Chapter 57: Hemophilia

Epidemiology

1. Hemophilia A is a congenital X-linked recessive bleeding disorder characterized by deficient or defective coagulation factor VIII

2. Overall incidence: 1 in 10,000 males

3. Annual incidence estimated at approximately 500 male births

4. Hemophilia A observed in all ethnic and racial groups

Work-up

1. Bleeding time of PFA-100—usually normal

2. Prothrombin time (PT)—normal

3. Activated partial thromboplastin time (aPTT)—usually prolonged except in certain cases of mild hemophilia; it is corrected by the addition of an equal volume of normal plasma

4. Factor VIII coagulant activity—low

   1. Classification of severity

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      Factor VIII Coagulant
      Activity	Severity	Bleeding Episodes
      <1%	Severe	Spontaneous and traumatic bleeding, predominately in joints/muscles
      1–4%	Moderate	Severe bleeding after trauma
      ≥5%	Mild	Bleeding, infrequent, usually after surgery or trauma

5. Factor VIII von Willebrand Factor antigen (FVIII VWF:Ag) and FVIII Ristocetin cofactor (FVIII VWF:RCo)—normal

6. The 1-stage FVIII coagulant assay is the most widely used method for the determinations of the FVIII clotting activity because of its reproducibility, simplicity, and low cost. In many centers, particularly in Europe, use for the chromogenic assay to determine FVIII levels is more frequent. The results obtained with both assays usually correlate with each other. No significant differences in the results between the 2 methods have been detected in normal donors and in those with chronic liver disease (Chandler WL et al. Am J Clin Pathol 2003;120:34–39). However, discrepancies in the assays are observed in patients with mild hemophilia who have missense mutations (Verbruggen B et al. Haemophilia 2008;14(Suppl 3):76–82). Very low FVIII coagulant activities can sometimes be better diagnosed by a chromogenic assay

7. Differential diagnosis of an isolated prolongation of a PTT (Ragni MV, Kessler CM, Lozier JN. Clinical aspects and therapy for hemophilia. In Hoffman R, Benz EJ, eds. Hematology Basic Principles and Practice. Philadelphia, PA: Church Livingstone Elsevier; 2009:1918)

   1. Heparin use

   2. Factor VIII deficiency or inhibitor to factor VIII

   3. von Willebrand disease (VWD)—especially the type II-N variant of VWD

   4. Factor IX deficiency or inhibitor to factor IX

   5. Factor XI deficiency or inhibitor to factor XI

   6. Factor XII deficiency

   7. Contact factor deficiency or inhibitor

   8. Lupus anticoagulant

   9. Factor VIII and factor XI deficiency; factor VIII and factor XII deficiency

Treatment Options

1. Factor VIII replacement

2. Desmopressin acetate

3. Antifibrinolytic therapy

4. Topical agents

5. Platelet concentrates

6. Recombinant Factor VIIIa

7. Prothrombin complex concentrates (PCC)

Acute bleeds should be treated early (immediately, or as soon as possible within 2 hours of onset). Home therapy should be used to manage uncomplicated mild bleeding episodes (eg, hemarthrosis, small muscle bleeds), while more severe bleeds should be evaluated in the clinic or hospital setting, if needed, with subsequent management as needed under the care of a hematologist with expertise in hemophilia care. Patients should avoid use of drugs affecting platelet function;—that is, aspirin or aspirin-containing compounds, or nonsteroidal antiinflammatory drugs (NSAIDs). Use of acetaminophen-containing analgesics is a safe alternative. If possible, intramuscular injections should be avoided, unless performed under coverage of clotting factor VIII