Postoperative Deep Vein Thrombosis (DVT) In Patients With Hemophilia Undergoing Major Orthopedic Surgery
Authors: Buckner Tyler W. , Andrew Leavitt , Ragni Margaret V. , Eyster M. Elaine , Kempton Christine L. , Key Nigel S 
Published: October 2019

Abstract

Background
Patients undergoing major orthopedic surgery such as hip and knee arthroplasty are at particularly high risk for venous thromboembolism (VTE) due to the nature of the surgery and postoperative immobilization, and thus routine thromboprophylaxis has been the standard of care for more than 15 years. Peri-operative clotting factor concentrate replacement is administered to reverse the inherent hemostatic defect in persons with hemophilia (PWH), potentially rendering these patients at risk for developing deep vein thrombosis (DVT) postoperatively. Currently, no published guidelines address the risk of DVT or the indications for thromboprophylaxis in PWH undergoing hip or knee arthroplasty. Consequently, given their underlying bleeding risk, thromboprophylaxis practice in individuals with hemophilia undergoing orthopedic procedures varies considerably among Hemophilia Treatment Centers (HTCs).

Objective
To determine the rate of ultrasound-detectable lower extremity DVT (asymptomatic or symptomatic) or clinically apparent pulmonary embolism (PE) in PWH undergoing total hip or knee arthroplasty.

Methods
This was a prospective, multicenter observational study. All patients with hemophilia A or B scheduled for knee or hip replacement at participating centers were eligible to participate. Patients with a prior history of VTE or those receiving anticoagulation prior to surgery were excluded. Baseline venous duplex ultrasounds of the lower extremities (proximal and distal) were obtained within 7 days prior to surgery, and follow-up ultrasounds were performed 4-6 weeks after surgery. Patients were otherwise evaluated and treated per the local institutional standard of care. Coagulation factor dosing and plasma factor activity levels were recorded, as was use of mechanical (intermittent pneumatic compression) or pharmacologic thromboprophylaxis. Major bleeding was defined as bleeding that resulted in a decrease of hemoglobin of 2 g/dL or more over a 24 hour period, bleeding that led to transfusion of 2 or more units of packed red blood cells, bleeding into a critical site, or bleeding that led to death. Minor bleeding was defined as clinically overt bleeding that did not satisfy any of the major bleeding criteria.

Results
11 HTCs enrolled a total of 46 patients between February 2010 and June 2013. 44 patients completed the study (2 withdrew due to surgery cancellation); 13 had hip replacement (median age 50.9 years) and 31 had knee replacement (median age 49.1 years). 15 patients (34.1%) had a history of inhibitor prior to surgery. 6 patients (13.6%) were treated with bypassing agents perioperatively; 3 of these patients had active inhibitors present at the time of surgery. The remaining 38 patients received factor VIII or IX replacement. 22 patients (50%) received some form of mechanical prophylaxis during hospitalization, and 3 patients (6.8%) also received low molecular weight heparin (LMWH) prophylaxis. 22 patients (50%) did not receive any form of prophylaxis. 1 patient (2.3%, 95% CI 0-12%) with moderate hemophilia A and no history of inhibitor who received mechanical prophylaxis was diagnosed with symptomatic distal DVT on postoperative day 6 (confirmed by ultrasound). No patients (0%, 95% CI 0-8.0%) had asymptomatic DVT or clinically apparent PE. 16 patients (36.4%) had major bleeding during hospitalization. 4 of the 6 patients treated with a bypassing agent had major bleeding, and 1 of these patients required a re-operation due to bleeding in the replaced joint. 2 of the 3 patients who received LMWH prophylaxis had major bleeding events. 4 patients (9.1%) experienced minor bleeding.

Conclusions
In this prospective study, the observed prevalence of ultrasound detectable DVT in PWH following total knee or hip arthroplasty was very low. In the general population, when thromboprophylaxis is not administered, DVT prevalence (measured by venography) after knee and hip replacement is 40-84% and 40-57%, respectively. With mechanical prophylaxis, these rates decrease to 20.3% for hip replacement and 28.3% for knee replacement. Although these prevalence rates are expected to be somewhat lower when ultrasound is used for diagnosis, the low prevalence of DVT (2.3%) and the high rate of bleeding complications (36.4% major; 9.1% minor) in this study suggest that pharmacologic prophylaxis should not be used following knee or hip replacement in PWH with no prior history of VTE.

Disclosures:
Kempton: Baxter Healthcare: Membership on an entity’s Board of Directors or advisory committees; Novo Nordisk: Research Funding.