Hemophilia
Hemophilia: Excerpt from The 5-Minute Pediatric Consult
Char Witmer, MDDon E. Eslin, MD (4th Edition)
Hemophilia - BASICS
Hemophilia - description
- Hemophilia A is factor VIII deficiency and hemophilia B is factor IX deficiency. Both are inherited in an X-linked recessive manner.
- Deficiency or absence of FVIII or FIX leads to a delay and disruption of blood clotting that results in prolonged bleeding.
- The severity of bleeding depends on the percentage of clotting activity. No activity (<1%) results in severe disease, 1–5% is moderate and 6–30% is mild hemophilia.
Hemophilia - general prevention
- Prophylaxis: The regularly-scheduled infusion of clotting factor concentrate with the goal of preventing bleeding episodes. Primarily used in patients with severe disease.
- Primary prophylaxis: Regularly scheduled infusion of clotting factor before joint bleeding has typically initiated before 1 year of age.
- Secondary prophylaxis: Regularly scheduled infusion of clotting factor after joint bleeding has occurred.
- Anticipatory guidance and prevention:
- Good dental hygiene
- Immunizations: No IM injections; give subcutaneously with a small-gauge needle and apply direct pressure for several minutes.
- Rapid treatment of hemarthrosis to avoid chronic joint damage
- Avoidance of aggressive contact sports (e.g., football, hockey, rugby)
- Encourage physical fitness to ensure strong muscles to maintain joint health and prevent joint bleeding. Some recommended activities include swimming, bicycle riding, and walking/hiking. Other sports that can be considered include baseball, soccer, tennis and basketball.
- Home infusion therapy for prophylaxis as appropriate
- Self-infusion training: Usually starts at age 11 years
Hemophilia - epidemiology
- Most common severe inherited bleeding disorder
- Distribution:
- Hemophilia A: 80–85%
- Hemophilia B: 10–15%
- No geographic or ethnic associations
- 30% of cases are sporadic (no family history)
Hemophilia - incidence
- Hemophilia A: 1 per 5,000 male births
- Hemophilia B: 1 per 30,000 male births
Hemophilia - risk factors
Hemophilia - genetics
- X-linked recessive disorder
- Daughters of fathers with hemophilia are obligate carriers for the hemophilia gene mutation. An obligate carrier has a 50% chance of passing the hemophilia gene mutations to her offspring.
- Carrier status and prenatal testing available
- Hemophilia A:
- The intron 22 inversion mutation in the factor VIII gene is found in 44–45% of patients with severe hemophilia A; detectable by direct gene mutation analysis.
- Hemophilia B (Christmas disease):
- Most factor IX gene defects are single–base pair changes that result in missense, frameshift, or nonsense mutations. Mutations have been detected in all regions of the factor IX gene.
Hemophilia - pathophysiology
- Both factors VIII and IX are crucial for normal thrombin generation via the intrinsic pathway. The absence or decrease in activity of either protein severely impairs the ability to generate thrombin and fibrin.
- Hemophilia patients do not bleed more rapidly; rather, there is delayed formation of an abnormal clot.
- The friable clot formed has a tendency to ooze and rebleed.
- In closed spaces (e.g., joint), bleeding stops by tamponade; in open spaces (e.g., iliopsoas muscle, open wounds), significant amounts of blood may be lost.
- Repeated joint hemorrhages lead to synovial thickening and joint cartilage erosion. Joint space becomes narrowed and eventually fuses.
Hemophilia - DIAGNOSIS
Hemophilia - signs & symptoms
Hemophilia - history
- Family history:
- Familial history of hemophilia in male offspring of female blood relatives is present in only 70% of cases. 30% of the time there is no family history of hemophilia.
- Excessive bleeding in a male neonate:
- Excessive bleeding with circumcision may be an initial presentation of hemophilia, although only 50% of patients with hemophilia will have excessive bleeding with circumcision.
- Muscle bleeding from intramuscular injections e.g., vitamin K or immunizations; presents as increasing swelling at the site of injection
- Oral bleeding from a torn frenulum or prolonged bleeding from venipuncture or heel puncture can be seen.
- 1–2% of neonates with hemophilia may present with an intracranial hemorrhage.
- Pattern of bleeding in severe hemophilia:
- Characterized by easy, excessive, and palpable bruising with normal activity, spontaneous joint and muscle hemorrhages, and prolonged and potentially fatal hemorrhage after trauma or surgery
- Age of onset of bleeding:
- Bleeding events occur frequently when the child begins to crawl and walk or with the eruption of teeth.
- Location of hemarthroses:
- Large weight-bearing joints are most often involved: Knees, ankles, and hips also elbows and shoulders.
- Early symptoms of a hemarthroses:
- Aura of tingling or warmth, visible swelling, followed by increasing pain and decreasing range of motion
Hemophilia - physical exam
Joint examination:
- Acute hemarthrosis: Limitation and pain with range of motion of the joint, warmth, swelling, tenderness
- Chronic joint changes: Crepitus, decreased range of motion, synovial hypertrophy, boney abnormalities, and proximal muscle weakness
- Intramuscular hematomas: May not have external bruising, there will be pain with motion and swelling. With larger bleeds there will be a discrepancy in limb circumference
- Distal extremity neurovascular compromise can be a sign of compartment syndrome from bleeding into forearm or calf muscles.
Hemophilia - tests
- Neonates have a physiologic reduction in the vitamin K–dependent factors, including factor IX, making a determination of the degree of factor IX deficiency difficult in the neonatal period. The factor IX level must be confirmed after 6 months of age.
- When interpreting coagulation testing in a neonate, neonatal normal values for the PT and aPTT are different from those in adults.
Hemophilia - lab
Patients with hemophilia either A or B will have a normal PT and a prolonged aPTT. Assay for factor VIII and factor IX levels:
- <1%: Severe hemophilia, characterized by spontaneous bleeding; hemarthroses and deep-tissue hemorrhages; will need frequent factor replacement therapy
- 1–5%: Moderate hemophilia. Bleeding following mild to moderate trauma; hemarthrosis and muscle bleeding, seldom-spontaneous hemorrhage
- 5–30%: Mild hemophilia. Bleeding from trauma only, no spontaneous hemorrhages; patients require factor replacement only with significant trauma or surgery
Hemophilia - differencial diagnosis
- Isolated prolonged aPTT associated with increased bleeding tendency:
- von Willebrand disease
- “Acquired hemophilia” owing to development of an inhibitory antibody to factor VIII or IX (extremely rare in children)
- Hereditary factor deficiency of either VIII, IX, or XI
- Afibrinogenemia
- Prolonged aPTT without increased bleeding tendency:
- Factor XII deficiency
- High-molecular-weight kininogen deficiency
- Prekallikrein deficiency
- Antiphospholipid antibody (lupus anticoagulant)
- Heparin artifact
- Under filling of the specimen tube
- Polycythemia
Hemophilia - TREATMENT
Hemophilia - initial stabilization
Life-threatening hemorrhages:
- CNS bleeding
- Bleeding into and around the airway
- Exsanguinating hemorrhage
- Prompt therapy with clotting factor concentrate should start immediately and prior to any diagnostic procedures.
Hemophilia - medication
Acute bleeding episodes:
- Factor replacement:
- Factor VIII replacement products:
- Recombinant, non–plasma-derived factor VIII
- Plasma-derived, monoclonal antibody–purified factor VIII concentrate; heat or solvent detergent treated for viral inactivation
- Cryoprecipitate (rarely used)
- Factor IX replacement products:
- Recombinant, non–plasma-derived factor IX
- Plasma-derived, immunoaffinity-purified factor IX concentrate; heat or solvent detergent treated for viral inactivation
- Prothrombin complex concentrate (PCC): Crude plasma fraction that contains variable amounts of activated factors II, VII, IX, and X; heat-treated for viral inactivation
- Fresh frozen plasma (rarely used)
- Calculation of dose for pediatrics:
- Recombinant Factor VIII dosing (units) = % desired rise in plasma factor VIII × body weight (kg) × 0.5
- Recombinant Factor IX dosing (units) = % desired rise in plasma factor IX level × body weight (kg) x 1.4
- Target factor levels:
- Joint bleed: 30–50% for 24–48 hours
- Large muscle bleed: 70–100% repeated over 12–48 hours for large muscle bleeds
- CNS bleeding: 80–100% maintained for 10–14 days
- Desmopressin (DDAVP):
- Synthetic vasopressin analog that stimulates release of endogenous factor VIII and von Willebrand factor
- Only suitable for patients with mild or moderate factor VIII deficiency who have shown a response to DDAVP in a trial
- Tachyphylaxis may occur with repeated dosing.
- Hyponatremia may also occur. Fluid restriction is recommended. Should not be used in neonates.
- Antifibrinolytic therapy:
- Antifibrinolytic therapy is used to stabilize a clot by inhibiting the normal process of clot lysis by the fibrinolytic system.
- Agents used for the treatment of oral hemorrhages and to minimize bleeding from dental and some surgical procedures: Aminocaproic acid (Amicar), 100 mg/kg/dose PO q6h (maximum, 6 g/dose), or tranexamic acid (Cyklokapron), 25 mg/kg/dose PO q8h (maximum, 1.5 g/dose)
Hemophilia - general measures
- Immobilization:
- Splints, casts, crutches, and/or bed rest
- Prolonged immobilization may reduce recovery of joint range of motion; initiation of physical therapy with factor coverage is recommended, particularly after joint surgery.
- Special bleeding situations:
- Intracranial hemorrhage:
- Significant bleeding can occur despite a minor mechanism of head injury and the absence of external bruising. In severe hemophilia spontaneous intracranial bleeding can occur.
- Factor replacement to 100% should be administered immediately followed by the diagnostic evaluation.
- Major surgery:
- Factor replacement to 100% preoperatively and postoperatively
- Regular dosing of factor for a minimum of 1 week postoperatively, even in mild hemophilia
- Compartment syndrome:
- Bleeding within the fascial compartments of muscles
- Most often occurs in the forearm and calf
- Neurovascular compromise can lead to Volkmann contracture.
- Iliopsoas bleed:
- Lower abdominal or upper thigh pain may be the 1st symptom.
- Examination is notable for inability to extend hip with preservation of internal and external rotation (allows distinction from hemarthrosis of hip joint).
- Diagnosis confirmed by ultrasound or CT scan
- Oral bleeding/epistaxis:
- Constant pressure for 15–20 minutes
- Aminocaproic acid or tranexamic acid
- Topical thrombin directly to the site of bleeding
- Dental care:
- Factor replacement is required for significant dental procedures like tooth extraction or mandibular block injection.
- Preferably done in a hospital setting where hematology consultation is available.
- Factor replacement is not required for routine teeth cleaning.
- Lacerations:
- Factor replacement is necessary at time of placement and removal of the sutures.
- Hematuria:
- Increased fluid intake and bed rest as initial treatment
- If hematuria persists 24–48 hours, 30–40% factor replacement
- Antifibrinolytics are contraindicated in the setting of hematuria because of the concern of obstructive uropathy from excessive clot formation.
- Patients should be followed regularly at a comprehensive hemophilia treatment center.
Hemophilia - FOLLOW UP
Hemophilia - complications
- Complications of disease:
- Hemophilic arthropathy: Joint contractures, limited range of motion, and chronic pain
- Intracranial bleeding (can occur without known trauma in severe hemophilia)
- Compartment syndrome
- Airway compromise owing to bleeds in the pharynx, tongue, or neck
- Life-threatening hemorrhage owing to GI, posttraumatic, or perioperative bleeds
- Complications of therapy:
- Viral transmission (HIV, hepatitis B and C) through clotting factor concentrates derived from pooled plasma preparations (>22,000 donors per lot)
- Inhibitors: Antibodies against factor VIII or IX, which can inactivate infused factor
- Anaphylaxis: Seen primarily with infusions of factor IX.
- Thromboembolic disease: Use of activated prothrombin complex concentrates has been associated with thrombotic complications.
Hemophilia - bibliography
- Dunn AL, Abshire, TC. Recent advances in the management of the child who has hemophilia. Heme/Oncol Clin North Am. 2004;18:1249–1276.
Lee CA, Berntorp EE, Hoots WK. Textbook of Hemophilia. Malden, Massachusetts: Blackwell Publishing Ltd; 2005.- Manco-Johnson MJ, Riske B, Kasper CK. Advances in care of children with hemophilia. Semin Thromb Hemost. 2003;29:585–594.
- Mannucci PM, Tuddenham EGD. The hemophilias: From royal genes to therapy. NEJM. 2001;344:1773–1779.
- Pruthi RK. Hemophilia: A practical approach to genetic testing. Mayo Clin Proc. 2005;80:1485–1499.
Hemophilia - CODES
Hemophilia - icd9
286.0 Hemophilia
Hemophilia - FAQ
- Q: Are there any medications contraindicated in a child with hemophilia?
- A: Aspirin should not be given, as it interferes with platelet function. Nonsteroidal anti-inflammatory agents cause a milder effect on platelets and should also be avoided when possible. Patients with hemophilia should use acetaminophen for fever or pain.
- Q: Can immunizations be given to a child with hemophilia?
- A: Immunizations should be given subcutaneously (instead of intramuscularly) with the smallest gauge needle available. Ice or cold packs should be applied to the area to minimize hematoma formation.
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
More About Hemophilia
More Medical Textbooks Online about Hemophilia
Review other book chapters online related to Hemophilia:
Medical Books Excerpts
- Hemophilia
- "Professional Guide to Diseases (Eighth Edition)" (2005)
- [ read ]
Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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