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Rare bleeding disorders


Factor XI deficiency and other rare bleeding disorders


Bleeding problems associated with rare coagulation disorders differ from those experienced with haemophilia A and B, and are discussed below


Paula HB Bolton-Maggs DM FRCP FRCPath Consultant Haematologist and Honorary Senior Lecturer, University of Manchester and Manchester Blood Centre, Manchester, UK


The rare coagulation disorders comprise those other than haemophilia A and B, and von Willebrand disease. Congenital deficiencies have been reported for all of the other coagulation factors. Although they are rare, they occur with increased frequency in particular racial groups. The bleeding problems differ from haemophilia A and B in some important respects and will be considered below. In addition to these disorders, congenital platelet disorders occur where there may be major dysfunction in the presence of normal platelets or, in some disorders, reduced numbers of platelets.


Background 14


Haemostasis occurs when a disturbance of the blood vessel wall triggers both coagulation activation and platelet aggregation. Immediate reaction includes constriction of the blood vessel to reduce blood loss. Platelet activation leads to primary plug formation at the site of the injury and, together with exposure of tissue factor, triggers the coagulation system. The coagulation system involves several different factors, either as enzymes (for example factors VII and X), which require activation, or as cofactors


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(for example factors V and VIII), which act by bringing the active factors into proximity with one another. Rather than a ‘cascade’ or waterfall, this system is better understood as a sequence of molecular dances or interactions on phospholipid surfaces of platelets, endothelial cells and others such as monocytes (particularly in sepsis). Deficiencies of any of the coagulation


factors, with the exception of factor XII, can result in excessive bleeding, which may occur spontaneously in severe disorders, or be provoked by accidents and surgery. Factor XII has no role in clot


formation, and a deficiency of this factor, even if severe, is not associated with any bleeding risk. Mild factor XII deficiency is relatively common in the general population and causes confusion because it causes prolongation of the screening test (activated partial thromboplastin time) for the more serious deficiencies, particularly factors VIII, IX or XI. Therefore, the diagnosis has to be made but then the individual can be told that there is no bleeding risk and given information to carry in order to avoid inappropriate re-investigation or management in future. Deficiencies of factors with bleeding risk can be divided into four types: ● Deficiencies of single factors with severe bleeding risk in people with complete deficiency. Parents have partial deficiency and are usually free of symptoms.


● Severe inherited platelet disorders.


● Single gene defects resulting in deficiencies of multiple factors that tend to be less severe. Parents are completely normal, with normal coagulation factor levels.


● Factor XI deficiency – a mild bleeding disorder where the bleeding risk is not well related to the measured factor level. Some general features of management of these disorders include: ● Care from appropriate experts. All people with inherited bleeding disorders should be registered with a haemophilia centre to ensure access to appropriate expertise, not only from a haematologist but also from other associated experts for surgery and pregnancy management.


● Avoiding (or very careful assessment of risks of) the use of any medications that increase bleeding risk, for example, aspirin and non-steroidal anti-inflammatory agents.


● Avoiding intramuscular injections. ● Use of anti-fibrinolytic medication (such as tranexamic acid) for mucous membrane bleeding, particularly to assist control of menstruation but also for repeated epistaxis, and use in relation to surgery. The dose of tranexamic acid is often inappropriately low. For menorrhagia in an adult, the dose is 1g, three or four times a day.


● Use of hormonal control for menorrhagia in women – this symptom may be underestimated and indeed may be the first major symptom


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