A descriptive investigation of the ultrastructure of fibrin networks in thrombo-embolic ischemic stroke

Pretorius, Etheresia; Swanepoel, Albe C.; Oberholzer, Hester Magdalena; Spuy, Wendy Jeannette Van der; Duim, Wiebren; Wessels, Philippus L.

doi:10.1007/s11239-010-0538-5

Cited by 36 publications

(29 citation statements)

References 19 publications

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“…Figure 2a-f shows micrographs from the patient stroke group. As previously noted by Pretorius et al [9], in ischemic stroke patients, fibrin fiber arrangement changes after the addition of thrombin to citrated blood, to form a matted and netted fibrin mass. As can be seen in Fig.…”

Section: Discussionsupporting

confidence: 57%

“…In our ongoing study of thromboembolic ischemic stroke patients, we have analysed 25 individuals. They were diagnosed according to the Trial of Org 10172 in Acute Stroke Treatment criteria [9]. From this sample, micrographs of 12 patients were chosen for the current study.…”

Section: Samplesmentioning

confidence: 99%

“…Also, there was an increased (by 10.2%) overall fiber thickness with 8% shorter lag phase of fibrin formation. In 2011, Pretorius et al [9] showed that in thromboembolic ischemic stroke, fibrin networks have a changed ultrastructure. Fibrin networks were created within 24 h of stroke, using citrated blood, after the addition of thrombin.…”

Section: Introductionmentioning

confidence: 99%

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Differences in fibrin fiber diameters in healthy individuals and thromboembolic ischemic stroke patients

Pretorius¹,

Steyn

Engelbrecht³

et al. 2011

Blood Coagulation &Amp; Fibrinolysis

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Cerebrovascular disease is one of the leading causes of death and the cause of long-term adult disability. An important characteristic of thromboembolic ischemic stroke is a prothrombotic or hypercoagulable state and altered fibrin clot structure, whereas a resistance to fibrinolysis is also present. An expansive fibrin network is created when adding thrombin, and in stroke, the network appears thickened, netted and matted, compared with that of healthy individuals. Although this is clearly visible in micrographs of patients, there is a need to quantify the changes. The current study, therefore, investigates fibrin fiber diameters in stroke patients and compares it to healthy individuals. The fiber diameters were measured in nanometres, with University of Texas Health Science Center at San Antonio (UTHSCSA) Image Tool. A total of 100 measurements were done for each of the 12 patients in the healthy control group, and the same number of measurements was done for 12 stroke patients. These measurements were statistically analysed with NCSS 2007, using a significance level of 0.05. Normality was assessed with the Shapiro-Wilk W test and the thickest and thinnest fiber of each individual in the two groups was quantified and differences between groups were assessed with the Student's t-test. Results showed that there is a statistical difference in fibrin fiber thickness during thromboembolic ischemic stroke. We conclude that the changed coagulation and hemostasis, typically associated with stroke, causes a statistically relevant change in fibrin thickness, and that this netted and matted network is more resistant to lyses.

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Section: Discussionsupporting

confidence: 57%

Section: Samplesmentioning

confidence: 99%

See 1 more Smart Citation

Differences in fibrin fiber diameters in healthy individuals and thromboembolic ischemic stroke patients

Pretorius¹,

Steyn

Engelbrecht³

et al. 2011

Blood Coagulation &Amp; Fibrinolysis

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“…Where the major fibers are more abundant in control individuals, minor fibers appear to become more prevalent in LD and increased in HD groups. Generally, increased thrombin concentrations are associated with the formation of stiffer clots and increased thrombin activity on platelet surfaces has also been accredited to fibrin mesh architecture [31] as seen in the figures. In both experimental groups, the fibrin clots also presented with a matted, layered morphology and thicker, fused fibers.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Sibutramine, a Serotonin-Norepinephrine Reuptake Inhibitor, on Platelets and Fibrin Networks of Male Sprague-Dawley Rats: A Descriptive Study

Schoor¹,

Oberholzer²,

Bester³

et al. 2014

Ultrastructural Pathology

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Sibutramine is used in the treatment of obesity due to its ability to influence feelings of hunger and satiety by inhibiting the re-uptake of serotonin and noradrenalin in the central nervous system (CNS). Sibutramine use has been associated with numerous adverse events in particular cardiovascular complications possibly due to the formation of thrombi. This ultrastructural descriptive study investigated the effect of sibutramine on blood coagulation, specifically the effect on morphology of platelets and fibrin networks using scanning electron microscopy. Male Sprague-Dawley rats treated with either a recommended therapeutic dose [low dosage 1.32 mg/kg] or a toxicological higher dose [high dosage 13.2 mg/kg] of sibutramine for 28 days were used and compared to control animals. Blood samples were collected and plasma smears were prepared for platelet evaluation. Following the addition of thrombin to the plasma samples, the morphology of the fibrin clots was evaluated. Platelet evaluation by scanning electron microscopy revealed morphology typical of a prothrombotic state with a characteristic excessive platelet activation in both low-dose (LD) and high-dose (HD) rats. The fibrin clots of sibutramine-treated rats, LD and HD revealed fused thick fibers with thin fibers forming a netlike structure over the thick fibers which differ considerably from the organized structure of the control animals. It can be concluded that sibutramine alters the ultrastructure of platelets and fibrin networks creating a prothrombotic state.

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“…2C shows an extensive fibrin network created with added human thrombin. These figures are representative micrographs chosen from our database of hundreds of micrographs let and erythrocyte morphology to be drastically altered in stroke 15,16,[49][50][51][52] , showing thrombo-embolic ischaemic stroke to be a hypercoagulable or prothrombotic condition 16) . This technique provides detailed, high resolution images that can show specific changes to ultrastructure.…”

Section: Sem In Thrombo-embolic Ischaemic Strokementioning

confidence: 99%

Novel Diagnostic and Monitoring Tools in Stroke: an Individualized Patient-Centered Precision Medicine Approach

Villiers

Swanepoel

Bester

et al. 2016

J Atheroscler Thromb

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Central to the pathogenesis of ischaemic stroke are the normally protective processes of platelet adhesion and activation. Experimental evidence has shown that the ligand-receptor interactions in ischaemic stroke represent a thrombo-inflammatory cascade, which presents research opportunities into new treatment. However, as anti-platelet drugs have the potential to cause severe side effects in ischaemic stroke patients (as well as other vascular disease patients), it is important to carefully monitor the risk of bleeding and risk of thrombus in patients receiving treatment. Because thrombo-embolic ischaemic stroke is a major health issue, we suggest that the answer to adequate treatment is based on an individualized patient-centered approach, inline with the latest NIH precision medicine approach. A combination of viscoelastic methodologies may be used in a personalized patient-centered regime, including thromboelastography (TEG®) and the lesser used scanning electron microscopy approach (SEM). Thromboelastography provides a dynamic measure of clot formation, strength, and lysis, whereas SEM is a visual structural tool to study patient fibrin structure in great detail. Therefore, we consider the evidence for TEG® and SEM as unique means to confirm stroke diagnosis, screen at-risk patients, and monitor treatment efficacy. Here we argue that the current approach to stroke treatment needs to be restructured and new innovative thought patterns need to be applied, as even approved therapies require close patient monitoring to determine efficacy, match treatment regimens to each patient's individual needs, and assess the risk of dangerous adverse effects. TEG® and SEM have the potential to be a useful tool and could potentially alter the clinical approach to managing ischaemic stroke. As envisaged in the NIH precision medicine approach, this will involve a number of role players and innovative new research ideas, with benefits that will ultimately only be realized in a few years. Therefore, with this ultimate goal in mind, we suggest that an individualized patient-orientated approach is now available and therefore already within our ability to use. J Atheroscler Thromb, 2016; 23: 493-504.

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A descriptive investigation of the ultrastructure of fibrin networks in thrombo-embolic ischemic stroke

Cited by 36 publications

References 19 publications

Differences in fibrin fiber diameters in healthy individuals and thromboembolic ischemic stroke patients

Differences in fibrin fiber diameters in healthy individuals and thromboembolic ischemic stroke patients

The Effect of Sibutramine, a Serotonin-Norepinephrine Reuptake Inhibitor, on Platelets and Fibrin Networks of Male Sprague-Dawley Rats: A Descriptive Study

Novel Diagnostic and Monitoring Tools in Stroke: an Individualized Patient-Centered Precision Medicine Approach

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