Hematology · Coagulation Disorders
The facts most likely to be tested
Hemophilia B is an X-linked recessive disorder caused by a deficiency of Factor IX.
Patients present with hemarthrosis, deep tissue hematomas, and prolonged bleeding after minor trauma or surgery.
Laboratory evaluation reveals an isolated prolonged aPTT with a normal PT and normal platelet count.
The diagnosis is confirmed by a low Factor IX activity level assay.
Hemophilia B is clinically indistinguishable from Hemophilia A (Factor VIII deficiency) and requires factor activity assays to differentiate.
The first-line treatment for acute bleeding episodes is the administration of recombinant Factor IX concentrate.
Desmopressin (DDAVP) is ineffective in Hemophilia B because it only increases levels of Factor VIII and von Willebrand factor.
Vignette unlocked
A 5-year-old boy is brought to the clinic by his mother due to persistent swelling and pain in his right knee after a minor fall while playing. He has a history of easy bruising and prolonged bleeding following a recent tooth extraction. Physical examination reveals a swollen, warm, and tender right knee with limited range of motion. Laboratory studies show a prolonged aPTT of 68 seconds (normal 25-35 seconds), a normal PT, and a normal platelet count.
What is the most appropriate next step in management to confirm the diagnosis?
Factor IX activity assay
The patient's clinical presentation of hemarthrosis and isolated prolonged aPTT is classic for hemophilia; a factor activity assay is required to distinguish between Factor VIII (Hemophilia A) and Factor IX (Hemophilia B) deficiency.
Full handout
High yield triage
Etiology / Epidemiology
X-linked recessive deficiency of Factor IX (Christmas disease) primarily affecting males.
Clinical Manifestations
Deep tissue bleeding, hemarthrosis, and delayed post-traumatic bleeding.
Diagnosis
Activated Partial Thromboplastin Time (aPTT) is prolonged; Factor IX assay confirms diagnosis.
Treatment
Factor IX concentrate is the first-line treatment; avoid aspirin/NSAIDs.
Prognosis
Life expectancy is near normal with prophylactic factor replacement.
Full handout
Epidemiology & Etiology
Hemophilia B is an X-linked recessive disorder caused by mutations in the *F9* gene. It is significantly less common than Hemophilia A, occurring in approximately 1 in 30,000 live male births. Spontaneous mutations account for roughly 30% of cases, meaning a negative family history does not rule out the diagnosis.
Pertinent Anatomy
The coagulation cascade relies on the intrinsic pathway, where Factor IX acts as a cofactor for Factor VIII to activate Factor X. Deficiencies lead to impaired fibrin clot formation at sites of injury. Bleeding is most common in weight-bearing joints and deep muscle compartments.
Pathophysiology
The deficiency of Factor IX prevents the formation of the tenase complex, stalling the intrinsic pathway. This results in a failure to generate sufficient thrombin to stabilize the platelet plug. Clinical severity correlates with residual factor activity: severe (<1%), moderate (1-5%), or mild (5-40%).
Clinical Manifestations
Patients present with hemarthrosis (joint bleeding), deep muscle hematomas, and excessive bleeding after minor trauma or surgery. Intracranial hemorrhage is a life-threatening emergency and a leading cause of death. Unlike platelet disorders, mucocutaneous bleeding and petechiae are typically absent.
Diagnosis
The aPTT is characteristically prolonged, while the Prothrombin Time (PT) and platelet count remain normal. A mixing study will correct the aPTT, confirming a factor deficiency rather than an inhibitor. The Factor IX activity assay is the definitive diagnostic test.
Treatment
The primary treatment is Factor IX concentrate infusion to restore clotting activity. For mild cases, desmopressin is ineffective, unlike in Hemophilia A. Avoid NSAIDs and aspirin due to antiplatelet effects that exacerbate bleeding risk. Patients should be screened for transfusion-transmitted infections if using plasma-derived products.
Prognosis
Long-term complications include chronic arthropathy due to recurrent joint bleeds and the development of inhibitor antibodies (though less common than in Hemophilia A). Regular prophylactic factor replacement is the standard of care to prevent joint damage and life-threatening bleeds.
Differential Diagnosis
Hemophilia A: distinguished by Factor VIII deficiency
Von Willebrand Disease: distinguished by prolonged bleeding time and normal aPTT
Vitamin K Deficiency: distinguished by prolonged PT/INR
DIC: distinguished by thrombocytopenia and elevated D-dimer
Liver Disease: distinguished by abnormal PT and low albumin