Thrombin generation: a comparison of assays using platelet‐poor and ‐rich plasma and whole blood samples from healthy controls and patients with a history of venous thromboembolism

Tappenden, Kerry A.; Gallimore, Michael J.; Evans, Gillian; Mackie, Ian; Jones, David

doi:10.1111/j.1365-2141.2007.06732.x

Cited by 42 publications

(53 citation statements)

References 19 publications

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“…ETP and peak thrombin were found to be increased in patients with a history of VTE compared to healthy individuals and were related to the risk of a first event of VTE. 56,57 Hron et al reported on the relationship between recurrent VTE and peak thrombin generation and concluded that patients with a peak thrombin less than 300 nM (lower tertile) had a significantly lower risk of recurrence compared to patients with peak thrombin generation above the upper tertile of 400 nmol/L (relative risk [95% CI]: 0.37 [0.20 to 0.67]). 58 Data on the ETP and other parameters of the TG assay are not given in this report.…”

Section: Thrombin Generationmentioning

confidence: 99%

Biomarkers and Venous Thromboembolism

Pabinger

2009

ATVB

136

109

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Abstract-Venous thromboembolism (VTE) represents a significant health concern because of its high morbidity and mortality and is moreover characterized by high rates of recurrence. It would be useful to know biomarkers that enable early identification of patients at high or low risk of primary and recurrent VTE. enous thromboembolism is a frequent disease with an age-adjusted incidence of 1 to 2 events per 1000 of the general population and constitutes a major health care problem because of its high morbidity and mortality. 1 About one-third of patients suffering from a first episode of deep venous thrombosis (DVT) or pulmonary embolism (PE) develops a recurrence of VTE within 10 years. 2 From a clinical perspective, it would be extremely helpful to have biomarkers that enable early identification of patients at high or low risk of primary and recurrent VTE and allow prompt diagnosis and therapy assessment.In this brief overview only some selected biomarkers associated with a first or recurrent event of VTE are highlighted that are either well-investigated (D-Dimer and coagulation factor VIII), novel and promising (P-selectin and endogenous thrombin potential), or controversially discussed (inflammatory cytokines). D-DimerD-Dimer is a degradation product of cross-linked fibrin that is formed immediately after thrombin-generated fibrin clots are degraded by plasmin and reflects a global activation of blood coagulation and fibrinolysis. As D-Dimer levels rise during an acute event of VTE, testing for D-Dimer was explored as a tool for the diagnosis of VTE and has been integrated into diagnostic algorithms in the management of patients with suspected VTE. [3][4][5] Being the best-recognized biomarker for the initial assessment of suspected VTE, a negative value of D-Dimer may safely rule out both DVT and PE with a high sensitivity of up to 95% and a negative predictive value of nearly 100%, using the various commercially available D-Dimer assays. However, because of its poor specificity to prove VTE, D-Dimer testing has to be included in comprehensive sequential diagnostic strategies that incorporate clinical probability assessment and imaging techniques.Elevated D-Dimer levels may also indicate the presence of hypercoagulability. In a case-control study high D-Dimer levels (Ͼ70 th percentile of levels in healthy controls) measured at least 6 months after a first event of DVT in 474 patients and 474 age-and sex-matched control individuals have been shown to be associated with a 2.2-fold increase in the risk of thrombosis. 6 In a population-based cohort study D-Dimer was investigated as a risk factor for the occurrence of a future first event of VTE and was associated with a 3-fold increased risk. 7 Moreover, D-Dimer levels are a wellinvestigated biomarker for the prediction of the risk of VTE recurrence after discontinuing oral anticoagulant therapy in prospective cohort studies. 8 Palareti et al measured D-Dimer levels 1 month after withdrawal of oral anticoagulation in subjects with previous unprovoked VTE and de...

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Section: Thrombin Generationmentioning

confidence: 99%

Biomarkers and Venous Thromboembolism

Pabinger

2009

ATVB

136

109

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“…The method is, however, not applicable for measuring TG in whole blood. Variable quenching of the fluorescent signal by hemoglobin and red blood cells that sediment, cluster, and retract with the clot lead to highly erratic signals (10,11 ). The use of fibrin as an indicator product for TG in whole blood, as in thromboelastography (TEG), does not reflect the thrombin-generating capacity of patients, because fibrinogen as a substrate is quickly exhausted and therefore informs about TG only at the earliest phases of the coagulation process (5,12 ).…”

confidence: 99%

Whole-Blood Thrombin Generation Monitored with a Calibrated Automated Thrombogram-Based Assay

et al. 2012

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BACKGROUND The calibrated automated thrombogram (CAT) assay in plasma is a versatile tool to investigate patients with hypo- or hypercoagulable phenotypes. The objective was to make this method applicable for whole blood measurements. METHODS Thin-layer technology and the use of a rhodamine 110–based thrombin substrate appear to be essential for a reliable thrombin generation (TG) assay in whole blood. Using this knowledge we developed a whole blood CAT-based assay. RESULTS We demonstrated that the whole blood CAT-based assay is a sensitive and rapid screening test to assess function of the hemostatic system under more nearly physiological conditions than the TG assay in plasma. Under conditions of low tissue factor concentration (0.5 pmol/L) and 50% diluted blood, the intraassay CV of the thrombogram parameters, endogenous thrombin potential and thrombin peak height, were 6.7% and 6.5%, respectively. The respective interassay CVs were 12% and 11%. The mean interindividual variation (SD) of 40 healthy volunteers was 633 (146) nmol · min/L for the endogenous thrombin potential and 128 (23) nmol/L for the thrombin peak. Surprisingly, erythrocytes contributed more than platelets to the procoagulant blood cell membranes necessary for optimal TG. Statistically significant (P < 0.001) and potentially clinically significant correlations were observed between circulating factor-VIII concentrations in blood of hemophilia A patients and endogenous thrombin potential (r = 0.62) and thrombin peak height (r = 0.58). CONCLUSIONS We have developed a reliable method to measure TG in whole blood. The assay can be performed with a drop of blood and may provide a useful measurement of TG under more physiological conditions than plasma.

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“…Ayrıca literatürde tromboz riski ile ilgili yapılmış çalışmalarda, trombin formasyonundaki çeşitliliklere bağlı olarak TGA testi parametrelerinin hepsi artmaktadır; fakat en önemli ve trombin oluşumunu gösteren en hassas parametre ETP değeridir. [39][40][41][42] Macey ve ark.nın preeklamptik gebeler, sağ-lıklı gebeler ve sağlıklı gebe olmayan kadınlarda yaptığı çalışmada ise duraklama zamanı ve pik zamanı preeklamptik gebelerde preeklampsisi olmayan gebelere göre, preeklampsisi olamayan gebelerde ise sağlıklı kadınlara göre daha kısa bulunmuştur. 35 Bu çalışmada hastaların trombofili göstergeleri hakkında veri bulunmamaktadır.…”

Section: Discussionunclassified