Clinical Aspects of and Therapy for Hemophilia A. Incidence. Clinical Severity, страница 2

The choice of treatment for factor VIII deficiency depends on its severity. Those with severe or moderate disease are treated with factor concentrate. Patients with mild disease (factor VIII levels >10%) can receive desmopressin (deamino-D-arginine vasopressin [DDAVP]). Cryoprecipitate is also used in some centers to treat mild hemophilia A. However, since it cannot be virally inactivated, most physicians use factor concentrate in patients with mild hemophilia A who do not respond to DDAVP.

Within a given hemophilia kindred, the clinical and laboratory severity of the disorder is relatively consistent. The appearance of a more severe clinical course in a family relative should raise the question of either established anatomic lesions that predispose to frequent or severe hemorrhage, or the development of an inhibitor.

Clinical Manifestations

The clinical hallmarks of hemophilia A are (1) lack of excessive hemorrhage from minor cuts or abrasions due to the normalcy of platelet function; (2) joint and muscle hemorrhages, which lead to the most difficult and disabling long-term sequelae; (3) easy bruising; (4) prolonged and potentially fatal postoperative hemorrhage; and (5) a panoply of social psychologic, vocational, and economic problems. For many patients treated with blood products prior to 1985, acquisition of human immunodeficiency virus (HIV) exacerbated already severe clinical problems. MLID87239713  16 Finally, slowly progressive hepatocellular disease, mainly attributable to chronic hepatitis C, remains a threat to patients. 17

Hemarthroses

The joints most frequently involved (in descending order of frequency) are the knees, elbows, ankles, shoulders, hips, and wrists. Bleeding into the hand is rare and usually follows significant trauma, while the spine is rarely, if ever, involved.

The first episodes of acute hemarthrosis occur in childhood, but often not until the child begins to walk. Infants and small children may develop large ecchymoses from being carried or lifted. Hemarthrosis is usually either spontaneous or associated with imperceptible trauma. The onset of hemorrhage is signaled by an "aura," consisting of vague warmth, a tingling sensation, and/or a sense of mild restlessness or anxiety; this aura may last up to 2 hours. Mild discomfort and slight limitation of joint motion occur next, followed (after 1 to several hours) by pain, joint swelling, cutaneous warmth, and eventual severe limitation of motion. Once bleeding has stopped, the blood is reabsorbed, and the joint returns to normal over several days to several weeks.

When pain, swelling, and severe limitation of motion are present, the hemorrhage is far advanced and the process of synovitis begins; this may predispose the joint to further episodes of hemarthrosis and to hemophilic arthropathy 18 (Fig. 106-1). Joint hemorrhage should be treated after the earliest symptoms are noted and before any physician findings to prevent the long-term disabling sequelae. Adults may demonstrate periodic joint pain due to established hemophilic arthropathy rather than bleeding and may have considerable fibrosis of the joint capsule, thus preventing joint swelling. They may develop chronic limitation of motion, removing the value of this finding in diagnosing an acute bleed. Prophylactic correction of the hemostatic defect over several weeks or months can help the patient to differentiate acute hemarthrosis from the background of chronic symptoms and signs.

An episode of bleeding into a joint predisposes to further episodes for at least two possible reasons. MLID75088474  19 First, hemarthrosis stimulates proliferation, chronic inflammation, and hypervascularity of the synovial membrane. Second, hemarthrosis is accompanied by rapid atrophy of the periarticular musculature and a subsequent compromise in joint protection exerted by these muscles (Fig. 106-2).

Chronic Arthritis

Recurrent hemarthrosis may lead to a self-perpetuating condition in which joint abnormalities persist in intervals between bleeding episodes. Clinically, the involved joint is chronically swollen, although painless and slightly warm. There are clinical findings of chronic synovitis, including prominent synovial bogginess with or without effusion (Fig. 106-3). Mild limitation of motion may be present, often with flexion deformity. Factor replacement does not modify these parameters. The likelihood of developing chronic arthritis is directly related to the overall severity of the underlying coagulation defect. In one study of 139 hemophiliac patients, only 42% were found to have definite and an additional 14% possible hemophilic arthritis, based on clinical and radiographic features. 20 Despite any previous history of hemarthrosis, however, no patient with a factor level >20% had hemophilic arthritis, while up to one-third with levels between 6% and 20% had possible or definite arthritis. In those patients who develop chronic arthritis, it is not clear whether the phenomenon is due to repeated subclinical minor hemorrhage or to irreversible synovial proliferation induced by major hemarthroses. However, it is this clinical state that often progresses to the severe destructive arthritis seen in advanced hemophilic arthropathy. The radiologic changes are seen in Figures 106-4 and 106-5. Nonsteroidal anti-inflammatory agents have been found to offer significant pain relief without routinely causing increased bleeding difficulties.