Total hip arthroplasty: Concerns and precautions in sickle-cell trait

1. Introduction

The sickle cell disease (SCD) is one of the most common inherited severe monogenic disorders in the world. A single amino acid substitution in the β1-globin gene, is responsible for the production of an abnormal haemoglobin, the sickle haemoglobin (HbS). When both genes are abnormal (in homozygous or heterozygous in association with other beta globin mutation) SCD occurs.

In deoxygenated erythrocyte HbS polymerizes distorting the cell architecture and flexibility (sickling).

The sickling process is influenced by the HbS concentrations and haplotype, the β-thalassemia gene deletion, the oxygen content of the inspired air, the cardiac and pulmonary status.¹ Other factors involved may be dehydration, infection, acidosis and hypothermia.² Vaso-occlusion and haemolytic anemia are the major features of the SCD. The most common clinical manifestation is bone involvement: as painful vaso-occlusive crises, and as a source of chronic disability as avascular necrosis³ (Fig. 1).

Fig. 1.

Due to the specific blood supply and lack of collateral circulation the femoral head is particularly susceptible to avascular necrosis in SCD.

The sickle cell trait (SCT), in which an abnormal mutated Sβ1-globine and a normal βA-globin gene are inherited, has been long considered a non-disease, partially protective against malaria.4, 5, 6 It is estimated that 300million people worldwide carry the sickle cell trait.² The carriers are generally asymptomatics and the condition is frequently a laboratory diagnosis. Individuals with SCT usually possess a normal complete blood cell count and normal red blood cells morphology in the peripheral blood smear.⁷ The diagnosis of SCT is made by demonstrating the presence of significant quantities of HbS, with a high-pressure liquid chromatography (HPLC).⁸

SCT carriers however are subject to sickling, leading to morbidities such as pulmonary embolism (PE), deep vein thrombosis (DVT), and rhabdomyolysis, when exposed to severe tissue hypoxia, acidosis, increased viscosity, dehydration, and hypothermia. Screening performed on athletes and soldiers also reported that under intense physical stresses HbS carrier condition can lead to sudden death.9, 10, 11, 12

Avascular necrosis of femoral head (AVNFH), a common manifestation of SCD, is seldom reported in association with SCT.13, 14, 15, 16, 17, 18, 19, 20 Though it is not fully established, a physically stressful event such total hip arthroplasty (THA) could act as a sickling-trigger and the surgeon should be aware of the possible complications arising from being HbS carrier.

2. Material and methods

We conducted a narrative review of the literature aimed to highlight current concerns and precautions in SCT carriers undergoing THA.

Moreover, we retrospectively reviewed 3 patients, SCT carriers, with AVNFH. The patients were sub-Saharan middle-aged males: two reported pain in both groin regions and severe hip mobility limitation, the third patient referred severe hip pain and functional limitation in the left side. In the first two cases radiological results confirmed diagnosis of bilateral AVNFH in the third case, left AVNFH. All patients had a history of episodes of malaria during youth, but nobody had alteration in routine blood test.

The first patient (from Chad, 35yo) showed a walking almost impossible; he reported deep pain from about 10 years in both groin regions and severe limitation in both hip range of motion (ROM). Radiographs and CT showed a bilateral AVNFH stage IV of Ficat classification.²¹ The complete joint destruction, collapse and resorption of the femoral head and catastrophic acetabular bone loss (Fig. 2) addressed the diagnosis towards the outcomes of tuberculous coxitis or septic arthritis, but preoperative serology (parasitological and Tine tests), intraoperative aspirates, specimens cultured for growth of aerobic and anaerobic bacilli, and histologic section examined were negative for evidence of infections. A scintigraphic examination showed signs compatible with bone infarction in both hips and in the left humeral head. Hematologic consultation and HPLC test revealed a carrier condition for HbS (HbS<40%).

Fig. 2.

Complete joint destruction due to bilateral stage IV osteonecrosis of femoral head in SCT; radiographic and CT showed collapse and resorption of femoral head associated to severe acetabular bone loss.

The second patient (from Chad, 43yo), came to our observation for pain in both groin region. Medical history was positive for malaria, amebiasis and recurrent painful crises of unknown cause. Abdominal ultrasound imaging, serology and parasitological test did not yield any abnormal outcomes and blood count was normal. Hematologic consultation and HPLC test revealed a carrier condition for HbS, with HbS <40% (HbS 39,1%, HbF absent, HbA2 3,4%). Radiographies and MRI showed bilateral AVNFH stage IV, with complete joint destruction.

The younger patient (Senegal, 25yo) reported deep and throbbing pain, exacerbated by activity and weight-bearing, localized on the left groin. His medical history was positive for malaria, rare episodes of hematuria and painful crises, and family history for sickle cell disease. Radiographies and MRI showed an AVNFH stage IV of the left side. Hematologic consultation and HPLC test revealed a carrier condition for HbS (HbS <40%).

All the patients received a multidisciplinary approach, involving the orthopaedic surgeon, the haematologist and the anesthesiologist.

A senior orthopedic surgeon performed the hip replacement with cementless components through a posterolateral approach. Patients were under general anesthesia. Second-generation cephalosporins (4g per day) were administrated during surgery and 6 days after. All patients received postoperative thromboembolic prophylaxis (LMW-heparin) for 30 days. For each surgery intraoperative aspirates and specimens were cultured for growth of aerobic and anaerobic bacilli, and histologic section were examined for evidence of bacterial infection: all cultures and histologic examinations were negative. To avoid the extension of surgical-times, resulting in possible increased risk of sickling, bilateral implants were not performed simultaneously, but as soon as the clinical condition permitted. In the first case specific surgical difficulties were due to periacetabular bone-loss and isolated areas of sclerotic bone. In 3 out of 5 prosthesis bone defects made an additional fixation of the acetabular cup with two or more screws necessary.

The patients received a scrupulous monitoring in the intra- and post-operative period: oxygenation, hydration, acid-base balance, and body temperature in addition to a careful assessment of complications.

3. Results

All patients reported post-operative improvement in terms of relief of pain, function and ROM (Harris Hip Score preoperatively mean 33,3 ± 13,8, and postoperatively 94 ± 1,7 for 5 hips in 3 patients). Intraoperative blood loss and intra-post-operative cell transfusions were similar to those of patients who undergo total hip replacement without any hemoglobinopathy. No complications from transfusions were observed. No thromboembolic complications and no immediate or late infections occurred. It wasn't observed any major surgical complication, but a prolonged surgical time in two hips with massive acetabular bone loss and high-demanding surgical reconstruction.

4. Discussion

Literature shows an increased complication rate correlated with SCD in orthopedic surgery.22, 23, 24, 25, 26 The most common complications are excessive blood loss (71%), infections (between 16% and 20%), hypothermia (11%), acute chest syndrome and vaso-occlusive crisis (17% both strictly related with sickle cell crisis).²⁴ Less frequent complications are auto-splenectomy, renal impairment, intra-cerebral bleeding, leg ulcers, retinopathy and musculoskeletal complications.24, 25, 26 Due to chronic anaemia, bone marrow proliferates causing a widening of the medullary canals and thinning of the cortices.²⁴ Weaker and sclerotic bone, in addition to frequent large osteophytes, protrusio acetabuli, and adhesions produce a detrimental environment for prosthesis fixation^24,27 contributing to a higher failure rate of the implants in these patients. Surgical risk score based on the complexity and invasiveness of orthopedic surgery was the only preoperative predictor of postoperative complications in SCD.²² A few recommendations have been made regarding THA in SCD patients to improve results and decrease the perioperative complications²⁴: multidisciplinary evaluation including haematologist; pre-operative transfusion; peri-operative antibiotics; adequate hydration and oxygenation intra- and post-operatively; extensive baseline testing including room-air oxygen saturation and chest X-Ray; caution in the use of methylmethacrylate cement.

Although it is a benign condition in most of the affected individuals, pathologic processes that cause hypoxia, acidosis, increased viscosity, dehydration, and hypothermia can transform silent SCT into a SCD-like syndrome with significant morbidity and mortality.¹⁶,¹⁸,28, 29, 30, 31, 32, 33 Despite the evidence of the non-absolute benignity of SCT condition, literature does not clearly report a higher incidence of specific complication in major orthopedic surgery. However, many complications in HbS carriers may be more frequent than currently reported due to common unawareness of HbS carrier status by the patient and the health care provider. Despite our concerns about possible perioperative complications related to the SCT, in our case series we did not observe any early or late complications.

5. Conclusion

SCT status is widespread in the world, but for its generally asymptomatic nature is often an underdiagnosed condition. No clear indications of specific precautions aimed at minimizing the risk of perioperative morbidity in SCT carriers are present in literature: however, this could be due to the common unawareness of HbS carrier status, that underestimates the possible surgical complications associated with sickle cell trait. Waiting for greater and more focused number of studies, we encourage an adequate knowledge of the condition and the anamnestic data that may lead to a suspicion and the adoption of measures to prevent events that predispose red blood cell sickling. A more complete clinical picture could lead to a greater awareness of risks and to a reduction of unrecognized associated complications. The analysis of a greater number of data through targeted screening programs and adequately-powered studies in the future may lead to an evidence based management.

Declaration of competing interest

All the authors have no conflict of interest to declare.