Page 49 - Read Online

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

in diagnosing thrombotic events [24,73] , but the reported low specificity rate is expected because D-dimer is
elevated in different conditions, such as disseminated intravascular coagulation and sepsis [42,74,75] . However,
[42]
the negative predictive value of the test is significant . Negative test results will strengthen the diagnostic
value of other aspects and the need for more specific studies will be minimal. D-dimer only reflects
secondary fibrinolysis, and therefore, it can only have diagnostic value for the thrombosis that has occurred,
and cannot be used as a predictor of PVT.

Infection and inflammation
The spleen can produce immune substances such as immunoglobulins and complements to play an immune
[76]
role. In addition, the spleen also has the function of producing lymphocytes . Splenectomized patients are
at increased risk for infection, in particular, overwhelming post-splenectomy infection.

[77]
Infection and inflammation can cause a hypercoagulable state in the blood . Infection-related and
inflammation-induced coagulation activation is characterized by enhanced fibrin formation and impaired
fibrin degradation, where enhanced fibrin formation is caused by tissue factor (TF)-mediated thrombin
generation and inhibition of the anticoagulant system including proteins C and S. Inflammation increases
circulating levels of plasminogen activator inhibitor type 1, which inhibits endogenous thrombolytic
[78]
reactions, mediated by various pro-inflammatory cytokines .

Studies have shown that inhibiting IL-6 almost eliminates the coagulation effect of the TF-dependent
[79]
coagulation pathway . Monocytes stimulated by pro-inflammatory cytokines increase expression of TF in
sepsis [80,81] . In inflammation, platelets can be directly activated by endotoxin or proinflammatory mediators
(e.g., platelet activating factor). Platelets and granulocytes also can stimulate TF expression of monocytes
[82]
by activated NFκB . The interactions between inflammatory cells promote the expression of IL-1b, IL-8,
TNF-α, and P-selectin, and they have a role in mediating the adhesion of platelets to endothelial cells.

Other factors
Among all cirrhotic patients, 80%-100% of them have malnutrition. Malnutrition will further increase liver
[83]
damage, and exacerbate liver cirrhosis, so it can be seen as an indirect risk factor for PVT .
Among patients with liver cirrhosis, 70% of them have gene mutations before or after splenectomy. It mainly
includes prothrombin genes, coagulation factor genes and so on, which eventually make patients more prone
[84]
to thrombosis . For example, the G20210A mutation of the prothrombin gene has been found to play an
[85]
important role in forming PVT . Another study discovered that mutation rates of V-Leiden factor gene and
[86]
prothrombin gene were higher in patients with PVT than in controls , indicating that these genes may be
related to the onset and development of PVT.

In addition, low white blood cell count(≤ 2 × 10 /L), upper gastric bleeding history, and some underlying
3
diseases, such as hematologic diseases, are also thought to be independent risk factors for PVT [6,42,52] .

Pathological changes occur in the vessel wall because of intravascular pressure, leading to “atherosclerosis-
like” changes. It is an important factor that leads to PVT. As endothelial lesions are gradually aggravated, the
age of patients appears to be positively correlated with thrombosis. Older individuals are at increased risk
for PVT, which is linked to age-specific pathophysiological characteristics, including decreased blood flow,
endothelial injury, and hypercoagulability. Some authors have pointed out that > 50 years old might be an
independent risk factor for PVT. Patients who are over 50 are more than 20 times likely to suffer from PVT
[13]
than those younger .

Pancreatic fistula was reported as an independent risk factor for the development of PVT after the Hassab
[87]
operation . The reason may be that pancreatic fistula causes prolonged hospital stay for the patient and
increases the patient’s bed time.