Elevation of von Willebrand factor in plasma in diabetic patients with neuropathic foot ulceration

Aso, Yoshimasa; Fujiwara, Yukio; Tayama, K.; Iwamoto, Toshihiko; Takemura, Y

doi:10.1046/j.1464-5491.2002.00608.x

Cited by 12 publications

(5 citation statements)

References 34 publications

(36 reference statements)

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“…The concept of "vulnerable blood" has been proposed to refl ect the hypercoagulability associated with atherosclerosis and the predominant release of procoagulant factors occurring which characterizes this condition (Naghavi et al 2003). Increased circulating levels of vWF, PAI-1, t-PA, TFPI, and s-TM have been reported in patients with NIDDM (Collier et al 1992;McGill et al 1994;Bagg et al 2001;Aso et al 2002;Leurs et al 2002;Rigla et al 2006). In our study, plasma concentrations of all these markers of endothelial suffering were signifi cantly higher in patients with vascular complications than in control subjects.…”

Section: Discussionsupporting

confidence: 53%

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

Beer

Feihl²,

Ruiz³

et al. 2008

VHRM

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Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased cardiovascular risk due to an accelerated atherosclerotic process. The present study aimed to compare skin microvascular function, pulse wave velocity (PWV), and a variety of hemostatic markers of endothelium injury [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and the soluble form of thrombomodulin (s-TM)] in patients with NIDDM. Methods: 54 patients with NIDDM and 38 sex-and age-matched controls were studied. 27 diabetics had no overt micro-and/or macrovascular complications, while the remainder had either or both. The forearm skin blood fl ow was assessed by laser-Doppler imaging, which allowed the measurement of the response to iontophoretically applied acetylcholine (endotheliumdependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation), as well as the reactive hyperemia triggered by the transient occlusion of the circulation. Results: Both endothelial and non-endothelial reactivity were signifi cantly blunted in diabetics, regardless of the presence or the absence of vascular complications. Plasma vWF, TFPI and s-TM levels were signifi cantly increased compared with controls only in patients exhibiting vascular complications. Concentrations of t-PA and PAI-1 were signifi cantly increased in the two groups of diabetics versus controls. Conclusion: In NIDDM, both endothelium-dependent and-independent microvascular skin reactivity are impaired, whether or not underlying vascular complications exist. It also appears that microvascular endothelial dysfunction is not necessarily associated in NIDDM with increased circulating levels of hemostatic markers of endothelial damage known to refl ect a hypercoagulable state.

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Section: Discussionsupporting

confidence: 53%

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

Beer

Feihl²,

Ruiz³

et al. 2008

VHRM

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“…Laser Doppler studies have shown altered capillary circulation in the feet of patients with DPN ( 42 ). Increased plasma vWF has been associated with neuropathic foot ulceration ( 43 ). In addition to the vasculature, thalamic neurotransmitter mechanisms ( 44 ) and metabolic factors such as Vitamin D ( 45 ) may also play a role in painful-DPN.…”

Section: Discussionmentioning

confidence: 99%

Nerve and Vascular Biomarkers in Skin Biopsies Differentiate Painful From Painless Peripheral Neuropathy in Type 2 Diabetes

et al. 2021

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Painful diabetic peripheral neuropathy can be intractable with a major impact, yet the underlying pain mechanisms remain uncertain. A range of neuronal and vascular biomarkers was investigated in painful diabetic peripheral neuropathy (painful-DPN) and painless-DPN and used to differentiate painful-DPN from painless-DPN. Skin biopsies were collected from 61 patients with type 2 diabetes (T2D), and 19 healthy volunteers (HV). All subjects underwent detailed clinical and neurophysiological assessments. Based on the neuropathy composite score of the lower limbs [NIS(LL)] plus seven tests, the T2D subjects were subsequently divided into three groups: painful-DPN (n = 23), painless-DPN (n = 19), and No-DPN (n = 19). All subjects underwent punch skin biopsy, and immunohistochemistry used to quantify total intraepidermal nerve fibers (IENF) with protein gene product 9.5 (PGP9.5), regenerating nerve fibers with growth-associated protein 43 (GAP43), peptidergic nerve fibers with calcitonin gene-related peptide (CGRP), and blood vessels with von Willebrand Factor (vWF). The results showed that IENF density was severely decreased (p < 0.001) in both DPN groups, with no differences for PGP9.5, GAP43, CGRP, or GAP43/PGP9.5 ratios. There was a significant increase in blood vessel (vWF) density in painless-DPN and No-DPN groups compared to the HV group, but this was markedly greater in the painful-DPN group, and significantly higher than in the painless-DPN group (p < 0.0001). The ratio of sub-epidermal nerve fiber (SENF) density of CGRP:vWF showed a significant decrease in painful-DPN vs. painless-DPN (p = 0.014). In patients with T2D with advanced DPN, increased dermal vasculature and its ratio to nociceptors may differentiate painful-DPN from painless-DPN. We hypothesized that hypoxia-induced increase of blood vessels, which secrete algogenic substances including nerve growth factor (NGF), may expose their associated nociceptor fibers to a relative excess of algogens, thus leading to painful-DPN.

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“…Circulating levels of proinflammatory cytokines and adhesion molecules are elevated in patients with diabetes mellitus, linking endothelial dysfunction, atherogenesis and thrombogenesis to foot ulceration, and suggesting a role for systemic inflammation in diabetogenesis (23). Inflammatory activity can promote vascular injury by modifying lipoprotein structure and function, changing the composition of plasma proteins and causing alterations in the vascular endothelium (34,35). No clear correlation between the measured endothelial‐specific parameters and the extent of wound healing was found in this investigation.…”

Section: Discussionmentioning

confidence: 99%

Rheopheresis in Patients with Ischemic Diabetic Foot Syndrome: Results of an Open Label Prospective Pilot Trial

et al. 2003

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Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis, for extracorporeal hemorheotherapy. Safety and efficacy of Rheopheresis for wound healing and skin oxygenation were investigated in patients with ischemic diabetic foot syndrome. Eight patients with type 2 diabetes mellitus and non-healing foot ulcers caused by severe ischemic diabetic foot syndrome were treated by a series of seven Rheopheresis sessions in a time span of 11 weeks. Wound healing had not been detectable under conditions of standardized wound care during at least 2 months. Wound status was classified by its morphology, severity and location, according to the criteria of Wagner. Transcutaneous oxygen pressure (tcPO2), laser Doppler flowmetry and vital capillary microscopy were repeatedly performed to monitor the effects of the Rheopheresis treatment series on microcirculation and skin blood flow. Laboratory parameters of blood rheology, endothelial function and inflammatory state were measured in addition to safety parameters. In four patients (baseline Wagner stage 2), Rheopheresis accelerated wound healing of foot ulcers and was associated with an improvement of Wagner stage and a pronounced increase in tcPO2. In two patients (baseline Wagner stage 2), wound healing was unchanged but mean tcPO2 increased, allowing successful minor amputation. Values of tcPO2 remained stable and enhanced for the 3 months follow-up period. In two patients (baseline Wagner stage 4 or 5), no improvements in foot lesions were observed within the treatment period. As an adjunct therapeutic option, Rheopheresis may preserve a functional lower extremity, delay amputation or reduce the extent of amputation.

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Elevation of von Willebrand factor in plasma in diabetic patients with neuropathic foot ulceration

Abstract: Diabetic patients with neuropathic foot ulceration had severe impairment of cardiac autonomic and peripheral sympathetic nerves. Elevation of vWF in plasma was associated with neuropathic foot ulceration, linking endothelial dysfunction to foot ulceration.

Cited by 12 publications

References 34 publications

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

Nerve and Vascular Biomarkers in Skin Biopsies Differentiate Painful From Painless Peripheral Neuropathy in Type 2 Diabetes

Rheopheresis in Patients with Ischemic Diabetic Foot Syndrome: Results of an Open Label Prospective Pilot Trial

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