scholarly journals DDAVP enhances platelet adherence and platelet aggregate growth on human artery subendothelium

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 229-236 ◽  
Author(s):  
KS Sakariassen ◽  
M Cattaneo ◽  
A v.d. Berg ◽  
ZM Ruggeri ◽  
PM Mannucci ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Close Association ◽  
Aggregate Formation ◽  
Human Artery ◽  
Primary Hemostasis ◽  
Platelet Adherence ◽  
Normal Individuals ◽  
Before And After ◽  
Platelet Aggregate ◽  
Aggregate Growth

Abstract The effect of intravenous 1-deamino (8-D-arginine)vasopressin (DDAVP) administration on platelet interaction with human artery subendothelium was investigated with flowing blood from five normal individuals and 12 patients with von Willebrand's disease (vWD). Three of the patients were diagnosed as vWD subtype I, four as subtype IIa, and five as subtype IIb. DDAVP administration to normals enhanced platelet adherence, in parallel with increasing plasma levels of factor VIII- related antigen ( FVIIIR :Ag) and ristocetin cofactor activity ( FVIIIR :RCF). Platelet aggregate formation was transiently increased within 90 minutes. Platelet adherence in patient blood before DDAVP infusion was subnormal. In patients with subtype I, administration of DDAVP normalized the bleeding time, enhanced the platelet adherence, and transiently improved the platelet aggregate formation. The platelet adherence was more corrected than would have been expected on the basis of the FVIIIR :Ag and FVIIIR :RCF levels. In patients with subtype IIa, infusion of DDAVP increased the FVIIIR :Ag levels approximately threefold, without affecting the FVIIIR :RCF levels, and in only two of four patients was a transiently enhanced platelet adherence with a corresponding shortening of the bleeding time observed. In patients with subtype IIb, administration of DDAVP increased the FVIIIR :Ag levels about threefold and the FVIIIR :RCF levels five to tenfold, but decreased the platelet adherence significantly. The bleeding time values were not normalized. A close association between the bleeding time values and corresponding platelet adherence values before and after DDAVP infusion was observed. Normalization of the bleeding time was paralleled with normalization of platelet adherence. We conclude that DDAVP improves the primary hemostasis by causing enhanced FVIII- vWF-mediated platelet adherence. DDAVP has little or no effect on the bleeding time in patients with subtype IIa and subtype IIb, because the platelet adherence is not normalized.

scholarly journals DDAVP enhances platelet adherence and platelet aggregate growth on human artery subendothelium

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 229-236 ◽  
Author(s):  
KS Sakariassen ◽  
M Cattaneo ◽  
A v.d. Berg ◽  
ZM Ruggeri ◽  
PM Mannucci ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Close Association ◽  
Aggregate Formation ◽  
Human Artery ◽  
Primary Hemostasis ◽  
Platelet Adherence ◽  
Normal Individuals ◽  
Before And After ◽  
Platelet Aggregate ◽  
Aggregate Growth

The effect of intravenous 1-deamino (8-D-arginine)vasopressin (DDAVP) administration on platelet interaction with human artery subendothelium was investigated with flowing blood from five normal individuals and 12 patients with von Willebrand's disease (vWD). Three of the patients were diagnosed as vWD subtype I, four as subtype IIa, and five as subtype IIb. DDAVP administration to normals enhanced platelet adherence, in parallel with increasing plasma levels of factor VIII- related antigen ( FVIIIR :Ag) and ristocetin cofactor activity ( FVIIIR :RCF). Platelet aggregate formation was transiently increased within 90 minutes. Platelet adherence in patient blood before DDAVP infusion was subnormal. In patients with subtype I, administration of DDAVP normalized the bleeding time, enhanced the platelet adherence, and transiently improved the platelet aggregate formation. The platelet adherence was more corrected than would have been expected on the basis of the FVIIIR :Ag and FVIIIR :RCF levels. In patients with subtype IIa, infusion of DDAVP increased the FVIIIR :Ag levels approximately threefold, without affecting the FVIIIR :RCF levels, and in only two of four patients was a transiently enhanced platelet adherence with a corresponding shortening of the bleeding time observed. In patients with subtype IIb, administration of DDAVP increased the FVIIIR :Ag levels about threefold and the FVIIIR :RCF levels five to tenfold, but decreased the platelet adherence significantly. The bleeding time values were not normalized. A close association between the bleeding time values and corresponding platelet adherence values before and after DDAVP infusion was observed. Normalization of the bleeding time was paralleled with normalization of platelet adherence. We conclude that DDAVP improves the primary hemostasis by causing enhanced FVIII- vWF-mediated platelet adherence. DDAVP has little or no effect on the bleeding time in patients with subtype IIa and subtype IIb, because the platelet adherence is not normalized.

Role of the PAR4 Thrombin Receptor in Stabilizing Platelet-platelet Aggregates as Revealed by a Patient with Hermansky-Pudlak Syndrome

2002 ◽  
Vol 87 (04) ◽  
pp. 722-727 ◽  
Author(s):  
Lidija Covic ◽  
Christopher Singh ◽  
Hedy Smith ◽  
Athan Kuliopulos
Keyword(s):  
Thrombin Receptor ◽  
Aggregate Formation ◽  
Dense Granules ◽  
Normal Individuals ◽  
Platelet Aggregate ◽  
Adp Release ◽  
Platelet Aggregates ◽  
Adp Receptor ◽  
Hermansky Pudlak Syndrome

SummaryIndividuals with Hermansky-Pudlak Syndrome (HPS) lack platelet dense granules and have no ADP-autocrine response. Despite these platelet deficiencies, HPS patients exhibit a surprisingly mild bleeding phenotype. We hypothesize that activation of the PAR4 thrombin receptor compensates for the lack of an ADP-autocrine response by the P2Y12 ADP receptor in individuals with HPS. Here, we determine that PAR4 activation by thrombin occurs well after ADP release from dense granules in normal individuals. However, the signal from PAR4 stabilizes platelet-platelet aggregate formation in the absence of P2Y12 activation by ADP. Thus, the strong signal emanating from PAR4 during platelet aggregation would provide an explanation for the mild bleeding diathesis of HPS.

UREMIC PLASMA, AFTER INFUSION OF DESMOPRESSIN, IMPROVES THE INTERACTION OF NORMAL PLATELETS WITH VESSEL SUBENDOTHELIUM

1987 ◽  
Author(s):  
R Castillo ◽  
G Escolar ◽  
J Monteagudo ◽  
A Cases ◽  
M Garrido ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Surface Coverage ◽  
Glass Beads ◽  
Aggregate Formation ◽  
Perfusion System ◽  
Prolonged Bleeding Time ◽  
Perfusion Studies ◽  
Platelet Aggregate ◽  
Uremic Patients

Desmopressin (DDAVP) shortened the bleeding time and increased the platelet retention on glass beads and the platelet interaction on subendothelium measured by the Baumgartner perfusion system in 11 uremic patients in whom the three tests were abnormal previous to the treatment (1).Patients were chosen at random out of a group of 30 with prolonged bleeding time and decreased platelet retention on glass beads. All tests were performed on blood drawn before and one and six hours after a single dose of DDAVP (0.4 μg/kg body weight). Perfusion experiments were carried out at a shear rate of 800 sec-1.Levels of VIII:C, VIIIR:Ag and RiCof were at the upper limit of normality before DDAVP and significantly increased one hour after treatment. The multimeric structure of vWF in pretreatment plasma was normal ; one hour after DDAVP larger multimers appeared.After injection of DDAVP, the perfusion studies using reconstituted blood with uremic PPP in presence of isolated normal platelets and washed red cells, showed a statistically increased surface coverage and platelet aggregate formation on subendothelium (p < 0.05 respectively when compared to the pretreatment values). In the same perfusion assays, the in vitro addition to pretreatment plasmas of 1 u/ml of purified vWF with normal multimeric structure, or purified VIII:C and vWF (1 u/ml each) did not modify the decreased platelet interaction on subendothelium.These results confirm the shortening of bleeding time by DDAVP in uremic patients and reveal an increase of platelet interaction on vessel subendothelium mediated by a factor present in PPP. Besides, they show that the effect of DDAVP in these patients is not due to the quantitative increase of the plasmatic vWF and FVIII.(1) Blood, 68, 2:337-342, 1986.

scholarly journals Aspirin prolongation of the template bleeding time: influence of venostasis and direction of incision

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1139-1142
Author(s):  
CH Jr Mielke
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Bleeding Time ◽  
Bleeding Disorder ◽  
Prostaglandin Biosynthesis ◽  
Primary Hemostasis ◽  
Normal Subject ◽  
Normal Individuals ◽  
Vertical Incision

The template bleeding time is a measure of platelet participation in primary hemostasis. Aspirin alters platelet function through interference with prostaglandin biosynthesis. In many individuals, aspirin will consistently prolong the bleeding time. Despite this observation, normal individuals rarely develop a bleeding disorder. This prompted us to investigate the influence of technical variables on the prolongation of the bleeding time by aspirin. Both direction of incision and venostasis influenced the prolongation of the bleeding time by aspirin. A horizontal incision with venostasis produced the most pronounced prolongation, while a vertical incision without venostasis didn't prolong the bleeding time despite the characteristic changes in platelet aggregation and release. These studies suggest that the influence of aspirin on the template bleeding time is dependent on technical variables and is minimal in the normal subject.

Development and Practical Use of the New Quantitative Bleeding Time Test Apparatus

1998 ◽  
Vol 80 (07) ◽  
pp. 181-185 ◽  
Author(s):  
Hideki Takami ◽  
Rieko Nakahata ◽  
Yuka Nakui ◽  
Tomoaki Akagi ◽  
Akihiro Munakata ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Normal Subjects ◽  
Total Blood ◽  
Bleeding Rate ◽  
Primary Hemostasis ◽  
Before And After ◽  
New Apparatus ◽  
Time Test ◽  
Time Determination ◽  
Computerized System

SummaryWe have developed a new computerized system for measurement of quantitative bleeding time (QBT) to detect subtle abnormalities of primary hemostasis that are difficult to detect with the standard bleeding time determination. This new apparatus can simultaneously measure the bleeding time (BT; sec), amount of total blood loss (Tv; μl), maximum bleeding rate (Rmax; μl/sec) and bleeding pattern from the bleeding time incision. We have also developed a new holder for the Simplate that enables more consistent incisions and thus improves the reproducibility of the BT test.In this study, the newly developed QBT test was performed in 137 normal healthy volunteers and 10 patients having defined abnormalities of either primary or secondary hemostasis. Comparisons of the standard BT test and our QBT were made in 5 normal subjects and 7 thrombocytopenic patients. Additionally, 6 normal subjects were examined with both tests before and after administration of aspirin. Those results show that our QBT appears to be a more sensitive indicator of primary hemostasis than the standard BT method.

scholarly journals Aspirin prolongation of the template bleeding time: influence of venostasis and direction of incision

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1139-1142 ◽  
Author(s):  
CH Jr Mielke
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Bleeding Time ◽  
Bleeding Disorder ◽  
Prostaglandin Biosynthesis ◽  
Primary Hemostasis ◽  
Normal Subject ◽  
Normal Individuals ◽  
Vertical Incision

Abstract The template bleeding time is a measure of platelet participation in primary hemostasis. Aspirin alters platelet function through interference with prostaglandin biosynthesis. In many individuals, aspirin will consistently prolong the bleeding time. Despite this observation, normal individuals rarely develop a bleeding disorder. This prompted us to investigate the influence of technical variables on the prolongation of the bleeding time by aspirin. Both direction of incision and venostasis influenced the prolongation of the bleeding time by aspirin. A horizontal incision with venostasis produced the most pronounced prolongation, while a vertical incision without venostasis didn't prolong the bleeding time despite the characteristic changes in platelet aggregation and release. These studies suggest that the influence of aspirin on the template bleeding time is dependent on technical variables and is minimal in the normal subject.

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

1992 ◽  
Vol 68 (05) ◽  
pp. 500-505 ◽  
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.

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Stable Coronary Artery Disease ◽  
High Dose ◽  
Single Drug ◽  
Before And After ◽  
Serum Thromboxane ◽  
Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

Hemostatic Disorder of Uremia: The Platelet Defect, Main Determinant of the Prolonged Bleeding Time, Is Correlated with Indices of Activation of Coagulation and Fibrinolysis

1996 ◽  
Vol 76 (03) ◽  
pp. 312-321 ◽  
Author(s):  
Diego Mezzano ◽  
Rodrigo Tagle ◽  
Olga Panes ◽  
Marcos Pérez ◽  
Patricio Downey ◽  
...  
Keyword(s):  
Renal Failure ◽  
Bleeding Time ◽  
Degradation Products ◽  
Plasminogen Activator Inhibitor ◽  
Primary Hemostasis ◽  
Prolonged Bleeding Time ◽  
Fibrin Degradation Products ◽  
Von Willebrand ◽  
Pai 1 ◽  
Coagulation And Fibrinolysis

SummarySeveral parameters of primary hemostasis and markers of activation of coagulation and fibrinolysis were measured in 48 patients with severe (creatinine clearance <20 ml/min) chronic renal failure (CRF) without dialysis and diseases or drugs affecting hemostasis. Bleeding time (BT) was prolonged in 25/48 patients, and was correlated with age of patients, severity of renal failure, hematocrit, impairment in platelet aggregation-secretion and decrease in platelet ATP content. Defects in von Willebrand factor played no role in the prolongation of the BT. Multivariate analysis showed that only platelet dysfunction and severity of renal disease were independent predictors of the BT in uremia. The platelet functional disorder was significantly correlated with a reduction in platelet ATP and ADP.High levels of plasma thrombin-antithrombin complexes (TAT), prothrombin fragment F1+2, fibrinogen and factor VIIc were observed in patients with CRF, as described in prethrombotic states. Plasmin-antiplasmin complexes (PAP), fibrinogen and fibrin degradation products (FgDP, FnDP) were significantly increased, and the activity of plasminogen activator inhibitor (PAI-1) was slightly reduced, denoting an activation of fibrinolysis.A negative correlation was found between platelet levels of ATP and ADP with plasma TAT, F1+2 and PAP. Furthermore, plasma PAI-1 activity was negatively correlated with the BT and was lower in patients with prolonged BT as compared with controls and patients with normal BT. These links between primary hemostasis and activation of coagulation and fibrinolysis suggest that increased intravascular generation of thrombin and/or plasmin is an important mediator of the defects in primary hemostasis, prolongation of the BT and, probably, bleeding in CRF.

EFFECT OF DDAVP ON PRIMARY HEMOSTASIS WITH CONGENITAL AFIBRINOGENEMIA

1987 ◽  
Author(s):  
M Taki ◽  
M Inagaki ◽  
T Miura ◽  
N Saito ◽  
T Meguro ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Retention Rate ◽  
Platelet Membrane ◽  
Bleeding Tendency ◽  
Primary Hemostasis ◽  
Prolonged Bleeding Time ◽  
Before And After ◽  
Congenital Afibrinogenemia ◽  
Von Willebrand ◽  
Platelet Functions

It has been reported recently that DDAVP might be an useful tool in the therapy and prevention of bleeding in patients with congenital afibrinogenemia (CA).To study the mechanism of its efficacy, changes in the platelet functions of a patient with CA were examined prior to, and one hour after, the infusion of DDAVP (0.4 μg/Kg). A patient with Glanzmann's thrombasthenia (GT) was also examined, to allow a study of the role of platelet membrane glycoprotein IIb/IIIa (GP IIb/IIIa), a deficient platelet in GT, in the resulting effects of the drug. When both patients were infused with DDAVP, the level of plasma von Willebrand factor (vWF) increased two- to fourfold, accompanied by an enhancement of ristocetin-induced platelet agglutination. The level of plasma fibrinogen was never changed.The prolonged bleeding time observed was markedly improved only in the CA patient, remaining unchanged in the GT patient, after the infusion of DDAVP. This indicates that DDAVP is effective in diminishing the bleeding tendency in CA, but not in GT. Among the platelet functions tested, only the platelet retention rate on glass beads, ADP-induced platelet aggregation and collagen-induced platelet aggregation improved in CA, each remaining unchanged in GT. In particular, collagen-induced platelet aggregation was markedly improved in the CA patient. However, the platelet adhesion to collagen (50 μg/ml)-Sepharose remained normal, both before and after the infusion of DDAVP in CA.These results suggest that an increase in the plasma vWF level and the existence of platelet membrane GPIIb/IIIa may be necessary for the improvement of primary hemostasis, after the infusion of DDAVP. The vWF-mediated platelet aggregation by collagen or ADP may produce this effect in the CA patient.

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