Portal vein thrombosis in cirrhosis: Why a well-known complication is still matter of debate

Table 1 Reassessment between anti- and pro-hemostatic drivers in liver cirrhosis

Hemostasis phase	Anti-hemostatic drivers	Pro-hemostatic drivers
Primary hemostasis (vasoconstriction and platelet plug formation)	Thrombocytopenia	Platelet hyperactivity High molecular weight multimers von Willebrand factor levels Low ADAM TS 13 levels and activity
Secondary hemostasis (coagulation cascades)	Low anticoagulant factors levels: AT, protein C and S High procoagulant factor levels: factor VIII	Low procoagulant factors levels: fibrinogen, factor II, V, VII, IX, X, XI
Tertiary hemostasis (fibrinolysis)	Low plasminogen and high PAI levels	High t-PA levels Low TAFI and plasmin inhibitor levels

AT: Antithrombin; ADAM TS 13: A disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13; PAI: Plasminogen activator inhibitor; t-PA: Tissue plasminogen activator; TAFI: Thrombin-activatable fibrinolysis inhibitor[18].

Table 2 Studies on direct oral anticoagulants efficacy and safety in cirrhotics with portal vein thrombosis

Ref.	Study design	No. of patients	Thrombosis extension	Drug and dosage	Duration (mo)	Outcome	Bleeding complication
Martinez et al[80]	Case report	1	Complete PVT+ SMVT	UFH (BT) + rivaroxaban 20 mg daily	6	Complete recanalization	No
Intagliata et al[81]	Case series	5	3 PVT, 2 PVT + SMVT	2 Rivaroxaban 20 mg daily (1 VKA as BT) 3 Apixaban 2.5 mg twice daily	1-7	Complete recanalization (2 treated with rivaroxaban) Stable (1 treated with apixaban) Unkown (2 other cases)	No
De Gottardi et al[82]	Prospective	22	N/A	Rivaroxaban/Dabigatran/ Apixaban (60% VKA or LMWH as BT) mainly at lower dose	14.6 (mean)	N/A 1 recurrence of PVT with rivaroxaban	1 major GI bleeding and 4 minor bleedings
Yang et al[83]	Case report	1	PVT	Rivaroxaban 15 mg twice daily for 3 wk, then 20 mg daily	6	Complete recanalization	No
Nagakoky et al[84]	Prospective	20	PVT	Edoxaban 30 mg daily (16) or 60 mg daily (4) (2 wk of danaparoid sodium as BT)	6	Partial recanalization	3 major GI bleedings
Ponziani et al[85]	Case report	1	PV and intrahepatic branches thrombosis	Already on rivaroxaban 20 mg daily treatment, then LMWH	N/A	Portal cavernoma	No
Lenz et al[86]	Case report	1	Partial PVT	Rivaroxaban 10 mg daily	5	Complete recanalization (recurrence after withdrawal)	No
Qi et al[87]	Case report	1	Occlusive SMVT SVT	Rivaroxaban 15 mg daily for 1 mo then 10 mg daily	3	Partial	Upper GI bleeding
Pannach et al[88]	Case report	1	PV and intrahepatic branches thrombosis	Rivaroxaban 20 mg daily	N/A	Resolution	No

UFH: Unfractionated heparin; VKA: Vitamin K antagonists; BT: Bridging therapy; LMWH: Low molecular weight heparin; PVT: Portal vein thrombosis; SMVT: Superior mesenteric vein thrombosis; SVT: Splenic vein thrombosis; GI: Gastrointestinal.