The Clinical Utility of Thrombelastography in Guiding Prophylaxis of Venous Thromboembolism Following Trauma

This preliminary/pilot study involves a prospective, randomized, open-label, parallel group comparison of Denver Health's current standard of care for prevention of venous thromboembolism (VTE), commonly known as blood clots, using LMWH (Fragmin) 5000IU subcutaneously daily, with a thrombelastography (TEG)-guided, algorithm-based, individualized regimen of LMWH (Fragmin) plus/minus anti-platelet therapy (aspirin) guided by platelet mapping, in patients admitted to the SICU following trauma.

Approximately 50 trauma patients for whom prevention of VTE with LMWH is indicated, will be enrolled over a six month period.

The specific aims of this study are as follows:

• To determine the incidence of, and to characterize, hypercoagulability using TEG and conventional clinical coagulation testing (APTT, INR), Antithrombin III levels and Protein C activity.
• In the group of patients receiving LMWH (Fragmin) therapy alone for prevention of VTE:

• to assess the anticoagulant effect of standard LMWH (Fragmin) dosing (5000IU subcutaneously once daily) using TEG and Anti-Factor Xa level measurement, and
• to determine the extent of correlation of relevant TEG parameters with measured Anti-Factor Xa levels (U/ml).
• To assess whether TEG is a useful clinical tool for monitoring and optimizing prophylactic LMWH (Fragmin) therapy and for identifying the need for anti-platelet therapy to minimize the risk of VTE in these patients.
• To evaluate the clinical utility of platelet mapping for guiding anti-platelet therapy in those patients for whom it is indicated by TEG results.
• To determine the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in each randomized group and in the subgroup receiving anti-platelet therapy in addition to LMWH (Fragmin) for prevention of VTE.

The overall aim is to utilize the above data to evaluate a) the adequacy of our standard Fragmin dosing regimen (5000IU subcutaneously once daily) alone for prevention of VTE in our trauma/SICU patients, b) the need for anti-platelet agents in addition to LMWH (Fragmin) for prevention of VTE in our population, and c) to validate/further develop the TEG-guided algorithm for optimal prophylaxis of VTE using LMWH (Fragmin) plus/minus anti-platelet therapy guided by platelet mapping.

Inclusion criteria

• age at least 18 years,
• blunt or penetrating trauma requiring admission to the SICU
• requirement for LMWH (Fragmin) therapy for prophylaxis of VTE as standard of care, and
• informed consent by patient, legally authorized representative or proxy decision maker (if patient incompetent to provide) obtained and documented.

Exclusion criteria

Presence of any of the following absolute contraindications to LMWH (Fragmin) therapy:

• known hypersensitivity to dalteparin sodium,
• known hypersensitivity to heparin or pork products,
• thrombocytopenia associated with positive tests for antiplatelet antibody in the presence of Fragmin,
• history of heparin-induced thrombocytopenia (HIT),
• chronic liver disease (bilirubin >2 mg/dl) or kidney insufficiency (CrCl <30mL/min),
• intravascular thrombolytic therapy within 24 hours,
• resuscitation that required massive transfusion (>10 units RBC within 6 hours),
• ongoing resuscitation for hemorrhagic shock,
• known bleeding disorder or coagulopathy (INR >2 not on warfarin),
• thrombocytopenia (platelets <20K/uL),
• subdural or epidural hematoma.

Or

Presence of any of the following relative contraindications to LMWH (Fragmin) therapy:

• new intracranial lesions, neoplasms or monitoring devices,
• extravascular thrombolytic therapy,
• severe uncontrolled hypertension,
• arterial dissection
• recent (within 12 hours) intraocular surgery (prior or planned),
• recent (within 72 hours) intracranial or spine surgery (prior or planned),
• conditions associated with increased risk of hemorrhage, e.g. active gastrointestinal ulceration, angiodysplastic disease, gastrointestinal bleeding within the past six months, bacterial endocarditis, history of hemorrhagic stroke, diabetic retinopathy.

Or

Presence, or removal within the last 12 hours, of an indwelling epidural or spinal catheter, OR recent (within the last 12 hours) or planned neuraxial (spinal/epidural) anesthesia or spinal puncture.

Or

Per history taken from patient or family, concomitant or known use within one week prior to hospitalization, of drugs affecting hemostasis such as NSAIDS, platelet inhibitors or other anticoagulants, except as specified in this protocol.