Table 2:

Alternative LMWH Dosing Strategies - Summary of evidence and considerations for practice

Alternative Dosing Strategy	Study	Study Design	Summary of Evidence	Considerations for Practice
Using Anti-Xa Levels to Dose Adjust Low Molecular Weight Heparin	Studies suggesting reduction in VTE using anti-Xa levels to guide LMWH dosing:			• There is likely utility in using anti-Xa levels to guide dosing of LMWH. • Conflicting data regarding anti-Xa levels and VTE rates may be due to difficulty in consistently obtaining appropriately timed anti-Xa levels. • Antithrombin III may play a role in explaining the inconsistencies between anti-Xa levels and VTE rates. This role is still under investigation.
	Malinoski 2010	Single center, prospective cohort	50% of the study sample had low anti-Xa levels and were found to have significantly more DVT than those with prophylactic levels (37% vs. 11%, p=0.026)
	Lin 2011	Single center, retrospective	In burn patients, initial anti-Xa level was sub-prophylactic in 76.2% and never achieved prophylactic levels in 17.8% of the sample. Median LMWH dosing required to achieve prophylaxis was 40-mg every 12-hours.
	Singer 2016	Single center, retrospective	Anti-Xa level guided LMWH dosing reduced VTE incidence over 1 year to 7.1% from 20.5% in the historical cohort (p=0.031).
	Ko 2016	Single center, prospective cohort	Incidence of VTE in trauma was lower in the dose adjustment group than in the historical cohort (1.1% vs. 7.6%, p=0.046).
	Dhillon 2021	Single center, retrospective	LMWH dosing protocol changed from 30-mg twice daily (PRE) to 40-mg twice daily with dose adjustment by anti-Xa (POST). POST had fewer VTE (3.6% vs 6.9 %, p<0.01) and was independently protective for VTE (aOR 0.54, p=0.01).
	Gates 2022 *	Single center, retrospective	Anti-Xa LMWH titration protocol resulted in significant reduction in overall VTE (p=0.01) and DVT (p=0.01).
	Tran 2022	Systematic review, meta-analysis	Anti-Xa based dosing of LMWH associated with reduced DVT (aOR 0.52, 95% CI 0.40 to 0.69), PE (aOR 0.48, 95% CI 0.30 to 0.78) and any VTE (aOR 0.54, 95% CI 0.42 to 0.69).
	Studies which did not demonstrate a reduction in VTE despite achieving prophylactic anti-Xa levels:
	Louis 2014	Prospective, randomized control	Participants randomized to standard LMWH 30-mg twice daily or TEG to adjust LMWH dosing to achieve a ΔR of 1–2 minutes. TEG adjusted LMWH led to significant increases in anti-Xa activity but no correlation with rate of DVT.
	Karcutski 2018	Single center, retrospective	There was no difference in rates of VTE in those who received anti-Xa dose adjustment versus those on standard LMWH dosing in the overall sample (6% vs 6.8%, p=0.68) or after propensity matching (2.3% vs. 3.6%, p=0.57).
	Gates 2022 *	Single center, retrospective	Despite significant reduction in overall VTE, significant reduction in PE was not observed (p=0.21)
Weight-Based Dosing of Low Molecular Weight Heparin	Bickford 2013	Single center, prospective cohort	Implementation of a weight based LMWH dosing regimen in trauma patients resulted in 86% of the sample achieving target anti-Xa levels.	• Weight-based LMWH dosing should be used in obese trauma patients at low risk for bleeding. • More data are needed to support weight-based regimens in those who are older, underweight, or have reduced renal function
	Nunez 2015	Single center, prospective cohort	Weight-based dosing of 0.6mg/kg twice daily implemented in a trauma intensive care unit was associated with more prophylactic anti-Xa levels (61% vs 8%, p<0.01).
	Rodier 2021	Single center, prospective cohort	LMWH weight-based dosing of 0.5mh/kg every 12 hours was associated with increased prophylactic anti-Xa levels (25% vs. 5%, p=0.03).
	Stutsrim 2021	Single center, prospective cohort	In those without weight adjusted LMWH regimens, 34% of trough and 62% of peak anti-Xa levels were adequate, but with weight adjustment, 82% of trough and 97% of peak levels were prophylactic.
Using Thromboelastography to Guide Chemoprophylaxis	TEG and VTE in trauma:			• Hypercoagulable TEG results correlate with rates of VTE • TEG guided LMWH dosing demonstrate similar inconsistencies as anti-Xa levels • TEG with platelet mapping may help to uncover the role of platelets in trauma hypercoagulability
	Van 2009	Single center, prospective cohort	TEG used to assess trauma and non-trauma surgical intensive care unit (SICU) patients. There was a 28% rate of DVT overall. R time was 1.5 times shorter in those with DVT (p<0.001).
	Cotton 2012	Single center, prospective cohort	TEG obtained in 2,070 consecutive trauma patients. Found MA to independently predict PE with an OR of 5.8 if MA>72.
	Gary 2016	Single center, retrospective	Compared TEG in orthopedic trauma to non-orthopedic trauma. Those with orthopedic injuries were more hypercoagulable, corresponding to higher rates of VTE (6.5% vs 2.7%, p<0.01). They also found that admission MA was an independent predictor of VTE in severe extremity trauma (OR 3.6 if ≥65 and OR 6.7 if ≥72).
	Connelly 2016	Prospective, randomized control	TEG was used to guide LMWH dosing in surgical and trauma patients, they found no difference in rates of VTE or bleeding. There were also similar hypercoagulable TEG parameters and AT-III deficiency rates in both study groups.
	Brill 2017	Single center, prospective cohort	Found that increased MA (>75) and reduced Reaction (R) Time (<5 minutes) correlated with increased rates of DVT in trauma patients (15.6 vs. 8%, p=0.039). On multivariate analysis, there was a significant association between hypercoagulable TEG and DVT (OR 2.41).
	TEG to assess the role of platelets in trauma induced hypercoagulability:
	Harr 2013	Single center, randomized control	Found a positive correlation between platelet count and clot strength. Early in the study, LMWH was associated with increased contribution of platelets to clot strength, possibly due to heparin induced platelet activation.
	Kornblith 2014	Single center, prospective cohort	Demonstrated that platelets had a greater contribution to clot strength than fibrinogen in injured patients, suggesting that anti-platelet therapy may be of under-recognized importance to thromboprophylaxis in trauma.

^*Study with evidence that does and does not support VTE reduction with anti-Xa level dose adjustment