Abstract
OBJECTIVE To describe surgical techniques and perioperative management of dogs with von Willebrand disease (VWD) or factor VII (FVII) deficiency undergoing laparoscopic ovariohysterectomy or ovariectomy and evaluate outcomes.
DESIGN Retrospective case series.
ANIMALS 20 client-owned dogs with VWD (n = 16) or FVII deficiency (4).
PROCEDURES Dogs with VWD or FVII deficiency that underwent laparoscopic ovariohysterectomy or ovariectomy between 2012 and 2014 were retrospectively identified via a multi-institutional review of medical records.
RESULTS Median expression of von Willebrand factor was 19% (interquartile range, 18% to 30%). All 16 dogs with VWD were Doberman Pinschers, and all were pretreated with desmopressin; 4 also received cryoprecipitate. One of 4 dogs with FVII deficiency received plasma preoperatively, and 1 was treated with desmopressin; 2 dogs received no preoperative treatment. Laparoscopic ovariectomy was performed in 9 dogs with VWD and 2 dogs with FVII deficiency, laparoscopic ovariectomy with gastropexy was performed in 6 dogs with VWD and 1 dog with FVII deficiency, and laparoscopic-assisted ovariohysterectomy was performed in 1 dog with VWD and 1 dog with FVII deficiency. Iatrogenic splenic laceration requiring conversion to laparotomy occurred during trocar insertion in 1 dog with VWD. No postoperative complications, including signs of hemorrhage, were reported for any dogs.
CONCLUSIONS AND CLINICAL RELEVANCE Laparoscopic ovariohysterectomy or ovariectomy in dogs with VWD or FVII deficiency pretreated with desmopressin, cryoprecipitate, or plasma transfusions were not associated with clinical signs of hemorrhage, suggesting that minimally invasive ovariohysterectomy or ovariectomy may be considered in female dogs affected with these coagulopathies.
Von Willebrand disease, an inherited autosomal disease caused by a defect in von Willebrand factor (a high-molecular-weight glycoprotein), is the most commonly reported coagulopathy in dogs.1 Tissue factor or factor VII deficiency is less common in dogs than von Willebrand disease, but both can be associated with excessive hemorrhage during surgery.1–3 von Willebrand factor is essential for platelet adhesion to the subendothelium and for platelet aggregation when there is damage to blood vessels.1,4 von Willebrand disease is estimated to affect 1% to 2% of humans,5,6 which is similar to the 1.5% reported prevalence in dogs.7 In affected individuals, a G96E mutation is responsible.2,8 This prevents the activation of factor VII, delays the extrinsic pathway of coagulation, and prolongs prothrombin time.2,8 There are limited studies available on the prevalence of factor VII deficiency in both humans and animals. Although this condition reportedly affects a small percentage of the canine population,7 when present, it results in an increased risk of hemorrhage in dogs undergoing routine, elective surgical procedures such as ovariohysterectomy and ovariectomy.2,3,9 As such, surgeons must take particular care to minimize tissue injury in these patients.10,11
Multiple studies12–15 in human patients have demonstrated more pronounced inflammatory and coagulation cascade disruption in patients undergoing open versus laparoscopic surgery. In human patients, laparoscopic hysterectomy may result in similar or reduced blood loss, compared with blood loss associated with the conventional, open surgical approach.16,17 Ovariohysterectomy and ovariectomy are commonly performed in small animal veterinary patients, and laparoscopic techniques for both of these procedures are well described.18–26
We are not aware of prior published research describing the management and outcome of dogs with von Willebrand disease or factor VII deficiency undergoing laparoscopic ovariohysterectomy or ovariectomy. As such, the objectives of the study reported here were to describe the surgical techniques and perioperative management of dogs with von Willebrand disease or factor VII deficiency that underwent laparoscopic ovariohysterectomy or ovariectomy and to determine the prevalence of intraoperative and postoperative complications. We hypothesized that female dogs with von Willebrand disease or factor VII deficiency undergoing laparoscopic ovariohysterectomy or ovariectomy would not experience major intra- or postoperative hemorrhage requiring blood transfusion.
Materials and Methods
Case selection criteria
Medical records of all dogs with von Willebrand disease or factor VII deficiency that underwent laparoscopic ovariohysterectomy or ovariectomy between January 2012 and December 2014 at any of 4 referral hospitals were retrospectively reviewed. Dogs were eligible for inclusion if they were sexually intact females, had a preoperative plasma von Willebrand factor antigen concentration < 70% or a preoperative buccal mucosal bleeding time > 5 minutes, had a preoperative plasma factor VII activity < 57% or a prolonged preoperative prothrombin time, underwent laparoscopic-assisted ovariohysterectomy or laparoscopic ovariectomy, and had at least 2 weeks of follow-up information available in the record.
Medical records review
Data collected from the medical records included history, signalment, body weight, physical examination findings, and clinical laboratory findings, including, prothrombin time, buccal mucosal bleeding time, and type of coagulopathy. To evaluate type of coagulopathy, plasma von Willebrand factor antigen concentration was determined with an ELISA and with a plasma factor VII activity antigen assay. Results of the von Willebrand factor antigen assay were reported as a percentage, compared with a 100% standard. A von Willebrand factor antigen concentration of 70% to 180% was considered within reference limits,1,9 a concentration of 50% to 69% was considered borderline, and a concentration < 50% was considered abnormal. Results for factor VII activity were reported as a percentage of the activity of a canine plasma standard, which was assigned a value of 100%. Samples for coagulation testing were sent to the Cornell University Comparative Coagulation Laboratory.
Any treatments, including drug doses administered perioperatively to lower the risk of hemorrhage, were recorded, as was the laparoscopic approach (ie, multi-incision or single incision), the specific procedures performed (ie, ovariohysterectomy, ovariectomy, or gastropexy), and the surgery time (time from initial incision to completion of skin closure). Additional data recorded included duration of hospitalization, whether any perioperative complications occurred (eg, postoperative hemorrhage), whether any blood products were administered, outcome (survived to hospital discharge vs died or was euthanized prior to discharge), and cause of death or euthanasia (if applicable). The perioperative period was defined as the time from initial admission for surgery until the scheduled recheck examination 2 weeks after surgery.
Surgical procedures
Laparoscopic ovariectomy, laparoscopic-assisted ovariohysterectomy, and laparoscopic ovariectomy with concurrent laparoscopic-assisted gastropexy were performed by means of a single-port or multiport approach. Choice of anesthesia and analgesia protocols was at the discretion of the supervising anesthesiologist; standard-of-care monitoring was provided. All patients were placed in dorsal recumbency on a laparoscopic tilt table or a standard surgical table and were aseptically prepared for surgery. For single-port laparoscopic ovariohysterectomy and ovariectomy, a 2.5-cm midline skin incision was made and continued through the linea alba just caudal to the umbilicus, and a SILSa port was then placed in the incision. For single-port laparoscopic ovariectomy with concurrent laparoscopic-assisted gastropexy, a 2.5-cm incision was made on the right side of the rectus abdominis muscles 2 to 5 cm caudal to the right 13th rib. A SILS port was then placed in the incision as previously described.27 Multiport procedures were performed with either a 2- or 3-port technique.23
Once the single-port or multiport instruments were in place, the abdomen was insufflated with CO2 to a pressure of 8 to 12 mm Hg with a pressure-regulating mechanical insufflator and maintained at that pressure throughout surgery. A vessel-sealing deviceb was used to achieve hemostasis and to seal the ovarian pedicles and suspensory ligament in all patients. For ovariectomy, the same device was used to seal the uterine horn at the level of the proper ovarian ligament and completely excise the ovaries.23,24,27 For ovariohysterectomy, the ovaries and uterine horns were removed from the most caudal incision, and extracorporeal double ligation of the uterus and both uterine arteries was performed cranial to the cervix before removal.22 Multiport laparoscopic-assisted gastropexy was performed with the technique described by Rawlings et al.28 All surgical procedures were performed by a board-certified surgeon experienced in laparoscopic surgery or by a surgical resident directly supervised by an experienced, board-certified surgeon.
Statistical analysis
Descriptive statistics were calculated. Numeric, continuous data were summarized as median and interquartile ranges. All calculations were performed with standard software.c
Results
Signalment
Twenty female dogs met the study selection criteria. There were 16 dogs with von Willebrand disease and 4 dogs with factor VII deficiency. All dogs with von Willebrand disease were Doberman Pinschers. Dogs with factor VII deficiency consisted of a Beagle, Springer Spaniel, Scottish Deerhound, and Alaskan Klee Kai. The median age of all dogs was 9 months (IQR, 7 to 19.2 months), and median body weight was 25.4 kg (55.9 lb; IQR, 19.5 to 32.7 kg [42.9 to 71.9 lb]).
History and physical examination findings
Two of 20 dogs had historical signs of spontaneous hemorrhage from the nose; 1 of these 2 dog had von Willebrand disease and the other had factor VII deficiency. A third dog with factor VII deficiency had previously been noted to have spontaneous bruising and swelling around the face. Two other dogs (1 with deficiency von Willenbrand disease and 1 with factor VII) had undergone previous surgeries, including ear cropping (n = 1) and percutaneous transjugular coil embolization of an intrahepatic liver shunt (1), with no reported abnormal hemorrhage. No other relevant historical or physical examination findings were reported.
Clinicopathologic findings
Sixteen of 20 dogs had a CBC and serum biochemical analysis performed before surgery. One dog with an intrahepatic portosystemic shunt had microcytic, normochromic anemia (Hct, 35.6%; reference range, 40% to 56%]). The same dog had a low BUN concentration (5.0 mg/dL; reference range, 8 to 25 mg/dL) and hypoalbuminemia (2.0 g/dL; reference range, 2.9 to 3.8 g/dL) as well as high alanine transaminase (165 U/L; reference range, 18 to 64 U/L) and aspartate transaminase (94 U/L; reference range, 15 to 52 U/L) activities. Two other dogs had slightly high alkaline phosphatase activity. Results were within reference ranges for the remaining 13 dogs. The von Willebrand factor antigen assay was performed in 14 of the 16 dogs. Eleven of the 14 dogs were considered positive for von Willebrand disease solely on the basis of assay results; 1 dog was borderline, and 2 dogs had assay results within reference limits. The median for all dogs was 19% (IQR, 18% to 30%). The 2 dogs with von Willebrand factor antigen assay results within reference limits and the 2 dogs in which von Willebrand factor antigen concentration was not measured had buccal mucosal bleeding times > 5 minutes (reference limit, < 5 minutes29), which was considered highly suggestive of von Willebrand disease. Given that all 4 dogs were Doberman Pinschers, they were considered to have von Willebrand disease. Buccal mucosal bleeding time was measured in 11 of the 16 dogs with von Willebrand disease and was prolonged (> 5 minutes) in 10 of the 11. Factor VII activity was measured in 3 of the 4 dogs with factor VII deficiency and was 18%, 19%, and 30% (reference interval, 57% to 181%2,30). Median prothrombin time was 96.3 seconds for the 4 dogs with factor VII deficiency (IQR, 34.2 to 100 seconds; reference interval, 6.0 to 8.5 seconds31).
Preoperative treatments
Twelve of the 16 dogs with von Willebrand disease received desmopressin (1 μg/kg [0.45 μg/lb]) IV (n = 1), SC (6), or by an undocumented route (5) prior to surgery. The remaining 4 dogs with von Willebrand disease received desmopressin (1 μg/kg, IV) and cryoprecipitate (10 mL/kg [4.5 mL/lb], IV) prior to surgery. Of the 4 dogs with factor VII deficiency, 1 received a plasma transfusion (10 mL/kg, IV) and 1 received desmopressin (1 μg/kg, IV) prior to surgery; the other 2 dogs did not receive any preoperative coagulation prophylaxis.
Anesthesia and analgesia
Dogs were premedicated with methadone (0.3 mg/kg [0.14 mg/lb], IM), hydromorphone (0.01 mg/kg [0.0045 mg/lb], IM), or hydromorphone (0.01 mg/kg, IM) with dexmedetomidine (5 μg/kg [2.3 μg/lb], IM). General anesthesia was induced with propofol (4 mg/kg [1.8 mg/lb], IV), patients were endotracheally intubated, and anesthesia was maintained with either sevoflurane or isoflurane in oxygen. Standard anesthetic monitoring included electrocardiography, direct or indirect blood pressure measurement, and measurement of oxygen saturation (by means of pulse oximetry) and end-tidal partial pressure of carbon dioxide (by means of capnography). Dogs received either methadone (0.2 mg/kg [0.09 mg/lb], IV) or hydromorphone (0.5 mg/kg [0.23 mg/lb], IV) at the time of extubation. Tramadol hydrochloride (3 to 4 mg/kg [1.4 to 1.8 mg/lb], PO, q 8 to 12 h) was prescribed at the time of discharge from the hospital.
Surgical management
Ovariectomy only was performed in 11 dogs, 9 of which had von Willebrand disease and 2 of which had factor VII deficiency. In 4 of the dogs with von Willebrand disease, a 2-port approach was used to remove the ovaries, and in 5 of the dogs with von Willebrand disease and both of the dogs with factor VII deficiency, the SILSa port system was used to remove the ovaries. Ovariectomy and gastropexy were performed concurrently in 7 dogs, 6 of which had von Willebrand disease and 1 of which had factor VII deficiency. In the dogs with von Willebrand disease, a 2-port approach in 1 dog, a 3-port approach in 3 dogs, and the SILS port system was used in 2 dogs. The SILS port system was also used in the dog with factor VII deficiency. Ovariohysterectomy only was performed in 1 dog with von Willebrand disease (2-port approach) and 1 dog with factor VII deficiency (3-port approach). The median surgery time for laparoscopic ovariectomy or ovariohysterectomy performed alone was 60 minutes (IQR, 45 to 87.5 minutes; n = 13). The median surgery time for ovariectomy with concurrent gastropexy was 100 minutes (IQR, 70 to 120 minutes; n = 7). In 1 patient with von Willebrand disease undergoing laparoscopic ovariohysterectomy, an iatrogenic splenic laceration occurred during insertion of the cannula via the Hasson technique. Spontaneous resolution of hemorrhage did not occur, and conversion to laparotomy was required to suture the laceration in that patient.
Outcome
No postoperative complications occurred in any of the 20 dogs. Dogs were discharged a median of 25 hours (IQR, 24 to 48 hours) after surgery. A median follow-up period of 14 days (range, 14 to 720 days) was recorded.
Discussion
Results of the present retrospective multi-institutional study of 20 dogs treated over a 2-year period suggested that laparoscopic or laparoscopic-assisted ovariohysterectomy and ovariectomy with or without gastropexy was associated with a low risk of perioperative hemorrhage in dogs with von Willebrand disease (n = 16) or factor VII deficiency (4) when managed and treated as described. Of the patients described, only 1 dog had hemorrhage that required conversion to open laparotomy; no patients experienced postoperative complications. In view of these results and the minimally invasive nature of the procedures, we suggest that laparoscopic ovariohysterectomy and ovariectomy in dogs with von Willebrand disease or factor VII deficiency may be safe and clinically beneficial, versus traditional surgery, because of decreased tissue trauma.
In the present study, all 16 dogs with von Willebrand disease were Doberman Pinschers. Previous reports7,9 indicate a breed predisposition for von Willebrand disease in Doberman Pinschers and a prevalence of 33% to 63% for factor VII deficiency in Beagles and Alaskan Klee Kai.2,8,32 The median age of all dogs in the present study was 9 months (IQR, 7 to 19.2 months), and the median weight was 25.4 kg (55.9 lb; IQR, 19.5 to 32.7 kg [42.9 to 71.9 lb]); these values were similar to data reported for dogs in previous studies20–23 describing laparoscopic ovariohysterectomy or ovariectomy. Historical and physical examination abnormalities were rare in the patients in the present study. Only 3 of 20 dogs had a history of clinical signs of coagulopathy prior to evaluation for elective ovariohysterectomy or ovariectomy. Two additional dogs had undergone prior surgical procedures, with no documented hemorrhage complications. In a study7 of 350 dogs in São Paulo, Brazil, the authors reported that 1.4% of dogs had von Willebrand disease, but none of the affected dogs had clinical signs of hemorrhage. In a Canadian study9 of 165 dogs, 48.6% of dogs with low von Willebrand factor antigen concentration experienced clinical signs of hemorrhage. Collectively, these reports3,7,9 and the results of the present study would seem to indicate that affected dogs that are surgical candidates may or may not have a history of overt signs of hemorrhage. As such, we suggest that it is important to consider these coagulopathies when examining susceptible breeds. In the present study, results of routine preanesthetic laboratory testing were mainly within reference ranges indicating that such tests should not be relied on to screen for coagulopathies. One patient with factor VII deficiency that also had a preexisting diagnosis of an intrahepatic portosystemic shunt had microcytic, normochromic anemia and increased hepatic enzyme activities.
Fourteen of the 16 dogs with von Willebrand disease in this study had von Willebrand factor antigen concentration measured. The median concentration was 19%, which was well below the range (70% to 180%) designated as normal for dogs.1,9 von Willebrand disease can be classified into 3 different types. Patients with type I disease have normal functioning von Willebrand factor but in low concentrations; this is the type commonly seen in most Doberman Pinschers.1,3 Patients with type II von Willebrand disease have low concentrations of the high-molecular-weight multimers responsible for platelet binding, and patients with type III von Willebrand disease completely lack von Willebrand factor.1,3,9 These differences in von Willebrand disease type have important implications for pretreating affected patients before any invasive procedures. The factor VII activity was low in the 3 of the 4 dogs with factor VII deficiency in the present study, measuring 18%, 19%, and 30%, with the previously reported reference range being 57% to 181%.2,30 The 2 dogs that did not have the von Willebrand factor antigen assay performed were considered to have the disease because of their breed (Doberman Pincher) and because they had a buccal mucosal bleeding time > 5 minutes.29 Similarly, the 1 dog with factor VII deficiency in which factor VII activity was not measured was considered to be deficient because of its breed (Alaskan Klee Kai) and because it had a prolonged prothrombin time.2
Desmopressin is commonly administered to dogs with von Willebrand disease because it causes the release of von Willebrand factor from endothelial cells, thereby increasing the circulating concentration.1,4,33 However, because of this mechanism of action, it is effective only in patients with type I disease; patients with type III von Willebrand disease would not be expected to respond because they completely lack von Willebrand factor. All 16 dogs with von Willebrand disease in the present study received desmopressin, and none of those patients experienced intraoperative or postoperative complications. Because cryoprecipitate and fresh-frozen plasma replenish von Willebrand factor and factor VII, administration of these products has been reported to be a valuable preoperative treatment for dogs with von Willebrand disease and factor VII deficiency.1,34
In the present study, the specific laparoscopic technique varied, with 10 of the 20 procedures performed with a single-incision approach using the SILS port system. Whereas an increased incidence of hemorrhage was not documented in patients in which a multiport approach was used, minimizing the number of incisions in patients with bleeding disorders may be important to avoid perioperative complications, as has been investigated in human patients.10,12–15 Furthermore, although we did not directly compare affected dogs undergoing ovariohysterectomy or ovariectomy via a laparoscopic or laparoscopic-assisted approach with a comparable group of patients treated by means of open surgery, evidence for the benefits of a minimally invasive approach to abdominal procedures in veterinary patients with coagulopathies may be extrapolated from the human medical literature. When compared with conventional open surgery, laparoscopic surgery in human patients has been reported to result in significantly decreased concentrations of prothrombin fragments, thrombin-antithrombin complex, and D-dimers immediately after surgery.10,13,14 Because any type of surgery may produce hypercoagulability in the postoperative period, procedures that decrease the extent to which the coagulation cascade is stimulated are likely to benefit patients with a concurrent coagulopathy, possibly decreasing the likelihood of postoperative complications.10,13–15 Several studies12,13 in human patients have also demonstrated a greater increase in the concentrations of interleukin-1β and −6, important cytokines in the inflammatory cascade, for patients undergoing conventional open surgical procedures versus laparoscopic surgery. Increased inflammation increases pain and the potential for hemodynamic instability.10,12,13
In the present study, median surgery time for ovariohysterectomy or ovariectomy performed alone was similar to times given in previous reports,19,21,22,25 with most procedures being completed in < 60 minutes (IQR, 45 to 87.5 minutes; n = 13). Concurrent laparoscopic-assisted gastropexy performed with ovariectomy increased surgery time, but did not appear to result in hemorrhage or other complications. The only perioperative complication noted was an iatrogenic splenic laceration that occurred in 1 patient with von Willebrand disease during insertion of a cannula with the Hasson technique, requiring conversion to open surgery. This has previously been reported as a complication of laparoscopic surgery in both veterinary and human patients; certain patients, such as those of the present study, may be more likely to require conversion, depending on the underlying disease.20,23,24,35,36 None of the patients in the present study developed complications during the immediate postoperative period or during the minimum 2-week postoperative follow-up period. However, further investigation is indicated and should include comparison of laparoscopic ovariohysterectomy or ovariectomy with traditional ovariohysterectomy or ovariectomy in a larger number of dogs with von Willebrand disease or factor VII deficiency.
Multiple studies21,37,38 in the veterinary literature have reported use of the bipolar vessel-sealing device for effective and safe ligation of the ovarian pedicle in dogs without apparent complications. The device that was used for all procedures in the present study functioned by coagulating and sealing tissues and had a continuous-feedback mechanism that detected changes in tissue impedance and a computer generator to actively sense when the tissue and vessels were adequately sealed. A blade mechanism was then activated that divided the selected tissue and vessels. The device has been recommended for use in arteries and veins up to 7 mm in diameter.21,39 The advantage of using a vessel-sealing device, versus laparoscopic suturing or endoscopic clips, is that the potential for slippage of sutures or clips is eliminated.21,40 Excellent hemostasis with vessel-sealing devices, compared with the use of ligatures or clips, has been demonstrated in dogs undergoing laparoscopic-assisted ovariohysterectomy.21 As such, we consider the vessel-sealing device to be the current standard of care for laparoscopic ovariohysterectomy or ovariectomy procedures in small animal veterinary patients.
The present study was limited by the small sample size of 20 patients (16 dogs with von Willebrand disease and 4 dogs with factor VII deficiency). The retrospective nature of the study also inherently limited the data that were available, and there was no open laparotomy group against which to compare our findings. Although results of the present study suggested that laparoscopic or laparoscopic-assisted ovariohysterectomy or ovariectomy had a low risk of hemorrhage in affected dogs, further investigation is indicated.
ABBREVIATIONS
| IQR | Interquartile (25th to 75th percentile) range |
| SILS | Single-incision laparoscopy surgery |
Footnotes
SILS port, Covidien, Mansfield, Mass.
Blunt Tip Ligasure, 5mm, Covidien, Mansfield, Mass.
JMP, version 8.0, SAS Institute Inc, Cary, NC.
References
1. Barr JW, McMichael M. Inherited disorders of hemostasis in dogs and cats. Top Companion Anim Med 2012; 27:53–58.
2. Kaae JA, Callan MB, Brooks MB. Hereditary factor VII deficiency in the Alaskan Klee Kai dog. J Vet Intern Med 2007; 21:976–981.
3. Brooks MB, Erb HN, Foureman PA, et al. von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers. Am J Vet Res 2001; 62:364–369.
4. Federici AB, Castaman G, Mannucci PM. Guidelines for the diagnosis and management of von Willebrand disease in Italy. Haemophilia 2002; 8:607–621.
5. Werner EJ, Broxson EH, Tucker EL, et al. Prevalence of von Willebrand disease in children: a multiethnic study. J Pediatr 1993; 123:893–898.
6. Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand's disease. Blood 1987; 69:454–459.
7. Mattoso CRS, Takahira RK, Beier SL, et al. Prevalence of von Willebrand disease in dogs from São Paulo State, Brazil. J Vet Diagn Invest 2010; 22:55–60.
8. Callan MB, Aljamali MN, Mararitis P, et al. A novel missense mutation responsible for factor VII deficiency in research Beagle colonies. J Thromb Haemost 2006; 4:2616–2622.
9. Burgess HJ, Woods JP, Abrams-Ogg ACG, et al. Use of a questionnaire to predict von Willebrand disease status and characterize hemorrhagic signs in a population of dogs and evaluation of a diagnostic profile to predict risk of bleeding. Can J Vet Res 2009; 73:241–251.
10. Zezos P, Christoforidou A, Kouklakis G, et al. Coagulation and fibrinolysis activation after single-incision versus standard laparoscopic cholecystectomy: a single-center prospective case-controlled pilot study. Surg Innov 2014; 21:22–31.
11. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 2009; 37:1528–1542.
12. Leung KL, Lai PBS, Ho RLK, et al. Systemic cytokine response after laparoscopic-assisted resection of rectosigmoid carcinoma. Ann Surg 2000; 231:506–511.
13. Schietroma M, Carlei F, Mownah A, et al. Changes in the blood coagulation, fibrinolysis, and cytokine profile during laparoscopic and open cholecystectomy. Surg Endosc 2004; 18:1090–1096.
14. Tsiminikakis N, Chouillard E, Tsigris C, et al. Fibrinolytic and coagulation pathways after laparoscopic and open surgery: a prospective randomized trial. Surg Endosc 2009; 23:2762–2769.
15. Nguyen NT, Owings JT, Gosselin R, et al. Systemic coagulation and fibrinolysis after laparoscopic and open gastric bypass. Arch Surg 2001; 136:909–916.
16. Carter JE, Ryoo J, Katz A. Laparoscopic-assisted vaginal hysterectomy: a case control comparative study with abdominal hysterectomy. J Am Assoc Gynecol Laparosc 1994; 1:S7.
17. Elia G, Vermesh M, Bergman A. A cohort study comparing laparoscopic-assisted vaginal hysterectomy and extrafascial hysterectomy. J Am Assoc Gynecol Laparosc 1995; 2:395–398.
18. Culp WT, Mayhew PD, Brown DC. The effect of laparoscopic versus open ovariectomy on postsurgical activity in small dogs. Vet Surg 2009; 38:811–817.
19. Hancock RB, Lanz OI, Waldron DR, et al. Comparison of postoperative pain after ovariohysterectomy by harmonic scalpel-assisted laparoscopy compared with median celiotomy and ligation in dogs. Vet Surg 2005; 34:273–282.
20. Manassero M, Leperlier D, Vallefuoco R, et al. Laparoscopic ovariectomy in dogs using a single-port multiple-access device. Vet Rec 2012; 171:69.
21. Mayhew PD, Brown DC. Comparison of three techniques for ovarian pedicle hemostasis during laparoscopic-assisted ovariohysterectomy. Vet Surg 2007; 36:541–547.
22. Devitt CM, Cox RE, Hailey JJ. Duration, complications, stress, and pain of open ovariohysterectomy versus a simple method of laparoscopic-assisted ovariohysterectomy in dogs. J Am Vet Med Assoc 2005; 227:921–927.
23. Case JB, Marvel SJ, Boscan P, et al. Surgical time and severity of postoperative pain in dogs undergoing laparoscopic ovariectomy with one, two, or three instrument cannulas. J Am Vet Med Assoc 2011; 239:203–208.
24. Dupré G, Fiorbianco V, Skalicky M, et al. Laparoscopic ovariectomy in dogs: comparison between single portal and two-portal access. Vet Surg 2009; 38:818–824.
25. Davidson EB, Moll HD, Payton ME. Comparison of laparoscopic ovariohysterectomy and ovariohysterectomy in dogs. Vet Surg 2004; 33:62–69.
26. Hand R, Rakestraw P, Taylor T. Evaluation of a vessel-sealing device for use in laparoscopic ovariectomy in mares. Vet Surg 2002; 31:240–244.
27. Runge JJ, Mayhew PD. Evaluation of single port access gastropexy and ovariectomy using articulating instruments and angled telescopes in dogs. Vet Surg 2013; 42:807–813.
28. Rawlings CA, Foutz TL, Mahaffey MB, et al. A rapid and strong laparoscopic-assisted gastropexy in dogs. Am J Vet Res 2001; 62:871–875.
29. Jergens AE, Turrentine MA, Kraus KH, et al. Buccal mucosa bleeding times of healthy dogs and of dogs in various pathologic states, including thrombocytopenia, uremia, and von Willebrand's disease. Am J Vet Res 1987; 48:1337–1342.
30. Mischke R. Optimization of coagulometric tests that incorporate human plasma for determination of coagulation factor activities in canine plasma. Am J Vet Res 2001; 62:625–629.
31. Kelmer E, Segev G, Codner C, et al. Assessment of a portable prothrombin time analyzer (CoaguChek-XS) in dogs. JVECC 2014; 24:455–460.
32. Spurling NW, Burton LK, Peacock R, et al. Hereditary factor-VII deficiency in the Beagle. Br J Haematol 1972; 23:59–67.
33. Johnstone IB. Canine von Willebrand's disease: a common inherited bleeding disorder in Doberman Pinscher dogs. Can Vet J 1986; 27:315–318.
34. Stokol T, Parry BW. Efficacy of fresh-frozen plasma and cryoprecipitate in dogs with von Willebrand's disease or hemophilia A. J Vet Intern Med 1998; 12:84–92.
35. Fiorbianco V, Skalicky M, Doerner J, et al. Right intercostal insertion of a Veress needle for laparoscopy in dogs. Vet Surg 2012; 41:367–373.
36. Cuss A, Bhatt M, Abbott J. Coming to terms with the fact that the evidence for laparoscopic entry is as good as it gets. J Minim Invasive Gynecol 2015; 22:332–341.
37. Öhlund M1, Höglund O, Olsson U, et al. Laparoscopic ovariectomy in dogs: a comparison of the Ligasure and the Sono-Surg systems. J Small Anim Pract 2011; 52:290–294.
38. van Nimwegen SA, Kirpensteijn J. Laparoscopic ovariectomy in cats: comparison of laser and bipolar electrocoagulation. J Feline Med Surg 2007; 9:397–403.
39. Tobias KM, Johnston SA. Veterinary surgery: small animal. St Louis: Elsevier/Saunders, 2012; 182.
40. Shettko DL, Frisbie DD, Hendrickson DA. A comparison of knot security of commonly used hand-tied laparoscopic slipknots. Vet Surg 2004; 33:521–524.
