Viscoelasticity and Ultrastructure in Coagulation and Inflammation: Two Diverse Techniques, One Conclusion

Swanepoel, Albe C.; Nielsen, Vance G.; Pretorius, Etheresia

doi:10.1007/s10753-015-0148-7

Cited by 23 publications

(20 citation statements)

References 197 publications

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“…Fibrin formation is catalysed by the enzyme thrombin from fibrinogen and stabilized by thrombin-catalysed factor XIII (FXIII) [33]. Both these components depend on the presence of calcium, as calcium is a co-factor in the formation of FXIII and thrombin and it is known that heavy metals deplete calcium levels [15, 49]. The increased trend seen in K time indicates that the initial clot formation, after it starts forming is rapid.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural, Confocal and Viscoelastic Characteristics of Whole Blood and Plasma After Exposure to Cadmium and Chromium Alone and in Combination: An Ex Vivo Study

Venter

Oberholzer

Bester

et al. 2017

Cell Physiol Biochem

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Background/Aims: Heavy metal pollution is increasing in the environment, contaminating water, food and air supplies. This can be linked to many anthropogenic activities. Heavy metals are absorbed through the skin, inhalation and/or orally. Irrespective of the manner of heavy metal entry in the body, the blood circulatory system is potentially the first to be affected following exposure and adverse effects on blood coagulation can lead to associated thrombotic disease. Although the plasma levels and the effects of cadmium (Cd) and chromium (Cr) on erythrocytes and lymphocytes have been described, the environmental exposure to heavy metals are not limited to a single metal and often involves metal mixtures, with each metal having different rates of absorption, different cellular, tissue, and organ targets. Therefore the aim of this study is to investigate the effects of the heavy metals Cd and Cr alone and whether Cr synergistically increases the effect of Cd on physiological important processes such as blood coagulation. Methods: Human blood was exposed to the heavy metals ex vivo, and thereafter morphological analysis was performed with scanning electron- and confocal laser scanning microscopy (CLSM) in conjunction with thromboelastography®. Results: The erythrocytes, platelets and fibrin networks presented with ultrastructural changes, including varied erythrocytes morphologies, activated platelets and significantly thicker fibrin fibres in the metal-exposed groups. CLSM analysis revealed the presence of phosphatidylserine on the outer surface of the membranes of the spherocytic erythrocytes exposed to Cd and Cr alone and in combination. The viscoelastic analysis revealed only a trend that indicates that clots that will form after heavy metal exposure, will likely be fragile and unstable especially for Cd and Cr in combination. Conclusion: This study identified the blood as an important target system of Cd and Cr toxicity.

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Section: Discussionmentioning

confidence: 99%

Ultrastructural, Confocal and Viscoelastic Characteristics of Whole Blood and Plasma After Exposure to Cadmium and Chromium Alone and in Combination: An Ex Vivo Study

Venter

Oberholzer

Bester

et al. 2017

Cell Physiol Biochem

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“…In the past our laboratory has focussed specifically on using the TEG [160][161][162][163][164][165]. See Table 1 for a comprehensive list of measurements that can be done using thromboelastography.…”

Section: Methods For Determining the Clotting Processmentioning

confidence: 99%

Substoichiometric molecular control and amplification of the initiation and nature of amyloid fibril formation: lessons from and for blood clotting

Pretorius

2016

Preprint

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The chief and largely terminal element of normal blood clotting is considered to involve the polymerisation of the mainly α-helical fibrinogen to fibrin, with a binding mechanism involving ‘knobs and holes’ but with otherwise littl change in protein secondary structure. We recognise, however, that extremely unusual mutations, or mechanical stressing, can cause fibrinogen to adopt a conformation containing extensive β-sheets. Similarly, prions can change morphology from a largely alpha-helical to a largely β-sheet conformation, and the latter catalyses both the transition and the self-organising polymerisation of the β-sheet structures. Many other proteins can do this, where it is known as amyloidogenesis. When fibrin is formed in samples from patients harbouring different diseases it can have widely varying diameters and morphologies. We here develop the idea, and summarise the evidence, that in many cases the anomalous fibrin fibre formation seen in such diseases actually amounts to amyloidogenesis. In particular, fibrin can interact withthe amyloid-β (Aβ) protein that is misfolded in Alzheimer's disease. Seeing these unusual fibrin morphologies as true amyloids explains a great deal about fibrin(ogen) biology that was previously opaque, and provides novel strategies for treating such coagulopathies. The literature on blood clotting can usefully both inform and be informed by that on prions and on the many other widely recognised (β)-amyloid proteins.“Novel but physiologically important factors that affect fibrinolysis have seldom been discovered and characterized in recent years” [1]

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“…[22][23][24] Platelets are important role players in a hypercoagulable state during inflammation and their activation occurs in three stages (initiation, extension, and perturbation). [25][26][27] Besides hemostasis, platelets also appear to have a role in the immune system. 28 Low-grade inflammatory conditions are associated with a high mean platelet volume (MPV).…”

Section: Circulating Inflammatory Markers and Their Effects On The Hementioning

confidence: 99%

“…28 Low-grade inflammatory conditions are associated with a high mean platelet volume (MPV). 27 Platelets can also be classified as natural inflammatory cells. They have the ability to aggregate/gather around microorganisms, and to assist with the removal from the blood.…”

Section: Circulating Inflammatory Markers and Their Effects On The Hementioning

confidence: 99%

Pathological Clotting and Deep Vein Thrombosis in Patients with HIV

Jackson

Pretorius

2018

Semin Thromb Hemost

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The number of people infected with human immunodeficiency virus (HIV) is rapidly increasing and the majority of those infected are living in sub-Saharan Africa. Some hallmarks of HIV are inflammation and upregulation of inflammatory markers. A pathological coagulation system may accompany these inflammatory changes and potentially result in venous thromboembolism such as a deep vein thrombosis (DVT). In this review, the authors describe the inflammatory profile in HIV, the treatment regimens currently in place in South Africa, and in particular how HIV affects the hematological system, with specific focus on platelets, red blood cells (RBCs; erythrocytes), and fibrin(ogen). They also discuss the presence of DVT in HIV, focus on screening tests, and suggest a more proactive approach to track the inflammatory profile of HIV patients, by specifically using parameters that might point to pathological coagulation; these should involve platelet, RBC, and fibrin(ogen) analysis. They conclude by suggesting that including coagulation function tests to study the effect of treatment interventions would improve outcomes in these individuals, as it could help in the diagnosis of thromboembolic disease. Furthermore, this approach could streamline treatment strategies due to improved monitoring. A better understanding of hypercoagulability of HIV-infected patients is therefore urgently needed. In conclusion, the authors suggest a panel of pathology tests that should be considered as standard procedures when HIV is present.

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Viscoelasticity and Ultrastructure in Coagulation and Inflammation: Two Diverse Techniques, One Conclusion

Abstract: The process of blood clotting has been studied for centuries.

Cited by 23 publications

References 197 publications

Ultrastructural, Confocal and Viscoelastic Characteristics of Whole Blood and Plasma After Exposure to Cadmium and Chromium Alone and in Combination: An Ex Vivo Study

Ultrastructural, Confocal and Viscoelastic Characteristics of Whole Blood and Plasma After Exposure to Cadmium and Chromium Alone and in Combination: An Ex Vivo Study

Substoichiometric molecular control and amplification of the initiation and nature of amyloid fibril formation: lessons from and for blood clotting

Pathological Clotting and Deep Vein Thrombosis in Patients with HIV

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