The role of diabetes mellitus on the thrombus composition in patients with acute ischemic stroke

Purpose Diabetes mellitus indicated poor clinical prognosis for patients with acute ischemic stroke. Furthermore, diabetes mellitus could also impact the hemostatic system, while its influence on the histological composition of thrombus is unclear. Methods Consecutive patients with retrieved clots were included. Histologic staining for thrombus included hematoxylin and eosin, Martius Scarlet Blue, immunohistochemistry for von Willebrand factor. The differences in clot composition were compared according to diabetes mellitus history or hyperglycemia (≥7.8 mmol/L) on admission. Results A total of 52 patients were included; half of them were diagnosed as diabetes mellitus previously. Diabetic patients showed higher serum glucose on admission (8.90 vs. 7.40, p = 0.012). The baseline characteristics (expect smoking history and thrombus location), procedural, and clinical outcomes were similar between diabetic patients and nondiabetic patients. As for histologic composition, thrombus in patients with diagnosed diabetes mellitus had more fibrin (44.2% vs. 28.3%, p = 0.004) and fewer red blood cells (26.0% vs. 42.9%, p = 0.013) and equivalent content of platelets (24.0% vs. 21.5%, p = 0.694) and von Willebrand factor (0.041 vs. 0.031, p = 0.234) than patients without diabetes mellitus. However, there was no statistical difference in the content of red blood cells (41.6% vs. 27.3%, p = 0.105), fibrin (37.6% vs. 34.3%, p = 0.627), platelets (21.2% vs. 24.2%, p = 0.498), and von Willebrand factor (0.038 vs. 0.034, p = 0.284) between patients with or without hyperglycemia on admission. Conclusion Clots in diabetic patients had more fibrin and fewer erythrocyte components compared with patients without diabetes mellitus, while hyperglycemia on admission did not show association with clot composition. Further studies are needed to confirm these results.

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Characterization of the ‘White’ Appearing Clots that Cause Acute Ischemic Stroke

10.21203/rs.3.rs-45700/v1 ◽

2020 ◽

Author(s):

Oana Madalina Mereuta ◽

Seán Fitzgerald ◽

Rosanna Rossi ◽

Andrew Douglas ◽

Abhay Pandit ◽

...

Keyword(s):

Ischemic Stroke ◽

Red Blood Cells ◽

Acute Ischemic Stroke ◽

Blood Cells ◽

White Blood Cells ◽

Fatty Acid Binding ◽

Blue Stain ◽

Von Willebrand ◽

Willebrand Factor

Abstract Background: Most clots retrieved from patients with acute ischemic stroke are ‘red’ in color and are predominantly composed of red blood cells and fibrin. ‘White’ clots represent a less common entity and their histological composition is largely unknown.The aim of this study was to investigate the composition, imaging and procedural characteristics of ‘white’ clots retrieved by mechanical thrombectomy.Materials and Methods:Nineteen ‘white’ thrombi selected by visual inspection from 293 cases were collected as part of the multi-institutional RESTORE registry. Non-contrast computed tomography (NCCT), histological and immunohistochemical analyses were performed. Components were quantified using Orbit Image Analysis.Results:Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in ‘white’ clots’ (63%) followed by fibrin (26%), red blood cells (7%) and white blood cells (4%). ‘White’ clots presented significantly more platelets/other and less red blood cells compared to the ‘red’ clots which showed a mean of 23% and 44%, respectively. The mean platelet (CD42b) content in ‘white’ clots was 43%; von Willebrand Factor (vWF) mean expression was 38%.Collagen and calcification were associated in one case. Fatty acid binding protein 4 was expressed in two cases.‘White’ clots were also significantly smaller (9.5 versus 12 mm) and less hyperdense (52 versus 61 Hounsfield Units) on NCCT compared to the other cases.Conclusions:‘White’ clots represented 6% of our cohort and are platelet and vWF-rich. Calcification, collagen and adipocytes were found occasionally. ‘White’ clots differ from other clots in composition, size and density on NCCT.

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The Sma I Polymorphism in the von Willebrand Factor Gene Associated with Acute Ischemic Stroke

Thrombosis Research ◽

10.1016/s0049-3848(01)00389-9 ◽

2001 ◽

Vol 104 (6) ◽

pp. 389-395 ◽

Cited By ~ 22

Author(s):

Kesheng Dai ◽

Weiqiang Gao ◽

Changgeng Ruan

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Von Willebrand Factor ◽

Factor Gene ◽

Von Willebrand ◽

Willebrand Factor

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Abstract WP268: Von Willebrand Factor Expression in Various Subtypes of Acute Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.wp268 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Oana M Mereuta ◽

Sean Fitzgerald ◽

Mehdi Abbasi ◽

Daying Dai ◽

Ramanathan Kadirvel ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Von Willebrand Factor ◽

Cryptogenic Stroke ◽

Cardioembolic Stroke ◽

Unknown Etiology ◽

Learning Software ◽

Von Willebrand ◽

The Relationship ◽

Willebrand Factor

Introduction: Von Willebrand factor (VWF) is a key component of acute ischemic stroke (AIS) thrombi. The aim of our prospective study was to investigate the immunohistochemical expression of VWF in clots and to evaluate whether VWF is associated with certain subtypes of AIS. Methods: VWF immunostaining was performed on 79 thrombi collected as part of the multi-center Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) registry. The cases were classified according to TOAST criteria. The VWF expression was quantified using Orbit Image Analysis (www.Orbit.bio) machine learning software. IBM SPSS statistics 25 was used to assess the relationship between the VWF levels and different etiology subtypes. Results: A cardioembolic stroke was defined in 39 cases (49.4%) whereas an atherosclerotic origin was identified in 13 patients (16.5%). Other causes accounted for 12 cases (15.1%). Unknown etiology was reported in 15 cases (19%). The mean VWF content in the clots was 12.8%. According to the Mann-Whitney U-test, the level of VWF was significantly higher in the cases with unknown etiology compared to cardioembolic origin (p=0.044). We found also that patients with unknown etiology of stroke had higher VWF expression as compared to the other two subtypes, although this difference was not statistically significant. Conclusions: Among the patients with ischemic stroke included in this study, the VWF expression was significantly increased in those with unknown etiology compared to the group with cardioembolic stroke. Our finding provides new insights into clot composition in cryptogenic stroke and may influence the treatment and secondary prevention in these cases.

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Platelet-Independent Adhesion of Red Blood Cells to Von Willebrand Factor

Blood ◽

10.1182/blood.v124.21.2769.2769 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2769-2769

Author(s):

Michel WJ Smeets ◽

Alexander PJ Vlaar ◽

Herm Jan M Brinkman ◽

Jan J Voorberg ◽

Peter L Hordijk

Keyword(s):

Endothelial Cells ◽

Blood Cell ◽

Red Blood Cells ◽

Von Willebrand Factor ◽

Cold Storage ◽

Blood Cells ◽

Storage Lesion ◽

Microparticle Formation ◽

Von Willebrand ◽

Willebrand Factor

Abstract Background/Objectives Red blood cell (RBC) transfusion can be lifesaving and is an essential therapy in conditions associated with tissue hypoxia due to anemia. However, recent clinical studies show that both the number of RBCs and the age of RBCs transfused are independent risk factors for an increase in transfusion related morbidity and mortality. It has been suggested that the so called “storage lesion” of RBCs, a reduction of quality of erythrocytes and changes in the erythrocyte concentrate storage medium, is the causal factor. Recently it has been shown that cold storage of erythrocytes induces microparticle formation. These erythrocyte microparticles are pro-coagulant and can cause thrombin formation. Another phenomenon of the storage lesion is the rapid and considerable loss of donor erythrocytes from the circulation of transfused patients. We wondered whether thrombin generated by transfused erythrocyte microparticles could contribute to red blood cell adherence to the vascular endothelium. Cytoadherence of red blood cells could contribute to the loss of circulating transfused red blood cells and vascular obstruction and could explain the observed transfusion associated complications in clinical practice. Methods/Results Employing FACS analysis and a microparticle analyzer we showed that erythrocyte cold storage indeed induces microparticle formation. We confirmed the pro-coagulant properties of these microparticles using a chromogenic substrate specific for thombin and a thrombin-anti-thrombin complex ELISA. To determine whether thrombin could induce adhesion of red blood cells to endothelial cells, we cultured human umbilical vein endothelial cells in micro-perfusion chambers and used live-imaging to define the adherence potential of the erythrocytes to endothelial cells at post-capillary flow rate. Thrombin stimulation of the endothelial cells did increase erythrocyte adhesion to endothelial cells. Moreover, the adhesion of erythrocytes followed a pattern resembling platelets binding to von Willebrand factor (VWF). By using live immunofluoresence imaging we confirmed that the erythrocytes did bind to VWF secreted from endothelial cells. Since erythrocyte-VWF interactions may be mediated by platelets, we used fluorescence cell sorting to remove platelets and erythrocyte-platelet complexes from erythrocyte concentrates. The purified erythrocytes did also bind to VWF secreted by endothelial cells and thereby we confirmed that erythrocytes can bind to VWF in a platelet-independent fashion. We further analyzed the specificity of the erythrocyte-VWF interaction by using different protein coatings in micro-perfusion chambers. Erythrocytes did bind to recombinant high molecular weight VWF multimers. Furthermore, they adhered more potently to VWF when compared to fibrinogen or fibrin but showed little binding to fibronectin, collagen type I, or subendothelial extra-cellular matrix proteins. Conclusion Our results suggest that transfusion of RBCs is able to induce endothelial binding of erythrocytes based on a VWF-erythrocyte interaction. We propose that passive infusion of cold stored erythrocyte derived microparticles promotes thrombin generation which subsequently activates endothelial cells and induces VWF secretion. This results in binding of red blood cells to endothelial cells in a platelet-independent fashion which requires the presence of VWF. Based on our results we hypothesize that binding of erythrocytes to VWF may occlude micro-capillaries thereby contributing to transfusion associated complications. Disclosures No relevant conflicts of interest to declare.

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When Flow Goes Slow, von Willebrand Factor Can Bind Red Blood Cells

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.117.309991 ◽

2017 ◽

Vol 37 (9) ◽

pp. 1595-1595 ◽

Cited By ~ 1

Author(s):

Scott L. Diamond

Keyword(s):

Red Blood Cells ◽

Von Willebrand Factor ◽

Blood Cells ◽

Von Willebrand ◽

Willebrand Factor

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The markers of platelet functions and von willebrand factor serum content from patients with type 2 diabetes mellitus and ischemic stroke

Biomedical Research and Therapy ◽

10.7603/s40730-016-0011-y ◽

2016 ◽

Vol 3 (3) ◽

Cited By ~ 1

Author(s):

Tetiana Tsarenko ◽

Oleksandra Kostiuk ◽

Olha Kravchenko ◽

Oleksiy Savchuk ◽

Liudmyla Ostapchenko

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Ischemic Stroke ◽

Von Willebrand Factor ◽

Von Willebrand ◽

Willebrand Factor ◽

Platelet Functions

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The Role of von Willebrand Factor, ADAMTS13, and Cerebral Artery Thrombus Composition in Patient Outcome Following Mechanical Thrombectomy for Acute Ischemic Stroke

Medical Science Monitor ◽

10.12659/msm.908441 ◽

2018 ◽

Vol 24 ◽

pp. 3929-3945 ◽

Cited By ~ 11

Author(s):

Vaclav Prochazka ◽

Tomas Jonszta ◽

Daniel Czerny ◽

Jan Krajca ◽

Martin Roubec ◽

...

Keyword(s):

Patient Outcome ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Von Willebrand Factor ◽

Cerebral Artery ◽

Mechanical Thrombectomy ◽

Von Willebrand ◽

Willebrand Factor

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Abstract TP440: Heart Failure is Associated With Elevated von Willebrand Factor (vWF) Antigen but not Factor VIII (FVIII) in Acute Ischemic Stroke (AIS)

Stroke ◽

10.1161/str.47.suppl_1.tp440 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Alyana Samai ◽

Karen Albright ◽

Eleni Antzoulatos ◽

Laurie Schluter ◽

Sheryl Martin-Schild

Keyword(s):

Heart Failure ◽

Ischemic Stroke ◽

Factor Viii ◽

Acute Ischemic Stroke ◽

Von Willebrand Factor ◽

Left Ventricular ◽

Lv Function ◽

Stroke Registry ◽

Von Willebrand ◽

Willebrand Factor

Introduction: von Willebrand Factor (vWF) and factor VIII (FVIII) contribute to thrombosis and are important risk factors in acute ischemic stroke (AIS). Elevated vWF has been correlated with depressed left ventricular (LV) function, but has not been examined in a cohort of patients with AIS, particularly with regard to concurrent elevation in FVIII. Hypothesis: We hypothesized that vWF is associated with HF and that combined elevation of vWF and FVIII would strengthen this association. Methods: From our prospective stroke registry, AIS patients >18 years of age admitted from 09/2011 to 01/2015 were included if both FVIII and vWF were measured during hospitalization and an echocardiogram was performed. Comparisons were done between the following groups: patients with normal (-) vs. elevated (+) vWF, patients with (-) vs. (+) FVIII, and patients with (-) vs. (+) levels of both factors. Results: Of 1,091 patients in the study period, 212 patients met inclusion criteria. In all groups, patients differed significantly according to history of DM. +vWF had higher frequency of female gender than -vWF, but did not differ according to any other demographic or baseline characteristics. +vWF patients had higher frequency of HF (p=0.007) and higher frequency of depressed LV function (p=0.028) compared to those with -vWF. vWF level correlated with HF (r=0.189, p=0.006) and reduced LV function (r=0.187, p=0.006). Similar findings were found with dual elevation, but we found no relationship between FVIII and HF. After adjustment for HTN, CAD, and DM, vWF remained an independent predictor of HF (OR 1.003, 95%CI 1.000-1.007, p=0.036). While we found no relationship between LV function and FVIII level, median vWF levels increased with decreasing LV function (p=0.027). Conclusion: The results of our study suggest an association between HF and elevated vWF in the setting of AIS, irrespective of FVIII elevation. These results suggest the potential utility of vWF as an independent biomarker for heart failure in the AIS patient population.

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