DDAVP normalized the bleeding time in patients with congenital platelet TxA2
 receptor abnormality

SummaryFive patients with mild bleeding tendencies characterized by defective thromboxane A2 (TXA2)-induced platelet aggregation are reported. The platelets of all the patients had the ability to bind exogenous TXA2. Bleeding time was markedly prolonged in one patient. In three of the five patients, synthetic TXA2 mimetic (STA2)-induced platelet responses, including IP3 formation, Ca2+ mobilization, phosphatidic acid formation and GTPase activities were selectively defective, suggesting impaired coupling between the TXA2 receptor and phospholipase C activation. However, in the remaining two patients, these responses were all within normal limits. This suggests that the defective site of this type of platelet disorder is heterogenous and that signaling mechanisms other than the TXA2 receptor-phospholipase C pathway are also involved in TXA2-induced platelet aggregation.

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Varicose vein surgery under anti-platelet therapy

Phlebologie ◽

10.1055/s-0037-1622242 ◽

2008 ◽

Vol 37 (06) ◽

pp. 287-297 ◽

Cited By ~ 1

Author(s):

P.-M. Baier ◽

Z. T. Miszczak

Keyword(s):

Varicose Vein ◽

Bleeding Time ◽

Varicose Veins ◽

Bleeding Risk ◽

Bleeding Complications ◽

Review Of The Literature ◽

Varicose Vein Surgery ◽

Anti Platelet Therapy ◽

Male Patients ◽

Acute Atherothrombosis

Summary Background: Platelet function inhibitors (PFI) are used for prophylaxis of atherothrombosis. These drugs cause a prolongation of the bleeding time and should eventually be stopped before an elective operation. However, there is a risk that a perioperative pause of PFI lead to acute atherothrombosis. Objective: Our aim was to study whether a discontinuation of PFI therapy is necessary to avoid bleeding complications in patients undergoing varicose vein surgery. Methods: Selective review of the literature and retrospective analysis of clinical data of our own patients. Results: In the years 2002 to 2007 a total of 10 827 patients have been operated on varicose veins, 673 (6.2%) of these aged 32–86 years (67 ± 7.9) receiving permanent PFI therapy: 256 male patients (38.0%) and 417 female (62.0%), 39.1% categorized as ASA III patients: male 11.6%, female 27.5%. 38 patients who continued PFI therapy did not demonstrate haemorrhagic complications and none of those pausing anti-platelet medication experienced thromboembolic complications. The literature survey confirmed our finding that it is not necessary to suspend PFI medication for varicose vein surgery as the bleeding risk can be controlled for by technical means. Conclusion: Discontinuation of PFI therapy prior to interventions on varicose veins does not seem to be necessary, further studies are essential though.

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ADP Plays a Key Role in Thrombogenesis in Rats

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642759 ◽

1988 ◽

Vol 59 (02) ◽

pp. 225-230 ◽

Cited By ~ 63

Author(s):

J P Maffrand ◽

A Bernat ◽

D Delebassée ◽

G Defreyn ◽

J P Cazenave ◽

...

Keyword(s):

Platelet Aggregation ◽

Bleeding Time ◽

Thrombus Formation ◽

Vascular Wall ◽

Cyclooxygenase Inhibitors ◽

High Dose ◽

Silk Thread ◽

Dense Granules ◽

Prolonged Bleeding Time ◽

Venous Shunt

SummaryThe relative importance of ADP, arachidonic acid metabolites and serotonin as thrombogenic factors was evaluated in rats by comparing, after oral administration, the effects of two inhibitors of ADP-induced platelet aggregation (ticlopidine and PCR 4099), three cyclo-oxygenase inhibitors (aspirin, triflusal and indobufen) and a selective serotonin 5HT2 receptor antagonist (ketanserin) on platelet aggregation, in four platelet-dependent thrombosis models and on bleeding time. Platelet aggregation induced by ADP and collagen was completely inhibited by ticlopidine and PCR 4099 whereas only the collagen aggregation was reduced by the cyclo-oxygenase inhibitors. Ketanserin or a depletion of platelet serotonin by reserpine did not affect platelet aggregation. Ticlopidine and PCR 4099 greatly prolonged rat tail transection bleeding time. This is probably related to their known ability to inhibit ADP-mediated platelet aggregation. In contrast, the cyclooxygenase inhibitors did not affect bleeding time at all. Reserpine and ketanserin prolonged bleeding time by interfering with the action of serotonin on the vascular wall. Ticlopidine and PCR4099 were very potent antithrombotics in all the models. Aspirin, only at a high dose, inhibited poorly thrombus formation on a silk thread in an arterio-venous shunt, suggesting that the inhibition of cyclo-oxygenase was not responsible. Triflusal was inactive in all models while indobufen slightly reduced thrombus formation in the silk thread and metallic coil models. Ketanserin and reserpine reduced thrombus only in the metallic coil model. Thrombus formation was greatly reduced in fawn-hooded rats, which lack ADP in their platelet dense granules because of a genetic storage pool deficiency. Taken together, the results obtained with the drugs and with the fawn-hooded rats support the concept that ADP plays a key role in thrombogenesis in rats.

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Antithrombotic Effects and Bleeding Time Prolongation with Synthetic Platelet GPIIb/llla Inhibitors in Animal Models of Platelet-Mediated Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642390 ◽

1994 ◽

Vol 71 (01) ◽

pp. 095-102 ◽

Cited By ~ 43

Author(s):

Désiré Collen ◽

Hua Rong Lu ◽

Jean-Marie Stassen ◽

Ingrid Vreys ◽

Tsunehiro Yasuda ◽

...

Keyword(s):

Platelet Aggregation ◽

Bleeding Time ◽

Bolus Injection ◽

Cell Injury ◽

Ex Vivo ◽

Thrombus Formation ◽

Femoral Vein ◽

Thrombotic Occlusion ◽

Antithrombotic Effects

SummaryCyclic Arg-Gly-Asp (RGD) containing synthetic peptides such as L-cysteine, N-(mercaptoacetyl)-D-tyrosyl-L-arginylglycyl-L-a-aspartyl-cyclic (1→5)-sulfide, 5-oxide (G4120) and acetyl-L-cysteinyl-L-asparaginyl-L-prolyl-L-arginyl-glycyl-L-α-aspartyl-[0-methyltyrosyl]-L-arginyl-L-cysteinamide, cyclic 1→9-sulfide (TP9201) bind with high affinity to the platelet GPIIb/IIIa receptor.The relationship between antithrombotic effect, ex vivo platelet aggregation and bleeding time prolongation with both agents was studied in hamsters with a standardized femoral vein endothelial cell injury predisposing to platelet-rich mural thrombosis, and in dogs with a carotid arterial eversion graft inserted in the femoral artery. Intravenous administration of G4120 in hamsters inhibited in vivo thrombus formation with a 50% inhibitory bolus dose (ID50) of approximately 20 μg/kg, ex vivo ADP-induccd platelet aggregation with ID50 of 10 μg/kg, and bolus injection of 1 mg/kg prolonged the bleeding time from 38 ± 9 to 1,100 ± 330 s. Administration of TP9201 in hamsters inhibited in vivo thrombus formation with ID50 of 30 μg/kg, ex vivo platelet aggregation with an ID50 of 50 μg/kg and bolus injection of 1 mg/kg did not prolong the template bleeding time. In the dog eversion graft model, infusion of 100 μg/kg of G4120 over 60 min did not fully inhibit platelet-mediated thrombotic occlusion but was associated with inhibition of ADP-induccd ex vivo platelet aggregation and with prolongation of the template bleeding time from 1.3 ± 0.4 to 12 ± 2 min. Infusion of 300 μg/kg of TP9201 over 60 min completely prevented thrombotic occlusion, inhibited ex vivo platelet aggregation, but was not associated with prolongation of the template bleeding time.TP9201, unlike G4120, inhibits in vivo platelet-mediated thrombus formation without associated prolongation of the template bleeding time.

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1-Desamino-8-D-Arginine Vasopressin (DDAVP) Infusion in Type IIB von Willebrand’s Disease: Shortening of Bleeding Time and Induction of a Variable Pseudothrombocytopenia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647265 ◽

1990 ◽

Vol 64 (01) ◽

pp. 117-120 ◽

Cited By ~ 22

Author(s):

Alessandra Casonato ◽

M Teresa Sartori ◽

Luigi de Marco ◽

Antonio Girolami

Keyword(s):

Monoclonal Antibody ◽

Platelet Count ◽

Arginine Vasopressin ◽

Calcium Concentration ◽

Sodium Citrate ◽

Bleeding Time ◽

Blood Collection ◽

Von Willebrand's Disease ◽

Blood Samples ◽

Von Willebrand’S Disease

SummaryWe have investigated the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) infusion on platelet count and bleeding time in 4 patients with type IIB von Willebrand’s disease (vWd). Three of four patients showed a normalization of the bleeding time within 1 h after the infusion, while bleeding time was not modified in the fourth. In accordance with the literature, thrombocytopenia was observed after DDAVP infusion, but this thrombocytopenia was due to the anticoagulants used for blood collection. In two patients (F. I., G. F.) no thrombocytopenia was observed when platelets were counted by fingerstick method but there was a 20% platelet decrease in blood samples collected in sodium citrate and a 50% decrease in samples collected in EDTA. Dramatic falls in platelet counts (70–95%) were observed in the additional two patients (C. A., D.Z.) after DDAVP infusion, when both sodium citrate or EDTA were used as anticoagulants. In the latter two patients there was also a 50% decrease in platelet count when the fingerstick method was used. The decrease in the patient’s platelet count in EDTA samples after DDAVP infusion could be prevented, in part, by the previous additions of an anti GPIb monoclonal antibody and an anti GPIIb-IIIa monoclonal antibody.Thus, the thrombocytopenia observed in the four IIB vWd patients studied after DDAVP infusion seems to be, at least partially, a pseudothrombocytopenia depending on the calcium concentration in the blood samples and the availability of GPIb and GPIIb-IIIa receptors. These findings and the normalization of the bleeding time observed in three of the four patients has led us to reconsider the possible use of DDAVP in the treatment of our IIB vWd patients.

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Comparative Arterial Antithrombotic Activity of Clopidogrel and Acetyl Salicylic Acid in the Pig

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646307 ◽

1992 ◽

Vol 68 (05) ◽

pp. 500-505 ◽

Cited By ~ 32

Author(s):

Ch M Samama ◽

Ph Bonnin ◽

M Bonneau ◽

G Pignaud ◽

E Mazoyer ◽

...

Keyword(s):

Platelet Aggregation ◽

Femoral Artery ◽

Bleeding Time ◽

Ex Vivo ◽

Flow Reduction ◽

Cyclic Flow ◽

Left Femoral Artery ◽

Before And After ◽

The Right ◽

Induced Aggregation

SummaryWe investigated the comparative antithrombotic properties of clopidogrel, an analogue of ticlopidine, and aspirin, using the Folts' model on femoral arteries in 22 pigs. On each animal, clopidogrel or aspirin were used to treat the thrombotic process on the left femoral artery and to prevent this process on the right femoral artery. Sequentially: an injury and stenosis were carried out on the left femoral artery; the thrombotic process was monitored with a Doppler during a 30-min observation period for cyclic flow reductions or permanent cessation of flow; after the first cyclic flow reduction occurred, clopidogrel (5 mg kg-1) or aspirin (2.5, 5, 100 mg kg-1) were injected intravenously; if cyclic flow reductions were abolished, epinephrine (0.4 µg kg-1 min-1) was injected to try to restore cyclic flow reductions and/or permanent cessation of flow; then injury and stenosis were applied on the right femoral artery. Before and after injection of clopidogrel or aspirin, ear immersion bleeding times and ex-vivo platelet aggregation were performed. Clopidogrel (n = 7) abolished cyclic flow reductions in all animals and epinephrine did not restore any cyclic flow reduction. On the right femoral artery, cyclic flow reductions were efficiently prevented, even for two injuries. Basal bleeding time (5 min 28) was lengthened (>15 min, 30 min after clopidogrel and remained prolonged even after 24 h). ADP-induced platelet aggregation was inhibited (more than 78%). Comparatively, aspirin had a moderate and no dose-dependent effect. Aspirin 2.5 mg kg-1 (n = 6) abolished cyclic flow reductions in 2 animals, CFR reoccurred spontaneously in one animal and epinephrine restored it in a second animal. Aspirin 5 mg kg-1 (n = 6) abolished cyclic flow reductions in only 3 animals and epinephrine always restored it. Aspirin 100 mg kg-1 (n = 3) was unable to abolish cyclic flow reductions. On the right femoral artery, aspirin did not significantly prevent cyclic flow reductions which occurred in all animals after one (n = 14) or two injuries (n = 1), except for one animal. Basal bleeding time was lengthened but it shortened rapidly, reaching its basal value after 24 h. ADP-induced aggregation was not significantly inhibited, whereas arachidonic acid induced aggregation was always inhibited. Clopidogrel appears as a more potent antithrombotic drug than aspirin in this model, in treating and preventing spontaneous or epinephrine-induced cyclic flow reductions and lengthening bleeding time.

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Platelet Function and the Bleeding Time in Progressive Renal Failure

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647640 ◽

1988 ◽

Vol 60 (01) ◽

pp. 083-087 ◽

Cited By ~ 30

Author(s):

M P Gordge ◽

R W Faint ◽

P B Rylance ◽

G H Neild

Keyword(s):

Renal Failure ◽

Platelet Aggregation ◽

Platelet Function ◽

Bleeding Time ◽

C Reactive Protein ◽

Severe Renal Failure ◽

Reactive Protein ◽

Thromboxane Production ◽

Von Willebrand ◽

Willebrand Factor

SummaryBleeding time and platelet function tests were performed on 31 patients with progressive chronic renal failure (CRF) due to non-immunological (urological) causes, and compared with 22 healthy controls. Patients were classified as mild (plasma creatinine <300 μmol/l), moderate (300-600 μmol/l) or severe renal failure (>600 μmol/l). Bleeding time was rarely prolonged in mild and moderate CRF and mean bleeding time significantly elevated only in severe CRF (p <0.005). Haematocrit was the only index which correlated with bleeding time (r = -0.40). Platelet counts, collagen stimulated thromboxane generation, and platelet aggregation responses to ADP, collagen and ristocetin were all either normal or increased in all three CRF groups, but thromboxane production in clotting blood was reduced. Plasma fibrinogen, C reactive protein and von Willebrand factor (vWF) were elevated in proportion to CRF. We found no evidence that defects in platelet aggregation or platelet interaction with vWF prolong the bleeding time in patients with progressive CRF.

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Essential Athrombia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647881 ◽

1975 ◽

Vol 33 (02) ◽

pp. 278-285 ◽

Cited By ~ 3

Author(s):

Şeref Inceman ◽

Yücel Tangün

Keyword(s):

Platelet Aggregation ◽

Bleeding Time ◽

Bleeding Tendency ◽

Clot Retraction ◽

Platelet Factor ◽

Prolonged Bleeding Time ◽

Normal Platelet ◽

Aggregation Response ◽

Platelet Disorder ◽

Fibrinogen Content

SummaryA constitutional platelet function disorder in a twelve-year-old girl characterized by a lifelong bleeding tendency, prolonged bleeding time, normal platelet count, normal clot retraction, normal platelet factor 3 activity and impaired platelet aggregation was reported.Platelet aggregation, studied turbidimetrically, was absent in the presence of usual doses of ADP (1–4 μM), although a small wave of primary aggregation was obtained by very large ADP concentrations (25–50 μM). The platelets were also unresponsive to epinephrine, thrombin and diluted collagen suspensions. But an almost normal aggregation response occurred with strong collagen suspensions. The platelets responded to Ristocetin. Pelease of platelet ADP was found to be normal by collagen and thrombin, but impaired by kaolin. Platelet fibrinogen content was normal.The present case, investigated with recent methods, confirms the existence of a type of primary functional platelet disorder characterized solely by an aggregation defect, described in 1955 and 1962 under the name of “essential athrombia.”

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Effects on Coagulation and Fibrinolysis of Desmopressin in Patients Undergoing Total Hip Replacement

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646480 ◽

1991 ◽

Vol 66 (06) ◽

pp. 652-656 ◽

Cited By ~ 7

Author(s):

Per Anders Flordal ◽

Karl-Gösta Ljungström ◽

Jan Svensson ◽

Brenda Ekman ◽

Gustaf Neander

Keyword(s):

Total Hip Replacement ◽

Hip Replacement ◽

Bleeding Time ◽

Antithrombin Iii ◽

Postoperative Bleeding ◽

Double Blind ◽

Total Hip ◽

Von Willebrand ◽

Willebrand Factor ◽

Coagulation And Fibrinolysis

SummaryTwelve patients undergoing total hip replacement, with regional anaesthesia and with dextran infusion for plasma expansion and thromboprophylaxis, were given the vasopressin analogue desmopressin (DDAVP) or placebo in a randomized, double-blind prospective study. In controls (n = 6) we found a prolongation of the bleeding time, low factor VIII (FVIII) and von Willebrand factor (vWF) and a decrease in antithrombin III to levels known to be at risk for venous thrombosis. Desmopressin shortened postoperative bleeding time, gave an early FVIII/vWF complex increase, prevented antithrombin III from falling to critically low values and appeared to activate the fibrinolytic system, both by tPA increase and PAI-1 decrease.Thus in the controls we found changes in both coagulation and fibrinolysis indicating a haemorrhagic diathesis as well as a risk for thromboembolism. Desmopressin induced factor changes that possibly reduce both risks.

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The Venous Antithrombotic Profile of Naroparcil in the Rabbit

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648977 ◽

1994 ◽

Vol 72 (06) ◽

pp. 874-879 ◽

Cited By ~ 11

Author(s):

Jean Millet ◽

Jocelyne Theveniaux ◽

Neil L Brown

Keyword(s):

Oral Administration ◽

Bleeding Time ◽

Dermatan Sulfate ◽

Factor Xa ◽

Bleeding Risk ◽

Thrombin Time ◽

Heparin Cofactor Ii ◽

Antithrombotic Activity ◽

Thrombin Inhibition ◽

Maximal Reduction

SummaryThe venous antithrombotic profile of naroparcil or (4-[4-cyanoben-zoyl]-phenyl)-1.5-dithio-β-D-xylopyranoside was investigated in the rabbit following single i. v. and oral administration. Naroparcil attenuated thrombus development in a Wessler stasis model of venous thrombosis (jugular vein) employing bovine factor Xa as a thrombogenic stimulus giving ED50 values of 21.9 mg/kg and 36.0 mg/kg after respectively i. v. and oral administration. Venous antithrombotic activity was maximal 2-3 h after i. v. administration and 4-8 h after oral administration. Four hours after the oral administration of maximal antithrombotic (Wessler model, factor Xa) doses (100 and 400 mg/kg), naroparcil had no significant effect on bleeding time. In platelet poor plasma obtained from animals treated 4 h previously with various doses (25 to 400 mg/kg) of naroparcil, there was no detectable anti-factor Xa nor antithrombin activity. Similarly, naroparcil had no effect on APTT nor on thrombin time. A sensitized thrombin time (to about 35 s) was modestly but significantly increased following oral administration of the compound at 400 mg/kg. However, thrombin generation by the intrinsic pathway was reduced in a dose-related manner, maximal reduction being 65% at 400 mg/kg. The same doses of naroparcil enhanced the formation of thrombin/heparin cofactor II complexes at the expense of thrombin/antithrombin III complexes in plasma incubated with (125I)-human a-thrombin and induced the appearance of dermatan sulfate-like material in the plasma of treated rabbits, as measured by a heparin cofactor II-mediated thrombin inhibition assay. The results suggest that naroparcil could have a safe venous antithrombotic profile following oral administration (antithrombotic effect compared to bleeding risk). It is probable that part of the mechanism of action of the β-D-xyloside, naroparcil, is due to the induction of chondroitin sulfate-like glycosaminoglycan biosynthesis, this material being detectable in the plasma.

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