Abstract

Blood stasis syndrome (BSS) is an important pathological condition in traditional East Asian medicine and is associated with ischemic heart disease, cerebral vascular accident, diabetes mellitus, chronic renal failure, severe traumatic injury, and dysmenorrhea. However, previous studies have been unable to reveal the clinical and biological characteristics or biological markers of BSS. We hypothesized that the heterogeneity among the manifestations of BSS or non-BSS could interfere with an analysis to describe the characteristics of BSS. In this study, male participants based on the severity of BSS-associated symptoms and signs were clustered and classified into four subgroups: BSS subgroups (1), (2), (3), and (4). Non-BSS core subgroup was redefined using manifestation cluster analysis. Biological characteristics of subgroups BSS(1) and BSS(2) belong to the range of the non-BSS core subgroup (1), whereas that of subgroups BSS(3) and BSS(4) are characterized by different biological parameters such as systemic inflammatory conditions and elevated D-dimer level. Our results suggested that patients in subgroups of BSS(3) and BSS(4) are more likely to be exposed in an inflammatory state than other BSS subgroups. We found the heterogeneity among the manifestations which could mask the characteristics of BSS and identified the clinical and biological profiles of the four BSS subgroups through comparisons of the redefined non-BSS and BSS subgroups. This finding could provide accurate diagnostic criteria and new approaches for BSS treatments in different subgroups.

Highlights

  • Blood stasis is a pathological concept in traditional East Asian medicine that refers to stagnant blood that has lost its physiological function within the body [1,2,3] and leads to blood stasis syndrome (BSS), which is characterized by multiple signs and symptoms, such as sublingual varicosis, angiotelectasis, a slow and choppy pulse, local fixed pain, nyctalgia, menstrual cramps, a dark-purple tongue, or infraorbital darkness [2, 4]

  • BSS and non-BSS participants classified in the same cluster could have substantial similarities in their biological characteristics

  • The non-BSS(1) group had a lower proportion of participants who smoke, but age, Body mass index BSS (BMI), SBP, DBP, drinking status, and medication were similar among the five groups (Table 1)

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Summary

Introduction

Blood stasis is a pathological concept in traditional East Asian medicine that refers to stagnant blood that has lost its physiological function within the body [1,2,3] and leads to blood stasis syndrome (BSS), which is characterized by multiple signs and symptoms, such as sublingual varicosis, angiotelectasis, a slow and choppy pulse, local fixed pain, nyctalgia, menstrual cramps, a dark-purple tongue, or infraorbital darkness [2, 4]. Clinical studies have reported that these manifestations are observed in patients with ischemic heart disease, cerebral vascular accident, diabetes mellitus, chronic renal failure, severe traumatic injury, and dysmenorrhea [3, 5]. Many studies have clustered pattern of symptoms with a psychoneurological symptom cluster intensity score because they have showed high heterogeneity which lead diagnosis and therapeutic failures [13, 14]. Clustering analysis is a method to define subgroups of individuals with high heterogeneity to explore clinical phenotypes in patients with various diseases [15]. Classification of disease into subtypes which have different clinical signs in terms of prognosis and individual differences might be needed to explain between clinical phenotype and biological mechanisms [16]

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