Risk of Venous Thrombosis in Patients with Sickle Cell Trait after Orthopedic Surgery
Authors: Gollamudi Jahnavi , Al-Kindi Sadeer , Martin Petra , Little Jane , Nayak Lalitha V. 
Published: October 2019

Abstract
Introduction
Sickle cell trait (SCT) is considered to confer a hypercoagulable state. Historically, venous thromboembolism (VTE, deep vein thrombosis and PE) rates for untreated patients after major orthopedic surgery (hip or knee replacement or hip fracture surgery) have been close to 4.3%, however with the introduction of post-op anticoagulation, the rates have been as low as 1.15%. Although guidelines exist regarding anticoagulation for up to 35 days after major orthopedic surgery, there are no specific recommendations for patients with SCT. The purpose of this retrospective study is to examine the rates of VTE after major orthopedic surgery in a cohort of patients with SCT. We hypothesize that rates of VTE would be higher in patients with SCT and the risk of VTE would persist beyond 35 days.
Methods
A commercial database (Explorys Inc, Cleveland, OH, USA), an aggregate of electronic health record data from 26 major integrated US healthcare systems representing a sixth of the US population, was queried for data, using Systematized Nomenclature of Medicine (SNOMED) clinical terms or codes. Cases were defined as patients with SCT who underwent major knee or hip surgery. Since a majority of the US population with SCT are African American (AA) patients, controls were defined as AA patients without SCT undergoing major orthopedic surgery. For the primary end point of VTE, only adult patients (≥18 years) were selected. Those with previous history of VTE, thrombophilia, malignant disease, antiphospholipid antibody syndrome and other hemoglobinopathies such as sickle cell disease were excluded. 30 and 90-day rates of VTE were recorded for both groups. Logistic regression models were used to adjust of confounding variables (defined a priori as age > 65 or< 65, smoking, gender and presence or absence of body mass index > 30). Of note, SCT is likely under-estimated due to incomplete diagnosis. Rates or proportions were compared using Chi-squared testusing Medcalc software (2018). Logistic regression analysis was done using Statistical Package for Social Sciences (SPSS, version 21, IBM Corp, Armonk, NY). P< 0.05 was considered statistically significant.
Results
A total of 1360 major orthopedic surgeries in patients with SCT and 74040 surgeries in non-SCT patients were identified. 30 and 90-day VTE for SCT patients undergoing major orthopedic surgery was 9.7% each. 30 and 90 day VTE for non-SCT patients undergoing major hip and knee surgery were 5.9 % and 6.4 % respectively. The difference in 30-day and 90-day VTE rates between the SCT and non-SCT group was statistically significant (30 day VTE difference 3.1%, 95% CI 1.6650-4.7569, p < 0.001; 90 day VTE difference=3.6%; 95% CI 2.1658-5.2562, p= <0.001). The rates of anticoagulant dispensation (oral Xa inhibitors, enoxaparin or warfarin) after surgery were 56% and 46% in SCT and non-SCT group respectively (difference = 10%, 95% CI 7.32-12.64, p <0.001). Despite the higher proportion of patients prescribed for anticoagulants in the SCT population, there was still a higher 30 and 90-day VTE rate in that group. Compliance to anticoagulation and mortality from VTE could not be assessed in this study.
Logistic regression of risk factors associated with risk of VTE revealed age over 65 years of age, female gender, active smoking status, obesity (BMI >30), and presence of sickle cell trait were all significantly associated with increased risk of both 30 and 90 day VTE post major orthopedic surgery. Please see Table 1 and 2 for further details.
Conclusion
Our study represents real life data outside of a clinical trial. We found that patients with SCT who underwent major hip and knee surgery had an increased 30 and 90-day VTE rates compared to non-SCT patients undergoing the same procedures. Overall, this cohort of AA patients had VTE rates higher than that were described in literature. Of note, AA patients overall are at a higher risk of VTE than are their Caucasian counterparts. The results from the study seem to suggest a role for extended prophylaxis in people with SCT who are undergoing orthopedic procedures, and warrants further study.

Disclosures
Little: Doris Duke Charitable Foundations: Research Funding; NHLBI: Research Funding; PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria.