Changes in Coagulation Testing During a National Shortage of Blue-Top Tubes.

OBJECTIVES: Manufacturer recalls and altered supply chains during the coronavirus disease 2019 (COVID-19) pandemic caused a nationwide shortage of blue-top tubes (BTTs). Most non-point-of-care coagulation tests use these tubes, leaving laboratories and health care facilities in short supply. The Department of Pathology and Laboratory Medicine at Cedars-Sinai Medical Center implemented interventions to conserve supply without sacrificing patient safety. METHODS: In a retrospective quality improvement analysis, we examined coagulation testing and BTT utilization over the 3-month interval during which our interventions were applied. Our study assessed the interventions' effectiveness by evaluating changes in BTT utilization, coagulation testing volume, and patient impact. RESULTS: Average daily use (ADU) of BTT before and after the intervention were 476 and 403, respectively-a 15.2% reduction. Notably, the Emergency Department had a reduction in ADU of 43.3%. Average daily volumes of coagulation assays performed decreased from 949 to 783-a 17.5% reduction. No adverse events from the Pharmacy Department were identified during the study period. CONCLUSIONS: Interventions resulting in significant reductions were in divisions with effective management and supervision. Success in navigating the BTT shortage stemmed from timely announcements, action, and effective communication. Our recommendations established more effective coagulation assay utilization, decreased overall BTT use, and prevented patients with coagulopathic disorders from experiencing adverse consequences.

Reply to Bareille et al. Are Viscoelastometric Assays of Old Generation Ready for Disposal? Comment on "Volod et al. Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices. J. Clin. Med. 2022, 11, 860".

We are pleased to see that Bareille et al. have written a Commentary: "Are viscoelastometric assays of old generation ready for disposal?" [...].

Viscoelastic Testing in the Management of Adult Patients on Mechanical Circulatory Support Devices with Focus on Extracorporeal Membrane Oxygenation.

Thromboembolic and hemorrhagic complications continue to remain frequent complications that significantly impact the morbidity and mortality of patients implanted with mechanical circulatory support devices (MCSDs). The severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) has resulted in a number of COVID-19 patients being supported by MCSDs, specifically extracorporeal membrane oxygenation (ECMO), which in turn has created a crucial need for rapid assessment of hemostatic status in these patients to avoid bleeding and thrombotic complications. Currently, conventional plasma-based coagulation assays such as prothrombin time and activated partial thromboplastin time (aPTT) are used to assess hemostasis, and the activated clotting time (ACT) and aPTT are the most common tests used to monitor heparin anticoagulation in patients on ECMO. Unfractionated heparin remains the mainstay anticoagulation therapy for patients on ECMO. Extracorporeal Life Support Organization (ELSO) offers little guidance on the subject but does state that each institution should create its internal anticoagulation protocols. Viscoelastic assays (VEAs) are increasingly recognized by ELSO and ECMO community for their potential to assess hemostatic derangements in patients implanted with MCSDs as well as guidance for appropriate hemostatic therapy. This review focuses on the evidence for the use of viscoelastic assays to assess overall hemostasis and to guide the treatment of adult patients connected to an ECMO circuit. Limitations of the use of conventional assays, ACT, and VEA are also discussed.

Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices.

Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy.

Improvement in plasma D-dimer level in severe SARS-CoV-2 infection can be an indicator of fibrinolysis suppression: Case reports.

RATIONALE: Fibrinolysis shutdown associated with severe thrombotic complications is a recently recognized syndrome that was previously seldom investigated in patients with severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It presents a unique therapeutic dilemma, as anticoagulation with heparin alone is insufficient to address the imbalance in fibrinolysis. And while the use of fibrinolytic agents could limit the disease severity, it is often associated with bleeding complications. There is a need for biomarkers that will guide the timely stratification of patients into those who may benefit from both anticoagulant and fibrinolytic therapies. PATIENT CONCERNS: All 3 patients presented with shortness of breath along with comorbidities predisposing them to severe SARS-CoV-2 infection. One patient (Patient 3) also suffered from bilateral deep venous thrombosis. DIAGNOSES: All 3 patients tested positive for SARS-CoV-2 RNA by reverse transcription polymerase chain reaction (RT-PCR) and were eventually diagnosed with respiratory failure necessitating intubation. INTERVENTIONS: All 3 patients required mechanical ventilation support, 2 of which also required renal replacement therapy. All 3 patients were also placed on anticoagulation therapy. OUTCOMES: In Patients 1 and 2, the initial D-dimer levels of 0.97 µg/ml fibrinogen equivalent units (FEU) and 0.83 µg/ml FEU were only slightly elevated (normal <0.50 µg/ml FEU). They developed rising D-dimer levels to a peak of 13.21 µg/ml FEU and >20.0 µg/ml FEU, respectively, which dropped to 1.34 µg/ml FEU 8 days later in Patient 1 and to 2.94 µg/ml on hospital day 13 in Patient 2. In Patient 3, the D-dimer level on admission was found to be elevated to >20.00 µg/ml FEU together with imaging evidence of thrombosis. And although he received therapeutic heparin infusion, he still developed pulmonary embolism (PE) and his D-dimer level declined to 5.91 µg/ml FEU. Despite "improvement" in their D-dimer levels, all 3 patients succumbed to multi-system organ failure. On postmortem examination, numerous arterial and venous thromboses of varying ages, many consisting primarily of fibrin, were identified in the lungs of all patients. LESSONS: High D-dimer levels, with subsequent downtrend correlating with clinical deterioration, seems to be an indicator of fibrinolysis suppression. These findings can help form a hypothesis, as larger cohorts are necessary to demonstrate their reproducibility.

Viscoelastic hemostasis assays in septic, critically ill coronavirus disease 2019 patients: a practical guide for clinicians.

Coronavirus disease 2019 (COVID-19)-associated coagulopathy is unusual, poorly defined and is linked with significant hypercoagulability and microthrombotic and macrothrombotic complications leading to worse outcomes and higher mortality. Conventional coagulation assays do not always actively reflect these derangements and might fail to detect this coagulopathy. Viscoelastic hemostatic assays (VHA) provide a possible tool that adds to conventional coagulation assays in identifying this hypercoagulable state. VHA has been mostly used in surgery and trauma but it's still not well defined in sepsis patients with lack of large randomized trials. Few studies described VHA findings in patients with COVID-19 showing significant hypercoagulability and fibrinolysis shutdown. Clinicians taking care of these patients might have little experience interpreting VHA results. By reviewing the available literature on the use of VHA in sepsis, and the current knowledge on COVID-19-associated coagulopathy we provide clinicians with a practical guide on VHA utilization in patients with COVID-19.

Acute ophthalmic artery occlusion in a COVID-19 patient on apixaban.

We report a case of ophthalmic artery occlusion (OAO) in a young patient with COVID-19 infection that was on therapeutic anticoagulation with apixaban for deep venous thrombosis (DVT). A 48-year-old man with obesity was hospitalized with a severe form of COVID-19 infection, complicated with acute respiratory failure, septic shock, dilated cardiomyopathy and fungemia. Despite treatment with prophylactic enoxaparin (initial D-Dimer 1.14 µg/ml FEU (normal < 0.05 µg/ml FEU), D-Dimer increased to above 20 µg/ml FEU and patient continued to spike high fevers. This prompted further investigations and upper and lower extremities DVTs were confirmed and managed with enoxaparin 1 mg/kg twice daily. D-dimer level decreased to 4.98 µg/ml FEU while on therapeutic anticoagulation. Three weeks later pending hospital discharge, the anticoagulation was switched to oral apixaban 10 mg twice daily. Patient developed acute severe right eye visual loss of no light perception and was diagnosed with incomplete OAO. D-Dimer was elevated at 2.13 µg/ml FEU. Stroke etiological work-up found no embolic sources, resolution of the dilated cardiomyopathy and negative antiphospholipid antibodies. Treatment was changed to enoxaparin and no thrombotic events were encountered to date. Ocular vascular complications have not yet been reported in COVID-19. Controversy exists on the best management algorithm for the hypercoagulable state associated to COVID-19 Either direct oral anticoagulants or low-molecular-weight-heparin are considered appropriate at discharge for patients with venous thromboembolism. The optimum regimen for ischemic stroke prevention and the significance of D-Dimer for anticoagulation monitoring in COVID-19 remain unclear.