Table 2 Research priorities identified by the panel

Timing of pharmacologic VTE prophylaxis in non-operative blunt solid organ injuries

• Further high-quality RCTs or prospective multi-center studies are important to provide greater certainty comparing early pharmacological VTE prophylaxis versus late prophylaxis in patients with solid organ injuries

• Future studies shall consider reporting direct clinical outcome (bleeding including major and minor such as hematoma requiring evacuation or retroperitoneal bleeding) rather than reporting post-prophylaxis blood transfusion as surrogate markers of bleeding complications

None identified

Timing of pharmacologic VTE prophylaxis in TBI [102]

Isolated blunt TBI with low risk of bleeding progression:

• Further high-quality RCTs with adequate power are important to provide greater certainty comparing early pharmacological VTE prophylaxis versus late prophylaxis in patients with TBI and low risk of ICH progression. There is a plan for a definitive follow-up RCT in the low-risk Parkland arm (DEEP II)

• Future research could focus on clarifying what characteristics of TBI low risk of ICH progression utilizing Brain Injury Guideline criteria and Parkland criteria and using more practical cut-off for definition of early pharmacological VTE prophylaxis

• Future research could focus on correlating radiographic TBI progression with clinical neurologic status as dichotomizing TBI radiographically as either having “progressed” or “not progressed” may fail to quantify the degree of expansion and association with clinical sequelae

• Future research is needed on cost-effectiveness studies in Saudi Arabia

There is currently a prospective RCT completed recruitment which is looking at the timing of pharmacological VTE prophylaxis in TBI comparing early (36–48 h) versus late (> 96 h) initiation of pharmacological VTE prophylaxis (OPTTICH trial)

ClinicalTrials.gov Identifier: NCT01589393

Isolated blunt TBI with high risk of bleeding progression:

• Further high-quality RCTs with adequate power are important to provide greater certainty comparing early pharmacological VTE prophylaxis versus late prophylaxis in patients with TBI and high risk of ICH progression

There is a plan for pilot RCT on the medium Parkland arm known as delayed Versus Early Enoxaparin Prophylaxis III study (DEEP III)

TBI requiring neurosurgical intervention:

• Further high-quality RCTs with adequate power are important to provide greater certainty comparing early pharmacological VTE prophylaxis versus late prophylaxis in patients with TBI requiring ICP monitoring or EVD or craniotomy or craniectomy

None identified

Timing of pharmacologic VTE prophylaxis for spine trauma or fracture and/or SCI [102]

• Further high-quality RCTs with adequate power are important to provide greater certainty comparing early pharmacological VTE prophylaxis versus late prophylaxis in patients with SCI and managed non-operatively and operatively

• Future studies shall consider reporting direct outcome (intraspinal hematoma, epidural hematoma development or expansion after starting VTE prophylaxis) rather than using surrogate outcomes

• More studies are needed to evaluate the subsets of spine-injured patients who require more or less aggressive approaches to early VTE prophylaxis initiation and the impact by spine segment involved (cervical, thoracic, or lumbar), or completeness of injury (complete versus incomplete SCI)

• Pharmacoeconomic studies are needed to compare the cost-effectiveness between the two arms

• More studies are needed to evaluate the need for routine follow-up imaging to check for hematoma expansion after initiation of VTE prophylaxis and MRI role in the diagnosis or exclusion of epidural hematoma prior to VTE prophylaxis

None identified

Type of pharmacologic VTE prophylaxis

• Bleeding complications in trauma patients is limited by inconsistent and non-validated bleeding definitions. Clinically meaningful outcomes are required for future research

• The commonly used enoxaparin 30 mg subcutaneously twice a day regimen which is considered to be an underdosing (new WTA guideline suggests enoxaparin 40 mg subcutaneously twice a day for VTE prophylaxis [5]). Therefore, true comparative studies are needed with this new dosing regimen regarding efficacy for VTE prevention and safety

None identified

Dose of pharmacologic VTE prophylaxis

• More studies are needed focusing on patient-centered outcomes (VTE, mortality) as primary outcome rather than using surrogate marker (on-target anti-Xa level) as primary outcome and differentiate between major and minor bleeding complications when reporting results

• Further investigations are needed to determine specific patient subgroups most likely to benefit from intermediate dose prophylaxisCost-effectiveness analysis studies are also needed

• Implications of ATIII activity in VTE formation

There is an ongoing study investigating weight-based enoxaparin dosing in trauma patients would provide valuable information once completed

ClinicalTrials.gov Identifier: NCT01916707

Mechanical VTE prophylaxis

• Further high-quality comparative studies in trauma patients using appropriate clinical outcomes would be of value to add more certainty to recommendation

• Studies enabling identification of baseline risk would be valuable to identify patients particularly likely to benefit from combined prophylaxis strategies

• The duration of compression (hours per day) needed for VTE prevention with IPC; device standardization

• Need for economics study to assess the cost-effectiveness of these interventions

There is an ongoing study investigating sequential compression device versus combined sequential compression device and dalteparin in TBI patients

ClinicalTrials.gov Identifier: NCT03559114

Routine duplex ultrasonography (US) surveillance [103]

• More RCTs with possible adaptive study design and Bayesian statistical methods are needed for comparing effectiveness of surveillance US versus prophylactic inferior vena cava filter versus combination approach to prevent fatal PE as clinically important VTE outcomes

• More study is needed to define the frequency of surveillance US

• Further investigation is needed to further characterize the method of VTE risk assessment in determining which subpopulations will benefit most from routine surveillance

• More studies are needed for the utility of upper extremities and neck US screening

There is currently an ongoing RCT (Diagnosing Deep-vein Thrombosis Early in Critically ill Patients “DETECT” trial) comparing surveillance US for lower limb DVT in high-risk medical-surgical ICU patients to a clinician-directed approach

ClinicalTrials.gov Identifier: NCT05112705

Prophylactic IVCFs

• Cost-effectiveness analysis is probably needed in Saudi Arabia to determine if costs of using prophylactic filter offset by the savings from having a lower incidence of symptomatic PE and its complications

• Newly developed, absorbable IVC filters, which are absorbed over a 32-week period, have demonstrated an ability to prevent PE for at least 5 weeks after placement in a swine mode. RCT in humans is needed

• RCT with adequate power is probably also needed for evaluating the effect of retrievable IVC filter in reducing PE-related death rather than composite outcome of PE or death or reporting all-cause of mortality

None identified

Other areas [104,105,106]

• In trauma patients, PE frequently occurs in the absence of DVT (are not embolic) and is thought to originate de novo in the lungs (pulmonary thrombosis) as a result of inflammation, endothelial injury, and the hypercoagulable state caused by the injury itself. More studies are needed to evaluate the impact of available VTE prophylaxis strategies in prevention of this distinct clinical entity

None identified