Disease relevance of Bleeding Time

• In a randomized double-blind cross-over trial we gave either 1-deamino-8-D-arginine vasopressin or placebo to 12 patients with uremia, hemorrhagic tendencies, and prolonged bleeding times [1].
• Both cryoprecipitate and desmopressin effectively shorten the prolonged bleeding time and favorably influence clinical bleeding, but the former carries the risk of transmitting blood-borne infectious diseases, and both cryoprecipitate and desmopressin have a short duration of action [2].
• Importantly, PAR4-deficient mice had markedly prolonged bleeding times and were protected in a model of arteriolar thrombosis [3].
• In vivo, the lack of P2Y1 expression increased bleeding time and protected from collagen- and ADP-induced thromboembolism [4].
• In functional assays including tail bleeding time, plasma clotting times, and tissue factor- or LPS-induced disseminated intravascular coagulation models, no significant difference was found between hepsin-/- and wild-type litter mates [5].

High impact information on Bleeding Time

• However, platelet shape changes are decreased in Gsn- mice, causing prolonged bleeding times [6].
• The bleeding time doubled, indicating an occupancy of platelet thromboxane receptors of more than 95 percent [7].
• The aspirin regimen produced a selective, cumulative inhibition of platelet cyclooxygenase activity and a doubling of bleeding time [7].
• Estrogen shortened the bleeding time in all six patients [2].
• Our findings indicate that 1-deamino-8-D-arginine vasopressin can be used for temporary correction of bleeding time and may prevent surgical bleeding in patients with uremia [1].

Chemical compound and disease context of Bleeding Time

• Specimens of venous tissue from three normal subjects and three patients with renal failure and very prolonged bleeding-times showed prostacyclin-like activity (inhibition of platelet aggregation) during incubation at room temperature [8].
• Desamino-D-arginine vasopressin and bleeding time in von Willebrand's disease [9].
• Fifty-two of 55 consecutive patients with acute myocardial infarction and template bleeding times (Ivy method) of less than 9.5 minutes were treated with rt-PA in a total dose of 55-212 mg (mean, 109 mg) over 90 to 360 minutes (median, 240 minutes) combined with heparin [10].
• One hundred six patients with storage pool deficiency (SPD) were studied with respect to platelet count, bleeding time, total platelet ATP and ADP, platelet serotonin, and in vitro aggregation [11].
• Shear stress activation of platelet glycoprotein IIb/IIIa plus von Willebrand factor causes aggregation: filter blockage and the long bleeding time in von Willebrand's disease [12].

Biological context of Bleeding Time

• Thus, chlorpromazine, added to human blood at concentrations which diminish haemoylsis but do not directly affect platelet aggregation, prolonged the 'bleeding time' from small holes in artificial vessels where extravasation is terminated, as in living arterioles, by aggregated platelets [13].
• These rehydrated lyophilized platelets (RL platelets) restore hemostasis in thrombocytopenic rats and become incorporated in the hemostatic plug of bleeding time wounds of normal dogs as well as von Willebrand disease dogs with partially replenished plasma von Willebrand factor [14].
• The bleeding time was greater than 15 minutes in all patient groups and the initial bleeding, as reflected by the initial slope of the fitted blood volume curves, was increased in ITP, BSS, and SPD (delta-SPD in particular), but not in vWD and TSA [15].
• Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets [16].
• Treatment with either desmopressin acetate or cryoprecipitate normalized both bleeding time and kaolin-activated partial thromboplastin time [17].

Anatomical context of Bleeding Time

• We conclude that DDAVP causes an increase in vWF:Ag levels but does not alter platelet aggregation, bleeding time, or blood loss in uncomplicated coronary artery bypass patients [18].
• The effect of heparin on jugular vein bleeding times was also measured in a separate group of animals [19].
• The plasma vWF of each individual lacked large multimers; each had a prolonged bleeding time; and both platelet and leukocyte counts were elevated [20].
• In a cuticular bleeding time study, these animals also had only a partial correction, but in an FeCl3 carotid artery, thrombosis assay correction was equivalent to a 50% to 100% level [21].
• In contrast, beta3(-/-) mice expressing hbeta3(S752P) continued to exhibit prolonged bleeding times and dysfunctional osteoclasts in vitro and ex vivo [22].

Associations of Bleeding Time with chemical compounds

• After vasopressin infusion, all patients had shortened bleeding times, with the effect lasting for at least four hours in most cases [1].
• Ethanol potentiation of aspirin-induced prolongation of the bleeding time [23].
• The bleeding time was also prolonged by apyrase, consistent with the conclusion that the chlorpromazine acted through decreasing plasma ADP [13].
• Prolonged bleeding time associated with 'low-dose' moxalactam therapy [24].
• There is evidence that in a crossover trial of 21 patients with PAD and IC, aspirin alone, or clopidogrel alone, significantly increased bleeding times, but cilostazol alone did not [25].

Gene context of Bleeding Time

• The bleeding-time corrective factor and the ristocetin-related vWF or platelet-aggregating factor are dissociable, distinct activites [26].
• Importantly, in vWf-deficient mice, rhIL-11 also induced a significant increase in FVIII independent of vWf and was able to reduce skin bleeding time [27].
• Surprisingly, Par3(-/-) and Par4(-/-) mice showed similar degrees of protection in these models and similar prolongation of tail bleeding times [28].
• Syk null platelets adhered normally to immobilized fibrinogen, and mice with these platelets exhibited normal tail bleeding times [29].
• The ashen (ash) mouse, a model for Hermansky-Pudlak syndrome (HPS) and for a subset of patients with Griscelli syndrome, presents with hypopigmentation, prolonged bleeding times, and platelet storage pool deficiency due to a mutation which abrogates expression of the Rab27a protein [30].

Analytical, diagnostic and therapeutic context of Bleeding Time

• We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 microgram/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo [31].
• Intravenous infusion of 1.0 mg/kg streptokinase or 0.25 mg/kg recombinant staphylokinase in two groups of four baboons each given intravenous heparin (200-unit bolus and 50 units.kg-1 x hr-1) and aspirin (10 mg/kg) did not produce a significant prolongation of the median template bleeding time [32].
• The prolongation of bleeding time and the decrease of factor VIII:C and factor VIII:von Willebrand factor 90 min after treatment were significantly lower (p less than .001) in the DDAVP group as compared with the placebo group [33].
• The hemostatic abnormalities identified were restricted to tests of platelet procoagulant activity, whereas platelet count, platelet morphology under light microscopy, bleeding time, clot retraction, and platelet aggregation and secretion in response to thrombin, collagen, and adenosine diphosphate stimulation were all within normal limits [34].
• Both mutants had prolonged bleeding times accompanied by abnormalities of dense granules as determined by whole mount electron microscopy of platelets and by labeling platelets with mepacrine [35].

References