Thrombin generation and international normalized ratio in inherited thrombophilia patients receiving thromboprophylactic therapy

Luna-Záizar, Hilda; González-Moncada, Ana Isabel; Padilla-López, Emily Lizbeth; Ramírez-Anguiano, Ana Cristina; Pacheco-Moisés, Fermín Paul; Velasco-Ramírez, Sandra Fabiola; Padilla-Romo, María Guadalupe Zavelia; Borjas-Gutiérrez, César; Jaloma‐Cruz, Ana Rebeca

doi:10.1016/j.thromres.2015.10.026

Cited by 10 publications

(14 citation statements)

References 30 publications

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“…In contrast, the plasma-based CAT did not discriminate between bleeding and non-bleeding patients. Other studies showed that plasma CAT was indicative of bleeding in different patient populations [19, 23, 24]. However, this finding could not be repeated in our study.…”

Section: Discussioncontrasting

confidence: 85%

Prediction of bleeding risk in patients taking vitamin K antagonists using thrombin generation testing

et al. 2017

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Until recently, vitamin K antagonists (VKAs) were the mainstay of oral anticoagulant treatment with bleeding as the most prevalent adverse effect. One to four percent of patients experience major bleeding episodes, while clinically relevant bleeding occurs in up to 20%. At this moment no laboratory assays are available to identify patients at risk for bleeding. With this study we aimed to investigate whether thrombin generation tests might identify a bleeding risk in patients taking VKAs. This prospective cohort study included 129 patients taking VKAs for more than three months. Calibrated automated thrombinography (CAT) was performed in whole blood, platelet rich and platelet poor plasma. Hematocrit, hemoglobin concentrations and the International Normalized Ratio (INR) were defined and coagulation factor levels were measured. Forty clinically relevant bleeding episodes were registered in 26 patients during follow-up. No differences were found in plasma CAT parameters or INR values. Bleeding was not associated with age, sex, hematocrit, hemoglobin levels or coagulation factor levels. In whole blood a significantly lower endogenous thrombin potential (ETP) and peak were found in patients with bleeding (median ETP: 182.5 versus 256.2 nM.min, p = 0.002; peak: 23.9 versus 39.1 nM, p = 0.029). Additionally, the area under the receiver operating curve (AUC ROC) was significantly associated with bleeding (ETP: 0.700, p = 0.002; peak: 0.642, p = 0.029). HAS-BLED scores were also significantly higher in bleeding patients (3 versus 2, p = 0.003), with an AUC ROC 0.682 (p = 0.004). In conclusion, bleeding in patients taking VKAs is associated with a decreased whole blood ETP and peak as well as with an increased HAS-BLED score.

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Section: Discussioncontrasting

confidence: 85%

Prediction of bleeding risk in patients taking vitamin K antagonists using thrombin generation testing

et al. 2017

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“…Thrombin generation assay is considered to be the best available tool to fill the gap between in vivo and ex vivo coagulation because thrombin is generated under the action of all pro‐ and anticoagulant drivers . Previous studies reported that ETP is the most robust parameter that, in general, is able to identify patients with increased thrombotic and hemorrhagic risk, correlating with severe clinical complications . For hemorrhagic risk, increased bleeding occurs at ETP levels < 20% in both patients on VKA and patients with single factor deficiencies .…”

Section: Discussionmentioning

confidence: 99%

“…For hemorrhagic risk, increased bleeding occurs at ETP levels < 20% in both patients on VKA and patients with single factor deficiencies . The risk of arterial and venous thrombosis has been established, but how diminution of ETP corresponds to adequate anticoagulation is not clear from the literature . Furthermore, large inter‐individual variation in clinical phenotype despite the same ETP levels exists .…”

Section: Discussionmentioning

confidence: 99%

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Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists

Koning

Fischer

Laat

et al. 2017

Journal of Thrombosis and Haemostasis

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Essentials It is unknown if hemophilia patients with atrial fibrillation need anticoagulation. Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared. Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR). In non-severe hemophilia, 33% had higher ETP than therapeutic INR and may need anticoagulation. Click to hear Dr Negrier's perspective on global assays for assessing coagulation SUMMARY: Background It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKAs) to the same extent as the normal population. Objective To compare hemostatic potential in hemophilia patients and patients on VKAs using thrombin generation (TG). Methods In this cross-sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII < 1%, n = 15) and non-severe (FVIII 1-50%, n = 118) hemophilia A, 97 patients on a VKA with an international normalized ratio (INR) ≥ 1.5 and healthy controls. Endogenous thrombin potential (ETP) (nm*min) was compared according to FVIII level (< 1%, 1-19% and 20-50%) with healthy controls and patients with sub-therapeutic INR (1.5-1.9) and therapeutic INR (≥ 2.0). Medians and interquartile ranges (IQRs) were calculated. Results Compared with healthy controls (898 [IQR 803-1004]), both hemophilia patients and patients on VKAs had lower median ETPs at 304 (196-449) and 176 (100-250), respectively. ETP was quite similar in severe hemophilia patients (185 [116-307]) and patients with a therapeutic INR (156 [90-225]). Compared with patients with therapeutic INR, ETP in patients with FVIII 1-19% and patients with FVIII 20-50% was higher at 296 (203-430) and 397 (219-632), respectively. All patients with therapeutic INR had an ETP < 400. Considering this threshold, 93% of severe hemophilia patients, 70% of patients with FVIII 1-19% and 52% of patients with FVIII 20-50% had an ETP < 400. Conclusion In severe hemophilia patients, TG was comparable to that in patients with a therapeutic INR. In one-third of non-severe hemophilia patients, TG was higher. These results suggest that anticoagulation therapy should be considered in a substantial proportion of non-severe hemophilia patients.

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“…1,18 Its formation rate can reflect the potential hemostatic activity in plasma. 17,18 Thrombin generation (TG) has been experimentally used in human medicine to assess anticoagulant and reversal efficacy 19,20 and also correlated with bleeding tendencies or hypercoagulability in malignancies, thrombocytopenia, sepsis, or hyperadrenocorticism. 18,[21][22][23] Calibrated automated thrombography (CAT) is a thrombin generation assay, and has been used to detect alterations in hemostasis.…”

Section: Introductionmentioning

confidence: 99%

Reproducibility, stability, and biological variability of thrombin generation using calibrated automated thrombography in healthy dogs

Cuq

Blois

Wood

et al. 2018

Veterinary Clinical Pathol

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Thrombin generation and international normalized ratio in inherited thrombophilia patients receiving thromboprophylactic therapy

Cited by 10 publications

References 30 publications

Prediction of bleeding risk in patients taking vitamin K antagonists using thrombin generation testing

Prediction of bleeding risk in patients taking vitamin K antagonists using thrombin generation testing

Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists

Reproducibility, stability, and biological variability of thrombin generation using calibrated automated thrombography in healthy dogs

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