Hemophilia is an X-linked recessive disorder of coagulation caused by deficiency of factor VIII (hemophilia A) or factor IX (hemophilia B), occurring in one in 5000 males.^1,2 The percentage of factor present determines the severity of disease. Six percent to 50% factor activity levels denote mild disease with no tendency for spontaneous hemorrhage and bleeding occurring usually only with surgery or severe trauma. One percent to 5% implies moderate disease with bleeding following mild trauma. Less than 1% is severe disease with proclivity to spontaneous hemorrhage.¹ Approximately 35% of male patients with hemophilia have severe disease.² In both hemophilia A and B, the prothrombin time (PT) is normal and partial thromboplastin time (PTT) is prolonged. The same types of bleeding occur in both factor VIII and factor IX deficiency. Bruising, hemarthroses, and intramuscular hematomas predominate. Intracranial hemorrhage is less common but can be devastating. It is important to listen to the patient and their parents, as the initial presentation of bleeding may not be dramatic. Most patients are treated prophylactically with long-acting factor concentrates to reduce long-term bleeding complications^1,3,4; however this does not eliminate risk due to compliance and other clinical issues.

ACUTE HEMARTHROSIS

Knees, elbows, ankles, hips, and shoulders are the most commonly affected joints (Fig. 106-1). Older patients may be aware of a bleed prior to the onset of pain and swelling, whereas younger patients may present with new-onset limp or limited range of motion. It is generally agreed that even if joint bleeding cannot be confirmed, treatment is indicated. This is based on the potentially crippling sequelae of hemarthrosis. Intraarticular bleeding provokes a strong synovial inflammatory reaction causing erosion of the cartilage, synovial hypertrophy, and friability. Muscle atrophy around the joint leads to instability, which increases the likelihood of more frequent hemarthroses. Unless treated early and adequately, repeated bleeding into a “target joint” can lead to complete cartilaginous destruction, causing secondary osteoarthritis. Joint swelling that is persistent and associated with fever may indicate a septic joint. Aspiration preceded by appropriate factor replacement may be necessary, but should only occur after discussion with the child’s hematologist. Joint aspiration is not recommended for most cases of bleeding.

Symptomatic treatment of hemarthroses consists of splinting, ice, immobilization, elastic bandages, and non-NSAID analgesia. A single-factor infusion to raise levels to 40% to 60%² is usually sufficient to terminate bleeding. A joint that has bled repeatedly may require several doses of factor. Range of motion and physical therapy are instituted as soon as possible. Bleeding into the hip is especially worrisome because pressure within the joint can lead to necrosis of the femoral head. Factor replacement to 80% to 100% levels with subsequent daily replacement to 50% may be necessary.

INTRAMUSCULAR BLEEDING

Such hemorrhage usually affects the large weight-bearing muscles such as the iliopsoas, calf, gluteal, and forearm muscles, but can affect any muscle of the body. Bleeding is often slow, occurring over extended periods of time before symptoms of pain, tenderness, and swelling appear. Therefore, such hemorrhages often present as a large hematoma. Treatment consists of factor replacement to a level of 40% to 60%.² Forearm, calf, and hand bleeding can result in a compartment syndrome.^5,6 Vascular compromise or nerve paralysis may occur if not treated promptly with factor replacement. Iliopsoas hemorrhage, which can be massive, presents with flexion of the thigh (hip flexion contracture), groin, or iliac fossa pain, and paresthesias along the anterior thigh from femoral nerve compression. Factor replacement to a level of 80% is recommended.² This characteristic triad of symptoms is secondary to femoral nerve compression by the swollen iliopsoas muscle as it passes under the anterior ligament. Ultrasound or computed tomography (CT) can confirm the diagnosis. Additionally, compartment syndrome can result in pain, weakness, and/or paresthesia/numbness, requiring factor replacement to higher levels and potential surgical fasciotomy—a decision that should be made in conjunction with a hematologist.^5,6

INTRACRANIAL HEMORRHAGE

Intracranial bleeding may be traumatic or spontaneous. Minor trauma may present with neurologic changes days after the event.^2,4 Symptoms include headache, lethargy, loss of consciousness, vomiting, and seizures. Forceful blows to the head, regardless of symptoms, are empirically treated with factor replacement. If intracranial hemorrhage is suspected, immediate factor replacement to a 100% level is necessary, which should not be delayed by imaging studies.²

OTHER BLEEDING MANIFESTATIONS

Subcutaneous hemorrhage, abrasions, and lacerations that do not require sutures do not require factor replacement. However, factor replacement is necessary prior to laceration repair, lumbar puncture, surgery, and dental extractions. Men with hemophilia can also present with painless, gross hematuria. An anatomic source of the bleeding is often not found and treatment with factor may or may not be necessary. In cases such as this, close consultation with the child’s hematologist is invaluable. Intramuscular injections, antiplatelet agents, and jugular and femoral venipuncture are to be avoided in this patient population. Simple peripheral venipuncture is followed by at least 5 minutes of pressure to the site.

MANAGEMENT ISSUES

Factor replacement for hemophilia A or B is accomplished by transfusion with a variety of factor VIII or IX concentrates, respectively. These products are made recombinant proteins. The amount of factor to be delivered will be dependent on the nature and severity of the bleeding episode. For minor bleeding, the target factor level is 30% to 40%. For major bleeding or prior to surgery, a minimum of 50% factor level is required. For life- or limb-threatening bleeds, 80% to 100% factor level is needed, and treatment with factor replacement is required every 12 hours or by continuous infusion until healing occurs.

The following formulas may be used to calculate factor replacement:

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  Factor VIII (units) = weight (kg) × 0.5 × desired increment (percent) of factor VIII level (i.e., 1 U/kg of factor VIII raises the level by 2%).²

  
  
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  Example: To achieve 50% factor VIII level in an 80-kg patient:

  
  

    80 × 0.5 × 50 = 2000 units of factor VIII given as a bolus

  
  
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  Factor IX (units) = weight (kg) × 1.0 × desired increment (percent) of factor IX level (i.e., 1 U/kg of factor IX raises the level by approximately 1%).²

  
  
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  Example: To achieve a 50% factor IX level in an 80-kg patient:

  
  

    80 × 1.0 × 50 = 4000 units of factor IX given as bolus