Dp Mikhailidis

The effect of ethanol on platelet function and vascular prostanoids

The present review will discuss the effects of ethanol on platelet function and vascular prostanoids. Whenever possible we have considered human studies because there are marked species differences in platelet function and vascular prostanoid release even in the absence of ethanol. Because of the specialised nature of some parts of the text, we have included brief introductions to help readers who are not familiar with this field.

Plasma albumin and platelet function: relevance to atherogenesis and thrombosis.

Two papers published in this journal(1,2) during the past year remind us that plasma albumin concentrations can influence platelet function. These publications, together with epidemiological evidence showing that low plasma concentrations of albumin predict mortality from cardiovascular disease(3,4) have prompted this review.

Gamma-glutamyl Transferase Activity in Human Platelets: Quantification of Activity, Isoenzyme Characterization and Potential Clinical Relevance

Gamma-glutamyltransferase (GGT) activity in human platelet sonicates was 13.6 u/g of protein (range: 7.9-25.0) in 13 healthy, non-smoking, female volunteers; corresponding values in 16 males were: 20.3 (10.1-26.0). These values Mered significantly (p = 0.034). Platelet and serum GGT activity correlated significantly (p > 0.04). Platelets seem to contain only the isoenzyme GGT 4. Part of this enzyme activity is in the form of aggregates or linked with membranes/proteins. This activity is released by Triton X-100 and trypsin and migrates as GGT 4. Serum GGT activity, a measurement in routine use, could be influenced by GGT released by platelets. It is therefore of interest that serum GGT activity can be increased in clinical conditions (e.g. myocardial infarction, diabetes, peripheral vascular disease) associated with platelet hyperactivity. Platelet GGT may influence intracellular S-nitrosoglutathione (a putative nitric oxide donor) levels. Potential associations between serum GGT activity and platelet function indices deserve investigation.

N-formyl-methionine-leucine-phenylalanine (fMLP), a Bacterial Chemotactic Peptide, Stimulates Platelet Shape Change in Human Whole Blood

In order to investigate platelet-leucocyte interactions, the effect of N-formyl-methionine-leucine-phenylalonine (fMLP) a bacterial peptide, on platelet shape change (PSC) was studied. fMLP stimulated PSC in human platelets in a dose dependent manner in whole blood but did not cause PSC in platelet rich plasma. Furthermore, PSC induced by fMLP was inhibited by a PAF-antagonist indicating that PAF (a leucocyte release substance) is central to this effect. The present data suggests that PSC in whole blood constitutes a convenient method for the assessment of platelet-leucocyte interactions in health and disease.

Mean platelet volume in patients with type 2 diabetes mellitus

Papanas et al. evaluated the association between mean platelet volume (MPV) and diabetic complications [1]. The MPV was higher in type 2 diabetic patients than in non-diabetic patients [1]. Furthermore, among type 2 diabetics the MPV was higher in those with microvascular complications (retinopathy or microalbuminuria) [1]. This work is of considerable interest. Whole blood was collected in sodium citrate and the MPV values ranged from 7.1 to 15.8 fl [1]. In our experience using this anticoagulant we would expect MPV readings in platelet-rich plasma (PRP) that are much lower (e.g., 4.5–6.5 fl) [2–12]; others also reported similar values with citrate [13]. The MPV of diabetic patients is significantly larger than that of controls [14–16]. However, previously reported values were not as big as those described by Papanas et al. [1], except when EDTA was used [17–19]. Moreover, the difference in MPV between diabetic and non-diabetic groups was not as marked. Is there a reason for these differences? The MPV measurements were performed using two cell counters, Sysmex SF 3000 and Cell-Dyn 3700; the resolution of these machines was not mentioned [1]. Probably this is of the order of 0.28 fl like many routine haematology counters. We assess MPV using a Coulter ZM-34 counter coupled to a C-256 channelyzer (Coulter Electronics, Luton, Beds, UK). This equipment has the advantage of a high resolution (0.07 fl) [2–12]. However, our method [2–12] has the disadvantage that a centrifugation step is required for the preparation of citrated PRP. Hyperactive platelets could be lost or further activated during this step [20, 21]. In contrast, Papanas et al. [1] have the advantage of using whole blood. Clearly, whole blood MPV methods [1], are ideal for the prediction of vascular risk in contrast to our slower (research) technique [2–12] that requires the preparation of PRP. However, the resolution of whole blood techniques appears to be poor. In one study, the MPV in type 2 diabetic patients correlated with fasting plasma glucose and HbA11c levels [22]. Therefore, it is relevant to know the glucose levels in the Papanas et al. [1] study and whether any correlations were found. The search for a practical and cheap marker of platelet hyperactivity remains a priority.

The effect of tiaprofenic acid and indomethacin administration of human platelet function

The present study compares the effects of two non-steroidal anti-inflammatory drugs (NSAIDs) on platelet function. Tiaprofenic acid (300 mg twice daily) and indomethacin (25 mg thrice daily) were administered to healthy volunteers for 6 days. Platelet aggregation and thromboxane A2 (TXA2) release (assessed as TXB2, the stable, spontaneous breakdown product of TXA2) were assessed before the adminstration of NSAIDs; on day 6 (2–3 h after the last dose of NSAID); and on days 7 and 8 (24 h and 48 h after the last dose of NSAID). Both tiaprofenic acid and indomethacin significantly inhibited platelet aggregation and TXA2 release. The extent and duration of inhibition was similar for both drugs, and the inhibition tended to reverse within 24–48 h of cessation of medication. The time required for reversal of the inhbitiory effect of NSAIDs on platelets may be of relevance in patients who are bleeding (e.g. from gastric erosions caused by NSAIDs). Tiaprofenic acid in the present study and in previous work has not been shown to be a selective inhibitor of prostanoid synthesis, as was originally claimed.