Effects of biological variations on platelet count in healthy subjects in China

The effects of biological variations on platelet counts were investigated in 694 healthy subjects aged 18 to 60 years living in three cities including Chengdu (Sichuan Province), Suzhou (Jiangsu Province) and Harbin (Heilongjang Province) in China. Platelet counts in healthy subjects were significantly lower in Chengdu (52-202 x 10(9)/L) and Suzhou (60-259 x 10(9)/L) than in Harbin (154-348 x 10(9)/L) (p <0.0001), but the mean platelet volume (MPV) determined concurrently was negatively correlated with platelet count, the MPV values were significantly higher in Chengdu (11.8-15.6 fl) and Suzhou (10.9-15.8 fl) than in Harbin (9.5 approximately 12.9 fl) (p < 0.0001). Platelet counts were significantly higher in summer (73-289 x 10(9)/L) than in winter (52-202 x 10(9)/L) (p <0.0001), but the MPV values were lower in summer (11.2-14.7 fl) than in winter (11.8-15.6 fl) (p <0.05) in Chengdu. Platelet associated immunoglobulin (PA-IgG) in Chengdu was revealed to be significantly higher in the low platelet count group (<150 x 10(9)/L, 13.5 +/- 7.1 ng/10(7) PLT) than in the normal platelet count group (> or =150 x 10(9)/L, 8.3 +/- 2.7 ng/10(7) PLT) (p <0.0001). Similar results were observed in Suzhou for the reticulated platelet ratio, which was significantly higher in the low platelet count group (19.5 +/- 7.1%) than in the normal platelet count group (11.6 +/- 2.7%) (p <0.01). The bleeding time in Chengdu showed a significantly longer time in the low platelet count group (8.6 +/- 2.3 min) than in the normal platelet count group (6.0 +/- 1.2 min)(p <0.01). With regard to the effects of lipids on platelet counts, the HDL values were significantly higher in the normal platelet count group (1.60 +/- 0.76 mmol/L) than the low platelet count group (1.23 +/- 0.31 mmol/L) (p <0.01); but no significant differences in cholesterol and triglycerides values between the normal and low platelet count groups (p >0.05) were recorded. These findings suggest that the platelet counts could be greatly influenced in healthy subjects by biological variations such as geographical, seasonal, and lipid variations.     

Platelet reactivity in acute coronary syndromes: evidence for differences in platelet behaviour between unstable angina and myocardial infarction.

Previous work has shown that P-selectin and mean platelet volume, two markers associated with platelet reactivity, are elevated in acute coronary syndromes. This study investigated the possibility that these markers may define unstable angina (UA) and acute myocardial infarction (MI) as two separate conditions based on platelet behaviour. Mean platelet volume (MPV) was higher in UA patients (n = 15) than in those diagnosed with MI (n = 15) (10.7 +/- 0.25 fL, vs. 9.8 +/- 0.27 fL, P = 0.005). Platelet count was lower in UA than in MI (215 +/- 13 x 10(9)/L vs. 271 +/- 20 x 10(9)/L, P = 0.03). The percentage of platelets expressing P-selectin was higher in MI than in UA (9.1 +/- 1.9% vs. 4.2 +/- 0.85%, P = 0.03). This parameter was positively correlated with MPV in UA (r = 0.5, P = 0.04) but negatively correlated in MI (r = -0.6, P = 0.01), with no correlation for ACS as a whole (r = -0.32, P = 0.1). Our results suggest that in MI there is an acute process of generalised platelet activation that is unrelated to changes in MPV, whereas in UA there is an ongoing process of platelet consumption that leads to an increase in platelet size to compensate for a persistent decrease in platelet count. This study suggests that there is a fundamental difference in platelet biology between these two diseases.     

Platelet monoamine oxidase B and plasma beta-phenylethylamine in Parkinson's disease

OBJECTIVE: To evaluate the correlation between changes in platelet monoamine oxidase type B (MAO-B) activity and plasma beta-phenylethylamine (PEA) concentrations in patients with Parkinson's disease and controls. METHODS: Platelet MAO-B activity and plasma PEA were measured with gas chromatography-mass spectrometry (GC-MS) in patients with Parkinson's disease treated with levodopa (12 men and 12 women) or selegiline (three men and three women), and physically healthy subjects as a control group (10 men and 10 women). RESULTS: Platelet MAO-B activity was significantly higher in the Parkinson's disease group (mean 542 (SD 318) pmol/10(7) platelets/30 min) than in the control group (mean 349 (SD 307) pmol/10(7) platelets/30 min) (p<0.05). By contrast, the plasma PEA concentrations in patients with Parkinson's disease were significantly lower than in the control group (mean 532 (SD 243) pg/ml; 931 (SD 560) pg/ml) (p<0.01). The plasma PEA concentrations in patients with Parkinson's disease treated with selegiline were prominently higher than in patients with no selegiline treatment (p<0.001). There was a significantly negative correlation between platelet MAO-B activity and plasma PEA concentrations in patients (n=24, r=-0.466, p<0.001). CONCLUSIONS: The increase in platelet MAO-B activity and decrease in plasma PEA concentrations in patients with Parkinson's disease may be involved in the pathophysiological processes of the disease, and these changes are reversed by treatment with selegiline.     

Platelet P-selectin and platelet mass, volume and component in sickle cell disease: relationship to genotype

BACKGROUND AND PURPOSE: Excess platelet activation (e.g. increased soluble P selectin [sPsel] and beta thromboglobulin [beta-TG]) is well established in sickle cell disease (SCD) and may contribute to the prothrombotic/hypercoagulable state and vascular occlusion characteristic of the disease. We hypothesised altered whole platelet P-selectin (pPsel), and morphological platelet indices mass, volume and component in SCD and two of its major genotypes. METHODS: We recruited 35 SCD patients [mean age 31 years, 54% men]. Of these, 16 had homozygous sickle cell (HbSS) disease and 19 had sickle-haemoglobin-C (HbSC) disease. Patients were compared with 29 subjects with normal haemoglobin (HbAA) matched for age and ethnicity. Platelet mass, volume and component were measured by flow cytometry, pPsel in platelet lysate, sP-sel and beta-TG by ELISA. RESULTS: SCD patients had lower pP-sel and mean platelet volume (MPV) but elevated platelet component (MPC), and, as expected, elevated platelet count, and sP-sel (all p<0.05) compared to HbAA subjects. In both groups, pPsel correlated with MPV, and MPV correlated positively with mean platelet mass (MPM) and negatively with MPC. sPsel correlated with platelet count only in SCD, not in the controls. Platelet count alone was different (higher) in HbSS compared to HbSC, and sPsel correlated with platelet count only in HbSC disease, not in HbSS disease. CONCLUSION: Patients with SCD have various abnormalities in their platelets regardless of genotype: there are more numerous platelets, which are smaller, contain less P selectin per cell, but have a higher concentration of granules than those of HbAA subjects. These differences may mark and/or promote the prothrombotic state in SCD.     

Platelet volume, aggregation, and adenosine triphosphate release in cerebral thrombosis

We compared whole blood platelet aggregation, adenosine triphosphate release, platelet count, platelet crit (percentage volume of platelets), and mean platelet volume during the acute, subacute, and chronic periods of cerebral thrombosis in 22 patients with value in 29 controls. During the acute and subacute periods, platelet aggregation, platelet count, platelet crit, and mean platelet volume were significantly less in the patients than in the controls (p less than 0.05-0.01) while the adenosine triphosphate release rate per volume of platelets was significantly greater (p less than 0.05). During the acute period, infarct size showed a significant positive correlation with platelet aggregation (r = 0.59, p less than 0.01) and adenosine triphosphate release rate (r = 0.70, p less than 0.001) but a negative correlation with platelet count (r = -0.44, p less than 0.05). Our results suggest that platelet aggregation is reduced during the acute period due to the consumption of platelets during thrombogenesis but that the remaining individual platelets are hyperactive. Platelet consumption during the acute period increases with infarct size. During the chronic period, platelet crit and mean platelet volume were significantly less in the patients than in the controls (p less than 0.01) while the adenosine triphosphate release rate was significantly greater (p less than 0.01), suggesting sustained platelet consumption and chronically enhanced secretion of individual platelets.     

Acute and chronic changes in platelet volume and count after cardiopulmonary bypass induced thrombocytopenia in man

Patients undergoing surgery for coronary artery bypass graft or heart valve replacement had their platelet count and mean volume measured pre-operatively, immediately post-operatively and serially for up to 48 days after the surgical procedure. The mean pre-operative platelet count of 1.95 +/- 0.11 X 10(11)/1 (n = 26) fell significantly to 1.35 +/- 0.09 X 10(11)/1 immediately post-operatively (p less than 0.001) (n = 22), without a significant alteration in the mean platelet volume. The average platelet count rose to a maximum of 5.07 +/- 0.66 X 10(11)/1 between days 14 and 17 after surgery while the average mean platelet volume fell from preparative and post-operative values of 7.25 +/- 0.14 and 7.20 +/- 0.14 fl respectively to a minimum of 6.16 +/- 0.16 fl by day 20. Seven patients were followed for 32 days or longer after the operation. By this time they had achieved steady state thrombopoiesis and their average platelet count was 2.44 +/- 0.33 X 10(11)/1, significantly higher than the pre-operative value (p less than 0.05), while their average mean platelet volume was 6.63 +/- 0.21 fl, significantly lower than before surgery (p less than 0.001). The pre-operative values for the platelet volume and counts of these patients were significantly different from a control group of 32 young males, while the chronic post-operative values were not. These long term changes in platelet volume and count may reflect changes in the thrombopoietic control system secondary to the corrective surgery.     

Effects of endotoxemia on thrombopoiesis in men

BACKGROUND: Febrile conditions are often associated with increased platelet turnover and refractoriness to platelet transfusions, although several pyrogenic cytokines enhance thrombopoiesis. This study aimed to characterize the effects of experimental human endotoxemia on platelet turnover and thrombopoiesis. METHODS: Endotoxin (4 ng/kg) was infused into 30 healthy men to study the regulation of thrombopoiesis in systemic human inflammation. Platelet counts, plasma thrombopoietin (TPO) and glycocalicin levels, and reticulated platelets (RP) were measured to evaluate the effect of acute endotoxemia on thrombopoiesis. Ten subjects received pretreatment with 1000 mg aspirin po. to evaluate possible effects of aspirin on platelet turnover, and ten subjects received paracetamol to control for effects of antipyresis. RESULTS: Platelet counts dropped by about 15% (p <0.001) one hour after LPS infusion, began to recover at 24 h, and exceeded baseline values by 81% (CI: 5-12; p <0.001 ) at 7 days after LPS iv. Reticulated platelet counts increased from 1.62% (CI: 1.24-2.0) to a maximum of 2.39% (CI: 1.81-2.98; p = 0.003) at 6 h. TPO levels increased from baseline values of 10 A.U/ml (CI: 8.8-11.2) to 15.5 A.U/ml (CI: 13.6-17.3) at 24 h (p <0.001), whereas plasma glycocalicin was not changed (p >0.05). The number of circulating platelet-neutrophil aggregates increased more than 100% at 6 h (p <0.001). Neither aspirin nor paracetamol affected changes in any of the parameters measured. CONCLUSION: Low grade endotoxemia induces a rapid fall of platelet counts, which is followed by an early increase in reticulated platelets and TPO levels but not of glycocalicin levels. Finally peripheral platelet counts increase several days after LPS infusion.     

Platelet alpha granule depletion: findings in patients with prosthetic heart valves and following cardiopulmonary bypass surgery

The alpha granule content of platelets, as indicated by the amount of beta-thromboglobulin (beta-TG) in lysed platelet rich plasma was measured to determine whether platelet stimulation resulted in a circulating population of granule-depleted platelets. In 101 normal controls, with a mean platelet count of 242.6 +/- 6.5 X 10(9)/1, the mean platelet beta-TG content was 55.9 +/- 1.2 ng/10(6) platelets. There was a significant reduction in both these parameters (mean platelet count 195.5 +/- 5.8 X 10(9)/1 (P less than 0.001), mean platelet beta-TG 50.0 +/- 1.2 ng/10(6) platelets (P less than 0.01)) in 74 patients with prosthetic cardiac valves. In 24 patients, cardiopulmonary bypass surgery caused a much greater reduction in median platelet count from 210 X 10(9)/1 to 11.1 X 10(9)/1, two hours after surgery (P less than 0.001) but no overall change in platelet beta-TG. However, five patients who experienced diffuse haemorrhage in the postoperative period had a lower median platelet beta-TG (35.5 ng/10(6) platelets) than the other 19 patients (51.0 ng/10(6) platelets) (P less than 0.05).     

Thrombin generation in severe haemophilia A and B: the endogenous thrombin potential in platelet-rich plasma

Thrombin generation was investigated in platelet-rich plasma (PRP) from 11 healthy controls, 17 patients with severe haemophilia A and 7 patients with severe haemophilia B. Mean endogenous thrombin potential (ETP) in arbitrary fluorescence units (FU) was 226.9 +/- 44.6, 186.4 +/- 22.5, 154.2 +/- 41.3 in controls, haemophilia A and B, respectively, all at a platelet count of 200 x 10(9)/l (p = 0.004 for controls vs. haemophilia A, p = 0.003 for controls vs. haemophilia B, no significant difference between haemophilia A and B). The contribution of FVIII to thrombin generation in haemophilia A was 1.31 +/- 0.16 FU/% of FVIII:C activity, while for FIX in haemophilia B this was 0.80 +/- 0.21 FU/% of FIX activity. There was an almost linear relationship between increasing platelet count and thrombin generation up to a mean platelet count of 100 x 10(9)/l. Further increase in platelet count has only a marginal influence on thrombin generation. Platelets increase ETP in haemophilia A by 0.184 +/- 0.022 FU/10(9) platelets/l and in haemophilia B by 0.319 +/- 0.085 FU/10(9) platelets/l, and this was significantly different between the two groups (p = 0.0002). This influence of plate-lets diminishes with increasing concentration of either FVIII or FIX. In conclusion, there is a difference in thrombin generation between haemophilia A and B, and this may be attributed to the role of platelets in the assembly of the tenase complex on their surface.     

Mean platelet volume as marker of restenosis after percutaneous transluminal coronary angioplasty in patients with stable and unstable angina pectoris

INTRODUCTION: Several experimental and clinical studies have demonstrated that platelet size and function correlate since large platelets are hemostatically more reactive than platelets of normal size. Since platelets play a crucial role in vascular remodeling after percutaneous transluminal coronary angioplasty (PTCA), we investigated the influence of the mean platelet volume (MPV), a parameter of platelet size, on restenosis after PTCA. METHODS: The retrospective study comprised 174 patients who underwent elective PTCA and follow-up angiography within 6 months thereafter. According to the follow-up angiograms, the patients were assigned to group A ("restenosis", n=74) or group B ("no restenosis", n=100). Both groups were compared in regard to pre-procedural hematological routine parameters including MPV, platelet count, hematocrit, white blood cell count and fibrinogen. RESULTS: MPV was significantly increased in group A, compared with that in group B (8.75+/-0.99 fl vs. 8.04+/-0.74 fl, p<0.001). This difference in MPV was evident in patients with stable and unstable angina pectoris. In addition, MPV had an impact on the time-related incidence of angiographic restenosis, as early restenosis was associated with higher pre-procedural MPV values. Platelet count correlated inversely with MPV (r=-0.36, p<0.01) and was significantly lower in group A than in group B. The remaining hematological parameters were not different in both groups. CONCLUSIONS: The MPV seems to be a marker of coronary restenosis in patients undergoing PTCA. Patients with high pre-procedural MPV values might benefit from an intensified antiplatelet therapy after coronary interventions.     

Autologous platelet-labeling in thrombocytopenia

Field studies performed with peripheral platelets obtained from 6 male volunteers aged 23 to 29 years revealed an extraordinary dependence of labeling efficiency on incubation time and platelet concentration after 111In-oxine platelet labeling. Since the monitoring of in vivo-platelet function in patients with thrombocytopenia may cause problems due to insufficient labeling results and homologous platelets may show a different in vivo behaviour to autologous ones, we have searched for the minimal amount of platelets necessary to allow appropriate labeling and imaging in patients with thrombocytopenia. In 15 patients with untreated thrombocytopenia aged 14 to 79 years demonstrating a mean peripheral platelet count of 2.509 +/- 1.45 x 10(4) cells/microliters autologous 111In-oxine platelet labeling was performed. The results indicate that approximately 1 x 10(8) (concentrated) platelets/ml are necessary to obtain an adequate labeling efficiency and recovery. This platelet concentration can be easily achieved by drawing one more Monovette of whole blood per each 5 x 10(4) platelets/microliter peripheral platelet count less than 2 x 10(5)/microliter. It is concluded, that calculation of the required number of platelets in advance, variation of the blood volume drawn and the volume of incubation buffer allow informative, qualitative and quantitative results using autologous platelets. The method presented effectively circumvents the requirement of homologous platelets for radiolabeling in thrombocytopenia.     

Effects of chronic smoking on platelet function

Platelet function was investigated in 20 healthy cigarette smokers and 23 nonsmokers. Cigarette consumption was 1.4 +/- 0.5 packs/day (mean +/- SD) and the duration of smoking was 19 +/- 12 years. Platelet surface activation in vitro, aggregation in vivo and in vitro, as well as the release of platelet-specific proteins in vivo were evaluated. The mean number of platelet aggregates counted on an activating surface (Formvar film) was higher in smokers (80 +/- 59) than in nonsmokers (43 +/- 27) (P less than .01), indicating enhanced activity following exposure to an activating surface. Smokers who were 50 years of age or older showed an enhanced platelet aggregation following an in vitro stimulation in comparison to younger smokers (105 +/- 54 vs 54 +/- 55 aggregates) (P less than .05). Those who smoked 20 years or more also showed enhanced aggregation in comparison to those who smoked less than 20 years (112 +/- 60 vs 53 +/- 45 aggregates) (P = .02). Circulating platelets showed no significant difference among smokers and nonsmokers in the following tests: platelet aggregate ratio (0.67 +/- 0.30 vs 0.86 +/- 0.76), platelet count per mm3, (310,000 +/- 82,000 vs 278,000 +/- 78,000/mm3), levels of platelet factor 4 (9.8 +/- 5.2 vs 9.4 +/- 5.3 ng/ml), and plasma concentrations of beta-thromboglobulin (53.9 +/- 23.5 vs 49.1 +/- 25.5 ng/ml). The data suggest that chronic smoking primes platelets, causing them to aggregate more readily when exposed to an activating stimulus in vitro.     

Measurement of aspirin concentrations in portal and systemic blood in pigs: effect on platelet aggregation, thromboxane and prostacyclin production

Low doses of enteric-coated aspirin were administered orally to pigs. Plasma aspirin concentrations measured in blood obtained simultaneously from permanent catheters in a systemic artery and portal vein for 6 hours after dosage showed a large variation in the plasma aspirin concentration: time profile between pigs. After 50 mg single dose the ratio of the arterial: portal area under the plasma concentration versus time curve (AUC) was 0.63 +/- 0.08 (mean +/- SE, n = 6). In three pigs which received all three dosage regimens, the arterial: portal AUC ratios were 0.48 +/- 0.05 after 50 mg single dose, 0.52 +/- 0.02 after 100 mg single dose and 0.47 +/- 0.02 after 100 mg daily for 1 week. Platelet aggregation in response to sodium arachidonate (1.65 mM) was completely abolished after chronic aspirin administration of 100 mg daily. Thromboxane production (pg/10(6) platelets) induced by this stimulus decreased from 536 +/- 117 before aspirin to 57 +/- 14 after aspirin (mean +/- SE, n = 4; p = 0.03). Aortic prostacyclin synthesis, measured as 6-keto PGF1 alpha (ng/disc after 10 min incubation), was 1.66 +/- 0.28 (mean +/- SE, n = 4) in untreated pigs and 0.95 +/- 0.25 (n = 5) in treated pigs (p = 0.07). Results from this study support the idea that a difference between aspirin concentrations in the portal and systemic circulations can be achieved. Whether this can be translated into a clinically useful differential effect on the vessel wall compared to the platelet remains to be determined.     

Cigarette smoking increases thromboxane A2 formation without affecting platelet survival in young healthy females.

Smoking is a risk factor for the development of atherosclerotic cardiovascular disease, in men as well as in women. An increased urinary excretion of the thromboxane metabolite 2,3-dinorthromboxane B2 (Tx-M) has been observed in smokers of both genders, suggesting that cigarette smoking may facilitate cardiovascular disease via an action on the platelets. The present study addressed the hypothesis that the increased Tx-M excretion in female smokers reflects a true facilitation of platelet reactivity in vivo, rather than an increased destruction of the platelets. In healthy female volunteers (aged 20-46 years, 18 smokers and 17 non-smokers) platelet life-span and indices of platelet activity were determined, together with plasma levels of plasminogen activator inhibitor-1 (PAI-1), fibrinogen, peripheral blood cell counts and hematocrit. The urinary excretion of Tx-M was higher in smokers than in non-smokers (361 vs. 204 pg/mg creatinine, respectively, p < 0.05), while plasma and urinary beta-thromboglobulin, plasma platelet factor 4, platelet mean life-span and platelet production rate did not differ between the groups. PAI-1 activity, white blood cell count and hematocrit were higher in smokers than in non-smokers (p < 0.05). These data indicate that smoking facilitates platelet formation of thromboxane A2 without affecting platelet survival; i.e. it increases the activity of platelets without affecting their viability to a measurable extent. Such an increase in platelet activity, operating in parallel to a reduced fibrinolytic activity and a higher hematocrit and white blood cell count, may play an etiological role in smoking-induced cardiovascular disease in women.     

Platelet serotonin levels in pervasive developmental disorders and mental retardation: diagnostic group differences, within-group distribution, and behavioral correlates

OBJECTIVE: To investigate group differences, the within-group distributions, and the clinical correlates of platelet serotonin (5-HT) levels in pervasive developmental disorders (PDD). METHOD: Platelet 5-HT levels were measured in Dutch children and young adults, recruited from 2001 through 2003, with PDD (autism, Asperger's, and PDD-not otherwise specified [PDD-NOS]; n = 81) or with mental retardation (MR; n = 54) but without PDD, and in normal controls (n = 60). The distribution of platelet 5-HT levels was assessed using mixture-modeling analyses. Relationships between platelet 5-HT levels and a full range of demographic, clinical, and behavioral variables were examined. RESULTS: Group mean (+/- SD) platelet 5-HT levels (nmol/10 platelets) were significantly higher in the autistic (4.51 +/- 1.61, n = 33) and PDD-NOS (4.90 +/- 1.54, n = 43) groups compared to the MR (3.48 +/- 1.33, n = 54) or the normal control (3.58 +/- 1.08, n = 60) groups (F4,190 = 9.35, p <.001). Platelet 5-HT values in the combined PDD group showed a bimodal distribution, and an empirical cutpoint for hyperserotonemia was determined. None of the behavioral variables examined was significantly associated with platelet 5-HT levels. CONCLUSIONS: The platelet hyperserotonemia of autism was replicated in Dutch subjects. Platelet 5-HT levels were also increased in PDD-NOS, while no elevation was seen in MR. Platelet 5-HT levels appeared to be bimodally distributed in the PDD group, with an apparent hyperserotonemic subgroup.     

Physiological characteristics of platelet/circulatory serotonin: study on a large human population

The aim of this work was the study of platelet/circulatory serotonin (5-hydroxytryptamine, 5-HT), specifically alternative ways of its measurement and main physiological characteristics. The study was performed on a large human population (N=500) of blood donors of both sexes over the course of a longer time period (17 months). Owing to the heterogeneity in measurement of circulatory serotonin encountered in the literature, three ways of expression were comparatively studied: per unit number of platelets, per unit mass of platelet protein and per unit volume of whole blood. Results demonstrated unimodal distribution of individual frequencies of platelet/circulatory serotonin in the human population with the mean values of 579+/-169 ng 5-HT/10(9) platelets; 332+/-89.9 ng 5-HT/mg protein and 130+/-42.3 ng 5-HT/ml blood (mean+/-S.D.). A progressive decrease of serotonin level with age (18-65 years) was demonstrated, reaching statistical significance between the extreme age groups. No significant differences in the serotonin level between the sexes were observed. No seasonal oscillations in platelet/circulatory serotonin were found. Platelet serotonin demonstrated intra-individual stability over time. Finally, regarding the methodology of measurement, our results demonstrated a good correlation among the above-mentioned ways of expression of platelet/circulatory serotonin. This indicates the possibility of intercomparison of the literature reports expressing this physiological parameter either as 5-HT concentration in platelets or as 5-HT level in the circulation.     

Effect of altitude on thrombopoietin and the platelet count in healthy volunteers

Although there is evidence that altitude increases the platelet count, its effect on the platelet precursor stimulating factor, thrombopoietin (TPO), is unclear. Unlike erythropoietin, TPO appears largely unresponsive to exogenous signals. In a study in 16 healthy volunteers, we report the effects of altitude exposure at between 1000 and 1822 m for 1 or 2 weeks on TPO, the platelet count (+ indices), erythropoietin, hemoglobin, hematocrit and erythrocytes (+ indices). There were significant post-exposure increases in TPO (57.9 vs 37.1 U/l; P=0.0006), platelet count (219.1 vs 208.0 x 10(3)/ml; P=0.031) and erythropoietin (16.1 vs 9.9 U/l; P=0.0032). There was a positive correlation between the increases in TPO and platelet count (r=0.52, P=0.043). Hemoglobin and hematocrit remained unchanged. Our results provide clear evidence for a relationship, presumably driven by hypoxia, between altitude exposure, TPO production and the platelet count.     

Interactions of liposomes and platelets

Rats were injected intravenously with liposomes of various compositions and sizes and blood platelet count measured. It was found that negatively-charged liposomal systems produced a transient reduction in platelet count in the first 5 minutes after injection which recovered by 60 minutes post-injection. This effect was most striking for multilamellar vesicles (MLV's) containing phosphatidylglycerol (PG). Dose levels of 25 mg/kg of MLV's containing 10 mole% PG caused the platelet count to drop from a control value of 1,086 +/- 21 X 10(9)/l to 193 +/- 14 X 10(9)/l by 2 minutes post-injection, an 82% decline. This thrombocytopenic effect was observed to diminish as vesicle size or vesicle dose was decreased. Positively-charged liposomes produced a less pronounced transient reduction in platelet count while neutral liposomes caused only a mild, transient platelet decline. This transient thrombocytopenic effect was not blocked by common anticoagulants and fibrinolytic agents but was prevented by liposomal pretreatment. Radiolabeled platelet studies revealed that transient sequestration of platelets occurs in the liver and spleen 2 minutes after PG:EPC:CHOL MLV injection with a normalization of platelet distribution by 60 minutes post-injection. In vitro studies, using an automated blood counter, suggest a transient association of liposomes and platelets occurring following injection. Liposomally-induced transient thrombocytopenia suggests a role for platelets in the biodistribution of liposomes.     

Increased plasma noradrenaline during severe sodium restriction does not stimulate platelet release in essential hypertension

Seventeen 50-year old hypertensive men, previously untreated with blood pressure 157 +/- 4/110 +/- 2 mmHg (means +/- SE) were given a low sodium diet for 2 weeks. During the second week, the diet was supplemented with potassium. The urinary Na+/K+ excretion ratio changed from 2:1 to 1:4 and 1:11, respectively. Sympathetic noradrenergic tone increased considerably during the first week. Thus, venous plasma noradrenaline increased from 254 +/- 22 to 347 +/- 28 pg/ml (p less than 0.001) and arterial concentration from 253 +/- 36 to 317 +/- 42 pg/ml (n = 10, p less than 0.001). No significant change was observed in sympathetic adrenal tone as reflected by normal plasma adrenaline in venous (42 +/- 5 vs 43 +/- 6 pg/ml, ns) or arterial blood (71 +/- 10 vs 82 +/- 15 pg/ml, n = 10, ns) or in venous plasma concentration of the blood platelet release product beta-thromboglobulin (BTG) (50 +/- 8 vs 43 +/- 5 ng/ml, ns). During the second week sympathetic noradrenergic tone remained highly significantly elevated compared to baseline but still no change in plasma adrenaline or plasma BTG was found. Thus, whereas sodium depletion did increase plasma noradrenaline concentration markedly in these hypertensive men, no change in adrenaline concentration was observed, and blood platelet release reaction was unchanged. Plasma noradrenaline within the physiological concentration range does not seem to serve as a regulator of in vivo platelet function.     

Decreased platelet-free dopamine and unchanged noradrenaline and adrenaline in essential hypertension

The content of free-catecholamines in blood platelets is much higher than in plasma and platelet catecholamines must be taken up from plasma, since platelets lack the enzymes for catecholamine synthesis. There is some evidence that platelet catecholamine content under certain circumstances may be an integrated measure of plasma catecholamine concentrations over time. Platelet-free catecholamines were therefore assayed in 18 untreated patients with essential hypertension and in 16 normotensive control subjects. Mean platelet-free dopamine in the hypertensive group was 3.7 +/- 0.4 pg/mg platelet weight, i.e. significantly less than the 6.5 +/- 0.9 pg/mg found in the normotensive (p less than 0.005). Platelet contents of noradrenaline and adrenaline did not differ. Decreased platelet-free dopamine and unchanged platelet noradrenaline and adrenaline persisted after adjustment for increased body weight in the hypertensive group. Although the reasons for decreased platelet-free dopamine in the hypertensive group remain unknown, this finding may add to previous result showing facilitated release of granular contents from blood platelets in patients with essential hypertension. Our data do not support platelet levels of free-catecholamines to be a marker of increased sympathetic tone in essential hypertension.