Last updated: November 4, 2014
Synonyms: Hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency).
ICD-9 Code: Hemophilia A, 286.0; hemophilia B, 286.1; hemarthrosis, 719.10.
ICD-10 Code: D66 – D68
Definition: Hemophilia A and B are congenital, X-linked recessive disorders of the coagulation cascade that may manifest with hemorrhage into weight-bearing joints, muscle, or soft tissues. Hemophilia A and B are clinically similar; hemophilia A accounts for >80% of cases. Disease severity is based on the amount of factor present (2% is severe, 2%–5% is moderate, and 5%–25% is mild). Factor levels >25% are rarely associated with hemorrhagic events.
Etiology: Hemophilia is caused by congenital deficiency of factors VIII or IX. Acquired deficiencies have been reported.
Pathology: Intraarticular blood does not coagulate because of the lack of prothrombin, fibrinogen, and tissue thromboplastin. Red blood cells may incite inflammation and may lead to synovial proliferation (without inflammatory cells), pannus, and cartilage damage. Hemosiderin is found in synovium and chondrocytes.
Demographics: Hemophilia A affects one in 10,000 males. Females are asymptomatic. Males are commonly affected and the first episode of bleeding occurs before the age of 5 years.
Cardinal Findings: Acute hemarthrosis may begin as stiffness or warmth that is followed by intense pain. Low-grade fever may occur. Intraarticular hemorrhage commonly affects the knees, ankles, and elbows and manifests as an acute, erythematous, warm mono- or oligoarthritis. Involvement of small joints (fingers, wrist, sternoclavicular) is unusual and should suggest other diagnoses. Repetitive hemarthrosis may cause secondary OA, deformity, or less commonly a chronic synovitis (with or without effusion). Other common sites of bleeding include muscle (resulting in myonecrosis or compartments syndrome), bone, CNS, or kidney (manifest as hematuria).
Complications: Transfusions and factor VIII therapy have resulted in HIV positivity, acquired immunodeficiency syndrome (AIDS), hepatitis B or C infection, and chronic liver disease. Septic arthritis rarely accompanies hemarthrosis. Nonetheless, staphylococcal, pneumococcal, and Salmonella septic arthritis have been well described in hemophilia.
Diagnostic Tests: Activated PTT is prolonged; prothrombin time and platelet counts are normal. Assays for factor VIII are commonly available, and titers are low during bleeding episodes. Synovial fluid shows a predominance of red blood cells.
Imaging: Radiographs may show soft tissue swelling, juxtaarticular osteopenia, joint space narrowing, and subchondral cyst formation. Marginal erosions may be seen with chronic disease. Widening of the femoral intercondylar notch is said to be characteristic of hemophilia.
Keys to Diagnosis: Look for a positive family history or antecedent diagnosis of hemophilia associated with hemorrhage into joints or soft tissues.
Differential Diagnosis: Hemorrhagic joint effusions may also be owing to von Willebrand’s disease, vitamin K deficiency, platelet disorders, crystal-induced arthritis, trauma, fracture, ligament tear (cruciate), neuropathic arthritis, and pigmented villonodular synovitis. Acute hemophiliac hemarthrosis must be distinguished from septic arthritis, HIV-related arthropathies, and crystal-induced arthritis.
Therapy: Long-term use of aspirin and NSAIDs should be avoided. Acute bleeding can be treated with sufficient recombinant factor VIII to elevate levels to 40% to 50%. The dose is calculated from the patient’s weight and factor VIII level. Ice, rest, analgesia, and joint extension (to avoid contractures) is advised. Do not attempt invasive procedures (e.g., arthrocentesis) until factor VIII levels are >50%. Arthrocentesis is indicated if infection is suspected. Septic arthritis may accompany an acute hemarthrosis. The therapeutic value of arthrocentesis to remove blood and red blood cells that may exacerbate in- flammation is controversial. Intraarticular steroids should not be used. Major bleeding (e.g., CNS) requires chronic factor VIII levels >50% until resolved. Prophylactic administration of factor VIII (three times weekly) has been ad- vocated for patients with recurrent or severe bleeding. Although seldom used, reports suggest that chronic inflammatory synovitis may benefit from penicillamine or gold therapy.
Surgery: Arthroscopic synovectomy is seldom required for chronic synovitis. Surgical procedures (e.g., total joint replacement) can be cautiously performed with adequate factor replacement.
Avina-Zubieta JA, Galindo-Rodriguez G, Lavalle C. Rheumatic manifestations of hematologic disorders. Curr Opin Rheumatol 1998;10:86–90.PMID:9448995