**3. Deep vein thrombosis in developing countries**

Deep vein thrombosis is a preventable disease and the incidence of VTE is 1-3 per 100 per year (Nordstrőm et al., 1992; Anderson et al., 1991; Oger et al., 2000; Cushman et al., 2004, ). DVT is a significant cause of morbidity and mortality and without prophylaxis, the risk of a DVT event is especially high in patients admitted to medical orthopedic surgery wards (Geerts et al., 2008), with an incidence of venographic DVT without prophylaxis estimated at 40% to 60% (Geerts et al., 2008). Given its silent nature; the incidence, prevalence, morbidity and mortality rates of DVT are probably under-estimated in developing countries. Although most patients survive DVT, yet serious and costly long-term complications may occur; almost one-third of patients will suffer from venous stasis syndrome (postphlebitic syndrome) (Prandoni et al., 1996). DVT is a major burden on US healthcare systems: estimates put costs at nearly \$500 million per year (Hawkins, 2004).

#### **3.1 Scale of DVT problem in the developing countries**

DVT in developed counties is considered a public health problem and over the years this has led to elaboration of numerous strategies directed towards reducing the risks of DVT.

Emerging Issues in Deep Vein Thrombosis; (DVT) in Liver Disease and in Developing Countries 105

perhaps the Middle East. In developing countries there is very scanty and non-conclusive data on the prevalence, incidence, risk factors, genetic predisposition, distribution of DVT occurrences among different age groups and gender, and the burden of DVT on different patient groups (e.g. post-surgical, pregnancy etc…). Most importantly, how physicians manage DVT is also unknown and no cost-effective analysis is available on the current treatment regimens deployed in these countries. Such registry for DVT should include demographic data and extensive medical history (past and present). Detailed information on environmental, lifestyle and occupational factors could help identifying certain groups who are at increased risk of developing DVT or its complications. There is also need to accumulate laboratory data which should include blood group, factor VIII, inherited thrombophilic defects (such as factor V Leiden and prothrombin mutations), fibrinogen level, as well as routine laboratory investigations. Screening for inherited thrombophilia and other genetic diseases that predispose to DVT is crucial and has gained popularity worldwide. The available data on the prevalence of thrombophilic risk factors for VTE, particularly factor V Leidin, prothrombin G20210A, mutations C677T methylenetetrahydrfolate reductase and hyperhomocysteinaemia) in developing countries is scanty but agree on their rarity and much lower prevalence than in developed countries (Jun et al 2006,

The burden of DVT in the developing world is unknown due to lack of documentation and large-scale research projects aiming at identifying the different epidemiology aspects. Some of the developing countries (Saudi Arabia, United Arab of Emirates and the rest of the Arab Gulf countries), have the financial resources to setup such registries. However, setting up registries requires substantial training to the current and future personnel who are working fulltime in maintaining them. Policymakers, represented by the governments, academic medical centers and, most importantly, local and regional funding agencies, must work together in order to consider emphasizing DVT as a public health problem so that the appropriate increasing proportion of public health resources is reallocated to address DVT and its related issues.

Registries will not only allow tracking DVT in terms of its epidemiology, but also how much it burdens each country's economy. Pharmacoeconomic analysis is of great value in the evaluation of the cost of medical care. For example, cost-identification analysis seeks to identify the cost of providing the treatment of the disease. Cost-minimization analysis seeks to identify the least expensive alternative intervention to get the same outcome after treating the disease. Most importantly, cost-of-illness analysis estimates the total financial burden of DVT or its associated disability (e.g. reduced working hours, sick days, less life-expectancy etc…) to the country. This is done by estimating the total cost of diagnosing DVT, its management and the DVT-associated lost productivity. Cost-benefit analysis evaluates one or more treatment regimens in terms of pure currency expressions (e.g. dollars). This will allow the governments to identify which diseases cost higher. For example, in this form of analysis, we can compare the cost of DVT awareness, prevention and treatment to the cost of chronic kidney disease. Such analysis guides the policymakers to identify the top ranked

et al 2002, Lim et al 2004, Omar et al 2007).

**3.2.4 The cost and value of pharmacoeconomics research** 

diseases affecting the economy and allocates more dollars to combat them.

**3.2.3 Epidemiology** 

Given this to be the situation in the developed countries, the the magnitude of the problem would be much lower in the developing countries. Indeed many population studies that are carried in Western developed countries documented the lower incidence of VTE in Asians and Hispanics compared to Caucasians (Kearon 2001, White et al 2009).

Although there is strong evidence that the prevalence of venous thrombo-embolism (VTE) varies significantly among different ethnic/racial groups, the genetic, physiologic and/or clinical basis for these differences remain largely undefined (White et al ., 2009).

Identifying the scale of DVT in developing countries is difficult due to scanty and conflicting available published literature on the scale of the problem, the diagnostic tools, management and treatment challenges facing these countries. Most published information on the DVT was generated from small hospital-based studies that documented DVT as a significant complication of orthopedic surgery particularly total knee arthroplasty (Chung et al 2010, Ko et al. 2003, Leizorovicz et al 2005, Sen et al 2011, Sen et al 2011), and general hospital patients (Ogeng'o et al 2001, Angchaisuksiri et al 2007, Sakon et al. 2006, Lee et al. 2009). Essentially all these and other similar studies advocated the importance of thrombohphylaxis to avoid the risk of VTE.

As to population studies very few could be identified and almost all from Asian Far Eastern countries particularly China and Korea. In one study from Korea the incidence of VTE, DVT and PE per 100,000 individuals was found to be 8.83, 3.91 and 3.74 in 2004 and increased to 13.8, 5.31 and 7.01 in 2008 (Jang et al 2001). Another recent study from Hong Kong documented an annual incidence of of VTE at 16.6 events per 100,000 populations (Lui et al 2002). Another Chinese study reported the incidence of DVT and PE of 17.1 and 3.9 per 100,000 populations (Cheuk et al 2004). The incidence of DVT in all three studies is almost one tenth that reported from developed counties; yet the problem of DVT remains to be a health problem that clinicians should be aware of.

#### **3.2 Challengesof DVT In developing countries**

#### **3.2.1 Health disparity in the developing world**

There is remarkable disparity in standards of the health care among developing countries, especially the percentage of the Grand National Product that is expended in health care. Also, when comparing developed to developing countries, some countries like Saudi Arabia, Egypt, Jordan and the UAE could take the lead: Egypt (5.8%), Saudi Arabia (4%), Pakistan (2.4%) and India (4.8%) have limited total expenditure on health, compared to the United States (15.2%), Switzerland (11.5%), France (10.1%) and Norway (10.3%) (WHO Health Report, 2006). Such disparity shows up as unequal distribution of healthcare personnel and deficiency in training programs in the developing world. This is also reflected on the life expectancy and disease outcome and survival in these countries.

#### **3.2.2 Registries**

In reviewing the available evidence on the epidemiology of deep vein thrombosis (DVT) in the developing countries, it is quite clear that there are few on-going registries that track data on patients with DVT. Most of those registries are hospital-based rather than national. For example in Saudi Arabia there is the Saudi Thrombosis and Familial Thrombophilia (S-TAFT) Registry (Saour et al., 2009), which is considered the only registry in Gulf Region and perhaps the Middle East. In developing countries there is very scanty and non-conclusive data on the prevalence, incidence, risk factors, genetic predisposition, distribution of DVT occurrences among different age groups and gender, and the burden of DVT on different patient groups (e.g. post-surgical, pregnancy etc…). Most importantly, how physicians manage DVT is also unknown and no cost-effective analysis is available on the current treatment regimens deployed in these countries. Such registry for DVT should include demographic data and extensive medical history (past and present). Detailed information on environmental, lifestyle and occupational factors could help identifying certain groups who are at increased risk of developing DVT or its complications. There is also need to accumulate laboratory data which should include blood group, factor VIII, inherited thrombophilic defects (such as factor V Leiden and prothrombin mutations), fibrinogen level, as well as routine laboratory investigations. Screening for inherited thrombophilia and other genetic diseases that predispose to DVT is crucial and has gained popularity worldwide. The available data on the prevalence of thrombophilic risk factors for VTE, particularly factor V Leidin, prothrombin G20210A, mutations C677T methylenetetrahydrfolate reductase and hyperhomocysteinaemia) in developing countries is scanty but agree on their rarity and much lower prevalence than in developed countries (Jun et al 2006, et al 2002, Lim et al 2004, Omar et al 2007).
