A 14-year-old boy is brought to the emergency department for severe pain and swelling in his right knee that began several hours after he fell while playing basketball. He has a history of prolonged bleeding after a tooth extraction at age 6 and a maternal uncle who reportedly bruised easily and had joint problems. Vital signs are within normal limits. On physical examination, the right knee is erythematous, warm, and exquisitely tender, with a significantly decreased range of motion due to swelling.
Laboratory studies reveal the following:
Platelet count: 240,000/μL
Prothrombin Time (PT): 12 seconds (Normal: 11–13.5s)
Partial thromboplastin time (PTT): 62 seconds (Normal: 25–35s)
Bleeding time: Normal
Which of the following is the most likely primary defect in this patient?
The correct answer is:
B) Deficiency of a clotting factor in the intrinsic pathway
This patient is presenting with Hemophilia A, an X-linked recessive disorder caused by a deficiency of Factor VIII. Factor VIII is a critical component of the intrinsic pathway of the coagulation cascade. It serves as a cofactor for Factor IXa in the activation of Factor X. Unlike disorders of primary hemostasis, like von Willebrand disease or immune thrombocytopenic purpura, which present with mucocutaneous bleeding, hemophilia typically presents with deep tissue bleeding, such as hemarthrosis (bleeding into joints) or intramuscular hematomas. Because the intrinsic pathway is impaired, the partial thromboplastin time (PTT) is prolonged. However, the extrinsic pathway (measured by PT) and platelet function (measured by bleeding time or platelet count) remain perfectly normal.
Answer choice A: Deficiency of a clotting factor in the extrinsic pathway, is incorrect. The extrinsic pathway is initiated by tissue factor and involves Factor VII. A deficiency here would cause a prolonged PT, not a prolonged PTT.
Answer choice C: Impaired platelet adhesion to the subendothelium, is incorrect. This describes von Willebrand Disease (vWD) or Bernard-Soulier Syndrome. While vWD can cause a mildly prolonged PTT, its primary manifestation is mucocutaneous bleeding (nosebleeds, heavy menses) and a prolonged bleeding time, which this patient does not have.
Answer choice D: Inability of platelets to aggregate, is incorrect. This describes Glanzmann thrombasthenia. Like other platelet disorders, it presents with primary hemostasis symptoms, such as petechiae and mucosal bleeding, and a prolonged bleeding time, rather than hemarthrosis.
Answer choice E: Qualitative defect in the vWF protein, is incorrect. This refers to type 2 von Willebrand disease. While vWF stabilizes Factor VIII, the classic presentation of a male with isolated joint bleeding and a significantly prolonged PTT strongly favors a primary Factor VIII deficiency (Hemophilia A).
Key Learning Point
Hemophilia A is characterized by a deficiency in Factor VIII, leading to a prolonged PTT with a normal PT and platelet count. The clinical hallmark is hemarthrosis, often following minor trauma. Because it is X-linked recessive, it almost exclusively affects males. Treatment involves factor replacement therapy or emicizumab, a bispecific antibody that mimics Factor VIII function.
