Portal vein thrombosis in cirrhosis: Controversies and latest developments

Table 1 Key studies of portal vein thrombosis and liver transplantation

	Number of patients	Prevalence PVT, n (%)	PVT characteristics	Outcomes
Englesbe et al[65]	22291 (2001-2007)	897 (4.02)	Not described	PVT was not predictive of waiting list mortality (HR = 0.90, P = 0.23)
				PVT was predictive of post-transplant mortality (HR = 1.32, P = 0.02)
Sringeri et al[61]	1491 (2000-Aug 2012)	119 (8.0)	Not described	Prolonged theatre timea, increased blood transfusion rates1. No difference mortality up-to 140 mo
Ravaioli et al[13]	889 (1998-2008)	91 (10.2)	Partial 51 (56%)	No difference 1 yr (85% vs 86%) and 5 yr (68% vs 73%) survival between PVT and non-PVT subjects
			Complete 40 (44%)	Survival improved significantly for patients with complete PVT in the second era (2003-2008) (57% vs 89% at 1 yr1)
Yerdel et al[15]	779 (1987-1996)	63 (8.1)	Grade 1: 24,	Reduced 5 yr survival between PVT and non-PVT subjects (65.3% vs 76.3%1)
			Grade 2: 23,
			Grade 3: 6,	But improved 5 yr survival from 1st to 2nd era in all patients (from 72% to 83%1)
			Grade 4: 10

¹The P value is < 0.05. PVT: Portal vein thrombosis.

Table 2 Summary of studies reporting the use of anticoagulation for portal vein thrombosis in cirrhosis

	Study type	n (controls)	Baseline severity liver disease	Duration and type of anticoagulation	PVT characteristics(none/partial/complete occlusion)	Recanalisation	Partial recanalisation/ stabilisation	Progression	Bleeding complicaitons
Francoz et al[7]	Prospective case control	19 (10)	mean MELD 12.8	Warfarin (INR 2-3)	0/18/1	8/19 (42%) vs 0/10 non-anti-coagulated (P = 0.002)	0	1	1 bleeding episode following endoscopic variceal band ligation
				Mean 8.1 mo
Amitrano et al[83]	Prospective	28	?	Enoxaparin 200 IU/kg per day: 6 mo for responders and non-responders. Partial responders continue until end of follow up.	0/23/5	21 (75%) at median 11 mo	5 (17.9%)	2	Mild anaemia in patient with portal hypertensive gastropathy
Delgado et al[84]	Retrospective	55	mean MELD 12.8 +/- 3.8	Warfarin (INR 2-3) or enoxaparin mean 6.8 mo	0/41/14	25 (45.5%)	30 (54.5%)	0	6 variceal bleeds, 1 lower GI bleed, 1 obscure GI bleed, 1 oral bleed post-dental extraction, 1 severe vaginal bleed
Senzolo et al[85]	Prospective case control	33 (21)	MELD 12.6 (controls MELD 13.7)	Nadraparin low molecular weight heparin until end of follow up, or until 6 mo following complete recanalisation.	0/24/11	12/33 (36%) active arm vs 1/21 (5%) controls	Partial: 9/33 active arm. Stabilisation: 7/33 active arm. Partial recanalisation or stabilisation in 5/21 controls.	5/33 (14.3%) active arm vs 15/21 (71.4%) control arm (P < 0.001)	Active arm: 1 cerebral haemorrhage, 1 epistaxis, 1 haematuria, 1 variceal bleed
									Control arm: 5 variceal bleeds
Werner et al[86]	Retrospective	28	MELD 7-29	Warfarin	not described	11 (39.3%)	17 (60.7%)	0	1 significant vaginal bleed
				Mean 302 d
Villa et al[55]	Prospective randomised controlled trial	34 (36)	Child’s 7-10	Enoxaparin 4000 IU/d	Primary prevention study: No PVTs at baseline	N/A	N/A	Treatment arm: No PVT at 2 yr. Control arm: PVT in 10/36 (27.8%) at 2 yr (P = 0.001)	Active arm: 2 variceal bleeds, 2 epistaxis
				48 wk treatment. Follow up to 2 yr					Control arm: 1 variceal bleed, 1 epistaxis

PVT: Portal vein thrombosis.

Table 3 Summary of new oral anti-coagulants

Name	Dabigatran	Apixaban	Edoxaban	Rivaroxaban
Action	Direct thrombin inhibitor	Activated factor Xa inhibitor	Activated factor Xa inhibitor	Activated factor Xa inhibitor
Clearance	80% renal clearance	73% hepatic	50% hepatic	65% hepatic
		27% renal clearance	50% renal clearance	35% renal clearance
CYP3A4 interaction?	No	Yes (minor)	Minimal	Yes
Absorption with food?	No effect	No effect	Up to 20% more	40% more therefore intake with food
Elimination half life	12-17 h	12 h	9-11 h	8-9 h young
				11-13 h elderly

Table 4 Summary of retrospective case series reporting the use of transjugular intrahepatic portosystemic stent-shunt for portal vein thrombosis in cirrhosis

	Study type and stent characteristics	n	Baseline severity liver disease: Child’s A/B/C (%)	TIPSS indication (%)	PVT characteristics: Complete/ partial/ cavernoma (%)	Successful cannulation (%)	Outcome	Significant complications/ notes
Luca et al[102]	Series 2003-2010	70	A: 17 (24)	Bleeding: 48	Complete: 24	70/70 (100) cannulation.	Complete recanalisation in 40 (57%): 38 maintained patency at mean follow up 20.7 mo.
	13 bare Wallstent, 57 covered Viatorr ePTFE covered (WL Gore and Associates)		B: 42 (60)	Ascites/ hydrothorax: 18	Cavernoma: 2	Complete recanalisation or significant reduction in thrombosis: 61 (87)
			C: 11 (16)	Specific treatment of PVT: 4
Perarnau et al[100]	Series 1990-2004	34	A: 3 (14)	Bleeding: 27 (79)	Complete acute: 15	No cavernoma: 15/15 (100)	Mean F/U 30 mo.	Failed cannulation in presence of thrombosed intrahepatic PV branches or peri-hilar cavernoma
	Palmaz (Cordis) or Wallstent (Boston Scientific) bare stents		B: 11 (52)	Ascites: 5 (15)	Complete + cavernoma: 19	Cavernoma: 12/19 (63)	26/34 (72%) long-term patency
			C: 7 (33)	Other: 2
			(incomplete details)
Senzolo et al[104]	Series 1994-2005	28 (15 non-cirrhotic)	Not stated	Bleeding: 15	Complete: 8 (3 with, 5 without cavernoma)	19/28 (73%)	Primary patency mean 18 mo in 14/19.
	26 Memotherms (Angiomed) bare stents, 3 Viatorr covered stents			Ascites: 5	Partial: 5		Stent thrombosis in 2 non-cirrhotic subjects (Budd-Chiari syndrome)
				Portal biliopathy: 3
				Specific treatment PVT: 1
Han et al[99]	Series 2001-2008	57	A: 25 (44)	Bleeding: 56	Complete: 14	Overall: 43/57 (75)	Primary patency maintained in 26/43 (17 required shunt revisions to maintain patency)	Failure related to presence of cavernoma.
	Uncovered stents in all patients		B: 26 (46)	Ascites: 1	Cavernoma: 30	Complete PVT: 8/14 (57)		1 case of delayed severe intra-abdominal haemorrhage following percutaneous trans-hepatic approach.
			C: 6 (30)		Partial: 35	Partial PVT: 35/35 (100)
						Cavernoma: 16/30 (53%)
Van Ha et al[106]	Series 1995-2003	15	B: 11 (73)	Bleeding: 10	Complete: 4/partial: 7/complete with cavernoma: 4	Overall: 13/15 (87)	Mean F/U 17 mo.
	12 bare Wallstent (Boston Scientific), 1 bare Zilver stent (Cook)		C: 4 (27)	Ascites: 5		Cavernoma: 3/4	1 stent occlusion
						No cavernoma: 10/11 (91)
D’Avola et al[101]	Series 1995-2009	15 (+ 8 controls with PVT)	Mean Child’s 8	Prevention of complete PVT pre-liver transplant: 8	All partial PVT	Series describes only patients who successfully underwent TIPSS	3/15 TIPSS thrombosis: all successfully treated.
	Bare and covered stents			Bleeding: 6			Median time TIPSS to transplant: 185 d.
				Ascites: 1			100% portal vein patency at time of transplant vs 50% patency at transplant in controls (P = 0.008)
Bauer et al[103]	Series 1999-2005	9	Cirrhosis: disease severity not stated	Primary indication: maintain PV patency for future liver transplantation	Complete: 7	Series describing only patients who successfully underwent TIPSS	1/9 re-thrombosed.
	3 covered stents: others bare stent				Partial: 2		2 patients transplanted with no PVT present
					Cavernoma: 4
Blum et al[114]	Case series	7	Cirrhosis: disease severity not stated	Bleeding: 7	PVT severity not stated.	Series of successful cases
	All bare stents				No cavernoma.

PVT: Portal vein thrombosis; TIPSS: Transjugular intrahepatic portosystemic stent-shunt; F/U: Follow up.