Global coagulation assays in patients with diabetes mellitus

Lim, Hui Yin; Lui, Brandon; Tacey, Mark; Kwok, Anna; Varadarajan, Suresh; Donnan, Geoffrey A; Nandurkar, Harshal; Ho, Prahlad

doi:10.1002/rth2.12611

Cited by 11 publications

(11 citation statements)

References 35 publications

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“…Using the same methodology as described above, the OHP results of the VTE cohort were compared to those of a previously published cohort of 144 healthy controls (34.7% male, median age 42 years) [ 22 ]. The inclusion criteria for healthy controls were strict and included the absence of any known cardiovascular risk factors, a history of thrombosis, use of oral contraceptives, anticoagulants, or antiplatelets, and a negative thrombophilia screen.…”

Section: Methodsmentioning

confidence: 99%

Overall Hemostatic Potential Assay Detects Risk of Progression to Post-Thrombotic Syndrome in Anticoagulated Patients following Deep Vein Thrombosis

et al. 2022

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Deep vein thrombosis (DVT) frequently leads to post-thrombotic syndrome (PTS) which is challenging to predict and prevent. Identifying those at high risk of developing PTS may help to focus preventative strategies. Adults were recruited within 3 months of DVT diagnosis. Blood was sampled during the therapeutic anticoagulation phase. Overall hemostatic potential (OHP) assay, a spectrophotometric assay, was performed on platelet-poor plasma (PPP). In this assay, fibrin formation is triggered by small amounts of thrombin and termed the overall coagulation potential (OCP). Simultaneously, thrombin and tissue plasminogen activator are added to PPP and the resulting fibrin aggregation curve is the overall hemostatic potential (OHP). Fibrinolysis is expressed by the parameter overall fibrinolytic potential (OFP%). Patients were followed up at regular intervals. PTS was diagnosed if the Villalta score was ≥5 at least 3 months after the DVT diagnosis. Results were obtained from 190 patients (53.7% male, mean age 56.9 years). PTS developed in 62 (32.6%) patients. Patients with PTS displayed significantly higher median OCP (45.8 vs. 38.8 units, p=0.010), OHP (12.8 vs. 9.2 units, p = 0.005) and significantly lower OFP (74.1 vs. 75.6%, p = 0.050). PTS patients had higher neutrophil/lymphocyte ratios (NLR) (2.3 vs. 1.9, p = 0.007). After multivariate analysis, proximal DVT location, history of varicose veins, NLR ≥ 2.6, OHP > 13.0 units and weight >108 kg were independent predictors for PTS. The c-statistic of the multivariate model was 0.77. This pilot study suggests that OHP testing while patients are still anticoagulated may assist in the prediction of PTS development and could assist in prognostication and targeting of preventative measures. However, larger prospective studies are needed to confirm these findings.

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Section: Methodsmentioning

confidence: 99%

Overall Hemostatic Potential Assay Detects Risk of Progression to Post-Thrombotic Syndrome in Anticoagulated Patients following Deep Vein Thrombosis

et al. 2022

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“…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%

“…A study demonstrated that glycated hemoglobin levels (HbA1c) positively correlated with PAI-1 activity ( r = 0.50, p = 0.002) and negatively correlated with tPA activity ( r = −0.452, p = 0.004) [ 44 ]. Previous studies using the overall hemostatic potential assay (OHP), a spectrophotometric assessment of fibrin aggregation, have shown that the intake of omega-3 polyunsaturated can reduce fibrin generation in healthy subjects [ 45 ] and that the overall fibrinolytic potential is impaired in patients with diabetes and those with stable coronary heart disease [ 37 , 46 ]. Another more recent assay to show potential in identifying fibrinolytic dysfunction is plasmin generation using a modified CAT technique by Miszta et al [ 47 ] that was delayed in the plasma of mice fed a high-fat diet to induce obesity [ 48 ].…”

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

confidence: 99%

“…Hence, a multimodality, integrated approach should be adopted. We have recently demonstrated a risk prediction model using a combination of global coagulation assays, age, gender and HbA1c in diabetes patients to be superior to HbA1c alone in predicting diabetic complications [ 37 ]. New data from our work and of others demonstrate that biomarkers such as global coagulation assays and endothelial markers may be reporters of the biological effects of traditional risk factors.…”

Section: Clinical Implications and Future Prospectsmentioning

confidence: 99%

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The Need for Individualized Risk Assessment in Cardiovascular Disease

Lim

Burrell

Brook

et al. 2022

JPM

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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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“…The Overall Haemostatic Potential (OHP) assay is a global coagulation assay that can examine both fibrin production and lysis within the same test system [ 14 ]. This assay has been shown to be able to detect hypercoagulable states following PE [ 15 ] and pregnancy-associated VTE [ 16 ], as well as potentially predict thrombosis in other hypercoagulable states such as diabetes mellitus [ 17 ], ischaemic heart disease [ 18 ] and antiphospholipid syndrome [ 19 ]. However, its role in risk stratification of future VTE recurrence has not been previously explored.…”

Section: Introductionmentioning

confidence: 99%

Overall haemostatic potential (OHP) assay can risk stratify for venous thromboembolism recurrence in anticoagulated patients

Wang

Lim

Brook

et al. 2022

J Thromb Thrombolysis

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Assessing the risk of recurrent venous thromboembolism (VTE), particularly when patients are anticoagulated, remains a major challenge largely due to the lack of biomarkers. Blood was sampled from adult VTE patients recruited between January 2018 and September 2020, while receiving therapeutic anticoagulation. Results were compared to 144 healthy subjects (34.7% male, median age 42 years). Overall haemostatic potential (OHP) assay, a spectrophotometric assay, was performed on platelet-poor plasma, in which fibrin formation (triggered by small amounts of thrombin (overall coagulation potential, OCP)) and fibrinolysis (by the addition of thrombin and tissue plasminogen activator (OHP)) are simultaneously measured. Results were obtained from 196 patients (52.6% male, mean age 57.1 years). Compared to healthy subjects, VTE patients displayed significantly higher OCP (39.6 vs 34.5 units, p < 0.001) and OHP (9.3 vs 6.4 units, p < 0.001) as well as lower overall fibrinolytic potential (75.6 v s81.1%, p < 0.001). All 16 VTE recurrences, including 11 unprovoked, occurred above an OCP cut-off of 40th percentile (recurrence rate 4.32/100 patient-years (100PY), 95% confidence interval (CI) 2.39–7.80, p = 0.002). Of 97 patients who subsequently discontinued anticoagulation, all unprovoked VTE recurrences (n = 9) occurred above the 40th OCP percentile (recurrence rate 9.10/100PY, 95% CI 4.74–17.49, p = 0.005) and the 40th OHP percentile (recurrence rate 8.46/100PY, 95% CI 4.40–16.25, p = 0.009). Our pilot study demonstrates that the OHP assay can detect a hypercoagulable and hypofibrinolytic state in anticoagulated VTE patients and may be able to risk stratify VTE recurrence, allowing for more individualised decision on long-term anticoagulation. Further larger prospective studies are required.

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Global coagulation assays in patients with diabetes mellitus

Cited by 11 publications

References 35 publications

Overall Hemostatic Potential Assay Detects Risk of Progression to Post-Thrombotic Syndrome in Anticoagulated Patients following Deep Vein Thrombosis

Overall Hemostatic Potential Assay Detects Risk of Progression to Post-Thrombotic Syndrome in Anticoagulated Patients following Deep Vein Thrombosis

The Need for Individualized Risk Assessment in Cardiovascular Disease

Overall haemostatic potential (OHP) assay can risk stratify for venous thromboembolism recurrence in anticoagulated patients

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