Blood coagulation abnormalities in multibacillary leprosy patients

Abstract

BackgroundLeprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae infection. In 2016, more than 200,000 new cases of leprosy were detected around the world, representing the most frequent cause of infectious irreversible deformities and disabilities.Principal findingsIn the present work, we demonstrate a consistent procoagulant profile on 40 reactional and non-reactional multibacillary leprosy patients. A retrospective analysis in search of signs of coagulation abnormalities among 638 leprosy patients identified 35 leprosy patients (5.48%) which displayed a characteristic lipid-like clot formed between blood clot and serum during serum harvesting, herein named ‘leprosum clot’. Most of these patients (n = 16, 45.7%) belonged to the lepromatous leprosy pole of the disease. In addition, formation of the leprosum clot was directly correlated with increased plasma levels of soluble tissue factor and von Willebrand factor. High performance thin layer chromatography demonstrated a high content of neutral lipids in the leprosum clot, and proteomic analysis demonstrated that the leprosum clot presented in these patients is highly enriched in fibrin. Remarkably, differential 2D-proteomics analysis between leprosum clots and control clots identified two proteins present only in leprosy patients clots: complement component 3 and 4 and inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP). In agreement with those observations we demonstrated that M. leprae induces hepatocytes release of IHRP in vitro.ConclusionsWe demonstrated that leprosy MB patients develop a procoagulant status due to high levels of plasmatic fibrinogen, anti-cardiolipin antibodies, von Willebrand factor and soluble tissue factor. We propose that some of these components, fibrinogen for example, presents potential as predictive biomarkers of leprosy reactions, generating tools for earlier diagnosis and treatment of these events.

Altered composition and functional profile of high-density lipoprotein in leprosy patients

“…A worrying fact, since the Brazilian Longitudinal Multicentric Study of Adult Health (ELSA Brazil) [55] classified as desirable levels of HDL-cholesterol �40 mg/dL for men and �50 mg/dL for women. These data are in agreement with recent findings from Silva et al (2018) and Negera et al (2018), which also observed lower levels of HDL-cholesterol in Mb patients compared to Pb and HC [56,57]. Other studies on serum lipids in leprosy also described lower levels of HDL-cholesterol in Mb patients [58,59].…”

The Role of Lipid and the Benefit of Statin in Augmenting Rifampicin Effectivity for a Better Leprosy Treatment

“…The result of the studies has been sum up in Table 1. Among the 15 studies, we summarize that the main topics discussed related to lipid and leprosy include: (1) Serum lipid profile alterations in leprosy in six studies [20], [21], [22], [25], [27], [28] (2); lipid metabolism in leprosy and role of their metabolites [23], [24], [32];…”

“…Five most apparent facts elucidated by the obtained studies are: Alterations of serum lipid profile in leprosy patients [20], [21], [22], [25], [27], [28], lipid metabolism and its metabolites [23], [24], [32], lipid bodies formation [10], [30], [31], and oxidative stress result from lipid metabolism enhanced by MH is proportional to the severity of the infection and the survival of M. leprae itself [26]. Furthermore, interestingly statin found has benefit in leprosy treatment regarding lipid involvement in the immunopathogenesis of leprosy [11] Related to serum lipid profile in leprosy, a study from Sarwar et al [22] found decreased total cholesterol, low-density lipoproteins (LDL), and triglyceride as well as an increased high-density lipoproteins (HDL) on newly diagnosed multibacillary (MB) and paucibacillary (PB) leprosy patients.…”

Involvement of TNF-Producing CD8+ Effector Memory T Cells with Immunopathogenesis of Erythema Nodosum Leprosum in Leprosy Patients

“…being able to provoke injuries in several organs, such as coagulation disorders and kidney failure, and may lead patients to death. 7,16 Thus, it is crucial to study the immune mechanisms triggering reactional episodes, as presented in this work, not only for the identification of the cell subsets involved with the genesis of these processes, but also for the detection of biomarkers of reactions, as well as contributing to an earlier clinical management and to the reduction of reactional morbidity.…”