Hemophilia C 

Updated: Mar 08, 2022
Author: Vineeta Gupta, MD, DNB, MAMS, FRCPCH, FUICC; Chief Editor: Hassan M Yaish, MD 


Practice Essentials

Hemophilia C (deficiency of factor XI) was described first in two sisters and a maternal uncle of an American Jewish family. All three bled after dental extractions, and the sisters also bled after tonsillectomy. (See Etiology and Epidemiology.)

The entity missing from the patients’ plasma was initially referred to as plasma thromboplastin antecedent (PTA), as named by Robert Rosenthal. In 1961, however, to distinguish it from the missing factors in hemophilia A (factor VIII) and B (factor IX) and in Hageman trait (factor XII), the International Committee for the Nomenclature of Blood Clotting Factors proposed that this entity be designated factor XI.[1, 2, 3]

Clinicians and basic scientists have faced practical and conceptual challenges with regard to the bleeding disorder in factor XI–deficient patients (sometimes called Rosenthal syndrome). Of the known congenital coagulation factor deficiencies, it has been found that factor XI deficiency has the poorest correlation between factor levels and symptoms.[2]  Unlike the bleeding tendency in hemophilia A or hemophilia B, which is clearly related to the factor level, some patients with severe deficiency of factor XI do not have a bleeding tendency. On the other hand, some patients with mild deficiency of factor XI bleed excessively, and this unpredictability, which is not fully understood, makes hemophilia C more difficult to manage than hemophilia A or B.[4]

Severe deficiency is defined as factor XIc activity of 15-20 U/dL or lower. However, this is no longer suitable terminology, since the bleeding disorder is not clinically severe, even at very low levels of factor XI; a better term would be "major deficiency." Spontaneous bleeding rarely occurs, but bleeding may occur after surgery, more commonly in those with the lowest levels. The levels in this range, less than about 15 U/dL, generally identify individuals who have 2 FXI gene mutations. Patients with partial deficiency, generally heterozygous with a single FXI gene mutation, have levels of about 20-60 U/dL (ie, the lower limit of the normal range). About 30-50% of individuals with partial deficiency may still have excessive bleeding; however, identifying these persons in advance is difficult. Furthermore, normal infants without hemophilia C are likely to have low factor XIc levels until they are older than 6 months. (See Etiology and History and Physical Examination.)

Brenner et al used a logistic regression model to analyze parameters influencing bleeding tendency in subjects with factor XI deficiency from 45 families.[5]  Odds ratios for bleeding were 13 in homozygotes or double heterozygotes and 2.6 in heterozygotes. Bleeding was negatively correlated with the level of factor XI, and severe factor XI deficiency was a strong predictor of bleeding. Minor factor XI deficiency and blood group O contributed minimally to bleeding. levels of factor VIII and von Willebrand factor were not predictors of bleeding. Bleeding was most common after surgical procedures involving mucosal membranes.

Other possible explanations for variations in patient bleeding tendencies include the following:

  • Additional clotting factor disorders, especially von Willebrand disease, or a more subtle change in hemostatic balance

  • Variant factor XI molecules (ie, those with a discrepancy between factor XI clotting activity compared with antigen): These variants are rare, and no correlation between mutation type and bleeding tendency has been identified.

  • Increased fibrinolysis at certain surgical sites

With regard to the last item, factor XI deficiency has been associated with bleeding problems after surgery or trauma to areas of the body in which the fibrinolytic activity is particularly high (eg, urogenital tract, oral cavity after dental extraction or tonsillectomy). Hence, women can present with menorrhagia or with bleeding related to childbirth or gynecologic surgery. (See History and Physical Examination and Treatment.)

Go to Acquired Hemophilia, Hemophilia A, and Hemophilia B for complete information on these topics.

Signs and symptoms of hemophilia C

Physical findings are usually normal except when bleeding occurs. Bruising may occur at unusual sites. The patient may have signs of pallor, fatigue, and tachycardia with excessive bleeding.

Diagnosis of hemophilia C

Laboratory studies for suspected hemophilia C should include the following:

  • Complete blood count (CBC)
  • Measurement of factor XI levels
  • Measurement of factor VIII and von Willebrand factor
  • Prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) (usually performed before the measurement of factors)

Management of hemophilia C

In patients with hemophilia C undergoing a surgical procedure, replacement with plasma products may be needed in the preoperative, intraoperative, and postoperative periods, depending on the procedure, the patient's history with other surgical procedures, and the person's bleeding tendency, if any.


Complications of factor XI deficiency commonly involve the unpredictable nature of bleeding.

Patients who receive plasma products may be at risk for contracting unknown, virally transmissible infections.

Patients with absent factor XI may also develop inhibitors to factor XI.

In addition, some patients (with preexisting risk factors) who receive factor XI concentrates may be at risk for thrombotic events.


The prognosis is excellent in patients with partial factor XI deficiency without bleeding manifestations.


The severity of the deficiency is based on plasma factor XIc (clotting) activity. Major factor XI deficiency is present when the activity of factor XI in plasma is less than 15 IU/dL, but the level does not reflect the severity of the bleeding risk. However, a pediatric study by Barg et al suggested that in children, the severity of factor XI deficiency may be associated with such risk.[6]

Factor XI is a dimeric serine protease, which is composed of chains that each weigh 80,000 Da. Factor XIIa activates factor XI and factor IX in the original intrinsic pathway of blood coagulation. Also, thrombin directly activates factor XI, and this direct activation may be more important than the activation due to factor XII. Recently, it has been shown that thrombin activation of factor XI is triggered by polyphosphate release from activated platelets. These molecules provide a template for assembly of factor XI and factor IX. Patients with factor XII deficiency, even severe deficiency, do not necessarily have a tendency to bleed. Hence, the absence of factor XII appears to be irrelevant to factor XI.

Factor XI is a zymogen that, on activation, undergoes conversion to a serine protease that leads to activation of factor IX, followed by thrombin generation. The sustained generation of thrombin also leads to the activation of thrombin-activatable fibrinolysis inhibitor (TAFI), which impairs the conversion of plasminogen to plasmin. Thus, factor XI serves as a procoagulant and an antifibrinolytic agent, and the lack of factor XI in plasma results in a tendency to bleed. People with severe factor XI deficiency have a lower incidence of ischemic stroke.[7]

Factor XI has no role in the complement or kinin pathways but has been shown to activate fibrinolysis. Alpha-1 antitrypsin is the main inhibitor of factor XIa and is responsible for two thirds of its inhibition. C1 esterase inhibitor, antithrombin III, and alpha-2 antiplasmin cause the remaining inhibition.

In major deficiency factor XI, bleeding is related to injury, especially when trauma involves tissues rich in fibrinolytic activators, such as the oral mucosa, the nose, and the urinary tract. Unlike patients with severe hemophilia A or B, patients with major factor XI deficiency do not spontaneously bleed.

Gene mutations

Mutations in the factor XI gene cause the congenital deficiency of factor XI clotting activity.[8] The inheritance pattern of factor XI is autosomal but not completely recessive, because heterozygotes may have bleeding.[9]

The gene for factor XI is near the gene for prekallikrein on the distal arm of chromosome 4 (4q35). It is 23 kb, with 15 exons and 14 introns. Factor XI is synthesized in the liver and circulates in the plasma as a complex with high-molecular-weight kininogen. Factor XI has a half-life of about 52 hours.

The first 3 mutations in the factor XI gene were described in 6 persons of Ashkenazi Jewish descent who were severely affected.

More than 200 other mutations that cause factor XI deficiency have been described and are listed in online databases.

Databases include Mutations of Patients with Factor XI Deficiency, which is maintained by the University of North Carolina School of Medicine, and an interactive database maintained by University College London.[10] The published mutations include missense mutations, nonsense mutations, deletions and/or insertions, and splice-site mutations. Those described so far are associated mainly with failed or reduced production of the active protein, and only a few are related to the production of a dysfunctional molecule.

Four mutations (types I-IV) have been identified in people of Ashkenazi Jewish descent. Two of these mutations occur with increased frequency in this population. Type II, which is a nonsense mutation (Glu117stop) is prevalent in Ashkenazi and Iraqi Jews. Type III, a missense mutation (Phe283Leu), is present only in Ashkenazi Jews. Homozygotes for type II or type III mutations have a factor XI activity of 1 and 10 U/dL, respectively, whereas compound heterozygotes for type II or type III have factor XI activity of 3-5 U/dL.

Various mutations have been identified in persons who are not Jewish. Two ancestral mutations are described: a mutation with a Cys38Arg substitution in exon 3 (observed in the French Basque Country) and the mutation C128X in exon 5 (occurring in England).[9] Both mutations result in a factor XI level of less than 1 U/dL in affected homozygotes.

A study by Asselta et al found significant differences between various populations with regard to heterozygote frequencies for factor XI deficiency. Allele frequencies for these populations were reported to be as follows[11] :

  • African = 0.0016
  • East Asian = 0.0045
  • European = 0.0036
  • Finnish = 0.00030
  • Latino = 0.0021
  • South Asian = 0.0015

People with mutations leading to absent protein (eg, Glu117Stop, C128X) are at risk of development of inhibitors (antibodies) to factor XI; this should be considered when selecting treatment for these patients.

Acquired factor XI deficiency occurs in patients who develop inhibitors to this protein, as is sometimes observed in patients with systemic lupus erythematosus or other immunologic diseases.

Factor XI deficiency is a common finding in patients with Noonan syndrome, which is characterized by congenital cardiac abnormalities, short stature, and mental retardation.


Hemophilia C (major form) occurs with an estimated prevalence of 1 case per 100,000 population in the United States, a rate that makes hemophilia A 10 times more common than hemophilia C.

Internationally, deficiency of factor XI is reported in most racial groups, with the highest frequency in persons of Ashkenazi or Iraqi Jewish descent[12, 13] ; in Israel, the estimated rate for heterozygosity is 8%. In the United Kingdom national database, 1696 patients (many of whom were non-Jewish) with factor XI deficiency were registered in a population of about 60 million (data for 2006), but most of these have partial deficiency[14] ; factor XI deficiency is more common than factor IX deficiency (hemophilia B). In the French Basque country (home to the most ancient ethnic group of Western Europe, the Basques), 39 patients were identified among the general population of 290,000.[15]

A study from Austria, by Gebhart et al, found that out of 418 patients with mild to moderate bleeding disorders, at least 3 (0.7%) had factor XI deficiency, compared with 11 (2.6%), 3 (0.7%), and 1 (0.2%) with factor VIII, IX, and XIII deficiency.[16]

Hemophilia C equally affects males and females. Moreover, people of any age group can be affected. Note that normal infants younger than age 6 months have low levels of factor XI because of the time required for factor XI to reach normal levels observed in adults. After this is reached, factor XI levels do not change with age.

Patient Education

Patients must be counseled about the unpredictable nature of their bleeding tendency, and they should be informed of the preparations needed before elective surgery.

The usual precautions regarding physical activity for individuals with a bleeding disorder apply to patients with factor XI deficiency who have a bleeding tendency. Patients should be encouraged to wear seat belts, to use protective gear (eg, bike helmets), and to avoid contact sports.

Patients should be advised to keep up to date with their vaccinations, especially hepatitis A virus and hepatitis B virus vaccinations.

Stress the importance of annual visits to hemophilia treatment centers.

Patients should receive genetic counseling with regard to their marriage partners and the potential risks to their offspring.

For patient education information, see Hemophilia.



History and Physical Examination

Suspect hemophilia C in any patient with a prolonged activated partial thromboplastin time (aPTT), especially if the family history suggests a mild-to-moderate lifelong bleeding disorder that affects both male and female individuals.

Acquired factor XI deficiency occurs in patients who develop inhibitors to the protein, as is sometimes observed in patients with systemic lupus erythematosus and other immunologic diseases.

Factor XI deficiency is described as a common finding in patients with Noonan syndrome, which is characterized by congenital cardiac abnormalities, short stature, and mental retardation. These individuals may have other coagulation defects and should be carefully assessed prior to surgery.

Bleeding after surgery or after injury is the usual presenting symptom in individuals with hemophilia C (but many individuals are now diagnosed after preoperative coagulation screening reveals an abnormal aPTT).

Individuals with factor XI levels of less than 15-20 U/dL are at greater risk of excessive bleeding after surgery or trauma (but a review of all published evidence and a review of four databases noted that there is a very poor relationship between factor XI level and bleeding[17] ). Some unusual presentations with spontaneous bleeding have been reported. In these cases, other pathologic features may contribute to the bleeding, because spontaneous bleeding is generally not a feature of hemophilia C. The unusual presentations include the following:

  • Massive hemothorax

  • Cerebral hemorrhage

  • Subarachnoid hemorrhage

  • Spinal epidural hematoma with the Brown-Sequard syndrome

Hematuria and spontaneous hemarthrosis are rare.

In women, menorrhagia is an important finding, and abnormal bleeding after childbirth may also occur.

Physical findings are usually normal except when bleeding occurs. Bruising may occur at unusual sites. The patient may have signs of pallor, fatigue, and tachycardia with excessive bleeding.



Diagnostic Considerations

Conditions to consider in the differential diagnosis of hemophilia C include the following:

  • Abnormalities in platelet function

  • Other clotting factor deficiencies

  • Combined deficiencies of clotting factor

  • Uncommon coagulopathies

Go to Acquired Hemophilia, Hemophilia A, and Hemophilia B for complete information on these topics.

Differential Diagnoses



Approach Considerations

Laboratory studies

Laboratory studies for suspected hemophilia C should include the following:

  • Complete blood count (CBC)

  • Measurement of factor XI levels

  • Measurement of factor VIII and von Willebrand factor

  • Prothrombin time (PT), aPTT, and thrombin time (TT) (usually performed before the measurement of factors)

With regard to the last item, the aPTT is usually prolonged in factor XI deficiency (but depends on the sensitivity of the reagent and test system--partial deficiency can be missed), whereas the PT and TT are normal.

A specific assay for factor XI activity is necessary to confirm the diagnosis. Assays of other clotting factors and platelet function may be needed to exclude a combined hereditary deficiency of factor XI and other factors. In terms of predicting bleeding tendency, findings show that the aPTT test measures factor XI activation via the contact system, which is not the relevant physiologic pathway. Research demonstrates that the thrombin-generation test, under conditions of low tissue factor and with inhibition of contact factors, may give a better indication of the risk of bleeding than the specific factor XI activity assay based on the aPTT. A retrospective study by Désage et al found that among factor XI–deficient operative patients who were not prescribed hemostatic treatment for surgery and had three impaired thrombin-generation assay parameters, 15 out of 34 operations (44%) reportedly led to bleeding.[18, 19]

A study by Gidley et al indicated that bleeding risk in patients with severe or partial factor XI deficiency can be assessed by using turbidity assays to reveal decreased clot formation and reduced fibrinolysis resistance in corn trypsin inhibitor–treated platelet-poor plasma.[20]

Imaging studies

No imaging studies are necessary in diagnosing factor XI deficiency. However, imaging studies may be obtained to evaluate the extent of bleeding in the management of bleeding at any site.

Genetic analysis

Genetic analysis for the mutation in factor XI is helpful in determining which mutation caused the deficiency.



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.


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.


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:

  • Monitoring of bleeding episodes

  • Planning for any elective surgical procedures

  • Monitoring for the development of hepatitis

  • Administering preventive immunizations as needed

Continuing patient education about the bleeding condition and applying any therapeutic advances that may become available.



Medication Summary

Bleeding may not require specific treatment. When therapy is required, available options for patients with factor XI deficiency include antifibrinolytics; fresh-frozen plasma (FFP), ideally pathogen-inactivated (eg, solvent-detergent treated FFP); and factor XI concentrates. Factor XI concentrates are available in Europe but not in the United States. Recombinant activated factor VII is useful for patients with inhibitors.

Antifibrinolytics are particularly useful and may be sufficient for dental extractions even in patients with severe deficiency.

Adjunctive measures include the use of fibrin glue and desmopressin (DDAVP). Desmopressin is a synthetic antidiuretic hormone with actions that mimic those of vasopressin. It also increases levels of factor VIII and von Willebrand factor. Although not in factor Xi deficiency, DDAVP has widely been used as an adjunct to control bleeding during surgery since its discovery in various congenital bleeding disorders. To date, little documentation addresses the use of DDAVP in factor XI deficiency and the evidence is not very convincing.

Although some patients may not bleed during surgery, the physician has no way to ascertain which patients will not bleed. A history of clinically significant surgery without therapy and without excessive bleeding strongly suggests, but does not guarantee, satisfactory hemostasis with subsequent surgery. In the United States, patients with factor XI deficiency should be given plasma products before surgery when their risk is in doubt.

Replacement therapy during and/or after vaginal delivery is not mandatory in women with severe deficiency, and it can be restricted to patients in whom severe hemorrhage occurs. For women undergoing cesarean delivery, the same policy can be advocated, but additional observations are required. Tooth extractions can be managed by using only antifibrinolytic agents without replacement therapy. Epidural anesthesia without replacement therapy is not recommended in these patients.

Development of inhibitors is a known complication of therapy in patients with hemophilia A or B. Factor XI inhibitors may develop in patients with severe congenital deficiency, particularly with mutations leading to chain termination. One reason for the infrequent presence of inhibitors may be that many patients with factor XI deficiency never receive treatment with plasma products. However, when inhibitors do develop, they may cause clinically significant inhibition and clinical problems similar to those occurring in hemophilia A or B. Surgery or bleeding episodes in those who have developed factor XI inhibitors may be treated successfully with plasma products or recombinant factor VIIa. Before patients with hemophilia C undergo elective surgery in which plasma products will be used, they should be screened for inhibitors, as is done in patients with hemophilia A or B.

Blood Product Derivatives

Class Summary

FFP is the first product used to treat patients with hemophilia C. The main advantage of FFP is its availability. Disadvantages to its use include the large volumes required, the potential for transmission of infective agents, and the possibility of allergic reactions.

Solvent-detergent–treated FFP has a factor XI half-life similar to FFP (mean, 45 h). It is safer than regular FFP, because it reduces the transmission of known enveloped viral agents. However, it is not protective against nonenveloped viruses, such as hepatitis A virus.

Fresh frozen plasma

This is the product of choice when factor XI concentrates are not available. FFP is easily available. It can be infused over a short period. Disadvantages include large infusion volumes to achieve appropriate control of bleeding, a potential for transmitting infective agents, and the possibility of allergic reactions.

Human coagulation factor Xl

Factor XI concentrates provide the best source for factor XI replacement. Two products available in Europe are Hemoleven (Laboratoire français du Fractionnement et des Biotechnologies [LFB], Les Ulis, France) and factor XI concentrate (Bio Products Laboratory [BPL], Elstree, Hertfordshire, United Kingdom). Both are heat treated and are not expected to transmit the human immunodeficiency virus (HIV) or hepatitis viruses. Both products also contain antithrombin III and heparin in different concentrations. These products appear to provide good treatment for selected patients.

The typical dose is 30 U/kg or less.

Advantages of factor XI concentrates include selective delivery of the deficient factor, a reduced volume of infusion, and viral safety. However, they are plasma-derived products; therefore, they can have all of the attendant disadvantages of any plasma-derived product.

Several issues are encountered with the use of factor XI concentrates. The 2 previously mentioned concentrates, Hemoleven (LFB) and factor XI concentrate (BPL), are hemostatically effective and virally safe but are associated with evidence of activation of the coagulation system and some thrombotic events, especially in patients with preexisting vascular disease.

Briggs et al studied 229 treatment episodes with factor XI concentrate (BPL) in 161 patients aged 3-88 years and observed 21 adverse events in 19 patients, 12 of whom were probably or definitely thrombotic. Good hemostatic efficacy was reported in all. No transmission of HIV or hepatitis was reported. The mean factor XI recovery was 91% of the injected dose, and the mean half-life was 52 hours.

The BPL Factor XI was also used in the United States in a study of elective surgery in 12 patients aged 24-81 years. Only 1 patient developed anaphylaxis, and laboratory (not clinical) evidence of disseminated intravascular coagulation (DIC) was present. In all other patients, BPL was used successfully. Hemoleven, (LFB) produced results similar to those of factor XI concentrate from BPL. Thirty-one patients, aged 5-76 years, undergoing 33 procedures received Hemoleven (LFB). Recovery was 80%, with a half-life of 46 hours (range, 32-52 h). Thromboembolic events occurred as complication in 3 infusions exceeding 30 U/kg.

Hemoleven and factor XI concentrate (BPL) are heat treated and are therefore not expected to transmit HIV or hepatitis viruses.

Fibrin sealant (Tisseel, Artiss, Evicel)

Fibrin glue is sometimes used as an adjunct to or substitute for plasma products. Centeon glue (Beriplast) has been used successfully in Israel in patients with congenital bleeding disorders who are undergoing dental extractions without blood product replacement. The glue is applied with a pair of syringes, one containing calcium and thrombin and one containing fibrinogen, factor XIII, and aprotinin.

The US Food and Drug Administration (FDA) approved a fibrin sealant (Tisseel VH; Baxter Healthcare Corporation, Westlake Village, Calif) for adjunctive topical hemostasis. Fibrin sealant contains fibrinogen (sealer protein) as the main active ingredient and fibrinolysis inhibitor (aprotinin) of bovine origin. Two reconstituted components, sealer protein, and thrombin solutions are mixed and applied topically. The viscous solution quickly sets into an elastic coagulum.

Antifibrinolytic agents

Class Summary

Antifibrinolytic agents are important adjuncts in patients undergoing surgery in areas of the body prone to increased fibrinolysis (oral cavity, uterus). These agents may be effective when used alone in patients who have severe factor XI deficiency and who are undergoing dental extractions.

Aminocaproic acid (Amicar)

This agent's antifibrinolytic effects result primarily from the inhibition of plasminogen activators and, to lesser degree, antiplasmin activity.


Questions & Answers


What is hemophilia C (deficiency of factor XI)?

What are the possible complications of hemophilia C (deficiency of factor XI)?

What is the prognosis of hemophilia C (deficiency of factor XI)?

What causes hemophilia C (deficiency of factor XI)?

What is the role of genetics in the etiology of hemophilia C (deficiency of factor XI)?

What is the prevalence of hemophilia C (deficiency of factor XI) in the US?

What are the ethnic and racial predilections of hemophilia C (deficiency of factor XI)?

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What is included in patient education about hemophilia C (deficiency of factor XI)?


Which clinical history findings are characteristic of hemophilia C (deficiency of factor XI)?

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Which physical findings are characteristic of hemophilia C (deficiency of factor XI)?


Which conditions are included in the differential diagnoses of hemophilia C (deficiency of factor XI)?

What are the differential diagnoses for Hemophilia C?


What is the role of lab tests in the workup of hemophilia C (deficiency of factor XI)?

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How are bleeding episodes predicted in hemophilia C (deficiency of factor XI)?

Which factors increase the risk of thrombotic events in hemophilia C (deficiency of factor XI)?

What is the role of plasma-derived factor XI concentrates, factor IX, and factor VIIa in the treatment of hemophilia C (deficiency of factor XI)?

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Which specialist consultations are beneficial to patients with hemophilia C (deficiency of factor XI)?

How does hemophilia C (deficiency of factor XI) present during surgical procedures?

How is hemophilia C (deficiency of factor XI) treated in patients undergoing surgical procedures and in pregnant patients?

What is included in long-term monitoring of hemophilia C (deficiency of factor XI)?


What is the role of medications in the treatment of hemophilia C (deficiency of factor XI)?

Which medications in the drug class Antifibrinolytic agents are used in the treatment of Hemophilia C?

Which medications in the drug class Blood Product Derivatives are used in the treatment of Hemophilia C?