Thrombelastography (TEG) is a point-of-care tool that can measure clot formation and breakdown using a whole blood sample. We have previously used serial TEG analysis to define hypercoagulability and increased venous thromboembolism (VTE) risk following a major fracture requiring surgical treatment. Additionally, we have used serial TEG analysis to quantify the prolonged hypercoagulable state and increased VTE risk that ensues following a hip fracture. Recently developed cartridge-based platelet mapping (PLM) using TEG analysis can be used to activate platelets at either the adenosine diphosphate (ADP) receptor or at the Thromboxane A2 (AA) receptor, in order to evaluate clot strength when platelets are activated only through those specific receptors. This study aim was to evaluate platelet contribution to hypercoagulability, in order to identify potential therapeutic targets for VTE prevention. We hypothesized that there would be a platelet-predominant contribution to hypercoagulability following a hip fracture.

Patients aged 50 years or older with a hip fracture treated surgically were enrolled in this prospective cohort study. Exclusion criteria were: prior history of VTE, active malignancy, or pre-injury therapeutic dose anticoagulation. Serial TEG and PLM analyses were performed at admission, post-operative day (POD) 1, 3, 5, 7 and at 2-, 4-, 6- and 12-weeks post-operatively. All patients received thromboprophylaxis with low molecular weight heparin (LMWH) for 28 days post-operatively. Hypercoagulability was defined as maximal amplitude (MA; a measure of clot strength) over 65mm based on TEG analysis. Independent samples t-tests were used to compare MA values with this previously established threshold and a mixed effects linear regression model was used to compare MA values over time. Independent samples t-tests and Chi-sqaured analyses were used to compare between the surgical fixation and arthroplasty groups.

Forty-six patients with an acute hip fracture were included, with a mean age of 77.1 (SD = 10.6) years, with 61% (N=11) being female. Twenty-six were treated with arthroplasty (56.5%), while the remainder underwent surgical fixation of their hip fractures. TEG analysis demonstrated post-operative hypercoagulability (mean MA over 65mm) at all follow-up timepoints until 12-weeks. PLM identified a platelet-mediated hypercoagulable state based on elevated ADP-MA and AA-MA, with more pronounced platelet contribution demonstrated by the AA pathway. Patients treated with arthroplasty had significantly increased AA-MA compared with ADP-MA at POD 3 and at the 12-week follow-up.

Thrombelastography can be used to identify hypercoagulability and increased risk for VTE following a hip fracture. Platelet mapping analysis from this pilot study suggests a platelet-mediated hypercoagulable state that may benefit from thromboprophylaxis using an anti-platelet agent that specifically targets the AA platelet activation pathway, such as acetylsalicylic acid (ASA). This research also supports differences in hypercoagulability between patients treated with arthroplasty compared to those who undergo fracture fixation.

Major orthopaedic fractures are an independent risk factor for the development of venous thromboembolism (VTE), which are significant causes of preventable morbidity and mortality in trauma patients. Despite thromboprophylaxis, patients who sustain a pelvic or acetabular fracture (PA) continue to have high rates of VTE (12% incidence). Thrombelastography (TEG) is a whole-blood, point-of-care test which provides an overview of the clotting process. Maximal amplitude (MA), from TEG analysis, is the measure of clot strength and values ≥65mm have been used to quantify hypercoagulability and increased VTE risk. Therefore, the primary aim was to use serial TEG analysis to quantify the duration of hypercoagulability, following surgically treated PA fractures.

This is a single centre, prospective cohort study of adult patients 18 years or older with surgically treated PA fractures. Consecutive patients were enrolled from a Level I trauma centre and blood draws were taken over a 3-month follow-up period for serial TEG analysis. Hypercoagulability was defined as MA ≥65mm. Exclusion criteria: bleeding disorders, active malignancy, current therapeutic anticoagulation, burns (>20% of body surface) and currently, or expecting to become pregnant within study timeframe.

Serial TEG analysis was performed using a TEG6s hemostasis analyzer (Haemonetics Corp.) upon admission, pre-operatively, on post-operative day (POD) 1, 3, 5, 7 (or until discharged from hospital, whichever comes sooner), then in follow-up at 2-, 4-, 6-weeks and 3-months post-operatively. Patients received standardized thromboprophylaxis with low molecular weight heparin for 28 days post-operatively. VTE was defined as symptomatic DVT or PE, or asymptomatic proximal DVT, and all participants underwent a screening post-operative lower extremity Doppler ultrasound on POD3. Descriptive statistics were used to determine the association between VTE events and MA values. For the primary outcome measure, the difference between the MA threshold value (≥65mm) and serial MA measures, were compared using one-sided t-tests (α=0.05).

Twenty-eight patients (eight females, 29%) with a mean age of 48±18 years were included. Acetabular fractures were sustained by 13 patients (46%), pelvic fractures by 14 patients (50%), and one patient sustained both. On POD1, seven patients (25%) were hypercoagulable, with 21 patients (78%) being hypercoagulable by POD3, and 17 patients (85%) by POD5. The highest average MA values (71.7±3.9mm) occurred on POD7, where eight patients (89%) were hypercoagulable. At 2-weeks post-operatively, 16 patients (94%) were hypercoagulable, and at four weeks, when thromboprophylaxis was discontinued, six patients (40%) remained hypercoagulable. Hypercoagulability persisted for five patients (25%) at 6-weeks and for two patients (10%) by three months.

There were six objectively diagnosed VTE events (21.4%), five were symptomatic, with a mean MA value of 69.3mm±4.3mm at the time of diagnosis. Of the VTE events, four occurred in participants with acetabular fractures (three male, 75%) and two in those with pelvic fractures (both males).

At 4-weeks post-operatively, when thromboprophylaxis is discontinued, 40% of patients remained hypercoagulable and likely at increased risk for VTE. At 3-months post-operatively, 10% of the cohort continued to be hypercoagulable. Serial TEG analysis warrants further study to help predict VTE risk and to inform clinical recommendations following PA fractures.

Surgical management for acute or impending pathologic fractures in metastatic bone disease (MBD) places patients at high-risk for post-operative venous thromboembolism (VTE). Due to the combination of malignancy, systemic cancer treatment, and surgical treatment, VTE-risk is increased 7-fold in patients with MBD compared to non-cancer patients undergoing the same procedure. The extent and duration of post-operative hypercoagulability in patients with MBD remains unknown and thromboprophylaxis guidelines were developed for non-cancer patients, limiting their applicability to address the elevated VTE-risk in cancer patients. Thrombelastography (TEG) analysis is a point-of-care test that measures clot formation, stabilization, and lysis in whole blood samples. The TEG parameter, maximal amplitude (MA), indicates clot strength and the threshold of ≥65 mm has been used to define hypercoagulability and predict VTE events in non-cancer patients requiring orthopaedic surgery. Therefore, this study aims to quantify the extent and duration of post-operative hypercoagulability in patients with MBD using serial TEG analysis.

Consecutive adults (≥18 years) with MBD who required orthopaedic surgery for acute or impending pathologic fractures were enrolled into this single-centre, prospective cohort study. Serial TEG analysis was performed onsite using a TEG®6s haemostasis analyzer (Haemonetics Corporation, Boston, MA) on whole blood samples collected at seven timepoints: pre-operatively; on post-operative day (POD) 1, 3, and 5; and at 2-, 6-, and 12-weeks post-operatively. Hypercoagulability was defined as MA ≥65 mm. Participants received standardized thromboprophylaxis for four weeks and patient-reported compliance with thromboprophylaxis was recorded. VTE was defined as symptomatic DVT or PE, or asymptomatic proximal DVT, and all participants underwent a screening post-operative lower extremity Doppler ultrasound on POD3. Descriptive statistics were performed and difference between pre-operative MA values of participants with VTE versus no VTE was evaluated using Student's t-test (p≤0.05).

Twenty-one participants (10 female; 47.6%) with a mean age of 70 ± 12 years were enrolled. Nine different primary cancers were identified amongst participants, with breast (23.8%), colorectal (19.0%), and lung cancer (14.3%) most frequently reported. Most participants (57.1%) were hypercoagulable pre-operatively, and nearly half remained hypercoagulable at 6- and 12-weeks post-operatively (47.1 and 46.7%, respectively). VTE occurred in 5 patients (23.8%) and mean MA was 68.1 ± 4.6 mm at the time of diagnosis. Mean pre-operative MA values were significantly higher (p=0.02) in patients who experienced VTE (68.9 ± 3.5 mm) compared to those who did not (62.7 ± 6.5 mm). VTE incidence was highest in the first week post-operatively, during which time four VTE events (80%) occurred. The proportion of patients in a hypercoagulable state increased at three consecutive timepoints, beginning on POD3 (85.0%), increasing on POD5 (87.5%), and peaking at 2-weeks post-operatively (88.9%).

Current thromboprophylaxis guidelines do not consider cancer-associated risk factors that contribute to increased VTE incidence and prescription duration may be inadequate to address prolonged post-operative hypercoagulability in patients with MBD. The high rate of VTE events observed and sustained hypercoagulable state indicate that thromboprophylaxis may be prematurely terminated while patients remain at high risk for VTE. Therefore, extending thromboprophylaxis duration beyond 4-weeks post-operatively in patients with MBD warrants further investigation.