Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory diseases—which
include CD and UC—that predominantly affect the gastrointestinal tract. The incidence
of IBD was reported to be 8–14 per 100,000 persons in the West.1 The crude annual
incidence of IBD was revealed to be 1.96–5.3 per 100,000 persons in Asia.2 The ratio
of UC to CD was 2.0 in Asia. IBD is increasing in both incidence and prevalence in
Asian area.3 IBD is associated with autoimmune disease and increased risk of thromboembolic
events. Venous thromboembolism (VTE) includes deep-vein thrombosis and pulmonary embolism.
VTE is associated with significant risk of mortality, chronic complications, and recurrence.
The 1-year case-fatality rate has been reported to be 22%–29% in Western countries.4
5 One-third of patients who survived deep vein thrombosis would experience long-term
post-thrombotic syndrome. Symptoms include pain, persistent swelling, and recurrent
ulcers of the affected extremity. Patients with pulmonary embolism may develop chronic
pulmonary hypertension. In this review, we would discuss the difference in VTE incidence
between Asian and Western countries and evaluate whether Asian patients with IBD should
receive routine thromboprophylaxis.
The incidence of VTE in Western countries has been reported to range from 0.73 to
1.82 per 1,000 persons.6
7 The VTE incidence has been reported to be 0.21–0.57 per 1,000 persons in Asia.8
9 In North America, VTE was most common in African-Americans, with an incidence of
1.38–1.41 cases per 1,000 individuals per year, followed by Europeans (1.03–1.49 cases
per 1,000 individuals) and Hispanic populations. The incidence of VTE in Asian-ancestry
populations (0.21–0.29 cases per 1,000 individuals) was less than one-fifth the incidence
of African-Americans.9
In Western countries, patients with IBD have a nearly 1.5- to 4.0-fold higher risk
of VTE when compared with the general population.10 The overall incidence of VTE in
patients with IBD has been reported as 2.4–2.6 cases per 1,000 patients per year,10
11 and the incidence was revealed to increase to 9 cases per 1,000 patients per year
when disease flare-up in the U.K. IBD population.11 The incidence of VTE among patients
with IBD in Taiwan was reported to be 1.38 per 1,000 patients per year in a nationwide
study.12 As moderate-severe disease activity and hospitalization for IBD flares both
increase the risk of VTE,11 routine anticoagulant thromboprophylaxis is recommended
in patients hospitalized with moderate-severe IBD flares and in patients who have
undergone major abdominal-pelvic surgery during hospitalization (Table 1).10
11
12
13 For the treatment of VTE, a minimum of 3 months of anticoagulant therapy for IBD
patients with a symptomatic deep vein thrombosis, pulmonary embolism, or splanchnic
vein thrombosis is strong recommended.13 Currently, there is no evidence of which
anticoagulants is the most effective, treatment choice is depended on consistency
and quality of anticoagulation, ease of use, monitoring needs, side-effects and cost.8
However, these guidelines are based on data gathered from Western populations. In
general, the incidence of VTE in Asian populations is lower than that in Western populations.
Routine thromboprophylaxis is infrequently used in Asian patients with IBD.
The pathogenesis of VTE in patients with IBD is multifactorial, involving both genetic
and acquired factors. The hypercoagulation status can be caused by loss of anticoagulants
or thrombophilia. Thrombophilia refers to familial or acquired hemostatic disorders
that increases the risk of thrombosis. Loss of anticoagulants includes deficiencies
of antithrombin, protein C, and protein S. Thrombophilia can be caused by factor V
Leiden, prothrombin 20210A mutations, and elevation of procoagulant factors, such
as von Willebrand factor or factors V, VII, VIII, IX and XI. The variation among ethnicities
in incidence of VTE is attributed to genetic disparity. Chinese patients have lower
levels of thrombosis markers, including factor VIII, D-dimer, plasmin-antiplasmin,
and von Willebrand factor, than Caucasian or Hispanic patients. Lower incidence of
factor V Leiden and prothrombin 20210A mutation was also reported in Asian populations.14
Obesity is an endogenous risk factor for VTE. Increasing BMI was associated with a
rising risk of VTE. Although the prevalence of obesity has increased in Asia with
economic development, the adult prevalence of metabolic syndrome remains higher in
the United States (34.7%) than in Malaysia (27.5%) and China (7.3%).15 Other risk
factors include prolonged immobilization, surgery, hospitalization for IBD flare-up,
patient or family history of VTE, corticosteroid and oral contraceptive use (Table
2).11
16
Currently, pharmacological thromboprophylaxis is not standard treatment for patients
with IBD in Asian countries. A multinational, web-based survey showed ≤24% of clinicians
provide adequate prophylaxis for VTE in Asia.17 Our multinational collaborative study
enrolled 2,562 hospitalized IBD patients from Korea, Japan and Taiwan showed the average
incidence of VTE was 0.72–1.38 per 1,000 persons per year in East-Asian patients with
IBD.18 In Western patients with IBD, the overall incidence of VTE has been determined
to be 2.4–2.6 per 1,000 persons per year.10
11 Because of the relatively low incidence of VTE, the benefits of pharmacological
prophylaxis are expected to be small in Asian patients with IBD. These results also
support our current practice of not treating with prophylaxis for VTE. However, we
did observe a 2-fold increase in VTE risk in patients with IBD when compared with
the general population, and we recommend close monitoring of symptoms in patients
with IBD with high risk factors for VTE.
The incidence of VTE is lower in Asia for both general and IBD populations than in
Western countries. Currently, VTE prevention is not standard for Asian patients with
IBD, and routine pharmacological prophylaxis is not recommended. However, patients
with additional risk factors such as previous surgery, hospitalization, and moderate-severe
disease must be considered for routine thromboprophylaxis. Guidelines for VTE prophylaxis
in Asian patients with IBD should be established.