Perioperative Management of Buprenorphine at an Urban Academic Medical Center.

Introduction: Buprenorphine is a partial mu opioid receptor agonist with high affinity to its receptor, which raises concerns of blocking or displacing full opioid agonists when used during the perioperative period of surgical patients. However, buprenorphine itself has high analgesic potency and discontinuing buprenorphine may lead to suboptimal pain control and risk for opioid use disorder relapse. There is limited data for the continuation of buprenorphine perioperatively.

Retrospective, multicenter analysis of the safety and effectiveness of direct oral anticoagulants for the treatment of venous thromboembolism in obesity.

Background: Direct oral anticoagulants (DOACs) are the preferred treatment for venous thromboembolism (VTE). However, DOAC use in patients with a BMI greater than 40 kg/m has not been well studied despite the growing prevalence of obesity, and current literature is often underpowered.

Methods: This multicenter, retrospective, observational study evaluated patients 18 years and older who received DOACs for acute VTE treatment.

Direct oral anticoagulants or vitamin K antagonists in emergencies: comparison of management in an observational study.

Background: Restoring hemostasis in patients on oral anticoagulants presenting with major hemorrhage (MH) or before surgical intervention has changed, with the replacement of vitamin K antagonist (VKA) with direct oral anticoagulants (DOACs).

Objectives: To observe the difference in urgent hemostatic management between patients on VKA and those on DOACs.

Methods: A multicenter observational study evaluated the variation in laboratory testing, hemostatic management, mortality, and hospital length of stay (LOS) in patients on VKA or DOACs presenting with MH or urgent hemostatic restoration.

Serotonin Release Assay: Functional Assay for Heparin- and Vaccine-Induced (Immune) Thrombotic Thrombocytopenia.

The serotonin release assay (SRA) has been the gold-standard assay for detection of heparin-dependent platelet-activating antibodies and integral for the diagnosis for heparin-induced thrombotic thrombocytopenia (HIT). In 2021, a thrombotic thrombocytopenic syndrome was reported after adenoviral vector COVID-19 vaccination. This vaccine-induced thrombotic thrombocytopenic syndrome (VITT) proved to be a severe immune platelet activation syndrome manifested by unusual thrombosis, thrombocytopenia, very elevated plasma D-dimer, and a high mortality even with aggressive therapy (anticoagulation and plasma exchange).

Platelet-activating functional assay resolution in vaccine-induced immune thrombotic thrombocytopenia: differential alignment to PF4 ELISA platforms.

Background: Anti-platelet factor 4 (PF4) antibodies in vaccine-induced immune thrombotic thrombocytopenia (VITT) appear to be transient, with discrepant persistence depending on the platform used for detection.

Objectives: We aimed to report a longitudinal study of antibody persistence using 2 ELISA platforms and 2 platelet-activating functional assays in a clinical cohort of patients with VITT referred for follow-up testing.

Methods: In total, 32 Australian patients with VITT or pre-VITT, confirmed by expert adjudication, with samples referred for clinical follow-up were included.

Vaccine-induced immune thrombotic thrombocytopenia post dose 2 ChAdOx1 nCoV19 vaccination: Less severe but remains a problem.

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but established complication of 1st dose ChAdOx1 nCoV19 vaccination (AZD1222), however this complication after dose 2 remains controversial.

Objectives: To describe the clinicopathological features of confirmed cases of VITT post dose 2 AZD1222 vaccination in Australia, and to compare this cohort to confirmed cases of VITT post 1st dose.

Methods: Sequential cases of clinically suspected VITT (thrombocytopenia, D-Dimer > 5x upper limit normal and thrombosis) within 4-42 days of dose 2 AZD1222 referred to Australia's centralised testing centre underwent platelet activation confirmatory testing in keeping with the national diagnostic algorithm.

A multicenter evaluation of the Technoscreen ADAMTS13 activity semi-quantitative screening test for thrombotic thrombocytopenic purpura diagnosis and exclusion.

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal microangiopathy, with an untreated mortality rate of around 90%. TTP is caused by severe deficiency in ADAMTS13, which results in accumulation of ultra large von Willebrand factor multimers, triggering a consumptive thrombocytopenia, microangiopathic hemolytic anemia and end-organ dysfunction and damage. Demonstration of severe ADAMTS13 deficiency is diagnostic for TTP, but long turnaround times for quantitative activity testing often necessitates empirical plasma exchange and/or caplacizumab treatment.

Assessment of immunological anti-platelet factor 4 antibodies for vaccine-induced thrombotic thrombocytopenia (VITT) in a large Australian cohort: A multicenter study comprising 1284 patients.

Background: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus-based vaccines aimed to prevent and minimize COVID-19 and related pathophysiology.

Objectives: To describe patterns of testing for anti-platelet factor 4 (PF4) antibodies using various ELISA assays in a large Australian cohort and comparative functional platelet activation assays in a subset.

Patients/methods: Asserachrom HPIA IgG ELISA was performed in 1284 patients over a period of 12 months, supplemented in select cohorts by comparative ELISA using three other methods (n = 78-179), three different functional assays (flow cytometry, serotonin release assay, and/or Multiplate; n = 476), and rapid immunological chemiluminescence anti-PF4 assay (n = 460), in a multicenter study.

Harmonizing factor assay-related testing performed in a large laboratory network.

Coagulation factor testing is commonly performed within haemostasis laboratories, either to assess for bleeding disorders, such as haemophilia, or to investigate unexplained prolongation in routine coagulation assays. The aim of this evaluation was to harmonize procedures and normal reference ranges (NRRs) for investigation of coagulation factors on the ACL TOP 50 family of instruments in a large laboratory network. We employed comparative evaluations using newly installed ACL TOPs 550 and 750 and HemosIL reagents vs.

Harmonizing platelet function analyzer testing and reporting in a large laboratory network.

Introduction: The platelet function analyzer (PFA) is a popular platelet function screening instrument, highly sensitive to von Willebrand disease (VWD) and to aspirin therapy, with moderate sensitivity to defects in platelet function and/or deficiencies in platelet number. There are two models, the original PFA-100 and the contemporary PFA-200. Normal reference ranges (NRRs) provided by the manufacturer are the same for both models, instead being based on the type of test cartridge, for which there are two main ones: collagen/epinephrine (C/Epi) and collagen/adenosine diphosphate (C/ADP).

A pilot study assessing the implementation of 96-well plate-based aggregometry (Optimul) in Australia.

Identification of disordered platelet function is important to guide peri-operative bleeding management as well as long term treatment and prognostic strategies in individuals with platelet bleeding disorders. Light transmission aggregometry (LTA), the current gold standard diagnostic test of platelet function is a time consuming technique almost exclusively performed in specialised laboratories and almost universally unavailable in regional centres in Australia, where there is an unmet need for access to specialised platelet function diagnostic services. 96-well plate-based aggregometry (Optimul, UK), has been utilised in research laboratories as a novel platform to investigate platelet function.

A novel flow cytometry procoagulant assay for diagnosis of vaccine-induced immune thrombotic thrombocytopenia.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe prothrombotic complication of adenoviral vaccines, including the ChAdOx1 nCoV-19 (Vaxzevria) vaccine. The putative mechanism involves formation of pathological anti-platelet factor 4 (PF4) antibodies that activate platelets via the low-affinity immunoglobulin G receptor FcγRIIa to drive thrombosis and thrombocytopenia. Functional assays are important for VITT diagnosis, as not all detectable anti-PF4 antibodies are pathogenic, and immunoassays have varying sensitivity.

The utility of flow cytometric platelet forward scatter as an alternative to mean platelet volume.

The use of mean platelet diameter (MPD) to classify inherited thrombocytopenia (IT) has been demonstrated in several studies. Alternatively, the mean platelet volume (MPV) may be used, but in macrothrombocytopenia this may not be available. We hypothesized that platelet forward scatter (FSC) measurements using flow cytometry may be used for the size-based classification of IT.

A multi-laboratory assessment of lupus anticoagulant assays performed on the ACL TOP 50 family for harmonized testing in a large laboratory network.

Introduction: Lupus anticoagulant (LA) testing is commonly performed within hemostasis laboratories, and the ACL TOP 50 family of instruments represent a new "single platform" of hemostasis instrumentation. Our aim was to evaluate these instruments and manufacturer reagents or alternatives for utility in LA testing.

Methods: Comparative evaluations of LA testing using newly installed ACL TOPs 550 and 750 as well as comparative assessments with existing "reference," predominantly Stago, instrumentation, and reagents.

Two Weeks of Low Molecular Weight Heparin for Isolated Symptomatic Distal Vein Thrombosis (TWISTER study).

Background: Treatment of low-risk patients with isolated symptomatic distal deep vein thrombi (IDDVT) is uncertain.

Objective: assess whether two weeks of therapeutic anticoagulation is efficacious/safe for IDDVT.

Primary Outcome: symptomatic three-month venous thromboembolism (VTE) incidence in the two-week anticoagulation group.

Building platelet phenotypes: Diaphanous-related formin 1 (DIAPH1)-related disorder.

Variants of the Diaphanous-Related Formin 1 () gene have recently been reported causing inherited macrothrombocytopenia. The essential/"diagnostic" characteristics associated with the disorder are emerging; however, robust and complete criteria are not established. Here, we report the first cases of -related disorder in Australia caused by the autosomal dominant gain-of-function DIAPH1 R1213X variant formed by truncation of the protein within the diaphanous auto-regulatory domain (DAD) with loss of regulatory motifs responsible for autoinhibitory interactions within the DIAPH1 protein.

A multi-laboratory assessment of congenital thrombophilia assays performed on the ACL TOP 50 family for harmonisation of thrombophilia testing in a large laboratory network.

Objectives: Thrombophilia testing is commonly performed within hemostasis laboratories, and the ACL TOP 50 family of instruments represent a new 'single platform' of hemostasis instrumentation. The study objective was to evaluate these instruments and manufacturer reagents for utility of congenital thrombophilia assays.

Methods: Comparative evaluations of various congenital thrombophilia assays (protein C [PC], protein S [PS], antithrombin [AT], activated protein C resistance [APCR]) using newly installed ACL TOPs 550 and 750 as well as comparative assessments with existing, predominantly STAGO, instrumentation and reagents.

Verification of the ACL Top 50 Family (350, 550, and 750) for Harmonization of Routine Coagulation Assays in a Large Network of 60 Laboratories.

Objectives: To verify a single platform of hemostasis instrumentation, the ACL TOP 50 Family, comprising 350, 550, and 750 instruments, across a large network of 60 laboratories.

Methods: Comparative evaluations of instrument classes (350 vs 550 and 750) were performed using a large battery of test samples for routine coagulation tests, comprising prothrombin time/international normalized ratio, activated partial thromboplastin time (APTT), thrombin time, fibrinogen and D-dimer, and using HemosIL reagents. Comparisons were also made against existing equipment (Diagnostica Stago Satellite, Compact, and STA-R Evolution) and existing reagents to satisfy national accreditation standards.

A multicenter laboratory assessment of a new automated chemiluminescent assay for ADAMTS13 activity.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal disorder caused by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency. Prompt identification/exclusion of TTP can thus be facilitated by rapid ADAMTS13 testing. The most commonly utilized (enzyme-linked immunosorbent assay [ELISA]-based) assay takes several hours to perform and so does not generally permit rapid testing.

A multicentre assessment of contemporary laboratory assays for heparin induced thrombocytopenia.

Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy. In some patients, HIT causes platelet activation and thrombosis (sometimes abbreviated HITT), which leads to adverse clinical sequalae ('pathological HIT'). The likelihood of HIT is initially assessed clinically, typically using a scoring system, of which the 4T score is that most utilised.