Arterial complications, venous thromboembolism and deep venous thrombosis prophylaxis after anterior cruciate ligament reconstruction: A systematic review

Table 1 Inclusion and exclusion criteria

Inclusion criteria

Studies (randomized, non-randomized, case series, prospective or retrospective design, case reports) evaluating vascular and thromboembolic complications after ACL reconstruction

All types of ACL reconstruction surgery related arterial and venous complications

All types of ACL reconstruction surgery related thromboembolic complications

Any arthroscopic surgical method of primary or revision intra-articular ACL reconstruction

All graft types for ACL reconstruction

Multiligament reconstructions including ACL

Combined ACL reconstruction and meniscal surgery

Human in vivo studies with reported outcome

English language

Full text available

Exclusion criteria

Animal studies

Cadaveric studies

Nonsurgical related vascular or thromboembolic complications

ACL: Anterior cruciate ligament.

Table 2 Risk of bias of studies reporting venous complications

Ref.	Study design	Patient selection1	Follow-up2	Classification3
Adala et al[6]	PC	+	-	+
Born et al[26]	RS	+	-	-
Cullison et al[10]	PC	?	-	+
Dong et al[8]	RS	?	-	+
Ettema et al[27]	RS	-	?	-
Gaskill et al[2]	RS	+	-	-
Hetsroni et al[30]	RS	?	?	-
Hirota et al[22]	PC	-	-	+
Hirota et al[25]	PC	-	-	+
Jameson et al[28]	RS	?	-	-
Jaureguito et al[7]	RS	+	-	+
Lind et al[23]	PC	+	?	-
Maletis et al[11]	PC	?	?	-
Marlovits et al[20]	RCT	-	-	+
Mohtadi et al[21]	RCT	+	+	-
Struijk-Mulder et al[5]	PC	+	-	+
Sun et al[29]	RS	+	-	+
Williams et al[24]	PC	-	-	+
Ye et al[4]	RS	?	-	+

¹Inclusion of consecutive patients;

²Was follow-up period adequate (minimum 1 year) for exposure of adverse event?

³Was the used classification shown to be valid and reliable? +: Yes; -: No; ?: Not clear; RCT: Randomized controlled trial; PC: Prospective cohort study; RS: Retrospective study.

Table 3 Results arterial injuries (case reports)

Ref.	ACLR	Graft type	Fixation femur	Fixation tibia	Vascular injury	Diagnosis after ACLR	Treatment	Cause vascular complication
Spalding et al[31]	Primary	Gore-Tex	?	?	Compression popliteal artery	8 yr	Cyst removal	Compression by cyst containing ruptured Gore-tex graft
Aldridge et al[32]	Primary	BPTB	Interference screw	Interference screw	Avulsion middle gen. artery	4 wk	Direct repair avulsion	Lesion artery by shaver
Evans et al[33]	Primary	BPTB	Interference screw	Interference screw	Pseudoaneurysm med. inf. gen. artery	5 wk	Ligation pseudoaneurysm	Elevation periosteum medial tibia (tunnel preparation)
Friederich et al[34]	Primary	BPTB	Staples	Staples	Lesion sup. lat. gen. artery	5 mo	Removal staples	Hardware femur
Kanko et al[35]	Primary	BPTB	Interference screw	Bicortical screw	Pseudoaneurysm popliteal artery	2 yr	Ligation pseudoaneurysm	Drill bit for bicortical tibia fixation?
Keçeci et al[36]	Primary	BPTB	Interference screw	Interference screw	Popliteal arteriovenous fistula	18 mo	Venous re-anastomosis	Break-out posterior femoral cortex
Lamo-Espinosa et al[37]	Primary	BPTB	Interference screw	Interference screw	Lesion lat. inf. gen. artery	1 d	Embolization	Simultaneous lateral meniscectomy
Mello et al[38]	Primary	BPTB	Interference screw	Interfererce screw	Pseudoaneurysm med. inf. gen. artery	6 wk	Embolization	Direct lesion artery by shaver
Pereira et al[39]	Primary	BPTB	Interference screw	Interference screw	Pseudoaneurysm sup. lat. gen. artery	11 d	Ligation pseudoaneurysm	Hardware femur
Roth et al[40]	Primary	BTPB + augmentation	Staple	?	Occlusion popliteal artery	6 wk	Venous bypass	Entrapment between graft and femur
Tam Kelvin et al[41]	Primary	BPTB	Endobutton	Interference screw	Pseudoaneurysm popliteal artery	8 d	Repair by venous graft	Direct trauma by guide pin femoral canal
Lee et al[42]	Rerevision	?	Rigidfix cross pin	?	2 lesions sup. to level of med. and lat. gen. artery	6 wk	Venous re-anastomosis	Drill tip for Rigidfix cross pin
Ambrosia et al[57]	Primary	Hamstring	TightRope	Interference screw	Pseudoaneurysm popliteal artery	7 wk	Venous bypass	Hamstring harvest/previous catheterization-angioplasty?
Buda et al[43]	Primary	Hamstring ACL + allograft PCL	Staples	Staples	Pseudoaneurysm post. tibial artery	1 wk	Embolization	Surgical approach PCL or hamstring harvest?
Galanakis et al[44]	Primary	Hamstring + extra-artic. rec.	Staples	Pes anserinus	Pseudoaneurysm popliteal artery	Day of surgery	Venous re-anastomosis	Lesion artery by shaver and popliteal entrapment syndrome
Janssen et al[45]	Primary	Hamstring	Bone Mulch Screw	WasherLoc	Pseudoaneurysm popliteal artery	12 d	Venous repair	Drill tip for bicortical tibial fixation
Janssen et al[47]	Primary	Hamstring	Bone Mulch Screw	WasherLoc	Subtotal occlusion popliteal artery	19 d	Embolectomy	Preexistent intimal lesion after knee dislocation
Janssen et al[47]	Primary	Hamstring	Bone Mulch Screw	WasherLoc	Pseudoaneurysm and occlusion popliteal artery	9 d	Venous re-anastomosis	Drill tip for bicortical tibial fixation
Milankov et al[48]	Primary	Hamstring	Interference screw	Interference screw	Pseudoaneurysm med. inf. gen. artery	1 d	Ligation pseudoaneurysm	Hamstring harvest?
Panigrahi et al[56]	Primary	Hamstring ACL + PCL	?	?	Occlusion popliteal artery	Day of surgery	Embolectomy	Preexistent thrombotic occlusion after knee dislocation
Tsubosaka et al[54]	Primary	Hamstring	Cortical buttons	Screw post	Pseudoaneurysm med. inf. gen. artery	2 d	Embolization	Anteromedial portal
Pereira et al[39]	Revision	Hamstring	Transverse screw	Interference screw	Pseudoaneurysm sup. lat. gen. artery	2 d	Ligation pseudoaneurysm	Hardware femur
Carr et al[49]	Primary	Achilles tendon allograft	Interference screw	Suture+ washer bone plug	Traumatic arteriovenous fistula	7 wk	Ligation fistula	Injury at medial superior portal site

ACL: Anterior cruciate ligament; ACLR: ACL reconstruction; BPTB: Bone-patellar tendon-bone; PCL: Posterior cruciate ligament.

Table 4 Data venous thromboembolism and thromboprophylaxis

Ref.	Study design	Number ACLR	Mean age(yr)	Male (M)Female (F)	Graft type	Mean duration surgery (min)	Mean tourniquet time (min)	BMI(kg/m2)	Thromboprophylaxis	Hospital stay (d)
Marlovits et al[20]	RCT	140 (87 vs 88 placebo)	29.9 ± 7.4 vs 30.2 ± 6.9	M 63% F 60%	BTPB	Mean > 120	?	Comparable between groups	Yes (enoxaparin 3-8 d + 20 d enoxaparin vs enoxaparin 3-8 d + placebo)	3-8
Mohtadi et al[21]	RCT	330	28.5 (14-50)	M 183 F 147	BPTB, hamstring	?	?	?	?	?
Adala et al[6]	PC	112	31.6	M 61 F 51	Hamstring	64.9 ± 7.8	?	?	None	2
Cullison et al[10]	PC	67	26.5 (19-39)	All men	BPTB	?	83 (0-115)	?	None	?
Hirota et al[25]	PC	30	24.1 ± 8.3	M 14 F 16	?	?	?	?	None	?
Hirota et al[22]	PC	40 (20 ACLR vs 20 TKA)	26.7 ± 13.4 vs 71.3 ± 6.8	M:F ACLR 10:10 vs TKA 6:14	?		87.1 ± 24.4 vs 87.2 ± 18.4	?	None	?
Lind et al[23]	PC	5818	?	M approximately 57%	BPTB and hamstring	Prim. ACLR 69.4 ± 21.1; rev. ACLR 90.0 ± 32.3	?	?	18.5% (prim. ACLR 15.7%; rev. ACLR 20.8%)	?
Maletis et al[11]	PC	Prim. ACLR 15101	Prim. ACLR 29.5 ± 11.5	M 9604 F 5497	Autograft 57.6%, allografts 42.4%	?	?	≥ 30 = 23.3%	?	?
		Rev. ACLR 1091	Rev. ACLR 29.8 ± 10.7	M 693 F 398	Autograft 20.9%, allografts 78.8%	?	?	≥ 30 = 20.8%	?	?
Struijk-Mulder et al[5]	PC	100	30.0 ± 10.0	M 77 F 23	Autograft HS 84, BPTB 14 allograft 2	68.0 ± 22.0	76.0 ± 23.0	25.0 ± 4.0	None	1 to 2
Williams et al[24]	PC	23	31 (19-42)	M 17 F 6	BPTB	?	103 (89-136)	?	None	2-3
Born et al[26]	RC	136 ACLR + multiligament rec.	VTE group 42 (24-43); Non-VTE group 31 (SD 11)	DVT group M:F 3:0; Non-VTE group 103:28	?	VTE group 152.0; Non-VTE group 233 ± 76	VTE group 78.0; Non-VTE group 102 ± 54	VTE group 35 (28-42); Non-VTE group 30 (SD 7)	Yes (before 2007, 3 wk aspirin. After 2007, LMWH 3 wk)	?
Dong et al[8]	RC	152 ACLR	34.9	M 91 F 61	Hamstring/allograft	?	3 groups < 90, 90-120, > 120	22.6	None	?
Ettema et al[27]	RC	?	?	?	?	?	?	?	50% prescribed LMWH or coumarin during hospital stay; 5% for 1-2 wk; 2% for 3-4 wk and 35% for 6 wk
Gaskill et al[2]	RC	15767 ACLR + HTO/PCL non specified	28.9 (SD 7.6)	M 13794	?	?	?	27.8	?	? ?
Hetsroni et al[30]	RC	58863 ACLR, total 418323 arthroscopies	PE group 50.3 (15-79) vs non-PE group 45.5 (0-100)	F 2764 PE group F 57.3% vs non-PE group	?	?	?	(SD 4.0) ?	?	?
Jameson et al[28]	RC	13941	29.3 (8-83)	F 46.8% M 79.5%	?	?	?	?	?	1-4
Jaureguito et al[7]	RC	131 group 1 (knee arthroscopy)	?	F 20.5% M 73	-	?	?	?	Aspirin (325 mg) daily for 3 wk postsurgery if age > 45 yr	?
		108 group 2 (ACLR, osteotomy)		F 58 M 60	?	?	?	?	Idem	?
Sun et al[29]	RC	231	23.6	F 48 M 69.3%	?	88.4	67.5	24.5	None	?
Ye et al[4]	RC	171	30.1 ± 10.0	F 30.7% M 123	Hamstring	86.9 ± 26.4	69.9 ± 15.9	24.4 ± 3.2	None	4
				F 48
Ackerman et al[55]	CR	1	45	F 1	BPTB	?	0	?	Aspirin 325 mg daily	Outpatient
Chien et al[50]	CR	1	34	M 1	?	110	?	30	none	?
Janssen et al[13]	CR	1	19	F 1	Hamstring	96	110	27.5	LMWH during hospital stay	3
Kang et al[51]	CR	1 (+MCL rec.)	48	F 1	Hamstring	?	90	?	None	?
Liu et al[52]	CR	1	34	M 1	Hamstring	110	119	30.1	None	5
Theron et al[53]	CR	1	30	F 1	?	?	?	?	?	Occurred day after surgery

ACLR: ACL reconstruction; BPTB: Bone-patellar tendon-bone; TKA: Total knee arthroplasty; LMWH: Low molecular weight heparin; HTO: High tibial osteotomy; VTE: Venous thromboembolism; PCL: Posterior cruciate ligament; prim: Primary; MCL: Medial collateral ligament; rev: Revision; RCT: Randomized controlled trial; PC: Prospective cohort study; RS: Retrospective study; CR: Case report; SD: Standard deviation; DVT: Deep venous thrombosis; rec.: Reconstruction.

Table 5 Incidence venous thromboembolism, risk factors and thromboprophylaxis recommendations

Ref.	Study design	Incidence DVT (symptomatic if specified)	Incidence PE (symptomatic if specified)	Detection method VTE	Risk factors DVT	Thromboprophylaxis recommendations
Marlovits et al[20]	RCT	2 = 2.8% with extended prophylaxis; 28 = 41.2% without extended prophylaxis	0%	MRI venography	Comparable between groups	Age > 30, prolonged immobilisation and complex procedures
Mohtadi et al[21]	RCT	1 (0.3%) symptomatic	1 (0.3%) symptomatic	Clinical, additional exam in suspected cases	None	-
Adala et al[6]	PC	2 = 1.78% (1 pt symptomatic)	0%	Ultrasound preop and day 2-3	None	None if absent high risk factors DVT or age < 45 yr
Cullison et al[10]	PC	1 = 1.5%	0%	Ultrasound preop, day 3 and 4 wk	None	None in male patients < 40 yr and absence of risk factors
Hirota et al[25]	PC	0%	Peak emboli 50s after tourniquet release	Transoesophageal echocardiography	?	-
Hirota et al[22]	PC	0%	0%	Transoesophageal echocardiography	?	-
Lind et al[23]	PC	?	?	?	?	-
Maletis et al[11]	PC	26 = 0.2% in primary ACLR	15 = < 0.1% in primary ACLR	Various methods	?	?
		2 = 0.2% in revision ACLR	0% in revision ACLR	Idem	?	?
Struijk-Mulder et al[5]	PC	9 = 9.0% (symptomatic 4 = 4.0%)	1 = 1%	Bilateral ultrasound	Age, contraceptive use	Further research for DVT prophylaxis, especially when risk factors are present
Williams et al[24]	PC	0%	0%	Bilateral ultrasound preop and 7-14 d postop	In 3 patients, non-specified	Future studies needed
Born et al[26]	RC	3 = 2.0% sympromatic	?	Clinical, ultrasound in suspected cases	Multiligamentous injury, age, history DVT	In multiligament reconstruction. cf guidlines ACCP "major orthopaedic surgery"
Dong et al[8]	RC	17 = 8.5% (44.1% nonsymptomatic of all DVT cases = 12.1% of all patients)	?	Color doppler ultrasound < 24 h after admission and 3 and 7 d postsurgery	Multiligament reconstruction, tourniquet time > 2 h, age	In case of PCL reconstruction and tourniquet time > 2 h
Ettema et al[27]	RC	?	?	?	?	None
Gaskill et al[2]	RC	55 symptomatic	35	Clinical, additional exam in suspected cases	Age ≥ 35, smoking, cocomitant HTO/PCL surgery	Further research for VTE prophylaxis
Hetsroni et al[30]	RC	?	117 = 0.0003% all symptomatic	Clinical, additional exam in suspected cases	Female gender, age, surgical time, previous cancer	Further research for thromboprophylaxis in high risk patients
Jameson et al[28]	RC	42 = 0.3% all symptomatic	25 = 0.8% all symptomatic	Clinical, additional exam in suspected cases	Age > 40	No advise due to lack of evidence
Jaureguito et al[7]	RC	Retrospectively clinically 0.24% Prospectively 7 (2.9%, 5 asymptomatic = 2.1%)	0%	Duplex ultrasonography pre-operatively and 5 and 10 d postsurgery	None	-
Sun et al[29]	RC	total 36 = 15.6% (4 prox DVT = 2.4%. Distal DVT 32 = 13.9%)	0%	Venography day 3 postsurgery	Age, multiligament surgery	None
Ye et al[4]	RC	24 = 14.0% (4 pts prox. DVT)	0%	Chest X-ray and venography day 3 post ACLR	Female gender, age > 35 yr	In female patients and age > 35 yr
Ackerman et al[55]	CR	1 = 100%	0%	Clinical, ultrasound, CT and venography	May-Thurner Syndrome	In case of high risk patient
Chien et al[50]	CR	?	1 = 100%	Clinical, CT scan	BMI, ACL surgery	Further investigation for thromboprophylaxis after knee arthroscopy needed
Janssen et al[47]	CR	1 = 100%	1 = 100%	Clinical, transoesophageal echocardiography	Misdiagnosis DVT, Protein S deficiency? ACL surgery, contraceptive use	Further investigation for thromboprophylaxis after knee arthroscopy needed
Kang et al[51]	CR	1 = 100%	0%	Clinical, ultrasound	Primary thrombocytopenia, Factor VIII, Proteine C and S	None
Liu et al[52]	CR	1 = 100%	1 = 100%	Clinical, cardiac sonography	BMI	Patients with increased risk and prolonged tourniquet time
Theron et al[53]	CR	?	1 = 100%	Clinical, CT	Contraceptive use	None

ACLR: ACL reconstruction; BPTB: Bone-patellar tendon-bone; TKA: Total knee arthroplasty; LMWH: Low molecular weight heparin; HTO: High tibial osteotomy; VTE: Venous thromboembolism; PCL: Posterior cruciate ligament; prim: Primary; RCT: Randomized controlled trial; PC: Prospective cohort study; RS: Retrospective study; CR: Case report; CT-scan: Computerized tomography-scan; BMI: Body mass index; DVT: Deep venous thrombosis; ACL: Anterior cruciate ligament; rec.: Reconstruction; pts: Patients; prox.: Proximal.

Table 6 Incidence of venous thromboembolism

Ref.	ACLR (n)	Incidence DVT (n)	Incidence sympt DVT (n)	Incidence PE(n)	Thromboprophylaxis	Risk of bias
Adala et al[6]	112	2	1	0	No	Low
Cullison et al[10]	67	1		0	No	-
Dong et al[8]	152	11		NA	No	-
Jamesonet al[28]	13941	42	42	25	NA	-
Maletis et al[11]	15101	26		15	NA	-
Marlovits et al[20]	140 (72 vs 68)	2 vs 28		0	Yes	-
Mohtadi et al[21]	330	1	1	1	NA	-
Struijk-Mulder et al[5]	100	9	4	1	No	Low
Sun et al[29]	231	36		0	No	Low
Williams et al[24]	23	0	0	0	No	-
Ye et al[4]	171	24		0	No	-

Pooled incidence: All DVT: 79/14093 = 9.7%; symptomatic DVT: 5/235 = 2.1%; all DVT of low risk bias studies: 47/443 = 10.6%; PE = 1/704 = 0.1%. ACLR: Anterior cruciate ligament reconstruction; DVT: Deep venous thrombosis; sympt: Symptomatic; PE: Pulmonary embolism; NA: Not applicable.