Bleeding symptoms at disease presentation and prediction of ensuing bleeding in inherited FVII deficiency^{[ * ]}

 

 Buy Article Permissions and Reprints

Summary

Individuals with inherited factor VII (FVII) deficiency display bleeding phenotypes ranging from mild to severe, with 30% of patients having always been asymptomatic (non-bleeding). In 626 FVII-deficient individuals, by analysing data from the International Factor VII (IF7) Registry and the Seven Treatment Evaluation Registry (STER), we determined whether bleeding type at disease presentation and FVII coagulant activity (FVIIc) predict ensuing bleeds. At disease presentation/diagnosis, 272 (43.5%) individuals were non-bleeding, 277 (44.2%) had minor bleeds, and 77 (12.3%) had major bleeds. During a median nine-year index period (IP) observation, 87.9% of non-bleeding individuals at presentation remained asymptomatic, 75.1% of minor-bleeders had new minor bleeds, and 83.1% of major-bleeders experienced new major bleeds. After adjusting for FVIIc levels and other clinical and demographic variables, the relative risk (RR) for ensuing bleedings during the IP was 6.02 (p <0.001) and 5.87 (p <0.001) in individuals presenting with major and minor bleeds, respectively. Conversely, compared to non-bleeding individuals, a 10.95 (p = 0.001) and 28.21 (p <0.001) RR for major bleedings during the IP was found in those with minor and with major bleeds at presentation, respectively. In conclusion, in FVII deficiency, the first major bleeding symptom is an independent predictor of the risk of subsequent major bleeds.

^* Presented as an oral presentation at the 53rd Annual Meeting of the American Society of Hematology (ASH), San Diego, California (Blood, ASH Annual meeting abstracts) 2011; 118: Abstract 30.

^** A complete list of the members of the Seven Treatment Evaluation Registry (STER) Study Group appears in the Appendix.

• References

• 1 Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood 2004; 104: 1243-1252.
  CrossrefPubMedGoogle Scholar
• 2 Mariani G, Bernardi F. Factor VII Deficiency. Semin Thromb Hemost 2009; 35: 400-406.
  Article in Thieme ConnectPubMedGoogle Scholar
• 3 Perry DJ. Factor VII Deficiency. Br J Haematol 2002; 118: 689-700.
  CrossrefPubMedGoogle Scholar
• 4 Borhany M, Pahore Z, Ul Qadr Z. et al. Bleeding disorders in the tribe: result of consanguineous in breeding. Orphanet J Rare Dis 2010; 05: 23.
  CrossrefPubMedGoogle Scholar
• 5 Mariani G, Herrmann FH, Dolce A. et al. Clinical phenotypes and factor VII genotype in congenital factor VII deficiency. Thromb Haemost 2005; 93: 481-487.
  Article in Thieme ConnectPubMedGoogle Scholar
• 6 Giansily-Blaizot M, Biron-Andreani C, Aguilar-Martinez P. et al. Inherited factor VII deficiency and surgery: clinical data are the best criteria to predict the risk of bleeding. Br J Haematol 2002; 117: 172-175.
  CrossrefPubMedGoogle Scholar
• 7 Rodeghiero F, Castaman G, Tosetto A. et al. The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study. J Thromb Haemost 2005; 03: 2619-2626.
  CrossrefPubMedGoogle Scholar
• 8 Tosetto A, Rodeghiero F, Castaman G. et al. 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; 04: 766-773.
  CrossrefPubMedGoogle Scholar
• 9 Mariani G, Dolce A, Batorova A. et al. Recombinant, activated factor VII for surgery in factor VII deficiency: a prospective evaluation - the surgical STER. Br J Haematol 2011; 152: 340-346.
  CrossrefPubMedGoogle Scholar
• 10 Mariani G, Herrmann FH, Bernardi F. et al. Clinical manifestations, management, and molecular genetics in congenital factor VII deficiency: the International Registry on Congenital Factor VII Deficiency (IRF7). Blood 2000; 96: 374.
  CrossrefPubMedGoogle Scholar
• 11 Mariani G, Herrmann FH, Schulman S. et al. Thrombosis in inherited factor VII deficiency. J Thromb Haemost 2003; 01: 2153-2158.
  CrossrefPubMedGoogle Scholar
• 12 Ingerslev J, Christiansen K, Sorensen B. Inhibitor to factor VII in severe factor VII deficiency: detection and course of the inhibitory response. J Thromb Hae-most 2005; 03: 799-800.
  CrossrefPubMedGoogle Scholar
• 13 Bernardi F, Dolce A, Pinotti M. et al. Major differences in bleeding symptoms between factor VII deficiency and hemophilia B. J Thromb Haemost 2009; 07: 774-779.
  CrossrefPubMedGoogle Scholar
• 14 Bernardi F, Arcieri P, Bertina RM. et al. Contribution of factor VII genotype to activated FVII levels. Differences in genotype frequencies between northern and southern European populations. Arterioscler Thromb Vasc Biol 1997; 17: 2548-2553.
  CrossrefPubMedGoogle Scholar
• 15 Mariani G, Mazzucconi MG, Hermans J. et al. Factor VII deficiency: immunological characterization of genetic variants and detection of carriers. Br J Hae-matol 1981; 48: 7-14.
  PubMedGoogle Scholar
• 16 Mariani G, Mazzucconi MG. Factor VII congenital deficiency. Clinical picture and classification of the variants. Haemostasis 1983; 13: 169-177.
  PubMedGoogle Scholar
• 17 Roberts HR, Escobar MA. Inherited disorders of prothrombin conversion. In: Hemostasis and Thrombosis: basic principles and clinical practice. Lippincott Williams & Wilkins; Fifth Edition. 2006
  Google Scholar
• 18 Ragni MV, Lewis JH, Spero JA. et al. Factor VII deficiency. Am J Hematol 1981; 10: 79-88.
  CrossrefPubMedGoogle Scholar
• 19 Peyvandi F, Palla R, Menegatti M. et al. Introduction. Rare bleeding disorders: general aspects of clinical features, diagnosis, and management. Semin Thromb Hemost 2009; 35: 349-355.
  Article in Thieme ConnectPubMedGoogle Scholar
• 20 Peyvandi F, Palla R, Menegatti M. et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European network of rare bleeding disorders. J Thromb Haemost 2012; 10: 615-621.
  CrossrefPubMedGoogle Scholar
• 21 Siboni SM, Zanon E, Sottilotta G. et al. Central nervous system bleeding in patients with rare bleeding disorders. Haemophilia 2012; 18: 34-38.
  PubMedGoogle Scholar
• 22 Mariani G, Dolce A, Napolitano M. et al. Invasive procedures and minor surgery in factor VII deficiency. Haemophilia 2012; 18: e63-e65.
  CrossrefPubMedGoogle Scholar
• 23 Tosetto A, Castaman G, Rodeghiero F. Bleeding scores in inherited bleeding disorders: clinical or research tools?. Haemophilia 2008; 14: 415-422.
  CrossrefPubMedGoogle Scholar
• 24 Tosetto A, Castaman G, Rodeghiero F. Evidence-based diagnosis of type 1 von Willebrand disease: a Bayes theorem approach. Blood 2008; 111: 3998-4003.
  CrossrefPubMedGoogle Scholar
• 25 Rodeghiero F, Tosetto A, Abshire T. et al. ISTH/SSC joint VWF and Perinatal/ Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010; 08: 2063-2065.
  CrossrefPubMedGoogle Scholar
• 26 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 03: 692-694.
  CrossrefPubMedGoogle Scholar
• 27 Napolitano M, Giansily-Blaizot M, Dolce A. et al. Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER). Haematologica. 2013 Epub ahead of print
  PubMedGoogle Scholar
• 28 Mariani G, Napolitano M, Dolce A. et al. on behalf of the Seven Treatment Evaluation Registry (STER) and the International Factor VII Deficiency Study Groups. Replacement therapy for bleeding episodes in factor VII deficiency. A prospective evaluation. Thromb Haemost 2013; 109: 238-247.
  Article in Thieme ConnectPubMedGoogle Scholar
• 29 Bernardi F, Marchetti G, Dolce A. et al. How to evaluate phenotype-genotype relationship in rare coagulation haemorrhagic disorders: examples from FVII deficiency. Haemophilia 2004; 10 (Suppl. 04) 177-179.
  CrossrefPubMedGoogle Scholar