What are the clinical signs of a factor XI deficiency?

Clinical Signs of Factor XI Deficiency

Factor XI deficiency presents with a variable bleeding tendency that does not correlate well with factor XI activity levels, with mucocutaneous bleeding being the most common manifestation.

Clinical Presentation

• Bleeding after surgery, dental extractions, or trauma is the most common presentation of factor XI deficiency, rather than spontaneous bleeding 1, 2
• Mucocutaneous bleeding (particularly epistaxis) is frequently observed in patients with factor XI deficiency 3
• Post-surgical hemorrhage is a hallmark clinical sign, often being the first manifestation of the disorder 4, 2
• Menorrhagia (heavy menstrual bleeding) is common in women with factor XI deficiency 5
• Hemarthroses (joint bleeding) and soft tissue bleeding may occur but are less common than in hemophilia A or B 2, 3

Severity and Clinical Correlation

• Unlike other factor deficiencies, there is poor correlation between factor XI activity levels and bleeding tendency 1, 2
• Individuals with severe deficiency (factor XI:C level <15 IU/dL) may have only a mild bleeding tendency 2, 3
• Bleeding risk varies between individuals with similar factor XI levels, and sometimes an individual's bleeding tendency may vary over time 2
• In pediatric patients, there appears to be a stronger association between the severity of factor XI deficiency and bleeding tendency than in adults 3

Specific Clinical Scenarios

• Dental extractions frequently trigger bleeding episodes and may be the first manifestation of severe factor XI deficiency 4
• Trauma-related injuries can lead to excessive bleeding in patients with factor XI deficiency 3
• In children with severe factor XI deficiency, triggered intracranial hemorrhage has been reported, though spontaneous intracranial bleeds are rare 3
• Abnormal clot formation and decreased resistance to fibrinolysis are observed in laboratory testing of patients with bleeding tendency 6

Laboratory Findings

• Prolonged activated partial thromboplastin time (aPTT) that corrects in a 50:50 mix with normal plasma 5
• Normal prothrombin time (PT) is typically observed 5
• Specific factor XI activity assays confirm the diagnosis 5
• Turbidity-based fibrinolysis assays may help predict bleeding risk in patients with factor XI deficiency 6

Age of Presentation

• Unlike factor X deficiency, severe forms of factor XI deficiency do not typically present with umbilical stump or CNS bleeding in newborns 3
• Diagnosis is often made later in childhood or adulthood, typically after a bleeding episode following surgery or trauma 2, 3
• The median age at diagnosis in a pediatric cohort was 4.2 years 3

Common Pitfalls in Diagnosis and Management

• Relying solely on factor XI levels to predict bleeding risk can lead to inappropriate treatment decisions 1, 6
• Failure to provide hemostatic preparation before surgery can result in excessive bleeding (25% of surgical procedures without preparation) 3
• Overtreatment with factor concentrates carries thrombotic risk, especially in older patients 2
• Using non-CTI (corn trypsin inhibitor) treated plasma for laboratory testing may mask differences between bleeders and non-bleeders 6