FACTOR XII
DEFICIENCY
AN INHERITED
BLEEDING DISORDER
AN INFORMATION
BOOKLET
Acknowledgements
This information booklet on Factor XII Deficiency was prepared by:
Nathalie Aubin
Nurse Coordinator, Hemophilia Centre
Montreal Children’s Hospital
2300 Tupper Street, A216
Montreal, Quebec H3H 1P3
Claudine Amesse
Nurse Coordinator, Hemophilia Centre
Sainte-Justine Hospital
3175 Côte Sainte-Catherine Road
Montreal, Quebec H3T 1C5
Louisette Baillargeon
Nurse Coordinator, Hemophilia Centre
CHUS –Fleurimont Hospital
3001 12th Avenue North
Fleurimont, Quebec J1H 5N4
Sylvie Lacroix
Nurse Coordinator, Hemophilia Centre
Quebec Reference Centre for the Treatment of Patients with Inhibitors
Sainte-Justine Hospital
3175 Côte Sainte-Catherine Road
Montreal, Quebec H3T 1C5
Ginette Lupien
Nurse Coordinator
Centre régional de l’hémophilie de l’est du Québec
Hôpital de l’Enfant Jésus
1401, 18ième Rue
Québec, Québec G1J 1Z4
We are very grateful to the following people who kindly undertook to review this information in
this booklet. Their suggestions were very much appreciated.
Francine Derome, RN
Nurse
Sainte-Justine Hospital
Dr. George Etienne Rivard
Hematologist
Sainte-Justine Hospital
Claude Meilleur, RN
Nurse
Sainte-Justine Hospital
Dr. Molly Warner
Hematologist
Montreal Children’s Hospital
We would like to thank Natalie Ross for her contribution to the word processing of the text.
This brochure provides general information only. The Canadian Hemophilia Society does
NOT practice medicine and does not suggest specific treatments. In all cases, we suggest
that you speak with a doctor before you begin any treatment.
ISBN 0-920967-52-3 ©2004
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FACTOR XII DEFICIENCY – AN INHERITED BLEEDING DISORDER
CONTENTS
Introduction ...............................................................................4
How Factor XII Deficiency is Inherited ......................................5
What is Factor XII Deficiency.....................................................7
Incidence ....................................................................................9
Diagnosis ....................................................................................9
Symptoms ...................................................................................9
Treatment ...................................................................................9
Recommendation for the Patient with Factor XII Deficiency ....10
The Comprehensive Care Team...............................................10
For More Information ..............................................................11
References ................................................................................11
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FACTOR XII DEFICIENCY – AN INHERITED BLEEDING DISORDER
Introduction
Severe Factor XII deficiency is a very rare condition and is not well
known, even among health professionals.
The purpose of this booklet is to describe the deficiency with the
hope that it will permit those affected to better understand the
issues.
4
FACTOR XII DEFICIENCY – AN INHERITED BLEEDING DISORDER
How Factor XII Deficiency is Inherited
Congenital Factor XII deficiency is an inherited coagulation
protein deficiency disorder. This means that it is passed on from
parent to child at the time of conception. The coagulation protein
deficiency is caused by an abnormal gene.
Each cell of the body contains structures called “chromosomes.”
A chromosome is a long chain of chemicals known as DNA.
This DNA is arranged into about 30,000 units called genes. These
genes determine such things as the colour of a person’s eyes. In the
case of Factor XII deficiency, one of these genes has a defect.
The defective gene in Factor XII deficiency is on a chromosome
that does not decide the sex of the child. This means that Factor
XII deficiency can affect females as well as males.
A carrier is a person who carries the defective gene. This person
may have few symptoms or no symptoms at all. In order for a
person to inherit Severe Factor XII deficiency, both parents must
be carriers. In such a case, the baby inherits two defective Factor
XII genes, one from the mother and the other from the father.
If a person inherits the defective gene from only one of the
parents, he/she will be a carrier. Her Factor XII level will be lower
than normal. Symptoms of the disease may be absent or only
slightly present.
5
FACTOR XII DEFICIENCY – AN INHERITED BLEEDING DISORDER
The three illustrations below show how Factor XII deficiency
can be passed on:
FIGURE 1 below shows what can happen when a carrier of Factor XII
deficiency has children with another carrier. There is a 1 in 4 chance that
a child will have severe Factor XII deficiency, a 1 in 2 chance that a child
will be a carrier and a 1 in 4 chance that a child will not be affected.
FIGURE 2 shows what can happen when someone with severe Factor
XII deficiency has children with a non-carrier. All the children will be
carriers, but the disease will affect none of them.
FIGURE 3 shows what can happen when someone with severe Factor
XII deficiency has children with a carrier. There is a 1 in 2 chance that a
child will be a carrier. There is also a 1 in 2 chance that a child will have
a severe Factor XII deficiency.
6
FACTOR XII DEFICIENCY – AN INHERITED BLEEDING DISORDER
What is Factor XII Deficiency?
Factor XII deficiency is a rare inherited coagulation factor
deficiency. It was first identified in 1955. Factor XII is also known
as Hageman Factor, named after the patient in whom this
condition was first diagnosed.
Factor XII is a protein in the blood. It plays a role in the
coagulation cascade. Blood is carried throughout the body in a
network of blood vessels. When tissues are injured, damage to a
blood vessel may result in leakage of blood through holes in a
vessel wall. The vessels can break near the surface, as in the case of
a cut. Or they can break deep inside the body, causing a bruise or
internal hemorrhage.
Clotting or coagulation, is a complex process that makes it
possible to stop injured blood vessels from bleeding. As soon as a
blood vessel wall breaks, the components responsible for
coagulation come together to form a plug at the break. There are
several steps involved in forming a plug:
• Blood platelets, which are very tiny cell fragments, are the
first to arrive at the break. They clump together and stick
to the wall of the damaged vessel.
• These platelets then emit chemical signals calling for help
from other platelets and from clotting factors.
• The clotting factors, which are tiny plasma proteins, lead to
the deposition of fibrin, an efficient plug. The strands of
fibrin join together to weave a mesh around the platelets.
7
FACTOR XII DEFICIENCY – AN INHERITED BLEEDING DISORDER
The following diagram was devised by a Toronto laboratory technician.
It shows the stages in clot formation in a way that makes it easier to
understand the theoretical notions explained above.
Factor XII is a protein involved in that complex process. It plays a
role, as described before, in the chain reaction that is set in motion
when there is an injury to a blood vessel.
Surprisingly, Factor XII deficiency does not lead to abnormal
bleeding, even with major surgical procedures or trauma.
Although Factor XII is part of the complex coagulation chain, a
deficiency of Factor XII does not appear to be important in “real
life” clotting.
The deficiency is somewhat of a medical mystery. It does not cause
abnormal bleeding. It has been suggested that people with Factor
XII deficiency may be at increased risk of forming blood clots in
the bloodstream when they are not wanted. This is called
“thrombosis,” and it remains unproven.
8
FACTOR XII DEFICIENCY – AN INHERITED BLEEDING DISORDER
Incidence
Severe Factor XII deficiency is an extremely rare disorder. It affects
only 1 in 1 million people. Factor XII levels are lower in patients
of Asian descent than in other ethnic groups.
Diagnosis
Factor XII deficiency is usually discovered by accident in a patient
through a routine coagulation blood test done prior to surgery or
following a family history of coagulation problems.
The physician will order a blood test called PT and PTT. These
tests measure the time it takes for a clot to form. In the case of
Factor XII deficiency, the PTT will be markedly prolonged but the
PT will remain normal. The coagulation time will be longer than
normal. Following this abnormal result, the physician will then
order specific Factor level, including a Factor XII level.
Symptoms
There are no symptoms of bleeding in Factor XII deficiency.
The explanation for the lack of bleeding problems is unknown.
The opposite is sometimes true. It is suggested, but unproven, that
patients may not be as well protected from thrombotic disease
(clots forming in the blood vessels) as the normal population.
Treatment
Contrary to most other coagulation disorders, hemorrhaging and
excessive bleeding are not associated with the deficiency. Therefore
treatment is generally unnecessary. However, always notify your
dentist, doctor and/or specialist of this problem in order to
prevent a delay or even a cancellation of a surgical procedure.
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FACTOR XII DEFICIENCY – AN INHERITED BLEEDING DISORDER
Recommendation for the Patient with
Factor XII Deficiency
Even though you will not have bleeding problems, it is important
to wear a bracelet or a Medic-Alert type chain and a wallet card at
all times. The wallet card will provide a summary of information
relating to your condition.
It will inform the medical professionals of your coagulation
disorder and your ability to form a clot within a normal time.
The Comprehensive Care Team
As the name suggests, a comprehensive care team provides most of
the medical services required by a child or adult with an inherited
bleeding disorder. The team is composed of several professionals,
including:
• a medical director, usually a hematologist
• a nurse coordinator
• a physiotherapist, and
• a social worker.
The team works closely with other specialists – a surgeon, an
orthopedist, a rheumatologist, a dentist, a geneticist and a
psychiatrist, among others. The purpose of this multidisciplinary
team is to ensure the well being of the patient and, in the case of
a child, the parents as well.
10
FACTOR XII DEFICIENCY – AN INHERITED BLEEDING DISORDER
For More Information
You can obtain a list of Hemophilia Treatment Centres by
contacting the National Office of the Canadian Hemophilia
Society:
Canadian Hemophilia Society
625 President-Kennedy Avenue, Suite 505
Montreal, Quebec H3A 1K2
Tel. (514) 848-0503
Toll-free: 1-800-668-2686
E-mail: [emailprotected]
Web site: www.hemophilia.ca
References
1. Amesse C, Lacroix S, Lupien G. Canadian Hemophilia Society. Factor XIII
Deficiency: An Inherited Bleeding Disorder, 2001.
2. Bernardi F, Marchetti G, Volinia S, Patracchini P, Casomato A, Girolami A,
Conconi F. A Frequent Factor XII Gene Mutation in Hageman Trait.
Human Genetics Springer-Verlag. 1988;80:149-151.
3. Colman RW. Contact Activatin Pathway: Inflammatory, Fibrinolytic, Anticoagulant
Antiadhesive and Antiangiogenic Activities. In: Colman RW, Hirsch J, Marder VJ,
Salsman EW, eds. Hemostasis and Thrombosis Basic Principles and Clinical
Practice, Philadelphia: JB Lippinnott Co, 1982: 111-115.
4. Colman RW. Deficiencies of Factor XII and Prokallikrein and High Molecular
Weight Kininogen. In: Colman RW, Hirsch J, Marder VJ, Salsman EW, eds.
Hemostasis and Thrombosis Basic Principles and Clinical Practice, Philadelphia:
JB Lippincott Co, 1982: 1919-1920.
5. Harrington A, Lacroix S, Schwetz N. Canadian Association of Nurses in Hemophilia
Care. Acquired Hemophilia, 2001.
6. Harrison’s Online; Chapter 62: Bleeding and Thrombosis.
7. McDonough RJ, Nelson CL. Clinical Implications of Factor XII Deficiency.
Oral Surg. Oral Med. Oral Pathol. 1989;68:264-266.
8. National Hemophilia Foundation. Orientation Manual for Health Care
Professionals: Factor XII Deficiency. (Hageman Factor), p19.
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FACTOR XII
DEFICIENCY
AN INHERITED
BLEEDING DISORDER
AN INFORMATION
BOOKLET
