Differential Diagnosis for Bleeding in a 53-year-old Woman

Single Most Likely Diagnosis

• Factor 8 inhibitor (Acquired Hemophilia A): This is the most likely diagnosis given the patient's prolonged PTT that corrects partially with a 1:1 mix with normal plasma, suggesting an inhibitor rather than a factor deficiency. The patient's lack of bleeding history despite significant hemostatic challenges in the past also supports an acquired condition.

Other Likely Diagnoses

• Factor 8 deficiency (Hemophilia A): Although less likely due to the patient's age and lack of previous bleeding episodes, a mild factor VIII deficiency could be considered, especially if the patient has a family history. However, the partial correction with a 1:1 mix suggests an inhibitor.
• Factor 9 deficiency (Hemophilia B): Similar to factor VIII deficiency, this would typically present with a bleeding history from a younger age, making it less likely. The partial correction of PTT with a 1:1 mix also points away from this diagnosis.
• Factor 12 deficiency: This is a consideration for prolonged PTT, but factor XII deficiency is usually asymptomatic and not associated with bleeding, as factor XII is not crucial for hemostasis in vivo.

Do Not Miss Diagnoses

• Lupus Anticoagulant: This can cause a prolonged PTT and is associated with an increased risk of thrombosis rather than bleeding. However, in some cases, it can lead to bleeding due to its effect on the coagulation cascade. It's crucial to rule out lupus anticoagulant due to its potential for significant morbidity.
• Disseminated Intravascular Coagulation (DIC): Although the fibrinogen level is within the normal range, which argues against DIC, this condition can present with a wide range of coagulation abnormalities and should be considered in the differential diagnosis due to its potential severity.

Rare Diagnoses

• Other factor deficiencies or inhibitors (e.g., factor XI deficiency): These are less common and would typically present with bleeding episodes earlier in life. However, acquired inhibitors can occur at any age, making them a consideration in the differential diagnosis.
• Von Willebrand Disease: Typically presents with mucocutaneous bleeding and would have been expected to cause symptoms earlier in life, especially with the significant hemostatic challenges the patient has faced.