrombosis in patients with autoimmune diseases or infections. Paediatric LAHPS exhibits various degrees of bleeding, ranging from mild to severe; however, adrenal haemorrhage due to LAHPS and its long-term clinical course have not been sufficiently described.

Case Presentation: A 9-year-old boy presented with prolonged abdominal pain and abnormal coagulation screening tests.

Survey of actual conditions of erythema marginatum as a prodromal symptom in Japanese patients with hereditary angioedema.

Background: Hereditary angioedema (HAE) is a rare but life-threatening condition. HAE types I and II (HAE-1/2) result from C1-inhibitor (C1-INH) deficiency. However, recent genetic analysis has established a new type of HAE with normal C1-INH (HAEnC1-INH).

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.

International Council for Standardization in Haematology (ICSH) laboratory guidance for the evaluation of haemostasis analyser-reagent test systems. Part 1: Instrument-specific issues and commonly used coagulation screening tests.

Before a new method is used for clinical testing, it is essential that it is evaluated for suitability for its intended purpose. This document gives guidance for the performance of verification, validation and implementation processes required by regulatory and accreditation bodies. It covers the planning and execution of an evaluation of the commonly performed screening tests (prothrombin time, activated partial thromboplastin time, thrombin time and fibrinogen assay), and instrument-specific issues.

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).

Microparticles and Nucleosomes Are Released From Parenchymal Cells Destroyed After Injury in a Rat Model of Blunt Trauma.

We investigated the relationships between circulating procoagulants and trauma severity, including cellular destruction, and the effects of thrombin generation on procoagulants in a rat blunt trauma model. The rats were subjected to tumbling blunt trauma, where they were tumbled for 0, 250, 500, or 1000 revolutions. Creatine kinase, nucleosome, and microparticle plasma levels increased gradually with trauma severity.

Novel assay based on diluted prothrombin time reflects anticoagulant effects of direct oral factor Xa inhibitors: Results of multicenter study in Japan.

Background: Direct oral anticoagulants targeting factor Xa (DXaIs) are administered as prophylaxis for various venothrombotic diseases without routine monitoring required. However, assessment of their anticoagulant effects is necessary to prevent severe events, including major bleeding and/or refractory thrombosis.

Objectives: We examined the correlation of ratio of inhibited thrombin generation (RITG), determined using a novel assay based on dilute prothrombin time (dPT), with coagulant markers and laboratory test results to show drug effects.

Knockdown of long noncoding RNA dreh facilitates cell surface GLUT4 expression and glucose uptake through the involvement of vimentin in 3T3-L1 adipocytes.

Glucose uptake in adipocytes is crucial for regulating systemic metabolism. Long noncoding RNAs (lncRNAs), defined as being transcripts with lengths exceeding 200 nucleotides that are not translated, are recently identified regulators of cellular functions. Previously, we have shown that an lncRNA, "down-regulated expression by hepatitis B virus X" (dreh), is involved in glucose transport in skeletal muscle cells.

Overshoot of FVIII activity in patients with acquired hemophilia A who achieve complete remission.

Acquired hemophilia A (AHA) is a rare, life-threatening bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII). Immunosuppressive therapy for AHA aims to arrest bleeding by eliminating FVIII inhibitors. Factor VIII activity overshoot after complete remission (CR) has been reported anecdotally, but details remain unclear.