Deep vein thrombosis and pulmonary embolism in cirrhotic patients: Systematic review

Table 1 Hemostasis changes in chronic liver disease patients

Factors favoring anticoagulant state	Factors favoring prothrombotic state
Thrombocytopenia (decreased thrombopoietin, splenic sequestration)	Decreased liver synthesis of antithrombin III, protein C, protein S
Thrombocytopathy (impaired platelet function)	Elevated von Willebrand factor levels
Vitamin K deficiency	Increased factor VIII levels
Decreased synthesis of coagulation factors including Factor II, VII, IX, X, V, fibrinogen	Genetic predispositions like Factor V Leiden
Reduced clearance of tissue plasminogen activator

Table 2 Risk of venous thromboembolism in chronic liver disease patients: major studies

Ref.	Type	n	Control	VTE% (n) DVT/PE	RR/OR (95%CI)	Comments
Northup et al[6], 2006	Case control	21000 cirrhotics	113 (cirrhotic patients without VTE)	0.5 (113) (74 DVT, 22 PE, 17 both)	Risk factor for VTE: low albumin 0.25 (0.10-0.56)	INR, MELD: no correlation
García-Fuster et al[31], 2008	Retrospective	2074 cirrhotic patients		0.8 (17) (11 DVT, 7 PE, 1 both)		5 patients had antiphospholipid antibodies
Gulley et al[5], 2008	Case control	963 cirrhotics	Control 1:12405 non cirrhotic patients without selected co-morbidities Control 2: non cirrhotic patients with CKD (1692), HF (4489), or solid organ cancer-673	1.87 (18)	Risk factor for VTE: Albumin 0.47 (0.23-0.93) PTT: 0.88 (0.84-0.94)	Cirrhosis not a risk factor on multivariate analysis OR 0.87 (0.2-2.6)
Dabbagh et al[32], 2010	Retrospective cohort	190 chronic liver disease patients stratified by INR quartiles		6.3 (12)		Higher INR or higher Child-Pugh stage does not prevent VTE
Lesmana et al[33], 2010	Case control	256 cirrhotic patients		4.7 (12)	Risk factor for VTE: Diabetes 4.26 (1.21-15.0)
Anthony Lizarraga et al[34], 2010	Case control	108 CLD patients with VTE (includes 22 patients with PVT)	108 CLD patients without VTE	0.73 (108 out of 14,790 admissions) Includes PVT as well		Cases had lower albumin and hematocrit, higher platelet count, bilirubin and aPTT
Aldawood et al[9], 2011	Retrospective cohort	226 cirrhotic patients		2.7 (6)		Significantly longer median LOS in patients with VTE (43 vs 8 d, P = 0.004)
Walsh et al[11], 2013	Case control	27 CLD patients with VTE	81 CLD patients without VTE	0.65 (17 out of 2606 admissions) (14 DVT, 3 PE)	Risk factor for VTE: low albumin 5.14 (1.05-25.2)	VTE patients had lower transaminases, albumin and hematocrit
Søgaard et al[35], 2009	Population based, case control	VTE = 99444	Population controls without VTE 496872		Cirrhosis: RR 1.74 (1.54-1.95)	RR 2.06 (1.79–2.38) for unprovoked VTE
Wu et al[8], 2010	Population based, case control	Compensated cirrhotics = 408253 Decompensated = 241626	Non cirrhotic controls = 575057	0.8% for cirrhotics,	Age < 45 yr	VTE associated with increased mortality and LOS in both compensated and decompensated cirrhotics
					compensated: 1.23 (1.04-1.46)
					decompensated: 1.39 (1.15-1.69)
					Age > 45 yr
					compensated: 0.90 (0.85-0.95)
					decompensated: 0.97 (0.91-1.04)
Saleh et al[37], 2011	Population based	Alcoholic CLD: 4927000		0.6% for alcoholicCLD
		Non-alcoholic CLD: 4565000		0.9% for non-alcoholic CLD
Ali et al[10], 2011	Population based cross-sectional	449798 cirrhotic patients		1.80%	Greater morbidity, malnutrition, black race, central venous line associated with higher risk of VTE	DVT associated with longer LOS
				(1% DVT, 0.9% PE)

DVT: Deep vein thrombosis; PE: Pulmonary embolism; INR: International normalized ratio; MELD: Model for end stage liver disease; CLD: Chronic liver disease; VTE: Venous thromboembolism; CKD: Chronic kidney disease; PVT: Paroxysmalventriculartachycardia; LOS: Length of stay.