Presentation on theme: "Bleeding disorders in women"— Presentation transcript:
1Bleeding disorders in women Dr. Paul GiangrandeOxford Haemophilia & Thrombosis CentreandNuffield Department of Clinical MedicineUniversity of Oxford
2How to secure early diagnosis and appropriate treatment? What are the commonest disorders?What are the obstacles to diagnosis?What can be done to facilitate diagnosis and treatment?
3Frequency of bleeding disorders in women with heavy menstrual bleeding: Kadir RA et al: Lancet 351: (1998)150 women with heavy menstrual bleeding but no pelvic abnormality screenedInherited bleeding disorder in 26 (17%)Commonest disorders: von Willebrand disease, platelet disorders, factor XI deficiency.“Inherited bleeding disorders are found in a substantial proportion of women with menorrhagia and a normal pelvis.”
4Congenital bleeding disorders: Rare conditions:Few doctors ever see a caseLow public awarenessPatients often only mildly affected:Few, if any, problems in day-to day lifeFrequently diagnosed in middle ageOften no apparent family historyDiagnostic tests are complex, expensive and not readily available
5Normal platelet count: x 109/lMegakaryocyte in bone marrow: platelets bud off from the cytoplasm of these polyploid cells. Life span of platelets is around 10 days.
7Von Willebrand disease: Common but usually mild bleeding disorderUp to 1% of population affected as defined by reduced plasma level of VWF, although only125 / million have significant bleeding disorderSadler JE Thromb. Haemostasis 84: (2000)Autosomal dominant inheritance (gene on chromosome 12p): females also affectedAutosomal dominant inheritance: women affected as frequently as menTypical features include:Easy bruisingProlonged bleeding from cuts and scratchesNose bleeds (epistaxis)Heavy menstrual periods (menorrhagia)Joint bleeding not a typical feature
8Rare bleeding disorders: Women affected just as much as menUsually parental consanguinity:More common in certain ethnic groupsMore common in certain parts of the world(e.g. S.E Asia, Middle East)“Orphan diseases,” hitherto neglected by:patient advocacy groupsdrug manufacturersSpecific factor concentrates often not available:even if they are, usually not licensed by regulatorslittle or no brand choicenot necessarily recombinant
11Obstacles to diagnosis (1): Lack of awareness of problem by women themselves: what is “normal”?Long-term problem of menorrhagia may be regarded as normal, and positive family history may ironically reinforce this ideaFailure of health care professionals to think of the possibility of underlying bleeding disorder:Tendency to look for physical conditions such as fibroids in women with menorrhagiaFull medical history not elicitedReferrers discouraged after run of negative cases
12Obstacles to diagnosis (2): Poor sensitivity of laboratory tests:Common misconception that normal screening test results (PT, APTT and platelet count) completely excludes possibility of underlying bleeding problemSpecialist interpretation of tests often required:No single test sufficesSpecialist tests like platelet function tests and factor assays may not be available in local hospitalOverdiagnosis of bleeding disorders such as VWD is also a significant problem
13Normal range in our laboratory: 26-36 seconds, using Triniclot reagent Factor XICephActin FSActin FSLTriniclotPathromtin1146.152.642.645.865.83036.638.834.736.952.55032.733.831.246.86930.431.729.031.543.68928.729.726.930.141.5Normal range in our laboratory: seconds, using Triniclot reagent
14Normal range in our laboratory: 26-36 seconds, using Triniclot reagent Factor IXCephActin FSActin FSLTriniclotPathromtin1238.742.438.240.753.83932.935.432.333.844.96930.932.429.731.642.29529.030.428.430.841.012128.829.427.629.540.2Normal range in our laboratory: seconds, using Triniclot reagent
17A diagnosis of bleeding disorder can have significant adverse social consequences: Self-esteemSchoolEmploymentParticipation in sportsLife insuranceCredit rating (e.g mortgage)Travel insuranceMarriage prospects
18Von Willebrand’s disease (VWD): …..or would either“deficiency” or “disorder”be better?
19How to promote awareness among health care professionals: Publications and presentations aimed at health care professionals (e.g. gynaecologists, ENT surgeons)Use of bleeding scores to better identify patients requiring more detailed evaluationProfessional guidelines (“recipes” describing work up of patients)NGOs and not-for-profit organizations expanding their mandates (e.g. WFH, EHC)
20Book published by Royal College of Obstetricians and Gynaecologists in UK: specifically aimed at trainees preparing for their specialist examinations
21Importance of history taking: Easy bruisingNose bleeds (epistaxis)Heavy menstrual periods (menorrhagia)Bleeding after:operationsdental extractionsgiving birthFamily history
22Guidelines on the management of menorrhagia in secondary care Royal College of Obstetricians & Gynaecologists, UK (1998)“This …. emphasises the importance of a carefulhistory specifically with regard to a long historyof menorrhagia since menarche, and a history ofbleeding after tooth extraction, operations andchildbirth. If these factors are present, testingfor bleeding disorders should be carried out.This should be arranged in conjunction with thelocal haematology department as many of thenecessary tests are not routine.”
23Objective criteria include: Anaemia (low haemoglobin level)Need for blood transfusion after surgeryProlonged bleeding from trivial wounds lasting > 15 minutes and requiring medical attentionHaematoma at site of injections (e.g vaccination), bleeding from umbilical stumpOral cavity bleeding associated with tooth eruption, bites to lips and tongueExcessive menstrual blood loss
24Useful tool, but not specific for bleeding disorders Assessment of menstrualblood loss using a pictorial chart.Higham JM et al.Brit. J. Obs. Gynae. 97: (1990)
25Very rigorous with good sensitivity but far too long to use in routine clinical work
27Simple to use in daily practice. Philipp C et al. Am. J. Obs. Gyne. 204: 209.e1-7 (2011)Simple to use in daily practice.Sensitivity of 89% for haemostatic defects.
28How to promote awareness among women: Be proactive and identify potential affected women from analysis of family trees of people already diagnosed with inherited bleeding disordersCommission articles in general press and leisure magazinesInternet websites (online social groups)
35On line social groups: Advantages: Disadvantage: Convenient & anonymousCost-effective, no time restrictionsNo geographical barriers (disability, pain)distance/ transport to face-to-face support groupsNo interference with family/work/commitmentsMore time to reflect on content of disclosure‘Expressive writing paradigm’ ‘Writing cure’ : written disclosure of about stressful or traumatic experiences yields significant improvements in physical and psychological health.Support is exchanged among patients - not only sought but also provided to othersExpert patients & website visitorsDisadvantage:Requires access to a home computer with internet connection and associated skillsBypass doctors’ opinion“Flaming”: aggressive /abusive/malicious messagesFalse informationAlthough can be corrected by referee or site moderator
36Conclusions:Von Willebrand disease is by far the commonest congenital bleeding disorderNormal basic clotting tests results do not exclude the possibility of a underlying bleeding disorderObjective assessment tools may be used to identify subjects requesting more detailed investigationAssessment of platelet function is desirablePatient organisations already focussing on conditions other than haemophiliaAwareness in the wider community can only be achieved by using media such as radio and leisure magazines.
37Acknowledgement:I would like to express my thanks to Ms Georgie Robinson, Services Manager with the UK Haemophilia Society, for helpful discussions and providing material for this talk.