Current practices of bleeding time in a developing country: an alert for noncompliance with the standard procedures.

INTRODUCTION: Bleeding time is still widely performed in many developing countries including Thailand. To generate an accurate result, the procedure should be complied with standard recommendations such as those from Clinical and Laboratory Standards Institute (CLSI) and World Federation of Hemophilia (WFH). The authors surveyed the current practices of bleeding time in Thailand in order to verify the practices that did not comply with the accepted standard. METHODS: The questionnaires were sent to hospitals participating Thailand National External Quality Assessment Scheme (NEQAS) for blood coagulation. Items in the questionnaire comprised information about preanalytical, analytical, and postanalytical issues of bleeding time. RESULTS: From a dispatch of 201 questionnaires, 155 (77.1%) were returned. The common noncompliance with standards observed in this survey included inappropriateness of indication, e.g. use for preoperative screening (95 of 126, 75.4%), use of devices other than standard template (130 of 132, 98.5%), and inappropriate reference range (125 of 127, 98.4%). CONCLUSIONS: The noncompliance shown in this survey can affect the accuracy of bleeding time results. The authors would like to address these problems as an alert for other laboratories especially in the developing countries where the standard templates are not widely available.

Aspirin resistance: focus on clinical endpoints.

INTRODUCTION: Via its antiplatelet effect, aspirin reduces the odds of an arterial thrombotic event in high-risk patients by approximately 25%. However, 10% to 20% of patients with an arterial thrombotic event who are treated with aspirin have a recurrent arterial thrombotic event during long-term follow-up. Nevertheless, the effectiveness of aspirin has been questioned by the emergence of the concept of aspirin resistance, which has been introduced as an explanation of the fact that a considerable proportion of patients treated with aspirin exhibit normal platelet function. OBJECTIVES AND METHODS: We systematically reviewed all available evidence till March 2008 on prevalence of aspirin resistance and its association with clinical outcome. We also collected articles showing the possible way of treatment. CONCLUSION: Analyzing the data of different laboratory methods aspirin resistance seems to be associated with poor clinical outcome, although currently no standardized or widely accepted definition of aspirin resistance exists. The widely used laboratory methods might not be comparable with each other; therefore, specific treatment recommendations for patients who exhibit high platelet reactivity during aspirin therapy or who have poor platelet inhibition by aspirin are not established.

Poor reproducibility of template bleeding time in horses.

BACKGROUND: Template bleeding time (TBT) is considered to be a useful test for detecting platelet function disorders and the effect of platelet-activating drugs, but studies in human medicine have concluded that the test has poor reproducibility and sensitivity. HYPOTHESIS: TBT has poor reproducibility in horses and has insufficient sensitivity to detect the effect of etamsylate on platelet function. ANIMALS: Twenty healthy horses. METHODS: TBT was determined and repeated 2 hours and 30 days later. TBT was also performed 2 hours after IV administration of etamsylate. RESULTS: Although no statistical differences were seen between the TBT values obtained at different times, the coefficients of variation for TBT replicates ranged from 26.8% to 45.5%. The reference range for TBT was 138.4-860.4 seconds. No statistically significant shortening of the mean TBT value was observed after etamsylate administration. CONCLUSION AND CLINICAL IMPORTANCE: TBT has poor reproducibility, and the reference range is too wide to make TBT useful in a clinical setting. Other tests with higher reproducibility should be considered when assessing platelet function disorders in horses.

[Sampling variables in examinees--skin site differences in the measurements of bleeding time and self-monitoring of blood glucose].

Differences in bleeding time and self-monitoring blood glucose (SMBG) level at various skin sites have been scarcely examined in humans. The within-run variation (n=6) of bleeding time in earlobes (Duke's method) ranged from 1 min to 3 min and 30 sec (mean = 1 min and 40 sec), and in day-to-day variation (n= 8), it ranged from 1 min to 3 min (mean = 1 min and 36 sec). Site difference in bleeding time was speculated. In SMBG, firstly, sequential measurement of blood collected from 10 sites in the left forearm was performed, and secondly, comparative measurements of venous blood and blood from finger tips (1-5th), palm (3 sites), forearm (4 sites) and earlobe (1 site) were sequentially performed within 30 min before and after glucose (Trelan-G, 75g) intake. Glucose levels in blood from the fingertips, palm and forearm were generally higher than that of venous blood, and site differences were observed among fingertips, palm and forearm. It was speculated that bleeding time and capillary blood glucose or SMBG level differ among skin sites.

[Standardization of bleeding time by IVY method in male Japanese healthy volunteers].

PURPOSE: In the development of new antithrombotic agents, the bleeding time has been used to evaluate the anti-hemostatic effects and predict the bleeding tendency. The Simplate bleeding time method (SIMP) has so far been used worldwide. However, the production of Simplate has been ceased. In this study, we introduced a new method which applies a thin taper needle to bleeding time measurement (IVY). There is no fundamental data of IVY in Japanese and the characters of two methods have never been compared in Japanese subjects. The purpose of this study is to find the standard values of bleeding time using IVY in 120 Japanese healthy male subjects and compare the inter-operator and inter-subject variability of IVY and SIMP. METHODS: In 120 subjects, bleeding time was measured by 1 operator using two different implements for IVY. In 6 volunteers, bleeding time was measured by 3 different operators using IVY and SIMP. RESULTS: The standards of bleeding time using IVY were 1'13"-2'44" (mean1'58" +/- 2SD, n = 117) by Glucoject Plus 2 and 1'4"-2'47" (mean1'56" +/- 2SD, n = 116) by auto-Lancet II. Average values by IVY were consistent, 1.8, 1.8 and 1.9 minutes among 3 operators. The corresponding values by SIMP were inconsistent, 5.3, 6.8 and 9.2 minutes. Bleeding time values measured by IVY were stable and consistent among subjects compared with values obtained by SIMP. CONCLUSION: The standard of bleeding time using IVY and less inter-operator and -subject variability of IVY were shown in this study. IVY might replace SIMP for measuring bleeding time.

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.

Comparison of PFA-100 testing and bleeding time for detecting platelet hypofunction and von Willebrand disease in clinical practice.

The PFA-100 instrument (Platelet Function Analyzer, Dade Behring) has been reported to be superior to the bleeding time (BT) as a screening test of primary hemostasis. However evaluation of this device has been principally limited to selected populations. The study's aim was to determine testing performance in clinical practice, by comparing the PFA-100 to the BT for the identification of von Willebrand disease (VWD) and intrinsic platelet hypofunction. From 1998-2000, PFA-100 closure time (CT) for epinephrinecollagen (EPI) and ADP-collagen (ADP) cartridges and modified Ivy BTs were performed on outpatients referred for testing for suspected or known hemorrhagic diathesis (n = 346). Evaluation included assays of von Willebrand factor and platelet aggregometry in addition to platelet flow cytometry and electron microscopy when indicated. The normal distribution of PFA-100 CTs was determined using blood samples from 61 normal donors studied on 155 occasions. Results show that thirty-four patients met the diagnostic criteria for VWD and 31 patients were diagnosed with congenital or acquired intrinsic platelet hypofunction. The sensitivity of the PFA-100 for identification of VWD was significantly better (p < 0.01) than the BT with similar specificity. In contrast, the PFA-100 was comparable, but not superior to the BT for detecting platelet hypofunction. We conclude that the PFA-100 performance compares favorably to the BT for the identification of intrinsic platelet hypofunction in clinical practice with superior sensitivity for detecting VWD. Therefore, the PFA-100 could replace the BT for purposes of screening for VWD and intrinsic platelet hypofunction. When clinical suspicion is strong, testing should be supplemented with assays of von Willebrand factor and platelet aggregometry.

[New in vitro analysis tested: bleeding time is still the best method for evaluation of primary hemostasis]. / Ny in vitro-analys prövad: blödningstid fortfarande bästa metod för test av den primära hemostasen.

The need is great for a simple, cheap and readily accessible method for the evaluation of primary hemostasis in work-ups at both out-patient clinics and units caring for surgical or intensive care patients. PFA-100 is a recently introduced instrument for in vitro testing of platelet function. We report experiences from Stockholm, Gothenburg and Malmo of PFA-100 measurements performed on samples from healthy controls and from patients with von Willebrand disease or platelet disorders. It is shown that the PFA-100 system has a high sensitivity for von Willebrands disease, while the sensitivity for hereditary platelet dysfunction is low. In its present design this new device could not replace the template bleeding time as a screening test for primary hemostasis.

[Measurement of bleeding time and study of thrombocyte aggregation. Standardization of methods, normal values and results in patients with suspected hemorrhagic diathesis]. / Messung der Blutungszeit und Untersuchung der Thrombozytenaggregation. Standardisierung der Methoden, Normalwerte und Resultate bei Patienten mit Verdacht auf hämorrhagische Diathese.

Bleeding time measurement and investigation of platelet aggregation in platelet rich plasma (PRP) are routine procedures for the diagnosis of defects in primary hemostasis. These tests are subject to methodological difficulties and should be well standardized in each individual laboratory. - In the present study, bleeding time was measured using the Simplate II device in 40 normal subjects. Furthermore, platelet aggregation in PRP induced by ADP, collagen, arachidonate, and ristocetin was examined. 26 patients referred for investigation of a suspected mild bleeding disorder, who had a normal plasmatic coagulation profile, a normal von Willebrand factor activity, and a normal platelet count, were similarly studied. - Based on the reference values established in the 40 normal subjects, platelet aggregation was found to be pathologic in 7 patients and normal in 12. In 7 patients platelet aggregation was considered to be borderline-pathologic as defined by the range of platelet aggregability found in the 10% of our normal subjects showing the weakest aggregation responses. Bleeding time was prolonged in only 3 patients whereas it was normal in the remaining 23. There was strong evidence of a hemostatic defect as assessed by systematic patient history in 6 out of 7 patients with pathologic platelet aggregation, but in only 3 out of 19 showing normal or borderline-pathologic aggregation. - Pathologic platelet aggregation, therefore, represents not only an abnormal laboratory finding but is likely to be associated with a hemorrhagic diathesis. Platelet aggregation studies do not permit etiologic diagnosis of the thrombocytopathy except for the well-defined membrane glycoprotein deficiencies. The bleeding time appeared to be of low sensitivity for the diagnosis of mild platelet dysfunction.

The bleeding time: current practice in the UK.

A questionnaire survey of current practice in the bleeding time test has been undertaken by the UK External Quality Assessment Scheme in blood coagulation. Completed returns have been received from 358 centres. Most centres (88.5%) perform bleeding times and of these the Ivy test is the most commonly performed. Only 13.6% perform the Duke method. Templates are used to control the procedure by approximately half of the hospitals. There is considerable variability in the type and depth of incision and interpretation of the endpoint. The upper limit of normality not unexpectedly differs considerably between the centres with both Ivy and Duke methods. The use of a commercial template method, 'Simplate', provides a measure of agreement amongst the group of hospitals using this instrument but it remains to be established whether this is the most reliable procedure. In the interim, gross discrepancies in technique or interpretation should be corrected in the light of the findings of the survey.