Chapter 6 Discussion
6.3 Clinical Characteristic of VTE
In our study, 70.8% (definition 1) and 59.4% (definition 2) of VTE events occurred
within 1 year after the first diagnosis of cancer, with 35.8% (definition 1) and 18.0%
(definition 2) of events occurred at index date (Table 5.3). In a retrospective study based
on California cancer registry, 12% of VTE events were diagnosed at the time cancer was
diagnosed.5 The highest risk of VTE in the initial period after the diagnosis of cancer is
consistent with other studies.1,5-7,52,59,62
Thrombosis of portal vein is common in our study. Among patients with VTE,
51.5% (definition 1) and 18.2% (definition) of patients had portal vein thrombosis alone
(Table 5.4). More than 80% of the portal vein thrombosis occurred in patients with
primary diagnosis of liver cancer. Infectious diseases, inflammatory abdominal foci, and
malignant conditions of abdominal (including gastric, pancreatic, and liver cancer) are
well-known risk factors for portal vein thrombosis.95,96 Malignancies, especially liver or
pancreas cancer, are responsible for 21% to 24% of overall cases of portal vein
thrombosis.96 Liver cancer is the third common cancer in Taiwan and the most common
cause of cancer death each year.97 The high prevalence of liver cancer in Taiwan may
result in the high prevalence of portal vein thrombosis in our study cohort.
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6.4 Risk Factors for VTE
In multivariate logistic regression models, cancer site, prior history of VTE,
hypertension, arterial embolism, obesity, rheumatologic diseases, major surgery,
chemotherapy, and combination therapy were significantly associated with higher risk
of VTE (Table 5.9). Several risk factors, including arterial embolism,51 obesity,46,50,51
and chemotherapy48,51,52,98
were also reported in previous studies. Consistent with
previous studies, 48,50,51,53,54
we also found that cancer of GI tract, brain, lung,
gynecology, and liver were significantly associated with higher risk of VTE when
compared with other solid tumors.
Prior history of VTE is an important risk factor for VTE.99,100 In a prospective study
on VTE after cancer surgery, previous VTE history was a significant risk factor for
VTE.57 In our study, prior history of VTE was defined as being hospitalized with VTE
diagnosis within 2 years before index date. The definition of prior history of VTE based
on appearance of VTE diagnosis in inpatient claims is consistent with previous studies
in Taiwan based on NHIRD.10,101
Although the association of hypertension and development of VTE has been limited
in cancer patients,50 hypertension had been identified as an independent risk factor for
VTE in antiphospholipid antibody carriers.102 It was also found that hypertension was
associated with increased risk of PE in a study of 112,822 women based on biennial,
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mailed questionnaires.103 In a meta-analysis of association between cardiovascular risk
factors and VTE, patients with hypertension had higher risk of VTE (OR 1.51; 95% CI
1.23-1.85).104 From a laboratory perspective, an association between venous and arterial
events is plausible because they share common characteristics such as activation of
platelets and coagulation.104
Rheumatologic diseases were first identified as an independent risk factor for VTE
among cancer patients in our study. Rheumatologic diseases were not found to be risk
factors for VTE in previous studies.42,105 However, recent epidemiological studies
suggested that certain rheumatologic diseases, including rheumatic arthritis (RA),106,107
dermatomyositis/polymyositis and systemic lupus erythematous (SLE) were associated
with increased risk of VTE.106 Changes in expression of selectins and cellular adhesion
molecules of vessel endothelium induced by inflammation may contribute to the
initiation of venous thrombus formation.106
Many cancer therapies (including surgery, chemotherapy, antiangiogenic, and
hormone therapy) place cancer patients at greater risk for VTE. The risk of
postoperative VTE in cancer patients exceeds that of non-cancer surgical patients by 2-
to 3-folds.55 Without perioperative thromboprophylaxis, reported incidence of
proximal-vein thrombosis and PE can be as high as 10-20% and 1-5%, respectively.1
Our study found that major thoracic (OR 2.35, 95% CI 1.91-2.89), abdominal (OR 1.99,
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95% CI 1.62-2.45), and urogenital surgery (OR 2.12, 95% CI 1.52-2.94) is significantly
associated with higher risk of VTE. Furthermore, chemotherapy (OR 3.61, 95% CI
2.95-4.41) and combination therapy (OR 4.95, 95% CI 3.08-7.96) were also significant
risk factors for VTE.
In addition to cancer therapy, certain supportive care used in cancer patients also
appears to increase the risk of VTE. Khorana et al.51,108 found that both red blood cell
and platelet transfusions are associated with increased risks of venous thrombotic events
in hospitalized patients with cancer. However, our study showed conflicting result that
transfusion of blood and blood components was associated with reduced risk of VTE.
Further investigations are needed to confirm the association of blood transfusion and
VTE among cancer patients.
When the potential risk factors were recorded during the same hospitalization with
VTE admission, the causal relationship between the exposure to potential risk factors
and the development of VTE may be uncertain. Therefore, we conducted a sensitivity
analysis which included potential risk factors that documented in inpatient or outpatient
claims within 3 months before VTE event/end of follow up date only. The result of the
multiple logistic regression analysis was shown in Table 6.1. Primary cancer sites of GI
tract, brain, lung, gynecologic and renal, prior history of VTE, hypertension, arterial
embolism, obesity, abdominal surgery, chemotherapy, and combination therapy are
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significantly associated with greater risk of VTE in cancer patients. Besides, comorbid
renal failure and hospitalization ≥ 3 days within 3 months are also significant risk
factors for VTE. In contrast, blood transfusion was significantly associated with reduced
risk of VTE. The identified risk factors are consistent with previous studies.50,51,100
Table 6.1 Sensitivity analysis of risk factors for VTE
Variable Odds ratio 95% CI P-value
Cancer sites
Low risk (referent) High risk
Hematologic
1.78 1.51
1.44 - 2.22 0.95 - 2.39
<0.0001 0.0823
Prior history of VTE 4.67 1.80 - 12.09 0.0015
Comorbid diseases
Hypertension 1.38 1.14 - 1.66 0.0008
Renal failure 1.40 1.04 - 1.87 0.0273
Arterial embolism 2.91 1.32 - 6.43 0.0080
Obesity 3.31 1.33 - 8.21 0.0100
Potential risk factors
Abdominal surgery 1.32 1.03 - 1.69 0.0309
Chemotherapy 1.99 1.58 - 2.51 <0.0001
Combination therapy 3.89 2.36 - 6.39 <0.0001 Hospitalization ≥ 3 days 2.23 1.78 - 2.79 <0.0001
Blood transfusion 0.28 0.17 - 0.48 <0.0001
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