Disorders that affect any of the coagulation factors besides FVIII, FIX and VWF are called extremely rare bleeding disorders because they are less prevalent than haemophilia or VWD.
Below you will find a table of information on extremely rare bleeding disorders.
People affected by extremely rare bleeding disorders in Europe are faced with many issues including a lack of diagnosis and treatment. In fact, only a few specialised centres in Europe have the resources and the expertise to diagnose extremely rare bleeding disorders. Furthermore, for many of these disorders there are no treatments available. This is because these conditions are so rare that it is difficult to develop products and run clinical trials. Moreover, once the product is developed, it may not be commercially attractive to market. This is why many people with extremely rare bleeding disorders are still relying on completely inadequate treatments such as Fresh Frozen Plasma and Cryoprecipitate.
Characteristics of Extremely Rare Bleeding Disorders(Also known as Rare Clotting Factor Deficiencies) |
||||
Missing Factor |
Incidence* |
Inheritance |
Severity of Bleeding |
Treatment |
|
Factor I Afibrogenemia Hypofibrogenemia Dysfibrogenemia |
5 in 10 million Not available 1 in 1 million |
Autosomal recessive Recessive or dominant Recessive or dominant |
Usually mild, except in Afibrogenemia |
Figrinogen concentrate Cryoprecipitate Fresh frozen plasma |
|
Factor II |
1 in 2 million |
Autosomal recessive** |
Usually mild |
Prothrombin complex concentrate Fresh frozen plasma |
|
Factor V |
1 in 1 million |
Autosomal recessive |
Usually mild |
Fresh frozen plasma |
|
Combined factor V and factor VIII |
1 in 1 million+ |
Autosomal recessive++ |
Usually mild |
Fresh frozen plasma Factor VIII concentrate Desmopressin |
|
Factor VII |
1 in 500,000 |
Autosomal recessive** |
Severe when factor levels are low |
Recombinant factor VIIa concentrate Factor VII concentrate Prothrombin complex concentrate Fresh frozen plasma |
|
Factor X |
1 in 1 million |
Autosomal recessive |
Moderate to severe when factor levels are low |
Prothrombin complex concentrate Fresh frozen plasma |
|
Combined deficiency of vitamin K-dependent clotting factor |
Not available |
Autosomal recessive** |
Usually mild but a few families have reported very low levels and more severe symptoms |
Vitamin K Prothrombin complex concentrate Fresh frozen plasma |
|
Factor XI |
1 in 100,000 |
Recessive or dominant |
Mild to moderate when factor levels are low |
Factor IX concentrate Antifibrinolytic drug Fibrin glue Fresh frozen plasma |
|
Factor XIII |
1 in 3 million |
Autosomal recessive |
Severe |
Factor XIII concentrate Cryoprecipitate Fresh frozen plasma |
“*” estimates only
“**” Can be acquired later in life because of another medical condition, certain medication, etc.
“+” 1 in 100,000 in some populations, including Israel, Iran, Italy
“++” very rarely, factor VIII deficiency can be inherited separately from only one parent
Resources:
For more detailed information regarding each disorder, we advise you to consult the website of the World Federation of Haemophilia.
Informations about the disease, ongoing clinical trials, available products and registries can be found for each disorder on the website of Orpha.net. The website provides information in English, French, German, Italian, Dutch, Portuguese and Spanish.
We also recommend that you consult the booklet on “Rare Bleeding Disorders” from the Irish Haemophilia Society and read the proceedings of the EHC Round Table on: “Rare Bleeding Disorders” held in March 2014.
The Rare Bleeding Disorders Database (Pro-RBDD), a component of the EUHANET Project.
The booklet developed by the European Network of Rare Bleeding Disorders.
Jim is aged 66 and has Haemophilia A with a high titer inhibitor which he developed at age 14.
Maria Elisa Mancuso (MD, PhD) is a Haematologist and works as a Senior Haematology Consultant at the Center for Thrombosis and Haemorrhagic Diseases of IRCCS Humanitas Research Hospital in Rozzano, Milan, Italy. She is Adjunct Clinical Professor at Humanitas University. She obtained a post-degree in Clinical and Experimental Haematology and a PhD in Clinical Methodology. She is involved in clinical research and has published several original articles in peer-reviewed journals a The Lancet, Blood, Journal of Thrombosis and Haemostasis, Haematologica, Thrombosis and Haemostasis, British Journal of Haematology and Haemophilia. She is reviewer for several peer-reviewed journals and member of the Editorial Board of JTH. She is a member of several scientific societies (ISTH, WFH, ASH, EAHAD, SISET, AICE) and was a medical member of the Inhibitor Working Group of the European Hemophilia Consortium. She is co-chair of the ADVANCE Study Group. She has acted also as co-chair of the Scientific and Standardization Subcommittee of ISTH on FVIII, FIX and rare bleeding disorders. She has been involved as principal and co-investigator in several clinical trials, and she takes care of both children and adults with hemophilia and other congenital bleeding disorders with a specific scientific interest in novel therapies, prophylaxis, inhibitors, and chronic hepatitis C.
As a patient with factor II deficiency, the diagnostic and treatment of rare bleeding disorders is a matter dear to my heart. My motivation to participate in the work of the ERIN committee is to improve both diagnostic and treatment for patients with rare bleeding disorders across Europe.
Economist and financial expert by profession, executive coach and trainer by passion and haemophilia advocate by every drop of my blood through my son (who has severe haemophilia A with inhibitors). Bringing a good decade of practical experience from the corporate insurance world, laser focus, growth mindset and resilience from my own experience, offering you anything I can just do, in hope that together we can make life more fulfilled for those impacted by bleeding disorders.
Amy Owen-Wyard is a Registered Mental Health Nurse. With experience working with children, young people, their families and adults with severe and enduring mental health conditions. Amy was also involved in a service improvement to provide a holistic care approach for those in general hospitals to support both their mental and physical health, whilst sharing her expertise and knowledge in mental health with the wider multidisciplinary team.
