Incidence of Deep Venous Thrombosis and Sickle Cell Disease in Patients Undergoing Spinal Surgery in South Gujarat, India: A Prospective Observational Study

Introduction: Our objective of this study was to assess the incidence of Deep Venous Thrombosis in patients including those with sickle cell disease who underwent spine surgery, and also to determine the association of Sickle Cell Disease as a clinical predictor for Deep Venous Thrombosis in spinal surgery patients. Materials and methods: All patients who underwent spinal surgery from January 2016 to October 2016 were included in this study. Detailed history, demographic data, physical findings, pre-operative haematological and radiological investigations were documented. All the patients underwent daily clinical evaluation for clinical signs of Deep Venous Thrombosis and also underwent a post-operative venous Doppler and D-dimer test. Results: Seventy-nine consecutive patients were included in the study with the mean age of 41 years. All patients had normal venous Doppler pre-operatively. A total of 2.5% patients had deep vein thrombosis in bilateral lower limbs while 2 patients (2.5%) had evidence of venous stasis but no thrombosis on Doppler ultrasound done post-operatively. Nine patients (11.4%) were sickle cell positive from which 4 patients showed evidence of Deep Venous Thrombosis or Venous Stasis. D-dimer was positive in 5 (8.3%) patients which included 4 patients with Sickle Cell Disease. Conclusion: This study concludes that Sickle Cell Disease is a risk factor for developing Deep Venous Thrombosis in patients undergoing spinal surgery. The study also concludes the effectiveness of mechanical prophylaxis in preventing Deep Venous Thrombosis and recommends pharmacological prophylaxis after assessing the risk profile or positive D-dimer test.


INTRODUCTION
Deep venous thrombosis (DVT) is an established complication of all major and time dependent surgeries which may require immobilisation of a patient for a long period of time as in the case of many orthopaedic procedures and spinal surgeries 1,2 . Spinal surgeries may be lengthy, on certain frames and may involve patients with motor paralysis of lower limb which may have an association with Deep vein Thrombosis 1 .
Chemoprophylaxis against DVT and Pulmonary Embolism (PE) is being used in all surgical specialties except for spine surgery, when the fear of causing an unforgiving postoperative epidural hematoma may result in an irreversible neurologic disability for the patient 3-7 .
About 10-15% of the tribal population of India resides in Gujarat, particularly in South Gujarat. A high prevalence (13-31%) of sickle cell trait has been demonstrated among the different tribes of Gujarat. Venous thromboembolism is common in adults with sickle cell disease 8 . There is a gap in medical literature regarding incidence of thromboembolism in patients undergoing spine surgery, especially in South Gujarat region.
The purpose of this study was to demonstrate the incidence of venous thromboembolism in patients including those with sickle cell disease who underwent spine surgery and to formulate a protocol to provide prophylaxis to patients undergoing spine surgery in the future if the incidence was found to be significant with positive association between these two variables.

MATERIALS AND METHODS
A prospective non-randomised observational study was conducted at a Tertiary Health Setup in Surat between the period of January 2016 to October 2016 to assess the incidence of DVT in patients including those with sickle cell disease who underwent spine surgery. The purpose of the study was to determine if Sickle Cell Disease is a positive clinical predictor for Deep Venous Thrombosis in spinal surgery patients. All patients undergoing major spinal surgery at our institute, aged 18 years or more at time of surgery, of both genders, who accepted the terms set out in the study and signed the written informed consent form were included in the study. Patients with previous history of thromboembolic complications, on anticoagulant medication before surgery, peripheral vascular disease, diseases of the hematopoietic system, disseminated malignancy, surgery done under local anaesthesia and polytrauma patients were excluded. A total of 96 patients fulfilled the criteria and were enrolled in the study of which 17 patients were lost to follow-up and were excluded from statistical analysis.
Detailed history, clinical and neurological examination as per American Spinal Injury Association (ASIA) Grade, appropriate lab and radiological investigations were documented. Patient related data included: age, gender, body mass index (BMI), history of smoking, drug history (including contraceptives, hormonal therapy), pregnancy and other comorbidities. Surgery related data included diagnosis, level and type of the procedure, operative time, intraoperative blood loss, and duration of post-operative recumbency, post-operative neurological status which was also documented.
For radiological diagnosis of Deep Venous Thrombosis, Colour Doppler ultrasound was performed pre-operatively as well as on 7th and 14th post-operative day using 3-7 MHz convex probe on GE LOGIEQ F8 USG machine. All ultrasound procedures were done by a single radiologist to minimise inter-observer/subjective errors.
Sickling Test was conducted for all patients pre-operatively to screen them for Sickle Cell Disease. From each patient a complete hemogram (haemoglobin, platelets), coagulation profile [Prothrombin Time (PT), International Normalized Ratio (INR)], lipid profile, random blood sugar (RBS) was collected pre-operatively and 7th -10th day post-operatively. D-dimer test was done in the post-operative period from 7th to 10th day.
During hospitalisation, patients were evaluated every day, in search of clinical changes consistent with thromboembolic events. In post-operative period mechanical prophylaxis (crepe bandaging in bilateral lower limbs) was given to every patient. Each patient was encouraged to mobilise from bed as soon as post-operative pain subsided and according to patient's neurological status. Passive physiotherapy was given to all the patients with complete neurological injury. Pharmacological prophylaxis in form of Low Molecular Weight Heparin (LMWH), was provided to the patients, only when there was an evidence of Deep Venous Thrombosis on Doppler study. Outcomes in terms of incidence of Evidence of Deep Venous Thrombosis in spinal surgery patients was calculated and multiple binomial logistic regression analysis was conducted to find out association of various patient characteristic and sickle cell disease to that of the incidence of Deep Venous Thrombosis. The value of p<0.05 was taken to be significant in association of Deep Venous Thrombosis.

RESULTS
Seventy-nine patients who underwent spine surgeries and gave consent to be a part of this study, were included as study sample. The mean age of study group was 41 Years. Majority of patients belonged to 31-40 age group. 75% (n=59) patients included in the study sample were males (Table I). Only 8 patients (10.1%) were neurologically intact (ASIA grade E), while 12 patients (15.2%) had complete neurological injury (ASIA grade A).
All 79 patients had normal venous Doppler pre-operatively. Two patients (2.5%) developed evidence of deep vein thrombosis in bilateral lower limbs on Doppler ultrasound done on 7th and 14th post-operative day. Two patients (2.5%) had evidence of venous stasis on Doppler ultrasound with sluggish flow in anterior tibial vein (bilateral), but no evidence of thrombosis (Table II). None of the patients had shown clinical signs of Deep Venous Thrombosis in daily post-operative clinical examination of the patient.
One patient developed pulmonary embolism (PE). The patient was managed in ICU with mechanical ventilatory support and subcutaneous Low Molecular Weight Heparin (LMWH). Patient was extubated within two days and recovered well. Patient was a known case of Diabetes Mellitus (DM-Type2) and hypertension, under regular treatment.
Total 9 patients (11.4%) out of 79 patients were sickle cell positive from which 4 patients showed evidence of Deep Venous Thrombosis or Venous Stasis post-operatively. The association of sickle cell disease as risk factor for Deep venous thrombosis was statistically significant in-patient undergoing spinal surgeries, (Fischer exact test after Haldane Anscombe correction, p value<0.002) 69 patients (87%) patients were mobilised within 5 days of surgery, of which 46 patients (58%) were mobilised within 3 days of surgery. Many patients (n=25) were mobilised on the next day of surgery. Two patients diagnosed with Deep Venous Thrombosis later on, were also mobilised on 1st post-op day and were operated for lumbar disc pathology. Two patients who were diagnosed with venous stasis on 7th post op day were mobilised on 3rd post op day. We could not find any statically significant association with the incidence   of Deep Venous thrombosis with the period of immobilisation. Also, all the patients irrespective of the period of immobilisation were given mechanical prophylaxis.
Patients with ASIA grade D and E were advised to walk with brace with/without assistance. Patients with ASIA grade A, B and C were advised to log roll and start wheel-chair mobilisation as soon as their post-operative pain subsided.
All the patients and their relatives were advised and taught passive and/or active mobilisation of peripheral limbs and joints under supervision of a physical therapist.  (Table III  and IV).

DISCUSSION
DVT and PE caused by long period of immobilisation are life threatening medical complications following all major orthopaedic surgeries. Surgery of any kind is known to create prothrombotic state due to stress which may increase thrombotic complications post-operatively 9 . The incidence of Deep Venous Thrombosis after spine surgery ranges from 0.3% to 31% and further studies are needed for the same. The reason for this variability in the incidence of Deep Venous Thrombosis is most likely due to the differences in epidemiological characteristics of the studied populations, lack of standard diagnostic and treatment protocol for DVT 1,2,10 .  13,14 .
Prophylaxis consists of mechanical and pharmacological measures which has been most effective for venous thromboembolism as demonstrated in several previous studies [3][4][5][6]12,15,16 . Mechanical prophylaxis (compression stocking or sequential compression devices) after spine surgery is considered both effective and safe but chemoprophylaxis with anticoagulation therapy is not accepted to be safe as early anticoagulation chemoprophylaxis has the potential risk for bleeding complications, specifically, acute post-operative formation of epidural haematomas which has significant neurological sequalae 17,18 . Timing for starting chemoprophylaxis postoperatively is also controversial as there is no conclusive evidence that exists in the literature to guide management for such patients 3,5,6,7,15,18 . In our study, all the patients who underwent spinal surgeries were given mechanical prophylaxis to mitigate the risk of epidural haematoma associated with use of pharmacological prophylaxis. In the present study, risk factors for each patient were calculated to produce an overall risk factor score according to Caprini s risk factor score, which corresponded from low to very high potential for development of In our study, 11.4% patients (n=9) were diagnosed with sickle cell disease. All the 4 patients with evidence of thrombosis or stasis on Doppler study were positive for sickle cell disease indicating positive association of sickle cell disease with incidence of Deep Venous Thrombosis. For a patient with sickle cell disease a careful pre-operative check must include an assessment of the patient's known crisis triggers, hematologic profile, evaluation of risk of surgical procedure and anticipated volume of blood loss, period of immobilisation after surgery and opioid dependence. Hypoxia, hypothermia, acidosis, and intravascular volume depletion should be prevented in such sickle cell patients in the perioperative period 24 .
Drawbacks of this study includes the limited available sample size and the lack of advanced investigations like high performance liquid chromatography (HPLC) and electrophoretic study which would have helped in finding out the type of sickle cell disease (trait or disease) and its association with the incidence of Deep Vein Thrombosis.

CONCLUSION
The findings of this study report the incidence of Deep Vein Thrombosis in patients undergoing spine surgeries to be 2.5%. Also, 2.5% of patients had venous stasis on Doppler ultrasound but no evidence of thrombosis. Clinician should have a higher index of suspicion for Deep Vein Thrombosis in patient with sickle cell disease undergoing spinal surgeries. Post-operative D-dimer measurements in patients from high-risk group who are undergoing spine surgery, may provide a complementary diagnostic screening for Deep Venous Thrombosis during early post-operative days. Mechanical prophylaxis should be provided to all patients who undergoing spine surgery. Pharmacological prophylaxis should be reserved for patients showing D-dimer positive and/ or Doppler findings positive.

CONFLICT OF INTERESTS
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.