43 Reduced thrombin generation and/or decreased platelet response in women with HMB Data analysis Mean and standard deviations were calculated for each parameter. Reference ranges (mean ±2 * standard deviation) for platelet func- tion and for VWF function were determined in freshly collected blood of 123 healthy employees of the University Medical Center Utrecht (UMCU). Reference limits for TG (mean ±2* standard deviation) were calculated from platelet-poor plasma samples of 126 healthy volunteers in and around the Maastricht University Medical Center (MUMC). The reference values from the PT, APTT and VWF anti- gen and ristocetin cofactor activity were obtained from the guide- lines of the diagnostic test (Diagnostica Stago, Asnieres, France) and verified in a control population at the Gelre Hospitals (Apeldoorn, the Netherlands). If a platelet function parameter, VWF function or a thrombin generation parameter dropped outside these reference ranges, then the patient with HMB was defined as having impaired or enhanced function for that parameter. RESULTS In Table 1, the results are cut-off values of platelet function measurements in blood collected from 123 healthy employees of the UMCU and the cut-off values of TG measurements plasma collected from 126 healthy employees of the MUMC. The cut-off values for VWF-AG, VWF ristocetin co-factor activity, PT and APTT were established by the local hospital laboratory (department of Clinical Chemistry and Hematology of the Gelre Hospitals in Apeldoorn). The APTT and PT were measured in all 58 patients with HMB and 26 controls (Figure 1). Figure 1: APTT and PT of patients (n = 58) with HMB and controls (n = 26). The grey area represents the reference ranges for prolonged APTT and PT, with upper cut-off values of 35s and 15s, respectively. Three patients had a prolonged APTT vs one control. None of the patients or controls had a PT that fell out of the reference ranges. The APTT showed not statistically significant difference between cases and controls. Remarkably, there were three patients who had a prolonged APTT, while only one control had an APTT that had a value outside the reference borders (Figure 1A). Using PT, we observed no difference between cases and controls, with median (IQ-border) of 13s (13s-14s) in controls and 13s (13s-13s) in patients. 3
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