scholarly journals Plasma concentrations of platelet-specific proteins correlated with platelet survival

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 82-84 ◽  
Author(s):  
DJ Doyle ◽  
CN Chesterman ◽  
JF Cade ◽  
JR McGready ◽  
GC Rennie ◽  
...  
Keyword(s):  
Life Span ◽  
Plasma Concentrations ◽  
Specific Protein ◽  
Platelet Factor ◽  
In Vivo Release ◽  
Platelet Survival ◽  
Specific Proteins ◽  
Artery Disease ◽  
Multiple Hit

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.

scholarly journals Plasma concentrations of platelet-specific proteins correlated with platelet survival

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 82-84
Author(s):  
DJ Doyle ◽  
CN Chesterman ◽  
JF Cade ◽  
JR McGready ◽  
GC Rennie ◽  
...  
Keyword(s):  
Life Span ◽  
Plasma Concentrations ◽  
Specific Protein ◽  
Platelet Factor ◽  
In Vivo Release ◽  
Platelet Survival ◽  
Specific Proteins ◽  
Artery Disease ◽  
Multiple Hit

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.

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
Keyword(s):  
Coronary Artery Bypass Surgery ◽  
Artery Bypass ◽  
Plasma Concentrations ◽  
Platelet Factor ◽  
Normal Distributions ◽  
Platelet Survival ◽  
Specific Proteins ◽  
Highly Correlated ◽  
Multiple Hit

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.

scholarly journals In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)

Blood ◽  
1980 ◽  
Vol 56 (4) ◽  
pp. 596-607
Author(s):  
J Musial ◽  
S Niewiarowski ◽  
LH Jr Edmunds ◽  
VP Jr Addonizio ◽  
KC Nicolaou ◽  
...  
Keyword(s):  
Rhesus Monkey ◽  
Slow Component ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
In Vivo Release ◽  
Specific Proteins ◽  
Monkey Plasma

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.

Plasma Concentrations of Platelet-Specific Proteins in Different Stages of Essential Hypertension: Interactions between Platelet Aggregation, Blood Lipids and Age

1985 ◽  
Vol 54 (02) ◽  
pp. 539-543 ◽  
Author(s):  
J Yamanishi ◽  
H Sano ◽  
K Saito ◽  
Y Furuta ◽  
H Fukuzaki
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Blood Lipids ◽  
Plasma Concentrations ◽  
Strong Positive Correlation ◽  
Platelet Factor ◽  
Hypertensive Group ◽  
Group A ◽  
Specific Proteins

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.

scholarly journals In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)

Blood ◽  
1980 ◽  
Vol 56 (4) ◽  
pp. 596-607 ◽  
Author(s):  
J Musial ◽  
S Niewiarowski ◽  
LH Jr Edmunds ◽  
VP Jr Addonizio ◽  
KC Nicolaou ◽  
...  
Keyword(s):  
Rhesus Monkey ◽  
Slow Component ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
In Vivo Release ◽  
Specific Proteins ◽  
Monkey Plasma

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.

Clearance and In Vivo Release by Heparin of Human Platelet Factor 4 (PF4) in the Rabbit

1984 ◽  
Vol 52 (02) ◽  
pp. 157-159 ◽  
Author(s):  
M Prosdocimi ◽  
N Scattolo ◽  
A Zatta ◽  
F Fabris ◽  
F Stevanato ◽  
...  
Keyword(s):  
Half Life ◽  
Human Platelet ◽  
Slow Component ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
In Vivo Release ◽  
Partial Release ◽  
Different Doses ◽  
New Zealand Rabbits

Summary13 male New Zealand rabbits were injected with two different doses (25 μg/Kg and 100 μg/Kg) of human platelet factor 4 antigen (PF4). The disappearance of the protein was extremely fast with an half-life for the fast component of 1.07 ± 0.16 and 1.76 ± 0.11 min respectively. The half-life for the slow component, detectable only with the highest dosage, was 18.8 min.The administration of 2500 I.U. of heparin 30 min after PF4 administration induced a partial release of the injected protein and its clearance from plasma was slow, with half-life of 23.3 ± 5.9 min and 30.9 ± 2.19 min respectively.

Partially desulfated heparin modulates the interaction between anti-protamine/heparin antibodies and platelets

2016 ◽  
Vol 115 (02) ◽  
pp. 324-332 ◽  
Author(s):  
Rabie Jouni ◽  
Heike Zöllner ◽  
Ahmad Khadour ◽  
Jan Wesche ◽  
Anne Grotevendt ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Platelet Factor ◽  
Standard Drug ◽  
Platelet Surface ◽  
Minimal Impact ◽  
Platelet Survival ◽  
Heparin Complexes ◽  
The Impact

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.

scholarly journals Primary Structure of Human Platelet Factor 4.

1977 ◽  
Author(s):  
F.J. Morgan ◽  
G.S. Begg ◽  
C.N. Chesterman
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Structural Information ◽  
Human Platelet ◽  
Specific Protein ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Tryptic Peptides

The amino acid sequence of human platelet factor 4 (PF4) has been studied. PF4 is a platelet specific protein with antiheparin activity, released from platelets as a proteoglycan complex, whose measurement may provide an important index of platelet activation both in vivo and in vitro. These studies were undertaken to characterize fully the PF4 molecule. PF4 is a stable tetramer, composed of identical subunits, each with a molecular weight based on the sequence studies of approx. 7,770. Each PF4 subunit contains 69 amino acids, including 4 half-cystine (# 10, 12, 36, 37), one tyrosine (# 59), 3 arginine and 8 lysine, but no methionine, phenylalanine or tryptophan residues. The basic residues are predominantly in the C-terminal region. The tryptic peptides were aligned after studies which included tryptic digestion of citraconylated RCM-PF4, and automated Edman degradation of RCM-PF4 and citraconylated tryptic peptides. No glycopeptides were detected. This structural information should enable clear distinction to be made between PF4 and other platelet proteins such as β thromboglobulin. The provisional amino acid sequence of each subunit is:Glu-Ala-Glu-Glu-Asp-Gly-Asp-Leu-Gln-Cys-Leu-Cys-Val-Lys-Thr-Thr-Ser-Gln-Val-Arg-Pro-Arg-His-Ile-Thr-Ser-Leu-Glu-Val-Ile-Lys-Ala-Gly-Pro-His-Cys-Cys-Pro-Thr-Ala-Gln-Ile-Leu-Ala-Thr-Leu-Lys-Asn-Gly-Arg-Lys-Ile-Pro-Leu-Asp-Leu-Gln-Ala-Tyr-Leu-Lys-Ile-Lys(Lys, Lys, Ser, Glx, Leu, Leu)

Heparin Induced Release of Low Affinity Platelet Factor Four

1979 ◽  
Author(s):  
A.K. Rao ◽  
P. James ◽  
S. Niewiarowski
Keyword(s):  
Important Implication ◽  
Specific Protein ◽  
Final Concentration ◽  
Antigenic Determinants ◽  
Platelet Factor ◽  
Normal Individuals ◽  
The Mean ◽  
Minute Sample

Heparin has been reported to effect platelet function. We studied the effect of commercial beef lung heparin on the release of a platelet specific protein, the low affinity platelet factor 4(LA-PF4) in vitro and vivo. LA-PF4 shares Common antigenic determinants with B thromboglobulin, LA-PF4 was measured in platelet poor plasma (PPP) by radioimmunoassay. The mean levels of LA-PF4 in PPP from citrated blood and citrated blood with added heparin (final concentration 1.5 unit/ml) were 78.3±18.3 and 242.5±117.1 ng/ml respectively. (Mean ± SD, p <0.01). Addition of heparin to blood collected in a mixture of E EDTA, prostaglandin El, and theophylline did not result in an increase in LA-PF4 in PPP. A single intravenous bolus of heparin was administered to two normal individuals and the levels of LA-PF4 measured before and at 15,30 and 180 minutes later. An increase in the levels of LA-PF4 in the PPP from a baseline of 66.7 and 30.2 ng/ml/106 platelets to 166.7 and 167.4 ng/ml/106 platelets respectively were noted in 30 minute sample. There was no increase in LA-PF4 at 15 minutes. At 180 minutes levels were at baseline. It is concluded that heparin stimulates release of LA-PF4 from platelets both in vitro and in vivo. LA-PF4 has antiheparin action and is being investigated as a marker for thrombosis. Its release by heparin may, therefore, have an important implication.

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