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Year : 2020  |  Volume : 7  |  Issue : 4  |  Page : 415-419

Assessment of risk factors in established cases of venous thrombosis

Department of General Surgery, Southern Railway Head Quarters Hospital, Chennai, Tamil Nadu, Ex-Pfizer Ltd., Mumbai, Maharashtra, India

Date of Submission10-May-2020
Date of Decision13-Jun-2020
Date of Acceptance11-Aug-2020
Date of Web Publication24-Dec-2020

Correspondence Address:
R Chithra Barvadheesh
Department of General Surgery, Southern Railway Head Quarters Hospital, Chennai, Tamil Nadu, Ex-Pfizer Ltd., Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijves.ijves_56_20

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Background: Despite prevalence of venous thrombosis (VT) in Indians, there are few prospective studies. Objective: To analyze the demographic profile, proven risk factors, and coagulation profile of south Indian patients with proven VT. Materials and Methods: This single-center prospective observational study was conducted among patients with proven VT from August 2013 to July 2019. Hypercoagulable workup (serum homocysteine, activity of protein C, protein S and anti-thrombin III, antiphospholipid antibodies immunoglobulin [IgM] and IgG, factor V [Leiden] mutation) was performed. Results: Out of 295 patients (mean age 56 years; male 64%) of VT, 85.76% had deep vein thrombosis (DVT) whereas 14.24% had superficial vein thrombosis (SVT). Patients with DVT were significantly older than those with SVT (P < 0.05). DVT was most common in the femoropopliteal segment 132 (52.17%), followed by the iliofemoral segment 78 (30.83%). Unprovoked primary cases (58%) were common. A total of 123 (41.69%) patients had identifiable provoking risk factors, of which malignancy 30 (24.39%) and postsurgery status 29 (23.58%) were the most common causes. A total of 101 (34.47%) patients were tested for coagulation abnormalities of whom 14 (13.86%) had normal profiles. Hyperhomocysteinemia was the commonest coagulation anomaly 59 (58.41%). Factor V (Leiden) mutation tested in 48 (16.27%) patients of which six (12.5%) were positive. Conclusions: Study population of VT revealed male predominance. Immobilization due to either medical or surgical causes, emerged as a major risk factor. The most common modifiable factor is postoperative care and the common coagulation anomaly is hyperhomocysteinemia.

Keywords: Factor V mutation, hyperhomocysteinemia, venous thrombosis

How to cite this article:
Barvadheesh R C, Gandhi R K, Dhandapani B S, Uchit GP. Assessment of risk factors in established cases of venous thrombosis. Indian J Vasc Endovasc Surg 2020;7:415-9

How to cite this URL:
Barvadheesh R C, Gandhi R K, Dhandapani B S, Uchit GP. Assessment of risk factors in established cases of venous thrombosis. Indian J Vasc Endovasc Surg [serial online] 2020 [cited 2022 Nov 26];7:415-9. Available from:

  Introduction Top

Venous thrombosis (VT) is a well-known entity including superficial vein thrombosis (SVT), deep vein thrombosis (DVT), and pulmonary embolism (PE). DVT is treatable, but is also an established cause for PE, which is a potentially fatal condition leading to considerable morbidity and mortality.[1] Most cases of DVT are silent in nature and are only identified when it has progressed for long, inside the body. Hence, it can be concluded that the incidence recorded can be compared to the tip of an ice-berg. It contributes substantially to patient morbidity, mortality, and cost of management.[2]

DVT is more common in western countries,[3] yet published literature mentions that it is no more than a rare entity among the Indian population.[4],[5] Each year, about two million Americans are diagnosed with DVT as per the statistics of American Heart Association.[6] Annual morbidity due to DVT in the United States outranks even the morbidity from heart attack or stroke. DVT contributes to hospitalization of about 0.6 million people in the USA every year and in the UK the hospitalization rate is about 1 in 2000. In India and other South Asian countries, the incidence shows huge variation of around 6%–75%.[7],[8]

Worldwide proven provoking factors are advancing age, obesity, previous history of venous thromboembolism, ongoing malignancy, immobilization, long bone fracture, multiple trauma, stroke, congestive heart failure, myocardial infarction, increased use of central venous line, presence of varicose veins, estrogen treatment, pregnancy, and surgical conditions[7] such as prolonged surgeries, abdominal, pelvic, and orthopedic surgery to lower limb.[9]

Although a number of surveys have been conducted to find out the incidence of DVT, such data is still lacking among the Indian population.[8] We found that there is a reasonable gap due to lack of information on the risk factors of VT in the Indian population. Hence, a prospective observational study was conducted among the south Indian patients with proven VT to assess their demographic profile, proven risk factors, and coagulation profile status.

  Materials and Methods Top

We conducted a prospective observational study from August 2013 to July 2019, at a tertiary care Hospital in Chennai, India. The Hospital Ethical committee permission obtained. All patients with proven VT attending the vascular clinic during the study period were included in the study. Patients with VT involving great saphenous vein, deep veins in both extremities, central veins, and splanchnic vein were included in the study, whereas patients admitted with PE with-out VT were excluded.

All data regarding the patient particulars, presentation of the disease, and provoking factors were recorded. Diagnostic confirmation was by duplex ultrasonography in all patients. All patients were treated according to the standard protocol, with parenteral heparin followed by oral anticoagulants. Patients without any identifiable primary provoking cause were evaluated with hypercoagulable profile workup (antiphospholipid antibodies immunoglobulin [IgG] and IgM, Factor III activity, Protein C and S deficiency, Serum Homocysteine). Factor V (Leiden) mutation assay was not included in the initial period due to techno-logistic constraints, but was included from 2016.

Statistical analysis

The data were entered in MS Excel 2007 worksheet and analyzed by descriptive statistical tools. Categorical data are presented as numbers and percentages whereas continuous data are presented as mean and standard deviation (SD). Unpaired t-test was used for comparison of continuous data between two groups. P < 0.05 was considered statistically significant.

  Results Top

A total of 295 patients (64% male; median age 55.5 years) were included in the study [Table 1]. There was no significant difference in the mean age of male and female patients (P > 0.05). With the total admissions of 112,133 patients during the study period, the incidence was 26.3/10,000 (<1%).
Table 1: Baseline characteristics of study population

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Of the total 295 patients, 253 (85.76%) had DVT whereas 42 (14.24%) had SVT [Table 2]. The mean (SD) age of patients with DVT and SVT was 56.33 (14.09) and 50.31 (13.36) years respectively [Figure 1]. The difference in the age group of patients with DVT and SVT was statistically significant (P < 0.010). DVT was found to be common in males 168 (66.40%), whereas occurrence of SVT was equal in male 21 (50%) and female patients 21 (50%). One interesting fact was that the mean age of SVT in females (47.2 years) is earlier than that of males (53.4 years).
Table 2: Prevalence of venous thrombosis in study population

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Figure 1: Age and gender distribution of study population in deep vein thrombosis and superficial vein thrombosis

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The disease distribution was more in extremities with preponderance of femoropopliteal segment (n = 132), followed by iliofemoral segment (n = 78) [Table 3]. Left side involvement was common in both males (n = 104) and females (n = 64).
Table 3: Distribution of venous thrombosis in study population

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A total of 123 patients (41.69%) had identifiable provoking risk factors, of which malignancy (n = 30, 24.39%) and postsurgery status (n = 29, 23.58%) were the common causes [Figure 2]a and [Figure 2]b. The common malignancies in male were those of anorectal and genitourinary system. In females, breast and cervical malignancies were common. There were four female patients, two with oral contraceptive pill (OCP) use and two due to pregnancy related factors. In the postsurgery patients, neurosurgery topped the list with 11 patients, followed by orthopedic surgery [Table 4]. Local causes included cellulitis and lymphangitis causing SVT, pancreatitis, and splenic abscess causing splanchnic thrombosis and huge hydronephrosis causing iliofemoral DVT.
Figure 2: (a) Identifiable causes of venous thrombosis. (b) Sites of malignancy in patients with venous thrombosis

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Table 4: Incidence of venous thrombosis in surgical specialties

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A total of 101 patients were tested for coagulation abnormalities, 14 had normal profile. Hyperhomocysteinemia was found to be the commonest coagulation anomaly (n = 59, 58.41%) followed by protein S deficiency [Figure 3]. Factor V (Leiden) mutation tested in 48 patients, of which only 6 were positive. Nearly half the patients had more than one factor abnormality. Distribution of coagulation abnormalities in patients with primary and secondary VT is given in [Table 5]. One patient developed subsequent contralateral limb DVT, and on evaluation, was found to have carcinoma prostate. One patient developed Lymphoma after 10 months and one became National AIDS Control Organisation positive after 3 months, from the initial event.
Figure 3: Coagulation profile in study

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Table 5: Coagulation abnormalities in patients with venous thrombosis

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  Discussion Top

This study consists of the prospectively collected data of 295 patients with VT over a period of 6 years. The incidence rate of 26.3/10,000 hospital admissions is almost identical to the studies conducted at Vellore[10] and Chennai.[11] In the published literature,[1],[2],[10] females are commonly affected by DVT, but our study has male preponderance (64%), similar to the ARRIVE study of 70%[12] and Indian subgroup of ENDORSE study of 69%.[13] Male dominance is seen only in the DVT group, not in the SVT group, where there is equal distribution between both genders.

The age group commonly affected in both genders is between 51 and 60 years and the mean age is 55.5 years. This correlates with other Indian studies, but contrasts with western studies,[14] where the common age group is 61–70 years. After 60 years of age, a decreasing trend was noted in our study, while a western study revealed 13-fold increase in those of 85 years old, when compared to those aged 45–55 years.[15]

Left lower extremity involving femoropopliteal segment (46%) is the commonest presentation in our series, which is similar to world literature. However, in contrast to western literature, showing the occurrence of unprovoked primary DVT, in the range of 25%–40%,[16] our study had a total of 58% and the gender-based subanalysis revealed the same trend in males (63%) and not in females (50%). One reason for this disparity may be the higher incidence of hyperhomocysteinemia in Indian males.[17]

The observation that malignancy and postoperative status are the most common provoking factors, is similar to the results of other Indian studies[10],[18] and an American study by Caprini et al.[19] On the contrary, an African study by Hagos et al.[20] portrayed medical conditions as the most common risk factors (25%), followed by postdelivery (19%), and major surgery (15%). Immobilization (including posttrauma, fracture, bedridden, and medical patients with restricted mobility) emerged as a single major factor (n = 45, 37%), more than malignancy. These patients should be considered as high risk patients and managed accordingly.

During the study period, with the total admission of 28,340 patients in the surgical specialties of Neuro, Orthopedic and General surgery, the incidence of VT is 6.70/10,000 surgical admissions. The individualized incidence rates are 11.75, 3.65, and 1.9/1000 operations, respectively. Both near and orthopedic surgical patients have prolonged immobilization in comparison with general surgical patients. This fact strengthens the prime role of early mobilization in the postoperative period on the prevention of VT.

Some studies have highlighted a high incidence (14.5%) of DVT as a subsequent appearance to SVT,[21],[22] but we are not able to establish any relationship between SVT and DVT. Forty-two patients who had SVT did not develop DVT during the study period, with a follow up period of 10 months–6 years.

In western literature, cancer of ovary, pancreas, lung, and stomach top the list in relation to VT.[23] In our study, anorectal and genitourinary malignancies in males and breast and cervical malignancies in females, tops the list. This can be explained by the prevailing trend of malignancies in India. In unprovoked VT, occult malignancy may be considered up to 10%.[24] In our study 2 patients (<1%) developed malignancy (one prostate carcinoma and another lymphoma) during the study period.

Low incidence of pregnancy related thrombosis (n = 2) in the study, may be the result of early mobilization and prophylactic use of anticoagulants in selected high risk patients. The role of OCPs in increasing thrombotic risk is well known.[25] But with the advent of new mini pills used as OCP, the risk of VT seems to be less. Only 2 patients have the history of OCP intake and with the distribution of more than 2000 pockets of OCP during the study period, the incidence is negligible.

In most studies published across the world, Factor V (Leiden) mutation is the most common anomaly,[26],[27] whereas we found hyperhomocysteinemia as the commonest coagulation anomaly. Literature evidence was present for higher incidence in general population[28],[29],[30] and incidence of 31.43% in DVT patients[31] However, Mouravas et al. disagreed completely in their study at Greece, the role of serum homocysteine in the development of DVT.[32] Another interesting study from North India by Sharma et al. suggested the presence of hypercoagulability parameters were higher than general population, but none were significantly associated with the risk of DVT.[33] As majority of Indians are vegetarians, the prevalence of dietary deficiency of vitamins involved in homocysteine metabolism may be responsible for the high incidence of hyperhomocysteinemia. Hyperhomocysteinemia, being a treatable condition, by folic acid and Vitamin B12 supplements, the question arises whether the supplements can prevent the occurrence of VT. The prophylactic role of these vitamins in high risk patients may need a randomized study to prove.

Factor V mutation (Leiden factor) is tested in 48 patients, yielding positive results in six patients only. Being less common in our population, it may not be advisable to include it in routine coagulation profile workup.

Single-center study, small sample size and not including Factor V (Leiden) mutation during the initial period were few limitations of the study. In spite of these limitations, the results of this prospective study revealed some Indian population specific findings:

  1. Male predominance
  2. Common age group is 51–60 years and no increase in risk, as age progresses after 60
  3. Immobilization is the single major risk factor
  4. Common malignancy associated with VT are breast and cervix in females and ano-rectal and genitourinary in males
  5. Hyperhomocysteinemia being commonest prethrombotic factor and rare occurrence of Factor V (Leiden) mutation.

  Conclusions Top

Our study revealed that the common modifiable risk factors for VT were immobilization, both medical and surgical and the commonest coagulation anomaly was hyperhomocysteinemia. Considering the nutritional deficiency, the role of folic acid and Vitamin B12 supplementation as prophylaxis for VT may be considered. With different genetic and environmental factors in India, we need a different risk stratification score on VT risk analysis. Venous registry would be the first step toward it.


The authors of this study wish to thank Dr. Anant Patil for his assistance in editing the manuscript.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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