Approach Considerations
The unpredictable nature of bleeding is a concern, especially in patients with partial deficiency. Bleeding episodes cannot be predicted on the basis of factor XI levels alone.
Thrombotic events are a risk in some patients who receive factor XI concentrates, particularly those with preexisting risk factors such as older age, known peripheral or central vascular disease, or morbid obesity. A study by Batty et al reported thrombotic events (transient ischemic attack and pulmonary emboli) in two of 29 patients with factor XI deficiency who were treated with plasma-derived factor XI concentrate. However, the investigators concluded that the concentrate was safe and effective in most cases of the disorder. [21]
In a study of one of the plasma-derived factor XI concentrates, Hemoleven, Bauduer et al found the drug’s efficacy to be excellent/good in 63 of 67 treatments (performed in 44 patients total), but noted that two serious adverse effects occurred, with one patient developing factor XI inhibitor and another dying from a sudden massive pulmonary embolism. The investigators recommended that Hemoleven be used sparingly and that new prescription procedures be developed to adapt the dosage, particularly in the presence of intrinsic and/or acquired thrombotic risk factors. [22]
An in vitro study by Bakhtiari and Meijers observed a beneficial effect from treatment with recombinant factor IX (BeneFix) in factor XI deficiency. The findings suggested that in factor XI–deficient patients, bleeding episodes may be treatable or bleeding prior to invasive procedures preventable via infusion of available factor IX concentrates. However, this remains to be confirmed in human trials. [23, 24]
Also in patients with factor XI deficiency who are undergoing surgery, low-dose, off-label recombinant factor VIIa has been used for management. [25]
In patients with major deficiency, administer all vaccinations subcutaneously because of the risk of inducing a muscle hematoma. These patients should be vaccinated against hepatitis A virus and hepatitis B virus, because they have or may be exposed to plasma products as part of their treatment.
Go to Acquired Hemophilia, Hemophilia A, and Hemophilia B for complete information on these topics.
Activity
Advise patients with factor XI deficiency to participate only in age-appropriate activities. In general, this means few restrictions. Physical activity precautions also apply to patients with factor XI deficiency who have a bleeding tendency. Advise them against participating in contact sports if the patient has severe disease.
Consultations
Consult a pediatric or adult hematologist when the patient presents with excessive bleeding or when a preoperative laboratory evaluation reveals a prolonged aPTT.
Managing Bleeding in Surgical Procedures
Treatment of patients with factor XI deficiency is a challenge. Patients with severe deficiency are clearly and commonly at risk of bleeding from surgical procedures. Bleeding in these patients can start at the time of injury, or it can be delayed for several hours; it may persist until specific treatment is administered or it can stop on its own.
Bleeding is much more likely in relation to surgery in areas of high fibrinolytic activity and is less common in other procedures.
Patients with severe factor XI deficiency usually require replacement therapy before they undergo a surgical procedure, even if they have never bled after surgery before. Patients with partial deficiency can also have bleeding episodes, and plans for replacement therapy depend on previous history and the site of surgery. Antifibrinolytic agents alone may be suitable for some patients.
Depending on the surgical procedure, the patient's history with other surgical procedures, and the patient's bleeding tendency, if any, replacement with plasma products may be needed in the preoperative, intraoperative, and postoperative periods in patients with hemophilia C.
The management of the patient should be discussed jointly between surgeon, hematologist and anesthesiologist, and a management plan set out in writing. Generally, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided.
Replacement with plasma products must be coordinated with the hemophilia treatment center.
After a surgical procedure, discharge depends on the type of surgery and how long replacement therapy is needed, which may be 5-7 days after major surgery.
The basic principle of management consists of altering the balance between bleeding and clotting. Therapy consists of replacing the deficient factor and using other measures, such as fibrin glue and antifibrinolytics.
Management During Pregnancy
Pregnancy is not associated with a change in factor XI’s activity level. However, the paucity of studies dealing with the management of factor XI–deficient women means that there are no evidence-based guidelines regarding this treatment. In women with a bleeding phenotype, administration of fresh-frozen plasma (FFP) or factor XI concentrate, if available at the time of delivery, is used in standard management. The risk of postpartum hemorrhage (PPH) is commonly reduced with an antifibrinolytic such as tranexamic acid (TXA) or epsilon aminocaproic acid (EACA). Concerns regarding spinal hematoma mean that the use of neuraxial anesthesia (epidural or spinal) is frequently avoided. [26]
A study by Gerber et al of 64 pregnancies in 28 women with factor XI deficiency indicated that most patients with this condition have uncomplicated deliveries, with minimal use of hemostatic agents needed. Pregnancy losses (17%) and antenatal bleeding rates were comparable to those in the general population, although the PPH rate (17%) was higher. Only women with severe factor XI deficiency received antifibrinolytic agents and FFP. The investigators also found that most women with factor XI deficiency can safely be administered neuraxial anesthesia. [27]
Long-Term Monitoring
Annual visits to a hemophilia treatment center are recommended to provide the following care:
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Monitoring of bleeding episodes
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Planning for any elective surgical procedures
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Monitoring for the development of hepatitis
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Administering preventive immunizations as needed
Continuing patient education about the bleeding condition and applying any therapeutic advances that may become available.
