Increased Clot Formation in the Absence of Increased Thrombin Generation in Patients with Peripheral Arterial Disease: A Case-Control Study

Marie-Claire F. Kleinegris; Joke Konings; Jan W. Daemen; Yvonne Henskens; Bas de Laat; Henri M. H. Spronk; Arina J. ten Cate-Hoek; Hugo ten Cate

doi:10.3389/fcvm.2017.00023

Increased Clot Formation in the Absence of Increased Thrombin Generation in Patients with Peripheral Arterial Disease: A Case-Control Study

Marie-Claire F. Kleinegris^*, Joke Konings, Jan W. Daemen, Yvonne Henskens, Bas de Laat, Henri M. H. Spronk, Arina J. ten Cate-Hoek, Hugo ten Cate

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: In peripheral arterial disease (PAD), activation of the hemostatic system may contribute to atherosclerosis progression and atherothrombotic events.

Objective: This case control study assesses the overall coagulation status in PAD patients by evaluating coagulation markers in combination with thrombin generation potential, whole blood (WB) clot formation, and fibrinolysis.

Methods: In blood from 40 PAD patients (n = 20 with cardiovascular event within 1 year after initial diagnosis, n = 20 without) and 40 apparently healthy controls, thrombin generation was determined in WB and platelet poor plasma. Whole blood rotational thromboelastometry (ROTEM) measurements were triggered with tissue factor with/ without tissue plasminogen activator.

Results: We observed increased levels of erythrocyte sedimentation rate, leukocytes, eosinophil granulocytes, vWF antigen, fibrinogen, and D-dimer in PAD patients (p <0.05). Markers of thrombin generation potential showed no difference between patients and healthy controls. In PAD patients with event compared to patients without, WB-thrombin generation showed a lower thrombin potential when triggered with 0 and 2.5 pM tissue factor. The ROTEM clotting assay showed significantly faster clot formation and increased clot firmness in PAD patients compared to controls. No significant differences were found for parameters of clot degradation.

Conclusion: There are no significant differences between the thrombin generation profiles of PAD patients and healthy controls. Between PAD patients with and without cardiovascular event, the WB thrombin generation appears to differ. Mechanistically, PAD patients show an increased ability to form a stable clot in WB in comparison to healthy controls. This is most likely due to the increased fibrinogen levels related to the inflammation in atherosclerosis, confirming the importance of the inflammation-coagulation axis.

Original language	English
Article number	23
Number of pages	10
Journal	Frontiers in Cardiovascular Medicine
Volume	4
DOIs	https://doi.org/10.3389/fcvm.2017.00023
Publication status	Published - 20 Apr 2017

Keywords

coagulation
intermittent claudication
peripheral arterial disease
thrombin generation
thromboelastometry
FIBRIN D-DIMER
HEMOSTATIC FACTORS
RISK-FACTORS
HYPERCHOLESTEROLEMIC PATIENTS
VASCULAR-DISEASE
DETERMINANTS
SIMVASTATIN
POPULATION
ACTIVATION
EVENTS

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Kleinegris, M.-C. F., Konings, J., Daemen, J. W., Henskens, Y., de Laat, B., Spronk, H. M. H., ten Cate-Hoek, A. J., & ten Cate, H. (2017). Increased Clot Formation in the Absence of Increased Thrombin Generation in Patients with Peripheral Arterial Disease: A Case-Control Study. Frontiers in Cardiovascular Medicine, 4, Article 23. https://doi.org/10.3389/fcvm.2017.00023

@article{b82eaaa75ef24da29a52df00ad40a7f0,

title = "Increased Clot Formation in the Absence of Increased Thrombin Generation in Patients with Peripheral Arterial Disease: A Case-Control Study",

abstract = "Background: In peripheral arterial disease (PAD), activation of the hemostatic system may contribute to atherosclerosis progression and atherothrombotic events.Objective: This case control study assesses the overall coagulation status in PAD patients by evaluating coagulation markers in combination with thrombin generation potential, whole blood (WB) clot formation, and fibrinolysis.Methods: In blood from 40 PAD patients (n = 20 with cardiovascular event within 1 year after initial diagnosis, n = 20 without) and 40 apparently healthy controls, thrombin generation was determined in WB and platelet poor plasma. Whole blood rotational thromboelastometry (ROTEM) measurements were triggered with tissue factor with/ without tissue plasminogen activator.Results: We observed increased levels of erythrocyte sedimentation rate, leukocytes, eosinophil granulocytes, vWF antigen, fibrinogen, and D-dimer in PAD patients (p <0.05). Markers of thrombin generation potential showed no difference between patients and healthy controls. In PAD patients with event compared to patients without, WB-thrombin generation showed a lower thrombin potential when triggered with 0 and 2.5 pM tissue factor. The ROTEM clotting assay showed significantly faster clot formation and increased clot firmness in PAD patients compared to controls. No significant differences were found for parameters of clot degradation.Conclusion: There are no significant differences between the thrombin generation profiles of PAD patients and healthy controls. Between PAD patients with and without cardiovascular event, the WB thrombin generation appears to differ. Mechanistically, PAD patients show an increased ability to form a stable clot in WB in comparison to healthy controls. This is most likely due to the increased fibrinogen levels related to the inflammation in atherosclerosis, confirming the importance of the inflammation-coagulation axis.",

keywords = "coagulation, intermittent claudication, peripheral arterial disease, thrombin generation, thromboelastometry, FIBRIN D-DIMER, HEMOSTATIC FACTORS, RISK-FACTORS, HYPERCHOLESTEROLEMIC PATIENTS, VASCULAR-DISEASE, DETERMINANTS, SIMVASTATIN, POPULATION, ACTIVATION, EVENTS",

author = "Kleinegris, {Marie-Claire F.} and Joke Konings and Daemen, {Jan W.} and Yvonne Henskens and {de Laat}, Bas and Spronk, {Henri M. H.} and {ten Cate-Hoek}, {Arina J.} and {ten Cate}, Hugo",

year = "2017",

month = apr,

day = "20",

doi = "10.3389/fcvm.2017.00023",

language = "English",

volume = "4",

journal = "Frontiers in Cardiovascular Medicine",

issn = "2297-055X",

publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - Increased Clot Formation in the Absence of Increased Thrombin Generation in Patients with Peripheral Arterial Disease

T2 - A Case-Control Study

AU - Kleinegris, Marie-Claire F.

AU - Konings, Joke

AU - Daemen, Jan W.

AU - Henskens, Yvonne

AU - de Laat, Bas

AU - Spronk, Henri M. H.

AU - ten Cate-Hoek, Arina J.

AU - ten Cate, Hugo

PY - 2017/4/20

Y1 - 2017/4/20

N2 - Background: In peripheral arterial disease (PAD), activation of the hemostatic system may contribute to atherosclerosis progression and atherothrombotic events.Objective: This case control study assesses the overall coagulation status in PAD patients by evaluating coagulation markers in combination with thrombin generation potential, whole blood (WB) clot formation, and fibrinolysis.Methods: In blood from 40 PAD patients (n = 20 with cardiovascular event within 1 year after initial diagnosis, n = 20 without) and 40 apparently healthy controls, thrombin generation was determined in WB and platelet poor plasma. Whole blood rotational thromboelastometry (ROTEM) measurements were triggered with tissue factor with/ without tissue plasminogen activator.Results: We observed increased levels of erythrocyte sedimentation rate, leukocytes, eosinophil granulocytes, vWF antigen, fibrinogen, and D-dimer in PAD patients (p <0.05). Markers of thrombin generation potential showed no difference between patients and healthy controls. In PAD patients with event compared to patients without, WB-thrombin generation showed a lower thrombin potential when triggered with 0 and 2.5 pM tissue factor. The ROTEM clotting assay showed significantly faster clot formation and increased clot firmness in PAD patients compared to controls. No significant differences were found for parameters of clot degradation.Conclusion: There are no significant differences between the thrombin generation profiles of PAD patients and healthy controls. Between PAD patients with and without cardiovascular event, the WB thrombin generation appears to differ. Mechanistically, PAD patients show an increased ability to form a stable clot in WB in comparison to healthy controls. This is most likely due to the increased fibrinogen levels related to the inflammation in atherosclerosis, confirming the importance of the inflammation-coagulation axis.

AB - Background: In peripheral arterial disease (PAD), activation of the hemostatic system may contribute to atherosclerosis progression and atherothrombotic events.Objective: This case control study assesses the overall coagulation status in PAD patients by evaluating coagulation markers in combination with thrombin generation potential, whole blood (WB) clot formation, and fibrinolysis.Methods: In blood from 40 PAD patients (n = 20 with cardiovascular event within 1 year after initial diagnosis, n = 20 without) and 40 apparently healthy controls, thrombin generation was determined in WB and platelet poor plasma. Whole blood rotational thromboelastometry (ROTEM) measurements were triggered with tissue factor with/ without tissue plasminogen activator.Results: We observed increased levels of erythrocyte sedimentation rate, leukocytes, eosinophil granulocytes, vWF antigen, fibrinogen, and D-dimer in PAD patients (p <0.05). Markers of thrombin generation potential showed no difference between patients and healthy controls. In PAD patients with event compared to patients without, WB-thrombin generation showed a lower thrombin potential when triggered with 0 and 2.5 pM tissue factor. The ROTEM clotting assay showed significantly faster clot formation and increased clot firmness in PAD patients compared to controls. No significant differences were found for parameters of clot degradation.Conclusion: There are no significant differences between the thrombin generation profiles of PAD patients and healthy controls. Between PAD patients with and without cardiovascular event, the WB thrombin generation appears to differ. Mechanistically, PAD patients show an increased ability to form a stable clot in WB in comparison to healthy controls. This is most likely due to the increased fibrinogen levels related to the inflammation in atherosclerosis, confirming the importance of the inflammation-coagulation axis.

KW - coagulation

KW - intermittent claudication

KW - peripheral arterial disease

KW - thrombin generation

KW - thromboelastometry

KW - FIBRIN D-DIMER

KW - HEMOSTATIC FACTORS

KW - RISK-FACTORS

KW - HYPERCHOLESTEROLEMIC PATIENTS

KW - VASCULAR-DISEASE

KW - DETERMINANTS

KW - SIMVASTATIN

KW - POPULATION

KW - ACTIVATION

KW - EVENTS

U2 - 10.3389/fcvm.2017.00023

DO - 10.3389/fcvm.2017.00023

M3 - Article

C2 - 28473975

SN - 2297-055X

VL - 4

JO - Frontiers in Cardiovascular Medicine

JF - Frontiers in Cardiovascular Medicine

M1 - 23

ER -