A Study of Haematological and  Haemostasis Parameters and  Hypercoagulable State in Tuberculosis  Patients in Northern India and the  Outcome with Anti Tubercular Therapy

Kutiyal, Aditya Singh; Gupta, Naresh; Garg, Sandeep; Hira, Harmanjit

doi:10.7860/jcdr/2017/24022.9249

Cited by 11 publications

(13 citation statements)

References 33 publications

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“…Other studies, however, have associated thrombocytopenia with tuberculosis. For example, in 128 Indian patients, thrombocytopenia was observed in 37.5% ( 50 ).…”

Section: Clinical Evidence For the Role Of Platelets In The Response To Tbmentioning

confidence: 99%

Platelet Activation and the Immune Response to Tuberculosis

2021

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In 2019 10 million people developed symptomatic tuberculosis (TB) disease and 1.2 million died. In active TB the inflammatory response causes tissue destruction, which leads to both acute morbidity and mortality. Tissue destruction in TB is driven by host innate immunity and mediated via enzymes, chiefly matrix metalloproteinases (MMPs) which are secreted by leukocytes and stromal cells and degrade the extracellular matrix. Here we review the growing evidence implicating platelets in TB immunopathology. TB patients typically have high platelet counts, which correlate with disease severity, and a hypercoagulable profile. Platelets are present in human TB granulomas and platelet-associated gene transcripts are increased in TB patients versus healthy controls. Platelets most likely drive TB immunopathology through their effect on other immune cells, particularly monocytes, to lead to upregulation of activation markers, increased MMP secretion, and enhanced phagocytosis. Finally, we consider current evidence supporting use of targeted anti-platelet agents in the treatment of TB due to growing interest in developing host-directed therapies to limit tissue damage and improve treatment outcomes. In summary, platelets are implicated in TB disease and contribute to MMP-mediated tissue damage via their cellular interactions with other leukocytes, and are potential targets for novel host-directed therapies.

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“…Other studies, however, have associated thrombocytopenia with tuberculosis. For example, in 128 Indian patients, thrombocytopenia was observed in 37.5% ( 50 ).…”

Section: Clinical Evidence For the Role Of Platelets In The Response To Tbmentioning

confidence: 99%

Platelet Activation and the Immune Response to Tuberculosis

2021

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“…It was first observed that platelet activation status was correlated with TB disease severity [7]. In active TB, a hypercoagulable state exists with an increased risk of thrombosis, which improves after treatment [8]. Furthermore, it is now recognized that platelets play a role in tissue destruction and pro-inflammation in TB disease [9].…”

Section: Introductionmentioning

confidence: 99%

Use of Antiplatelet Agents and Survival of Tuberculosis Patients: A Population-Based Cohort Study

Lee

Chang

et al. 2019

JCM

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While evidence is accumulating that platelets contribute to tissue destruction in tuberculosis (TB) disease, it is still not known whether antiplatelet agents are beneficial to TB patients. We performed this retrospective cohort study and identified incident TB cases in the Taiwan National Tuberculosis Registry from 2008 to 2014. These cases were further classified into antiplatelet users and non-users according to the use of antiplatelet agents prior to the TB diagnosis, and the cohorts were matched using propensity scores (PSs). The primary outcome was survival after a TB diagnosis. In total, 74,753 incident TB cases were recruited; 9497 (12.7%) were antiplatelet users, and 7764 (10.4%) were aspirin (ASA) users. A 1:1 PS-matched cohort with 8864 antiplatelet agent users and 8864 non-users was created. After PS matching, antiplatelet use remained associated with a longer survival (adjusted hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.88–0.95, p < 0.0001). The risk of major bleeding was not elevated in antiplatelet users compared to non-users (p = 0.604). This study shows that use of antiplatelet agents has been associated with improved survival in TB patients. The immunomodulatory and anti-inflammatory effects of antiplatelet agents in TB disease warrant further investigation. Antiplatelets are promising as an adjunct anti-TB therapy.

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“…Thrombocytosis is a recognized biomarker for advanced TB, and infection is often accompanied by a hyper-coagulable state, resulting in increased risk of deep vein thrombosis (DVT) and stroke [4,5]. Recent evidence hints that mycobacteria may drive hemostasis, and that hemostasis may aid their growth.…”

mentioning

confidence: 99%

Thrombocyte Inhibition Restores Protective Immunity to Mycobacterial Infection in Zebrafish

Hortle

Johnson

Johansen

et al. 2019

The Journal of Infectious Diseases

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Background Infection-induced thrombocytosis is a clinically important complication of tuberculosis infection. Recent studies have highlighted the utility of aspirin as a host-directed therapy modulating the inflammatory response to infection but have not investigated the possibility that the effect of aspirin is related to an antiplatelet mode of action. Methods In this study, we utilize the zebrafish-Mycobacterium marinum model to show mycobacteria drive host hemostasis through the formation of granulomas. Treatment of infected zebrafish with aspirin markedly reduced mycobacterial burden. This effect is reproduced by treatment with platelet-specific glycoprotein IIb/IIIa inhibitors demonstrating a detrimental role for infection-induced thrombocyte activation. Results We find that the reduction in mycobacterial burden is dependent on macrophages and granuloma formation, providing the first in vivo experimental evidence that infection-induced platelet activation compromises protective host immunity to mycobacterial infection. Conclusions Our study illuminates platelet activation as an efficacious target of aspirin, a widely available and affordable host-directed therapy candidate for tuberculosis.

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A Study of Haematological and Haemostasis Parameters and Hypercoagulable State in Tuberculosis Patients in Northern India and the Outcome with Anti Tubercular Therapy

Cited by 11 publications

References 33 publications

Platelet Activation and the Immune Response to Tuberculosis

Platelet Activation and the Immune Response to Tuberculosis

Use of Antiplatelet Agents and Survival of Tuberculosis Patients: A Population-Based Cohort Study

Thrombocyte Inhibition Restores Protective Immunity to Mycobacterial Infection in Zebrafish

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