Peripheral arterial disease (PAD) is a common but under-recognized problem affecting older patients. Intermittent claudication is the most frequent symptom of PAD, although the diagnosis of PAD is often overlooked until the patient presents with limb-threatening ischemia. Importantly, PAD is a marker for generalized atherosclerosis and is closely associated with coronary and cerebrovascular disease. The severity of PAD has been correlated with an increased risk of myocardial infarction, stroke, and cardiovascular death. The recognition and diagnosis of PAD, combined with its appropriate medical management, may well reduce the overall risk of cardiovascular morbidity. When diagnosed early, both exercise and pharmacotherapy can ameliorate symptoms of claudication, augment functional performance, and improve quality of life.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1520-037X.2002.00558.x

Peripheral Arterial Disease: Medical Care and Prevention of Complications

A rational approach to diagnosis and treatment of intermittent claudication.

The aim of this thesis was to assess several aspects of platelet function, especially in
response to drugs.
Peripheral arterial disease (PAD) is associated with hyperactive platelets that may be
resistant to aspirin. Therefore, the effect of the administration of clopidogrel, aspirin or both
anti-platelet agents was investigated in patients with PAD. Platelet function was assessed by
different techniques including platelet shape change (PSC), an early phase of platelet
activation that precedes aggregation. PSC was measured using a high-resolution channelyzer
and expressed as median platelet volume (MPV). There was an increased inhibitory effect of
clopidogrel plus aspirin on platelet activation. Clopidogrel was a more potent inhibitor of
ADP-induced platelet activation than aspirin.
The ADP receptors, P2Y1, P2Y12 and P2X1 influence platelet activation. The P2Y1
receptor antagonist MRS 2179 blocked ADP-and ADP plus serotonin-induced PSC in vitro.
The P2Y12 receptor antagonist AR-C69931MX significantly inhibited ADP-induced PSC.
We demonstrated for the first time that the IC50 of a P2Y1 receptor-blocker can be derived
using PSC.
Tirofiban is a glycoprotein IIb/IIIa receptor antagonist and therefore a powerful
inhibitor of platelet aggregation. Tirofiban did not affect fibrinogen/agonist-induced PSC but
inhibited platelet aggregation in vitro. A lack of inhibition of PSC may limit the use of
tirofiban in clinical practice.
Current methods to measure platelet cholesterol (PC) involve complex extraction
processes. A faster and simpler technique to measure PC was developed. There was a
significant correlation between PC and some circulating lipid levels. This method may be
useful for multiple sampling. PC may represent ‘tissue’ cholesterol levels. Furthermore,
because high PC is associated with increased platelet activity, statins may decrease both PC
and risk of thrombosis.
The findings in this thesis may provide a better understanding of platelet function
and how to assess it. Furthermore, potential therapeutic targets are discussed.

Effect of antithrombotic drugs on platelet function and receptors and an investigation into platelet cholesterol

Treating intermittent claudication secondary to peripheral arterial disease

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Treating intermittent claudication secondary to peripheral arterial disease