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PubMedDate not supplied

Excessive prolongation of the bleeding time by aspirin in essential thrombocythemia is related to a decrease of large von Willebrand factor multimers in plasma.

Patients with essential thrombocythemia (ET), who frequently have bleeding complications, may manifest an excessive prolongation of the bleeding time (BT) after ingestion of aspirin (ASA). The reason for this excessive prolongation of the BT is unknown, but it is attributed to qualitative platelet defects. Since patients with ET may also have acquired abnormalities of plasma and platelet von Willebrand factor (vWF), we questioned whether the excessive prolongation of the BT by ASA was related to changes in either plasma or platelet vWF. To that end, we studied BT and plasma and platelet vWF in ten ET patients, ten patients with reactive thrombocytosis (RT), and ten normal individuals, both before and after administration of 500 mg ASA for 7 days. In a second study, the effect of DDAVP infusion on plasma vWF in relation to the BT was studied in ten normal individuals and ten ET patients after treatment with 100 mg ASA for 3 days. In the first study, treatment with ASA resulted in a significant prolongation of the BT in normal subjects, RT patients, and ET patients. However, in five ET patients an excessive (> 2 SD) prolongation of the BT by ASA was observed. Although ASA induced no direct changes in either plasma or platelet vWF levels in either normal subjects, RT patients, or ET patients, all five ET patients who showed an excessive prolongation of the BT by ASA had significantly decreased levels of large vWF multimers in plasma. In the second study, infusion with DDAVP resulted in a significant increase in plasma large vWF multimers, paralleled by a normalization of (excessively) prolonged BT. Our data suggest that in ET inhibition of platelet function by ASA in the presence of concurrently decreased levels of large vWF multimers in plasma may have provoked the excessive BT prolongation.

Adult↗

PubMed2004

Template bleeding time and PFA-100 have low sensitivity to screen patients with hereditary mucocutaneous hemorrhages: comparative study in 148 patients.

OBJECTIVES AND PATIENTS: We compared the template bleeding time (BT) and closure time (CT) in the PFA-100 as screening tests in 148 consecutive patients with unequivocal mucocutaneous bleeding and positive family history. EXCLUSION CRITERIA: drug intake, concomitant diseases including minor infections, low platelet count, diseases of secondary hemostasis. RESULTS: Type 1 von Willebrand disease (VWD-1) was diagnosed in 26 patients, primary platelet secretion defect (PSD) in 33, VWD-1 + PSD in nine, whereas 80 patients did not comply with the criteria for known hemostatic disorders (UD, unknown diagnosis). BT and CT were prolonged in 35.8% and 29.7% of all the patients, respectively (P = 0.23). Sensitivity increased to 48% if an abnormality of BT and/or CT was considered. Same comparisons for BT and CT in each diagnostic category were, respectively: 42 vs. 61.5% in VWD-1 (P = 0.18), 42 vs. 24% in platelet secretion defects (P = 0.11), 67 vs. 89% in VWD-1 + PSD (P = 0.50), and 27.5 vs. 15% in UD (P = 0.06). CONCLUSION: Both tests were relatively insensitive and not significantly different in detecting incoming patients with mucocutaneous hemorrhages. In patients with VWD-1, the PFA-100 performed slightly better, whereas the opposite occurred in those patients with platelet secretion defects. In the UD group, both tests lost sensitivity, but the BT detected 1.8 times more patients than the PFA-100. Given the large proportion of undiagnosed bleeders and the overall low sensitivity of these tests, clinical decisions still rely on the medical history and etiological diagnosis of the bleeding disorder.

Bleeding Time↗

PubMed1990

Aspirin at very ultra low dosage in healthy volunteers: effects on bleeding time, platelet aggregation and coagulation.

Aspirin at very ultra low dosage was tested in healthy volunteers (n = 20) in a randomized, double-blind and placebo-controlled trial. The results showed a bleeding time reduction (p less than 0.05) in volunteers having previously ingested aspirin. Platelet aggregation on platelet-rich plasma was not statistically modified after aspirin ingestion. Thrombin clotting time was always higher (p less than 0.05) in the treated group.

Adenosine Diphosphate↗

PubMed1996

Evaluation of platelet function using the in vitro bleeding time and corrected count increment of transfused platelets. Comparison between platelet concentrates derived from pooled buffy coates and apheresis.

The functional capacity of transfused platelets was evaluated with in vitro bleeding time (IVBT) and corrected count increment (CCI) in order to compare platelet concentrates (PCs) derived from pooled buffy coats (BC-PCs) with PCs collected by apheresis (A-PCs). The suspension medium in the BC-PCs was 30% CPD plasma and 70% of an additive solution (containing sodium and potassium chloride, sodium citrate and phosphate, mannitol), and in the A-PCs the medium was 100% CPD plasma. IVBT was evaluated using a Thrombostat 4000/2. BC-PC and A-PC were transfused 57 and 41 times, respectively to 36 patients with chemotherapy-induced thrombocytopenia. PCs transfused within 2 days of donation were considered fresh, and those transfused within 3-5 days were considered stored. IVBT was determined before, as well as 10-30 min and 24 h after transfusion; CCI was determined 10-30 min and 24 h after transfusion. The median pretransfusion IVBT value was 486 s. It was measurable in 21 of 98 (21%) of the transfusions, i.e. below the cutoff limit of 486 s. Ten to 30 min after transfusion, the IVBT showed a measurable reduction in 90% of the transfusions with fresh BC-PCs, 92% of those with fresh a-PCs, 63% of those with stored BC-PCs and 79% of those with stored A-PCs. After 24 h, the corresponding values were 63% for fresh BC-PCs, 50% for fresh A-PCs, 26% for stored BC-PCs and 38% for stored A-PCs. The median value of CCI 10-30 min after transfusion was 20 for fresh BC-PCs, 17 for fresh A-PCs, 16 for stored BC-PCs and 14 for stored A-PCs. The difference in IVBT between fresh and stored BC-PCs was significant (p = 0.032), unlike that between fresh and stored A-PC. After 24 h the corresponding values were 7 for fresh BC-PCs, 4 for fresh A-PCs, 4 for stored BC-PCs and 3 for stored A-PCs. When all transfusions with fresh PCs (BC-PCs + A-PCs) were compared with all transfusions with stored PCs, a statistical difference was demonstrated in both CCI (p = 0.027) and IVBT (p = 0.043). Spearman's rank correlation coefficient (rs) was -0.41 between CCI and IVBT < 486 s 10-30 min after transfusion, and -0.55 between the posttransfusion platelet count and IVBT, indicating a relatively poor correlation between CCI and IVBT, and a slightly better correlation between platelet count and IVBT. In conclusion, BC-PCs showed a slightly higher CCI and a better response in IVBT than A-PCs. No statistical difference was demonstrated between BC-PCs and A-PCs transfused within 2 days after donation, with respect to function and recovery in vivo. BC-PCs stored for 3 days or more showed about the same CCI and IVBT as stored A-PC but significantly lower CCI and higher IVBT than fresh BC-PCs. This may indicate that the preparation and/or storage conditions were not optimal. IVBT seems to be a useful possibility to test the in vivo behavior of transfused platelets.

Adolescent↗

PubMed1981

Impaired platelet aggregation and increased bleeding time during general anaesthesia with halothane.

A significant correlation was found between the inhibition produced by 1% halothane with nitrous oxide and oxygen on platelet aggregation in vitro and the increase in bleeding time during anaesthesia with halothane, nitrous oxide and oxygen in 10 patients. It is suggested that halothane in nitrous oxide with oxygen inhibits platelet aggregation in vivo and in vitro. The inhibition is not seen when platelet aggregation is studied in platelet-rich plasma from anaesthetized patients because the agents evaporate during preparation of platelet-rich plasma and during analysis in the aggregometer.

Anesthesia, Inhalation↗

PubMed1984

Prolonged bleeding time associated with moxalactam administration.

A case of moxalactam-induced coagulopathy is reported. The authors think that this coagulopathy is caused by an effect on platelet aggregation and not by inhibition of vitamin K-dependent clotting factors. It is recommended that bleeding times be routinely checked preoperatively in patients being treated with moxalactam.

Bleeding Time↗

PubMed2002

Desmopressin in the treatment of menorrhagia in women with no common coagulation factor deficiency but with prolonged bleeding time.

The objective of this study was to investigate the efficacy and safety of desmopressin (1-desamino-8-D-arginine vasopressin) compared with placebo in the reduction of menstrual blood loss in women with menorrhagia and prolonged bleeding time, but without common coagulation factor deficiencies. We performed a randomized, double-blind, cross-over study using 300 microg desmopressin nasal inhalation or placebo treatment in one of the two first treatment cycles. Desmopressin was given only for the 2 days during which the bleeding had been at a maximum in the previous baseline cycle. A third open cycle involved combined treatment with desmopressin and tranexamic acid during the 2 days for all patients. Menstrual blood loss during the treatment periods was compared with blood loss during placebo-treated periods using objective measurement. A significant reduction of menstrual blood loss was found in the cycles treated with combined desmopressin and tranexamic acid compared with placebo. When analyzing the blood loss during the two treatment days, there was a significant reduction in blood loss for the 2 days with desmopressin alone versus placebo. The treatment was well tolerated and no serious adverse events were recorded. In conclusion, we find that nasal desmopressin is a possible complement for the medical treatment of menorrhagia.

Adult↗

PubMed1990

Fluoxetine and the bleeding time.

Fluoxetine (Prozac) is a nontricyclic serotonin (5-hydroxytryptamine) reuptake inhibitor commonly prescribed for the treatment of depression. Fluoxetine also blocks 5-hydroxytryptamine reuptake in platelets and could potentially lead to clinically significant platelet dysfunction. We describe a patient who developed petechiae and prolongation of the bleeding time while receiving fluoxetine therapy.

Adult↗

PubMed1986

Prolongation by warfarin of "template" bleeding time in rats: a vitamin K-dependent effect.

Administration of warfarin to rats induced not only the well-known anticoagulant effect, but also an impairment of primary hemostasis as reflected by a significant prolongation of the "template" bleeding time. This effect was very closely associated with lowering of the prothrombin complex level and was reversed by administration of vitamin K. It is suggested that some of the clotting factors known to be vitamin K-dependent also play a role in primary hemostasis; alternatively, a putative vascular "bleeding factor" could be modulated by vitamin K availability.

Animals↗

PubMed1987

Effect of a moderate fish intake on blood pressure, bleeding time, hematology, and clinical chemistry in healthy males.

This paper describes the outline and first results of an international study to investigate the effect of a reasonable amount of dietary fish on some aspects of cardiovascular risk. In Maastricht and Zeist, The Netherlands, and Tromsø, Norway, healthy male volunteers were given a dietary supplement consisting of 100 g/d of mackerel or meat for a 6-wk period. Compliance was monitored on the basis of the urinary excretion of lithium, which was added to the supplements. Average compliance was approximately 80% and this decreased slightly in time. Systolic blood pressure decreased in both groups to a comparable degree; consequently no specific effect of the fish supplement was observed. The fish supplement significantly prolonged bleeding times. Hematology was hardly affected but platelet counts decreased significantly. No indications were obtained for adverse effects of the fish supplement.

Adult↗

PubMed1996

Molecular markers near the mouse brachymorphic (bm) gene, which affects connective tissues and bleeding time.

Several inherited skeletal/connective tissue defects are associated with hemorrhagic disorders in humans. Accordingly, three mouse mutants (brachymorphic [bm], hemimelic extra toes [Hx], and ulnaless [Ul]), with inherited skeletal abnormalities, were analyzed for hemorrhagic tendencies. All three had prolonged bleeding times. Platelet numbers, size, and function, as well as common soluble plasma clotting factors, were not measurably affected. To further define the bm mutation, its chromosomal location relative to 19 other molecular markers was determined to a high resolution in a large interspecific backcross. Several microsatellite markers were found to be very closely linked to bm and should provide useful entry points for the eventual identification of this gene by positional/candidate cloning techniques. These results suggest that inherited skeletal abnormalities and bleeding tendencies are associated more frequently in both humans and animal models than is commonly recognized. Identification of these genes may reveal novel relationships between osteogenesis and hemostasis.

Animals↗

PubMed1987

Effect of low molecular weight heparin on coagulation parameters and bleeding time in healthy volunteers.

In a randomized intraindividual cross-over study 8 healthy volunteers received subcutaneously 1500 IU, 2000 IU and 25,00 IU, respectively, of low molecular weight heparin (LMWH) in 24-h intervals, as well as 12-hourly 3 applications of 5000 IU of unfractionated heparin. The wash-out phases between the different medications lasted 7 days each. The course of the activated partial thromboplastin time showed no difference between the medications given, whereas the inhibition of factor Xa was significantly stronger after application of all dosages of LMWH than after unfractionated heparin injections. Bleeding time was prolonged only under 1500 IU of LMWH as compared to heparin. Neither LMWH nor unfractionated heparin caused an influence on the antithrombin III levels.

Antithrombin III↗

PubMed1987

Correction of the bleeding time in treated patients with severe von Willebrand disease is not solely dependent on the normal multimeric structure of plasma von Willebrand factor.

Even though it is generally held that cryoprecipitate and fraction I-O correct the prolonged bleeding time (BT) in patients with von Willebrand disease (VWD), perusal of reported data indicates that the correction is usually short-lasting and often partial. We decided to do a controlled study of the relationship between the multimeric structure of von Willebrand factor (VWF) and the BT in five patients with severe (type III) VWD after infusion of three plasma concentrates ("wet" cryoprecipitate, lyophilized cryoprecipitate, and fraction I-O) given in random order. The dosage of concentrates was tailored from in vitro measurements to achieve post-infusion levels of ristocetin cofactor above the lower normal limit (50 U/dL) for at least 3 hours. The postinfusion BT became transiently normal in only two of five patients treated with wet cryoprecipitate, whereas it remained prolonged in all five patients treated with lyophilized cryoprecipitate or fraction I-O. For all the concentrates, the proportion of large VWF multimers calculated by scanning the electrophoretic gels were the same as those for normal standard plasmas. An intact multimeric structure was recovered in postinfusion plasmas of patients treated with wet cryoprecipitate, whereas there was a postinfusion loss of large multimers after lyophilized cryoprecipitate and fraction I-O. These findings indicate that the attainment of a normal BT is the exception rather than the rule after the infusion of three plasma fractions used in the treatment of severe VWD, and that an intact multimeric structure in concentrates and postinfusion plasmas is necessary but not sufficient to sustain a normal BT.

Bleeding Time↗

PubMed1991

Evaluation of the buccal bleeding time and platelet glass bead retention as assays of hemostasis in the dog: the effects of acetylsalicylic acid, warfarin and von Willebrand factor deficiency.

The study evaluated two hemostatic assays in the dog, a modified version of the buccal mucosal bleeding time (BMBT) and the platelet glass bead retention (PR), to describe the aspects of hemostasis measured by these assays. Von Willebrand factor (vWf)-deficient Doberman pinscher dogs were used in evaluating the effects of altered platelet adhesion. Normal dogs were treated with either acetylsalicylic acid (ASA) or warfarin to evaluate the effects of altered platelet aggregation and coagulation. There was significant prolongation of the BMBT and reduction of the PR in vWf-deficient dogs as compared to normal dogs. In ASA treated dogs the BMBT was slightly prolonged; the PR was significantly reduced. The change in ASA-induced BMBT did not correlate with the sensitivity of the dog platelets to arachidonic acid. In warfarin treated dogs there was no change in the BMBT; however, the PR was significantly reduced. The BMBT is a test of hemostasis that is sensitive to platelet adhesion and aggregation deficits. The PR is useful in detecting general abnormalities in hemostasis including platelet adhesion defects due to reduced vWf.

Animals↗

PubMed1991

The decreased circulating platelet mass and its relation to bleeding time in chronic renal failure.

The mean platelet volume, measured optically and by the electrical impedance method, was analysed in the patients with chronic renal failure. All parameters describing the circulating platelet biomass except the platelet volume heterogeneity were decreased in these patients. There is a strong inverse relation between the Ivy bleeding time and the platelet mass in the patient group. Our results indicate that the smaller platelets circulating in the patients with chronic renal failure may contribute to the uremic bleeding diathesis, and disturbed thrombocytopoiesis occurs in chronic renal failure.

Adult↗

PubMed1984

The haemostatic plug in haemophilia A: a morphological study of haemostatic plug formation in bleeding time skin wounds of patients with severe haemophilia A.

Haemostatic plug formation in four patients with severe haemophilia A (VIII:C less than 1%) was studied in skin biopsies taken at 3, 10 and 30 min and 2 h after a template bleeding time wound had been made. The primary haemostatic plug showed relatively minor changes, consisting of a delay in platelet degranulation and interdigitation. Some platelet aggregates not attached to vessels were encountered in the wound. Subsequently the primary haemostatic plug changed into a firm stable degranulated mass of interdigitated platelets. The major abnormality occurred during the fibrinous transformation. At 2 h many haemostatic plugs consisted of a thin peripheral layer of fibrin and platelet remnants around a central area containing red and white blood cells with a varying amount of plasma and only relatively few fibrin fibres. These observations suggest that fibrin formation in the periphery of the plug is less dependent of factor VIII than in central areas. The lack of fibrin formation in the centre of the plug compensating for the platelet lysis at 2 h may have caused the central erosion of the plug.

Adult↗

PubMed1996

Effects of inogatran, a new low-molecular-weight thrombin inhibitor, in rat models of venous and arterial thrombosis, thrombolysis and bleeding time.

Inogatran (MW 439 Da), a new, selective, active site inhibitor of thrombin, was evaluated in three rat models of thrombosis. In the venous thrombosis model, inogatran dose-dependently inhibited thrombus formation with a > 80% antithrombotic effect at a plasma concentration of 0.45 mumol l-1. In the arterial thrombosis model, inogatran dose-dependently inhibited thrombus formation, preserved vessel patency and the mean blood flow. Acetylsalicylic acid (ASA) potentiated the effects of low plasma concentrations of inogatran in the arterial thrombosis model. In the model of rt-PA-induced thrombolysis of a thrombus in the carotid artery, inogatran improved the patency time and the cumulative blood flow during the two hour thrombolysis period more than rt-PA alone. At high therapeutic plasma concentration of inogatran, there was only a moderate prolongation of bleeding time compared with the control value. It is concluded that inogatran is an effective antithrombotic agent both in the venous and arterial thrombosis models and also as adjuvant to rt-PA in the thrombolysis model.

Animals↗

PubMed1991

Prolonged bleeding time as a marker of venous clot lysis during streptokinase therapy.

Despite their expense and inconvenience, serial ultrasound or venographic examinations are currently the only available methods to assess the efficacy of thrombolysis for deep venous thrombosis (DVT). We therefore tested whether the bleeding time (BT), a simple and inexpensive test, is useful in assessing lytic efficacy and might thus be a valuable adjunct in guiding the dose and duration of the thrombolytic agent. Serial BTs were obtained daily in 16 patients (eight men and eight women, average age 45.5 years, range 19 to 70) receiving streptokinase (SK) for proximal lower extremity DVT (n = 5), for upper extremity DVT (n = 10), or for renal vein thrombosis (n = 1). Duration of treatment averaged 89.9 +/- 43.6 hours (range 35 to 198 hours). Clot lysis on ultrasound, venogram, or magnetic resonance imaging (MRI) was defined as: complete (greater than or equal to 90%), moderate (50% to 90%), minimal (less than 50%), or none. Important (complete or moderate) clot lysis occurred in 9 of 15 patients for whom follow-up studies were available. BT prolongation was defined as greater than 9.5 minutes and, during SK therapy, had a sensitivity of 0.67 and a specificity of 0.67 for important clot lysis. The positive predictive value of prolonged BT for clot lysis was 0.75. Calculated likelihood ratios revealed that a patient with BT prolongation was twice as likely to have important clot lysis rather than minimal or no lysis. These findings suggest that the BT should undergo further investigation as a simple, adjunctive, noninvasive marker of thrombolytic efficacy among DVT patients treated with SK.

Adult↗