Monocytes Express Tissue Factor in Young Patients with Cerebral Ischemia

Objective Obstructive thrombi or thrombotic emboli are the pathogenic basis of ischemic stroke. In vitro blood clots and in vivo thrombi can undergo platelet-driven contraction (retraction), resulting in volume shrinkage. Clot contraction can potentially reduce vessel occlusion and improve blood flow past emboli or thrombi. The aim of this work was to examine a potential pathogenic role of clot contraction in ischemic stroke. Approach and Results We employed a novel automated method that enabled us to quantify time of initiation, extent and rate of clot contraction in vitro. The main finding is clot contraction from the blood of stroke patients was reduced compared to healthy subjects. Reduced clot contraction correlated with a lower platelet count and their dysfunction, higher levels of fibrinogen and hematocrit, leukocytosis and other changes in blood composition that may affect platelet function and properties of blood clots. Platelets from stroke patents were spontaneously activated and displayed reduced responsiveness to additional stimulation. Clinical correlations with respect to severity and stroke etiology suggest that the impaired clot contraction has the potential to be a pathogenic factor in ischemic stroke. Conclusions The changeable ability of clots and thrombi to shrink in volume may be a novel unappreciated mechanism that aggravates or alleviates the course and outcomes of ischemic stroke. The clinical importance of clot or thrombus transformations in vivo and the diagnostic and prognostic value of this blood test for clot contraction needs further exploration.

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“…55,56 Also ischemic stroke patients have increased TF-bearing microparticles 57 and TF expression on monocytes. 58 …”

Section: Discussionmentioning

confidence: 99%

Contraction of Blood Clots Is Impaired in Acute Ischemic Stroke

Tutwiler

Peshkova

Andrianova

et al. 2017

ATVB

115

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“…Some of these may also be identified by biochemical methods. We have recently shown [51]that the activation of blood coagulation via activated monocytes can be detected in these patients and can act as a further component of enhanced coagulation in cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

Natural Coagulation Inhibitor Proteins in Young Patients with Cerebral Ischemia

Oláh¹,

Misz²,

Kappelmayer

et al. 2001

Cerebrovasc Dis

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Disturbances of coagulation and fibrinolytic pathways were studied in 53 young patients with cerebral ischemia. Upon admission 26 of 53 patients had abnormality in at least one of the antithrombin-III, protein C, protein S activities or in activated protein C (APC) ratios. Three months after the first examination the majority of the previously detected abnormalities returned to normal values and the most frequent alterations were decrease in protein S activity (3 patients) and APC resistance (3 patients). Conditions resulting in impaired fibrinolysis were frequently detected upon admission. Elevation of plasminogen activator inhibitor-1, lipoprotein (a), and alpha-2-antiplasmin was present in 23, 10, and 4 cases, respectively. It is concluded that abnormalities of coagulation as well as of the fibrinolytic systems are prevalent in the acute phase of cerebral ischemia, however, the results may be significantly influenced by the disease process or the acute phase effect.

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“…Activated macrophages are a major source of TF in unstable coronary lesions [7]. Monocytes from patients with coronary disease or cerebral ischemia express TF [5,[8][9][10], and raised blood TF activity, possibly derived from microvesicles shed by circulating monocytes, is found in coronary and peripheral artery disease, and in autoimmune and infectious diseases [5,[11][12][13]. Monocytes are the only cell type among peripheral blood mononuclear cells (PBMC) to express TF and lymphocytes are required for optimal TF expression [14]: adhesive interactions and CD40-CD40L ligation [15] contribute to this process.…”

Section: Introductionmentioning

confidence: 99%

C‐reactive protein contributes to the hypercoagulable state in coronary artery disease

Song

Nakagomi

Chandar

et al. 2006

Journal of Thrombosis and Haemostasis

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Summary. Objectives: Elevated plasma C-reactive protein (CRP) levels predict coronary events, but it is unclear whether CRP plays a role in thrombosis associated with these events. We investigated tissue factor (TF) induction by CRP on peripheral blood mononuclear cells (PBMC) from patients with coronary disease. Patients and Methods: PBMC from 35 patients with stable angina (SA) in study 1, 10 male patients with SA, 10 with unstable angina (UA) and 10 matched controls in study 2, and 25 patients with inflammatory disorders (ID) and 24 normal controls in study 3 were stimulated with CRP, interferon-c (IFN) or lipopolysaccharide (LPS), or their combination. PBMC from additional normal donors were also stimulated with CRP in adherent and non-adherent conditions, and TF activity, antigen and mRNA expression detected. Results: CRP (5-25 lg mL )1 ) dose dependently induced more TF on PBMC from SA patients than 42 contemporary controls (P ¼ 0.001, study 1). Compared with controls, patients with SA or UA had higher basal, and much higher CRP-or CRP/LPS-induced monocyte TF activity although serum CRP levels were similar (study 2). IFN induced monocyte TF activity in patients with angina, but not in controls. Basal or CRP-induced TF levels did not differ between controls and ID, even though ID patients had much higher serum CRP levels (study 3). CRP-induced monocyte TF activity correlated with serum CRP levels in controls (P ¼ 0.005) and ID (P ¼ 0.007) in study 3, but not in patients with angina (P ¼0.84) in study 2. CRP induced more TF activity, protein and mRNA under adherent than nonadherent conditions implying that it may mainly target macrophages in lymphocyte-rich lesions. Conclusions: Our results indicate that monocytes from patients with angina are preactivated and express TF but CRP is unlikely to be a major priming factor in vivo. IFN and CRP further increase TF levels that may contribute to the hypercoagulable state in coronary disease.

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Monocytes Express Tissue Factor in Young Patients with Cerebral Ischemia

Cited by 13 publications

References 18 publications

Contraction of Blood Clots Is Impaired in Acute Ischemic Stroke

Contraction of Blood Clots Is Impaired in Acute Ischemic Stroke

Natural Coagulation Inhibitor Proteins in Young Patients with Cerebral Ischemia

C‐reactive protein contributes to the hypercoagulable state in coronary artery disease

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