The patient should undergo factor VIII testing. He has had abnormal bleeding following a surgical procedure and dental extractions. The activated partial thromboplastin time (aPTT) is prolonged but corrects fully in a 1:1 mixing study. This could occur with clotting factor deficiencies VIII, IX, and XI; however, this patient's bleeding disorder appears to be familial. Because his maternal grandfather may have had a bleeding disorder resulting in intracerebral bleeding at a young age, and his brother had abnormal bleeding, the likely inheritance pattern is X-linked recessive; only hemophilia A and B are inherited in this fashion. Hemophilia A results from factor VIII deficiency and hemophilia B from factor IX deficiency; both produce a prolongation of the aPTT that fully corrects in a mixing study. Persons with severe hemophilia have less than 1% factor VIII or IX activity; they will have severe recurrent hemarthroses as well as retroperitoneal and intramuscular bleeding. Central nervous system hemorrhage is especially hazardous and is a leading cause of death. Mild hemophilia may present in adulthood and is characterized by posttraumatic or surgical bleeding.

The bleeding time test is performed by blotting away excess blood, which tests primary hemostasis rather than fibrin formation. The bleeding time is prolonged in patients with platelet dysfunction, von Willebrand disease (vWD), thrombocytopenia, and anemia. The bleeding time will be abnormal in this patient because of his anemia and will not assist in establishing the diagnosis.

Patients with factor XI deficiency will have a prolonged aPTT, as in this patient, but the inheritance pattern is autosomal recessive, not X-linked. Additionally, bleeding is not spontaneous, tends to be milder in degree, and typically affects mucocutaneous surfaces. It is highly unlikely to cause an intracerebral hemorrhage in a younger person, such as this patient's grandfather.

The antiphospholipid syndrome is defined by the presence of antiphospholipid antibodies and typical clinical manifestations. This disorder may occur as an independent syndrome (primary antiphospholipid syndrome) or secondary to underlying systemic lupus erythematosus. Antiphospholipid antibodies include anticardiolipin, anti-β₂-glycoprotein I, and the lupus anticoagulant. The lupus anticoagulant does prolong the aPTT, but the aPTT will not correct in a 1:1 mixing study. Lupus anticoagulant is also more likely to lead to abnormal thrombosis rather than bleeding.