A 6-year-old boy presents to the emergency department after falling from his scooter. He has dull, aching pain along his left side where he hit the ground. He fell sideways off the scooter as he rounded a curve in the road. He has never had any serious injuries but that he always seems to bruise easily, especially after he started playing soccer this fall. His parents deny that he has an abnormal number of nosebleeds or bleeding from the gums. They have never seen blood in his stool or urine. His mother notes that her brother has had similar problems. His temperature is 98.6°F (37°C), blood pressure is 112/74 mmHg, pulse is 82/min, and respirations are 11/min. On physical exam, the patient has extensive bruising of the lateral left thigh and tenderness to palpation. Laboratory tests are performed and reveal the following:

Hemoglobin: 14 g/dL
Hematocrit: 41%
Mean corpuscular volume: 89 µm3
Reticulocyte count: 0.8%
Leukocyte count: 4,700/mm3
Prothrombin time (PT): 13 seconds
Partial thromboplastin time (PTT): 56 seconds
Bleeding time (BT): 4 minutes

Which of the following is the most likely underlying pathophysiology?
Anti-platelet antibodies
Von Willebrand factor deficiency
GP1b deficiency
Factor 8 deficiency
Factor 8 deficiency
This young patient presents with extensive bruising following an injury, a family history of blood disorder, and a prolonged partial thromboplastin time (PTT) with a normal prothrombin time (PT) and bleeding time. These findings suggest a diagnosis of hemophilia A caused by factor 8 deficiency.

Hemophilia is a deficiency of factor 8 (hemophilia A) or factor 9 (hemophilia B). Common symptoms of hemophilia include hemarthrosis, intramuscular hematoma, and gastrointestinal or genitourinary bleeding. Laboratory testing is helpful in confirming the diagnosis, as hemophilia is characterized by an isolated prolongation of PTT without a change in PT. The factors involved in hemophilia participate only in the indirect cascade of coagulation factor activation. Similarly, since bleeding time depends only upon platelet function and not coagulation factors, hemophilia presents with a normal bleeding time. Treatment of hemophilia includes desmopressin in mild cases and factor replacement in moderate to severe disease.

Berntorp et al. present a review of the evidence regarding the diagnosis and treatment of hemophilia. They discuss how these patients now have normal life expectancies with the advent of factor replacement therapy. They recommend being vigilant for the development of anti-factor antibodies.

Incorrect Answers:
Answer A: Anti-platelet antibodies are responsible for idiopathic thrombocytopenic purpura (ITP). This disease is caused by autoimmune antibody formation that damages platelets and causes them to be removed by splenic macrophages in the reticuloendothelial system. It usually occurs in children after an acute viral infection and it presents with bleeding from mucosal surfaces with laboratory findings showing an increased bleeding time, decreased platelets, and a normal PT/PTT.

Answer C: Factor 9 deficiency (hemophilia B) presents nearly identically to hemophilia A with a normal PT, prolonged PTT, and normal bleeding time with a history of bleeding in male relatives. However, because hemophilia B is epidemiologically less common than hemophilia A, hemophilia A is a more likely diagnosis.

Answer D: GP1b deficiency causes Bernard-Soulier syndrome, which is a bleeding disorder characterized by unusually large platelets and a low platelet count. Like von Willebrand disease (vWD), patients often present with cutaneous and mucosal bleeding, abnormal bleeding from minor trauma, and a prolonged bleeding time, which this patient does not have. It can be distinguished from vWD by a ristocetin assay. Treatment can include tranexamic acid.

Answer E: Von Willebrand factor deficiency results in vWD, which is a bleeding disorder characterized by cutaneous and mucosal bleeding, menorrhagia, and gastrointestinal bleeding. Unlike this patient, patients with vWD also present with a prolonged bleeding time. Patients with vWD will also have an increased PT because this factor is responsible for stabilizing coagulation factor 8.

Bullet Summary:
Hemophilia A is caused by factor 8 deficiency and presents with hemarthrosis, frequent bruising, intramuscular hematoma, and gastrointestinal bleeding with a prolonged PTT with a normal PT and bleeding time.