What are the most recent recommendations/guidelines for DVT prophylaxis following below the knee amputation (duration and agents)?

What are the most recent recommendations/guidelines for DVT prophylaxis following below the knee amputation (duration and agents)?

Comment by InpharmD Researcher

There are limited data to support the optimal DVT prophylactic agent of choice following the below-knee amputation. Guidelines prefer extended LMWH (also unfractionated heparin from one guideline) prophylaxis for major orthopedic surgeries up to 35 or 42 days. Two limited studies observing patient groups undergoing below-knee amputation did not observe significant differences between UFH versus LMWH or UFH versus placebo.

Background

The 2019 American Society of Hematology (ASH) guidelines for managing venous thromboembolism (VTE) in surgical hospitalized patients did not discuss DVT prophylaxis specifically for post-below-knee amputation. Pharmacological or mechanical prophylaxis is conditionally recommended based on bleeding risk (mechanical prophylaxis favored) or VTE risk (combined if the risk is high). For major surgeries, low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) is the preferred pharmacological agent. The authors favor extended antithrombic prophylaxis (19 to 42 days) versus short-term prophylaxis (4 to 14 days). Most suggestions are based on low to very low certainty in the evidence. [1]

The 2012 CHEST guidelines for the prevention of VTE in patients undergoing major orthopedic surgery also do not specifically address amputations. Low-molecular-weight heparin is favored over alternative agents for major orthopedic surgery involving total hip arthroplasty, total knee arthroplasty, or hip fracture surgery, and the extended prophylaxis of up to 35 days post-surgery is recommended. Additionally, an intermittent pneumatic compression device is suggested during hospital inpatient stays. [2]

A Cochrane review published in 2013 (N=288) could not conclude on an optimal thromboprophylaxis agent in lower-extremity amputee patients due to a lack of quality data. Two studies were included in the review, yet neither could effectively address the inquiry [Tables 1, Table 2]. The study in Table 1 did not observe UFH's improvement in the prevention of pulmonary embolism (PE) compared to placebo (odds ratio [OR] 1.02; 95% confidence interval [CI] 0.44 to 2.37), and when the level of amputation was considered, the incidence of PE was similar between the two treatment groups: above knee amputation (OR 0.79, 95% CI 0.31 to 1.97) and below-knee amputation (OR 1.53, 95% CI 0.09 to 26.43). The study in Table 2 did not observe a difference between the LMWH and UFH in the prevention of DVT (OR 1.23; 95% CI 0.28 to 5.35). [3]

An update of that Cochrane review was published in 2020. It did not identify any eligible new studies for this update. [4]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

What are the most recent recommendations/guidelines for DVT prophylaxis following below the knee amputation (duration and agents)?

Please see Tables 1-2 for your response.

Failure of Low Dose Heparin to Prevent Pulmonary Embolism After Hip Surgery or Above The Knee Amputation
Design	Randomized, double-blind trial N=212
Objective	To investigate the effect on pulmonary embolism (PE) of 5,000 USP units of sodium heparin given twice daily to patients undergoing hip surgery or major amputation of a lower extremity
Study Groups	Study participants (N=212) Below-knee amputation - Heparin (n=16) Below-knee amputation - Saline (n=24)
Methods	Inclusion criteria: Patients requiring hip surgery, total hit replacement, or major lower extremity amputation due to hip, joint, or vascular disease. Exclusion criteria: Patients that develop acute pulmonary embolism. Patients were randomized to receive either heparin beef lung sodium 10,000 USP u/mL SubQ or saline placebo 0.5 mL SubQ at least two hours before the surgery and at 12 hours intervals thereafter for two weeks or until discharge.
Duration	January 1974 to July 1977
Outcome Measures	Primary outcome measure: Number of PEs.
Baseline Characteristics		Study participants (N=212)
	Age, years	64.5 (23 to 87)
	Women	30
	Patients requiring below-knee amputation These patients present with complicating diseases including: Carcinoma Diabetes Mellitus Congestive Heart Failure Cerebrovascular Accident Venous Disease Resolving Pulmonary Perfusion Defect	40 2 8 5 5 4 0
Results	Endpoint	Above-knee amputation - Heparin (n=53)	Above-knee amputation - Saline (n=41)	Probability
	Number of PEs	13 (25%)	12 (29%)	0.39
	Endpoint	Below-knee amputation - Heparin (n=16)	Below-knee amputation - Saline (n=24)	Probability
	Number of PEs	1 (6%)	1 (4%)	0.85
Adverse Events	N/A
Study Author Conclusions	We conclude that the regimen used had no significant effect on the incidence of acute PE in patients undergoing hip surgery or above the knee amputation.
InpharmD Researcher Critique	The incidence of bilateral below-knee amputation was underreported and the data are too limited to suggest a conclusion. Yet the data presented here suggest that bovine heparin may not be beneficial in relation to major orthopedic surgeries.

References:

Williams JW, Eikman EA, Greenberg SH, et al. Failure of low dose heparin to prevent pulmonary embolism after hip surgery or above the knee amputation. Ann Surg. 1978;188(4):468-474.

Prophylaxis of Deep-Vein Thrombosis After Lower Extremity Amputation. Comparison of Low Molecular Weight Heparin With Unfractionated Heparin
Design	Randomized, controlled trial N=75
Objective	To compare the efficacy and safety of low molecular weight heparin (enoxaparin) with unfractionated heparin (UFH) in this prophylaxis
Study Groups	Study participants (N=75) Below-knee amputation (n=45)
Methods	Inclusion criteria: Age > 18 years, undergoing elective or emergency lower-limb amputation for critical-limb ischemia. Exclusion criteria: Previous VTE or contraindication to anticoagulant prophylaxis. Patients were randomized to be given UFH 5,000 IU SubQ TID or enoxaparin 40 mg/day during hospitalization. Prophylaxis began 12 hours before surgery (unless emergency cases where treatment began first day postoperatively). Patients were observed for the development of deep-vein thrombosis (DVT) which included a duplex scanning before and ~1 week after surgery along with a final scan before discharge.
Duration	1995 to 1996
Outcome Measures	Primary outcome measures: Incidence of DVT within subgroups, including above-knee amputation.
Baseline Characteristics		Study participants (N=75)
	Age, years	18 to 86
	Women/Men	16/59
	Above-knee amputation	30
	Lower-knee amputation	45
Results	Subgroup	Study participants (N=75)	Incidence of DVT in the particular subgroup	p-value
	Female Male	16 59	1 (6.2%) 7 (11.8%)	- p=0.85
	Above-knee amputation Below-knee amputation	30 45	5 (16.6%) 3 (6.6%)	- p=0.32
	Unfractionated heparin Low-molecular-weight heparin	34 41	4 (11.7%) 4 (9.7%)	- p=0.92
Adverse Events	N/A
Study Author Conclusions	Enoxaparin and UH were both efficient and safe for the prophylaxis of DVT in patients submitted to lower extremity amputation.
InpharmD Researcher Critique	Unfortunately, the results were not categorized based on those who received UH versus LMWH in the below-knee group. Whether surgery involved bilateral amputation was also not discussed. There was also no comparable placebo group which limits the application of the study. For both upper and lower leg amputation, it is suggested that UH and LMWH are similar yet patients with thigh amputation observed the highest rate of DVT (16.6%) despite coverage from either anticoagulant.

References:

Lastória S, Rollo HA, Yoshida WB, et al. Prophylaxis of deep-vein thrombosis after lower extremity amputation: comparison of low molecular weight heparin with unfractionated heparin. Acta Cir Bras. 2006;21(3):184-186.