Abstract
Sickle cell disease is a genetic hemoglobinopathy that has the potential to affect any organ of the body. Patients with sickle disease have high morbidity and mortality creating safety concerns among patients and physicians about surgery in this subset of population. Factors that predispose SCD patient to complications are divided into patient-related and surgery-related factors. Patient factors associated with increased complication rate include the type and severity of SCD.
Orthognathic surgery involves osteotomies, major movement of upper or lower jaw that, although safe, have the potential of list of complications in healthy individuals. Therefore, complications are expected to be higher in SCD population. This complicates the decision of surgery and mandates careful perioperative management.
Highlights
Key points
- •
Sickle cell disease is a genetic hemoglobinopathy that has the potential to affect any organ of the body. Patients with sickle disease have high morbidity and mortality creating safety concerns among patients and physicians about surgery in this subset of population.
- •
SCD is characterized by anemia and four types of crises, namely: hemolysis, sequestration, aplastic and vaso-occlusive crises. The latter is a painful condition that could not be attributed to any diagnosis. VOCs resemble and predispose infarcted tissues to infections (e.g. osteomyelitis).
- •
Factors that predispose SCD patient to complications are divided into patient-related and surgery-related factors. Patient factors associated with increased complication rate include the type and severity of SCD.
- •
As Part of head and neck surgeries, orthognathic surgeries may be considered moderate-risk procedures. Orthognathic surgery is an invasive procedure that involves osteotomies, major movement of upper or lower jaws and the possibility of blood loss have the potential of list of complications in healthy individuals.
- •
The selection of surgical procedures in SCD population may be based on individual variations in disease baseline, oral hygiene and the demand of the surgical procedure. Careful perioperative management with experienced medical team and nursing staff is necessary.
Sickle cell disease (SCD) is a multisystem disease of genetic origin characterized by the presence of abnormal hemoglobin S (HbS) which polymerizes under deoxygenated conditions rendering the flexible biconcave red blood cells (RBCs) to halfmoon or sickled shape and rigid nature. Hemolysis and vaso-occlusion crises are the hallmarks of SCD and lead to a variety of clinical manifestations where nearly all body systems are affected [ ]. SCD was first reported by the American cardiologist James Herrick in 1910 in a 20-year-old 1st year dental student who suffered from frequent bronchitis and pneumonia. Further investigation revealed anemia with peculiar elongated RBCs under microscopic examination [ ]. The condition was named as “Herrick’s anemia” till 1922 where the name “Sickle cell anemia” was suggested by the internist Verne Manson.
Pauling was the first to reveal that the cause of the disease is actually in the hemoglobin molecule and therefore, SCD is a molecular disease [ ]. Hemoglobin is a tetrameric structure composed of four polypeptide chains; 2α and 2 non-α (β, γ, δ, ε, ζ) and four heme groups of porphyrin and iron atom. Normal adult hemoglobin (HgA) is composed of HgA (2α, 2β), HgA2 (2α, 2γ) and HgF (2α, 2δ) with concentrations of 95–97 %, 2.5–3.5 % and <1 % of total hemoglobin, respectively. Sickled hemoglobin may be present in both molecules, homozygous genotype (HgSS) while, heterozygous forms, would have HbS combined with another variant of hemoglobin such as the normal HgA (as in sickle cell trait; SCT), hemoglobin C, or β-thalassemia. Sickle cell anemia (SCA) refers to either homogenous sickled hemoglobin (HgSS) or those with absent β chain thalassemia (HgSβ 0 ) while SCD comprises all forms of hemoglobinopathy associated with sickled hemoglobin. Molecular properties of HgS are altered by the positively charged hydrophobic valine in replacing the negatively charged hydrophilic glutamic acid by mainly causing configurational and solubility changes [ , ].
SCD is characterized by anemia and four types of crises: hemolytic, squestrative, aplastic crises and vaso-occlusive crisis (VOC) [ , ]. Chronic hemolysis occurs secondary to membrane damage by repeated sickling and unsickling. In addition, exposure of RBCs cell membrane elicits immune response with autoantibodies formation that facilitate their phagocytosis [ ]. Characteristic total hemoglobin level in SCD is between 6 and 8 g/dL for SCA, 10–15 g/dL for HbSC while 9–12 for those with HbSβ+-thalassemia [ ]. This results in reduced oxygen carrying capacity and increased blood viscosity which is compensated for by high cardiac output state. Consequent cardiac abnormalities include left ventricular hypertrophy and heart failure [ ]. In addition, low oxygen affinity to HgS helps in the process of compensatory mechanism [ ]. Acute hemolysis may lead to acute anemia defined as decline in hemoglobin below baseline level by 2 g/dL or more. Acute hemolysis may be caused by severe infection or transfusion reaction. RBCs breakdown products may also cause hyperbilirubinemia, liver dysfunction and gallstone formation. At early age, SCD patients are at risk of acute splenic crisis. Spleen trapping sickled RBCs causes splenomegaly with rapid decline in hemoglobin level (about 3 units) from the baseline or below 6 g/dL. Splenic infarctions may lead to splenic atrophy and fibrosis, known as auto-splenectomy or functional asplenia [ ]. Aplastic crisis causes massive suppression of erythropoiesis with decline in hemoglobin by 1 g/dL per day and decreased reticulocyte count. Infectious causes like Para-virus B 19, Epstein Barr virus, salmonella or pneumonia [ ].
VOC is defined as intermittent episodes of severe pain not attributed to pathology other than SCD [ ]. Ischemic injuries may involve any tissue and those with minimal collateral circulation, as in subchondral bone and areas of sluggish blood flow as in bone marrow and spleen, are at greater risk [ ]. Early in life as the concentration of HgF declines, SCD starts to manifest as VOCs. Commonly affected bones include the extremities, joints, lumbar spine, ribs and mandible [ , ]. Identifiable triggers include cold, hypoxia, infection, dehydration, acidosis and stressful events although subclinical triggers of ischemia-reperfusion injuries were suggested [ , ]. Risk factors for VOC include, HgSS or HgSβ 0 genotypes, low HgF level, high total hemoglobin level. VOC peaks at the age range between 20 and 40 years with average of 0.8/year [ ]. The presence of bone infarction, along with impaired immunity due to hyposplenism, creates favorable environment for osteomyelitis [ ]. About 90 % of HgSS genotype would be affected by osteomyelitis before the age of 10 years. Various species have been identified with Salmonella and Staphylococcus aureus as the most common responsible microorganisms. Salmonella appears to utilize hematogenous routes through mesenteric vessels from infarcted bowel while S. aureus infect bones by direct extension through periodontal ligament space or after oral surgical procedures [ ]. Features of osteomyelitis may be confused with those of VOC as both may present with fever, leukocytosis, tender affected site and mixed signs of osteolysis and osteosclerosis in plain radiographs [ ]. Although the gold standard diagnostic method of osteomyelitis involves bone biopsy and culture, the presence of positive blood culture, subperiosteal fluid collection on ultrasound, radionucleotide studies or MRI may suggest osteomyelitis rather than aseptic bone necrosis [ , ].
1
Case report
A 22-year-old female, known to have SCD visited Qatif Central Hospital, (Eastern Province of Saudi Arabia) with an esthetic and functional complaint of prognathic mandible and discomfortable nasal breathing. She was diagnosed with sickle cell anemia disease (HbSS, 74.6 %) at early age through local sickle cell screening program. Positive history of several family members with sickle cell anemia was reported. The patient was followed by her hematologist and was admitted to the hospital several times (the number was not specific) which required hydration and mild pain management with paracetamol and infrequently, tramadol (75 mg, IM). She was on calcium, cholecalciferol (vitamin D3), Omega 3 and hydroxyurea (1 g/day). Her dental history was positive for an orthodontic growth modification attempt at the age of 9 years which was unsuccessful (see Fig. 1 ).
Clinically she showed a concave facial form, class III skeletally, depressed nasolabial area, flat cheeks, and dropped nasal tip. Nasal examination with a speculum showed deviated nasal septum. Her dentition was well aligned with no crowding no spacing. Occlusion was Angle class III at both canines and molars. Teeth show was 0 mm during rest and 4 mm while smiling, maxillary midline was shifted 2 mm to the right while the mandible and nasal tip coincided with facial midline. No canting of maxilla, mandible or chin. The deformity was about 6 mm reverse overjet and 2 mm vertical deficiency. Lateral cephalometric analysis showed retruded maxilla (SNA 77°), while the mandible was in normal AP position (SNB 78°). The patient was planned for surgery-first, single jaw orthognathic surgery to advance the maxilla. The rationale was to correct the nasal septum while preserving the chin position and prevent narrowing of the airway. Maxillary advancement would harmonize the facial skeleton, increase the teeth show, elevate the nasal tip, and provide fullness in the midface projection. Table 1 provides summarizes the history of the case.
| Demographic data | |
| Age | 22 years |
| Sex | Female |
| Race | Arabian |
| Body Mass Index | 18 kg/m 2 |
| Medical history | |
| Diagnosis | Sickle cell disease (HBSβ 0 ) |
| Family history | Close relatives positive sickle cell disease |
| Psychological | Normal development |
| Medical treatment | Hydroxyurea 1g/day (2 years) Calcium, Vitamin D Omega −3 |
| Crisis History | |
| Number | Undetermined |
| Frequency | 1-2/year |
| Precipitating factors | Undetermined |
| Severity | Moderate to severe |
| Blood Transfusion | None |
| Current clinical condition | |
| Last Crisis | Within six months |
| Last transfusion | None |
| Diagnostic tests | Hemoglobin electrophoresis HgbS % (74.4 %) |
| Laboratory assessment | Hgb (12.2 g/dL) Liver function (WNL) 25OH VIT.D (52.7 nmol/L) |
| Dentofacial examination | |
| Chief complain | Protruded mandible |
| Facial examination | Concave profile Reverse overjet Hypoplastic maxilla Normal TMJ function |
| Dental examination | Restorations: No 3 and 19 Impacted: no 17 Missing (extracted): no 1, 5, 13, 16, Vitality pulp testing (all vital) Periodontal: good oral hygiene |
| Obstructive Sleep Apnea | No signs or symptoms |
| Cephalometric analysis | SNA, 75° (normal 82 ± 2°) SNB, 78° (normal 80° ± 2°) |
Classic Le fort I osteotomy to advance the maxilla 6 mm into the planned position. Descending palatine arteries were preserved to provide maximum blood perfusion. Nasal septal deviation was corrected using the provided access after the down-fracture of the maxilla. Stabilization was achieved with appropriate plates and screws. Signs of adequate perfusion was ensured before the surgical field was closed. The duration of surgery was about 2 hours and the blood loss of about 150 mL. Postoperatively, the patient was on continuous oxygen saturation (SpO2) monitoring, with instruction to maintain oxygen level above the 95 %. Blood transfusion was not needed (postoperative hemoglobin 10mg/dL). Strict adherence to hematologist recommendations with regard to avoiding triggers of sickling was followed. Medications used were amoxicillin-clavulanic acid and paracetamol. The patient was encouraged to ambulate, use incentive spirometer every 4 hours and start orally as educated preoperatively. No SCD-related or surgical complications were encountered during her postoperative period. She was discharged in the third day after surgery and followed weekly for one month, then every 6 months for one year. Orthodontic phase was started 2 months postoperatively to finalize occlusion as planned with her orthodontist. Table 2 provides summary of summary of preoperative, intraoperative and postoperative management of the reported case.
