Localization of factor-VIII-related antigen in human vascular subendothelium

Rand, JH; Sussman, II; G, Re; Chu, SV; Solomon, V

doi:10.1182/blood.v55.5.752.bloodjournal555752

Cited by 12 publications

(12 citation statements)

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“…The ante-mortem involvement of both established DAD and disseminated intravascular coagulation (DIC) models may explain the serious hypoxemia that characterizes ARDS in subjects with COVID-19 [ 46 ]. Finally, the FVIII-von Willebrand Factor (vWF) complex is another prothrombotic unit responsible for the adhesion of platelets to subendothelial structures, released by endothelial cells when injured, in association with severe endothelial dysfunction; thus, it has been suggested as a biomarker of endothelial dysfunction, which is largely involved in COVID-19 pathogenesis [ 47 , 48 , 49 , 50 , 51 , 52 ]. Moreover, it is interesting that COVID-19, ACE, and FVIII positivity were collected in the same fields.…”

Section: Discussionmentioning

confidence: 99%

Preliminary Post-Mortem COVID-19 Evidence of Endothelial Injury and Factor VIII Hyperexpression

et al. 2020

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(1) Background: The current outbreak of COVID-19 infection is an ongoing challenge and a major threat to public health that requires surveillance, prompt diagnosis, as well as research efforts to understand the viral pathogenesis. Despite this, to date, very few studies have been performed concerning autoptic specimens. Therefore, this study aimed: (i) to reiterate the importance of the autoptic examination, the only method able to precisely define the cause of death; (ii) to provide a complete post-mortem histological and immunohistochemical investigation pattern capable of diagnosing death from COVID-19 infection. (2) Methods: In this paper, the lung examination of two subjects who died from COVID-19 are discussed, comparing the obtained data with those of the control, a newborn who died from pneumonia in the same pandemic period. (3) Results: The results of the present study suggest that COVID-19 infection can cause different forms of acute respiratory distress syndrome (ARDS), due to diffuse alveolar damage and diffuse endothelial damage. Nevertheless, different patterns of cellular and cytokine expression are associated with anti-COVID-19 antibody positivity, compared to the control case. Moreover, in both case studies, it is interesting to note that COVID-19, ACE2 and FVIII positivity was detected in the same fields. (4) Conclusions: COVID-19 infection has been initially classified as exclusively interstitial pneumonia with varying degrees of severity. Subsequently, vascular biomarkers showed that it can also be considered a vascular disease. The data on Factor VIII discussed in this paper, although preliminary and limited in number, seem to suggest that the thrombogenicity of Sars-CoV2 infection might be linked to widespread endothelial damage. In this way, it would be very important to investigate the pro-coagulative substrate both in all subjects who died and in COVID-19 survivors. This is because it may be hypothesized that the different patterns with which the pathology is expressed could depend on different individual susceptibility to infection or a different personal genetic-clinical background. In light of these findings, it would be important to perform more post-mortem investigations in order to clarify all aspects of the vascular hypothesis in the COVID-19 infection.

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Section: Discussionmentioning

confidence: 99%

Preliminary Post-Mortem COVID-19 Evidence of Endothelial Injury and Factor VIII Hyperexpression

et al. 2020

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“…These functions are carried out primarily through the tethering of GP Ibα in the platelet membrane GP Ib‐IX‐V receptor complex 6 to the A1 domain of immobilized VWF exposed to flowing blood. As a constitutive component of the ECM of endothelial cells 129 , in which it is associated with collagen type VI filaments 128 36 , subendothelial VWF can directly support platelet adhesion 147 168 173 11 . Nonetheless, hemostasis can be normal in the absence of endogenous endothelial VWF if plasma VWF is present.…”

Section: The Unique Role Of Von Willebrand Factor In Platelet Adhesiomentioning

confidence: 99%

Platelet Adhesion under Flow

2009

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Platelet adhesive mechanisms play a well-defined role in hemostasis and thrombosis, but evidence continues to emerge for a relevant contribution to other pathophysiological processes including inflammation, immune-mediated responses to microbial and viral pathogens, and cancer metastasis. Hemostasis and thrombosis are related aspects of the response to vascular injury, but the former protects from bleeding after trauma while the latter is a disease mechanism. In either situation, adhesive interactions mediated by specific membrane receptors support the initial attachment of single platelets to cellular and extracellular matrix constituents of the vessel wall and tissues. In the subsequent steps of thrombus growth and stabilization, adhesive interactions mediate platelet to platelet cohesion (aggregation) and anchoring to the fibrin clot. A key functional aspect of platelets is their ability to circulate in a quiescent state surveying the integrity of the inner vascular surface, coupled to a prompt reaction wherever alterations are detected. In many respects, therefore, platelet adhesion to vascular wall structures, to one another or to other blood cells are facets of the same fundamental biological process. The adaptation of platelet adhesive functions to the effects of blood flow is the main focus of this review. KeywordsHemostasis; Thrombosis; Vascular Biology; Extracellular Matrix; Collagen Physiopathological significance of platelet adhesionMammalian platelets are fragments of cytoplasm released into circulating blood by megakaryocytes, a precursor hematopoietic cell residing in the bone marrow [1,2]. Without a nucleus, platelets have no control on gene expression but possess a translational machinery that can direct protein synthesis [3]. The physiological role of platelets consists in a fundamental contribution to hemostasis, the defense mechanism that prevents blood loss when the continuity of the vascular tree is interrupted by traumatic injury to tissues [4,5]. To exert their function, platelets survey the vascular system and adhere where alterations of the endothelial cell lining, accompanied or not by exposure of subendothelial matrix components, are detected [6]. More recent studies have highlighted a different and equally important host defense role of platelets, namely the ability to maintain normal vascular permeability and direct other effector cells to sites where microbial and viral pathogens induce inflammatory responses [7]. As evidenced in a mouse model of infection by lymphocytic choriomeningitis virus, a reduced platelet count of 10-20% of normal is sufficient to maintain a normal hematocrit and permit viral clearance dependent on antigenspecific cytotoxic T-lymphocytes. Spontaneous hemorrhage, mostly mucocutaneous in NIH Public Access Author ManuscriptMicrocirculation. Author manuscript; available in PMC 2011 March 15. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript nature, and death develop when platelets are further reduced in number to ~1% of normal ...

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“…Later vWF was also found in the extracellular matrix of the cells. 4 Since then, our knowledge about synthesis, processing, and multimerization has been increased enormously. The first steps in the synthesis of vWF are now known due to the cloning of the molecule.…”

Section: Synthesis Of Vwf By Endothelial Cellsmentioning

confidence: 99%