Procoagulant Microvesicles in COVID-19 Patients: Possible Modulators of Inflammation and Prothrombotic Tendency

Hamali, Hassan A; Saboor, Muhammad; Dobie, Gasim; Madkhali, Aymen M; Akhter, Muhammad Saleem; Hakamy, Ali; Al-Mekhlafi, Hesham M.; Jackson, Denise E.; Matari, - Yahya H; Mobarki, Abdullah A

doi:10.2147/idr.s355395

Cited by 14 publications

(14 citation statements)

References 64 publications

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“…Several groups developed in-house human TF ELISAs that measure TF protein in plasma [26,45–69]. We found that the values for TF protein from our in-house TF ELISA correlated with our in-house TF activity assay (linear correlation coefficient r = 0.89) [26].…”

Section: Antigen Assaysmentioning

confidence: 59%

Measurement of tissue factor-positive extracellular vesicles in plasma: strengths and weaknesses of current methods

Mackman

Sachetto

Hisada

2022

Current Opinion in Hematology

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Purpose of review This review evaluates the different methods used to measure levels of tissue factor (TF) in plasma and on extracellular vesicles (EVs). Levels of TF-positive (TF+) EVs in blood are increased in a variety of diseases, such as cancer, sepsis, and viral infection, and are associated with thrombosis. Highly sensitive assays are required to measure the low levels of TF+ EVs in blood. Recent findings TF antigen levels in plasma have been measured using standard ELISAs, SimpleStep ELISA technology, and solid-phase proximity ligation assay. Some studies reported the detection of TF+ EVs in plasma by flow cytometry. In addition, TF+ EVs can be captured onto beads and chips using anti-TF antibodies. Several assays have been developed to measure TF activity in EVs isolated from plasma. Importantly, activity-based assays are more sensitive than antigen-based assays as a single TF/FVIIa complex can generate large amounts of FXa. Summary We recommend isolating EVs from plasma and measuring TF activity using a functional assay in the presence and absence of an anti-TF antibody. We do not recommend using antigen-based assays as these are not sensitive enough to detect the low levels of TF in plasma.

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Section: Antigen Assaysmentioning

confidence: 59%

Measurement of tissue factor-positive extracellular vesicles in plasma: strengths and weaknesses of current methods

Mackman

Sachetto

Hisada

2022

Current Opinion in Hematology

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“…This observation has been reported previously in malaria infection 18 and other disorders. 19,20,41 TF expression by ECs has been reported in Plasmodium falciparum infection, which has the ability to support coagulation complexes. 18 The expression of TF from ECs is mainly driven by the effect of parasitized RBC and parasitized RBC-derived MVs.…”

Section: Discussionmentioning

confidence: 99%

“…These findings are consistent with those of previous studies, which reported increased levels of procoagulant MVs in malaria patients [12][13][14][15][16] and also in inflammatory conditions. 19,20,32 Campos et al suggested that MVs play a role in the paroxysms of non-immune patients infected with Plasmodium vivax. 14 In addition, MVs contribute to the pathogenesis and mediate inflammatory response induced by Plasmodium falciparum 17 and play a role in the pathogenesis of severe malaria infection, including in neurological manifestation.…”

Section: Discussionmentioning

confidence: 99%

“…34 In the current study, the increase in the level of procoagulant MVs was ~3.8-fold, which is higher than the increase reported in dengue infection (~2.7-fold) 20 and known hypercoagulable state condition of sickle cell disease (~2.5-fold) 10 but less than that of coronavirus disease of 2019 (COVID-19) infection (~5.6-fold). 19 The method used in the study is a functional assay that can detect the ability of the procoagulant MVs to support thrombin formation. MVs have the ability to support coagulation complexes and subsequent thrombin generation in healthy individuals, 26 in malaria infection, 18 in other pathological conditions with inflammatory mechanism, including human endotoxemia, 35 and in cases of thrombosis (venous and arterial thrombosis).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, MVs can be derived from almost all cell types in vivo and in vitro and can be found in blood, tissues, urine, saliva, and all other body fluids. Elevated levels of MVs and tissue factor-bearing MVs (TF-bearing MVs) have been observed in a broad range of physiological (such as during physical exercise 7 and pregnancy) 8 and pathological conditions [9][10][11] and in infectious diseases, including parasitic infection (mainly malaria infection) [12][13][14][15][16][17][18] , viral infection, 19,20 and bacterial infection. 21 MVs have been proposed to play a key role in the pathogenesis, mediating inflammatory responses, severity and manifestation in different type of malaria infection.…”

Section: Introductionmentioning

confidence: 99%

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Elevated Levels of Procoagulant Microvesicles and Tissue-Factor Bearing Microvesicles in Malaria Patients

Madkhali¹,

Mobarki²,

Ghzwani³

et al. 2023

IJGM

Self Cite

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Background: Procoagulant microvesicles (MVs) are submicron membrane fragments released from activated cells and cells undergoing apoptosis. The procoagulant activity of MVs is enhanced in the presence of tissue factor (TF). MVs and TF are active mediators that induce pro-inflammatory response and prothrombotic tendency and have been linked to the severity of several disorders, including malaria infection. The current study aimed to measure the levels of circulating procoagulant MVs and TF-bearing MVs in malaria patients and correlate these levels with other hematological parameters and parasitemia. Materials and Methods: Levels of MVs and TF-bearing MVs in the plasma of children and adult patients infected with Plasmodium falciparum were measured alongside matched healthy controls. Results: Patients with Plasmodium falciparum infection had ~3.8 times MVs (p < 0.0001) and ~13.0 times TF-bearing MVs compared to the matched healthy controls. MVs showed inverse significant correlation with platelet count (p = 0.0055), hemoglobin (p = 0.0004) and parasitemia. Conclusion: Elevated levels of MVs and TF-bearing MVs could be useful biomarkers to evaluate the procoagulant activity, inflammatory response and parasitemia levels in malaria infection, aiding in better management of the disease.

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Extracellular Vesicles: The Invisible Heroes and Villains of COVID‐19 Central Neuropathology

Chang,

Chen,

et al. 2023

Advanced Science

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Acknowledging the neurological symptoms of COVID‐19 and the long‐lasting neurological damage even after the epidemic ends are common, necessitating ongoing vigilance. Initial investigations suggest that extracellular vesicles (EVs), which assist in the evasion of the host's immune response and achieve immune evasion in SARS‐CoV‐2 systemic spreading, contribute to the virus's attack on the central nervous system (CNS). The pro‐inflammatory, pro‐coagulant, and immunomodulatory properties of EVs contents may directly drive neuroinflammation and cerebral thrombosis in COVID‐19. Additionally, EVs have attracted attention as potential candidates for targeted therapy in COVID‐19 due to their innate homing properties, low immunogenicity, and ability to cross the blood‐brain barrier (BBB) freely. Mesenchymal stromal/stem cell (MSCs) secreted EVs are widely applied and evaluated in patients with COVID‐19 for their therapeutic effect, considering the limited antiviral treatment. This review summarizes the involvement of EVs in COVID‐19 neuropathology as carriers of SARS‐CoV‐2 or other pathogenic contents, as predictors of COVID‐19 neuropathology by transporting brain‐derived substances, and as therapeutic agents by delivering biotherapeutic substances or drugs. Understanding the diverse roles of EVs in the neuropathological aspects of COVID‐19 provides a comprehensive framework for developing, treating, and preventing central neuropathology and the severe consequences associated with the disease.

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Procoagulant Microvesicles in COVID-19 Patients: Possible Modulators of Inflammation and Prothrombotic Tendency

Cited by 14 publications

References 64 publications

Measurement of tissue factor-positive extracellular vesicles in plasma: strengths and weaknesses of current methods

Measurement of tissue factor-positive extracellular vesicles in plasma: strengths and weaknesses of current methods

Elevated Levels of Procoagulant Microvesicles and Tissue-Factor Bearing Microvesicles in Malaria Patients

Extracellular Vesicles: The Invisible Heroes and Villains of COVID‐19 Central Neuropathology

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