multilevel cervical spondylotic myelopathy ( mcsm ) is a serious disease which can lead to spinal cord dysfunction and a substantial decrease in quality of life . in addition , mcsm requiring multilevel cervical spine surgery can be accompanied by extensive blood loss . as spinal surgery has become increasingly complex , so control of perioperative bleeding has become an important clinical issue for spine surgeons .
excessive blood loss can lead to a range of comorbidities such as anemia , hypotension , hematoma formation , and inadequate oxygenation of organs , thereby affecting patient outcome .
excessive blood loss often requires allogeneic blood transfusion , the risks of which are numerous and among which immunological reactions and transmission of viruses are considered the most serious . in addition , hematoma formation within a few millimeters of the spinal canal can cause considerable neurological damage .
although occurrences of postoperative spinal hematoma formation requiring emergency surgery are rare , it is nevertheless important to control perioperative bleeding to decrease its incidence . tranexamic acid ( txa ) is a synthetic derivative of the amino acid lysine which operates through competitive inhibition of the activation of plasminogen to plasmin by binding specific sites on both plasminogen and plasmin , thereby retarding fibrinolysis , the degradation of blood clots .
it has been widely used in various medical fields such as cardiac surgery , gynecology , dentistry , urological surgery , and liver transplantation to reduce the perioperative blood loss , as it is relatively inexpensive and has not been cited in the literature as causing any significant untoward side effects . in addition , txa has been reported to reduce blood loss and transfusion requirements during orthopedic surgery , most commonly in knee and hip joint replacement . although the benefits of txa in spinal surgery have been reported
indeed , there are no studies of txa in cervical laminectomy with lateral mass screw fixation and bone grafting ( clf ) so far .
clf has been widely used for many years for treating mcsm caused by multilevel cervical spinal cord compression .
although some authors suggest that laminoplasty is superior to laminectomy with lateral mass screw fixation and bone grafting regarding preserved range of motion , indications for the use of clf are broader than that of laminoplasty and recent studies showed good outcomes for clf . thus , the aim of this study is to evaluate the efficacy and safety of txa in controlling blood loss during clf for the treatment of mcsm .
a retrospective comparative analysis was performed in patients with mcsm undergoing clf of vertebrae c3 to c6 .
patients with cirrhosis of the liver , serious cardiac disease , chronic renal failure , cancer , allergy to txa , a history of thromboembolic disease ( deep vein thrombosis , ischemic heart disease , pulmonary embolism , transient ischemic attack , strokes , or subarachnoid hemorrhage ) , bleeding disorders , hypercoagulation status , disseminated intravascular coagulation , pregnancy , combined anterior and posterior spinal fusions , patients receiving antiplatelet and/or anticoagulant therapy at the time of the study , and treatments of vertebrae outside of c3 to c6 were excluded from the study . between november 2014 and april 2016 , 119 clfs fitting the inclusion criteria were performed in our center . each surgeon ( hao , liu , he , wu , wang , zheng , and zhao ) in this study had more than 20 years of experience in spinal surgery .
the control group consisted of 46 patients who underwent clf for the treatment of mcsm in our institution without being given txa . in both groups
, we analyzed patient demographic trait ( age at surgery , gender , body weight , height , and body mass index ) and duration of surgery which was defined as the time from the initial incision to the completion of wound closure .
the quantity of intraoperative and postoperative blood loss and the preoperative and day 1 postoperative hematological data for each patient were obtained in the 2 groups .
total blood loss was calculated as the sum of intraoperative and postoperative blood loss ( the quantity during the 1st 16  hours ) .
the spinous processes , lamina , and lateral mass facet complexes were exposed using a standard posterior midline opening after longitudinally dividing the nuchal fascia in line with a midline skin incision .
laminectomy was performed using a high speed matchstick burr to drill troughs in the bone at the lateral edge of the lamina on each side , prior to complete removal of the entire lamina and associated ligamentum flavum of the target vertebrae ( c3c6 ) .
the excised lamina and spinous processes were cleaned of soft tissue and cut into pieces for use as autograft material .
lateral mass screws were placed bilaterally on vertebrae c3 to c6 then fixed with rods using the margerl technique .
all patients in the txa group were given a dose of 15  mg / kg of txa ( transamin ; daiichi pharmaceutical , tokyo , japan ) before a skin incision was made , followed immediately with a maintenance dose of 100  mg / hour , and continued until wound closure .
no patient in the control group received intraoperative administration of txa or any other antifibrinolytic drug .
continuous variable data were presented as mean and standard deviation while categorical variable data were presented as a number and its specific value .
statistical differences between the 2 experimental groups were compared using a chi - square test or fisher exact test for categorical variables and student t test for continuous variables .
all analyses were performed using ibm spss statistics for windows , version 19.0 ( ibm corp . , united states of america ) .
the spinous processes , lamina , and lateral mass facet complexes were exposed using a standard posterior midline opening after longitudinally dividing the nuchal fascia in line with a midline skin incision .
laminectomy was performed using a high speed matchstick burr to drill troughs in the bone at the lateral edge of the lamina on each side , prior to complete removal of the entire lamina and associated ligamentum flavum of the target vertebrae ( c3c6 ) .
the excised lamina and spinous processes were cleaned of soft tissue and cut into pieces for use as autograft material .
lateral mass screws were placed bilaterally on vertebrae c3 to c6 then fixed with rods using the margerl technique .
all patients in the txa group were given a dose of 15  mg / kg of txa ( transamin ; daiichi pharmaceutical , tokyo , japan ) before a skin incision was made , followed immediately with a maintenance dose of 100  mg / hour , and continued until wound closure .
no patient in the control group received intraoperative administration of txa or any other antifibrinolytic drug .
continuous variable data were presented as mean and standard deviation while categorical variable data were presented as a number and its specific value .
statistical differences between the 2 experimental groups were compared using a chi - square test or fisher exact test for categorical variables and student t test for continuous variables .
all analyses were performed using ibm spss statistics for windows , version 19.0 ( ibm corp . , united states of america ) .
there was no statistical difference in demographic values ( patients age , gender , body weight , height , and body mass index ) between the 2 groups ( table 1 ) .
no statistically significant difference in duration of surgery was observed between the 2 groups , with a mean time of 155.72    15.59 and 153.52    11.91  minutes in the control and txa groups , respectively ( p  =  0.387 ) .
there was significantly less intraoperative blood loss in the txa group compared to the control ( fig .
1 ) , at 179.66    81.45 and 269.13    94.68  ml , respectively ( p  <  0.001 ) .
the txa group had significantly less postoperative blood loss during the 1st 16  hours compared to the control group ( 108.08    44.31 vs 132.83    49.39  ml , p  =  0.005 ) .
total blood loss in the control group ( 401.96    127.88  ml ) was significantly higher than that in the txa group ( 287.74    115.40  ml , p  <  0.001 ) .
changes in blood hemoglobin ( hgb ) content and hematocrit ( hct ) were not statistically significantly different between the 2 groups : preoperative hgb :
138.28    9.12  g / l ( control ) and 140.42    10.05  g / l ( txa ) ; postoperative hgb : 122.35    10.74  g / l ( control ) and 125.21    11.29  g / l ( txa ) ; preoperative hct : 41.78    2.62% ( control ) and 42.07    2.08% ( txa ) ; and postoperative hct : 36.50    3.22% ( control ) and 37.32    2.41% ( txa ) .
although the hgb and hct values in the txa group were all higher than those of the control group , the differences were not statistically significant ( fig .
no patient required an allogeneic blood transfusion during or after the surgery in either group and no serious intra- or postoperative complications , for example , dural tear , infection , epidural hematoma formation , deep - vein thrombosis , pulmonary embolism , allergic reaction , renal failure , or cardiopulmonary complications were observed in either group .
furthermore , no minor side effects associated with the use of txa such as nausea , vomiting , headache , or diarrhea occurred in either of the groups . demographic parameters of patients in each group .
the txa ( tranexamic acid ) group had significantly less intraoperative , postoperative , and total blood loss compared to the control group . there were no significantly different in blood hgb hct between the control and txa groups .
hgb  =  hemoglobin , hct  =  content and hematocrit , txa  =  tranexamic acid .
numerous studies have supported the use of txa in orthopedic surgery . although it has been evaluated in many studies , the safety and efficacy of txa for blood loss reduction in spinal surgery has not been clearly demonstrated , especially for clf .
clf for the treatment of mcsm has proved to be a successful technique for restoring normal cervical lordotic alignment , recovering neurological function , and decreasing the morbidity of c5 palsy and axial pain .
the principal disadvantage of this approach is a significant decrease in motion due to the fixation of the target vertebrae .
laminoplasty allows a better range of neck motion although it becomes more restricted in flexion and extension over time . for patients with mcsm combined with simple instability or correctable kyphosis , clf is a more suitable method than laminoplasty , even if the consequence is neck stiffness .
fibrinolysis increases transiently when patients undergo surgery , and it has been shown that it contributes to perioperative blood loss during spinal surgery .
txa inhibits fibrinolysis by blocking the lysine - binding sites of plasminogen , plasmin , and tissue plasminogen activator .
since fibrinolysis is activated immediately during and after surgery , txa should be administered before surgery begins .
the half - life of txa is approximately 80 minutes in patients with normal renal function .
pharmacokinetic evidence suggests a loading dose of 10 to 15  mg / kg followed by a maintenance dose of 1  mg / kg / hour or repeated dosing .
li et al conducted a meta - analysis of 6 randomized controlled trials and believed that higher txa dosage ( 15 
yang et al conducted a meta - analysis of 9 randomized controlled trials which had a similar sample to li 's study .
the 2 meta - analyses arrived at a similar conclusion although the quantity of blood loss and incidence of blood transfusion were different .
elwatidy et al used a high single dose ( 30  mg / kg ) of txa and found that it reduced total blood loss and incidence of blood transfusion .
raksakietisak et al reported that 2 doses of txa ( 15  mg / kg ) reduced perioperative blood loss and incidence of blood transfusion among low - risk adult patients undergoing elective complex thoracolumbar spine surgery .
, we evaluated the effects of txa with a dose of 15  mg / kg followed by a maintenance dose of 100  mg / hour .
the txa treatment group lost significantly less blood than that of the control group , including during the intra- and postoperative periods .
total blood loss in the txa group was 28% less than that of the control group . although the hgb levels and hct in the txa group were higher than that of the control group , the differences were not significant , possibly because the sample size was too small and the perioperative blood loss in clf relatively minor .
a theoretical anxiety associated with the use of txa is its potential for inducing thromboembolic complications .
however , many studies have shown that the administration of txa does not increase this risk . in our study , there were no clinical symptoms or signs of thromboembolic events , such as deep - vein thrombosis or symptomatic pulmonary embolism .
thus , the use of txa in patients undergoing clf should be regarded as safe .
additionally , we are unsure whether the complexity of the surgery has an effect on the benefit of txa .
a prospective randomized controlled study would better determine the safety and efficacy of txa during laminectomy with lateral mass screw fixation and bone grafting .
in this study , blood loss ( both intra- and postoperative ) in the txa group was significantly lower than that in the control group , and no major intraoperative complications occurred .
our results indicate that the use of intravenous txa is both safe and effective in reducing blood loss in clf .
prophylactic txa may provide the benefit of limiting excessive blood loss in posterior approach cervical spinal surgery .
a future prospective randomized controlled trial will provide superior evidence of the efficacy and safety of txa .
 abstractto assess the safety and efficacy of tranexamic acid ( txa ) for decreasing perioperative blood loss in cervical laminectomy with lateral mass screw fixation and bone grafting ( clf ) , in which all surgical procedures are identical.from november 2014 to april 2016 , we performed a retrospective comparative analysis of 119 patients with multilevel cervical spondylotic myelopathy who had undergone a clf from c3 to c6 in our center . 
 all surgeries were performed on the patients using a consistent , standard procedure . 
 patients were divided into control ( 46 ) and txa ( 73 ) groups according to whether or not they had received txa treatment before and during surgery . 
 demographic profiles of patients such as gender , age , body weight , height , and body mass index were collated and differences between the 2 groups compared . 
 preoperative and postoperative hematological data in addition to intraoperative and postoperative blood loss were compared between the 2 groups . 
 additionally , any complications of txa were also evaluated to assess safety.there was no statistically significant difference in demographic traits between the 2 groups . 
 intraoperative blood loss in the txa group ( 179.66    81.45  ml ) was significantly lower than that of the control group ( 269.13    94.68  ml , p  <  0.001 ) , as was postoperative blood loss ( 108.08    44.31 and 132.83    49.39  ml , respectively ; p  =  0.005 ) . 
 total blood loss in the txa group ( 287.74    115.40  ml ) was also significantly lower than that of the control group ( 401.96    127.88 , p  <  0.01 ) . 
 no major intraoperative complications occurred in any of the cases.txa significantly reduced perioperative blood loss in clf with no major side effects . 
Introduction
Material and methods
Surgical procedure
Drug dose
Statistical analysis
Results
Discussion
Conclusions