Direct oral anticoagulant administration in cirrhotic patients with portal vein thrombosis: What is the evidence?

Table 1 Safety of direct oral anticoagulants in cirrhosis

Ref.	Drug administrated (n of patients)	Child-Pugh score at baseline	Indication for anticoagulant therapy	Definition of events	Events in cases vs control
Ai et al[87]	Rivaroxaban 20 mg once daily (26 pts)	Mean 7.2	PVT	No definition of events	3 vs 1 (P = 0.616); 1 hematuria in dabigatran; 1 hemoptysis in rivaroxaban; 1 melena in rivaroxaban
	Dabigatran 150 mg twice daily (14 pts)
	No anticoagulant (40 pts)	Mean 7.4
Hanafy et al[88]	Rivaroxaban 10 mg twice daily (40 pts)	Mean 6.4	PVT	Major bleeding	0 vs 17 (P = 0.001)
	Warfarin (40 pts)	Mean 6.2		Death bleeding related	0 vs 8 (P = 0.001)
Nagaoki et al[89]	Edoxaban 60 mg or 30 mg once daily (20 pts)	Child-Pugh A; (15 pts); Child-Pugh B; (5 pts)	PVT	Adverse events of grades 3/4 according to Common Terminology Criteria for Adverse Events version 4.0	3 vs 2 (P = 0.335)
	Warfarin (30 pts)	Child-Pugh A; (15 pts); Child-Pugh B; (10 pts); Child-Pugh C; (5 pts)
De Gottardi et al[83]	Rivaroxaban (30 pts); Dabigatran (4 pts); Apixaban (2 pts)	Mean 6	PVT (22 pts); Budd Chiari syndrome (5 pts); Cardiac Arrhythmia (5 pts); DVT (2 pts); Other (2 pts)	Major bleeding	1
				Minor bleeding	4
Intagliata et al[84]	Apixaban 5 mg or 2.5 mg twice daily or; Rivaroxaban 20 mg or 10 mg daily (20 pts)	Child A; (9 pts); Child B; (11 pts)	PVT (12 pts); Non-splanchnic VTE (4 pts); Atrial fibrillation (4 pts)	Major bleeding	1 vs 2 (P = 0.6)
	LMWH or VKA (19 pts)	Child A (9 pts); Child B (10 pts)		Moderate bleeding	1 vs 1
				Mild event	2 vs 1
Hum et al[85]	Rivaroxaban 15 mg daily (17 pts); Apixaban 5 mg twice daily (10 pts)	Child A; (11 pts); Child B; (12 pts); Child C; (4 pts)	PVT (4 pts); DVT (12 pts); Atrial fibrillation (15 pts)	Major bleeding	1 vs 5 (P = 0.03)
	LMWH or WKA (18 pts)	Child A; (7 pts); Child B; (9 pts); Child C; (2 pts)		Moderate bleeding	4 vs 5 (P = 0.45)
				Mild bleeding	3 vs 0 (P = 0.26)
Goriacko et al[91]	Dabigatran (35 pts); Rivaroxaban (29 pts); Apixaban (11 pts)	Child A; (48 pts); Child B; (26 pts); Child C; (1 pts)	Atrial fibrillation	Major bleeding	3.3% vs 3.9% (P = No significance)
	Warfarin (158)	Child A; (56 pts); Child B; (93 pts); Child C; (9 pts)

PVT: Portal vein thrombosis; DVT: Deep vein thrombosis; VTE: Venous thromboembolism; LMWH: Low molecular weight heparin; VKA: Vitamin K antagonist.

Table 2 Efficacy of direct oral anticoagulants in portal vein thrombosis treatment in cirrhosis

Ref.	Study design	Drug administrated (n of patients)	Duration of treatment	PVT type	Results (cases vs controls)
Ai et al[87]	Prospective cohort study	Rivaroxaban 20 mg once daily (26 pts)	6 mo	Chronic PVT;	At 3 mo:; Complete/partial recanalization: 5 vs 0 (P = 0.026); At 6 mo:; Complete/partial recanalization: 11 vs 1 (P = 0.003)
		Dabigatran 150 mg twice daily (14 pts)	6 mo
		No treatment (40 pts)
Hanafy et al[88]	Randomized, controlled, interventional, open-label study	Rivaroxaban 10 mg twice daily (40 pts)	Until recanalization and prolonged for 1 or 2 mo in complete recanalization of PVT which non-involvement/ involvement of SMV and for 6 mo in case of positive thrombogenic assay or partial recanalization;	Acute PVT	Complete recanalization: 34 vs 18 (P = 0.001); Partial recanalization: 6 vs 0 (P = 0.001)
		Warfarin (40 pts)
Nagaoki et al[86]	Retrospective cohort study	Edoxaban 60 mg or 30 mg once daily (20 pts)	6 mo	PVT	Complete recanalization: 14 vs 6 (P < 0.001); Partial recanalization: 4 vs 3 (P = 0.312)
		Warfarin (30 pts)

PVT: Portal vein thrombosis.