Working Group on Women’s Health Issues
July 20, 2002
08:00 to 12:00
Whittier Room
Boston Park Plaza Hotel

Chair:  M. J. Manco-Johnson, USA

This was the first open working party meeting on coagulation issues of women.  There were 40-50 persons attending and participation was active.  
  1. Organization of the Working Party, scope of activities, composition of the working group, method of approach and anticipated products.
Time was devoted to discussing and planning the above issues.  This working party will be focused on coagulation values and clinical syndromes that are influenced by hormones.  The working party will evaluate existing data, determine issues for which data is missing or deficient, identify areas of controversy and pressing clinical need and discuss methodologic approaches to answer questions raised.  The working group may suggest or organize future collaborative studies as a result of these activities.  The working group will incorporate laboratory scientists, epidemiologists, hematologists, high-risk obstetricians and gynecologists.  All interested parties are encouraged to join an e-mail tree through marilyn.manco-johnson@uchsc.edu .  The e-mail tree will be used to further discussions and continue active collaborations throughout the year.

Bleeding Disorders in women:
Anne Dilley, CDC, Atlanta, USA, discussed screening for von Willebrand’s disease and other genetic bleeding disorders in women with menorrhagia.  The use and limits of existing screening tools for menorrhagia were reviewed.  Difficulties in the diagnosis of vWD were discussed including cost, timing and number of evaluations, use of reference laboratories, and high prevalence of the trait. Current challenges include validation of a screening questionnaire for menorrhagia, exploration of screening tests, including whole blood and thrombin generation assays, for vWD, platelet dysfunction and other bleeding disorders.

Peter Kouides, Rochester, USA, addressed efficacy of various therapies (OCPs, DDAVP, tranexemic acid, etc.) for menorrhagia. He raised the issue of safety of intrapartum DDAVP, endometrial ablation, Mirena pretestational ring, use of DDAVP for sports, and safety of hormonal therapies in menopausal women.  Limitations of efficacy and adherence with various vWD therapies were reviewed. Dr. Kouides suggested an ISTH survey on DDAVP use, guidelines for screening vWD, guidelines for management, and a survey on the diagnosis of vWD while using OCPs.

James Bussel, New York, USA, reviewed current updating of the Platelet Immunology Subcommittee recommendations for the evaluation and management of neonatal alloimmune thrombocytopenia.  Dr. Bussel discussed advances in platelet antigen typing, serologic testing, and antenatal treatment.  Revisions to recommendations for fetal testing were discussed.  Current in-process studies of combined use of IVIG and steroids prenatally were presented.  New recommendations stratified by fetal risk were discussed.
  1. Influence of hormones on coagulation values in women.
Dr. Margareta Blombäck presented data for coagulation proteins relative to the menstrual cycle, trimesters of pregnancy and hormonal therapies, including oral and topical administration of HRT during menopause.  Professor Blombäck advised that data are lacking primarily for hormonal effects on fibrinolysis overall, and that data are weak for the three generations of contraceptive agents.   The recommendation was made to explore global assays of thrombin generation, coagulation potential and fibrinolytic potential and apply these to the various hormonally influenced states noted above.
  1. Risk factors for thrombosis and adverse outcome in pregnant women.
Dr. Ian Greer, Glasgow, UK, discussed risk factors for thrombosis during pregnancy.  He stressed the gap between knowledge of risk factors (obesity, age, caesarean section, prior venous thrombosis, personal and family history of thrombosis) and appropriate application of diagnosis and interventions in pregnancy.  Prof. Greer reviewed evidence for thrombosis and thrombosis recurrence during pregnancy, safety of prophylaxis with LMWH and cost of screening and complications.  Suggestions were made to collaborate the study cost/efficacy of targeted screening as well as the use of aspirin and compression stockings for prevention.

Dr. Jacqueline Conard gave an elegant presentation of venous thromboembolism in pregnancy complicated by genetic antithrombin deficiency.  Thrombosis risk was delineated by propositus vs relative for antithrombin presentation, history of previous thrombosis, history of previous pregnancy-associated thrombosis, anticoagulation prophylaxis and antithrombin concentrate prophylaxis.  Recommendations were made to proceed with similar data construction for all known thrombophilic traits.

Dr. Marilyn Manco-Johnson presented evidence for the role of thrombophilic genes in adverse pregnancy outcomes including preeclampsia, abruption, intrauterine growth retardation, recurrent miscarriage and fetal demise.  General trends support the role of thrombophilic genes to increase the risk of adverse pregnancy outcome and to worsen existent disorders.  There is a wide variation in presence and strength of these effects, diluting the power of metanalyses secondary to methodologic differences in case definition, sample size, referral patterns, elegibility criteria, and other genetic and environmental variations in the study populations.  Examples include divergent results regarding the role of antiphospholipid antibodies in adverse pregnancy outcome.  Two large studies of more than 1000 cases failed to support a relationship of adverse pregnancy outcome to factor V Leiden.  Suggestions were made for prospective, multi-center studies with large numbers, standardized case definitions and outcome determinations.
  1. New Business
Future efforts will address HRT effects on coagulation and thrombosis risk, oral contraceptives and HELLP syndrome.  The e-mail tree will be used to continue these discussions, identify new members and prepare for an open meeting next year.