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  1. Article ; Online: A decision-tree approach to treat platelet hyperactivity and anomalous blood clotting in acute COVID-19 patients

    Laubscher, Gert J / Lourens, Petrus J / Venter, Chantelle / Grobbelaar, Lize M / Kell, Douglas B / Pretorius, Etheresia

    medRxiv

    Abstract: The coronavirus disease 2019 (COVID-19) (SARS-Cov-2) has caused a worldwide, sudden and substantial increase in hospitalizations for pneumonia with multiorgan problems. An important issue is also that there is still no unified standard for the diagnosis ... ...

    Abstract The coronavirus disease 2019 (COVID-19) (SARS-Cov-2) has caused a worldwide, sudden and substantial increase in hospitalizations for pneumonia with multiorgan problems. An important issue is also that there is still no unified standard for the diagnosis and treatment of COVID-19. Substantial vascular events are significant accompaniments to lung complications in COVID-19 patients. Various papers have now also shown the significance of thromboelastrography (TEG) as point-of-care technology to determine the levels of coagulopathy (both clotting and bleeding) in COVID-19, in managing COVID-19 patients. Here we present two treatment protocols that may used to treat thrombotic and bleeding or thrombocytopenia pathologies. We also present a case study, where the thrombotic pathology was successfully treated with the thrombotic protocol. Both the protocols use clinical parameters like D-dimer and CRP, as well as the TEG, to closely follow the daily clotting propensity of COVID-19 patients. We conclude by suggesting that the treatment of COVID-19 patients, should be based on a combination of blood biomarkers, and results from point-of-care analyses like the TEG. Such a combination approach closely follow the physiological responses of the immune system, the haematological, as well as the coagulation system, in real-time.
    Keywords covid19
    Language English
    Publishing date 2021-07-07
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.07.05.21260012
    Database COVID19

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  2. Article ; Online: Prevalence of amyloid blood clots in COVID-19 plasma

    Pretorius, Etheresia / Venter, Chantelle / Laubscher, Gert J / Lourens, Petrus J / Steenkamp, Janami / Kell, Douglas B

    medRxiv

    Abstract: The rapid detection of COVID-19 uses genotypic testing for the presence of SARS-Cov-2 virus in nasopharyngeal swabs, but it can have a poor sensitivity. A rapid, host-based physiological test that indicated whether the individual was infected or not ... ...

    Abstract The rapid detection of COVID-19 uses genotypic testing for the presence of SARS-Cov-2 virus in nasopharyngeal swabs, but it can have a poor sensitivity. A rapid, host-based physiological test that indicated whether the individual was infected or not would be highly desirable. Coagulaopathies are a common accompaniment to COVID-19, especially micro-clots within the lungs. We show here that microclots can be detected in the native plasma of COVID-19 patient, and in particular that such clots are amyloid in nature as judged by a standard fluorogenic stain. This provides a rapid and convenient test (P<0.0001), and suggests that the early detection and prevention of such clotting could have an important role in therapy.
    Keywords covid19
    Language English
    Publishing date 2020-07-29
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.07.28.20163543
    Database COVID19

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  3. Article ; Online: Prevalence of amyloid blood clots in COVID-19 plasma

    Pretorius, Etheresia / Venter, Chantelle / Laubscher, Gert J. / Lourens, Petrus J. / Steenkamp, Janami / Kell, Douglas B.

    2020  

    Abstract: CITATION: Pretorius, E. et al. 2020. Prevalence of amyloid blood clots in COVID-19 plasma. medRxiv, doi:10.1101/2020.07.28.20163543. ... The original publication is available at https://www.medrxiv.org ... The rapid detection of COVID-19 uses genotypic ... ...

    Abstract CITATION: Pretorius, E. et al. 2020. Prevalence of amyloid blood clots in COVID-19 plasma. medRxiv, doi:10.1101/2020.07.28.20163543.

    The original publication is available at https://www.medrxiv.org

    The rapid detection of COVID-19 uses genotypic testing for the presence of SARS-Cov-2 virus in nasopharyngeal swabs, but it can have a poor sensitivity. A rapid, host-based physiological test that indicated whether the individual was infected or not would be highly desirable. Coagulaopathies are a common accompaniment to COVID-19, especially micro-clots within the lungs. We show here that microclots can be detected in the native plasma of COVID-19 patient, and in particular that such clots are amyloid in nature as judged by a standard fluorogenic stain. This provides a rapid and convenient test (P<0.0001), and suggests that the early detection and prevention of such clotting could have an important role in therapy.

    https://www.medrxiv.org/content/10.1101/2020.07.28.20163543v1

    Pre-print
    Keywords COVID-19 (Disease) ; Blood -- Coagulation ; Blood plasma ; covid19
    Language English
    Publisher medRxiv
    Publishing country za
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: Implications for microclot formation in COVID-19

    Grobbelaar, Lize M / Venter, Chantelle / Vlok, Mare / Ngoepe, Malebogo / Laubscher, Gert J / Lourens, Petrus J / Steenkamp, Janami / Kell, Douglas B / Pretorius, Etheresia

    medRxiv

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) -induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One of the most important pathologies, is hypercoagulation and ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) -induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One of the most important pathologies, is hypercoagulation and microclots in the lungs of patients. Here we study the effect of isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagen sui generis. Using scanning electron and fluorescence microscopy as well as mass spectrometry, we investigate the potential of this inflammagen to interact with platelets and fibrin(ogen) directly to cause blood hypercoagulation. Using platelet poor plasma (PPP), we show that spike protein may interfere with blood flow. Mass spectrometry also showed that when spike protein S1 is added to healthy PPP, it results in structural changes to β and γ fibrin(ogen), complement 3, and prothrombin. These proteins were substantially resistant to trypsinization, in the presence of spike protein S1. Here we suggest that, in part, the presence of spike protein in circulation may contribute to the hypercoagulation in COVID-19 positive patients and may cause substantial impairment of fibrinolysis. Such lytic impairment may result in the persistent large microclots we have noted here and previously in plasma samples of COVID-19 patients. This observation may have important clinical relevance in the treatment of hypercoagulability in COVID-19 patients.
    Keywords covid19
    Language English
    Publishing date 2021-03-08
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.03.05.21252960
    Database COVID19

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  5. Article ; Online: Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes.

    Grobler, Corlia / Maphumulo, Siphosethu C / Grobbelaar, L Mireille / Bredenkamp, Jhade C / Laubscher, Gert J / Lourens, Petrus J / Steenkamp, Janami / Kell, Douglas B / Pretorius, Etheresia

    International journal of molecular sciences

    2020  Volume 21, Issue 14

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.
    MeSH term(s) Betacoronavirus ; Blood Platelets/metabolism ; COVID-19 ; Coronavirus Infections/pathology ; Cytokine Release Syndrome/pathology ; Endothelial Cells/metabolism ; Erythrocytes/metabolism ; Fibrin Fibrinogen Degradation Products/metabolism ; Humans ; P-Selectin/metabolism ; Pandemics ; Pneumonia, Viral/pathology ; Point-of-Care Systems ; Precision Medicine/methods ; SARS-CoV-2 ; Thrombocytopenia/pathology ; Thrombosis/pathology ; von Willebrand Factor/metabolism
    Chemical Substances Fibrin Fibrinogen Degradation Products ; P-Selectin ; SELP protein, human ; fibrin fragment D ; von Willebrand Factor
    Keywords covid19
    Language English
    Publishing date 2020-07-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21145168
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Immuno-Thrombotic Complications of COVID-19: Implications for Timing of Surgery and Anticoagulation.

    Bunch, Connor M / Moore, Ernest E / Moore, Hunter B / Neal, Matthew D / Thomas, Anthony V / Zackariya, Nuha / Zhao, Jonathan / Zackariya, Sufyan / Brenner, Toby J / Berquist, Margaret / Buckner, Hallie / Wiarda, Grant / Fulkerson, Daniel / Huff, Wei / Kwaan, Hau C / Lankowicz, Genevieve / Laubscher, Gert J / Lourens, Petrus J / Pretorius, Etheresia /
    Kotze, Maritha J / Moolla, Muhammad S / Sithole, Sithembiso / Maponga, Tongai G / Kell, Douglas B / Fox, Mark D / Gillespie, Laura / Khan, Rashid Z / Mamczak, Christiaan N / March, Robert / Macias, Rachel / Bull, Brian S / Walsh, Mark M

    Frontiers in surgery

    2022  Volume 9, Page(s) 889999

    Abstract: Early in the coronavirus disease 2019 (COVID-19) pandemic, global governing bodies prioritized transmissibility-based precautions and hospital capacity as the foundation for delay of elective procedures. As elective surgical volumes increased, ... ...

    Abstract Early in the coronavirus disease 2019 (COVID-19) pandemic, global governing bodies prioritized transmissibility-based precautions and hospital capacity as the foundation for delay of elective procedures. As elective surgical volumes increased, convalescent COVID-19 patients faced increased postoperative morbidity and mortality and clinicians had limited evidence for stratifying individual risk in this population. Clear evidence now demonstrates that those recovering from COVID-19 have increased postoperative morbidity and mortality. These data-in conjunction with the recent American Society of Anesthesiologists guidelines-offer the evidence necessary to expand the early pandemic guidelines and guide the surgeon's preoperative risk assessment. Here, we argue elective surgeries should still be delayed on a personalized basis to maximize postoperative outcomes. We outline a framework for stratifying the individual COVID-19 patient's fitness for surgery based on the symptoms and severity of acute or convalescent COVID-19 illness, coagulopathy assessment, and acuity of the surgical procedure. Although the most common manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is COVID-19 pneumonitis, every system in the body is potentially afflicted by an endotheliitis. This endothelial derangement most often manifests as a hypercoagulable state on admission with associated occult and symptomatic venous and arterial thromboembolisms. The delicate balance between hyper and hypocoagulable states is defined by the local immune-thrombotic crosstalk that results commonly in a hemostatic derangement known as fibrinolytic shutdown. In tandem, the hemostatic derangements that occur during acute COVID-19 infection affect not only the timing of surgical procedures, but also the incidence of postoperative hemostatic complications related to COVID-19-associated coagulopathy (CAC). Traditional methods of thromboprophylaxis and treatment of thromboses after surgery require a tailored approach guided by an understanding of the pathophysiologic underpinnings of the COVID-19 patient. Likewise, a prolonged period of risk for developing hemostatic complications following hospitalization due to COVID-19 has resulted in guidelines from differing societies that recommend varying periods of delay following SARS-CoV-2 infection. In conclusion, we propose the perioperative, personalized assessment of COVID-19 patients' CAC using viscoelastic hemostatic assays and fluorescent microclot analysis.
    Language English
    Publishing date 2022-05-04
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2773823-1
    ISSN 2296-875X
    ISSN 2296-875X
    DOI 10.3389/fsurg.2022.889999
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

    Grobler, Corlia / Maphumulo, Siphosethu C / Grobbelaar, L Mireille / Bredenkamp, Jhade C / Laubscher, Gert J / Lourens, Petrus J / Steenkamp, Janami / Kell, Douglas B / Pretorius, Etheresia

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #670475
    Database COVID19

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  8. Article ; Online: Covid-19

    Grobler, Corlia / Maphumulo, Siphosethu C. / Grobbelaar, L. Mireille / Bredenkamp, Jhade C. / Laubscher, Gert J. / Lourens, Petrus J. / Steenkamp, Janami / Kell, Douglas B. / Pretorius, Etheresia

    the rollercoaster of fibrin(ogen), D-dimer, Von Willebrand Factor, P-selectin and their interactions with endothelial cells, platelets and erythrocytes

    2020  

    Abstract: CITATION: Grobler, C. et al. 2020. Covid-19 : the rollercoaster of fibrin(ogen), D-dimer, Von Willebrand Factor, P-selectin and their interactions with endothelial cells, platelets and erythrocytes. International Journal of Molecular Sciences, 21(14): ... ...

    Abstract CITATION: Grobler, C. et al. 2020. Covid-19 : the rollercoaster of fibrin(ogen), D-dimer, Von Willebrand Factor, P-selectin and their interactions with endothelial cells, platelets and erythrocytes. International Journal of Molecular Sciences, 21(14):5168, doi:10.3390/ijms21145168.

    The original publication is available at https://www.mdpi.com

    Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

    Medical Research Council of South Africa (MRC), grant number A0X331

    Self-initiated research and by The Novo Nordisk Foundation, grant number: NNF10CC1016517

    https://www.mdpi.com/1422-0067/21/14/5168

    Publisher's version
    Keywords COVID-19 (Disease) ; Thrombocytopenia ; Blood -- Coagulation ; Thrombosis ; covid19
    Subject code 610
    Language English
    Publishing date 2020-07-21
    Publisher MDPI
    Publishing country za
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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