The results of this study showed that angle α and k value, reflecting the Fib function, were potential biological indicators for evaluating the occurrence and severity of DF. In this study, patients with DF had higher angle α and Fib levels than diabetic patients without DF, and the levels of k value in patients with DF were significantly lower than those in diabetic patients without DF. More importantly, the angle α, Fib and k value were changed in the early stage of diabetic foot.
Diabetes mellitus, characterized by fasting hyperglycemia, is a risk factor for atherosclerotic thrombosis, and the diabetic foot is one of its serious chronic complications and a major cause of hospitalization and amputation in diabetic patients. Common risk factors that predispose to diabetic foot include poor glycemic control, peripheral neuropathy, and PAD. Domestic studies have shown that 19.5% of diabetic patients over 50 years of age and 35.4% of diabetic patients over 60 years of age have lower limb arterial lesions in China [1, 2]. In addition, the severity of the diabetic foot is associated with a higher rate of lower limb amputation, with 85% of DF patients progressing to low distal amputation. It has a high rate of disability and mortality, which seriously affects patients’ life and quality of life due to its psychological and social consequences.
The essence of lower extremity vasculopathy in the diabetic foot is atherosclerosis. Platelet hyperreactivity, coagulation status and abnormal fibrinolytic function are prevalent in patients with diabetic foot and worsen with the progression of the disease [14]. Prostacyclin and nitric oxide produced by normal endothelial cells have anti-platelet aggregation and adhesion functions, and metabolic abnormalities such as sustained elevation of blood glucose cause impaired endothelial function, inhibition of endothelial nitric oxide synthase activity, decreased nitric oxide release, and enhanced platelet adhesion and aggregation [15]. At the same time, metabolic abnormalities increase fibrinogen activator inhibitor and fibrinogen, causing a hypercoagulable state of blood in diabetic foot patients, which predisposes to thrombus formation and causes microvascular and lower extremity macroangiopathy [16]. It would be significant to predict the occurrence and development of diabetic foot in advance and intervene early when peripheral vasculopathy is present in diabetic patients but before diabetic foot complications develop.
Fibrinogen, synthesized mainly by hepatocytes, is the most abundant procoagulant factor in plasma. Fib is involved in atherosclerosis and thrombosis, reflects inflammatory changes and endothelial dysfunction in vascular lesions, contributes to a hypercoagulable state of blood, and is one of the underlying conditions for thrombosis and subclinical atherosclerosis [17]. Some studies have used fibrinogen for predicting diabetic foot and assessing the severity of diabetic foot, and its optimal cut-off points for determining the risk and severity of DF were 3.88 g/L and 4.74 g/L, respectively, with an area under the curve of 0.86 (sensitivity of 0.74, specificity of 0.87) and 0.73 (sensitivity of 0.76, specificity of 0.58) [18]. In the present study, we found that fibrinogen levels were significantly higher in patients with diabetic foot compared to those without diabetic foot, and the optimal cut-off points for predicting the occurrence and severity of DF were 3.85 g/L and 4.12 g/L, which were similar to the results of previous studies, further corroborating that Fib may be involved in the occurrence and development of diabetic foot as an important factor. Meanwhile, this study further confirmed that Fib was positively correlated with diabetic foot grading (r = 0.616), and the higher the Fib level, the higher the Wagner grading of diabetic foot, suggesting the need for timely clinical control of Fib levels to reduce or delay the occurrence and progression of diabetic foot.
TEG is a coagulation test technology that provides comprehensive testing of coagulation, fibrinolytic composition, and platelet function [19]. TEG has been used in the 1980 s for clinical applications such as immediate coagulation monitoring in a variety of conditions, predicting the risk of venous thrombosis, and guiding clinical component transfusion [20]. The angle α and k value represent the clot formation rate and reflect the Fib functional status. A decreased k value with an increased angle α indicates a high Fib level (hypercoagulation), while an increased k value with a decreased angle α indicates a low fibrinogen level (hypocoagulation). Several studies [21, 22] have found that increased angle α and decreased k value can be important observational indicators for the development of micro-vascular and macro-vascular lesions. In this study, we found that the best cut points for diagnosing diabetic foot were 62.85 deg (angle α 53-72 deg) and 1.75 min (k value 1-3 min), and the definition of the best cut point suggested that when angle α is higher than 62.85 deg and k value below 1.75 min alerted to the occurrence of diabetic foot. The sensitivity of angle α and k value for diabetic foot diagnosis was 78.6% and 82.1%, which was higher than that of fibrinogen for diabetic foot diagnosis. It suggests that TEG may be more sensitive than Fib test for earlier diagnosis of diabetic foot and thus early intervention. The present study also found that angle α and k value correlated with Wagner grade and Fib in patients with diabetic foot. Higher Wagner grade and higher fibrinogen content were associated with larger angle α and lower k value. The optimal cut-off point for angle α and k value to indicate a poor prognosis for patient with DF was 70.20 deg and 1.25 min. When monitoring for abnormalities in the above indicators, the addition of drugs that reduce blood hypercoagulation may have a beneficial effect on preventing and delaying the onset and progression of diabetic foot.