Some Effects of Fibrinogen Degradation Products (FDP) on Blood Platelets

1966 ◽  
Vol 15 (03/04) ◽  
pp. 413-419 ◽  
Author(s):  
Z Jerushalmy ◽  
M. B Zucker
Keyword(s):  
Platelet Aggregation ◽  
Connective Tissue ◽  
Degradation Products ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Serotonin Release ◽  
Fibrinogen Degradation Products ◽  
Inhibition Of Platelet Aggregation

Summary“Early” fibrinogen degradation products are more potent inhibitors of thrombin-induced clotting than “late” products and also interfere with the ability of thrombin to release serotonin from platelets. “Early” and “intermediate” FDP cause moderate inhibition of platelet aggregation induced by adenosine diphosphate or connective tissue particles. Serotonin release by connective tissue particles is probably not inhibited by FDP.

Inhibition of Platelet Aggregation by Dialysable Fibrinogen Degradation Products (FDP)

1970 ◽  
Vol 23 (01) ◽  
pp. 091-098 ◽  
Author(s):  
Jolanta Stachurska ◽  
Z Latałło ◽  
Maria Kopeć
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Platelet Aggregation ◽  
Active Component ◽  
Degradation Products ◽  
Aromatic Amino Acids ◽  
Inhibit Platelet Aggregation ◽  
Molecular Fragments ◽  
Fibrinogen Degradation Products ◽  
Inhibition Of Platelet Aggregation

SummaryDuring prolonged proteolysis of fibrinogen by plasmin dialysable, low molecular fragments accumulate which inhibit platelet aggregation induced by thrombin, ADP, adrenaline and noradrenaline. These fragments isolated by dialysis were separated on sephadex G-25 column. The active component has probably a molecular weight lower than 5,000 and does not contain aromatic amino acids.

The Inhibition of Platelet Aggregation by an Aorta Intima Extract

1974 ◽  
Vol 32 (02/03) ◽  
pp. 417-431 ◽  
Author(s):  
A. du P Heyns ◽  
D. J van den Berg ◽  
G. M Potgieter ◽  
F. P Retief
Keyword(s):  
Platelet Aggregation ◽  
Degradation Products ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Vascular Trauma ◽  
Wear And Tear ◽  
Sequential Addition ◽  
Aggregation Activity

SummaryThe platelet aggregating activity of extracts of different layers of the arterial wall was compared to that of Achilles tendon. Arterial media and tendon extracts, adjusted to equivalent protein content as an index of concentration, aggregated platelets to the same extent but an arterial intima extract did not aggregate platelets. Platelet aggregation induced by collagen could be inhibited by mixing with intima extract, but only to a maximum of about 80%. Pre-mixing adenosine diphosphate (ADP) with intima extracts diminished the platelet aggregation activity of the ADP. Depending on the relationship between ADP and intima extract concentrations aggregating activity could either be completely inhibited or inhibition abolished. Incubation of ADP with intima extract and subsequent separation of degradation products by paper chromatography, demonstrated a time-dependent breakdown of ADP with AMP, adenosine, inosine and hypoxanthine as metabolic products; ADP removal was complete. Collagen, thrombin and adrenaline aggregate platelets mainly by endogenous ADP of the release reaction. Results of experiments comparing inhibition of aggregation caused by premixing aggregating agent with intima extract, before exposure to platelets, and the sequential addition of first the intima extract and then aggregating agent to platelets, suggest that the inhibitory effect of intima extract results from ADP breakdown. It is suggested that this ADP degradation by intima extract may play a protective role in vivo by limiting the size of platelet aggregates forming at the site of minimal “wear and tear” vascular trauma.

The Effect of Mitomycin C on Platelet Aggregation and Adenosine 3′, 5′-Monophosphate Metabolism

1978 ◽  
Vol 39 (01) ◽  
pp. 177-185 ◽  
Author(s):  
Shuichi Hashimoto ◽  
Sachiko Shibata ◽  
Bonro Kobayashi
Keyword(s):  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Mitomycin C ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Cellular Membrane ◽  
Adenyl Cyclase ◽  
Cyclic Amp Phosphodiesterase ◽  
Membrane Structure And Function ◽  
And Function

SummaryThe effect of Mitomycin C on aggregation, adenosine 3′, 5′-monophosphate (cyclic AMP) metabolism and reactions induced by thrombin was studied in rabbit platelets. Mitomycin C inhibited the platelet aggregation induced by adenosine diphosphate or thrombin. The level of radioactive cyclic AMP derived from 8-14C adenine or 8-14C adenosine increased after incubating intact platelets with Mitomycin G. Formation of radioactive adenosine triphosphate also increased though mitochondrial oxidation was not stimulated. Similar effect was observed also in rabbit liver. Mitomycin C failed to stimulate platelet adenyl cyclase but inhibited cyclic AMP phosphodiesterase in the absence of theophylline. In the platelets preincubated with Mitomycin C, thrombin-induced inhibition of adenyl cyclase, stimulation of membrane-bound cyclic AMP phosphodiesterase, and release of 250,000 dalton protein from platelet membranes were prevented. These results suggest that Mitomycin C will affect cellular membrane structure and function, and this extranuclear effect of Mitomycin C will lead to inhibition of aggregation in blood platelets.

Interactions Between Blood Platelets and Vascular Endothelium in vitro Studies

1979 ◽  
Author(s):  
M.A. Gimbrone ◽  
K.D. Curwen ◽  
R. I. Handin
Keyword(s):  
Platelet Aggregation ◽  
Vascular Endothelium ◽  
Potent Inhibitor ◽  
Platelet Reactivity ◽  
Blood Platelets ◽  
Primary Cultures ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Platelet Adherence

Endothelial cells (EC) can actively influence the hemostatic response at sites of vascular injury through multiple mechanisms. For example, EC can degrade adenosine diphosphate, release plasminogen activator, and synthesize prostacyclin (PGI2), a potent inhibitor of platelet aggregation. We have examined whether PGI2 also might account for the normal lack of platelet adherence to the uninjured EC surface. In a monolayer adherence assay, radiolabeled human platelets in citrated plasma showed minimal interaction with primary cultures of human EC (<1 platelet adhering per cell). Platelets from aspirin-treated and untreated donors behaved similarly. However, aspirin pretreatment of EC consistently resulted in ~2-fold increases in platelet adherence which could be completely abolished by exogenous PGI2 (0.5–1.0 μg/ml). SV40-transformed human EC (SVHEC), which are deficient in PGI2 production compared to primary EC, showed 10-30 times more platelet adherence. Exogenous PGI2 produced a dose - related (.001-1.0 μg/ml) decrease in platelet adherence to SVHEC but did not result in the basal levels observed with normal EC monolayers. These data suggest that : 1) In addition to its effects on platelet aggregation, PGI2 can influence platelet endothelial cell interactions; 2) The increased platelet reactivity of transformed EC is associated with, but not completely attributable, to decreased PGI2 production; and 3) Factors other than PGI2 may play a role in the thromboresistance of normal vascular endothelium.

scholarly journals The synthetic RGDS peptide inhibits the binding of fibrinogen lacking intact alpha chain carboxyterminal sequences to human blood platelets

Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 950-952 ◽  
Author(s):  
EI Peerschke ◽  
DK Galanakis
Keyword(s):  
Platelet Aggregation ◽  
Human Blood ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Competitive Inhibitor ◽  
Minor Role ◽  
Solution Ph ◽  
Alpha Chain ◽  
A Minor ◽  
Human Blood Platelets

Abstract The alpha chain 572–574 Arg-Gly-Asp sequence of fibrinogen appears to play only a minor role in platelet aggregation based on the ability of fibrinogen preparations lacking alpha chain carboxyterminal segments to support platelet aggregation, but synthetic Arg-Gly-Asp-Ser (RGDS) peptides are capable of inhibiting platelet aggregation and fibrinogen binding. The present study thus examined the ability of RGDS peptides to inhibit platelet interactions with a plasmic degradation product of fibrinogen (8D–50) that resembles an intermediate fragment X. Gel- filtered, human blood platelets suspended in 0.01 mol/L HEPES-buffered modified Tyrode's solution, pH 7.5, were stimulated with 20 mumol/L adenosine diphosphate and the binding of 125I-labeled 8D–50 or intact fibrinogen (0.01 to 0.6 mg/mL) assessed in the presence of 0 to 117 mumol/L RGDS. The data revealed that RGDS decreased the apparent affinity of 8D–50 and intact fibrinogen for platelets but did not affect the maximum number of binding sites. RGDS thus appears to be a competitive inhibitor not only of intact fibrinogen (Ki = 12 +/- 2 mumol/L) but also of 8D–50 (Ki = 15 +/- 3 mumol/L) (mean +/- SD, n = 3).

scholarly journals Inhibition of platelet aggregation by protease inhibitors. Possible involvement of proteases in platelet aggregation

Blood ◽  
1978 ◽  
Vol 52 (1) ◽  
pp. 1-12 ◽  
Author(s):  
N Aoki ◽  
K Naito ◽  
N Yoshida
Keyword(s):  
Platelet Aggregation ◽  
Protease Inhibitors ◽  
Serine Proteases ◽  
Human Platelet ◽  
Serotonin Release ◽  
Second Phase ◽  
Inhibition Of Platelet Aggregation ◽  
Naturally Occurring ◽  
Human Platelet Aggregation ◽  
Platelet Receptor

Abstract The possible participation of proteases in human platelet aggregation was explored using various protease inhibitors and substrates. Protease inhibitors used included naturally occurring inhibitors of serine proteases and synthetic inhibitors that modify the active site of protease. Substrates used were synthetic substrates for the trypsin type as well as for the chymotrypsin type of protease. All these inhibitors and substrates inhibited platelet aggregation and serotonin release induced by ADP, collagen, epinephrine, or thrombin. In ADP- and epinephrine-induced platelet aggregation the second phase of aggregation was most efficiently inhibited. The inhibitors suppressed the formation of malondialdehyde during platelet aggregation. Release by aggregating agents of arachidonate and its metabolites from indomethacin-treated platelets as well as nontreated platelets was also inhibited. The inhibitors apperar to interact with stimulated platelets but not with unstimulated platelets. These observations suggest that the interaction of an aggregating agent with its platelet receptor activates a unique precursor serine protease that in turn activates platelet phospholipase to liberate arachidonic acid (the precursor of the potent platelet aggregating agent thromboxane A2) from platelet phospholipids.

Platelet Aggregation: Induction By Means Of a Complex Between Endotoxin and Copper (Cu2+)

1971 ◽  
Vol 49 (11) ◽  
pp. 1236-1244 ◽  
Author(s):  
A. F. Lewis ◽  
R. C. Dickson
Keyword(s):  
Platelet Aggregation ◽  
Clinical Significance ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Bacterial Endotoxin ◽  
Cupric Ion ◽  
Rabbit Blood ◽  
Initial Stage ◽  
Induced Aggregation

The presence of a complex formed between bacterial endotoxin and cupric ion (Cu2+) causes mammalian (human, pig, and rabbit) blood platelets to aggregate in suspension. Complexes formed between endotoxin and Zn2+, Co2+, Ni2+, Mn2+, Fe3+, Ca2+, Mg2+, Ba2+, Al3+, Be2+, Pb2+, Cd2+, Ag+, or Hg2+ do not cause aggregation. The initial stage of the aggregation induced by the complex is not inhibited by inhibitors of adenosine diphosphate (ADP) or collagen induced aggregation, and is not accompanied by release of measureable amounts of serotonin or ADP. The potential clinical significance of the phenomenon is noted.

Sign in / Sign up

Export Citation Format

Share Document