ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders

The clinical appreciation of the presence and severity of bleeding symptoms is a fundamental step in the evaluation of patients referred for a possible bleeding disorder [1Coller B.S. Schneiderman P. Clinical evaluation of hemorrhagic disorders: the bleeding history and differential diagnosis of purpura.in: Hoffman R Benz E Shattil J Furie B Cohen J Silberstein LE McGlave P Hematology. Basic Principles and Practice. Elsevier Churchill Livingstone, 2005: 1975-99Google Scholar]. A distinctive bleeding history is a prerequisite for the diagnosis of any bleeding disorder and should guide further laboratory investigations [2Rodeghiero F. Tosetto A. Castaman G. How to estimate bleeding risk in mild bleeding disorders.J Thromb Haemost. 2007; 5: 157-66Crossref PubMed Scopus (67) Google Scholar]. Retrospective data from cohorts of patients with von Willebrand disease (VWD) suggest that this strategy is a clinically useful approach. Furthermore, these data seem to indicate that the severity of bleeding symptoms correlates with the risk of future bleedings [3Rodeghiero F. Castaman G. Tosetto A. Batlle J. Baudo F. Cappelletti A. Casana P. De Bosch N. Eikenboom J.C.J. Federici A.B. Lethagen S. Linari S. Srivastava A. The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study.J Thromb Haemost. 2005; 3: 2619-26Crossref PubMed Scopus (291) Google Scholar, 4Tosetto A. Rodeghiero F. Castaman G. Goodeve A. Federici A.B. Batlle J. Meyer D. Fressinaud E. Mazurier C. Goudemand J. Eikenboom J. Schneppenheim R. Budde U. Ingerslev J. Vorlova Z. Habart D. Holmberg L. Lethagen S. Pasi J. Hill F. Peake I. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM‐1 VWD).J Thromb Haemost. 2006; 4: 766-73Crossref PubMed Scopus (438) Google Scholar]. In an attempt to standardize the diagnostic criteria of VWD, a bleeding questionnaire and a bleeding score were developed [3Rodeghiero F. Castaman G. Tosetto A. Batlle J. Baudo F. Cappelletti A. Casana P. De Bosch N. Eikenboom J.C.J. Federici A.B. Lethagen S. Linari S. Srivastava A. The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study.J Thromb Haemost. 2005; 3: 2619-26Crossref PubMed Scopus (291) Google Scholar], http://www.isth.org/default/assets/File/Bleeding_Type1_VWD.pdf [accessed 14 July 2010] and subsequently adapted by many different investigators to collect the hemorrhagic history in several published and ongoing studies. The questionnaire has proven to be useful for diagnostic purposes, allowing the establishment of quantitative cut‐offs discriminating healthy subjects and carriers of VWD [3Rodeghiero F. Castaman G. Tosetto A. Batlle J. Baudo F. Cappelletti A. Casana P. De Bosch N. Eikenboom J.C.J. Federici A.B. Lethagen S. Linari S. Srivastava A. The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study.J Thromb Haemost. 2005; 3: 2619-26Crossref PubMed Scopus (291) Google Scholar, 5Tosetto A. Castaman G. Rodeghiero F. Assessing bleeding in von Willebrand disease with bleeding score.Blood Rev. 2007; 21: 89-97Crossref PubMed Scopus (63) Google Scholar]. These cut‐offs are usually based on the cumulative bleeding score (BS), determined by the summative index of the maximum severity score of each bleeding symptom before diagnosis [5Tosetto A. Castaman G. Rodeghiero F. Assessing bleeding in von Willebrand disease with bleeding score.Blood Rev. 2007; 21: 89-97Crossref PubMed Scopus (63) Google Scholar]. Furthermore, the questionnaire and its associated BS systems have also been used for the description of symptoms in selected cohorts of patients [4Tosetto A. Rodeghiero F. Castaman G. Goodeve A. Federici A.B. Batlle J. Meyer D. Fressinaud E. Mazurier C. Goudemand J. Eikenboom J. Schneppenheim R. Budde U. Ingerslev J. Vorlova Z. Habart D. Holmberg L. Lethagen S. Pasi J. Hill F. Peake I. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM‐1 VWD).J Thromb Haemost. 2006; 4: 766-73Crossref PubMed Scopus (438) Google Scholar, 6Goodeve A. Eikenboom J. Castaman G. Rodeghiero F. Federici A.B. Batlle J. Meyer D. Mazurier C. Goudemand J. Schneppenheim R. Budde U. Ingerslev J. Habart D. Vorlova Z. Holmberg L. Lethagen S. Pasi J. Hill F. Hashemi Soteh M. Baronciani L. Hallden C. Guilliatt A. Lester W. Peake I. Phenotype and genotype of a cohort of families historically diagnosed with Type 1 von Willebrand Disease in the European study, molecular and clinical markers for the diagnosis and management of Type 1 von Willebrand Disease (MCMDM‐1VWD).Blood. 2007; 109: 112-21Crossref PubMed Scopus (321) Google Scholar, 7Bowman M. Riddel J. Rand M.L. Tosetto A. Silva M. James P.D. Evaluation of the diagnostic utility for von Willebrand disease of a pediatric bleeding questionnaire.J Thromb Haemost. 2009; 7: 1418-21Crossref PubMed Scopus (145) Google Scholar, 8Biss T.T. Blanchette V.S. Clark D.S. Bowman M. Wakefield C.D. Silva M. Lillicrap D. James P.D. Rand M.L. Quantitation of bleeding symptoms in children with von Willebrand Disease: use of a standardized pediatric bleeding questionnaire.J Thromb Haemost. 2010; 8: 950-6Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar]. The combination of a standardized bleeding questionnaire and a well‐defined interpretation grid (for the computation of the final BS) has been referred to as a Bleeding Assessment Tool (BAT). Some limitations of available BATs are however apparent, particularly concerning the overall scoring system: 1Existing tools are most useful to evaluate subjects referred for bleeding symptoms, as BATs were validated by comparison with normal or never referred subjects. Thus, less symptomatic mild bleeding disorder (MBD), e.g. mild hemophilia, may go undetected.2The severity of bleeding symptoms trumps other potentially clinically important features, such as the frequency of symptoms (i.e. the incidence of bleeding). Furthermore, existing tools were developed to evaluate MBD such as VWD, and are likely to become ‘saturated’ in severe bleeding disorders (homo/hemizygous forms). The ISTH/SSC Joint Working Group agreed to establish a single BAT to standardize the reporting of bleeding symptoms and that would be useful for both pediatric and adult populations (see Supporting Information). The revised BAT could improve upon the diagnosis of MBD (in continuity with previous questionnaires) and the grading of severity in patients with known inherited bleeding disorders. Several issues are to be addressed in the development of a revised BAT [9Koreth R. Weinert C. Weisdorf D.J. Key N.S. Measurement of bleeding severity: a critical review.Transfusion. 2004; 44: 605-17Crossref PubMed Scopus (42) Google Scholar]. Different types of validity need to be considered in the construct and analysis of a BAT. The BAT should be able to measure any change or abnormality which must be considered (content validity) and that is felt to be clinically significant for the disease under investigation (face validity). Therefore, a BAT should include questions regarding all symptoms that may be as a result of a haemorrhagic disorder. For instance, hemoptysis is rarely or never associated with a bleeding disorder, and including questions describing such symptoms is unlikely to add any valuable information. This is a critical issue as any BAT should be able to provide reproducible results. Future studies will be needed to evaluate inter‐rater and test‐retest reliabilities. We deployed two strategies to a priori improve the reliability of the proposed BAT. First, recall of symptoms from a patient should be enhanced by collecting data that may be unequivocally reported by the subjects. Assessment of the presence and severity of bleeding disorders is a retrospective task for physicians, which necessarily requires asking the patient (and/or his/her relatives) about bleeding symptoms that may have occurred months or years before. This is particularly important in the field of inherited bleeding disorders, where the presence of bleeding symptoms spans a lifetime and can be sporadic. Even when more objective data can be collected (e.g. quantification of menstrual blood loss by hematin or by a visual assessment tool [10Higham J.M. O’Brien P.M. Shaw R.W. Assessment of menstrual blood loss using a pictorial chart.Br J Obstet Gynaecol. 1990; 97: 734-9Crossref PubMed Scopus (813) Google Scholar]), the issue of reliability still remains, as what is measured at the time of observation may not accurately reflect the average presentation of a symptom over a longer period of time. In contrast, acquired bleeding disorders (e.g. ITP) are normally not lifelong and come to the physician’s attention within days to weeks of the initial bleeding event. In these disorders, a more detailed description of the bleeding symptoms is therefore possible and may be collected in a more detailed questionnaire. Second, the questionnaire will require some degree of assessor training (typically performed by a physician or other health professional) to ensure reliability and to reduce the timeload. With regard to this, one of the most challenging tasks of any BAT is the identification of ‘trivial’ bleeding, which is a symptom that falls within the definition of a normal event and that should not be recorded as a bleeding symptom, a task better performed by well‐trained personnel. The ISTH/SSC joint working group agreed to classify symptoms as significant whenever they: 1Cause emotional distress to the patient sufficient to interfere with his/her social life/activities (e.g. spontaneous epistaxis forcing the person to leave a meeting).2Require medical attention, either for reassurance or intervention (e.g. iron therapy, resuturing, etc.). Specific criteria for significant bleedings are reported in the Supporting Information. Furthermore, to improve the predictive value of BAT as a diagnostic tool, only symptoms reported before and at the time of diagnosis should be included, so as to exclude the confounding effects of prophylactic treatments given on the basis of a pre‐established diagnosis of a specific inherited bleeding disorder. Two bleeding scores have been proposed, one validated for diagnosis [3Rodeghiero F. Castaman G. Tosetto A. Batlle J. Baudo F. Cappelletti A. Casana P. De Bosch N. Eikenboom J.C.J. Federici A.B. Lethagen S. Linari S. Srivastava A. The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study.J Thromb Haemost. 2005; 3: 2619-26Crossref PubMed Scopus (291) Google Scholar] and another mainly for descriptive purposes [4Tosetto A. Rodeghiero F. Castaman G. Goodeve A. Federici A.B. Batlle J. Meyer D. Fressinaud E. Mazurier C. Goudemand J. Eikenboom J. Schneppenheim R. Budde U. Ingerslev J. Vorlova Z. Habart D. Holmberg L. Lethagen S. Pasi J. Hill F. Peake I. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM‐1 VWD).J Thromb Haemost. 2006; 4: 766-73Crossref PubMed Scopus (438) Google Scholar]. The latter, with some modifications, has been adapted for use in children [7Bowman M. Riddel J. Rand M.L. Tosetto A. Silva M. James P.D. Evaluation of the diagnostic utility for von Willebrand disease of a pediatric bleeding questionnaire.J Thromb Haemost. 2009; 7: 1418-21Crossref PubMed Scopus (145) Google Scholar]. Whereas in the first BS [3Rodeghiero F. Castaman G. Tosetto A. Batlle J. Baudo F. Cappelletti A. Casana P. De Bosch N. Eikenboom J.C.J. Federici A.B. Lethagen S. Linari S. Srivastava A. The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study.J Thromb Haemost. 2005; 3: 2619-26Crossref PubMed Scopus (291) Google Scholar] symptoms are scored from 0 (no symptom) to 3 (most severe), in the subsequently modified systems [4Tosetto A. Rodeghiero F. Castaman G. Goodeve A. Federici A.B. Batlle J. Meyer D. Fressinaud E. Mazurier C. Goudemand J. Eikenboom J. Schneppenheim R. Budde U. Ingerslev J. Vorlova Z. Habart D. Holmberg L. Lethagen S. Pasi J. Hill F. Peake I. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM‐1 VWD).J Thromb Haemost. 2006; 4: 766-73Crossref PubMed Scopus (438) Google Scholar, 7Bowman M. Riddel J. Rand M.L. Tosetto A. Silva M. James P.D. Evaluation of the diagnostic utility for von Willebrand disease of a pediatric bleeding questionnaire.J Thromb Haemost. 2009; 7: 1418-21Crossref PubMed Scopus (145) Google Scholar] the absence of bleeding after at least two hemostatic challenges was scored −1 and the grading spanned from −1 to 4. In both systems, only the most severe scores ever recorded for each symptom (and, in case, minus scores) are considered in obtaining the final total score. Since data comparing different BSs are unavailable, the ISTH/SSC joint working group agreed to develop a new Diagnostic Bleeding Score to be used mainly for the evaluation of patients referred for a possible bleeding disorder, that is for diagnostic purposes (see Table S1). The validity, reliability and predictive power of this new BS will need to be tested prospectively. Notably, although ‘negative scores’ for surgery, tooth extraction and postpartum bleeding were not icluded in the present BS, they can easily be extracted from the proposed questionnaire to allow comparison previously proposed BS. We acknowledge that a BS specifically adapted for severe bleeding disorders (homo‐emizygous bleeding disorders), including also the frequency of bleeding symptoms, could futher improve the description of the natural history of severe diseases. Achieving this goal will be one of the major future commitments of the ISTH/SSC Joint Working Group. Of note, the present questionnaire already includes two additional questions designed to approximate the ‘true’ incidence of bleeding. The first addresses the number of interventions per year of life; the second, the age of first occurrence, with the expectation that the earlier the onset, the more severe the disorder. In conclusion, we recommend to adopt the Consensus ISTH BAT (questionnaire and BS) for any future study addressing description of bleeding symptoms or diagnosis of bleeding disorders. Validation of the questionnaire and bleeding scale for clinical use is urgently needed for clinical application. The authors state that they have no conflict of interest. Data S1. The official communication of the SSC. Table S1. Bleeding score. Please note: Wiley‐Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. Download .doc (.35 MB) Help with doc files Supporting info item