Clinical Care Treatment Protocols, Sickle Cell Ulcer

What is sickle cell disease?

Sickle cell disease is an inherited hemoglobinopathy characterized by the predominance of hemoglobin S. The sickling of red cells is caused by inheritance of homozygous hemoglobin S, compound heterozygosity for hemoglobin S and hemoglobin C, or beta thalassemia.

Who does sickle cell disease affect?

Worldwide more than 100,000 neonates per year are born with sickle cell disease. In the United States, 3 in 1,000 African American neonates have some form of sickle cell disease. The significance of sickle cell disease is indicated by the presence of 80,000 patients in the United States alone.

Approximately 5% of patients age 10 and older with sickle cell anemia have leg ulcers on entry into the Cooperative Study of Sickle Cell Disease in the United States. Low steady-state hemoglobin is associated with a higher incidence of ulcer formation in sickle cell anemia patients. Also, the study found that males are more likely to have ulcers than females.

The Jamaica Sickle Cell Cohort Study found that chronic leg ulceration is a major cause of morbidity in homozygous sickle cell disease. The cumulative involvement of leg ulceration reaches 75% in patients age 30 and older.

According to the genotype of sickle cell disease, in patients age 20 and older with sickle cell anemia, the incidence rates range from 15 to 20 per 100 person-years.

Who is not affected by sickle cell ulcers?

The Cooperative Study of Sickle Cell Disease found that leg ulcers are not present in patients with sickle beta thalassemia and sickle hemoglobin C disease.

What pathological changes occur in vessel walls due to sickle cells?

The defective properties of the sickle hemoglobin lead to abnormal erythrocyte adhesiveness with reflexive vasoconstriction. Intimal proliferation leads to segmental narrowing of medium-size arteries and degenerative changes of the media, as well as obstruction of the vasa vasorum—all contributing to the vaso-occlusive events that characterize the sickle cell crisis.

These pathological changes in vessel walls predispose the person to superimposed thrombosis or embolization, blocking the arterial supply to all or part of the affected organ.

Who should be tested for sickle cell disease?

Any African-American person who does not have proven venous reflux disease or who has had an ulcer develop prior to age 30 should be tested for sickle cell disease. The threshold for testing should be negligible and the overall sensitivity is 100% for sickle cell disease.

What type of tests should be used to test for sickle cell disease?

The most widely used diagnostic test for sickle cell disease and traits is hemoglobin electrophoresis. Definitive diagnosis may require more specific hemoglobin analysis, including family studies, red-cell indices, and DNA studies.

What should be evaluated when a patient who has sickle cell disease arrives with a leg ulcer?

All patients should be evaluated for the more common systemic complications. The organs commonly affected by microcirculatory vascular occlusions are:

• Marrow
• Spleen
• Lungs
• Kidneys
• Brain (usually affected at the level of the large blood vessels)

Therefore, the status of the lungs, kidney, brain (such as stroke), bones, and liver should be documented by the wound care practitioner upon the patient's entry into the wound program.

What causes sickle cell ulcers?

In some instances, the same pathology that causes sickle cell disease complications also causes the ulcer. For example, blood vessel occlusion in the spleen and liver is similar to vascular infarcts in the skin, muscle, or bone of the leg. The latter three sites can contribute significantly to nonhealing ulcers.

Vascular infracts in the leg are directly related to musculoskeletal problems involved in sickle cell complications presenting with bone pain. Red blood cell sickling, which is advanced by slow circulation in the bone marrow, is the primary contributor to bone complications suffered by patients with sickle cell disease.

Impaired blood flow in the bone commonly results in infarcts in the leg, which in turn causes pain in a sickle cell patient's extremities. Damage to the microcirculation caused by sickling may be chronic.

What are the pathogenic pathways?

Two pathogenic pathways have been described for causing these bone complications, both involving an abnormal red blood cell shape. In the first pathway, sickling of the red cells produces thromboembolic infarcts in bone leading to pain, crises, and occasionally osteomyelitis. In the other pathway, increased destruction of sickled red cells produces hemolysis, an increase in erythroblastic activity, and expansion of the bone marrow cavity. Osteomyelitis, retardation of growth, dactylitis, described as avascular necrosis—particularly of the head of the femur—and leg ulcers are commonly encountered.

What are common characteristics of a sickle cell ulcer?

The ulcers usually begin as small, elevated, crusting wounds on the lower third of the leg, around the medial or lateral malleolus. They can also occur over the pretibial area or the dorsum of the foot. They can be single, multiple, unilateral, or bilateral. The person will usually report some form of minor trauma or insect bite as the precipitating factor. However, the history is often insignificant because the ulcers may occur spontaneously. The emphasis is to understand that as soon as a person with sickle cell disease presents with a break in the epidermis, treatment should begin immediately.

Is determining which type of ulcer important?

Sickle cell ulcers are frequently—and mistakenly—attributed to venous reflux disease because the symptoms are similar to those of venous stasis ulcers. Both sickle cell ulcers and venous stasis ulcers occur near the ankle and show hyperpigmentation and, frequently, dermatitis. Misdiagnosis—and thus, mistreatment—of a sickle cell ulcer as a Venous Ulcer is extremely dangerous.

What types of tests should be done to ensure proper diagnosis?

• Bone scan—the test of choice to evaluate for osteomyelitis
• X-rays—used to determine the presence of osteomyelitis and bone infarcts
• MRI (magnetic resonance imaging)—may demonstrate the striking marrow reconversion with low signal-intensity marrow replacement; may detect extensive superimposed infarcts involving diaphysis and metaphysis, as well as epiphysis before they are apparent on plain film
• Biopsy—all sickle cell ulcers lasting longer than 2 months should be examined by biopsy prior to treatment to rule out malignancy; biopsy can also reveal other histologic features related to diagnosis
• Culture—following tissue debridement, cultures of deep tissue must always be taken to determine the presence and type of bacteria in the tissue
• Arterial and venous reflux testing—mandatory to rule out other contributing wound healing impairments; it is now recognized that the pathogenesis of leg ulcers in sickle cell disease is not attributable to arterial or venous insufficiency, but is the result of multiple infarcts of the microcirculation

How is osteomyelitis differentiated from infarcts?

Infarcts and osteomyelitis may have similar clinical presentations, requiring imaging for differentiation. Osteomyelitis manifests on MRIs with inflammation replacing normal, reconverted, or ischemic marrow. The finding of associated soft tissue tracts, phlegmon, or abscess is helpful in differentiating intramedullary infarcts from abscesses. Bone scan may be particularly helpful to evaluate patients for osteomyelitis.

What should be done before the first assessment?

The establishment of and adherence to a clinical pathway—which includes affiliated services such as physical therapists, radiologists, nutritionists, pain specialists, hematologists, and social workers—enables efficient wound assessment, thereby promoting successful healing.

How is pain treated?

The nation's first evidence-based clinical practice guideline concerning pain was released in August 1999. The major recommendations follow:

• Clinicians should ask patients about pain. Patient self-reports should be the primary source of assessments.
• Patients should be reassessed at each visit and asked if pain management measures have been effective.
• Pain therapy should be tailored to the patient's individual needs.
• Pain management should ease pain, enable the patient to tolerate treatments, and attain maximal functional ability.

What medications are administered for pain?

Topical anesthetic agents, such as lidocaine (Xylocaine®) jelly 2% or lidocaine solution 2% to %5 compresses, are available to assist in wound care. Allow 10 to 15 minutes for the anesthetic to take effect. The person usually will have taken oral analgesics prior to the dressing change—opioids are frequently prescribed for pain management. Lidocaine patches are also useful for the periwound skin. The use of topical opioids, dissolved in 1 to 2 ml of water and mixed with a debriding ointment, has been reported to provide complete pain relief in two patients. However, the outcome of wound care for these patients was not reported, and more research is needed.

Is the "wet-to-dry" dressing effective?

No. The debridement method in which the dry dressing pulls off devitalized tissue is a nonselective one and has a limited role in contemporary wound healing. Allowing a gauze dressing to dry and the pulling it off not only produces acute pain but also causes reinjury to the wound, removing natural growth factors and enzymes near the wound's surface.

What dressings accelerate wound healing?

Slow-release silver topical medications provide broad-spectrum antibacterial coverage for long periods of time. Alternatively, Iodosorb® cadexomer iodine is antimicrobial and stimulates granulation tissue.

Today, dressings are used to accelerate the wound-healing process in addition to covering wounds and facilitating debridement. A multitude of wound care products are now available, the use of which is based on scientific evidence. Many of these products are superior alternatives to wet-to-dry dressings.

How is infection treated?

Wounds with infections must be treated with antibiotics. Due to poor vascularization, oral antibiotics may not be successful. In these patients, antibiotics administered parenterally may be more efficacious.

Is debridement necessary?

Surgical debridement should be performed on all sickle cell ulcers lasting longer than two months if the wound does not contract by a minimum of 10% over a two-week period, as measured by planimetry.

What should be done prior to debridement?

Debridement can result in a hemoglobin level that cannot be tolerated. It is therefore essential that the patient's hemoglobin is raised prior to surgery to compensate for any significant blood loss, common vasodilation and subsequent hypotension, which may result from the effects of general anesthesia.