Background Zinc is an important cofactor in many biological reactions. Zinc is proposed to be endocytosed from plasma into platelets, with pools within the cytoplasm and α-granules, which are subsequently released upon platelet activation. Several studies have shown a direct impact ofex vivomanipulation of zinc on platelet aggregation and other haemostatic parameters, including fibrinolysis. The bioavailability of zinc in the body entirely depends on dietary intake, despite this the impact of zinc deficiency on haemostatic parameters has not been studied. Aims To investigate how changes in the bioavailability of dietary zinc impacts on haemostatic function. Methods Healthy volunteers aged above 18 years were recruited and their zinc status on habitual diet recorded. Dietary zinc intake was then significantly restricted for 14 days (1 mg/day), followed by a repletion period for 14 days at various zinc concentrations (4.5-18 mg/day). Blood was collected from the habitual, depletion and repletion phases and platelet rich plasma (PRP) was isolated and haemostatic parameters assessed as detailed below. Results Maximal platelet aggregation induced by collagen was significantly decreased in the depletion phase (45.8 ± 23.2 %) compared to habitual diet phase (95.6 ± 11.2 %). Lagtime to thrombin generation during zinc restriction significantly increased (13.6 ±4 min) compared to habitual phase (18.1±3.2 min). Visualisation of real-time clot formation and lysis were observed using a Hemacore Thrombodynamics Analyzer. Rate of clot growth was significantly slower in depletion phase (33.5 ± 12.2 µm/min) compared to the rate in habitual phase (49.8 ± 11.1 µm/min). Clots formed from PRP during depletion phase showed defective clot retraction (final clot weight 486.2 ± 127.2 mg) compared to the habitual period (403.6 ± 77.8 mg). Fibrinolysis of PRP clots by tissue plasminogen activator (tPA) formed from the restricted phase in an absorbance based assay was delayed (100.6 ± 28.2 min) compared to the habitual phase (83.7 ± 24.5 min). Summary/Conclusions Around one-third of the world population currently living under zinc deficiency. Our data indicate that changes in dietary zinc impact its bioavailability and uptake by platelets. Restricted levels of zinc in platelets causes an attenuation in platelet aggregation, slower thrombin generation and clot formation, and delays fibrinolysis. Thus, highlighting how people living with zinc deficiency can experience defective haemostasis due to imbalance in these parameters.
Physiology 2019 (Aberdeen, UK) (2019) Proc Physiol Soc 43, C125
Oral Communications: Restricted Dietary Intake of Zinc Modulates Parameters of Haemostasis
U. Sumya1, J. Beattie2, N. Mutch1
1. School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom. 2. The Rowett Institute, Aberdeen, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.