The factor XI deficiency is a coagulation disorder. Factor XI is a coagulation factor, a part of the coagulation cascade, which in turn activates other parts and whose failure therefore affects the course of the entire coagulation cascade.
What is Factor XI Deficiency?
According to topbbacolleges.com, Factor XI is a proenzyme of the serine protease factor XIa and plays a role in blood clotting. There it stands together with prekallikrein, high molecular weight kininogen (HMWK) and factor XII at the beginning of the coagulation cascade. The enzyme is synthesized in the liver and has a half-life of 52 hours.
It circulates in the blood as an inactive form and is present in the platelets. In the plasma it is present in a concentration of five milligrams per deciliter. Activation takes place via negatively charged surfaces. In vitro activation can take place, for example, via kaolin or silicon. In the body, it probably takes place via proteoglycans from exposed vessel walls or RNA, but this has not yet been precisely proven.
While factor XI is circulating in the blood, it is bound to HMWK. This enables binding to negatively charged surfaces, in particular to the phospholipid surface of activated blood platelets. In the presence of calcium and phospholipids, factor XIa activates factor IX into factor Xa. In addition, the TAFI (thrombin activable fibrinolysis inhibitor) is activated by factor XIa.
The factor XIa in turn is activated by factor XII, thrombin or it can also activate itself. Factor XI is inactivated by antithrombin, alpha-1-antitrypsin, by alpha-2-antiplasmin plasmin inhibitor, C1 inhibitor and protein-Z dependent protease inhibitors (ZPI). If factor XI is not present in sufficient quantities, a coagulation disorder occurs, which is referred to as factor XI deficiency.
Factor XI deficiency can either be acquired or congenital. It can be acquired through a liver disease that prevents the liver from sufficiently synthesizing the coagulation factors. Likewise due to a vitamin K deficiency, which is often caused by anticoagulant drugs.
In autoimmune diseases through antibodies against coagulation factors or through protein loss in kidney diseases. Another cause of the deficiency are consumption coagulopathies. Consumption coagulopathy results from intravascular activation of blood clotting.
This leads to a high consumption of coagulation factors and platelets, which causes a deficiency. Any kind of shock can be the trigger, for example through multiple trauma after accidents, as well as obstetric or pregnancy complications such as preeclampsia and eclampsia.
Extensive necrosis, for example in the case of burns, can also promote a factor XI deficiency. Massive hemolysis, as can occur after a transfusion incident, sepsis from gram-negative bacteria or poisoning from snakebites are also considered causes.
Symptoms, ailments & signs
Congenital factor XI deficiency is rare, but occurs more frequently in certain ethnic groups, for example the Ashkenazi Jews or the Japanese. The deficiency is inherited in a recessive manner. There can be gene mutations in the gene responsible for factor XI, or sometimes there can be a complete lack of this gene.
This congenital variant is known as hemophilia C, PTA deficiency syndrome or Rosenthal syndrome. Factor XI deficiency varies in severity. The normal activity of factor XI is seventy to one hundred and fifty percent. In the case of a partial deficiency, this value drops to twenty to seventy percent.
A partial deficiency is caused by a heterozygous mutation in the corresponding gene. In the case of homozygous inheritance, there is a severe deficiency. Here the activity of factor XI is sometimes below fifteen percent.
The factor XI deficiency can appear as type I. This means a reduction in the activity and protein concentration of the coagulation factors in the blood. Type II, on the other hand, has the normal protein concentration, but the activity is reduced. This is called a dysfunction of the coagulation factor.
Diagnosis & course
The factor XI deficiency leads to an increased tendency to bleed, compared to healthy people it can bleed more easily and quickly. However, the disease can also be completely symptom-free. If symptoms occur, it is predominantly moderate bleeding.
This bleeding usually occurs after injuries or surgery. In particular, circumcisions, tooth extractions and operations in the ENT and urogenital areas are known to have a higher tendency to bleed in this deficiency disease. Spontaneous bleeding usually does not occur, but women may have prolonged periods.
Significant hematomas are occasionally observed after surgery in untreated patients with factor XI deficiency. In the case of a factor XI deficiency, however, there is only a slight correlation between the severity of the bleeding and the factor XI level.
As a rule, coagulation is disturbed in a patient with factor XI deficiency. This can have negative health effects, especially in the event of an accident, and lead to bleeding that cannot easily be stopped. Even minor injuries can lead to relatively heavy bleeding in a factor XI deficiency.
In most cases, there will be no further complications with this disease if the patient does not expose himself to special and unnecessary dangers. However, problems can arise when an operation is performed. This is the case, for example, when visiting the dentist when the bleeding cannot simply be stopped. With the right treatment, however, the disease will develop without any further symptoms.
Bleeding occurs spontaneously only in very rare cases. Women are affected by heavier and longer menstrual periods, which can have a negative impact on everyday life. Proper treatment is usually not carried out. The person concerned only has to be careful with bleeding and, if necessary, inform doctors if bleeding may occur during treatment. The factor XI deficiency does not result in a reduced service life.
When should you go to the doctor?
In the event of a factor XI deficiency, a visit to a doctor is always necessary. The doctor should then be consulted if the patient suffers from a significantly increased tendency to bleed. Even very slight injuries or cuts can lead to profuse bleeding. The bleeding itself is difficult to stop and takes a long time. Long and heavy menstrual periods in women can also indicate a factor XI deficiency and should always be checked.
Usually, a doctor should be seen the first time symptoms are recognized. Since the disease cannot be treated causally or causally, it can only be alleviated with the help of medication. This allows the bleeding to be stopped directly. An emergency doctor can also be called in an emergency.
In the case of factor XI deficiency, the attending physician should always be warned when a surgical procedure is involved in order to avoid complications. Diagnosis and treatment of the disease can usually be done by a pediatrician or a general practitioner. Furthermore, visits to the doctor are usually not necessary if bleeding can be prevented.
Treatment & Therapy
To determine a factor XI deficiency, the factor XI level must be checked. An extension of the activated partial thromboplastin time (aPTT) leads in the same direction. If the defect is severe, the factor XI level is below twenty units per deciliter. A partial deficiency is diagnosed with a value between twenty and seventy units per deciliter.
The diagnosis must be differentiated from the diagnoses of deficiencies in the other coagulation factors, II, V, VII, VIII, IX, X or XIII, against combined deficiency diseases of Factro V and VIII, against von Willebrand syndrome and a platelet dysfunction.
Outlook & forecast
Factor XI deficiency can be treated very well with tranexamic acid, aminocaproic acid and other antifibrinolytic agents. If there are no comorbidities, recovery is likely. The prognosis is poorer if the patient has an autoimmune deficiency or a skin condition accompanying the factor XI deficiency.
This can promote internal and external bleeding and thereby worsen the prognosis. The prognosis is also generally somewhat worse for children, pregnant women and the elderly, as well as patients who are exposed to an increased risk of accidents at work.
Since the factor XI deficiency mainly occurs after tooth extractions and surgical interventions, the risk of bleeding can be reduced in a targeted manner by prescribing the appropriate medication after appropriate interventions and by closely monitoring the patient by a doctor. This can improve the prognosis in the long term.
Since there is usually no spontaneous bleeding with factor XI deficiency, serious complications are unlikely. Factor XI deficiency does not reduce life expectancy. The responsible internist can make the diagnosis on the basis of an anamnesis and regular follow-up checks. In general, the prospect of a cure is good as the symptoms of bleeding are usually moderate.
Long-term treatment is not necessary as there is no spontaneous bleeding. Treatment is required in the event of bleeding or situations where bleeding is anticipated. Before tooth extraction or surgery, patients with factor XI deficiency are treated with factor XI concentrate or freshly frozen plasma. Sometimes antifibrinolytics such as aminocaproic acid and tranexamic acid are also given because factor XI deficiency leads to a hyperfibrinolytic status.
In the case of factor XI deficiency, the options for follow-up care are very limited in most cases. The person concerned is primarily dependent on the medical examination and treatment of this disease so that there are no further complications. As a rule, the person concerned should always point out the factor XI deficiency to the doctor during medical examinations so that it does not lead to excessive bleeding.
The treatment itself takes place through the administration of medication that can alleviate the symptoms. It is important to ensure the correct dosage and regular intake in order to counteract the factor XI deficiency correctly. As a rule, there are no particular complications and life expectancy is not reduced if the factor XI deficiency is treated correctly and in good time.
It is also advisable to have a card with you that indicates the factor XI deficiency, so that in the event of an accident or other severe injuries, the doctors are also notified of the disease. The affected person should protect himself from bleeding and other injuries, whereby parents in particular should take special care of their children with a factor XI deficiency. Contact with other people affected by the disease can also be useful.
You can do that yourself
The more detailed the social environment of those affected is informed about haemophilia C, the more natural it is to deal with it on a daily basis. Family members, friends, or teachers and colleagues should be informed about the disease. In the event of an emergency, this enables everyone involved to proceed in a routine and prudent manner.
Schoolchildren with haemophilia C are exposed to the risk of joint and muscle bleeding in physical education classes. An initiated sports teacher knows when the administration of the factor preparations is indicated or when cooling is sufficient.
Regular endurance sports such as swimming, cycling or hiking are suitable for people with Factor XI deficiency, as muscles and joints are strengthened evenly in this way. The risk of spontaneous bleeding decreases. It is not advisable to do sports in which muscles and joints are very stressed or in which there is a risk of injury. These include team sports with frequent physical contact such as basketball or soccer.
When you are out and about, you must have your haemophilia ID card with you so that the doctor you have called will treat the patient correctly in the event of an emergency. When traveling abroad, the international patient ID card is used for better communication. The shelf life of factor preparations is guaranteed when traveling if they are transported refrigerated. Medicines that are always at hand increase safety, although a supply of at least one week is recommended.