Clinical Aspects of and Therapy for Hemophilia B. Harold R. Roberts and T, Flint Gray III, страница 2

Clinical Manifestations

General Considerations

Clinical manifestations of hemophilia B, which are indistinguishable from those of hemophilia A, are sometimes noted at the time of circumcision, but excessive bleeding following this event is less frequent than commonly believed. More often, easy bruising and frequent hematomas are noted by mothers of affected infants. Hematomas and hemarthroses are characteristic of factor IX and other procoagulant deficiencies and distinguish them from bleeding resulting from qualitative and quantitative platelet disorders.

Bleeding in hemophilia B is sometimes delayed and may not become noticeable until several days after minor trauma. Hematomas in patients with hemophilia tend to dissect through tissues along fascial planes. For example, a small hematoma originating in the buttock after an intramuscular injection may dissect to involve muscles of the back and leg and may even become life-threatening.


The hallmark of severe hemophilia is repeated hemarthroses, resulting in chronic, crippling hemophilic arthropathy. 21 In decreasing order of frequency, the most commonly involved joints are the knee, elbow, ankle, shoulder, wrist, and hip. The first indication of a joint hemorrhage is a sensation of intra-articular burning, followed by a sensation of fullness, tightness, swelling, and increasing pain leading to limitation of motion. Although the intra-articular space is enclosed by a synovial lining that limits the extent of bleeding, joint swelling may be severe enough to compromise neurovascular function. Involuntary muscle splinting due to pain leads to joint immobilization and initiates a vicious cycle of atrophy and contracture. Repeated bleeding into a joint results in deposition of hemosiderin, which contributes to synovial inflammation and increased vascularity, predisposing to further bleeding. Joints with a chronically inflamed and hypertrophic synovium are referred to as "target joints" and are susceptible to recurrent hemarthroses unless treated for several weeks with factor IX replacement therapy. With repeated bleeding, destruction of intra-articular cartilage and adjacent bone occurs and leads to progressive deterioration of joint function with further muscle atrophy and contracture. The joint deformity that occurs in severe hemophilia is so characteristic that it is virtually diagnostic of hemophilia A or B. A detailed radiologic classification of hemophilic arthropathy based on eight criteria and level of severity has been used for initial orthopaedic evaluation and to evaluate the effect of prophylactic therapy. MLID81002554  22


Pseudotumors are cystic lesions that arise in patients with clotting factor deficiencies, most commonly hemophilia A or B. The cysts arise from hematomas and may begin in the subperiosteal area of bone or in soft tissue. Once formed, the lesions tend to expand, probably due to repeated bleeding and osmosis. When the cystic lesions become sufficiently large, they are referred to as pseudotumors, which may be lobulated and consist of a thick, brownish necrotic core of debris surrounded by a thick fibrous wall. Expansion may lead to obstruction or compression of adjacent organs, or rupture through the skin or into nearby viscera. Such complications may be accompanied by infection. Surgical resection is the therapy of choice, but may be unsuccessful when a pseudotumor becomes unduly large. For this reason, surgical excision is suggested early in the course of development of pseudotumors. Other types of treatment, such as radiation, drainage, or factor IX replacement therapy, are not effective.

Neurologic Symptoms

Intracranial hemorrhage is one of the major causes of death in hemophilia B and may occur even in the absence of recognizable trauma. However, few hemophilic infants have intracranial hemorrhage as a complication of vaginal delivery. Because intracranial hemorrhage is often catastrophic, such bleeding must be prevented if possible. Any sign or symptom suggestive of intracranial hemorrhage should be treated as a potential medical emergency. For example, any unusual or peculiar headache in a hemophilic patient should be considered due to an intracranial hemorrhage until proven otherwise. Thus, prompt treatment with factor IX concentrate is indicated prior to any diagnostic procedures such as computed tomography scans, skull radiographs, or other procedures. Appropriate diagnostic tests should be obtained only after the patient's clotting defect is corrected. Intracranial bleeding exemplifies the shortcomings of current replacement therapy of hemophilia B and points out the need for a continuous level of factor IX (such as that provided by prophylactic therapy), since hemorrhage into the central nervous system may result in serious or fatal complications before "on demand" treatment can be instituted. Other bleeding complications affecting nervous tissue include neuropathies that result from compression of nerves by hematomas or intraneural bleeding, or both. Peripheral nerve compression by a hematoma is a particularly common problem, as exemplified by femoral nerve palsy secondary to retroperitoneal hematoma that dissects into and compresses the femoral canal. The prognosis for recovery after prolonged nerve compression is poor, again necessitating an aggressive treatment approach based on clinical suspicion.