Key Guidelines and Evidence

American College of Chest Physicians Antithrombotic Guidelines (CHEST 2012):

• Recommends low-dose unfractionated heparin (LDUH) or low-molecular-weight heparin (LMWH) over no prophylaxis in critically ill patients.
• Suggests LMWH or LDUH over vitamin K antagonists like warfarin for prophylaxis.
• Mechanical prophylaxis with intermittent pneumatic compression is preferred in patients with high bleeding risk until it abates.
• In trauma patients with low-moderate VTE risk and low bleeding risk, suggests LMWH, LDUH or intermittent pneumatic compression over no prophylaxis.
• In surgical patients with moderate VTE risk and low bleeding risk, recommends LMWH, LDUH or intermittent pneumatic compression.

American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients | Blood Advances | American Society of Hematology (ashpublications.org)

Acutely ill medical patients: pharmacological VTE prophylaxis

Recommendations 1, 2, and 3.

In acutely ill medical patients,

• In acutely ill medical patients, the guidelines suggests using UFH, LMWH, or fondaparinux rather than no parenteral anticoagulant
• In acutely ill medical patients, the guidelines suggests using LMWH or fondaparinux compared to UFH

Critically ill medical patients: pharmacological VTE prophylaxis

Recommendations 4 and 5.

• In critically ill medical patients, the guidelines recommends using UFH or LMWH over no UFH or LMWH
• In critically ill medical patients, the guidelines suggests using LMWH over UFH

Prophylaxis of Venous Thrombosis in Neurocritical Care Patients: An Evidence-Based Guideline: A Statement for Healthcare Professionals from the Neurocritical Care Society

(FINAL_COPY_DVT.pdf (higherlogicdownload.s3.amazonaws.com)

• Patients with neurological conditions like stroke, brain tumors, spinal cord injury, and traumatic brain injury are at increased risk of venous thromboembolism (VTE) due to immobility and other factors.
• Evidence is limited, but pharmacologic VTE prophylaxis with heparin (unfractionated heparin or low molecular weight heparin) appears to reduce risk of DVT and PE in most neurocritically ill patients, with acceptable bleeding risk.
• Timing of initiation depends on type of neurological injury. For ischemic stroke, prophylaxis can start early. For hemorrhagic stroke, traumatic brain injury, or after neurosurgery, delay prophylaxis 1-2 days.
• For high bleeding risk, mechanical prophylaxis with intermittent pneumatic compression is recommended over pharmacologic prophylaxis. Graduated compression stockings are not recommended as sole prophylaxis.
• Combined pharmacologic and mechanical prophylaxis can be considered for additive risk reduction in some patients.
• Duration of prophylaxis should be at least for the acute hospital stay. Extended prophylaxis can be considered in those with impaired mobility.
• Key principles are assessing thrombosis and bleeding risks regularly and individualizing prophylaxis approach based on benefits versus harms. More research is needed on VTE prevention specifically in neurocritical care populations.

In summary, VTE prophylaxis is important in neurocritically ill patients but requires tailored approaches considering the neurological injury, bleeding risk, and individual factors of each patient.

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Relevant studies:

Select Studies of Dosing in the Obese Population

Study	Population	Intervention	Outcome
Sebaaly J, Covert K1	Low- and high-body-weight patients	Enoxaparin for VTE prophylaxis and treatment	Low-body-weight patients may benefit from 30 mg subcutaneously daily for VTE prophylaxis, and standard weight-based dosing for VTE treatment. In patients with BMIs ≥40 kg/m2, 40 mg subcutaneously twice daily is recommended, with consideration for higher doses in patients with BMIs ≥50 kg/m21.
Beall J, Woodruff A, Hempel C, Wovkulich M, Zammit K2	Obese hospitalized patients	High-dose (7500 units every 8 hours) vs conventional-dose (5000 units every 8 hours) subcutaneous unfractionated heparin for VTE prophylaxis	The study failed to demonstrate a statistically significant reduction in the rate of nosocomial VTE in obese patients who received high-dose heparin thromboprophylaxis. Despite receiving a higher heparin dose, no increased risk of bleeding was observed in the high-dose group2.
Joy M, Tharp E, Hartman H, et al3	Overweight and obese patients	High-dose (7500 units every 8 hours) vs low-dose (5000 units every 8 hours) subcutaneous unfractionated heparin for VTE prophylaxis	High-dose unfractionated heparin did not reduce the incidence of VTE in a cohort of hospitalized overweight and obese patients. However, high-dose unfractionated heparin was associated with an increased risk of major bleeding, particularly in those patients with a BMI >40 kg/m2 who were concomitantly receiving aspirin3.

VTE in Trauma Population

The article “Relationship between anti-Xa level achieved with prophylactic low-molecular weight heparin and venous thromboembolism in trauma patients: A systematic review and meta-analysis” by Verhoeff, Kevin MD, BMSc; Raffael, Kendra MD; Connell, Matthew MD; Kung, Janice Y. MLIS; Strickland, Matt MD, MBA; Parker, Arabesque MD; Anantha, Ram V. MD, MSc was published in the Journal of Trauma and Acute Care Surgery in August 2022¹.

This study aimed to answer three questions for trauma patients:

1. Is there any association between anti-Xa and VTE?
2. Does dose adjustment improve prophylactic anti-Xa rates?
3. Does dose adjustment improve anti-Xa adequacy and VTE compared with standard dosing?

The study included a systematic search of MEDLINE, Embase, Scopus, and Web of Science in May 2021. Two author reviews included trauma studies that evaluated low molecular weight heparin chemoprophylaxis, reported anti-Xa level, and evaluated more than one outcome.

The results showed that achieving adequate anti-Xa was associated with reduced odds of VTE (4.0% to 3.1%; odds ratio [OR], 0.52; p = 0.03). Analysis demonstrated that 768 (75.3%) patients achieved prophylactic anti-Xa with adjustment protocols. The study suggested that dose-adjusted chemoprophylaxis achieves prophylactic anti-Xa more frequently (OR, 4.05; p = 0.007) but without VTE (OR, 0.72; p = 0.15) or pulmonary embolism (OR, 0.48; p = 0.10) differences¹.

Verhoeff K, Raffael K, Connell M, et al. Relationship between anti-Xa level achieved with prophylactic low-molecular weight heparin and venous thromboembolism in trauma patients: A systematic review and meta-analysis. J Trauma Acute Care Surg. 2022;93(2):e61-e70