Factor XI deficiency is an autosomal recessive disorder first recognized in a patient who experienced severe bleeding after dental extraction. 1 

Although it is a very rare disorder the  prevalence is increased in certain populations such as Ashkenazi Jews  (8-9% )due to consanguinity (2). Factor XI deficiency does not correlate very well with the degree of bleeding and the diagnosis was often made prospectively after excessive bleeding is encountered unexpectedly during procedures (3). Prolonged APTT can indicate various underlying coagulopathies, necessitating further investigation to identify specific factor deficiencies.  We present case of patient who was diagnosed with factor XI deficiency during routine preoperative workup. This case illustrates the importance of thorough evaluation in patients with unexpected coagulation abnormalities.

A 40-year-old female was planned for excision of 5 cm right arm lipoma under general anesthesia.  She was referred to our Clinic as her routine preoperative laboratory tests revealed a prolonged APTT.  The past history was significant for two previous cesarean sections with no increased bleeding. Notably, the patient had no history of significant bleeding, including hematemesis, melena, epistaxis, or hematuria. She was not on any medications and denied any family history of bleeding disorders.

On examination, the patient was conscious and oriented, with stable vital signs: pulse rate of 88 beats per minute and blood pressure of 100/70 mm Hg. There were no signs of bruising or ecchymosis, and the systemic examination was unremarkable. Her lab results showed hemoglobin of 11.5 grams/L, White Blood Cell Count of6.68 x 10^9/L and Platelet Count of 291 x 10^9/L   Her APTT was prolonged at 78.60 seconds (normal range: 27-42). Her PT was 17.2 seconds (normal range: 11.7-15.3).  Her liver function tests, fibrinogen and ferritin levels were normal.

Mixing studies were performed to determine the cause of the prolonged APTT, which revealed correction, suggesting the presence of a factor deficiency.  The subsequent factor assays were done which revealed low factor XI activity of 4% (normal range: 65-150).  The factor VIII, IX and XII levels were normal. These results confirmed a diagnosis of Factor XI deficiency, a rare bleeding disorder often associated with a lower risk of bleeding compared to deficiencies of other clotting factors.

Factor XI deficiency, also known as hemophilia C, is a rare disorder of hemostasis with an estimated incidence of 1 in 1,000,000, predominantly found in Ashkenazi Jews due to intermarriage (4). This deficiency is characterized by reduced levels of coagulation Factor XI, although the severity of deficiency does not always correlate with bleeding risk (5). Factor XI is a glycoprotein that plays a critical role in the coagulation cascade and normal hemostasis. The bleeding tendency in patients with Factor XI deficiency can be unpredictable; many individuals with severe deficiency may be clinically unremarkable and show no signs of abnormal bleeding (6).

Inheritance of Factor XI deficiency is primarily autosomal recessive, though some cases are dominantly inherited, affecting both men and women equally. Patients may experience epistaxis, hypermenorrhea, or bleeding during surgical procedures, but joint and muscle bleeds are rare (7). The gene encoding Factor XI is located on the distal arm of chromosome 4 (4q35) and is synthesized in the liver, with a half-life of approximately 52 hours (8). Approximately 253 mutations have been described in literature (9). Patients with the homozygous or compound heterozygous disease show a more serious clinical course, whereas those with the heterozygous disease have milder clinical symptoms. Two types of mutations on FXI locus are found to cause FXI deficiency. The role of factor XI in coagulation is thought to involve amplification of thrombin generation via positive feedback and stabilization of new clots by inhibiting fibrinolysis. Additional pathways such as thrombin independent thrombin-activatable fibrinolysis inhibitor pathway has also been proposed to explain the variability in bleeding, and might be clinically useful in helping identify patients with increased bleeding risk (10).

Management of patients without spontaneous bleeding symptoms typically does not require treatment. However, for those experiencing bleeding, avoidance of platelet-inhibitory agents is crucial. Antifibrinolytic agents may prevent spontaneous nosebleeds and manage hypermenorrhea, while therapeutic plasma may be utilized to substitute lacking Factor XI, although high volumes are needed to achieve significant increases in activity (11). In patients with severe deficiency, FFP may be inadequate to correct the plasma factor levels. In 90% of the patients, FXI concentrate replacement showed adequate correction of deficiency, but 10% of patients can have increased risk of thrombosis (12). Monitoring of FXI activity and replacement of factor concentrate or FFP should be conducted as needed (13).

This case highlights the significance of routine preoperative screening for coagulation abnormalities. Factor XI deficiency, while often asymptomatic, can present as prolonged APTT and requires careful interpretation of laboratory findings. Early recognition is crucial for the management of patients undergoing surgical procedures to minimize potential bleeding risks.

Financial Disclosure

None to declare.

Conflict of Interest

There is no conflict of interest

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