Comparison of Closure Times and Bleeding Times in the Evaluation of Patients Referred for Mild Bleeding Disorder Evaluations.

Abstract

The bleeding time has largely been replaced by closure times using a PFA-100 device for the evaluation of patients with suspected platelet function defects or von Willebrand's disease. Initial studies showed concordance with both tests being abnormal in well defined thrombocytopathies (thrombasthenia, Bernard-Soulier syndrome, storage pool deficiency, and aspirin-like defects) and in von Willebrand's disease. However recent studies have suggested that the closure time may be particularly insensitive in the more common platelet secretion disorders. This is a retrospective medical record review study to compare the results of closure times and bleeding times performed the same day in a consecutive series of patients evaluated for mild bleeding disorders. Incusion criteria were all patients referred to the PI at the Hemostasis and Thrombosis outpatient clinic at the Institute for Transfusion Medicine for such an evaluation, who had both closure and bleeding times performed on the same day. Exclusions were patients who did not have these tests performed on the same day. Platelet function testing included platelet aggregation in platelet rich plasma (epinephrine-11 micromolar, ADP 2.5, 5, 10 and 20 micromolar, collagen 2 mg/ml, high and low dose Ristocetin), adenine nucleotides.If these were normal, whole blood aggregation and ATP secretion were also assessed. Von Willebrand parameters (on at least three different dates) and von Willebrand multimers were measured. Thirty-two patients were evaluated and of these, two had normal tests. The remaining thirty patients (8M:20F) had a median age of 51 (range = 18 to 80). Seventeen pts (57%) were referred for abormal surgical bleeding, four (13%) were evaluated for bleeding (CNS in two, menorrhagia in two), one pt for excessive bruising and the remainder because of abnormal tests.Their diagnoses were platelet secretion defects (n=20), storage pool deficiency (n=5), aspirin-like defects (n=4) and von Willebrand's disease type 1 (n=1). Bleeding times and closure times were both abnormal in only 3/30 pts (10%).CT coll/epi and CT coll/ADP results were abnormal in 5/30 (17%) and in 3/30 (10%) respectively. By contast, bleeding times were abnormal in 19/30 (63%). Only two/30 pts (7%) had isolated prolongation of the closure times. Of note, 9/30 patients (30%) had normal values in all three screening assay parameters. Using ROC analysis, the area under the curve was not significant for closure times with p values for CT:coll/epi of 0.387 and for CT:coll/ADP of 0.362. However, the p value for bleeding times was significant at <0.001. Using a cutoff bleeding time of greater or equal to 7.5 minutes, the sensitivity was 67% and specificity was 100% for this group of patients. We conclude that the closure time is not a good screening assay for patients with the more common thrombocytopathies. Unfortunately bleeding times also remain insensitive for screening for these disorders.