Sickle Cell Disease - Clinical Tree

Key Points

Sickle cell disease is a systemic disorder that requires a thorough preoperative evaluation in close coordination with multiple comanaging services.
Preoperative blood transfusion according to a standardized protocol managed by an experienced hematologist may reduce the risk of postoperative vaso-occlusive crisis and acute chest syndrome.
Cortical thinning and medullary sclerosis of the proximal femur increases the risk of intraoperative fracture and cortical perforation; modified surgical techniques should be employed to reduce this risk.
Postoperative management should focus on the maintenance of adequate hydration, oxygenation, and avoidance of hypothermia to prevent sickle cell complications.
Sickle cell patients should be counseled preoperatively on the higher rates of infection and aseptic loosening after total hip arthroplasty.

Sickle cell disease is a systemic disorder characterized by hemolytic anemia and small-vessel occlusion. The disorder stems from the polymerization of deoxygenated hemoglobin S (HbS), a variant of the normal adult hemoglobin gene, causing erythrocytes to take on a rigid, sickled shape. Heterozygosity of HbS with the normal adult hemoglobin gene (HbA) is referred to as sickle cell trait (SA genotype) and is generally asymptomatic. Sickle cell disease arises from the homozygous inheritance of HbS (SS genotype) or combined heterozygosity, the inheritance of a single HbS gene with another hemoglobin variant, such as hemoglobin C (SC genotype) or beta-thalassemia (Sβ ⁰ and Sβ ⁺ genotypes).

The prevalence of sickle cell disease is the highest in sub-Sarahan Africa, along the Mediterranean Sea, in the Middle East, and in India because of the protection that the sickle cell trait affords against severe malaria. Globally, 300,000 children per year are born with sickle cell anemia. In the United States, 100,000 individuals are estimated to have sickle cell disease. With increasing life expectancy in developed countries, the number of patients with sickle cell disease is expected to increase.

Dysfunction and damage to multiple organ systems is found in patients with sickle cell disease. Polymerization of deoxygenated HbS results in vaso-occlusion, hemolytic anemia, and a number of other pathologic processes, including vascular-endothelial dysfunction, functional nitric oxide deficiency, inflammation, oxidative stress, and hypercoagulability. Acute complications are generally related to vaso-occlusion. These include ischemic damage to the tissues resulting in severe pain crises and acute chest syndrome, a leading cause of hospitalization and mortality among the patients with sickle cell disease. Chronic complications such as stroke, pulmonary hypertension, and retinopathy may be related to large-vessel vasculopathy, whereas other chronic complications such as hyposplenism, renal failure, and osteonecrosis are related to ischemic organ damage.

Osteonecrosis of the femoral head is a debilitating chronic complication of sickle cell disease. The prevalence of femoral head osteonecrosis in sickle cell disease is dependent on the underlying genotype and is greatest in patients with the Sβ ⁰ genotype (13.1%), followed by those with the hemoglobin SS genotype (10.2%), SC genotype (8.8%), and Sβ ⁺ genotype (5.8%). Presence of the alpha-thalassemia genes increases the prevalence of femoral head osteonecrosis in the patients with Hb SS genotype. Femoral head osteonecrosis develops before the age of 35 years in nearly half of all patients with HbSS. Bilateral hip involvement is reported to occur in 40% to 91% of the patients.

The association between sickle cell disease and femoral head osteonecrosis was described in detail by Chung and Ralston in 1969. The precise mechanism is unknown. It is postulated that both intravascular occlusion by sickled erythrocytes and an increase in the intraosseous extravascular pressure due to marrow hyperplasia and edema would collectively lead to impaired intramedullary circulation and subsequent osteonecrosis.

Indications/Contraindications

Nonoperative treatment options of femoral head osteonecrosis in the patients with sickle cell disease consist of symptomatic management with physical therapy and pain control using nonsteroidal antiinflammatories and/or opiates. Preventive measures to reduce further vaso-occlusive crises that may result in the progression of the osteonecrosis, such as treatment with hydroxyurea, should be considered. There is conflicting evidence of the utility of bisphosphonates in reducing the risk of femoral head collapse in the patients with early-stage femoral head osteonecrosis. There is, however, no study that has specifically evaluated the efficacy of bisphosphonates in sickle cell patients.

Operative treatment options for precollapse femoral head osteonecrosis include core decompression, multiple drilling, and vascularized or nonvascularized bone grafting. The efficacy of these methods in patients with sickle cell disease is not well established. Total hip arthroplasty (THA) is indicated for those patients who have failed conservative treatment or other surgical treatments. As an alternative to THA, total hip resurfacing has been performed in selected patients. Absolute contraindications to THA include active infection, poor medical optimization, and active or recent sickle cell pain crisis or acute chest syndrome. Primary resection arthroplasty and hip fusion are poor options owing to the young age of presentation, the high probability of bilateral disease, and the difficulty in achieving fusion in necrotic bone. Femoral osteotomy is associated with a poor outcome, as it does not alter disease progression. Hemiarthroplasty and hemiresurfacing are generally not recommended because of the abnormal acetabular bone stock that may predispose the patient to progressive acetabular degeneration and protrusio.

Multiple staging systems have been proposed to describe the progression of femoral head osteonecrosis. The three most commonly used are the Ficat and Arlet, the University of Pennsylvania (Steinberg), and the Association Research Circulation Osseous (ARCO) classification systems ( Tables 85.1 through 85.3 ). Regardless of the classification system used, the size of the lesion and the presence of sclerosis or cysts, crescent sign, head depression, and/or collapse, as well as acetabular changes, should be noted. In 2007, McGrory and associates reported that among members of the American Association of Hip and Knee Surgeons, THA was the most frequent intervention for treatment of postcollapse (Steinberg stages III, IV, V, and VI) osteonecrosis. Core decompression was the most commonly offered intervention for symptomatic precollapse (Steinberg stages I and II) osteonecrosis. Less common treatments include osteotomy, vascularized or nonvascularized bone grafting, hemiarthroplasty, and arthrodesis.

TABLE 85.1

Ficat and Arlet Classification System

Stage	Radiographic Finding
I	None (evident only on magnetic resonance imaging [MRI])
II	Diffuse sclerosis, cysts (visualized on radiographs)
III	Subchondral fracture (crescent sign with or without head collapse)
IV	Femoral head collapse, acetabular involvement, and joint destruction (osteoarthritis)

TABLE 85.2

University of Pennsylvania (Steinberg) Classification System

Stage	Criteria
0	Normal radiograph, bone scan, and magnetic resonance imaging (MRI)
I	Normal radiograph, abnormal bone scan and/or MRI
	A: Mild (< 15% of femoral head affected)
	B: Moderate (15%–30% of femoral head affected)
	C: Severe (> 30% of femoral head affected)
II	Cystic and sclerotic changes in femoral head
	A: Mild (< 15% of femoral head affected)
	B: Moderate (15%–30% of femoral head affected)
	C: Severe (> 30% of femoral head affected)
III	Subchondral collapse without flattening (crescent sign)
	A: Mild (< 15% of articular surface)
	B: Moderate (15%–30% of articular surface)
	C: Severe (> 30% of articular surface)
IV	Flattening of the femoral head
	A: Mild (< 15% of surface and < 2 mm of depression)
	B: Moderate (15%–30% of surface and 2–4 mm of depression)
	C: Severe (> 30% of surface and > 4 mm of depression)
V	Joint narrowing or acetabular changes
	A: Mild
	B: Moderate
	C: Severe
VI	Advanced degenerative changes

TABLE 85.3

Association Research Circulation Osseous (ARCO) Classification System

Data from Mont MA, Marulanda GA, Jones LC, et al. Systematic analysis of classification systems for osteonecrosis of the femoral head. J Bone Joint Surg Am 2006;88(Suppl 3):16–26.

Stage	Findings	Techniques	Subclassification	Quantitation
0	None	Radiography, CT, scintigraphy, MRI	No	No
I	Radiography and CT normal. At least one other technique is positive.	Scintigraphy, MRI	Location of lesion	Area of involvement (percentage)
			Medial	A: Minimal (< 15%)
			Central	B: Moderate (15%–30%)
			Lateral	C: Extensive
				Length of crescent
				A: < 15%
				B: 15% to 30%
				C: > 30%
				Surface collapse and dome depression
				A: < 15% and < 2 mm
				B: 15% to 30% and 2 mm to 4 mm
				C: > 30% and > 4 mm
II	Sclerosis, osteolysis, focal porosis	Radiography, CT, scintigraphy, MRI	Same as stage I	Same as stage I
III	Crescent sign and/or flattening of articular surface	Radiography and CT	Same as stage I	Same as stage I
IV	Osteoarthritis, acetabular changes, joint destruction	Radiography only	No	No

CT, Computed tomography; MRI, magnetic resonance imaging.

Close monitoring and screening for osteonecrosis of the contralateral hip should be undertaken. Hernigou and associates studied the natural history of 121 asymptomatic contralateral hips in patients with sickle cell disease. The mean follow-up was 14 years. At the time of initial evaluation, 56 asymptomatic hips were classified as Steinberg stage 0, 42 hips as stage I, and 23 hips as stage II. At the time of final follow-up, pain had developed in 110 previously asymptomatic hips (91%), and head collapse had occurred in 93 hips (77%). Symptoms always preceded collapse. Of the 56 hips that were classified as Steinberg stage 0, 47 hips (84%) had developed symptoms, and 34 (61%) had experienced head collapse at final follow-up. Of the 42 asymptomatic stage I hips, 40 (95%) became symptomatic within 3 years, and 36 (86%) had head collapse. Of the 23 asymptomatic stage II hips, all became symptomatic (100%) within 2 years, and all (100%) had head collapse. The average interval between onset of pain and head collapse was 11 months. At the time of final follow-up, 91 hips (75%) had required surgical treatment. These findings validated the same authors’ previously published studies demonstrating that sickle cell disease patients with symptomatic femoral head osteonecrosis may deteriorate rapidly.

Preoperative Planning

Preoperative evaluation should be performed in close coordination with consultants from the hematology, internal medicine, and anesthesia disciplines. Moreover, presurgery consultation and discussion with the pain management team for postoperative pain control should be undertaken. In selected patients, specialists from the pulmonary, cardiology, and nephrology services may be needed as sickle cell patients are at increased risk of pulmonary hypertension, left-sided diastolic cardiac dysfunction, and renal dysfunction.

A comprehensive history should include the level of pain, functional limitation, duration of symptoms, history of nonsurgical management, prior infection, prior surgery, contralateral hip symptoms, history of pain crises and acute chest syndrome, and medical comorbidities. The physical examination should note the range of motion of both hips, any presence of contractures, prior incisions, limb length discrepancy, signs of vascular insufficiency, and the presence of skin ulcerations. Preoperative planning must include careful evaluation of the radiographs to identify any acetabular deformity, any femoral deformity, femoral bone remodeling and sclerosis, evidence of prior hip surgery, and retained hardware.

Recently, an expert panel recommended preoperative transfusion of sickle cell patients undergoing general anesthesia to achieve and maintain a minimum hemoglobin level of 10 g/dL. There are two broad approaches in transfusion medicine in this patient population: the aggressive and conservative preoperative transfusion protocols. The aggressive protocol uses a combination of both red blood cell exchange transfusion and routine packed red blood cell transfusions to achieve a hemoglobin level of 9 to 11 g/dL with the HbS concentration of less than 30%. The aim of this protocol is to substantially reduce the concentration of the HbS protein. This would reduce the risk of polymerization in hypoxic and acidotic conditions, which can cause vaso-occlusion and subsequent ischemic organ damage. The conservative protocol uses routine packed red blood cell transfusions to correct the anemia to the optimal hemoglobin value without any specific strategy to minimize the HbS concentration. There are evidence-based data supporting the use of the aggressive preoperative transfusion protocol.

In a randomized multicenter study, Vichinsky et al. reported that the conservative transfusion protocol was as effective as the aggressive protocol in reducing postoperative complications. Marulanda et al. reported that the conservative and aggressive protocols were both safe for patients undergoing orthopedic surgery. The strength of the data, however, was limited by small numbers and selection bias. Ould Amar et al. reported that the conservative protocol had fewer postoperative complications in a series of THAs compared with using the aggressive protocol. Similar to the previous study, however, the strength of the data was limited by patient selection bias. In another series of THAs, Hernigou et al. used a hybrid strategy with exchange transfusion to reduce the HbS concentration to below 30% in those patients with a history of acute chest syndrome, previous cerebrovascular accident, or severe anemia with hemoglobin less than 5 g/dL. This high-risk patient population accounted for only 10% of the patients in the series. Otherwise, routine packed red blood cell transfusions were used to maintain the hemoglobin level at between 8 and 10 g/dL during and after surgery. In another multicenter, randomized control trial, the conservative strategy was found to be more effective at reducing perioperative complications than using no transfusions. There was no comparison to the aggressive transfusion protocol in this study.

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