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Historically, patients with osteogenesis imperfecta (OI) have been reported to be at risk for significant surgical bleeding secondary to abnormalities in platelet function. By reviewing the operative blood loss in OI patients undergoing femoral osteotomies and rodding, we hoped to identify risk factors for excessive bleeding.
A retrospective review of 22 patients with 52 inserted femoral rods was conducted under Institutional Review Board approval. Information concerning patients and procedures was collected. Associations with mean blood loss were made for categorical variables using the unpaired t-test and for continuous variables using correlation. Multivariate linear regression was used to test the influence of potential risk factors for excessive bleeding.
The mean blood loss was 197 cc (standard deviation [SD] 129 cc, range 10–500 cc). The adjusted mean blood loss (ratio of actual blood loss divided by the total predicted blood volume [Custer and Rau in “The Harriet Lane Handbook,” 18th edn. Mosby-Elsevier, Philadelphia, p 382, 2009]) was 0.16 (SD 0.13, range 0.01–0.44). Six blood transfusions were required out of 42 cases for a transfusion rate of 14%. The mean blood loss in those patients who were transfused was 279 cc compared with 182 cc for those not transfused. There were no differences in the adjusted mean blood loss between acute fracture treatment versus elective reconstruction (P = 0.08), nor between primary rodding versus revision rodding (P = 0.66). Older patients tended to have lower adjusted mean blood loss, though this was not significant (P = 0.07). Increasing number of osteotomies tended to lead to increased adjusted mean blood loss (P = 0.05). There was no association between operative time and adjusted mean blood loss (P = 0.36). When adjusting for procedure characteristics, increasing age was associated with decreasing adjusted mean blood loss (P = 0.008).
Predicting blood loss for femoral rodding in patients with OI is difficult, with no differences between revision and primary procedures or elective versus trauma cases. The blood loss in our patients undergoing femoral rodding was manageable, and the transfusion rate was reasonably low. Although massive blood loss has been described in patients with OI in the literature, we found that femoral rodding did not pose excessive risk of transfusion in our OI population.
Osteogenesis imperfecta (OI) is well known for its clinical manifestations, including frequent fractures, deformities, and the need for frequent orthopedic procedures. OI is also associated with an increased metabolic state [2, 3], hyperthermia [2, 3], increased metabolic activity and oxygen consumption of leukocytes , and decreased platelet function, causing abnormal bleeding [5–7].
Excessive blood loss in OI has been described by Siegel et al.  in a case report of a 25-year-old man with OI and 30 mild to severe episodes of epistaxes during his life, with six episodes requiring life-saving blood transfusions. The subject of this case report was found to have a prolonged bleeding time, a positive Rumpel–Leede test, and abnormal prothrombin consumption .
Several studies have reported on abnormalities in bleeding measurements in OI patients [5, 8]. Hathaway et al. obtained the platelet count, bleeding time, petechiometer test, and platelet adhesiveness, in addition to inorganic pyrophosphate measurements, in 15 patients with OI, as well as their parents and siblings. Most patients and one or both of their parents demonstrated abnormalities in platelet function in vitro . Also, platelet abnormalities were often associated with an elevation of serum pyrophosphate [6, 7]. Part of the serum inorganic pyrophosphate originates from platelets during clotting, making this relationship notable, although causality to platelet dysfunction has not been definitively established .
When planning for the care of a pediatric patient with OI, addressing the possible problem of increased blood loss is an important part of management. Planning for peri-operative blood loss can include autologous donation or the availability of an adequate number of units of packed red blood cells and platelets. Aprotinin was used at our institution in the past in children with OI, but since the drug must be given through a central line, treatment requires planned use so that the line can be placed before draping the patient.
The goal of our study is to identify any clinical factors that increase the risk of blood loss during surgical procedures in an effort to determine recommendations for surgical planning for excessive blood loss.
Approval from the Institutional Review Board was obtained to conduct a retrospective chart review of patients with a known diagnosis of OI who had undergone lower extremity surgery at our institution.
Paper charts and electronic records were obtained for all hospitalizations related to orthopedic procedures for 23 patients. Anesthesia records, as well as physician orders during each hospitalization, daily progress notes, and initial history and physical examination, were reviewed for each patient.
Demographic information about each patient including age, sex, weight, and height was obtained from the charts. Information specific to the surgery performed was also collected, including the date of surgery, side of surgery or if the surgery was bilateral, indication for surgery, implant type and size, use of aprotinin during surgery, operative time, and estimated blood loss. Hematologic parameters were also obtained, including pre- and post-operative hemoglobin when available, discharge hemoglobin, and transfusion history. The length of hospital stay, complications, and length of follow-up were also recorded.
Our study is retrospective in nature; however, our institutional practice is to transfuse patients under the direction of the operating surgeons who, in turn, use the criteria of a hemoglobin level under 9 g/DL or instability in vital signs or low oxygen saturation as requirements for transfusion. Otherwise, children are given supplemental iron for post-operative anemia when possible to reduce the risk of disease transmission through transfusion.
A blood loss estimate was obtained from the surgeons’ notes and anesthesia records. Using the patients’ age and weight, the total predicted blood volume was calculated based on the guidelines from The Harriet Lane Handbook . Then, an adjusted blood loss was calculated as the ratio of actual blood loss divided by the total predicted blood volume for age. This adjusted blood volume allowed the standardization of blood loss for patient size.
Statistics were performed using Prism software, as well as SAS. Associations with mean blood loss were made for categorical variables using the unpaired t-test and for continuous variables using correlation. In addition, multivariate linear regression was used to test the influence of potential risk factors for excessive bleeding.
Our study group included a total of 22 patients who underwent 42 surgeries with the insertion of 52 femoral rods. One child who underwent bilateral procedures was excluded from the study, as he had sickle cell anemia in addition to OI, with the sickle cell management affecting his pre-operative fluid management.
Femoral surgical procedures were chosen in this study as tourniquets were not in use. All procedures were classified as either acute fixation for a femur fracture or elective realignment of the femur for a deformity. The study population consisted of nine females and 13 males. Seven patients had Sillence type 1 OI, seven were phenotypically described as having type 3 OI, and eight patients had type 4 OI. At the time of surgery, half of the patients had been actively treated with bisphosphonates. The youngest patient to undergo a surgical procedure in this cohort was a male patient who was aged 1 year and 7 months at the time of surgery. The oldest patient was 21 years and 2 months old at the time of surgery.
Indications for surgery included 27 procedures for fracture stabilization, 22 procedures for deformity correction, and three procedures were performed prophylactically for an imminent fracture. The most common implant was the Frassier–Duval rod, used in 25 procedures; the Bailey–Dubow rod was used in 17 procedures; Rush rods were used in four procedures; flexible titanium rods in two procedures; and the Howmedica humeral nail, Steinman pins, Foresight nail, and a TriGen nail in one procedure each. The average follow-up was 38 months per rodding procedure.
The length of stay in the hospital ranged from 1 to 5 hospital days. There were six post-operative complications. Three complications were related to infection; three others were due to implant migration or failure. One patient, who had the Bailey–Dubow rod separate, required return to the operating room 23 days post-operatively. One patient had rod migration into the knee joint, and at the time of revision of the rod, purulence was found intra-operatively, followed by continuous drainage post-operatively—and eventual removal of the rod 19 months after the first procedure. In two other patients, the rods migrated into the knee joint, requiring return to the operating room for revision, one at 7 weeks and the other at 9 weeks after the initial procedure. One patient had subacute osteomyelitis requiring removal of the rod 17 months after its insertion. The final complication was in a child who had superficial cellulitis initially treated with oral antibiotics at home but who required readmission 3 weeks post-operatively for intravenous antibiotics.
The surgery time ranged from 22 to 427 min. Two patients received aprotinin prior to surgery via a central line for prophylaxis against bleeding at the discretion of the anesthesiologist. Estimated blood loss ranged from less than 10 to 900 cc. One patient, who was scheduled for simultaneous bilateral femoral osteotomies and rodding, was converted to a staged procedure after a significant blood loss was encountered on the first side. The mean blood loss was 197 cc, with a standard deviation (SD) of 129 cc. The adjusted mean blood loss was 0.016 (SD 0.13, range 0.01–0.44). Six blood transfusions were required for a transfusion rate of 14%. The mean blood loss in those transfused was 279 cc, compared with 182 cc in the remainder of the cases where no transfusion was required. The adjusted blood loss in the patients that underwent a blood transfusion was 0.330, compared with an adjusted blood loss of 0.003 in those patients that did not have a blood transfusion.
No differences in blood loss were found comparing either primary versus revision procedures (Fig. 1) or reconstruction versus acute fracture management (Fig. 2). Older patients tended to have a lower adjusted mean blood loss, although this was not statistically significant (P = 0.07, Fig. 3). There was also no significant association between operative time and adjusted mean blood loss (P = 0.36). Increasing numbers of osteotomies lead to an increase in the adjusted mean blood loss (P = 0.05, Fig. 4). When adjusting for all of the procedural characteristics and variables analyzed together, increasing age was associated with a decrease in the adjusted mean blood loss (P = 0.03).
Patients with OI have been thought to be at risk for excessive blood loss during surgical procedures, but our study demonstrates a very manageable blood loss, with a 14% transfusion rate. Children with OI fracture easily, and some surgical procedures are able to take advantage of a fracture event, allowing the surgeon to avoid an open osteotomy. Whether the presence of a fracture could lead to an inflammatory state with subsequent hyperemia that would, in turn, increase blood loss is a theoretical concern; however, our data does not support any difference in blood loss when comparing urgent rodding for acute fracture treatment to rodding for deformity correction performed electively. The presence of scar tissues or previously operated bone sites also did not seem to alter the blood loss, with no appreciable difference found between primary and revision procedures in our OI patient population.
The number of osteotomies and patient age seem to be the best predictors of blood loss. Since raw bone surfaces can bleed and cannot be easily cauterized, the correlation between osteotomy and blood loss is a logical one. Patient age was inversely correlated to adjusted blood loss, which is not as intuitive, since a larger radius of diameter of the bone—and hence area from which the bone bleeds—might increase the amount of bleeding. However, a larger amount of bleeding could be better tolerated in the larger patient with a greater total blood volume.
One limitation to the study is the retrospective nature of the data collection. One operative report reflects aborting a bilateral procedure due to blood loss, and, in many cases, the surgeon can elect to reduce the number of bones addressed in any particular setting due to blood loss. But we feel that our study reports a reasonably small risk of transfusion for femoral osteotomy and rodding in OI patients—a change from the accepted teaching as defined by the historical literature.
Although blood loss requiring a blood transfusion can occur in children with OI, we feel our results show that blood loss is not much different from the blood loss of normal children undergoing similar procedures. Lynch et al.  studied 178 normal children with 181 femur fractures that presented to a level one children’s hospital. The authors evaluated the patients for blood loss, hemodynamic instability, and rates of transfusion. In their study, they divided the femur fractures based on treatment: group I had initial spica application, group II had initial skeletal traction followed by spica cast, and group III underwent early surgical open reduction and internal fixation or the application of an external fixator. There were 30 patients in group III. The authors noted three peri-operative transfusion events in group III for a transfusion rate of 10%. Although the operative group in this study is small, it does provide some estimate of transfusion rates in normal children undergoing femoral procedures. This transfusion rate is similar to the one found in our study; however, because our patient population also had osteotomies and bilateral procedures, a larger transfusion rate would be expected when comparing our patient population to trauma patients.
We do not want to suggest that children with OI cannot have a significant blood loss leading to transfusion, but the comparative transfusion rates among normal children and children with OI indicates that the preoperative work-up for a child with OI can be the same as a child without OI. Only age and number of osteotomies are helpful predictors in planning for operative blood loss.
Recent changes in medical management include the use of bisphosphonates in children with OI. Half of the patients in this study were receiving bisphosphonates at the time of surgery. Since this study did not find a significant problem with bleeding in a modern OI surgical population, the question remains as to whether bisphosphonates can have an effect on blood loss, particularly as there is some suggestion in the literature that pyrophosphates can have an effect on platelet function. However, more work will be needed in order to determine whether bisphosphonates or some other change in treatment in patients with OI is affecting blood loss when comparing modern populations to historical ones.
None of the authors received financial support for this research and have no financial or personal conflicts of interest.