Unfavourably altered plasma clot properties in patients with primary Raynaud\u2019s phenomenon: association with venous thromboembolism

Joanna Żuk,Elżbieta Papuga-Szela,Joanna Natorska,Krzysztof Piotr Malinowski,Agnieszka Snarska-Drygalska,Anetta Undas

doi:10.1007/s11239-019-01805-0

Abstract

Associations of Raynaud’s phenomenon (RP) with venous thromboembolism (VTE) are unclear. We investigated the occurrence of RP together with prothrombotic state markers and fibrin clot properties in VTE patients. In this prospective cohort study we enrolled 360 patients free of known autoimmune disease. D-dimer, von Willebrand factor (vWF), plasma clot permeability (Ks), clot lysis time (CLT) along with fibrinolysis activators and inhibitors were determined at least 3 months since the VTE event. The presence/absence of RP was diagnosed at least 6 months before VTE. Primary RP occurred in 57 subjects (17%) with a 3.6-fold higher prevalence among women. Patients with RP had 11% higher fibrinogen, 16% higher vWF, 5% lower Ks, and 10% longer CLT (all p < 0.05). Females with RP (21%) had 6.6% lower Ks, 11.2% longer CLT, and 18.5% higher vWF (all p < 0.05) compared with men. CLT was predicted by PAI-1 and vWF levels. Regression analysis showed that RP was a predictor of prolonged CLT in the whole patient group (OR 3.46, 95% CI 1.92–6.24) and in women following VTE (OR 2.75, 95% CI 1.31–5.78). Primary RP patients tend to form denser plasma fibrin clots displaying impaired lysability and increased endothelial damage. RP might be a novel risk factor for VTE, especially in women.

Highlights

Raynaud’s phenomenon (RP) is a vasospastic disorder usually involving peripheral small vessels of the fingers or toes in response to cold and/or emotional stress
Citrated plasma was mixed with 15 mmol/L calcium chloride, 10,000-diluted human tissue factor (Innovin, Siemens) with a final concentration of 0.6 pM, 12 μmol/L phospholipid vesicles and 60 ng/mL recombinant tissue plasminogen activator (Boehringer Ingelheim, Ingelheim, Germany)
When subjects with positive Antinuclear antibodies (ANA) were excluded, we found that in the ANA negative patients (n = 219), RP was associated with 29% higher plasma fibrinogen, 19% higher von Willebrand factor (vWF) and 15% higher platelet count

Summary

Introduction

Raynaud’s phenomenon (RP) is a vasospastic disorder usually involving peripheral small vessels of the fingers or toes in response to cold and/or emotional stress. This disorder is characterized by an episodic pallor, followed by cyanosis because of slow blood flow, and rubor reflects the Unfavourably altered plasma clot properties in patients with primary Raynaud’s phenomenon:. RP is categorized as primary (80% of patients) or secondary. RP is observed in the thoracic outlet syndrome, small- and medium-sized vessel vasculitis, polycythaemia, cryofibrynogenaemia, cold agglutinin disease, paraproteinaemia, vibration injury, and it can be provoked by drugs and toxins [1,2,3,4]

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