49 Reduced thrombin generation and/or decreased platelet response in women with HMB their role in haemostasis testing in the prediagnosis of many coagulation defects. Despite this, both tests have severe disadvantages, because they only represent the first seconds of coagu- lation and lack to provide information about co-factors, inhibitors and mildly impaired coagulation response. For this reason, the thrombin generation test is now rapidly taking its place in coagulation research in scientific studies and will soon develop into diagnostics. TG is not only more complete than the PT and APTT, but it is also more sensitive to subtle differences in coagulation response. Our findings that PT failed to find coagulation deficiencies in women with HMB and APTT measurements only distinguished three patients with a pro- longed APTT, while TG distinguished 17 patients with either a ttPeak or a lag time which was 2x the standard deviation longer than the mean lag time or ttPeak of controls. These findings are a clear illustration of the need for modernization of coagulation diagnostics with TG. This study has some limitations that must be pointed out. The small patient population does not allow us to give definitive recommendations for gynaecologists and general practitioners to measure platelet function and TG in any woman with complaints of HMB. Larger series with regard to platelet function, VWF and coagulation measure- ments in the different phases of the menstrual cycle in women with HMB without other gynaecologic pathophysiology are needed to confirm the effectiveness of our platelet function testing approach and the TG test and to establish whether these tests are easy accessible for routine measurements of patients and may therefore potential diagnostic devices for measuring impaired haemostasis in women with HMB. Another potential limitation is that the control group consisted of men and women, while the cases consisted of only women. Furthermore, the age of the patients (between 40 and 60 years) was significantly higher than in the controls. In a recent study, we have shown that, in our laboratory, there is no significant difference in TG parameters between men and women who are not using oral contraceptives (28). Similarly, we did not observe correlations between TG parameters and age within our cohort (28). This is not necessary a problem, because both platelet function and coagulation are not affected by age or gender (27). Another study showed that there are no discordant effects of age on the relation between platelet function and HMB (25). However, we cannot draw firm conclusions about the prevalence of coagulation or PFDs in younger women, and this will be the subject of ongoing studies. We conclude that, even with the considered limitations, our platelet function test approach and the TG test in women with HMB result in a prevalence of approximately 50% of the women with either. 3
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