Pulmonary Embolism and Deep Vein Thrombosis in Northern Iran
M. Nikparvar Fard MD, M.R. Zahed Pour Anaraki MD
Department of Internal Medicine, Tehran University of Medical Sciences, Tehran, Iran
Objective To determine the incidence
and case fatality rate of VTE and its associated risk
factors in northern Iran.
Design A retrospective medical chart review.
Setting Imam Hospital, one of the largest teaching hospitals of northern Iran.
Methods Review of medical records of all patients with the final diagnosis of deep vein thrombosis (DVT) and/or pulmonary embolism (PE), discharged between March, 1989 and June, 1997.
Results Out of 232,000 patients, 140 had DVT, and 70 had PE, giving a VTE hospital incidence of 9/10,000. The mean age of these patients was 43 years. The female/male ratio was 1.4. Ninety five percent of patients had one or more risk factors for VTE. Two or more risk factors presented among 67% of cases. The most common risk factors were age ( 40 years (45%), immobility (29%), pregnancy or puerperium (23%), previous VTE (16%), major surgery (16%), and deep venous insufficiency (12%)). No patient had received any prophylaxis. Case fatality rate of PE in(12%) our patients was 11%. The incidence of VTE increases with age.
Conclusion The hospital incidence of VTE in northern Iran, is much lower than that reported from Western countries. The most important reason are youthfulness of the Iranian population and probably, their hematological profiles. As the Iranian population's age increases, VTE will become a growing public health problem. The mean age of patients was 25 years lower than Western studies. Our study confirms earlier reported risk factors. Because of the high birth rate, pregnancy and puerperium are among the most important risk factors. Prophylaxis for VTE is highly under-used by our physicians. Clinical features and fatality rates are in keeping with Western reports. The fatality rate of VTE increases with number of risk factors.
Key Words: Deep vein thrombosis · pulmonary embolism · incidence · risk factor · Iran
Venous thromboembolism (VTE) is comprised of two related diseases, i.e., deep vein thrombosis (DVT), and pulmonary embolism (PE).
PE is the most common preventable cause of death in hospitalized patients of Europe and North America and accounts for 10% of in-hospital mortality.1-3 However, there are some studies indicating a low incidence of VTE in the Far East.4-6
Virchow proposed three basic factors, i.e., blood stasis, intimal injury, and hypercoagulability, that would result in thrombus formation. It is evident that the risk for VTE increases in direct proportion to the number of predisposing factors.7-9 In a review of 1,231 patients treated for VTE, 96% had one or more recognized risk factors.10
Because the signs and symptoms of VTE are nonspecific and may be confused with a variety of other cardiopulmonary disorders presenting in a similar way, the total incidence and mortality rates of VTE are still uncertain.11,12 On the other hand, in more than half of the patients with clinically suspected VTE, the diagnosis is excluded by objective methods.13-15
The diagnosis and treatment of VTE are difficult and expensive. PE is recognized in only < 30% of patients before death.1,2 Moreover, there is no distinctive feature separating these patients from those in whom the diagnosis of PE was not suspected before death.3 About two thirds of fatal PE's are not diagnosed and this situation has not changed over the past three decades.16 Although, VTE is less common in some regions but it is an indisputable fact that VTE is a silent and usually undetected killer worldwide. As a consequence, the only effective means of reducing the VTE related mortality is to establish prophylactic measures against the development of DVT.17,18
The current research was conducted to study the epidemiology of VTE in northern Iran.
Patients and Methods
In a retrospective study, the data of all patients with the final diagnosis of DVT and/or PE discharged between March, 1989 and June, 1997 from Imam Hospital, one of the largest teaching hospitals of northern Iran, were analyzed.
All medical records filed according to the 9th revision of International Classification of Diseases (ICD-9-CM) codes for DVT; 451.2, 451.11, 451.19, 451.81, 453.2, 453.8, 453.9, 671.30, 671.31, 671.33, 671.40, 671.42, 671.44, 671.9(0-4), 997.2, 999.2, and codes for PE; 415.1, 639.6, 673.20, 673.24, 996.7, were reviewed. A case was accepted if a written hospital discharge diagnosis of DVT and/or PE was present.
Factors studied included demographic characteristics, known risk factors for VTE, concurrent medical conditions, diagnostic methods, prophylaxis against VTE, signs and symptoms of VTE and outcome of the disease. Identification of risk factors was based on a careful review of the records. Obesity was defined as weight > 20% above the median recommended weight for height.19 Because most of the records did not give the height and weight of the patients, the physician's assessment of the patients as "obese" was accepted. Surgery was designated as "major procedure", if general or epidural anesthesia used for operation, lasted ³ 30 minutes. The classification of fractures was limited to patients who had a hip, leg or spine fracture. Atrial fibrillation was categorized as organic heart diseases. Catheterization included any diagnostic or therapeutic penetration into the central venous system. Prolonged immobility was defined as continuous bed rest for ³ 2 days.
For analysis, the patients were classified into two groups of DVT and PE. Patients in the PE category might have concomitant signs and symptoms of DVT too. Only the last episode of VTE in patients with recurrent form of the disease entered the analysis.
Differences in the ratio of categoric variables were evaluated by z test. Comparison of mean age between various group were made with the two sample t test.20
There were 232,000 acute-care discharges from the Imam Hospital during the study period, of which 210 carried a discharge diagnosis of DVT and/or PE. The characteristics of this group are summarized in Table 1. None of these patients had received any prophylaxis against VTE. The mean age of these patients was 43 years. The male patients were older than females by about 10 years (p<0.001). The age and sex distribution of VTE patients is shown in Fig. 1. We cannot calculate the incidence of VTE from the available data. However, the ratio of numbers in each age group will provide a reliable index of the age specific incidence rates of VTE (Table 2).21
It is well known that many patients with signs and symptoms of VTE will not have this disease when objective diagnostic tests are performed.13-15 One or more signs and symptoms suggestive of DVT (Table 3) or PE (Table 4) were observed in all of our patients. The diagnosis of the disease was confirmed objectively by doppler study in 93 (66%) of 140 patients with DVT. Among 70 patients with PE, the diagnosis was objectively confirmed in 57 (81%) cases by segmental or larger defect on pulmonary perfusion scan (53%) and/or doppler diagnosis of DVT (44%). Restricting diagnosis to objectively confirmed cases, proportionately reduced the incidences rates of VTE, however, the shape of the age distribution and other results were essentially unchanged.
For comparison purposes the relative frequency of risk factors among 210 patients with VTE in this study and the results of Worcester study,10 are shown in Table 5. Two or more risk factors were present among 67% of patients and only 5% had no apparent risk factor. The average number of risk factors for every all patients was 2, while this figure was 1.9, and 2.2 for DVT, and PE respectively. The calculation of risk factors was according to those mentioned in Table 5 and other probable risk factors were not considered. Among those not considered were prolonged travel (3 patients), prolonged walking (3 patients), systemic prednisolone therapy (3 patients) and diabetes mellitus (2 patients). Autoimmune diseases included Behcet's syndrome (4 patients) and lupus anticoagulant antibody (2 patients). Eleven patients had cancers of colon and rectum, gallbladder, breast, testes, prostate and leukemias. VTE complications occurred within 20 days of puerperium and 14 days after myocardial infarction. Thirty-three patients developed VTE within 40 days of major surgery. All of these patients had another risk factor in addition to surgery. The most common types of surgery were related to orthopedics, cancer, obstetrics and gynecology (Table 6).
In-hospital fatality rate of PE was 11%. The eight patients who died of PE, had an average of 4 risk factors and a mean age of 45 years. Their most common risk factors were age ³ 40 years, past history of VTE and surgery.
In our study, the hospital incidence rate of VTE was 9 per 10,000 of admissions, while 90 per 10,000 in the United States (p<0.001).22 Although this ratio cannot predict exactly the population-based annual incidence of VTE but indicates its relative infrequency in Iran. Many factors contribute to this relatively low incidence. There is an association between increasing age and a higher incidence of VTE.23-25 In the present study, the incidence of VTE increased about 5-fold from the age of 20 to 80 years (p<0.05). A community-wide study performed in 1986, based on the data abstracted form medical records in Massachusetts (The Worcester VTE study) 22 showed that the incidence of VTE increases exponentially with age by a factor of 200 between 20 and 80 years of age. The Iranian population, like other Middle Eastern countries, is very young; while about 43% of people in the West are aged 40 years, only 18% of Iranians are in this age range.26,27 This youthful demographic distribution results in not only a lower incidence of VTE, but also a lesser mean age of patients, which is about 25 years younger than their Western counterparts. However, with increasing age of the Iranian population VTE will become a growing public health problem.
The influence of race and geographic area on VTE was recently reported. DVT has a lower incidence among the black Caribbean population than among the North American blacks.28
Activated protein C resistance (factor V Leiden) is the most common inherited venous thrombophilia detected among 33-60% of patients with VTE in Europe and the United States.29,30 Factor V Leiden is relatively common (allele frequency 4.4%) in those with European ancestry but is rare among those with African or Asian origin.31-33 Also, most of the major known risk factors (cancer, surgery, estrogen therapy, deep venous insufficiency, obesity and pregnancy) have large regional differences. Recently, hyperlipidemia34 and alcohol abuse,7,23 which have higher prevalence in the West, were suggested as possible risk factors. Other possible causes for the regional differences might be higher fibrinolytic activity,35 greater susceptibility to anticoagulants,36 influence of climate and physical activity. Physically inactive individuals are more thrombogenic.37 Our findings are anticipated to stimulate more interest in the comparative study of the Iranian hematological profiles and ethnic particulars.
Without a non-PE, non-DVT control group and exact histories, we are not able to comment on the relative risk conferred by various factors. The prevalence of some risk factors is not similar to western studies because of diverse ethnic and social characteristics of each population. On average, every patient displayed 2 risk factors and only 5% of patients had none. Because retrospective studies underestimate the positive statistics, the real percentage of patients with no risk factor may be lower. This highlights the significance of detecting risk factors to determine the high risk group in order to institute proper prophylaxis.
Surgical patients with VTE had on average, 3 risk factors. Surgery constitutes a documented risk of VTE, however only in combination with other risk factor predispose to VTE.38 Most venous thromboembolic events occurred between 7 and 20 days after operation, however, 5 patients developed this complication 40 days after surgery. This analysis provides a useful basis for prolonged prophylactic measures after hospital stay. Other studies also support this finding.39
The crude birth rate in Iran is high (35/1000 in 1994) thus making pregnancy a major risk factor.26 Pregnancy or puerperium were present in 39% of female patients. This results in a lower mean age of female patients and a higher female/male ratio (1.4) compared to Western counterparts (1.1).22 A study in the Assir region of Saudi Arabia showed the same results.40
Most of recognized risk factors usually accompany others. Evaluation of patients who had only one risk factor (Table 5), clarifies those important risk factors that act more independently (age 40, pregnancy, past history of VTE, estrogen treatment, autoimmune diseases).
The clinical features in our patients conform well to those reported in the West, but perhaps appeared in a more symptomatic form, which may result from the fact that autopsies are less frequently performed as, indeed are screening tests for VTE.
Despite long-standing convincing evidence of the efficacy and safety of a number of prophylactic agents,41,42 studies have proved that of patients who fulfill criteria for moderate or high risk of VTE only a minority receive any form of prophylaxis. 17,18 In this study, prophylaxis against VTE was highly under used by physicians, indeed it was not provided to any of the patients in our case study, but however in the Worcester study, 13.5% of patients with a discharge diagnosis of VTE received it before the diagnosis was suspected.10 The use of prophylaxis will improve if physicians participate in continuing medical education programs on the prevention of VTE.43
The in-hospital fatality rate, observed in this study, appears similar to those reported from controlled clinical trials in major academic health centers.22,44
Presence of an average of four risk factors per patient who died of PE, denotes that the more the number of risk factors, the higher the probability of developing PE and its fatality. It is not clear whether this increase in fatality may be attributed to the accompanying risk factors, or from the severity of PE, certainly, both play an important role. This fact draws attention to the need to administer prophylaxis to those with high risk factors.
The cooperation of the staff of the Medical Records Department of Imam Hospital in supplying necessary data is appreciated. We wish to thank H. Younesi and N. Hooshmand for their helpful comments.
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