Pharmacological venous thromboembolism prophylaxis in elective cranial surgery: a systematic review of time of initiation, regimen and duration

Figures & data

Table 1. Summary of major national guidelines for pharmacological VTE prophylaxis in cranial neurosurgery.

Organization	Pharmacological prophylaxis guideline for cranial neurosurgery	Evidence
NICE^8	‘Consider adding pharmacological VTE prophylaxis with LMWH, starting 24 to 48 hours after surgery for people undergoing cranial surgery whose risk of VTE outweighs their risk of bleeding. Continue for a minimum of 7 days’	^9–13
ASH^14	‘For patients undergoing major neurosurgical procedures, the ASH guideline panel suggests against using pharmacological prophylaxis…’ ^a	^11^,^15–23
Thrombosis Canada^29	‘Suggests against pharmacological prophylaxis’^a	^14
RACP^24	‘Use pharmacological prophylaxis with extreme caution due to high surgical bleeding risk’	Expert consensus

NICE: National Institute for Health and Care Excellence; ASH: American Society of Hematology; RACP: Royal Australasian College of Physicians.

^aSpinal surgery.

Figure 1. PRISMA flow diagram of systematic search.

Table 2. Characteristics of eligible studies included in this systematic review.

	Methods	Participants	Interventions	Outcomes
^37	Single-centre retrospective observational study from 1999 to 2010 (IL, USA)	Inclusion criteria: Craniotomy for high-grade glioma (WHO grade III or IV) Exclusion criteria: WHO grade I or II; Age < 18; Not treated with craniotomy during study period Sample size: 336 (210 M, 126 F) Unknown number with prior anticoagulant use Mean age: 55.9 years	25 received prophylactic anticoagulation postoperatively: 2 received enoxaparin 40 mg once daily 23 received unfractionated heparin 5000 units twice daily	VTE (clinically symptomatic) ICH (method of measurement not specified) Mean follow-up: 15.1 months
^38	Single-centre retrospective observational study from 2012 to 2018 (Leipzig, Germany)	Inclusion criteria: Craniotomy for meningioma Exclusion criteria: Missing or unclear data on perioperative anticoagulation regimen; Age < 18; Loss to follow-up within 30 days Sample size: 286 (85 M, 201 F) 11 on prior anticoagulants, 28 on prior antiplatelets Mean age: 61.4 years	279 received prophylactic anticoagulation postoperatively: 146 received fraxiparin 2850 units 1 received fraxiparin 3500 units 132 received tinzaparin 3500 units	VTE – including ischaemic stroke (method of measurement not specified) ICH (identified on routine postoperative CT) Mean follow-up: 3 months
^39	Single-centre retrospective observational study from 2007 to 2013 (Utrecht, Netherlands)	Inclusion criteria: Craniotomy for high-grade glioma (WHO grade III or IV) Exclusion criteria: Age < 18; Previous craniotomy Unknown number with prior anticoagulant use Sample size: 301 (176 M, 125 F) Mean age: 57.7 years	301 received prophylactic anticoagulation postoperatively: 166 anticoagulated postoperatively for 0 − 7 days 135 anticoagulated postoperatively for 21 days All received dalteparin 5000 units once daily	VTE (clinically symptomatic confirmed by Doppler ultrasound or CT angiography) ICH requiring evacuation (method of measurement not specified) Mean follow-up: 3 months

VTE: venous thromboembolism; ICH: intracranial haemorrhage; WHO: World Health Organization; CT: computed tomography.

Figure 2. Risk of bias, determined according to the Cochrane ROBINS-I tool. Risk of bias in each domain is classed as serious, moderate, low or no information as seen in the legend. VTE: venous thromboembolism; ICH: intracranial haemorrhage; D1: bias due to confounding; D2: bias in selection of participants into study; D3: bias in classification of interventions; D4: bias due to deviations from intended intervention; D5: bias due to missing data; D6: bias in measurement of outcomes, D7: bias in selection of reported result.

Table 3. VTE and ICH Rates and time of initiating prophylactic anticoagulation after surgery.

	Anticoagulated	Not anticoagulated	VTE	No VTE	p	ICH	No ICH	p
	Number of outcome events		Mean hours after surgery in anticoagulated patients (SD)
^37	8/25 VTE (32.0%) 0/25 ICH (0%)	45/311 VTE (14.5%) 3/311 ICH (1.0%)	144 (225.6)	28.8 (57.6)	0.042	–	–	–
	Number of outcome events		Median hours after surgery in anticoagulated patients (SD)
^38	11/281 VTE (3.9%) 14/281 ICH (5.0%)	0/5 VTE (0%) 3/5 ICH (60.0%)	54 (69.2)	29 (21.9)	0.301	69 (54)	29 (22.4)	.0007

VTE: venous thromboembolism; ICH: intracranial haemorrhage; p: p value; SD: standard deviation.

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