Multicenter Registry for Comparative Effectiveness Analysis of Venous Thromboembolism in Trauma Patients

The VTE related research questions, identified by the EAST Management Guidelines as needing
further study, are:

1. While numerous risk factors for VTE have been identified and reported, there are only 2
that have Level 1 evidence to support them—spine fracture and spinal cord injury. Many
of the other reported risk factors were identified in studies that did not have
protocols for surveillance, reported only on patients with symptoms, or used data from
large administrative databases such as the National Trauma Data Bank4. It has also been
shown that the frequency of diagnosis of deep venous thrombosis (DVT) increases when
more duplex imaging of the extremities is undertaken5. Thus, if an aggressive
concurrent surveillance program for DVT and aggressive work up of suspected pulmonary
embolism (PE) is undertaken:

1. Are there unknown or under-reported risk factors?

2. Is there a hierarchy of risk among the factors? For example, is a long bone
fracture associated with a higher incidence of VTE than a closed head injury?

3. Do all closed head injuries with an AIS>3 have the same degree of risk or is an
epidural hematoma more risky than a subdural hematoma?

4. What constitutes high and very high risk?

2. What is the comparative efficacy and value6 of unfractionated heparin (UH), low
molecular weight heparin (LMWH) and direct thrombin inhibitors (DTI) with or without
associated mechanical prophylaxis (MP) in preventing VTE in trauma patients? In
examining this question, the morbidity of these agents must be carefully determined,
particularly with respect to intracranial injury and intra-abdominal solid viscus
injury.

3. In trauma patients who develop VTE what is the best treatment and for how long?

4. Should all trauma patients who develop proximal deep venous thrombosis (pDVT) undergo a
workup for thrombophilia or should this be based up the degree of "inverse risk"
(inverse risk meaning a patient with a minor injury, who is thought to be at low risk,
who develops pDVT)? Similarly, should trauma patients who develop pulmonary embolism
(PE) undergo a workup for thrombophilia or should this be based up the degree of
"inverse risk" [question 4 adds importance to answering questions 1a and 1b]?

5. A recent meta-analysis of observational studies suggests that prophylactic inferior
vena cava filters (PICVF) significantly reduce the risk of PE (OR: 0.09-0.49)7. The
authors of the meta-analysis point out a number of methodological flaws with the
studies selected for the analysis. Most importantly, all were retrospective studies
with historical controls and the use of pharmacologic prophylaxis was not uniform among
the studies evaluated. Despite this report, there is continued significant practice
variation in the use of PIVCF and the role of PIVCF in the care of trauma patients
remains at question. Thus, if an aggressive concurrent surveillance program for DVT and
aggressive work up of suspected PE is undertaken:

1. Are all patients perceived to be at high risk for VTE who also have a relative or
absolute contraindication to pharmacologic prophylaxis receiving a PIVCF?

2. Do PIVCF reduce the risk of PE in trauma patients in whom risk adjustment has been
done?

3. Do PIVCF have value for the trauma patient at very high risk for VTE, the high
risk trauma patient or the moderate risk trauma patient? In examining this
question, the morbidity of PIVCF must be carefully determined, particularly with
respect to their placement (including local complications at the insertion site,
their migration and degree of tilt) and long-term complications.

6. Because most DVT is asymptomatic the clinical examination is extremely insensitive.
Therefore, surveillance of the lower extremity venous systems is necessary. However,
the use of routine surveillance is controversial. It is also known that venous duplex
exams, while very accurate in the symptomatic patient, can be quite insensitive in the
asymptomatic patient. In addition, surveillance scanning is hampered by external
fixators and wounds (as many as 30% of extremities cannot be scanned for this reason10.
Finally, it is not uncommon for trauma patients to have a PE (even a fatal PE) with
negative followup surveillance of the lower extremity (LE) and upper extremity (UE)
venous systems. This would suggest either that the surveillance duplex was inaccurate,
or the clot arose in a vein that could not be well interrogated by duplex (i.e., the
hypogastric), or that the clot arose de novo in the pulmonary artery11. Thus, if an
aggressive concurrent surveillance program for DVT and aggressive work up of suspected
PE is undertaken:

1. Does "protocolized" surveillance (surveillance of asymptomatic patients) have
value? In other words, does the quality of the outcome (determining the presence
of asymptomatic thrombus in the vein of an extremity) justify the cost?

2. What constitutes the most effective protocol in terms of when the initial scan
should be done and the frequency of subsequent scans?

3. What is the fate of peroneal vein and tibial vein clot? Does it vary depending on
the degree of risk (i.e., more likely to propagate in patients who are at the
highest risk compared to patients with lower risk)? The same question could be
posed with respect to soleal vein or gastrocnemius vein clot.

4. Does magnetic resonance venography have a role in high risk trauma patients as a
surveillance modality—particularly those with pelvic fractures or severe LE
fractures that cannot be reliably scanned?

5. Does contrast venography have a role in high risk trauma patients as a
surveillance modality, particularly in patients who have had a PE and who have a
negative duplex?

6. Since it has been shown by numerous authors that there is surveillance bias with
regard to the diagnosis of DVT (i.e., the diagnosis is more often reported at
hospitals doing more frequent scanning5, does the frequency of the diagnosis of PE
increase as the number of chest CT angiograms are performed?

7. Recent studies suggest an association between local14 or systemic11 inflammation and
pulmonary thrombosis (perhaps not embolism). Is there an increased risk of DVT or
primary pulmonary thrombosis for trauma patients who have an associated inflammatory
process such as sepsis, urinary tract infection (UTI) or pneumonia (PNA)? What
constellation of local injury puts a patient at risk for pulmonary thrombosis?

We are proposing to perform an extensive literature review on each of these questions to
produce a state of the art publication in follow-up of the EAST Management Guidelines and to
provide a platform for a multicenter study of each or all of these questions.

METHODS

1. Literature Review. The literature review of each question will cover the period
1989-2011. The year 1989 was selected because that was the year of the last major
literature review (the exception is the review by Rogers (ref) who authored the EAST
Management Guidelines). Each review will begin with a literature search performed under
the guidance of a medical librarian using appropriate key words and MeSH (medical
subject headings). The bibliography of key articles will also be reviewed for pertinent
literature. Authors of the review will select criteria relevant to the question that
will be used to select articles to be used in the review.

2. Center Selection. Centers selected for inclusion in the multicenter studies must have
an interest in VTE, a research and publication track record on the subject, and be
willing to participate by submitting their de-identified data to Scripps Mercy. The
centers will be selected by Drs. Steven Shackford and Frederick Rogers, recognized
experts in the field of VTE in trauma.

3. Study Design. Observational cohort.

4. Patients. All adult (age > 18) trauma patients admitted to each of the centers with an
expected length of stay (LOS) of > 72 hours will be eligible for inclusion.

5. Interventions. Each patient will undergo a risk assessment for VTE in compliance with
the Surgical Care Improvement Program (SCIP-VTE 1 & 2)12, which is currently being done
by most hospitals. Provided that there are no absolute or relative contraindications,
each patient will receive appropriate VTE prophylaxis in compliance with the SCIP for
the duration of their hospitalization. The use of SCIP is a condition of participation
in Medicare and poses no additional risk and no alteration in care of trauma patients.
Surveillance for VTE will not be affected by participation in the study, but will be
whatever is usual and customary for the participating institution. Similarly, the
management of patients who develop VTE will not be affected by participation in the
study, but will be whatever is usual and customary for the participating institution.

6. Data. The following data will collected concurrent with care:

a. Institutional: i. Unique hospital identifier ii. Type:

1. Teaching, formal university affiliation

2. Teaching, free-standing surgical residency training program

3. Non-teaching (all not included in the above) iii. Participation in the American College
of Surgeons (ACS) Trauma Center Verification Program:

1. If yes, Level _____

2. No iv. Average number of trauma patients admitted annually over each of the last 5
years٭:

1. Year 1-______ Year 2-______ Year 3-______ Year 4-______ Year 5-______

v. VTE surveillance program description:

1. Duplex weekly

2. Duplex twice weekly

3. Duplex once during admission

4. Selective Surveillance (please describe, limit to 250 characters):
_________________________________________________ vi. Participation in the ACS National
Trauma Data Bank (may have more than one selection):

1. Yes

2. Participation in a home grown, regional or statewide registry vii. Do you have a
computerized order entry system with clinical decision support? If so, please specify
(250 characters).

________________________________________________________

b. Patient: i. Demographics and generic trauma-related data:

1. Age (in years) ٭

2. Gender

1. Male

2. Female

3. Race/Ethnicity

1. Caucasian

2. African American

3. Hispanic/Latino

4. Asian

5. Pacific Islander

6. Native American

7. Unknown ethnicity/Other

4. Admission vital signs

1. Systolic Blood Pressure (SBP)

2. Pulse Rate

3. Temperature

5. Shock (indicate all that apply):

a. SBP <80 mmHg (Y/N) b. Base deficit > -5 (Y/N) c. Arterial or venous lactate > 4
(Y/N)

6. Glasgow coma scale (GCS) (at time of admission)

7. Height (in meters)

8. Weight (in Kg)

9. Injury Severity Score

10. Mechanism:

1. Blunt

2. Penetrating

11. Probability of survival using the Trauma score- Injury Severity Score (TRISS)
methodology

12. Head Abbreviated injury score (AIS)

13. Lower extremity AIS

14. Chest AIS

15. Abdominal AIS

16. Spine AIS

17. List of all injuries٭ (No text! Coded from Vermont Performance Improvement Manual)
(n=1-∞)

18. List of all complications/morbidities not present on admission٭ (No text! Coded from
Vermont Performance Improvement Manual) (n=1-∞)

19. List of all surgical procedures (No text! current procedural terminology (CPT) or ICD-9
codes) ii. Pertinent past medical history (existing prior to admission):

1. History of PE (Y/N)

2. History of DVT (Y/N)

3. Any VTE in a first degree relative (Y/N)

4. History of a thrombophilic disorder٭ (Y/N)

5. History of concurrent cancer٭ a. Hematopoietic b.
Lymphatic c. Visceral d. Prostate e. Uterine f. Ovarian g. Breast h. Melanoma

6. History of previous cancer٭

a. Hematopoietic b. Lymphatic c. Visceral d. Prostate e. Uterine f. Ovarian g. Breast
h. Melanoma

7. History of inflammatory bowel disease٭

8. Hormone replacement therapy٭

a. If yes, what agent?

9. Contraceptive medications containing estrogen

10. Pregnant or recently post-partum٭

11. Smoking, current

a. If yes, estimate pack years:_______

12. Previous smoker, but quit.

a. If yes, estimate pack years:_______

13. Ambulatory prior to admission (Y/N)?٭

14. Taking Warfarin, Xa inhibitor, DTI, antiplatelet, or ASA (325mg) at time of admission?

a. If yes, was it held temporarily following admission?٭ c. Hospital Course٭ (TREK=Date
and [Military time] of each occurrence) of pt movement to new care > i. Resuscitation bay ii. ICU1 iii. ICU2 iv. ICU… v. OR1
vi. OR2 vii. OR… viii. Ward ix. Morgue x. Discharge form hospital

d. Treatment related data (recorded DAILY) i. Ventilation ٭ (Y/N)

1. If yes, total ventilator days _______ ii. Transfusion in last 24 hrs٭
(Y/N) (if yes, drop down below to indicate units given)

1. Fresh frozen plasma (FFP) _________

2. Packed Red Blood Cell (PRBC) _________

3. Prothrombin Complex Concentrate (PCC) ________

4. Cryoprecipitate __________

5. Platelets __________ iii. Central venous catheter placement in last 24
hrs (if yes, site)

1. Subclavian (R/L)

2. Femoral (R/L)

3. Internal jugular (R/L) iv. Infectious complications in preceding 24 hours

1. UTI

2. Pneumonia

3. Surgical site infection٭ a. Superficial b. Deep

4. Intra-abdominal abscess

5. Septicemia

6. Other: ___________ (50 characters) v. Activity status

1. Ambulatory

2. Bed rest

3. Non-weight bearing

a. One leg b. Both legs

e. VTE related data (recorded DAILY):

1. Patient risk level٭

1. Very high

2. High

3. Moderate

4. Low

2. Lower extremity duplex ultrasound (recorded on days performed):

a. Ordered for (Select one of the following): i. Institutional surveillance
ii. Symptoms b. Adequately imaged sites: (each site: Yes/No/Not attempted) i. Right
Gastrocnemius/soleus imaged ii. Right Tibials/peroneal imaged iii. Right Popliteal
imaged iv. Right Femoral imaged v. Right External iliac imaged vi. Left
Gastrocnemius/soleus imaged vii. Left Tibials/peroneal imaged viii. Left Popliteal
imaged ix. Left Femoral imaged x. Left External iliac imaged

3. Upper extremity duplex ultrasound (recorded on days performed):

a. Ordered for (Select one of the following): i. Institutional surveillance
ii. Symptoms b. Adequately imaged sites: (each site: Yes/No/Not attempted) i. Right
Basilic/Cephalic imaged ii. Right Subclavian/Axillary imaged iii. Right Brachial imaged
iv. Right Internal Jugular imaged v. Left Basilic/Cephalic imaged vi. Left Brachial
imaged vii. Left Subclavian/Axillary imaged viii. Left Internal Jugular imaged

4. Indicate cause of inadequate imaging (upper or lower extremity):

a. Patient uncooperative/refused b. Plaster immobilizer c. External fixators d. Wounds
or dressings e. Other: ____________________________ (limit to 50 characters) text>

5. VTE events٭ (indicate all that apply, recorded DAILY):

a. Intramuscular clot (gastrocnemius or soleus) b. Tibial or peroneal vein clot c.
Below knee popliteal vein clot d. Above knee popliteal vein clot e. Femoral vein clot
f. Iliac vein clot g. Cephalic or basilic vein clot h. Brachial vein clot i. Axillary
vein clot j. Jugular vein clot k. Subclavian vein clot l. Innominate vein clot i.
Method of detection? m. IVC clot i. Method of detection?
n. Mesenteric vein clot i. Method of detection? checked, free text> o. Portal vein clot i. Method of detection? text> p. Pulmonary embolism: i. Method of detection:

1. CT-PA

2. V/Q scan

3. Pulmonary angiogram

4. Incidental (consequent to imaging for another problem)

5. Autopsy

6. Other: __________________(limit to 50 characters) ii. Detail of clot
(indicate all that apply)

1. saddle

2. lobar

3. segmental

4. sub-segmental

5. unclassified

6. Work up for suspected VTE (recorded DAILY) in past 24 hours:

a. INDICATIONS-all that apply: i. Extremity pain ii. Extremity swelling
iii. Extremity discoloration iv. Shortness of breath/tachypnea v. O2 saturation
decrease vi. Tachycardia vii. Chest pain viii. Other_________________ (limit to 50
characters) b. Duplex: (Y/N) if Y, result: POS/NEG c. Venography: (Y/N) if
Y; result POS/NEG d. CT-PA protocol: (Y/N) if Y; result POS/NEG e. Pulmonary
angiogram:(Y/N) if Y; result POS/NEG f. Ventilation/perfusion scan: (Y/N) if Y; result
POS/NEG g. Diagnosed VTE by clinical suspicion (explain, 500 characters):
____________________________________

7. Treatment for VTE related event (recorded DAILY): menu> a. Heparin drip b. Enoxaparin c. Fondaparinux d. Rivoraxaban e. Coumadin f.
Agatroban g. Inferior vena cava filter (Y/N) rationale: i. PE on
adequate therapeutic anticoagulation ii. Hemorrhagic complication (see below) iii.
Contraindication to anticoagulation (specify): _____________________ (limit to 200
characters) iv. If therapeutic filter placed:

1. Insertion site

1. R/L Femoral vein

2. R/L Internal Jugular vein

3. R/L Subclavian vain

4. Other: ______ (limit 50 characters)

8. Complications (recorded DAILY on all patients): answers below>

1. HIT

2. Evidence of GI bleeding:

i. None ii. Bloody gastric secretions or emesis iii. Guaiac positive stools or hematochezia
iv. Other: _______ (limit 50 characters) c. Evidence of GU bleeding: i. None ii.
Gross blood in urine iii. Other: _______ (limit 50 characters) d. Wound hematoma
e. Hemorrhage from a recent wound٭ i. Major ii. Minor f. Transfusion during last 24 hours
(rationale): i. Gradual reduction in hemoglobin to our institutional transfusion
trigger ii. Near out institutional trigger and going to surgery with expected blood loss
iii. Hemorrhagic shock iv. Other: _________ (limit to 100 characters)

9. Prophylaxis (recorded DAILY):

a. Mechanical٭ (intermittent compression): below> i. Both legs below knee ii. One leg (rationale):

1. Orthopedic device (i.e., plaster immobilizer, external fixators, etc)

2. Wounds (i.e., dressings, wound vac, etc

3. Other: ___ (limit to 100 characters) iii. None (rationale):

1. Orthopedic device (i.e., plaster immobilizer, external fixators, etc)

2. Wounds (i.e., dressings, wound vac, etc

3. Other: ___ (limit to 100 characters) b. Pharmacologic:٭ expand with answers below> i. Heparin

1. Dose: (5000U, 7500U, other_______) (25 characters)

2. Frequency: (Q8/Q12, other _______) (25 characters) ii. Low molecular weight heparin

1. Dose: (30mg, 40mg, other_______) (25 characters)

2. Frequency: (Q12, Daily, other _____) (25 characters) iii. Other pharmacologic
prophylaxis agent

1. Name ____________ (25 characters)

2. Dose ____________ (25 characters)

3. Frequency ________ (25 characters) iv. Missed/held doses in last 24 hours (Y/N)

1. Rationale for missed/held dose: ________ (250 characters) c. Prophylactic inferior vena
cava (IVC) filter (recorded Daily): i. None ii. Rationale for placement (Cannot
receive pharmacologic prophylaxis because):

1. Hemorrhagic complication

2. HIT

3. Solid organ injury

4. Closed head injury

5. Spinal cord injury

6. Pelvic fracture with hemorrhage٭

7. Multiple long bone fractures

8. Spine fracture

9. Retroperitoneal hematoma

10. Other____________ (50 characters) iii. Insertion site

1. R/L Femoral vein

2. R/L Internal Jugular vein

3. R/L Subclavian vein

4. Other: _________ (50 characters)

10. IVC filter placement (prophylactic or therapeutic)

1. If placed, filter type:

1. Cook Celect™ 2. Cook Tulip™ 3. Cook Bird's Nest™ 4. Bard Simon Nitinol™ 5. Bard G2™
6. Bard Eclipse™ 7. Bard Meridian™ 8. Bard Denali™ 9. ALN filter™ 10. Cordis OptEase™
11. Cordis TrapEase™ 12. Argon Option filter™ 13. SafeFlo™ 14. Vena Tech LGM™ 15. Vena
Tech LP™ 16. Other:_______ (50 characters)

2. If placed, location of placement:

1. Bedside

2. Radiology

3. OR

3. Insertion site complications: 1. Local hematoma 2. Local hemorrhage
requiring intervention:

a. Transfusion b. Procedure 3. DVT at site 4. IVC occlusion 5. Device misplacement 6.
Other__________ (50 characters) d. Complications: (Indicate days from insertion to
occurrence)

1. Filter tilt _____ (day number or N/A)

2. Migration ______ (day number or N/A)

3. Caval thrombosis _____ (day number or N/A)

4. Strut fracture _____ (day number or N/A)

5. Pain ______ (day number or N/A)

6. Extrusion of filter ______ (day number or N/A) e. Filter retrieval

1. Unsuccessful, patient lost to followup 2. Unsuccessful, patient refused 3. Unsuccessful,
attempted, but failed to retrieve filter 4. Technical success without any complication 5.
Technical success with:

1. Hemorrhage

2. Hematoma

3. Other_________ (50 characters)

f. Service inserting filter:

1. Interventional radiology

2. Vascular surgery

3. trauma /critical care

4. other:___________ (50 characters)

7. Analysis. Patients will be stratified according to their perceived risk (based on the
existing literature) on their first hospital day into one of the risk categories specified
by the American College of Chest Physicians (ref). This initial risk assessment in the
current basis for the determination of the need for prophylaxis. The effectiveness and
morbidity of prophylaxis will be determined in the various risk categories concurrent with
care. The effectiveness and value of surveillance protocols as well as the rationale for the
use of prophylactic vena cave filters will be determined.

8. Patient Safety. Patients will remain anonymous; all patient identifiers will be purged
from the data at the originating center. Patient care will NOT be affected in any way by
participation in the study. Data recorded on paper will be kept in the Scripps Mercy Trauma
Research Office in locked filed cabinets. Digital data will be kept on either encrypted
disks or in computers requiring password access.

9. Importance. The results of this study will add greatly to our understanding of the
comparative effectiveness of the prophylaxis, surveillance and treatment of VTE in trauma
patients 10. Data Input/Quality Assurance. All data will be collected via a secure web based
data collection tool (Research Electronic Data Capture - REDCap). Each participating
institution will have a secure login access code to input de-identified patient information.
REDCap allows data acquisition with set perimeters per question to ensure data quality.
Limiters per response and questions with 'branching logic' points have been created with
'must answer' data protection elements enabling real time data quality assurance. Review of
interim data will be periodic and based on the REDCap report building function. Missing data
will be accessed and reported to the reporting data center for validation of values.
Depending on the type of analysis performed with the data elements, individual missing data
may be inputted or dropped from each of the final analysis.

Inclusion Criteria:

- Admitted to the hospital for care of injuries

- Have a greater than minimal (moderate to highest) level of VTE risk

Exclusion Criteria:

- Discharged prior to 24 hours in hospital

- Minimal VTE risk