Hemophilia A and B vs Von Willebrand Disease

Why Factor VIII and IX activity assays is correct

• An isolated prolonged PTT with a normal PT, normal platelet count, and absent petechiae points to an intrinsic-pathway factor deficiency rather than a primary hemostasis (platelet) problem.
• The mixing study correcting the PTT confirms a factor deficiency, because donor plasma supplies the missing factor; failure to correct would instead implicate a circulating inhibitor.
• Hemarthrosis after minor trauma in a young boy with an X-linked family history is the classic phenotype of hemophilia A or B, which are clinically indistinguishable. Specific factor VIII and factor IX activity assays are required to make the diagnosis and to direct factor-specific replacement.

Why the others are wrong

• Bethesda factor inhibitor titer assay quantifies a factor inhibitor and is reserved for when the mixing study fails to correct; here the PTT corrected, so an inhibitor is not the issue.
• Von Willebrand factor activity assay helps exclude von Willebrand disease, but vWD typically causes mucocutaneous bleeding rather than isolated hemarthrosis, and it is lower yield than the factor assays that define hemophilia.
• Platelet aggregation function studies evaluate primary hemostasis (platelet function disorders), which present with mucocutaneous bleeding and petechiae and show a normal PTT; the platelet count and PTT pattern here are inconsistent with a platelet defect.

Why Menorrhagia since menarche with prolonged bleeding after dental work is correct

• A mucocutaneous bleeding pattern with a normal platelet count, a normal PT, a mildly prolonged aPTT, and affected relatives of BOTH sexes is von Willebrand disease, the most common inherited bleeding disorder, usually autosomal dominant type 1.
• Von Willebrand factor has two jobs: it mediates platelet adhesion to subendothelial collagen, and it chaperones factor VIII in plasma.
• Deficiency therefore produces a platelet-type bleeding phenotype, heavy menstrual bleeding, epistaxis, easy bruising, and prolonged bleeding after dental extraction or surgery, together with a mildly low factor VIII that explains the modestly prolonged aPTT.
• Heavy menses dating from MENARCHE is the single most productive question in a young woman with suspected bleeding disorder, and von Willebrand disease is found in roughly 5-20 percent of women referred for menorrhagia.
• Confirm with von Willebrand antigen, ristocetin cofactor activity, and factor VIII; treat with desmopressin for type 1 and von Willebrand factor concentrate for severe bleeding or type 3.

Why the others are wrong

• Painful bleeding into the right knee after a soccer collision — hemarthrosis of hemophilia. It is X-linked, so the classic pedigree runs through males - but do not exclude it merely because an affected relative is female, as carriers can bleed significantly and women with hemophilia are recognized. What points to von Willebrand disease here is the mucocutaneous pattern in relatives of both sexes.
• Palpable purple spots on the buttocks after a sore throat — IgA vasculitis, an inflammatory purpura with normal coagulation studies.
• Bruising that first appeared after starting daily aspirin for headaches — aspirin causes an acquired platelet-function defect, but it does not prolong the aPTT and cannot account for easy bruising in her mother and brother; her pattern is inherited and lifelong.

Avoid aspirin and NSAIDs, and plan hemostatic cover before any procedure.