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Yang et al. Hepatoma Res 2020;6:37 I http://dx.doi.org/10.20517/2394-5079.2020.09 Page 5 of 13

continues to progress. The degree of cirrhosis worsens with time, and the occurrence of PVT is related to the
severity of cirrhosis directly or indirectly.

Platelet counts
The enlarged spleen secretes related factors that inhibit platelet release from the marrow and reduces
[63]
thrombopoietin during cirrhosis . Once the spleen is removed, the suppression and clearance of platelets
disappear, megakaryocytes proliferate in the marrow, causing platelets to skyrocket transiently. The formation
[64]
of PVT might be associated with the soaring platelet count after operation .

[11]
Preoperative decrease in platelet numbers is related to PVT , the incidence of PVT in patients with PLT
9
[11]
9
less than 50 × 10 /L before surgery is significantly different from patients with PLT greater than 50 × 10 /L .
And PLT is considered to be an independent risk factor for PVT after splenectomy [6,13,29] .
PLT often peaks at 3 to 20 days after splenectomy and gradually decreases to normal level. In one study,
[29]
9
PVT was detected on the 6th day after surgery in patients whose PLT exceeded 200 × 10 /L . Researchers
[65]
9
indicate that when the postoperative PLT exceeds 1000 × 10 /L, PVT is almost sure to take place . The ratio
of maximum postoperative PLT to preoperative PLT (r = 1.144; P = 0.007) and PLT increasing to > 8 times
[59]
baseline levels after surgery are risk factors for PVT after LS . Moreover, elevated platelets and D-dimers
can cause atherosclerotic changes in blood vessels, and make the smooth muscles thick in the intima of the
[11]
vein wall, thus causing fiber breakage, blood cell adhesion and formation of thrombi .
However, thrombosis does not always occur in high PLT patients after splenectomy. Some studies have
suggested that the function and quality of platelets have a greater impact on thrombosis than simple PLT
[64]
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elevation . But this view is currently being challenged. In a prospective study, patients with PLT > 300 × 10 /L
9
after splenectomy were given antiplatelet therapy, namely aspirin, while the rest < 300 × 10 /L were not given
any antiplatelet therapy, and the results showed that there was no significant difference between the two
groups (7.0% vs. 16.1%, P = 0.858), so the pathogenesis of PVT may have nothing to do with the function
[29]
of platelets . Some researchers regard primary thrombocytosis as the cause of thrombosis, rather than
[66]
secondary thrombocytosis, and thrombocytosis after splenectomy is secondary thrombocytosis .
Elevated PLT and mean platelet volume (MPV) after splenectomy have been considered to be the main
[69]
cause of PVT [67-69] , and average platelet volume may also be a risk for PVT after surgery . As for the large
platelets, they are more active in metabolism and enzymatic reactions, and they contain more dense particles,
α-particles and highly active proteases. When larger platelets are activated, they can release more thrombus
precursor material to induce thrombosis. Platelet membrane surface protein CD62P, also known as P-selectin,
is an indicator of the degree of platelet activation and functional status. Some researchers have found that
[70]
CD62P can be used as a sensitive high-risk indicator of PVT . Antiplatelet therapy should be adopted
[66]
when PLT exceeds 1000 × 10 /L , and the consensus about this aspect has not been well established. Some
9
9
clinicians believe that when the patient’s PLT is > 400 × 10 /L, anticoagulation therapy should be started
[71]
9
immediately . But for safety reasons, > 600 × 10 /L may be a more suitable PLT to start the treatment.
Level of D-dimer
D-dimer mainly reflects lytic function. It is used in the diagnosis and prevention of many thrombotic
diseases. The increase in D-dimer level is often associated with the enhanced lytic activity of secondary
[69]
[11]
fibrin . D-dimer has been reported as a diagnostic marker for PVT . In comparasion with PLT, D-dimer
performs better in predicting thrombosis. Some studies suggest that the combined application of D-dimer
[72]
and P-selectin can effectively diagnose PVT after splenectomy . Like platelets, increased D-dimer after
[11]
surgery can damage endothelial cells and cause PVT . Based on the views of some authors, the evaluation
of D-dimer serologic levels is considered to own the adequate sensitivity and high negative predictive value