Practice Essentials Hemophilia A is an X-linked, recessive disorder caused by deficiency of functional plasma clotting factor VIII (FVIII), which may be inherited or arise from spontaneous mutation. The development of inhibitory antibodies to FVIII can result in acquired hemophilia A or can complicate the treatment of genetic cases. Signs and symptoms Depending on the level of FVIII activity, patients with hemophilia may present with easy bruising, inadequate clotting of traumatic injury or—in the case of severe hemophilia—spontaneous hemorrhage. Signs of hemorrhage include the following: General: Weakness, orthostasis, tachycardia, tachypnea Musculoskeletal (joints): Tingling, cracking, warmth, pain, stiffness, and refusal to use joint (children) CNS: Headache, stiff neck, vomiting, lethargy, irritability, and spinal cord syndromes Gastrointestinal: Hematemesis, melena, frank red blood per rectum, and abdominal pain Genitourinary: Hematuria, renal colic, and post circumcision bleeding Other: Epistaxis, oral mucosal hemorrhage, hemoptysis, dyspnea (hematoma leading to airway obstruction), compartment syndrome symptoms, and contusions; excessive bleeding with routine dental procedures See Clinical Presentation for more detail. Diagnosis Laboratory studies for suspected hemophilia include the following: Complete blood cell count Coagulation studies FVIII assay Expected laboratory values are as follows: Hemoglobin/hematocrit: Normal or low Platelet count: Normal Bleeding time and prothrombin time: Normal Activated partial thromboplastin time (aPTT): Significantly prolonged in severe hemophilia, but may be normal in mild or even moderate hemophilia Normal values for FVIII assays are 50-150%. Values in hemophilia are as follows: Mild: >5% Moderate: 1-5% Severe: <1% Imaging studies for acute bleeds are chosen on the basis of clinical suspicion and anatomic location of involvement, as follows: Head computed tomography scans without contrast are used to assess for spontaneous or traumatic intracranial hemorrhage MRI scans of the head and spinal column are used for further assessment of spontaneous or traumatic hemorrhage MRI is also useful in the evaluation of the cartilage, synovium, and joint space Ultrasonography is useful in the evaluation of joints affected by acute or chronic effusions Testing for inhibitors is indicated when bleeding is not controlled after adequate amounts of factor concentrate are infused during a bleeding episode. Inhibitor concentration is titrated using the Bethesda method, as follows: Positive result: Over 0.6 Bethesda units (BU) Low-titer inhibitor: Up to 5 BU High-titer inhibitor: Over 5 BU See Workup for more detail. Management The treatment of hemophilia may involve the following: Management of hemostasis Management of bleeding episodes Use of factor replacement products and medications Treatment of patients with factor inhibitors Treatment and rehabilitation of patients with hemophilia synovitis Disposition of treatment is as follows: Management ideally should be provided through a comprehensive hemophilia care center Home administration of treatment and infusions by the family or patient is customary FVIII treatment may be given prophylactically or on demand Hospitalization is reserved for severe or life-threatening bleeds For treatment of acute bleeds, target levels by hemorrhage severity are as follows: Mild hemorrhages (eg, early hemarthrosis, epistaxis, gingival bleeding): Maintain an FVIII level of 30% Major hemorrhages (eg, hemarthrosis or muscle bleeds with pain and swelling, prophylaxis after head trauma with negative findings on examination): Maintain an FVIII level of at least 50% Life-threatening bleeding episodes (ie, major trauma or surgery, advanced or recurrent hemarthrosis): Maintain an FVIII level of 80-100% To find the number of units of factor VIII needed to correct the factor VIII activity level, use the following formula: Units factor VIII = (weight in kg)(50 mL plasma/kg)(1 U factor VIII/mL plasma)(desired factor VIII level minus the native factor VIII level) FVIII regimens are as follows: The second dose should be administered 12 hours after the initial dose and is one half the initial calculated dose Minor hemorrhage requires 1-3 doses of FVIII Major hemorrhage requires many doses and continued FVIII activity monitoring with the goal of keeping the trough activity level at least 50% Continuous infusions of FVIII may be considered for major hemorrhage. The following types of FVIII concentrates are available: Plasma-based products: Purified to inactivate viruses First-generation recombinant products: Produced in mammalian cell lines, with a small amount of human serum albumin added for stability Second-generation recombinant products: Manufactured without human albumin Third-generation products: Have no exposure to animal proteins Desmopressin vasopressin analog, or 1-deamino-8-D-arginine vasopressin (DDAVP), has the following attributes: Considered the treatment of choice for mild and moderate hemophilia A Not effective in the treatment of severe hemophilia Can be intravenously administered at a dose of 0.3 mcg/kg of body weight in the inpatient setting Peak effect is observed in 30-60 minutes A concentrated DDAVP intranasal spray is available for outpatient use The following antifibrinolytics are used in addition to FVIII replacement for oral mucosal hemorrhage and prophylaxis: Epsilon aminocaproic acid (Amicar) Tranexamic acid (Cyklokapron) Treatments used in patients with inhibitors of FVIII are as follows: High doses of FVIII for low-titer inhibitors Anti-inhibitor coagulant complex (FEIBA VH) Porcine FVIII, which has low cross-reactivity with human FVIII antibody Activated prothrombin complex concentrate (PCC) Activated FVII Desensitization Immune tolerance induction (ITI) Source
