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• W2075568520 abstract "SummaryMenorrhagia is a common clinical problem and is unexplained in more than 50% of women. Although studies suggest that von Willebrand's Disease (VWD) is found in a substantial number of women with unexplained menorrhagia, the prevalence of platelet defects in women with menorrhagia is unknown. To determine the prevalence of platelet and other hemostatic defects, we evaluated women ages 17–55 diagnosed with unexplained menorrhagia. Seventy-four women (52 white, 16 black, six other) were studied. Bleeding time was prolonged in 23 women (31.5%). Maximal percent platelet aggregation was decreased with one or more agonists in 35 (47.3%) women. The most commonly found platelet function defects were reduced aggregation responses to ristocetin in 22 women and to epinephrine in 16 women. Sixteen of 22 women with reduced ristocetin aggregation had von Willebrand ristocetin cofactor (VWF:RCo) and von Willebrand factor antigen (VWF:Ag) > 60%. Platelet ATP release was decreased with one or more agonists in 43 (58.1%) women. Of the black women studied, 11/16 (69%) had abnormal platelet aggregation studies compared with 20/52 white women (39%) (P = 0.06). Black women with menorrhagia had a higher prevalence of decreased platelet aggregation in response to ristocetin and epinephrine than did white women (P = 0.0075, P = 0.02). Ten women (13.5%) had VWF:RCo and/or VWF:Ag < 60%. Using race and blood group specific ranges, 5 (6.8%) women had decreased VWF:RCo, VWF:Ag and/or collagen binding (VWF:CB). Mild factor XI deficiency was found in two women and one woman with mild factor V deficiency and one hemophilia A carrier were identified. We conclude that the prevalence of platelet function defects and other inherited bleeding disorders is substantial in a multiracial US population of women with unexplained menorrhagia. Menorrhagia is a common clinical problem and is unexplained in more than 50% of women. Although studies suggest that von Willebrand's Disease (VWD) is found in a substantial number of women with unexplained menorrhagia, the prevalence of platelet defects in women with menorrhagia is unknown. To determine the prevalence of platelet and other hemostatic defects, we evaluated women ages 17–55 diagnosed with unexplained menorrhagia. Seventy-four women (52 white, 16 black, six other) were studied. Bleeding time was prolonged in 23 women (31.5%). Maximal percent platelet aggregation was decreased with one or more agonists in 35 (47.3%) women. The most commonly found platelet function defects were reduced aggregation responses to ristocetin in 22 women and to epinephrine in 16 women. Sixteen of 22 women with reduced ristocetin aggregation had von Willebrand ristocetin cofactor (VWF:RCo) and von Willebrand factor antigen (VWF:Ag) > 60%. Platelet ATP release was decreased with one or more agonists in 43 (58.1%) women. Of the black women studied, 11/16 (69%) had abnormal platelet aggregation studies compared with 20/52 white women (39%) (P = 0.06). Black women with menorrhagia had a higher prevalence of decreased platelet aggregation in response to ristocetin and epinephrine than did white women (P = 0.0075, P = 0.02). Ten women (13.5%) had VWF:RCo and/or VWF:Ag < 60%. Using race and blood group specific ranges, 5 (6.8%) women had decreased VWF:RCo, VWF:Ag and/or collagen binding (VWF:CB). Mild factor XI deficiency was found in two women and one woman with mild factor V deficiency and one hemophilia A carrier were identified. We conclude that the prevalence of platelet function defects and other inherited bleeding disorders is substantial in a multiracial US population of women with unexplained menorrhagia. Unexplained menorrhagia is a common clinical problem among women of reproductive age, frequently resulting in anemia, impairing women's daily activities, and often managed by surgery. Menorrhagia is the presenting symptom for the majority of the over 500 000 women who undergo hysterectomy yearly in the USA [1Lepine L. Hillis S. Marchbanks P. et al.Hysterectomy surveillance − United States 1980–93.MMWR. 1997; 46: 1-15PubMed Google Scholar]. More than a quarter of the USA female population undergo hysterectomy by age 60 [2Carlson K. Nichols D. Schiff I. Current concepts: indications for hysterectomy.NEJM. 1993; 328: 856-60Crossref PubMed Scopus (287) Google Scholar]. Approximately 20% of hysterectomies are performed for ‘dysfunctional’ uterine bleeding not attributable to uterine leiomyomas, polyps, endometrial or cervical cancer, prolapse, pregnancy, or endometriosis [3Lee N.C. Dicker R.C. Rubin G.L. Ory H.W. Confirmation of the preoperative diagnoses for hysterectomy.Am J Obstet Gynecol. 1985; 152: 803-8PubMed Google Scholar]. Despite the potential for excessive bleeding in women undergoing major surgical procedures, hysterectomy mortality rates ranging from six to 11 per 10 000 [4Wingo P. Huezo C. Rubin G. Ory H. Peterson H. The mortality risk associated with hysterectomy.Am J Obstet Gynecol. 1985; 152: 803-8Abstract Full Text PDF PubMed Scopus (195) Google Scholar], and the availability of potential alternative management approaches, women in the USA with unexplained menorrhagia are currently rarely evaluated for inherited bleeding disorders. Recent reports from the USA and Europe have suggested that the prevalence of von Willebrand's disease (VWD) in white women with menorrhagia ranges from 13% to 20% [5Kadir R.A. Economides D.L. Sabin C.A. Owens D. Lee C.A. Frequency of inherited bleeding disorders in women with menorrhagia.Lancet. 1998; 351: 485-9Abstract Full Text Full Text PDF PubMed Scopus (413) Google Scholar, 6Edlund M. Blomback M. Von Schoultz B. Andersson O. On the value of menorrhagia as a predictor for coagulation disorders.Am J Hematol. 1996; 53: 234-8Crossref PubMed Scopus (154) Google Scholar, 7Dilley A. Drews C. Miller C. et al.von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia.Obst Gynecol. 2001; 97: 630-6Crossref PubMed Scopus (198) Google Scholar], with a much lower prevalence reported in black women studied [7Dilley A. Drews C. Miller C. et al.von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia.Obst Gynecol. 2001; 97: 630-6Crossref PubMed Scopus (198) Google Scholar]. The frequency and characteristics of qualitative platelet disorders in women with menorrhagia are unknown. Based on results of previous studies which did not systematically include evaluations for platelet disorders, the commonly held presumption has been that VWD is the major bleeding disorder in women with menorrhagia [5Kadir R.A. Economides D.L. Sabin C.A. Owens D. Lee C.A. Frequency of inherited bleeding disorders in women with menorrhagia.Lancet. 1998; 351: 485-9Abstract Full Text Full Text PDF PubMed Scopus (413) Google Scholar, 6Edlund M. Blomback M. Von Schoultz B. Andersson O. On the value of menorrhagia as a predictor for coagulation disorders.Am J Hematol. 1996; 53: 234-8Crossref PubMed Scopus (154) Google Scholar, 7Dilley A. Drews C. Miller C. et al.von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia.Obst Gynecol. 2001; 97: 630-6Crossref PubMed Scopus (198) Google Scholar]. In this study, we evaluated women who had been diagnosed by their gynecologists with unexplained menorrhagia for underlying bleeding disorders. Our data demonstrate that the frequency of undiagnosed qualitative platelet disorders is substantial among women with menorrhagia in a USA multiracial population. Women between the ages of 17 and 55 years seen at the UMDNJ-Robert Wood Johnson faculty gynecology practice or collaborating community gynecology practices with a physician diagnosis of menorrhagia were eligible to participate in the study. In order to determine a list of potential subjects all medical charts coded with a diagnosis relating to menorrhagia during the period between 1 January 1996 and 4 January 2002 were reviewed. Eligibility required that a pelvic exam performed by their gynecologist be documented in their medical record. Women with known bleeding or endocrine disorders, submucuous uterine fibroids or uterine polyps on pelvic exam or ultrasonography, malignancy, use of an intrauterine device, or treatment with anticoagulants within the past two months were not eligible. Women who had a hysterectomy more than 36 months prior to anticipated study entry were not eligible. Potential study subjects were contacted for participation in the study. Women taking oral contraceptives or estrogen-based therapy were required to discontinue use for a minimum of one cycle prior to evaluation. Non-steroidal anti-inflammatory agents, aspirin and all medications and herbal agents which could potentially impair platelet function were discontinued at least 14 days prior to testing. Subjects were studied on days 3–9 of their menstrual cycle, unless they had previously undergone a hysterectomy. Participation in the study involved an in-person interview which elicited information on demographic and medical history, bleeding symptoms, family history, and a blood sample. All medical records were reviewed by study staff to confirm the diagnosis of menorrhagia. Laboratory controls for platelet studies were normal women selected from employees, housestaff, and students at the institution who reported no non-steroidal anti-inflammatory agents, aspirin, or other medications which could potentially impair platelet function for at least 14 days and no oral contraceptives or other hormonal based medication for at least one cycle. None of these women served as donors for the establishment of any laboratory reference ranges. Informed consent, which was approved by the Institutional Review Boards of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and the Centers for Disease Control and Prevention was obtained from all study participants. Bleeding time was performed by one of two experienced personnel using a Simplate device (Organon-Technica, Durham, NC, USA) and a modified Ivy technique. Citrated blood (3.2% sodium citrate in a 9 : 1 blood anticoagulant ratio) was obtained by clean venipuncture. Blood samples were also obtained for CBC and ABO blood typing. Platelet aggregation and ATP release were performed at 37° in platelet-rich plasma on an optical Chronolog platelet lumi-aggregometer (Chrono-Log Corp, Haverton, PA, USA) that simultaneously monitors aggregation by turbidity and secretion of ATP by luminescence [8Feinman R.D. Lubowsky J. Charo I. Zabinski M.P. The lumi-aggregometer: a new instrument for simultaneous measurement of secretion and aggregation by platelets.J Lab Clin Med. 1977; 90: 125-9PubMed Google Scholar] according to standard guidelines [9Machin S.J. Preston E. Guidelines on platelet function testing.J Clin Pathol. 1988; 41: 1322-30Crossref PubMed Scopus (111) Google Scholar]. Ristocetin induced platelet aggregation was performed with ristocetin (Chrono-Log Corp) at three final concentrations: 0.5, 1.0 and 1.25 mg mL−1. Platelet aggregation was also performed using 5, 10 and 20 µmol L−1 of adenosine-5′diphosphate (ADP), 0.5 mmol L−1 arachidonic acid, 10 µmol L−1 epinephrine, and 2 µg mL−1 collagen (Chron-Log Corp). Aggregation tracings were performed for at least 5 min and longer, if maximal aggregation had not been reached, and the maximal percent aggregation was recorded. ATP release was measured by luminescence using the luciferin luciferase assay [9Machin S.J. Preston E. Guidelines on platelet function testing.J Clin Pathol. 1988; 41: 1322-30Crossref PubMed Scopus (111) Google Scholar] with 50 µL luciferin-luciferase reagant (Chrono-Log Corp) in 450 µL platelet-rich-plasma. Luminescence was calibrated by addition of a 2 µmol L−1 ATP standard (Chrono-Log Corp). Reactions were initiated by the addition of 1 U mL−1 thrombin, 2 µg mL−1 collagen, 10 and 20 µmol L−1 ADP, and 0.5 mmol L−1 arachidonic acid (Chrono-Log Corp). ATP release was calculated by comparison of peak luminescence recorded from the patient sample with that of ATP standard. Reference ranges for platelet aggregation and ATP release were calculated as two standard deviations about the mean for 40 normal male and female subjects. Calculated maximal percentage platelet aggregation normal ranges were: arachidonic acid 74–99%; collagen 79–98%; ADP (20 µmol L−1) 72–103%; ADP (10 µmol L−1) 58–99%; ADP (5 µmol L−1) 45–105%; epinephrine 73–90%; ristocetin (1.25 mg mL−1) 87–102%; ristocetin 1.0 mg mL−1 75–98%; ristocetin (0.5 mg mL−1) 0.24–6.6. Calculated ATP release ranges (nmoles) were: arachidonic acid 0.56–1.40; collagen 0.74–1.92; ADP (20 µmol L−1) 0.56–1.16; ADP (10 µmol L−1) 0.50–1.06; thrombin >0.5. Platelet aggregation and ATP release responses were considered decreased if less than reference range. Activated partial thromboplastin time (APTT) was performed using rabbit brain cephalin with silica as activator (PTT A, Diagnostica Stago, Parsippany, NJ, USA). Prothrombin time (PT) was performed using Neoplastine CI Plus (Diagnostica Stago). Thrombin time was performed using human thrombin (Diagnostica Stago). Factors (F)II, V, VII, IX, X, XI, and XII were measured using factor deficient plasmas. FVIII activity was measured by one-stage assay (Diagnostica Stago) using silica as activator and partial thromboplastin. All coagulation tests were performed on automated analyzers (STA or STAR, Diagnostica Stago). VWF:Ag was measured by ELISA using polyclonal antiserum (Asserachrom vWF, Diagnostica Stago, Parsippany, NJ). VWF:RCo was measured by aggregation of lyophilized normal platelets by ristocetin in an optical aggregometer (Chrono-Log Corp) as previously described [10Miller C.H. Dilley A. Richardson L. Hooper W.C. Evatt B.L. Population differences in von Willebrand factor levels affect the diagnosis of von Willebrand disease in African-American women.Am J Hematol. 2001; 67: 125-9Crossref PubMed Scopus (74) Google Scholar] using ristocetin (American Biochemical and Pharmaceutical Corp, Marleton, NJ, USA) at a final concentration of 1 mg mL−1. Reference standards for FVIII and VWF were lyophilized commercial reference plasmas standardized against the 3rd International Standard for Factor VIII and VWF in Plasma. Blood type and race-specific reference ranges were calculated as two standard deviations about the mean for control subjects [10Miller C.H. Dilley A. Richardson L. Hooper W.C. Evatt B.L. Population differences in von Willebrand factor levels affect the diagnosis of von Willebrand disease in African-American women.Am J Hematol. 2001; 67: 125-9Crossref PubMed Scopus (74) Google Scholar]. VWF:CB was measured by ELISA using equine collagen. All samples were tested in duplicate. Differences in means of maximal percentage aggregation between cases and controls were evaluated by t-tests. Fisher exact test for 2 × 2 tables with 95% confidence intervals and mid-P-values were used to compare prevalences between cases and controls. A P-value of less than or equal to 0.05 is considered statistically significant. Confidence intervals for odds ratios are reported where appropriate. Women were provided at the time of study visit with a pictorial chart [11Higham J.M. O'Brien P.M.S. Shaw R.W. Assessment of menstrual blood loss using a pictorial chart.Br J Obst Gynecol. 1990; 97: 734-9Crossref PubMed Scopus (828) Google Scholar, 12Janssen C.A.H. Scholten P.C. Heintz A.P.M. A simple visual assessment technique to discriminate between menorrhagia and normal menstrual blood loss.Obstet Gynecol. 1995; 85: 977-82Crossref PubMed Scopus (235) Google Scholar] to complete with their next menses and an explanation of how it should be completed for estimating menstrual blood loss. The chart consisted of a series of diagrams representing lightly, moderately, and heavily soiled pads and tampons. Subjects recorded each discarded item for the duration of an entire cycle. Scoring of pads and tampons was done as previously described [11Higham J.M. O'Brien P.M.S. Shaw R.W. Assessment of menstrual blood loss using a pictorial chart.Br J Obst Gynecol. 1990; 97: 734-9Crossref PubMed Scopus (828) Google Scholar, 12Janssen C.A.H. Scholten P.C. Heintz A.P.M. A simple visual assessment technique to discriminate between menorrhagia and normal menstrual blood loss.Obstet Gynecol. 1995; 85: 977-82Crossref PubMed Scopus (235) Google Scholar] with tampons assigned 1, 5, and 10 and pads scored 1, 5, and 20 for lightly, moderately, and heavily soiled, respectively. Scoring of clots was performed in comparison with US coins, a modification of the previously reported comparison with Dutch coins [12Janssen C.A.H. Scholten P.C. Heintz A.P.M. A simple visual assessment technique to discriminate between menorrhagia and normal menstrual blood loss.Obstet Gynecol. 1995; 85: 977-82Crossref PubMed Scopus (235) Google Scholar], with one assigned to clots smaller than a quarter, and five assigned to clots a quarter or larger in size. Seventy-four women with unexplained menorrhagia were studied with a mean age of 40.4 ± 8.1(17–52) years. Participant characteristics are shown in Table 1. Four women (5.4%) had previously undergone hysterectomy for excessive bleeding. Fifty-two normal women with a mean age of 34.8 ± 9.7 (18–57 years) were controls for platelet studies.Table 1Participant characteristics (n = 74)Age (years)40.4 ± 8.1(17–52)Race White52(70.3%) Black16(21.6%) Other6(8.1%)Blood group O44(59.5%) Non-O30(40.5%)Age at menarche (years)12.1 ± 1.6(9–16) Open table in a new tab Pictorial blood loss assessment charts (PBAC) were returned by 59 subjects. Fifty-one (86%) had a PBAC score >100; 37 (63%) had a PBAC score >185. The mean hemoglobin of the women was 11.8 ± 1.9 g dL−1 (5.9–14.5 g dL−1). Thirty-one women had a hemoglobin < 12 g dL−1. The mean platelet count was 278 130 ± 72 702 µL−1 (102 000–439 000). Twenty-six subjects had platelet counts >300 000 µL−1. Two subjects had platelet counts between 100 000 and 150 000 µL−1. Mean corpuscular volume was < 78 fL in 18 women. Mean platelet volume was 8.7 ± 1.1 (6.9–14.1). Twenty-five women (33.8%) with menorrhagia had one hemostatic abnormality, as defined by a prolonged bleeding time, abnormal platelet aggregation with one or more agonists, abnormal ATP release with one or more agonists, decreased VWF ristocetin cofactor or antigen, or single factor deficiency. Eighteen (24.3%) demonstrated two hemostatic abnormalities, 12 (16.2%) had three hemostatic abnormalities, 3 (4.1%) had four abnormalities, and one woman (1.3%) had five hemostatic abnormalities. Twenty-three women (31.5%) had prolonged bleeding times (>9 min) (Fig. 1). In only two women, the prolonged bleeding time was unassociated with any other hemostatic abnormalities. Women who were found to have prolonged bleeding times were not more likely to be anemic than women with normal bleeding times (95% CI 0.3,2.3; P = 0.9). Moreover, we could find no relationship between bleeding time and hemoglobin (P = 0.27) or hematocrit (P = 0.14) using Pearson's correlation and linear regression. Maximal platelet aggregation was decreased with one or more agonists in 35 (47.3%) women. The prevalence odds of platelet aggregation abnormalities was 4.2-fold higher among women with menorrhagia than among control women (95% CI 1.8,9.8, P = 0.001) (Table 3). Twenty-two women (29.7%) had decreased aggregation in response to one agonist, seven women (9.5%) had decreased aggregation in response to two agonists, and six women (8.1%) had decreased aggregation in response to more than two agonists. Fifteen women (20.3%) had abnormal platelet aggregation and a prolonged bleeding time. Among controls with reduced aggregation response, 7/9 (77%) had a decreased response to one agonist.Table 3Platelet function testing abnormalities in women with menorrhagia and control womenWomen with menorrhagia (n = 74)Control women (n = 52)P-valueOdd's ratio (95% CI)Platelet aggregation*Below range with one or more agonists.3590.0014.2 (1.9, 9.8)Platelet ATP release*Below range with one or more agonists.43120.00024.3 (1.9, 9.4)* Below range with one or more agonists. Open table in a new tab Epinephrine (10 µmol L−1) induced platelet aggregation was decreased in 16 women (21.4%) with menorrhagia and in two controls (P = 0.005) (Table 4). With epinephrine as agonist, the mean percentage maximal aggregation of women with menorrhagia was significantly lower than female controls (76.33 ± 16.75 vs. 83.12 ± 13.07; P = 0.002) (Fig. 2c). Furthermore, most of the women with decreased epinephrine induced aggregation (11/16) had additional aggregation abnormalities, either with ristocetin, collagen or both agonists. All five women with isolated impaired epinephrine aggregation also had abnormalities in ATP release; three of these women had a prolonged bleeding time in addition.Table 4Platelet aggregation and platelet ATP release defects by agonistWomen with menorrhagia (n = 74)Control women (n = 52)P-valuePlatelet aggregation Epinephrine1620.005 Ristocetin*Ristocetin 1.0 mg mL−1 concentration.2040.007 Collagen920.105 ADP**ADP 20 µmol L−1 concentration.310.50 Arachidonic acid610.13Platelet ATP release ADP**ADP 20 µmol L−1 concentration.3070.0009 Collagen1850.04 Arachidonic acid1610.001 Thrombin10NA* Ristocetin 1.0 mg mL−1 concentration.** ADP 20 µmol L−1 concentration. Open table in a new tab Twenty-two women (29.7%) had decreased aggregation in response to ristocetin. Twenty women (27%) had decreased aggregation in response to 1.0 mg mL−1 ristocetin (Table 4); 16 women (21.6%) had decreased aggregation in response to ristocetin 1.25 mg mL−1; 14 women (18.9%) had decreased aggregation in response to both ristocetin 1.0 and 1.25 mg mL−1. Of 22 women with decreased ristocetin induced platelet aggregation, only six had VWF ristocetin cofactor and/or antigen < 60%; 12 had one or more other platelet aggregation abnormalities and an additional four had one or more ATP release abnormalities. The mean percentage maximal aggregation in response to both 1.0 and 1.25 mg mL−1 ristocetin was significantly lower in women with menorrhagia compared with control women (73.32 ± 27.93 vs. 82.96 ± 21.18; P = 0.017 and 86.31 ± 18.53 vs. 91.92 ± 4.04; P = 0.009)(Fig. 2a,b). Arachidonic acid induced platelet aggregation was decreased in six women (8.1%) and one control (P = NS) (Table 4). Mean percent aggregation was significantly lower (P = 0.008) in cases (78.81 ± 22.51), compared with controls (85.82 ± 6.98) (Fig. 2f). Platelet aggregation was decreased in response to collagen (2 µg mL−1) in 9 (12.1%) women (Table 4). ADP induced platelet aggregation was decreased in three women (Table 4). With collagen and ADP, the mean percentage maximal aggregation was not significantly different between cases and controls (Fig. 2d,e). Platelet ATP release was decreased in 43 women (58.1%) in response to one or more agonists (OR 4.3, 95% CI 1.9,9.4, P = 0.0002) (Table 3). Of the 43 women with abnormal ATP release, 19 women also had a prolonged bleeding time, 16 had abnormal platelet aggregation in response to one or more agonists, and 13 had both a prolonged bleeding time and abnormality in platelet aggregation. Thirteen women with abnormal ATP release, had neither an abnormality in platelet aggregation or bleeding time. Thirty women (35.2%) had decreased ADP-induced ATP release; seven of these women had an isolated reduction in ADP-induced ATP release without other abnormalities in release, aggregation or bleeding time. Of the black women with menorrhagia studied, 11/16 (69%) had abnormal platelet aggregation in response to one or more agonists compared with 20/52 white women (39%) with menorrhagia (OR 3.1, 95% CI 0.9,10.4, P = 0.06). Ristocetin induced platelet aggregation was decreased in 9/16 (56.3%) black women compared with 11/52 (21%) white women with 1.0 mg mL−1 concentration of ristocetin (P = 0.0075) (Table 5) and 8/16 black women compared with 6/52 white women with 1.25 mg mL−1 concentration of ristocetin (P = 0.001) in women with menorrhagia. Seven of nine black women with a ristocetin induced platelet aggregation defect had other platelet aggregation defects and/or a prolonged bleeding time. The mean percentage maximal aggregation was lower in black women compared with white women with menorrhagia using 1.0 mg mL−1 ristocetin (P = 0.015) and 1.25 mg mL−1 ristocetin (P = 0.006) as agonists. Defects in ristocetin induced platelet aggregation were also more prevalent in black women with menorrhagia compared with black controls (1.25 mg mL−1 ristocetin, P = 0.03; 1.0 mg mL−1 ristocetin, P = 0.05). Three of 15 black controls were identified with decreased ristocetin aggregation. Epinephrine-induced platelet aggregation was decreased in 7/16 (44%) black women compared with 8/52 (15%) white women (P < 0.02). Collagen induced platelet aggregation was decreased in 5/16 (31%) black women compared with 4/52 (8%) white women (P < 0.02) (Table 5). Abnormalities in epinephrine induced platelet aggregation were not seen in black controls; one black control had decreased collagen, ADP, and ristocetin aggregation. Bleeding time was prolonged in 5/16 (31%) black women compared with 16/52 (31%) white women. There were no significant differences between black and white women with menorrhagia in abnormalities of ATP release.Table 5Platelet aggregation and ATP release defects by race *Data for races other than white or black not shown (n = 6).Women with menorrhagiaP-valueWhite (n = 52)Black (n = 16)Platelet aggregation Epinephrine870.02 Ristocetin**Ristocetin concentration 1.0 mg mL−1.1190.0075 Collagen450.02 ADP***ADP concentration 20 µmol L−1.210.6 Arachidonic Acid50NAPlatelet ATP release ADP***ADP concentration 20 µmol L−1.2161.0 Collagen1250.5 Arachidonic acid1320.3 Thrombin10NA* Data for races other than white or black not shown (n = 6).** Ristocetin concentration 1.0 mg mL−1.*** ADP concentration 20 µmol L−1. Open table in a new tab Ten women (13.5%) were identified with VWF:RCo less than 60%. Using race and blood type specific reference ranges, 5/74 (6.7%) women (four white, one black) were below range for VWF:RCo, VWF:Ag, and/or VWF:CB. One woman had absent high and intermediate multimers and was classified as a type IIA VWD. There was a significant relationship between VWF:CB and VWF:RCo (P < 0.0001, by linear regression) regardless of blood type but not with ristocetin induced platelet aggregation (P > 0.5). Two women had FXI deficiency in the heterozygote range. One woman with FV activity in the heterozygote range was identified. She was also found to have a 14-min BT and abnormal platelet aggregation in response to arachidonic acid, epinephrine, and ristocetin. One woman was found to have a mild factor VIII deficiency with normal VWF:RCo, VWF:Ag, VWF:CB, normal factor VIII binding, and family history consistent with hemophilia A carrier status. Our results demonstrate that underlying hemostatic defects, in particular qualitative platelet abnormalities, occur in the majority of women with unexplained menorrhagia. We found that 49% of women we studied with menorrhagia had two or more hemostatic defects as previously defined. Our results are consistent with prior studies which have also found that a substantial number of women with unexplained menorrhagia have bleeding disorders [5Kadir R.A. Economides D.L. Sabin C.A. Owens D. Lee C.A. Frequency of inherited bleeding disorders in women with menorrhagia.Lancet. 1998; 351: 485-9Abstract Full Text Full Text PDF PubMed Scopus (413) Google Scholar, 6Edlund M. Blomback M. Von Schoultz B. Andersson O. On the value of menorrhagia as a predictor for coagulation disorders.Am J Hematol. 1996; 53: 234-8Crossref PubMed Scopus (154) Google Scholar, 7Dilley A. Drews C. Miller C. et al.von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia.Obst Gynecol. 2001; 97: 630-6Crossref PubMed Scopus (198) Google Scholar]. However, in contrast to previous studies, we found that in this multiracial group platelet dysfunction was more prevalent than VWD. The most likely explanation is that none of the prior studies included systematic examination of platelet function in their study population [5Kadir R.A. Economides D.L. Sabin C.A. Owens D. Lee C.A. Frequency of inherited bleeding disorders in women with menorrhagia.Lancet. 1998; 351: 485-9Abstract Full Text Full Text PDF PubMed Scopus (413) Google Scholar, 6Edlund M. Blomback M. Von Schoultz B. Andersson O. On the value of menorrhagia as a predictor for coagulation disorders.Am J Hematol. 1996; 53: 234-8Crossref PubMed Scopus (154) Google Scholar, 7Dilley A. Drews C. Miller C. et al.von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia.Obst Gynecol. 2001; 97: 630-6Crossref PubMed Scopus (198) Google Scholar]. Interestingly, Edlund et al. [6Edlund M. Blomback M. Von Schoultz B. Andersson O. On the value of menorrhagia as a predictor for coagulation disorders.Am J Hematol. 1996; 53: 234-8Crossref PubMed Scopus (154) Google Scholar] performed bleeding times and found that 5/30 had prolonged bleeding times without evidence of VWD, suggesting that these women may have had platelet defects. Based on these results one might surmise that platelet dysfunction may have been at least as prevalent as VWD in this population. In addition, our study population was composed of approximately 20% African-American women who have recently been reported to have a lower prevalence of VWD [7Dilley A. Drews C. Miller C. et al.von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia.Obst Gynecol. 2001; 97: 630-6Crossref PubMed Scopus (198) Google Scholar, 10Miller C.H." @default.
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• W2075568520 date "2003-03-01" @default.
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• W2075568520 title "Platelet functional defects in women with unexplained menorrhagia" @default.
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