In vivo thrombin generation and subsequent APC formation are increased in factor V Leiden carriers

Rühl, Heiko; Winterhagen, Franziska Isabelle; Berens, Christina; Müller, Jens; Oldenburg, Johannes; Pötzsch, Bernd

doi:10.1182/blood-2017-12-823831

Cited by 12 publications

(28 citation statements)

References 21 publications

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“…There was no correlation between resistance to activated protein C and TG parameters in the studied population. Because previous studies demonstrated an increase of TG in subjects with APC resistance, we did not expect, in the study group, to find no correlation between TG parameters and resistance to APC. However, this could be explained by the fact that none of the included healthy adults displayed APC resistance (Table S1).…”

Section: Discussionmentioning

confidence: 81%

“…In platelet‐poor plasma (PPP), TG testing can detect all coagulation factor deficiencies except factor XIII deficiency . It is sensitive to anticoagulant drugs and to procoagulant states such as deficiency in antithrombin, protein C, or protein S as well as to hyperprothrombinemia and resistance to activated protein C …”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4] In platelet-poor plasma (PPP), TG testing can detect all coagulation factor deficiencies except factor XIII deficiency. [5][6][7] It is sensitive to anticoagulant drugs 8,9 and to procoagulant states such as deficiency in antithrombin, 10 protein C, or protein S 11 as well as to hyperprothrombinemia 12 and resistance to activated protein C. 13,14 The method of TG testing developed by Hemker et al, 1,15 the socalled calibrated automated thrombography (CAT) has been used and studied in numerous conditions during the past 15 years. The use of a calibrator allows an accurate measurement of the amount and activity of the generated thrombin.…”

Section: Introductionmentioning

confidence: 99%

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Thrombin generation measurement using the ST Genesia Thrombin Generation System in a cohort of healthy adults: Normal values and variability

Calzavarini

Brodard

Quarroz

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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BackgroundThrombin generation (TG) assays evaluate the balance between pro‐ and anticoagulant forces, to better assess bleeding and thrombotic risks. Although TG readouts obtained with the calibrated automated TG have been investigated in multiple clinical conditions, TG still needs standardization and clinical validation. The automated TG instrument ST Genesia® (STG, Stago, Asnières‐sur‐Seine, France) provides a normalization of TG parameters based on a reference plasma aiming to reduce the interlaboratory variability and the variability between different measurement runs.ObjectivesTo evaluate STG in a group of healthy adults.MethodsReference intervals in healthy adults and variability of the new standardized reagents for bleeding (BleedScreen) and thrombophilic (ThromboScreen) conditions were determined using STG.Results TG was measured in platelet‐free plasma (PFP) samples of 123 healthy adults. Reference intervals were determined for TG parameters. Intra‐ and interassay coefficients of variation were calculated on quality controls and PFP samples from healthy adults. Oral contraception (OC) possibly influenced TG parameters, resulting in a higher median and a broader reference interval for peak height and endogenous thrombin potential (ETP) in women aged 20 to 49 years than in all other sex and age categories. Therefore, we propose the following reference interval categories: men, women aged <50 years not using OC, women aged <50 years using OC, and women aged ≥50 years. Normalization was effective to reduce the interassay variability of quality controls for ETP (BleedScreen assay), and peak height and ETP (ThromboScreen assay without thrombomodulin), but had little impact on PFP sample variability.Conclusion STG appears suitable for accurate measurement of TG in healthy adults.

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Thrombin generation measurement using the ST Genesia Thrombin Generation System in a cohort of healthy adults: Normal values and variability

Calzavarini

Brodard

Quarroz

et al. 2019

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

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“…The presence of platelet reactive antibody was not experimentally confirmed in the present report. Curtis BR et al reported that oxaliplatin tends to induce multiple drug-dependent platelet-reactive antibodies (DDAbs) which cause DITP ( 13 ). They experimentally confirmed the presence of DDAbs specific various drugs including dexamethasone.…”

Section: Discussionmentioning

confidence: 99%

Thrombocytopenia Caused by Dexamethasone in a Patient with Colorectal Cancer

et al. 2020

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Drug-induced immune thrombocytopenia (DITP) is an important cause of thrombocytopenia. A 73-year-old man with relapsed rectal carcinoma received S-1, oxaliplatin and bevacizumab combination therapy (SOX+ Bev). Dexamethasone was administered as an antiemetic prophylaxis. On day 2 of the first cycle, thrombocytopenia (8,000/μL) was observed. We sequentially omitted any drugs suspected to possibly induce thrombocytopenia and confirmed dexamethasone as the cause of thrombocytopenia. DITP induced by synthetic corticosteroids is very rare and this is the first case report of DITP induced by dexamethasone. Although rare, DITP due to synthetic corticosteroids including dexamethasone should be a differential diagnosis among patients receiving synthetic corticosteroids with thrombocytopenia.

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“…In the first clinical model, systemic thrombin formation was induced via the administration of low-dose recombinant activated factor VII (rFVIIa) to healthy volunteers and patients with thrombophilic risk factors. We have recently shown, using this stimulated hemostasis activity pattern evaluation (SHAPE) approach, different patterns of procoagulant and anticoagulant responses depending on the presence of hereditar y thrombophilia risk factors and the patients' history of venous thromboembolism (VTE) 24,25) . The second cohort comprised patients undergoing elective Advance Publication Journal of Atherosclerosis and Thrombosis Accepted for publication: October 12, 2020 Published online: December 9, 2020 generation.…”

Section: Aimmentioning

confidence: 99%

Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation

Rühl

Friemann

Reda

et al. 2022

JAT

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Aim: Feedback activation of factor XI (FXI) by thrombin is believed to play a critical role in the amplification phase of thrombin generation and to contribute to thrombosis development and hemostasis. However, the activation of FXI by thrombin has been shown in vitro to require a cofactor. In this study, the role of thrombin in activated FXI (FXIa) formation in vivo is investigated. Methods: The study population comprised probands in whom coagulation activation was triggered by low-dose (15 µg/kg) recombinant activated factor VII (rFVIIa, n =89), of whom 34 with (VTE+) and 45 without a history of venous thromboembolism (VTE−), and patients undergoing major orthopedic surgeries ( n =45). FXIa was quantified via an enzyme capture assay using a monoclonal FXI-specific antibody. Thrombin formation was monitored using an oligonucleotide-based enzyme capture assay and the thrombin activation markers prothrombin fragment 1＋2 (F1＋2) and thrombin–antithrombin complex (TAT). Results: In the rFVIIa cohort, FXIa and thrombin remained below their lower limit of quantification of 3.48 and 1.06 pmol/L, respectively. By contrast, during the surgeries, median FXIa levels increased from 3.69 pmol/L pre-operatively to 9.41 pmol/L mid-operatively ( P =4·10 −4 ) and remained significantly elevated 24 h thereafter, with 9.38 pmol/L ( P =0.001). Peak levels of F1+2 were comparable in the VTE+, VTE−, and surgery cohort (235, 268, and 253 pmol/L), whereas peak TAT levels were higher in the surgery cohort (53.1, 33.9, and 147.6 pmol/L). Conclusions: Under in vivo conditions, the activation of FXI requires specific local features that are present at the wounded site including potential cofactors of thrombin.

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In vivo thrombin generation and subsequent APC formation are increased in factor V Leiden carriers

Cited by 12 publications

References 21 publications

Thrombin generation measurement using the ST Genesia Thrombin Generation System in a cohort of healthy adults: Normal values and variability

Thrombin generation measurement using the ST Genesia Thrombin Generation System in a cohort of healthy adults: Normal values and variability

Thrombocytopenia Caused by Dexamethasone in a Patient with Colorectal Cancer

Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation

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