Splanchnic Vein Thrombosis: Current Perspectives

Figures & data

Table 1 Risk Factors For Splanchnic Vein Thrombosis

Risk Factors For SVT
Persistent Acquired Risk Factors	Transient Acquired Risk Factors	Inherited Risk Factors
Liver cirrhosis	Intra-abdominal Inflammations/infections	Factor V Leiden mutation
Solid cancer	Abdominal surgery	Prothrombin G20210A mutation
Myeloproliferative neoplasm	Hormonal therapy	JAK2V617F mutation
Inflammatory bowel disease	Pregnancy or puerperium	Protein C deficiency
Antiphospholipid syndrome		Protein S deficiency
Other hematologic disease (e.g. PNH)		Antithrombin deficiency
Autoimmune disease (e.g. Behçet’s disease)

Abbreviations: PNH, paroxysmal nocturnal haemoglobinuria; SVT, splanchnic vein thrombosis.

Table 3 Therapeutic Strategies For Patients With Splanchnic Vein Thrombosis And Thrombocytopenia, Kidney Failure Or Liver Cirrhosis

Comorbidity	Anticoagulant Therapy
Thrombocytopenia	LMWH	VKA	DOAC*
PLT 50-149,000/μl	Therapeutic dose	Therapeutic dose (INR target range 2.0–3.0)	Therapeutic dose**
PLT 25-<50,000/μl	50% of therapeutic dose or prophylactic dose***	Not recommended, consider switch to LMWH	Not recommended, consider switch to LMWH
PLT < 25,000/μl	Discontinue temporarily	Not recommended	Not recommended
Kidney failure
GFR 30–50 mL/min	Therapeutic dose	Therapeutic dose^§ (INR target range 2.0–3.0)	A, R therapeutic dose D, E consider dose reduction
GFR 15-<30 mL/min	50% of therapeutic dose^+		A, E, R use with caution and consider dose reduction D not recommended
GFR <15 mL/min	Not recommended		Not recommended
Liver cirrhosis
Child-Pugh A	Therapeutic dose	Therapeutic dose^# (INR target range 2.0–3.0)	Therapeutic dose
Child-Pugh B			A, D, E therapeutic dose^## R not recommended
Child-Pugh C			Not recommended

Notes: *In several countries the DOACs are currently not licensed for the treatment of SVT patients. **Limited experience is available in patients with platelet count <100l000/μL, consider switching to LMWH or VKA. ***In patients with acute thrombosis and high risk of thrombus progression, consider therapeutic LMWH dose and platelet transfusion support to maintain a platelet count of ≥ 40–50,000/μl. ⁺Consider monitoring the anti-factor Xa activity (target range 0.6–1.0 U/mL for enoxaparin BID, >1.0 U/mL for enoxaparin OD) or switching to UFH. Enoxaparin is the most studied LMWH in patients with kidney failure. ^§Patients with chronic kidney disease (low GFR values) might require lower doses to maintain the INR within the therapeutic range. ^#Since INR might not reflect the anticoagulation status, caution should be used in patients with Child-Pugh C class. ^##use with caution if liver enzymes > 2 ULN.

Abbreviations: A, apixaban; BID, twice daily; D, dabigatran; DOAC, direct oral anticoagulant; E, edoxaban, GFR, glomerular filtration rate; INR, international normalized ratio; LMWH, low molecular weight heparin; OD, once daily; PLT, platelet count; R, rivaroxaban; UFH, unfractionated heparin; ULN, upper limit of normal; VKA, vitamin K antagonist.

Table 2 Guidelines Recommendations For The Anticoagulant Treatment Of Splanchnic Vein Thrombosis

AASLD 2009^Citation71
Type Of Patients		Type Of Anticoagulation	Duration Of Anticoagulation
EHPVO	Acute	LMWH → VKA (I,B)	Transient risk factor	At least 3 months^ç (I,B)
			Persistent risk factor	Long-term (I,B)
	Chronic	Not specified	Transient risk factor	Not specified
		Persistent risk factor	Long-term (IIa,C)
BCS		LMWH → VKA (I,B)	Permanent anticoagulant therapy (I,C)
Cirrhotic		Case by case decision*
AISF 2011^Citation70
Type of patients		Type of anticoagulation	Duration of anticoagulation
EHPVO	Acute	LMWH → VKA	At least 6 months^$
	Chronic	Not specified	Not specified^£
BCS		LMWH → VKA	Not specified
ACCP 2012^Citation69
Type of patients		Type of anticoagulation	Duration of anticoagulation
SVT (except BCS)	Incidentally detected (2,C)		Not suggested°
	Symptomatic (1,B)	LMWH → VKA^#	Transient risk factor	3 months
Persistent risk factor or unprovoked			Extended anticoagulant therapy
BCS	Incidentally detected (2,C)		Not suggested°
	Symptomatic (2,C)	LMWH → VKA^#	Transient risk factor	Time-limited course
			Persistent risk factor or unprovoked	Extended anticoagulant therapy
Baveno VI 2015^Citation3
Type of patients		Type of anticoagulation	Duration of anticoagulation
EHPVO	Recent	LMWH → VKA (2b,B)	Transient risk factor	At least 6 months (1b,A)
			Persistent risk factor	Long-term (1b,A)
	Chronic	LMWH/VKA	Transient risk factor	Long-term therapy if history of intestinal ischemia or recurrent thrombosis (3b,B)
			Persistent risk factor	Long-term (3b,B)
BCS		Not specified	Long-term (5,D)
Cirrhotic			LMWH/VKA^§	Until liver transplantation (4,C) (no recommendation in non-candidates to liver transplantation^§)
EASL 2016^Citation2
Type of patients		Type of anticoagulation	Duration of anticoagulation
EHPVO (Non cirrhotic, non malignant)	Acute	LMWH (A1)→ VKA (B1)	Transient risk factor	At least 6 months (A1)
			Persistent risk factor	Long-term (B2)
	Chronic	Not specified	Transient risk factor	Long-term therapy if history of intestinal ischemia or recurrent thrombosis (B2)
			Persistent risk factor	Long-term (B2)
BCS (A,1)		LMWH → VKA	Indefinite period
Cirrhotic (A,1)		LMWH → VKA	At least 6 months (B1)**

Notes: Recommendations from each guideline have been graded with different classifications. For additional information, please refer to individual guideline texts. ^çConsider long term anticoagulation in patients with thrombus extension into the mesenteric vein (IIa,C). *Consider anticoagulation if known prothrombotic condition or thrombosis of the superior mesenteric vein (after adequate prophylaxis for variceal bleeding). ^$Consider long term anticoagulation in case of known thrombophilia, personal or family history of VTE, intestinal ischemia. ^£Consider anticoagulation in patients with persistent risk factors. ^°Consider anticoagulant therapy in case of acute and extensive SVT, progression of previous known thrombosis, and ongoing chemotherapies in cancer patients. ^#Consider LMWH alone in case of active cancer, liver disease or thrombocytopenia. ^§Consider anticoagulant therapy in selected cases: candidates to liver transplantation with thrombosis of the main portal vein trunk or progressive PVT (3a;B), thrombosis extension to superior mesenteric vein (5,D) and strong prothrombotic conditions (5,D). **Consider lifelong anticoagulation in patients with superior mesenteric vein thrombosis, with a past history suggestive of intestinal ischemia or liver transplant candidates (C,2). Consider prolonging anticoagulation for some months and until transplant in liver transplant candidates once PVT has been repermeated (B,2).

Abbreviations: AASLD, American Association for the Study of Liver Diseases; ACCP, American College of Chest Physician; AISF, Italian Association for the Study of the Liver; BCS, Budd-Chiari syndrome; EASL, European Association for the Study of the Liver; EHPVO, extrahepatic portal vein obstruction; LMWH, low-molecular weight heparin; RF, risk factor; SVT, splanchnic vein thrombosis; VKA, vitamin K antagonist; VTE, venous thromboembolism.

Figure 1 Suggested algorithm for the treatment of splanchnic vein thrombosis. *Consider prophylaxis of oesophageal bleeding (if varices).

Abbreviations: BCS, Budd-Chiari syndrome, RF, risk factor, SVT, splanchnic vein thrombosis.

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