Clopidogrel treatment may associate with worsening of endothelial function and development of new digital ulcers in patients with systemic sclerosis: results from an open label, proof of concept study

Ntelis, Konstantinos; Gkizas, Vasileios; Filippopoulou, Alexandra; Davlouros, Periklis; Alexopoulos, Dimitrios; Andonopoulos, Andrew P.; Daoussis, Dimitrios

doi:10.1186/s12891-016-1072-1

Cited by 13 publications

(3 citation statements)

References 35 publications

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“…However, one study reported that a standard dose of clopidogrel (75 mg) inhibits platelet activation in SSc patients but had no effect on plasma serotonin levels. Clopidogrel treatment even led to a significant increase in soluble VCAM-1, indicating endothelial dysfunction as adverse effect (226). Additionally, fibrosis has been successfully managed in an SSc murine model using the serotonin receptor inhibitors terguride, cyproheptadine, and SB 204741 (154, 227).…”

Section: Platelets Role In Skin Autoimmune Diseasesmentioning

confidence: 99%

Platelets in Skin Autoimmune Diseases

2019

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Systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and small vessel vasculitis are three autoimmune diseases frequently manifested in the skin. They share common pathogenic features, including production of autoantibodies, loss of tolerance to self-antigens, tissue necrosis and fibrosis, vasculopathy and activation of the coagulation system. Platelets occupy a central part within the coagulation cascade and are well-recognized for their hemostatic role. However, recent cumulative evidence implicates their additional and multifaceted immunoregulatory functions. Platelets express immune receptors and they store growth factors, cytokines, and chemokines in their granules enabling a significant contribution to inflammation. A plethora of activating triggers such as damage associated molecular patterns (DAMPs) released from damaged endothelial cells, immune complexes, or complement effector molecules can mediate platelet activation. Activated platelets further foster an inflammatory environment and the crosstalk with the endothelium and leukocytes by the release of immunoactive molecules and microparticles. Further insight into the pathogenic implications of platelet activation will pave the way for new therapeutic strategies targeting autoimmune diseases. In this review, we discuss the inflammatory functions of platelets and their mechanistic contribution to the pathophysiology of SSc, ANCA associated small vessel vasculitis and other autoimmune diseases affecting the skin.

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Section: Platelets Role In Skin Autoimmune Diseasesmentioning

confidence: 99%

Platelets in Skin Autoimmune Diseases

2019

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“…86 It was reported that clopidogrel treatment may be associated with the development of new digital ulcers in patients with SSc. 87 Riociguat and aminaphtone seem to be promising new treatment options for RP. 88,89 In a pilot study, a single dose of riociguat was well tolerated and resulted in a rapid improvement in digital blood flow in some patient subsets with primary and secondary RP.…”

Section: Monitoring Of Patients With Primary Raynaud Phenomenon For Tmentioning

confidence: 99%

Recent advances in the workup and management of Raynaud’s phenomenon

Lis‐Święty

2019

Polish Archives of Internal Medicine

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oxide synthase 1 gene as significantly correlated with RP in the general population. 4 Major risk factors for primary RP include, in addition to the female sex and family history, a previous sensation of cold hands, migraine, cardiovascular diseases, decreased body mass index, manual occupation (not including vibration tool use), and estrogen replacement therapy. 3-6 Cigarette smoking and alcohol consumption are still of unclear significance when concerning the prevalence of primary RP. 7 Secondary RP associated with a known disease, mainly with systemic sclerosis (SSc) (>80% of patients) or other connective tissue diseases (CTDs), is rare and accounts for 10% to 20% of all RP cases. 8 Other common causes of secondary RP include diseases of arteries in the upper limbs (60% of RP occurring in individuals older than 60 years), malignancies, endocrine diseases, occupational syndromes, hematologic disorders, and infections (TABLE 1). 8,9 In addition, several Introduction Raynaud phenomenon (RP) is defined as recurrent, reversible episodes of vasospasm involving peripheral small vessels of the fingers and toes, at times also of the other acral sites (nose, ears, oral mucosa, lips, or nipples), when exposed to a cold environment or stressful situation. 1 This is characterized by a series of color changes in the affected area: first white (lack of blood flow), then bluish (deoxygenation of remaining blood), and red (reperfusion). Attacks can cause distal pain, burning, numbness, and paresthesia. 2 Regarding its etiology, RP is classified as primary (idiopathic) or secondary. Primary RP, which is an isolated finding without an underlying pathology, is common, occurring in about 5% of the general population living in areas with cold climates. 3 The prevalence of RP is higher in women (female-to-male ratio of 9 to 1). There is an associated genetic predisposition: one polymorphic variant was identified within the nitric

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“…55 It was even hypothesized that clopidogrel treatment may be associated with the development of new DUs. 56 Moreover, the fact that many SSc patients have gastrointestinal involvement with a propensity to bleeding should be taken into account before administering antiplatelets, many of which can induce bleeding.…”

Section: Calcium-channel Blockersmentioning

confidence: 99%

<p>Management of digital ulcers in systemic sclerosis</p>

Barsotti¹,

Battista²,

Venturini³

et al. 2019

CWCMR

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Systemic sclerosis (SSc) is a rare disease characterized by autoimmune pathogenesis, alterations to the vascular system, and fibrosis of the skin and internal organs. Digital ulcers (DUs) are common in SSc patients, and represent a major burden for the patients. The management of DUs in systemic sclerosis is difficult, because it needs a multimodal therapeutic approach, as local treatment alone is usually insufficient and also systemic treatment with vasoactive drugs and modification of the lifestyle are usually required for healing of the wounds. In this review, we describe the optimal management of DUs according to recent literature and our clinical practice for systemic and local treatment of chronic digital wounds in SSc patients.

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Clopidogrel treatment may associate with worsening of endothelial function and development of new digital ulcers in patients with systemic sclerosis: results from an open label, proof of concept study

Cited by 13 publications

References 35 publications

Platelets in Skin Autoimmune Diseases

Platelets in Skin Autoimmune Diseases

Recent advances in the workup and management of Raynaud’s phenomenon

<p>Management of digital ulcers in systemic sclerosis</p>

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