Hemophilia A
Hemophilia A is an X-linked recessive deficiency of factor VIII that produces deep bleeding into joints, muscles, and after surgery in male patients, diagnosed by an isolated prolonged aPTT that corrects on a mixing study and confirmed by a reduced factor VIII activity assay. Management is factor VIII replacement or emicizumab for moderate to severe disease, desmopressin for mild disease, and antifibrinolytics for mucosal bleeding, with inhibitor development the most serious treatment complication.
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What this article covers
- Overview
Definition: hemophilia A is an X-linked recessive bleeding disorder caused by deficiency of coagulation factor VIII, producing deep tissue bleeding rather than mucocutaneous bleeding.
- Epidemiology
Rare disease: hemophilia A is more common than hemophilia B, but both are rare.
- Risk factors
Male sex with a maternal family history of hemophilia: the dominant risk factor given X-linked recessive inheritance.
- Pathophysiology
Factor VIII is a cofactor in the intrinsic coagulation pathway: it accelerates activation of factor X by factor IXa on a phospholipid surface; without it, thrombin generation and stable clot formation are impaired.
- Clinical features
Spontaneous hemarthrosis: the hallmark of moderate to severe disease, presenting as acute joint pain, warmth, swelling, and decreased range of motion, most often in the knees, ankles, and elbows; the…
- Differential diagnosis
Acquired hemophilia (factor VIII autoantibody): new bleeding in a previously healthy adult (often peripartum, or with malignancy, autoimmune disease, or a new medication) with an aPTT that fails to correct on a mixing study.
- Diagnosis
Establish the diagnosis with an isolated prolonged aPTT that corrects on a mixing study, plus a normal PT and platelet count, confirmed by a reduced factor VIII activity assay; classify severity by…
- Management
Treat every significant bleed as an emergency; give factor replacement before imaging or further workup when hemophilia is known or strongly suspected, because delay allows joint destruction, compartment syndrome, or intracranial extension.
- Complications
Intracranial hemorrhage: the leading cause of hemophilia-related death, requiring emergent factor replacement to 80%-100% activity before imaging is completed if suspicion is high.
- Prognosis
Prophylaxis has transformed outcomes: regular prophylactic factor VIII (or emicizumab) in severe disease markedly reduces spontaneous bleeding frequency and the chronic joint complications that dominated outcomes in the pre-prophylaxis era.
- Prevention
Prophylactic factor VIII or emicizumab in all patients with moderate to severe hemophilia A: factor VIII 25-40 IU/kg IV every other day or three times weekly, or emicizumab 1.5 mg/kg SC weekly after…
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Von Willebrand disease is the most common inherited bleeding disorder, caused by deficient or dysfunctional von Willebrand factor, producing mucocutaneous bleeding from impaired platelet adhesion plus a mild secondary factor VIII deficiency. Diagnosis rests on the vWF antigen, ristocetin cofactor activity, and factor VIII activity panel, and management centers on desmopressin for type 1, vWF concentrate for severe or desmopressin-unresponsive disease, and antifibrinolytics for mucosal bleeding.
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