Rare Bleeding Disorders: Worldwide Efforts for Classification, Diagnosis, and Management

 

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Abstract

Rare bleeding disorders (RBDs) comprise the inherited deficiencies of coagulation factors such as fibrinogen, factor (F)II, FV, FV + FVIII, FVII, FX, FXI, and FXIII, and are usually transmitted as autosomal recessive disorders. RBDs are characterized by a wide variety of symptoms from mild to severe; however, due to their rarity, only little information is available on the adequate management of patients affected with these deficiencies. Moreover, the limitations of laboratory assays and the lack of a definitive consensus concerning their classification have prevented adoption of optimal approaches to their individual management. To overcome these limitations, new strategies are therefore necessary, such as the establishment of global collaborations and networks among treatment centers, as well as increasing support provided by public health organizations.

• References

• 1 Regulation (EC) No 141/2000 of the European Parliament and of the Council. Available at: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2000:018:0001:0005:en:PDF . Accessed April 26, 2013
  PubMedGoogle Scholar
• 2 Rare Diseases Act 2002–USA Public Law. Available at: http://history.nih.gov/research/downloads/PL107-280.pdf . Accessed April 26, 2013
  PubMedGoogle Scholar
• 3 Tuddenham EGD, Cooper DN. The Molecular Genetics of Haemostasis and Its Inherited Disorders. Oxford; New York: Oxford University Press; 1994
  Google Scholar
• 4 Peyvandi F, Palla R, Menegatti M, Mannucci PM. Introduction. Rare bleeding disorders: general aspects of clinical features, diagnosis, and management. Semin Thromb Hemost 2009; 35 (4) 349-355
  Article in Thieme ConnectPubMedGoogle Scholar
• 5 Peyvandi F, Palla R, Menegatti M , et al; European Network of Rare Bleeding Disorders Group. 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 (4) 615-621
  CrossrefPubMedGoogle Scholar
• 6 Peyvandi F, Di Michele D, Bolton-Maggs PHB, Lee CA, Tripodi A, Srivastava A. Project on Consensus Definitions in Rare Bleeding Disorders of the Factor VIII/Factor IX Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Classification of rare bleeding disorders (RBDs) based on the association between coagulant factor activity and clinical bleeding severity. J Thromb Haemost 2012; 10 (9) 1938-1943
  CrossrefPubMedGoogle Scholar
• 7 Borhany M, Pahore Z, Ul Qadr Z , et al. Bleeding disorders in the tribe: result of consanguineous in breeding. Orphanet J Rare Dis 2010; 5: 23
  CrossrefPubMedGoogle Scholar
• 8 Jaouad IC, Elalaoui SC, Sbiti A, Elkerh F, Belmahi L, Sefiani A. Consanguineous marriages in Morocco and the consequence for the incidence of autosomal recessive disorders. J Biosoc Sci 2009; 41 (5) 575-581
  CrossrefPubMedGoogle Scholar
• 9 al-Gazali LI, Bener A, Abdulrazzaq YM, Micallef R, al-Khayat AI, Gaber T. Consanguineous marriages in the United Arab Emirates. J Biosoc Sci 1997; 29 (4) 491-497
  Google Scholar
• 10 Hafez M, El-Tahan H, Awadalla M, El-Khayat H, Abdel-Gafar A, Ghoneim M. Consanguineous matings in the Egyptian population. J Med Genet 1983; 20 (1) 58-60
  CrossrefPubMedGoogle Scholar
• 11 al Husain M, al Bunyan M. Consanguineous marriages in a Saudi population and the effect of inbreeding on prenatal and postnatal mortality. Ann Trop Paediatr 1997; 17 (2) 155-160
  CrossrefPubMedGoogle Scholar
• 12 Saadat M, Ansari-Lari M, Farhud DD. Consanguineous marriage in Iran. Ann Hum Biol 2004; 31 (2) 263-269
  CrossrefPubMedGoogle Scholar
• 13 Viswabandya A, Baidya S, Nair SC , et al. Correlating clinical manifestations with factor levels in rare bleeding disorders: a report from Southern India. Haemophilia 2012; 18 (3) e195-e200
  CrossrefPubMedGoogle Scholar
• 14 Peretz H, Mulai A, Usher S , et al. The two common mutations causing factor XI deficiency in Jews stem from distinct founders: one of ancient Middle Eastern origin and another of more recent European origin. Blood 1997; 90 (7) 2654-2659
  PubMedGoogle Scholar
• 15 Ali T, Schved JF. Registry of hemophilia and other bleeding disorders in Syria. Haemophilia 2012; 18 (6) 851-854
  CrossrefPubMedGoogle Scholar
• 16 Karimi M, Haghpanah S, Amirhakimi A, Afrasiabi A, Dehbozorgian J, Nasirabady S. Spectrum of inherited bleeding disorders in southern Iran, before and after the establishment of comprehensive coagulation laboratory. Blood Coagul Fibrinolysis 2009; 20 (8) 642-645
  CrossrefPubMedGoogle Scholar
• 17 Bolton-Maggs PHB, Favaloro EJ, Hillarp A, Jennings I, Kohler HP. Difficulties and pitfalls in the laboratory diagnosis of bleeding disorders. Haemophilia 2012; 18 (Suppl. 04) 66-72
  CrossrefPubMedGoogle Scholar
• 18 Bolton-Maggs PH, Patterson DA, Wensley RT, Tuddenham EG. Definition of the bleeding tendency in factor XI-deficient kindreds—a clinical and laboratory study. Thromb Haemost 1995; 73 (2) 194-202
  PubMedGoogle Scholar
• 19 Kohler HP, Ichinose A, Seitz R, Ariens RAS, Muszbek L. Factor XIII And Fibrinogen SSC Subcommittee Of The ISTH. Diagnosis and classification of factor XIII deficiencies. J Thromb Haemost 2011; 9 (7) 1404-1406
  CrossrefPubMedGoogle Scholar
• 20 Muszbek L, Bagoly Z, Cairo A, Peyvandi F. Novel aspects of factor XIII deficiency. Curr Opin Hematol 2011; 18 (5) 366-372
  CrossrefPubMedGoogle Scholar
• 21 Chitlur M. Challenges in the laboratory analyses of bleeding disorders. Thromb Res 2012; 130 (1) 1-6
  CrossrefPubMedGoogle Scholar
• 22 Hemker HC, Giesen P, Al Dieri R , et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33 (1) 4-15
  CrossrefPubMedGoogle Scholar
• 23 Chitlur M, Sorensen B, Rivard GE , et al. Standardization of thromboelastography: a report from the TEG-ROTEM working group. Haemophilia 2011; 17 (3) 532-537
  CrossrefPubMedGoogle Scholar
• 24 van Geffen M, Loof A, Lap P , et al. A novel hemostasis assay for the simultaneous measurement of coagulation and fibrinolysis. Hematology 2011; 16 (6) 327-336
  CrossrefPubMedGoogle Scholar
• 25 Al Dieri R, Peyvandi F, Santagostino E , et al. The thrombogram in rare inherited coagulation disorders: its relation to clinical bleeding. Thromb Haemost 2002; 88 (4) 576-582
  PubMedGoogle Scholar
• 26 Van Geffen M, Menegatti M, Loof A , et al. Retrospective evaluation of bleeding tendency and simultaneous thrombin and plasmin generation in patients with rare bleeding disorders. Haemophilia 2012; 18 (4) 630-638
  CrossrefPubMedGoogle Scholar
• 27 Strey RF, Siegemund A, Siegemund T , et al. Influence of factor V HR2 on thrombin generation and clinical manifestation in rare bleeding disorders. Pathophysiol Haemost Thromb 2005; 34 (6) 279-283
  CrossrefPubMedGoogle Scholar
• 28 Spiezia L, Radu C, Campello E , et al. Whole blood rotation thromboelastometry (ROTEM(®)) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V. Haemophilia 2012; 18 (3) 463-468
  CrossrefPubMedGoogle Scholar
• 29 Rugeri L, Quélin F, Chatard B, De Mazancourt P, Negrier C, Dargaud Y. Thrombin generation in patients with factor XI deficiency and clinical bleeding risk. Haemophilia 2010; 16 (5) 771-777
  CrossrefPubMedGoogle Scholar
• 30 Livnat T, Shenkman B, Spectre G , et al. Recombinant factor VIIa treatment for asymptomatic factor VII deficient patients going through major surgery. Blood Coagul Fibrinolysis 2012; 23 (5) 379-387
  CrossrefPubMedGoogle Scholar
• 31 van Veen JJ, Hampton KK, Maclean R, Fairlie F, Makris M. Blood product support for delivery in severe factor X deficiency: the use of thrombin generation to guide therapy. Blood Transfus 2007; 5 (4) 204-209
  PubMedGoogle Scholar
• 32 Riddell A, Abdul-Kadir R, Pollard D, Tuddenham E, Gomez K. Monitoring low dose recombinant factor VIIa therapy in patients with severe factor XI deficiency undergoing surgery. Thromb Haemost 2011; 106 (3) 521-527
  Article in Thieme ConnectPubMedGoogle Scholar
• 33 Jennings I, Kitchen DP, Woods TAL, Kitchen S, Walker ID. Emerging technologies and quality assurance: the United Kingdom National External Quality Assessment Scheme perspective. Semin Thromb Hemost 2007; 33 (3) 243-249
  Article in Thieme ConnectPubMedGoogle Scholar
• 34 de Moerloose P, Neerman-Arbez M. Congenital fibrinogen disorders. Semin Thromb Hemost 2009; 35 (4) 356-366
  Article in Thieme ConnectPubMedGoogle Scholar
• 35 Bolton-Maggs PH. Factor XI deficiency—resolving the enigma?. Hematology (Am Soc Hematol Educ Program) 2009; 97-105
  PubMedGoogle Scholar
• 36 Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood 2004; 104 (5) 1243-1252
  CrossrefPubMedGoogle Scholar
• 37 Registry of clotting factor concentrates, Ninth Edition, 2012 by Mark Brooker. Available at: http://www1.wfh.org/publication/files/pdf-1227.pdf
  PubMedGoogle Scholar
• 38 Bolton-Maggs PH, Perry DJ, Chalmers EA , et al. The rare coagulation disorders—review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia 2004; 10 (5) 593-628
  CrossrefPubMedGoogle Scholar
• 39 Castaman G. Prophylaxis of bleeding episodes and surgical interventions in patients with rare inherited coagulation disorders. Blood Transfus 2008; 6 (Suppl. 02) s39-s44
  PubMedGoogle Scholar
• 40 Peyvandi F, Garagiola I, Menegatti M. Gynecological and obstetrical manifestations of inherited bleeding disorders in women. J Thromb Haemost 2011; 9 (Suppl. 01) 236-245
  CrossrefPubMedGoogle Scholar
• 41 James AH. More than menorrhagia: a review of the obstetric and gynaecological manifestations of bleeding disorders. Haemophilia 2005; 11 (4) 295-307
  CrossrefPubMedGoogle Scholar
• 42 Siboni SM, Spreafico M, Calò L , et al. Gynaecological and obstetrical problems in women with different bleeding disorders. Haemophilia 2009; 15 (6) 1291-1299
  CrossrefPubMedGoogle Scholar
• 43 James AH, Kouides PA, Abdul-Kadir R , et al. Von Willebrand disease and other bleeding disorders in women: consensus on diagnosis and management from an international expert panel. Am J Obstet Gynecol 2009; 201 (1) e1-e8
  PubMedGoogle Scholar
• 44 Kadir RA, Chi C, Bolton-Maggs P. Pregnancy and rare bleeding disorders. Haemophilia 2009; 15 (5) 990-1005
  CrossrefPubMedGoogle Scholar
• 45 Salomon O, Steinberg DM, Tamarin I, Zivelin A, Seligsohn U. Plasma replacement therapy during labor is not mandatory for women with severe factor XI deficiency. Blood Coagul Fibrinolysis 2005; 16 (1) 37-41
  CrossrefPubMedGoogle Scholar
• 46 Myers B, Pavord S, Kean L, Hill M, Dolan G. Pregnancy outcome in factor XI deficiency: incidence of miscarriage, antenatal and postnatal haemorrhage in 33 women with factor XI deficiency. BJOG 2007; 114 (5) 643-646
  CrossrefPubMedGoogle Scholar
• 47 Lak M, Keihani M, Elahi F, Peyvandi F, Mannucci PM. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. Br J Haematol 1999; 107 (1) 204-206
  CrossrefPubMedGoogle Scholar
• 48 Evron S, Anteby SO, Brzezinsky A, Samueloff A, Eldor A. Congenital afibrinogenemia and recurrent early abortion: a case report. Eur J Obstet Gynecol Reprod Biol 1985; 19 (5) 307-311
  CrossrefPubMedGoogle Scholar
• 49 Burrows RF, Ray JG, Burrows EA. Bleeding risk and reproductive capacity among patients with factor XIII deficiency: a case presentation and review of the literature. Obstet Gynecol Surv 2000; 55 (2) 103-108
  CrossrefPubMedGoogle Scholar
• 50 Kobayashi T, Kanayama N, Tokunaga N, Asahina T, Terao T. Prenatal and peripartum management of congenital afibrinogenaemia. Br J Haematol 2000; 109 (2) 364-366
  CrossrefPubMedGoogle Scholar
• 51 Kumar M, Mehta P. Congenital coagulopathies and pregnancy: report of four pregnancies in a factor X-deficient woman. Am J Hematol 1994; 46 (3) 241-244
  CrossrefPubMedGoogle Scholar
• 52 Goodwin TM. Congenital hypofibrinogenemia in pregnancy. Obstet Gynecol Surv 1989; 44 (3) 157-161
  CrossrefPubMedGoogle Scholar
• 53 Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen. Thromb Haemost 1995; 73 (1) 151-161
  PubMedGoogle Scholar
• 54 Noia G, De Carolis S, De Stefano V , et al. Factor V deficiency in pregnancy complicated by Rh immunization and placenta previa. A case report and review of the literature. Acta Obstet Gynecol Scand 1997; 76 (9) 890-892
  CrossrefPubMedGoogle Scholar
• 55 Rizk DE, Castella A, Shaheen H, Deb P. Factor VII deficiency detected in pregnancy: a case report. Am J Perinatol 1999; 16 (5) 223-226
  Article in Thieme ConnectPubMedGoogle Scholar
• 56 Girolami A, Lazzarin M, Scarpa R, Brunetti A. Further studies on the abnormal factor X (factor X Friuli) coagulation disorder: a report of another family. Blood 1971; 37 (5) 534-541
  PubMedGoogle Scholar
• 57 Peyvandi F, Menegatti M, Siboni SM. Post-partum hemorrhage in women with rare bleeding disorders. Thromb Res 2011; 127 (Suppl. 03) S116-S119
  CrossrefPubMedGoogle Scholar
• 58 Soucie JM, McAlister S, McClellan A, Oakley M, Su Y. The universal data collection surveillance system for rare bleeding disorders. Am J Prev Med 2010; 38 (4, Suppl): S475-S481
  CrossrefPubMedGoogle Scholar
• 59 Makris M, Calizzani G, Fischer K , et al. EUHASS: The European Haemophilia Safety Surveillance system. Thromb Res 2011; 127 (Suppl. 02) S22-S25
  CrossrefPubMedGoogle Scholar