Plasma Concentrations of Platelet Specific Proteins Correlated with Platelet Survival

1979 ◽  
Author(s):  
D.J. Doyle ◽  
C.N. Chesterman ◽  
J.F. Cade ◽  
F.J. Morgan

Relationships between platelet survival (51Cr) and plasma concentrations (radioimmunoassay) of β-thromboglobulin (βTC) and platelet factor 4 (PF4) were analysed in 91 studies of patients prior to and after coronary artery bypass surgery. Platelet lifespans were calculated using the linear, exponential, weighted mean (WM) and multiple hit (MH) models. The values obtained approximated normal distributions and all the indices correlated, r values ranging from 0.69 to 6 (p<0,001 in all cases).βTC had significant negative correlations with all indices of platelet survival, the most significant being with MH (r = -0.39, p<0.001). Of interest was the correlation of βTG with the number of hits (n) in MH (r = -0.29, p<0.01). PF4 correlated with all indices of platelet survival except n, the most significant correlation was with WM (r = 0.33, p<0.01). BTC and PF4 were highly correlated (r = 0.62, p<0.001), however no benefit was obtained by combining measurements of the two proteins in any regression with platelet lifespan.The results suggest that shortened platelet survival in vascular disease is associated with platelet release of BTG and PF4 and that these platelet specific proteins are comparable as markers of platelet activation in vivo.

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 82-84 ◽  
Author(s):  
DJ Doyle ◽  
CN Chesterman ◽  
JF Cade ◽  
JR McGready ◽  
GC Rennie ◽  
...  

Abstract Relationships between 51Cr platelet survival and plasma concentrations of beta-thromboglobulin (betaTG) and platelet factor 4 (PF4) were analyzed in 91 studies of patients with coronary artery disease. betaTG was significantly correlated with platelet life-span, turnover, and the number of hits in the multiple hit model. PF4 was significantly correlated with life-span and turnover. The most significant relationship involving platelet-specific protein concentrations and life-span estimates was between betaTG and life-span estimated using the multiple hit model (r = -0.39, p less than 0.001). There was a high correlation between betaTG and PF4 (r = 0.62, p less than 0.001), and no improvement could be obtained by combining the measurements of the two proteins in any regression with life-span or turnover. The results indicate that the patients with the shortest platelet survival time in this group tended to have the highest plasma concentration of betaTG and PF4 and thus probably increased in vivo release of betaTG and PF4. They strengthen the claim that these platelet-specific proteins may be indicators of platelet involvement in disease.


Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 82-84
Author(s):  
DJ Doyle ◽  
CN Chesterman ◽  
JF Cade ◽  
JR McGready ◽  
GC Rennie ◽  
...  

Relationships between 51Cr platelet survival and plasma concentrations of beta-thromboglobulin (betaTG) and platelet factor 4 (PF4) were analyzed in 91 studies of patients with coronary artery disease. betaTG was significantly correlated with platelet life-span, turnover, and the number of hits in the multiple hit model. PF4 was significantly correlated with life-span and turnover. The most significant relationship involving platelet-specific protein concentrations and life-span estimates was between betaTG and life-span estimated using the multiple hit model (r = -0.39, p less than 0.001). There was a high correlation between betaTG and PF4 (r = 0.62, p less than 0.001), and no improvement could be obtained by combining the measurements of the two proteins in any regression with life-span or turnover. The results indicate that the patients with the shortest platelet survival time in this group tended to have the highest plasma concentration of betaTG and PF4 and thus probably increased in vivo release of betaTG and PF4. They strengthen the claim that these platelet-specific proteins may be indicators of platelet involvement in disease.


1985 ◽  
Vol 54 (02) ◽  
pp. 539-543 ◽  
Author(s):  
J Yamanishi ◽  
H Sano ◽  
K Saito ◽  
Y Furuta ◽  
H Fukuzaki

SummaryPlasma β-thromboglobulin (βTG) and platelet factor 4 (PF4) were significantly higher in a group of 116 hypertensive men than in a normotensive group of 142 men. They increased with the stage of hypertension but the level did not correlate with the age of the subjects. Platelet aggregation was similar in the two groups and positively correlated with the age of the subjects in the normotensive group but not in the hypertensive group. A strong positive correlation was observed between the levels of plasma βTG and PF4 and between platelet aggregation to ADP and that to epinephrine in both the hypertensive and normotensive groups. However, there was no correlation between the level of plasma βTG or PF4 and platelet aggregation. Plasma antithrombin III was lower in the hypertensive group than in the normotensive group.These studies suggest that plasma levels of PTG and PF4 are closely related to the stage of hypertension and are better indicators than aggregation of in vivo platelet activation in hypertensive subjects. Enhanced platelet activation may be involved in the acceleration of hypertensive arteriovascular damage and atherosclerosis.


2016 ◽  
Vol 115 (02) ◽  
pp. 324-332 ◽  
Author(s):  
Rabie Jouni ◽  
Heike Zöllner ◽  
Ahmad Khadour ◽  
Jan Wesche ◽  
Anne Grotevendt ◽  
...  

SummaryProtamine (PRT) is the standard drug to neutralise heparin. PRT/heparin complexes induce an immune response similar to that observed in heparin-induced thrombocytopenia (HIT). Partially desulfated heparin (ODSH) was shown to interfere with anti-platelet factor 4/heparin antibodies (Abs), which are responsible for HIT. In this study, we analyse the impact of ODSH on the interaction between anti-PRT/heparin Abs and platelets. The ability of ODSH to prevent anti-PRT/heparin Ab-induced platelet destruction in vivo was investigated using the NOD/ SCID mouse model. ODSH improved platelet survival in the presence of PRT, heparin and anti-PRT/heparin Abs (median platelet survival after 300 minutes (min) with 20 μg/ml ODSH: 75 %, range 70–81 % vs without ODSH: 49%, range 44–59%, p=0.006). Furthermore, when ODSH was applied 60 min after Ab injection platelet survival was improved (median platelet survival after 300 min with ODSH: 83 %, range 77–93 % vs without ODSH: 59 %, range 29–61 %, p=0.02). In in vitro experiments ODSH inhibited platelet activation at concentrations > 16 μg/mL (p< 0.001), as well as PRT/heparin complex binding to platelets (mean fluorescence intensity [MFI] without ODSH: 85 ± 14 vs with ODSH: 15 ± 0.6, p=0.013). ODSH also displaced pre-bound complexes from the platelet surface (MFI without ODSH: 324 ± 43 vs with 32 μg/ml ODSH: 53 ± 9, p< 0.001). While interfering with platelet activation by anti-PRT/heparin Abs, up to a concentration of 16 μg/ml, ODSH had only minimal impact on neutralisation of heparin by PRT. In conclusion, our study shows that ODSH is able to inhibit platelet activation and destruction suggesting a potential clinical use to reduce anti-PRT/heparin Ab-mediated adverse effects.


Blood ◽  
1980 ◽  
Vol 56 (4) ◽  
pp. 596-607
Author(s):  
J Musial ◽  
S Niewiarowski ◽  
LH Jr Edmunds ◽  
VP Jr Addonizio ◽  
KC Nicolaou ◽  
...  

Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p < 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.


1985 ◽  
Vol 53 (02) ◽  
pp. 260-263 ◽  
Author(s):  
A Boneu ◽  
P Sié ◽  
R Bugat ◽  
C Caranobe ◽  
M Eber ◽  
...  

SummaryA simultaneous investigation of platelet regeneration time (PRT) based upon malondialdehyde (MDA) recovery after a single oral intake of 500 mg of aspirin and of platelet survival time (PST) after labelling with 51chromium or 111Inindium oxine was performed in 25 cancerous patients. A pilot study conducted with 9 healthy volunteers demonstrated that the MDA assay was highly reproducible and specific for the platelet cycloxygenase activity. The pattern of MDA recovery after aspirin ingestion was linear in the healthy volunteers and in the patients presenting both a normal and an accelerated platelet turnover. PST were calculated using the four mathematical models recommended by the International Committee for Standardization in Hematology; the best fit was given by the multiple hit model in 22 cases and by the linear regression model in 3 cases. The mean results obtained in the patients investigated with the 51chromium were consistently shorter than those obtained in the patients investigated with the mindium oxine while the mean PRT were almost identical in the two groups. An excellent correlation between PRT and PST was observed after 111Indium oxine labelling and using the weighted mean method for PST determination. These results suggest that the 111Indium oxine technique is a better method for platelet labelling and that the results provided by the weighted mean method reflect more closely the in vivo platelet turnover than those provided by the multiple hit model.


Perfusion ◽  
2008 ◽  
Vol 23 (3) ◽  
pp. 165-171 ◽  
Author(s):  
K Svennevig ◽  
TN Hoel ◽  
AS Thiara ◽  
SO Kolset ◽  
A Castelheim ◽  
...  

The glycocalyx covering the endothelium is shed during ischemia and reperfusion. The shedding is accompanied by increased levels of the glycocalyx component syndecan-1 in the circulation. Our aim was to compare plasma levels of syndecan-1 in patients undergoing coronary artery bypass grafting (CABG), with or without the use of cardiopulmonary bypass (CPB). Syndecan-1 plasma concentrations were measured in patients undergoing CABG on-pump (n = 22) or off-pump (n = 22). The syndecan-1 concentration increased significantly from 29.5 ± 4.6 ng/mL at baseline to 98.7 ± 9.8 ng/mL (p < 0.01) after the start of CPB or 30 minutes after the induction of anesthesia in the off-pump group. There were no significant differences in peak syndecan-1 plasma concentrations between on-pump and off-pump patients. Plasma levels of syndecan-1 increased significantly during CABG, with or without the use of CPB. There were no significant differences in syndecan-1 concentrations in the two groups.


1981 ◽  
Vol 46 (04) ◽  
pp. 743-746 ◽  
Author(s):  
C A Ludlam ◽  
N Allan ◽  
R B blandford ◽  
R Dowdle ◽  
N J Bentley ◽  
...  

SummaryEight patients on warfarin with rheumatic heart disease and prosthetic cardiac valves were selected for study on the basis of persistently elevated plasma β-thromboglobulin (β-tg) and platelet factor 4 (PF4) concentrations. Platelet mean lifespan and fibrinogen half life were short, and positively correlated, and both were inversely related to the Plasma concentrations of the platelet specific proteins. Antithrombin III (ATIII) levels were also reduced. Treatment with sulphinpyrazone resulted in lengthening of both platelet and fibrinogen survival, a rise in ATIII but no change in the βtg or PF4 concentrations. It is concluded that patients with abnormal cardiac valves and raised plasma levels of βtg or PF4 have, despite warfarin, a consumption coagulopathy that can be inhibited by sulphinpyrazone.


1987 ◽  
Vol 58 (02) ◽  
pp. 718-723 ◽  
Author(s):  
E Minar ◽  
H Ehringer ◽  
R Ahmadi ◽  
R Dudczak ◽  
G Porenta

SummaryIn this study we have assessed the deposition of 111-In-oxine-labelled platelets - using a dual radiotracer method - at angioplasty sites of the lower extremities in 20 patients (14 male, 6 female; median age: 60 years) with ASA (1.0 g/day)-therapy. The platelet survival time (PST) - using the multiple hit model -was evaluated before and after percutaneous transluminal angio-plasry, and we also measured the plasma levels of β-thrombo-globulin (β TG) and platelet fuetui 4 (PF 4) before and after PTA.Before PTA, scintigraphy was positive in only one patient, while 24 hours after PTA a positive scintigraphic result was observed in 16/20 patients. The median target/non target-ratio was 1.0 (0.66-1.3) before PTA, and this ratio increased significantly (p <0.0005) to 1.53 (1.0-3.3) after PTA.The median PST decreased significantly (185.0 hours before PTA → 145.2 hours after PTA; p <0.001), while the median platelet turnover increased from 34,000/μl/day to 47,900/μl/day(p<0.01).The median plasma levels of the platelet specific proteins increased significantly immediately after PTA (p <0.001), but one day later they were not significantly different from the pretreatment values.The quantitative methods used in this study seem a valuable tool to evaluate the effects of different therapeutical - especially antiplatelet - interventions after PTA in humans, thus helping to find the best antithrombotic regimen for this widely used therapeutical procedure.


Blood ◽  
1980 ◽  
Vol 56 (4) ◽  
pp. 596-607 ◽  
Author(s):  
J Musial ◽  
S Niewiarowski ◽  
LH Jr Edmunds ◽  
VP Jr Addonizio ◽  
KC Nicolaou ◽  
...  

Abstract Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p &lt; 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.


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