The authors have declared that no competing interests exist.
Conceived and designed the experiments: CL ML. Analyzed the data: YX. Wrote the paper: MY JF. Collected the data from the medical file: ZL XS. Performed the surgery: XZ CW. Collected the data: HY.
The vast majority of AIS patients who require surgical intervention are women. Blood loss is a major concern during the operation.
The medical records of all female AIS patients who underwent posterior correction and fusion operations using the all-pedicle screw system from January 2012 to January 2014 were reviewed. Patients with irregular menstruation; underwent osteotomy; use coagulants were excluded from the study. The remaining patients were divided into 4 groups according to the operation date in the menstrual cycle (A: premenstrual group, 24–30 d; B: follicle group, 6–11 d; C: ovulatory group, 12–17 d; D: luteal group, 18–23 d). The information of patients from the 4 groups was reviewed. The data was analyzed using analysis of variance, the Student-Newman-Keels test and Kruskal-Wallis Test.
A total of 161 patients were included in this study. There were 40 patients included in group A, 38 patients in group B, 41 patients in group C and 42 patients in group D. The 4 groups were matched in age (P = 0.238), body height (P = 0.291), body weight (P = 0.756), Risser sign (P = 0.576), mean curve Cobb angle (P = 0.520), and bending flexibility index (P = 0.547), the number of levels fused (P = 0.397). The activated partial thromboplastin time (P = 0.235) and prothrombin time (P = 0.074) tended to be higher in group A, but the difference was not statistically significant. The fibrinogen level was lower in group B than the other 3 groups (P = 0.039). Blood loss and normalized intraoperative blood loss (NBL) was significantly higher in group A than the other 3 groups (P<0.01).
The hemostatic function tended to be lower in the premenstrual phase. The fibrinogen level was lowest in the mid-follicle phase. Female AIS patients tended to endure more intraoperative blood loss when the operation was performed in the premenstrual phase during the menstrual cycle.
Adolescent idiopathic scoliosis (AIS) is a structural, lateral, rotated curvature of the spine that arises in otherwise healthy children at or around puberty. AIS may affect 1–3% of the at-risk population when defined as a Cobb angle>10°
Intraoperative blood loss (IOBL) is a major concern during the operation and may lead to many complications such as hypotension, anemia, coagulopathy, infection, and the need for transfusion of large volume of blood products with associated risks
Sex hormone variations may affect the level of blood coagulation factors, thus, influence the hemostatic function in female adolescents
In this retrospective analysis, we investigated the effect of operation time during different phases of menstrual cycle on IOBL in female adolescent idiopathic scoliosis patients who underwent posterior correction and all pedicle screw fixation. Previous studies have shown that increase in blood sex hormone could cause blood coagulation changes. We speculate that natural hormone variation during normal menstrual cycle may affect blood coagulation too. This variation is especially meaningful considering that the majority of AIS patients who need surgical intervention are female and the large IOBL during posterior correction and fusion surgery for AIS patients.
Female AIS Patients, who sought medical help and underwent posterior correction and all pedicle screw fixation and fusion surgery in Chinghai hospital between January 2012 and January 2014, were retrospectively reviewed. The diagnosis of AIS followed the description of Weinstein et al
Parameters, including: patient age; body weight; body height; the number of levels fused; major curve Cobb angle; major curve bending flexibility index; blood type; albumin (Alb); hemoglobin (Hg); fibrinogen; platelet count (PLT); activated partial thromboplastin time (APTT); prothrombin time (PT); thrombin time (TT); IOBL; operation date and menstrual cycle data were reviewed. Normalized intraoperative blood loss (intraoperative blood loss per level fused per kilogram, NBL) was calculated using the following equation:
The study protocol was approved by the Institutional Review Board of the Second Military Medical University, Shanghai, China. Written informed consent was obtained from every participant. The protocols of this study have been approved by the institutional review board of Changhai Hospital.
Data from different groups was analyzed using analysis of variance (ANOVA), the number of levels fused was analyzed by Kruskal-Wallis Test. Differences between the groups were further analyzed using the Student-Newman-Keuls (SNK) test. The data was checked for normality and equal variances. A P value less than 0.05 was considered significant for each individual test in this study. Statistical Package for Social Science software 18.0 (SPSS Inc., Chicago, IL, USA) was used to perform the statistical analysis. Graphs were drawn using GraphPad Prism 5.0 (GraphPad Software Inc., San Diego, CA, USA).
A total of 276 female AIS patients underwent posterior correction and spinal fusion were screened. Among them, 115 patients were excluded because of: Ponte Osteotomy during the surgery (38); combined anterior approach (17); diagnosed coagulopathies (9); menstrual cycle problems (44, irregular menstrual cycle, menstrual cycle longer than 30 days or shorter than 28 days, before menarche); or intraoperative hemostasis (43). The remaining 161 patients were reviewed. There were 40 patients included in group A, 38 patients in group B, 41 patients in group C, 42 patients in group D. ANOVA showed that the 4 groups were matched in age (P = 0.246), body height (P = 0.359), body weight (P = 0.348), Risser sign (P = 0.628), mean curve Cobb angle (P = 0.596), bending Cobb (P = 0.993), bending flexibility index (P = 0.849). Kruskal-Wallis Test showed there was no difference in the number of levels fused (P = 0.497). The APTT (P = 0.168) and PT (P = 0.107) tended to be higher in group A than the other groups; however, the difference was not statistically significant. There were no significant differences in Hg (P = 0.875), PLT (P = 0.517), Alb (P = 0.247), and TT (P = 0.949) between the groups. There were significant differences in fibrinogen (P = 0.039), IOBL (P<0.01), and NBL (P<0.01) between the groups. The details of the 4 groups analyzed by ANOVA are shown in
Variable | Group A | Group B | Group C | Group D | Mean | P |
Number | 40 | 38 | 41 | 42 | ||
Age (y) | 15.22±2.03 | 14.57±1.66 | 14.66±1.53 | 15.13±1.74 | 14.90 | |
Height (cm) | 158.55±4.71 | 159.42±4.18 | 157.71±3.67 | 158.80±4.64 | 158.60 | |
Weight (kg) | 47.04±6.37 | 48.95±5.66 | 46.88±5.86 | 48.27±5.88 | 47.76 | |
Risser sign | 3.60±1.19 | 3.45±1.03 | 3.38±1.19 | 3.29±1.23 | 3.43 | |
Major curve (°) | 51.60±11.99 | 49.34±10.27 | 48.48±8.14 | 49.54±11.67 | 49.73 | |
Bending cobb (°) | 13.28±7.46 | 13.39±6.74 | 13.10±6.55 | 13.00±5.59 | 13.19 | |
B-Flexibility index | 0.75±0.10 | 0.73±0.12 | 0.73±0.12 | 0.74±0.08 | 0.74 | |
Alb (g/L) | 41.45±2.09 | 41.50±2.05 | 40.83±2.19 | 40.78±1.97 | 41.13 | |
Hg (g/L) | 123.98±7.04 | 125.08±8.67 | 125.31±8.72 | 125.17±7.89 | 124.89 | |
PLT | 215.85±35.67 | 221.37±38.53 | 222.21±52.09 | 230.46±46.79 | 222.53 | |
APTT (s) | 38.34±1.90 | 37.14±2.39 | 37.55±2.97 | 37.54±2.19 | 37.65 | |
PT (s) | 13.58±0.41 | 13.39±0.37 | 13.37±0.47 | 13.36±0.51 | 13.42 | |
Fibrinogen (g/L) | 2.62±0.44 | 2.35±0.47 | 2.57±0.47 | 2.60±0.43 | 2.54 | |
Thrombin time (s) | 16.90±1.67 | 16.97±1.70 | 16.87±1.30 | 16.77±1.50 | 16.88 | |
The number of levels fused | 10.65±1.67 | 10.79±1.70 | 10.64±2.08 | 10.15±2.22 | 10.55 | |
IOBL (ml) | 1078.75±295.28 | 952.11±194.27 | 863.81±201.77 | 847.80±266.03 | 933.98 | |
NBL (ml/f*kg) | 2.17±0.46 | 1.83±0.34 | 1.77±0.34 | 1.76±0.40 | 1.87 |
The SNK test (fibrinogen, blood loss, NBL) showed that the IOBL and NBL were significantly higher in group A than in other groups; there was no observed difference between groups B, C, and D. Fibrinogen was significantly lower in group B than groups A, C, and D; there was no observed difference between groups A, C, and D.
There were no difference between groups in PLT count(A), PT(B), APTT(C), TT(D); The Fibrigen level in group B was significant lower than other 3 groups(E).
NBL between groups (A) show NBL was significantly higher in group A than the other 3 groups, There was no difference between other 3 groups. Scatter diagram of NBL (B) in group A show the NBL has a tendency to increase during the last days of the menstrual cycle and achieve a peak during 1–2 days before Menstruation.
Group | N | Subset for alpha = 0.05 | |
1 | 2 | ||
B | 38 | 2.354211 | |
C | 42 | 2.569048 | |
D | 41 | 2.602927 | |
A | 40 | 2.618750 | |
Sig. | 1.000 | .876 |
Team | N | Subset for alpha = 0.05 | |
1 | 2 | ||
D | 42 | 1.755241 | |
C | 41 | 1.769632 | |
B | 38 | 1.829504 | |
A | 40 | 2.167856 | |
Sig. | 0.666477 | 1.000 |
Team | N | Subset for alpha = 0.05 | |
1 | 2 | ||
D | 41 | 847.80 | |
C | 42 | 863.81 | |
B | 38 | 952.11 | |
A | 40 | 1078.75 | |
Sig. | 0.136 | 1.000 |
The means for groups in homogeneous subsets are displayed.
Uses harmonic mean sample size = 40.195.
The group sizes are unequal. The harmonic mean of the group sizes is used. Type I error levels are not guaranteed.
Posterior correction with multilevel spinal fusion (PCSF) has been proven to be the most effective way to treat AIS
A significant finding in our study was that patients in group A experienced significantly higher IOBL (total: 1078.25±295.28 mL; NBL: 2.04±0.35 mL/kg) than those in group B (total: 952.11±194.27 mL; NBL: 1.80±0.30 (mL/kg*l), group C (total: 864.81±201.77 mL; NBL: 1.73±0.27 mL/kg*l), and group D (total: 846.83±266.63 mL; NBL: 1.71±0.34 (mL/kg*l). Even in group A, the NBL of patients tended to increase as the operation date approached menstruation. This indicates that patients who undergo surgery before menstruation may experience more blood loss. The differences between the groups may be attributed to the hormone-induced hemostatic function change. Van Roojen et al
However, studies on variations in hemostatic factors during the normal menstrual cycle are rare and show contradictory results. Miller et al
Another finding of this study was that the fibrinogen level was lowest in the follicle phase (group B: follicle group,
We normalized the IOBL by dividing blood loss by number of levels fused and by patients' weight. The number of levels fused has been reported to be a predictor of IOBL in scoliosis surgery
One of the concerns of our study was its retrospective design. We relied on the IOBL noted on the medical records when collecting the data. However, the estimation of IOBL in scoliosis surgery was performed by 2 senior anesthesiologists in our hospital, while following strict criteria. In other words, all the AIS patients were evaluated by the same group of physicians using the same criteria, thus, individual error was minimized. Another concern of the study might be lack the data of patients from 1st–5th days of menstrual cycle. Actually, we rarely perform the posterior correction and fusion surgery during menstruation. There were two reasons that we did not perform the surgery during menstruation. Firstly, the posterior correction and fusion surgery was featured by its large IOBL, but during menstruation the patients were experiencing fundamental blood loss. Secondly, we think menstruation was a kind of injury to the endometrium of the female AIS patient. We want to do our best to avoid these shortcomings since the surgery we are going to perform is a selective operation.
Our study had several strengths. First, our data was collected from a single institution. All the treatments followed a uniform procedure, and all the evaluations were performed using the same criteria. We confined our review time to 2 years to avoid confounding factors such as changes in the surgeon's surgical skills, improvement of equipment, etc. This minimized the system error of this study. Second, we eliminated any factors that may have affected our study, such as age over 18 years (patients may have a rigid curve as their age increases thus increase the IOBL), combined anterior and posterior approach, use of antifibrinolytic medication before or during surgery, and use of osteotomy during surgery. Finally, rather than only dividing the patients into follicle and luteal groups as in previous clinical and basic studies related to this field
Female AIS patients tended to endure more IOBL when the operation was performed in the premenstrual phase of the menstrual cycle. The hemostatic function tended to be lower in the premenstrual phase; however, statistical significance was not reached. The fibrinogen level was lowest during the mid-follicle phase.