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PubMed1999

Modifications in accessibility of membrane glycoproteins, binding of specific ligands and coagulation factor V during the activation of platelets in blood emerging from bleeding time wounds.

Dual color flow cytometric techniques were applied to micro-aliquots of whole blood obtained from bleeding time (BT) wounds. Modifications in platelet activation markers (P-selectin [CD62P]) and lysosomal related protein (UMPS [CD63]), presence of membrane glycoproteins (GPIb [CD42b], GPIIb-IIIa [CD41a], GDIV [CD36], binding of von Willebrand factor (vWF), fibrinogen (Fg) and factor V [FV]) were analyzed in normal donors (n = 10) and in a severe von Willebrand patient (type 3) von Willebrand disease [vWD]). Samples of blood (20 microl) were sequentially removed from BT wound edges for up to 5 min and fixed with paraformaldehyde. Antigens were detected using the corresponding tagged monoclonal antibodies (moAbs) and quantitative results were referred to those found on platelet samples obtained from venous blood obtained from the same individuals. A progressive increase in % of platelets positive for activation dependent antigens (CD62 from 7 +/- 2 to 48 +/- 19% and CD63 from 9 +/- 1 to 44 +/- 8%; initial vs. 4 min) was observed. Accessibility of GPIIb-IIIa epitopes on platelets from BT wounds remained slightly above levels observed in venous blood platelets, despite a progressive increase in the presence of platelets positive for Fgn. Binding of MoAb to GPIV increased at late stages of BT. A moderate decrease in the binding of a moAb to GPIb was observed on platelets obtained at late stages of the BT (14 +/- 9% and 20 +/- 6% at 4 and 5 min, respectively). This apparent decrease in GPIb epitopes paralleled an increased presence of platelets positive for vWF (26 +/- 12 and 38 +/- 15%). Binding of moAb to GPIb always remained above basal levels in platelets obtained from BTs performed in the patient with type 3 vWD. FV levels on platelets coming from the BT persisted at background levels in all the individuals and at all times studied.

Antibodies, Monoclonal↗
PubMed1985

[The role of erythrocyte deformability in the prolonged bleeding time in liver disease patients].

Hematocrit (Ht), red cell deformability (RCD) determined using a filtration method and bleeding time (BT) have been studied in 28 patients with severe chronic liver disease. Our results show a decrease of Ht (p less than 0.001), RCD (p less than 0.05) and a prolongation of BT (p less than 0.001) not related to the platelet count. Moreover, inverse relationships between Ht and BT (r = -0.52; p less than 0.01) and between RCD and BT (r = -0.54; p less than 0.01) have been found. We conclude that hemorheological alterations, such as decreased Ht and RCD, play an important role in primary hemostasis of patients with chronic liver disease.

Adult↗
PubMed2001

Platelet count may predict abnormal bleeding time among pregnant women with hypertension and preeclampsia.

BACKGROUND: Anesthesiologists often require laboratory data to estimate the bleeding risk among hypertensive pregnant women prior to administering regional anesthesia. Many rely on the bleeding time (BT) in making this determination. We examined whether the platelet count can adequately predict BT among a group of hypertensive parturients. METHODS: This retrospective subgroup analysis, taken from a cohort of 2,051 hypertensive pregnant women, comprises 87 individuals who underwent both a BT and platelet count prior to delivery. We calculated the correlation between the platelet count and BT at three platelet cut-off points with respect to prolonged BT of eight minutes or more. RESULTS: There was a significant negative correlation between platelet count at delivery and BT [r= -0.45, 95% confidence interval (CI) -0.26 to -0.60; P <0.0001]. All three platelet cut-off points had a sensitivity of less than 66% with negative predictive values below 75% for an abnormal BT. A platelet count > or =75 x 109/L [corrected] was specific for the presence of an abnormal BT (specificity 97.8%, 95% CI 91.7-100.0), with a positive predictive value of 95.5% (95% CI 83.1-100.0) and a positive likelihood ratio of 24 (95% CI 3.3-168). CONCLUSIONS: In a group of hypertensive parturients, the platelet count appears to be very specific for predicting a prolonged BT The platelet count may aid the anesthesiologist in determining the risk of bleeding from regional anesthesia. Given the study's potential for bias future research is needed to validate these findings.

Adult↗
PubMed1990

Acquired von Willebrand disease associated with free lambda light chain monoclonal gammopathy, normal bleeding time and response to prednisone.

We report a case of acquired von Willebrand's syndrome with severe gastrointestinal bleeding and associated free monoclonal lambda light chains. The patient had a rapid sustained clinical and laboratory response to the administration of prednisone. Of note in this patient was the occurrence of angiodysplasia which has previously been reported in association with acquired von Willebrand's syndrome. No inhibitors of VWF:Ag, VWF:RCoF, or factor VIII:C were detected by mixing studies and the bleeding time was normal. Very few high molecular weight von Willebrand multimers were present prior to prednisone; however, the pattern reverted to a normal distribution following treatment. In appropriate patients with acquired von Willebrand's syndrome and monoclonal para-proteins, a trial of prednisone may be indicated.

Bleeding Time↗
PubMed2005

Screening women with menorrhagia for underlying bleeding disorders: the utility of the platelet function analyser and bleeding time.

Menorrhagia is a very common clinical problem among women of reproductive age and recent studies have suggested that underlying bleeding disorders, particularly von Willebrand's deficiency and platelet function defects, are prevalent in women presenting with menorrhagia. The objective of this study was to determine the utility of the platelet function analyser (PFA-100) and bleeding time (BT) as initial screening tests for underlying bleeding disorders in women with menorrhagia. In this study, 81 women with a physician diagnosis of menorrhagia underwent PFA-100 testing, BT and comprehensive haemostatic testing. The effectiveness of the PFA-100 and BT as screening tools in women with menorrhagia was assessed using results of haemostatic testing for von Willebrand's disease (VWD) and platelet dysfunction. In women presenting with menorrhagia, the PFA-100 had a sensitivity 80%, specificity 89%, positive predictive value (PPV) 33%, negative predictive value (NPV) 98% and efficiency 88% for VWD. For platelet aggregation defects, the PFA-100 closure time had a sensitivity 23%, specificity 92%, PPV of 75%, NPV of 52% and efficiency 55%. The data suggest that the PFA-100 may be useful in stratifying women with menorrhagia for further von Willebrand testing; however, neither the PFA-100 nor the BT tests are effective for purposes of classifying women for standard platelet aggregometry testing in women presenting with menorrhagia.

Adolescent↗
PubMed1987

Aspirin prolongs bleeding time in uremia by a mechanism distinct from platelet cyclooxygenase inhibition.

We reported that aspirin (ASA) abnormally prolongs bleeding time (BT) in uremia. The present study was designed to investigate whether the abnormally prolonged post-ASA BT in uremia is due to different ASA pharmacokinetics and bioavailability that might be a consequence of uremic condition, platelet cyclooxygenase is peculiarly sensitive to ASA in uremia, and ASA affects primary hemostasis in uremia by a mechanism independent of cyclooxygenase inhibition. Our results showed that in patients with uremia, but not in normal subjects, ASA markedly prolongs the BT. This effect is transient and depends on the presence of ASA in the blood. The observed differences in ASA kinetic parameters are not an explanation of the exaggerated effect of ASA on primary hemostasis in uremia. The sensitivity of platelet cyclooxygenase to ASA inhibition is comparable in uremics and in normal subjects. The temporal dissociation between ASA-induced prolongation of BT and the effect on platelet thromboxane A2 generation suggests that ASA inhibits platelet function in uremia by a mechanism distinct from cyclooxygenase blocking. This possibility is strengthened by the observation that ibuprofen at a dose that fully inhibits platelet cyclooxygenase activity does not significantly prolong BT.

Acetylation↗
PubMed1992

The bleeding time in normal subjects is mainly determined by platelet von Willebrand factor and is independent from blood group.

Bleeding time (BT) is the most important test "in vivo" evaluating the primary hemostasis. No relationship between plasma von Willebrand factor (vWF) and BT has been found in normal subjects, whereas no data are available on the relationship between platelet vWF and blood group or BT in normal subjects. To clarify the reciprocal relationship between blood group, vWF and BT, we studied 177 normal subjects. The influence of blood group on BT was analyzed in 116 subjects and the distribution of platelet and plasma vWF between different blood groups in 111 subjects. Furthermore, in a subgroup of 50 subjects, a multivariate regression model, including age, platelet count, plasma and platelet vWF:Ag and Ristocetin Cofactor (RiCof), hematocrit, sex and O or non-O blood group was used to assess the joint influence of these variables on BT. BT was similar in O and non-O group (P = 0.310) and, although plasma vWF was significantly lower in O group (P less than 0.0001), platelet vWF content was similarly distributed (P = 0.873 vWF:Ag and P = 0.322 RiCof). Furthermore, platelet vWF was not correlated with plasma vWF (r = 0.06, P = 0.526). In the multivariate regression analysis, only platelet vWF, age and platelet count showed a significant, inverse correlation with BT (P = 0.004), explaining 25% of the total variation of this test. Platelet vWF resulted therefore the main determinant of BT.

Adolescent↗
PubMed1992

The d-enantiomer form of indobufen totally accounts for the anti-cyclooxygenase and antiplatelet activity ex vivo and for the increase in bleeding time by indobufen in man.

Indobufen is an antiplatelet drug able to inhibit thromboxane production and cyclooxygenase-dependent platelet aggregation by a reversible inhibition of cyclooxygenase. Indobufen exists in two enantiomeric forms, of which only d-indobufen is active in vitro in inhibiting cyclooxygenase. In order to verify that also inhibition of platelet function is totally accounted for by d-indobufen, ten patients with proven coronary artery disease (8 male, 2 female, age, mean +/- S.D., 58.7 +/- 7.5 years) were given, in random sequence, both 100 mg d-indobufen and 200 mg dl-indobufen as single administrations in a double-blind crossover design study with a washout period between treatments of 72 h. In all patients thromboxane (TX) B2 generation after spontaneous clotting (at 0, 1, 2, 4, 6, 8, 12, 24 h), drug plasma levels (at the same times), platelet aggregation in response to ADP, adrenaline, arachidonic acid, collagen, PAF, and bleeding time (at 0, 2, 12 h) were evaluated after each treatment. Both treatments determined peak inhibition of TXB2 production at 2 h from administration, with no statistical difference between the two treatments (97 +/- 3% for both treatments). At 12 h inhibition was 87 +/- 6% for d-indobufen and 88 +/- 6% for dl-indobufen (p = NS). Inhibition of TXB2 production correlated significantly with plasma levels of the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Hereditary thrombocytopenia with excessively prolonged bleeding time, corrected by infusions of platelet poor plasma.

In a family with hereditary thrombocytopenia, transfused normal platelets as well as their own platelets had a shortened survival in the patients' circulation (11). On the other hand, the patients' platelets survived normally when transfused to a normal recipient. Platelet-associated immunoglobulins or circulating platelet antibodies were not detected (immunofluorescence method). About 200 ml platelet poor plasma (PPP) from each of 4 normal donors was infused daily for 5 consecutive d to 1 afflicted family member, causing a rise of platelet count from 65 X 10(9)/l to 163 X 10(9)/l and a decrease of bleeding time from 28 to 11 min 7 d after the PPP was discontinued. The platelet count then gradually decreased and was 65 X 10(9)/l with a bleeding time of 30 min 16 d after the PPP was discontinued. In a repeated PPP infusion experiment a similar response was evoked. It is concluded that the afflicted family members must have a deficiency of some plasma principle necessary to keep platelets fit and circulating.

Antibodies↗
PubMed1995

DDAVP's shortening of the bleeding time seems due to plasma von Willebrand factor.

The pathomechanism of desmopressin (DDAVP) dependent shortening of the acetylsalicylic acid (ASA) prolonged bleeding time (BT) is still unclear. The mechanism of action is supposed to be related to the plasma levels of von Willebrand factor (vWf), but a platelet effect is also discussed. We tried to investigate whether this effect of DDAVP might be due to either plasma vWF or platelets or both. We measured the effect of DDAVP (0.4 micrograms/ml bw in 250 ml 0.9% NaCl) on the Thrombostat 4000 (in vitro bleeding test (IVBT)) after each of 16 volunteers ingested 100 mg of ASA twice. To measure the possible effect of DDAVP on plasma and platelets separately, a mixture of 800 microliters of platelet poor plasma (PPP) or 200 microliters of isolated platelets after DDAVP, respectively, was prepared and the IVBT monitored. Two hundred microliters of PPP or platelets, respectively, served as a control. In an additional experiment, vWF concentrate (12 U/ml) dissolved in 200 microliters of PPP after ASA ingestion, as described above, was added to 800 microliters of citrated whole blood from the same volunteers. The addition of PPP after DDAVP as well as the PPP or PRP after ASA enriched with vWf led to a significant shortening of the IVBT in comparison to the control, indicating that the effect of DDAVP on the prolonged BT seems to be an isolated effect of plasma vWf. By adding platelets we were not able to show a direct effect of DDAVP on platelets.

Adult↗
PubMed1989

Hermansky-Pudlak syndrome: correction of bleeding time by 1-desamino-8D-arginine vasopressin.

The effect of the synthetic vasopressin derivative 1-desamino-8D-arginine vasopressin (DDAVP = desmopressin) on bleeding time was studied in three patients with Hermansky Pudlak syndrome. A good response was observed in this type of storage pool disease. DDAVP might be useful in managing the bleeding disorder found in patients with the Hermansky-Pudlak syndrome.

Adolescent↗
PubMed1987

Buccal mucosa bleeding times of healthy dogs and of dogs in various pathologic states, including thrombocytopenia, uremia, and von Willebrand's disease.

The buccal mucosa bleeding time (BMBT; duration of hemorrhage from standardized cuts made with a spring-loaded disposable device in the mucosal surface of the upper lip) was used to evaluate the hemostatic competence of dogs. The mean (+/- SD) BMBT for 34 healthy dogs was 2.62 +/- 0.49 minutes. The BMBT of healthy dogs anesthetized with halothane or tranquilized with xylazine were not significantly different from the BMBT of healthy dogs evaluated without chemical restraint. The BMBT was significantly (P less than 0.01) prolonged 21 hours after aspirin (10 mg/kg of body weight) was administered orally to 10 healthy dogs; however, the mean aspirin-induced increase in BMBT was only 0.40 minutes. The BMBT of 28 of 30 dogs with various diseases not traditionally associated with hemostatic deficiencies were near or within the range of BMBT for healthy dogs; however, 2 dogs had BMBT of greater than 8 minutes. In contrast, BMBT were prolonged in most dogs with diseases known to induce deficient primary hemostasis; the 3 dogs with thrombocytopenia (less than or equal to 20,000 platelets/microliter), the 7 Doberman Pinschers with von Willebrand's disease (von Willebrand factor antigen; less than or equal to 18 U/dl), and 5 of the 6 dogs with severe azotemia (serum urea nitrogen; greater than or equal to 124 mg/dl) had prolonged BMBT. The BMBT of 16 dogs were determined immediately before they were subjected to various surgical procedures, and the severity of the hemorrhage encountered during these procedures was subjectively evaluated; the amount of hemorrhage from 12 of the 16 dogs was considered to be appropriate for the corresponding surgical procedures, but the remaining 4 dogs bled excessively during surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Prolonged bleeding time in Aleutian mink associated with a cyclo-oxygenase-independent aggregation defect and nucleotide deficit in blood platelets.

A prolonged mean template bleeding time of 13 minutes was present in nine Aleutian mink affected with Chediak-Higashi syndrome (CHS) compared with 4 minutes in dark control mink. The concentrations of blood platelets in normal and affected animals did not differ significantly. However, in mink with CHS, a marked disturbance of platelet response to collagen was present. Administration of aspirin and indomethacin completely blocked CH platelet response to collagen. Blood platelet adenosine triphosphate and adenosine diphosphate values from mink with CHS were significantly less than those of normal mink, and the platelet adenosine triphosphate/adenosine diphosphate ratios were 10.31 in affected mink and 2.74 in normal mink. These findings are consistent with our previous investigations in affectd cattle and persons and indicate that a "storage pool disease" of platelets exist in the mink with CHS.

Adenine Nucleotides↗
PubMed1979

[Comparative study on peroperative bleeding time in tonsillectomy performed according to 2 methods: Sluder's and Popper's].

The authors tried to find out of there was a difference in bleeding time during tonsillectomy by using the Popper and Sluder guillotine. They took three groups of children: one where the tonsils have been removed with both of the guillotines, then a group where only a Sluder was used, and the third group where only the Popper was used. After study of the results, one could only find out that there was no difference between the two instruments. But the authors proposed a tonsillectomy in children only by dissection.

Bleeding Time↗
PubMed1995

Prolonged bleeding time during ciprofloxacin therapy.

Ciprofloxacin is a broad spectum quinolone antibiotic. Side effects reported include nausea and other gastrointestinal symptoms; skin and musculoskeletal side effects may also occur. No bleeding abnormalities or alteration in coagulation have been documented. We report a case where ciprofloxacin appeared to contribute to an idiosyncratic prolongation of bleeding time although a rechallenge 8 months later did not reproduce the effect. Moreover, subsequent investigation of the influence of ciprofloxacin on bleeding parameters in 10 healthy volunteers demonstrated no alterations in bleeding parameters.

Administration, Oral↗
PubMed1994

von Willebrand factor is not altered in azotemic dogs with prolonged bleeding time.

The effects of azotemia on von Willebrand factor (vWf) plasma concentration, structure, and function were studied by utilizing canine models for both uremic bleeding and type I vWf deficiency (vWd). Seventy-five percent to 80% renal mass reduction in eight mixed-breed dogs induced marked azotemia (blood urea nitrogen [BUN] 103 +/- 7 mg/dl [mean +/- SEM]; creatinine 5.8 +/- 1 mg/dl) and prolonged mean buccal mucosal bleeding time (BMBT) from 1.8 +/- 0.2 minutes to 7.0 +/- 0.4 minutes. The mean vWf plasma concentration increased from 0.88 +/- 0.11 U/ml to 1.26 +/- 0.14 U/ml. The pre- and postsurgical sodium dodecyl sulfate-agarose gel electrophoresis multimeric patterns were similar in all dogs. Administration of cryoprecipitate from pooled azotemic mixed-breed dog plasma to five Doberman pinschers with type I vWd increased the mean plasma vWf from 0.14 +/- 0.01 U/ml to 0.48 +/- 0.04 U/ml and decreased the BMBT from 7.1 +/- 0.6 minutes to 3.14 +/- 0.09 minutes. After renal mass reduction, five type I vWd Dobermans developed marked azotemia (BUN 79 +/- 8.6 mg/dl; creatinine 3.7 +/- 0.6 mg/dl) and prolonged BMBT (16.1 +/- 3.6 minutes). Findings in the eight azotemic mixed-breed dogs indicated that (1) vWf plasma levels were normal to increased in azotemic dogs; (2) vWf structure and multimeric distribution were not altered in canine azotemia; and (3) vWf was functional when placed in a non-azotemic environment. The prolongation of the BMBT in azotemic vWd dogs indicated that factors other than alteration of vWf function were responsible for the prolonged BMBT in canine azotemia.

Animals↗
PubMed1993

[Prolongation and normalization of bleeding time during therapy with different doses of acetylsalicylic acid].

The present study investigated whether there is a statistically significant correlation between platelet aggregation inhibition (TAI) and prolongation of subaqueous bleeding time (SBT) under therapy with 40 mg (n = 20) and 500 mg (n = 20) acetylsalicylic acid (ASA) daily and when parameters return to normal after discontinuation of long-term (4 weeks) and short-term (1 week) treatment. The results of this study may be helpful in clinical practice when deciding upon indications for certain operative or anaesthetic procedures. RESULTS. Under ASA treatment, neither TAI nor prolongation of SBT was dependent on dosage or time (Figs. 1-4). After discontinuation of ASA, platelet aggregation returned to normal 1-4 days later than SBT, depending on the dosage and duration of medication. SBT declined to its initial value on the 3rd day following discontinuation of ASA in both dosage groups (Figs. 2 and 4). Normalisation of platelet aggregation depended on dosage: in those groups with 40 mg ASA, thrombocyte aggregation had normalised on the 4th day irrespective of duration of medication; in groups with 500 mg aggregation capacity was completely restored on the 5th day after 1-week therapy and on the 7th day after 4-week therapy (Figs. 1 and 3). Considering these results, an important factor is the time of discontinuation of ASA intake. Prior to scheduled operative procedures or regional anaesthetics near the spinal cord, ASA should be discontinued, depending on the dosage, 2-3 days ahead. At this time SBT has reached the initial value, however, the aggregation capacity of thrombocytes is still reduced for a few days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗