Global coagulation assays in hypercoagulable states

Lim, Hui Yin; Donnan, Geoffrey A; Nandurkar, Harshal; Ho, Prahlad

doi:10.1007/s11239-021-02621-1

Cited by 17 publications

(26 citation statements)

References 89 publications

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“…Assays require calibration, and although several commercial kits exist, limitations including a lack of standardisation and reference values across laboratories have been highlighted and are being addressed. 115,116 Thrombin generation assays are becoming more prevalent, but will require additional clinical trials with well-defined endpoints to fully determine utility.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Bleeding Propensity in Waldenström Macroglobulinemia: Potential Causes and Evaluation

et al. 2022

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Waldenström Macroglobulinaemia (WM) is a rare, incurable, low-grade, B cell lymphoma. Symptomatic disease commonly results from marrow or organ infiltration and hyperviscosity secondary to IgM paraprotein, manifesting as anaemia, bleeding and neurological symptoms among others. The causes of the bleeding phenotype in WM remain obscure but are likely to involve several intersecting mechanisms. Evidence of defects in platelet function is lacking in the literature, but factors impacting platelet function and coagulation pathways such as hyperviscosity, vascular bed disturbances, abnormal haematopoiesis, acquired von Willebrand Factor (VWF) syndrome and cryoglobulinaemia may contribute to bleeding. Understanding the pathophysiological mechanisms behind bleeding are important, as common WM therapies including chemo-immunotherapy and Bruton’s tyrosine kinase inhibitors, carry attendant bleeding risks. Furthermore, due to the relatively indolent nature of this lymphoma, most patients diagnosed with WM are often older and have one or more comorbidities requiring treatment with anticoagulant or antiplatelet drugs. It is thus important to understand the origin of the WM bleeding phenotype to better stratify patients according to their bleeding risk and thus enhance confidence in clinical decisions regarding treatment management. In this review, we detail the evidence for various contributing factors to the bleeding phenotype in WM and focus on current and emerging diagnostic tools that will aid evaluation and management of bleeding in these patients.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Bleeding Propensity in Waldenström Macroglobulinemia: Potential Causes and Evaluation

et al. 2022

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“…The complex interplay between three elements—the presence of hypercoagulable state, flow stasis and endothelial injury or dysfunction—provides the perfect storm for thrombogenesis [ 4 ]. Traditionally used to describe the pathophysiology of venous thrombosis, it has become evident that these three factors are also pertinent to the evolution of arterial thrombosis [ 4 , 27 , 28 ] and hence cardiovascular disease. In addition, atherosclerosis has been closely linked to venous thromboembolism (VTE); patients with VTE appear to have common risk factors with atherosclerosis, and patients with unprovoked VTE have also demonstrated higher prevalences of arterial thrombosis compared with healthy controls [ 29 , 30 ].…”

Section: Virchow’s Triad and Its Association With Thrombosis And Card...mentioning

confidence: 99%

“…In atherosclerosis, the triad are representative of abnormalities in the endothelium, platelets and coagulation and fibrinolytic pathways, as well as in hemorheology and turbulence at bifurcation and stenotic regions [ 4 , 27 , 28 ]. Atherosclerosis is a result of chronic inflammation involving circulating factors, endothelial cells, vascular smooth muscle cells and mononuclear cells due to repeated exposure to vascular injury such as plasma lipids, particularly low-density lipoproteins.…”

Section: Virchow’s Triad and Its Association With Thrombosis And Card...mentioning

confidence: 99%

“…While conventional coagulation assays are not useful in predicting thrombosis risks, global coagulation assays provide a more comprehensive assessment of coagulation including the evaluation of the final products of the coagulation cascade, thrombin and fibrin [ 34 , 35 ]. Although limited in their clinical use in thrombosis medicine in the current state, these assays appear promising, particularly in detecting hypercoagulable states [ 27 , 35 ]. Figure 2 shows some of the available global coagulation assays.…”

Section: Virchow’s Triad and Its Association With Thrombosis And Card...mentioning

confidence: 99%

“…Viscoelastic testing such as thromboelastography and rotational thromboelastometry measures the changes in the elastic properties of whole blood during clot formation and propagation, clot firmness and fibrinolytic dissolution [ 36 ]. It is clinically used to guide transfusion requirements in bleeding and trauma situations [ 35 ], and it is reported to be more hypercoagulable in diabetes, stroke, hematological and oncological malignancies, and pregnancy [ 27 , 37 , 38 , 39 ] in small observational studies. Furthermore, Rafiq et al found that patients undergoing coronary artery bypass grafting surgery with hypercoagulable maximum amplitude (a measure of clot strength) on thromboelastography had a higher risk of composite thromboembolic complications and mortality after surgery [ 40 ].…”

Section: Virchow’s Triad and Its Association With Thrombosis And Card...mentioning

confidence: 99%

See 2 more Smart Citations

The Need for Individualized Risk Assessment in Cardiovascular Disease

Lim

Burrell

Brook

et al. 2022

JPM

Self Cite

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Cardiovascular disease remains the leading cause of death in the era of modern medicine despite major advancements in this field. Current available clinical surrogate markers and blood tests do not adequately predict individual risk of cardiovascular disease. A more precise and sophisticated tool that can reliably predict the thrombosis and bleeding risks at an individual level is required in order for clinicians to confidently recommend early interventions with a favorable risk–benefit profile. Critical to the development of this tool is the assessment and understanding of Virchow’s triad and its complex interactions between hypercoagulability, endothelial dysfunction and vessel flow, a fundamental concept to the development of thrombosis. This review explores the pathophysiology of cardiovascular disease stemming from the triad of factors and how individualized risk assessment can be improved through the multimodal use of tools such as global coagulation assays, endothelial biomarkers and vessel flow assessment.

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Activity Sensing of Coagulation and Fibrinolytic Proteases

Sondag¹,

Verhoeven²,

Löwik³

et al. 2023

Chemistry A European J

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The blood coagulation cascade is a complex physiological process involving the action of multiple coupled enzymes, cofactors, and substrates, ultimately leading to clot formation. Serine proteases have a crucial role, and aberrations in their activity can lead to life-threatening bleeding disorders and thrombosis. This review summarizes the essential proteases involved in blood coagulation and fibrinolysis, the endogenous peptide sequences they recognize and hydrolyze, and synthetic peptide probes based on these sequences to measure their activity. The information in this review can contribute to developing novel anticoagulant therapies and specific substrates for point-of-care diagnosis of coagulation pathologies.

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Global coagulation assays in hypercoagulable states

Cited by 17 publications

References 89 publications

Bleeding Propensity in Waldenström Macroglobulinemia: Potential Causes and Evaluation

Bleeding Propensity in Waldenström Macroglobulinemia: Potential Causes and Evaluation

The Need for Individualized Risk Assessment in Cardiovascular Disease

Activity Sensing of Coagulation and Fibrinolytic Proteases

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