Activated Hemostatic Biomarkers in Patients with Implanted Left Ventricle Assist Devices: Are Heparin and/or Clopidogrel Justified?

Cardiology ◽  
2015 ◽  
Vol 131 (3) ◽  
pp. 172-176
Author(s):  
Jerzy Pacholewicz ◽  
Wiktor Kuliczkowski ◽  
Jacek Kaczmarski ◽  
Michał Zakliczyński ◽  
Marcin Garbacz ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Left Ventricle ◽  
Stress Test ◽  
Adenosine Diphosphate ◽  
Clot Formation ◽  
Gradual Improvement ◽  
Prothrombin Activity ◽  
International Normalization Ratio ◽  
D Dimer

Background: Adequate anticoagulation represents a major problem for left ventricle assist device (LVAD) utilization in patients awaiting heart transplantation as well as for regeneration of the native heart. The proper management of hemostatic abnormalities during LVAD support may improve survival by reducing the incidence of hemorrhagic and/or thromboembolic complications. Case Report: A 40-year-old man with implanted pulsatile LVAD due to dilated cardiomyopathy received aspirin and warfarin. The patient underwent serial weekly monitoring of hemostatic biomarkers including international normalization ratio, prothrombin time, prothrombin activity, activated partial thromboplastin time, fibrinogen, D-dimer, platelet aggregation induced by adenosine diphosphate and arachidonic acid, platelet count, and mean platelet volume. The external pump was exchanged three times - twice because of a clot formation in the blood chamber of the pump, and once according to the standard protocol. Results: LVAD use was consistently associated with enhanced adenosine diphosphate-induced platelet aggregation independent from the timing of clot formation or external pump exchange. Among coagulation indices, increased D-dimer holds predictive value for clot formation. The fibrinogen level peaked before the first pump exchange and was twice as high than the average values. Gradual improvement in exercise capacity was observed 2 years after implantation, after which the patient underwent a controlled stress test in the stop mode of the LVAD and the device was successfully explanted. Conclusions: Serial assessment of hemostatic biomarkers may benefit and triage LVAD patients. Consistent platelet activation during long-term LVAD may justify the addition of clopidogrel, while high D-dimer and/or elevated fibrinogen may indicate adding heparin to the conventional antithrombotic regimen. Randomized evidence is needed to test such a hypothesis.

scholarly journals Coagulation alterations in treating arrhythmias with radiofrequency ablation

Medicina ◽  
2009 ◽  
Vol 45 (9) ◽  
pp. 706 ◽  
Author(s):  
Vilma Kozlovaitė ◽  
Pranas Grybauskas ◽  
Jūratė Cimbolaitytė ◽  
Aušra Mongirdienė ◽  
Vytautas Šileikis ◽  
...  
Keyword(s):  
Radiofrequency Ablation ◽  
Platelet Aggregation ◽  
Blood Plasma ◽  
Cardiac Arrhythmias ◽  
Whole Blood ◽  
Fibrinogen Level ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Coagulation System ◽  
D Dimer

Objective. To determine an influence of radiofrequency ablation on changes in coagulation system. Material and methods. We investigated 30 patients with cardiac arrhythmias. Platelet aggregation, fibrinogen and D-dimer level were analyzed before, right after, 24 and 72 h after radiofrequency ablation. Platelet aggregation was explored in whole blood and platelet-rich plasma using adenosine diphosphate (ADP), epinephrine, and collagen for induction. Results. Platelet aggregation induced by ADP and collagen in whole blood plasma increased significantly (P<0.01) (by 45% and 43%, respectively) in 24 h after radiofrequency ablation and remained increased in 72 h after radiofrequency ablation (by 11% and 35%, respectively) (P<0.01) as compared with baseline results. Spontaneous aggregation of platelet-rich plasma as well as ADP- and collagen-induced platelet aggregation tended to decrease right after radiofrequency ablation. Epinephrine-induced platelet aggregation significantly decreased by 17.5% after radiofrequency ablation (P<0.01) and started to increase in 24 h after radiofrequency ablation. In 72 h after radiofrequency ablation, platelet aggregation induced by different agonists increased by 7–45% significantly (P<0.05), and values were higher than baseline ones. Fibrinogen level after radiofrequency ablation did not differ from that of the baseline (3.08±0.7 g/L), but D-dimer level increased significantly (from 0.39±0.3 to 1.29±2.4 mg/L, P<0.01). In 24 h after radiofrequency ablation, an increase in fibrinogen level and a decrease in D-dimer level were found. Fibrinogen level increased to 3.32±0.6 g/L significantly in 72 h after radiofrequency ablation (P<0.05). Meanwhile, D-dimer concentration decreased to 0.78±0.8 mg/L, but it was still significantly higher (P<0.05) than the baseline value. Conclusion. Despite diminished platelet aggregation and increased D-dimer level right after radiofrequency ablation, a risk of thrombosis increased in the next few days after radiofrequency ablation.

ADP and arachidonic acid induced platelet aggregation in schizophrenia and atypical psychoses

1984 ◽  
Vol 14 (1) ◽  
pp. 207-211 ◽  
Author(s):  
L. J. Whalley ◽  
H. W. Reading ◽  
R. Rosie
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Healthy Controls ◽  
Chronic Schizophrenics ◽  
Nervous System Function ◽  
Aggregation And Disaggregation ◽  
The Difference ◽  
Drug Free

SynopsisPlatelet aggregatory responses to adenosine diphosphate (ADP) and arachidonic acid were examined in 6 drug-free schizophrenics, 5 other drug-free psychotics, 8 ‘acute-on-chronic’ schizophrenics (on long-term neuroleptic therapy) and 38 healthy controls. Platelet aggregation and disaggregation following ADP was significantly lower in ‘acute-on-chronic’ schizophrenics (on drugs) compared with healthy controls, and disaggregation following 1 µM ADP was significantly less in drug-free schizophrenics. The difference between maximum aggregation induced by ADP and that induced by arachidonic acid was significantly greater in schizophrenics (both on drugs and drug-free) than in controls. These findings are related to possible abnormalities of central nervous system function in schizophrenia.

scholarly journals Antipsychotic Drugs Inhibit Platelet Aggregation via P2Y1and P2Y12Receptors

2016 ◽  
Vol 2016 ◽  
pp. 1-12
Author(s):  
Chang-Chieh Wu ◽  
Fu-Ming Tsai ◽  
Mao-Liang Chen ◽  
Semon Wu ◽  
Ming-Cheng Lee ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Antipsychotic Drugs ◽  
Calcium Influx ◽  
Ex Vivo ◽  
Adenosine Diphosphate ◽  
Underlying Mechanism ◽  
Clot Formation ◽  
Adp Receptors ◽  
Aggregation Of Platelets

Antipsychotic drugs (APDs) used to treat clinical psychotic syndromes cause a variety of blood dyscrasias. APDs suppress the aggregation of platelets; however, the underlying mechanism remains unknown. We first analyzed platelet aggregation and clot formation in platelets treated with APDs, risperidone, clozapine, or haloperidol, using an aggregometer and rotational thromboelastometry (ROTEM). Our data indicated that platelet aggregation was inhibited, that clot formation time was increased, and that clot firmness was decreased in platelets pretreated with APDs. We also examined the role two major adenosine diphosphate (ADP) receptors, P2Y1and P2Y12, play in ADP-mediated platelet activation and APD-mediated suppression of platelet aggregation. Our results show that P2Y1receptor stimulation with ADP-induced calcium influx was inhibited by APDs in human and rats’ platelets, as assessed byin vitroorex vivoapproach, respectively. In contrast, APDs, risperidone and clozapine, alleviated P2Y12-mediated cAMP suppression, and the release of thromboxane A2 and arachidonic acid by activated platelets decreased after APD treatment in human and rats’ platelets. Our data demonstrate that each APD tested significantly suppressed platelet aggregation via different mechanisms.

The Dysfunction of Platelets in Paroxysmal Nocturnal Hemoglobinuria

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4532-4532
Author(s):  
Rong Fu ◽  
Yinping Meng ◽  
Yihao Wang ◽  
Hui Liu ◽  
Yi Liu ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Conflicts Of Interest ◽  
Adenosine Diphosphate ◽  
Underlying Mechanism ◽  
Control Group ◽  
Type Ii ◽  
Clinical Tests ◽  
Terminal Complement ◽  
Normal Controls ◽  
D Dimer

Abstract Introduction Thrombosis is one of the most dangerous complications in PNH, which can cause high mortality. However, its underlying mechanism remains unclear. To explore the mechanism of thrombosis in PNH, the function of platelets and complements were investigated in our study. Material and Methods Serum level of terminal complement complex (sC5b-9) was detected by ELISA. The quantities of C5b-9,CD61 and CD62p on the membrane of platelets were detected by flow cytometry. Clinical tests were collected, including D-Dimer and platelet aggregation rates induced by adenosine diphosphate (ADP) and arachidonic acid (ARA). Results The serum sC5b-9 level was significantly lower in the PNH/PNH-AA group than that in the control group (p<0.01). The deposition of C5b-9 on CD59- platelets (17.53%±6.27%) was higher than those on CD59+ platelets in PNH/PNH-AA patients(11.33%±5.03%) and normal controls(10.88%±3.58%) (p<0.01). D-dimer was significantly higher in PNH/PNH-AA patients (485ng/dL) than that in normal controls (311ng/dL)(p<0.05),especially in patients with LDH>1000U/L(789ng/dL). CD61 and CD62p expression on CD59+ platelets in PNH patients (76.87%,39.99%) were significantly lower than those in normal controls(98.41%,64.21%)(p<0.05,p<0.01).CD62p expression on CD59- platelets (40.07%) was significantly lower than normal controls(p<0.01). Platelet aggregation stimulated by agonists ADP (37.54±24.25)% and ARA (24.60%) were lower in the PNH/PNH-AA group than that in the control group(59.20±23.30)%, (14.54%) (p < 0.05). Interestingly,CD61 expression on CD59+ platelets in PNH patients was higher in the patients with higher type II PNH clone. Conclusions The function of platelets was inversely inhibited,especially CD59+ platelets even if hypercoagulation continuously exists in PNH/PNH-AA. Disclosures No relevant conflicts of interest to declare.

609 Noninvasive left ventricle contractility assessment in patients with long-term volume overload

1999 ◽  
Vol 1 ◽  
pp. S101-S101
Author(s):  
O FOKINA ◽  
N TVERDOKHLEBOV ◽  
V SANDRIKOV ◽  
L KOUZNETZOVA
Keyword(s):  
Left Ventricle ◽  
Volume Overload

Ticlopidine Facilitates the Deaggregation of Human Platelets Aggregated by Thrombin

1994 ◽  
Vol 71 (01) ◽  
pp. 091-094 ◽  
Author(s):  
M Cattaneo ◽  
B Akkawat ◽  
R L Kinlough-Rathbone ◽  
M A Packham ◽  
C Cimminiello ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Before And After ◽  
Normal Human ◽  
Platelet Aggregates ◽  
Induced Aggregation

SummaryNormal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80–90% 14C-serotinin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5× the activity of thrombin) and PGE1 (10 μmol/1) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 μmol/1) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.

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.

Properties of Fibrinogen Cleaved by Jararhagin, a Metalloproteinase from the Venom of Bothrops jararaca

1994 ◽  
Vol 72 (02) ◽  
pp. 244-249 ◽  
Author(s):  
Aura S Kamiguti ◽  
Joseph R Slupsky ◽  
Mirko Zuzel ◽  
Charles R M Hay
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Fibrin Clot ◽  
Clot Formation ◽  
Human Fibrinogen ◽  
Activated Platelets ◽  
Bothrops Jararaca ◽  
Platelet Binding ◽  
Fibrin Monomers ◽  
Fibrinogen Molecule

SummaryHaemorrhagic metalloproteinases from Bothrops jararaca and other venoms degrade vessel-wall and plasma proteins involved in platelet plug and fibrin clot formation. These enzymes also cause proteolytic digestion of fibrinogen which has been suggested to cause defective platelet function. Fibrinogen degradation by jararhagin, a metalloproteinase from B. jararaca, and the effect of jararhagin fibrinogenolysis on both platelet aggregation and fibrin clot formation were investigated. Jararhagin was found to cleave human fibrinogen in the C-terminal region of the Aα-chain giving rise to a 285-290 kDa fibrinogen molecule lacking the Aα-chain RGD 572-574 platelet-binding site. Platelet binding and aggregation of ADP-activated platelets is unaffected by this modification. This indicates that the lost site is not essential for platelet aggregation, and that the remaining platelet binding sites located in the N-terminal portion of Aα chains (RGD 95-97) and the C-terminal of γ chains (dodecapeptide 400-411) are unaffected by jararhagin-digestion of fibrinogen. Fibrin clot formation with thrombin of this remnant fibrinogen molecule was defective, with poor polymerization of fibrin monomers but normal release of FPA. The abnormal polymerization could be explained by the loss of one of the two complementary polymerization sites required for side-by-side association of fibrin protofibrils. Jararhagin-induced inhibition of platelet function, an important cause of haemorrhage in envenomed patients, is not caused by proteolysis of fibrinogen, as had been thought, and the mechanism remains to be elucidated.

Adenosine Diphosphate (ADP) Breakdown in Human Plasma with Reference to Platelet Aggregation and Uraemia

1968 ◽  
Vol 19 (03/04) ◽  
pp. 438-450
Author(s):  
I. E. T Gan ◽  
B. G Firkin
Keyword(s):  
Platelet Aggregation ◽  
Human Plasma ◽  
Platelet Function ◽  
Adenosine Diphosphate ◽  
Plasma Enzyme ◽  
Aggregation Of Platelets ◽  
Plasma Activity

Summary1. A correlation between platelet aggregation and the plasma enzyme(s) ability to degrade Adenosine Diphosphate (ADP) has been confirmed.2. This plasma activity has been shown to be reduced in 6 patients with uraemia in whom platelet aggregation was demonstrably impaired but not in two whose platelet function was normal. The incorporation of 14C labelled ADP-8-14C was also only reduced in uraemic patients with abnormal platelet aggregation.3. These findings are discussed with particular reference to possible implication in mechanism involved in ADP aggregation of platelets.

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