Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 3  |  Page : 243-247

Prevalence of thrombophilia in indian patients with deep venous thrombosis – An 8-year single-center study


1 Vascular Surgery Department, Command Hospital Air Force, Bengaluru, Karnataka, India
2 Army Hospital (R and R), New Delhi, India
3 Command Hospital, Lucknow, Uttar Pradesh, India

Date of Submission04-May-2022
Date of Decision16-Jul-2022
Date of Acceptance16-Jul-2022
Date of Web Publication21-Aug-2022

Correspondence Address:
Suresh Reddy Thupakula
Army Hospital (R and R), New Delhi
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_26_22

Rights and Permissions
  Abstract 


Background: Thrombophilia is a recognized risk factor for deep venous thrombosis (DVT) and its recurrence. Routine thrombophilia testing is controversial because of low yield and high cost. However, screening for thrombophilia helps in deciding the duration of anticoagulant treatment. The aim of this study is to determine the prevalence of thrombophilia in DVT patients in India. Materials and Methods: This was a retrospective, prospective, observational study done from April 2012 to April 2020. Thrombophilia screening was done in DVT patients who were <40 years, with unprovoked DVT, or with recurrent DVT. Homocysteine, antithrombin III, protein C and S, factor V Leiden, and lupus anticoagulant (LAC) were assessed. Follow-up was done to assess post thrombotic syndrome (PTS), pulmonary embolism (PE), and recurrence of DVT. Results: One hundred and sixty-six patients selected for thrombophilia out of which 163 were males. Patients were ranging age from 35 to 70 years. 82 (49.4%) patients had abnormal thrombophilia. 66 had one abnormal factor, while 16 had more than one. A total of 102 abnormal factors found in 82 cases, of which 41 had hyperhomocysteinemia, 20 protein S deficiency, 12 protein C deficiency, 15 factor V Leiden mutations, 8 antithrombin III deficiency, and 6 LAC. 10.2% of patients developed PTS, 16.3% recurrence, 2% PE, and 0.3% mortality. Conclusion: DVT patients are at a substantial risk of recurrence. Although laboratory evaluation of thrombophilia is costly but it is essential for monitoring therapy in certain sets of patients. Identification of thrombophilic condition is worth and affects the overall standard clinical management. In our study we found prevalence of thrombophilia in about 50% of DVT patients who are <40 years, with unprovoked DVT or with recurrent DVT. Out of which hyperhomocysteinemia is most common. But more studies including RCTs are required for further clarifications.

Keywords: Deep vein thrombosis, thrombophilia, unprovoked deep vein thrombosis


How to cite this article:
Agrawal V, Deshpande SK, Biswas B, Thupakula SR, Anand V. Prevalence of thrombophilia in indian patients with deep venous thrombosis – An 8-year single-center study. Indian J Vasc Endovasc Surg 2022;9:243-7

How to cite this URL:
Agrawal V, Deshpande SK, Biswas B, Thupakula SR, Anand V. Prevalence of thrombophilia in indian patients with deep venous thrombosis – An 8-year single-center study. Indian J Vasc Endovasc Surg [serial online] 2022 [cited 2022 Sep 27];9:243-7. Available from: https://www.indjvascsurg.org/text.asp?2022/9/3/243/354073




  Introduction Top


Deep vein thrombosis (DVT) or venous thromboembolism (VTE) is a common preventable disorder, which is associated with significant morbidity and even mortality.[1] Important sequelae of DVT may be pulmonary embolism (PE), recurrent thrombosis, post thrombotic syndrome (PTS), and complications of anticoagulant therapy.[2]

DVT can be provoked or unprovoked. Provoked factors include trauma, surgery, immobilization, cancer, and high altitude.[3] Unprovoked or idiopathic venous thrombosis is defined as the development of DVT or PE in the absence of known apparent risk factor.

Patients with provoked DVT are at low risk of recurrent thrombosis,[4] whereas patients with unprovoked VTE have a recurrence risk of 5%–10% per year with nearly 50% by 10 years. Thrombophilia is one of the important risk factors for recurrent thromboembolic events in younger population. It has increased propensity to develop both venous and arterial thrombosis. However, not all patients of thrombophilia develop thrombosis.[5],[6]

Diagnostic thrombophilia testing is indicated in patients with unprovoked or recurrent VTE, first VTE at a young age (<40 years), VTE with strong family history, and recurrent pregnancy loss. Knowledge of risk of recurrence is relevant for clinical policy regarding screening for thrombophilia and duration of anticoagulant treatment.[7],[8]

There is a paucity of Indian data on thrombophilia. We present 8-year data of thrombophilia testing in our DVT patients admitted at our institution who qualifies for thrombophilia testing.


  Materials and Methods Top


This is a retrospective, prospective, observational study conducted among all the admitted patients of DVT who underwent thrombophilia testing from April 2012 to April 2020 at our hospital. DVT patients who were not investigated for thrombophilia profile were excluded from the study.

A detailed history was taken to differentiate between provoked and unprovoked DVT, and physical examination was done. Diagnosis of DVT was confirmed by color Doppler flow imaging (CDFI). In selected cases, computed tomography (CT) venography was done. Two-dimensional echo and CT pulmonary angiography were done for patients having chest discomfort or breathlessness to rule out PE. Patients following an unprovoked DVT underwent screening for cancer. A limited screening strategy including a thorough medical history, physical examination, basic laboratory investigations (i.e., complete blood count and liver function tests), chest X-ray, as well as age- and gender-specific cancer screening (breast, cervical, colon, and prostate) was done.

All the confirmed patients were treated with low-molecular-weight heparin (LMWH) along with compression bandage, rest, and limb elevation. Compression bandage was replaced by Class II compression stocking after subsided pain and swelling. LMWH was overlapped with oral anticoagulants (OACs) till international normalized ratio (INR) reached 2–3. In few cases, new OACs were also started which does not require monitoring of INR. All patients with iliofemoral DVT presenting within 14 days underwent catheter-directed thrombolysis (CDT) or pharmacomechanical thromboaspiration (PMT) by angiojet. Venous stenting was considered for May-Thurner syndrome.

CDFI and D-dimer were done after 6 months of treatment. If recanalized and found to have D-dimer within normal range, the patient was switched over to ecosprin; otherwise, OAC continued for 6 more months. Patients with unprovoked DVT, <40 years, recurrent DVT, or positive family history of DVT were selected for thrombophilia screening after discontinuation of OAC for 6 weeks. The thrombophilia screening included homocysteine, antithrombin III, protein C and S, factor V Leiden and lupus anticoagulant (LAC). Patients with 2 or more positive thrombophilia test were treated with extended anticoagulation. Thereafter, patients were clinically followed up 3 monthly, with CDFI and D-dimer. PTS, PE, complications of OAC, and recurrence of DVT were assessed.

Informed written consent was obtained from all the patients before including them in the study. Institute ethical committee clearance was sought and obtained before the study was begun. Descriptive statistics was prepared in the form of means and proportions for continuous and categorical variables, respectively.


  Results Top


A total of 166 patients were selected for thrombophilia testing who constituted the study group. Maximum patients were male (163, 98.2%). Age of the patients varied from 35 to 70 years with mean age of 43.02 years. Left lower limb was more commonly involved in 92 cases (55.4%). 39 cases (23.5%) had right lower limb involvement and 28 cases (16.9%) had both lower limbs involvement whereas 7 cases (4.2%) had involvement of upper limb and neck veins [Table 1].
Table 1: Body part involved in deep venous thrombosis

Click here to view


Patients presented with swelling and pain of affected part. Majority had pain preceded swelling by 2–3 days in 89%. The difference in circumference of two limbs varied from 2 to 8 cm. Majority 103 (62.1%) had difference between 4 and 7 cm.

DVT was confirmed by CDFI. Maximum patients had femoropopliteal DVT in 95 cases (57.2%). Forty-two cases (25.3%) had iliofemoral DVT [Table 2].
Table 2: Involve segment in deep venous thrombosis

Click here to view


Eight patients underwent CDT, two underwent angiojet PMT, and five underwent venous stenting for May-Thurner syndrome [Table 3].
Table 3: Procedures done for acute iliofemoral deep venous thrombosis

Click here to view


Out of 166 cases, 82 (49.4%) found to have abnormal thrombophilia profile. 66 cases had one factor abnormality and 16 patients (9.6%) had more than one abnormal factors (12 had two abnormal factors and 4 had three abnormal factors). [Table 4] Therefore, we found total 102 abnormal factors (82 + 12 × 2 + 4 × 3) in 82 cases, of which 41 were hyperhomocysteinemia, 20 were protein S deficiency, 12 were protein C deficiency, 15 were factor V Leiden mutations, 8 were antithrombin III deficiency, and 6 were LAC [Table 5].
Table 4: Positive thrombophilia factor

Click here to view
Table 5: Individual thrombophilia factors

Click here to view


Of 12 cases who had two factors abnormalities, 5 cases had protein C deficiency and one more factor, 3 cases had antithrombin III deficiency and one more factor, and 4 had hyperhomocysteinemia with one more factor abnormality. Four cases had three-factor abnormalities, out of which 2 had protein C, protein S deficiency, and antithrombin III deficiency and rest two had factor V Leiden, LAC, and protein C deficiency [Table 6]. We gave extended OACs up to 2 years for these 16 patients (9.6%) with every 3 monthly follow-up.
Table 6: Prevalence of more than one abnormal thrombophilia factor

Click here to view


On follow-up, 14 patients (6.4%) became asymptomatic, 69 patients (41.5%) showed significant improvement, 45 patients (27%) showed mild improvement, 12 patients (7.2%) remained static, and 26 patients (15.7%) had worsening of symptoms.

Three patients had PE confirmed with spiral CT angio. Two patients had mild symptoms which recovered with conservative management, whereas one patient succumbed because of massive PE with DVT extending up to infrarenal inferior vena cava. Four patients (3.2%) had minor petechial hemorrhage, which was controlled with adjustment of OAC, whereas 2 (1.2%) had hemarthrosis of knee, of which one required drainage. 17 (10.2%) had PTS whereas 16.3% had recurrence [Table 7].
Table 7: Complications

Click here to view



  Discussion Top


In a systematic review, the incidence of DVT in the general population was found as 0.5/1000 person-years.[9] DVT remains a major source of mortality and morbidity. The risk factors influencing DVT may be reversible or nonreversible. Patients with provoking risk factors have lower recurrent events. Patients with a proximal DVT with reversible risk factors should be treated with minimum 6 months of anticoagulation. Patients with permanent risk factors, such as cancer or thrombophilia, will require lifelong anticoagulation. These include protein C and S deficiencies and antithrombin deficiency. The recommended duration of anticoagulation for an idiopathic DVT is a minimum of 6 months, but it has higher risk of recurrent events if associated with proximal DVT (compared to calf), positive D-dimer following 1 month of withdrawal of OAC therapy, or hereditary thrombophilia.[10] Prospective studies had concluded tailoring therapy based on D-dimer and vein recanalization. If the D-dimer is elevated, OAC is restarted for secondary prevention.[10],[11]

According to many studies, because overall incidence of thrombophilia is low, routine testing is not justified.[12],[13] It is indicated for idiopathic or recurrent DVT, DVT at young age (<40 years), DVT with strong family history, or DVT at unusual site. It should be delayed for up to 6 months after onset of DVT until acute clinical condition subsides and should be performed after discontinuation of anticoagulant for 4–6 weeks.[8],[14],[15] We have followed the same protocol.

Different studies including one Indian study showed wide variation in the prevalence of thrombophilia in DVT patients ranging from 38% to 57.6%.[16],[17],[18] In our study, we found in 49.3%.

Deficiencies of the naturally occurring anticoagulant factors such as antithrombin III, protein C, and protein S are rare, representing <1% of the population. Antithrombin III, protein C, and protein S deficiency are seen in approximately 4%–7%, 2.5%–6%, and 1.3%–5%, respectively, of DVT patients.[14],[19] However, Bhattacharyya et al. reported a prevalence of antithrombin III, protein C, and protein S deficiency in north Indian population as 6.4%, 10.5%, and 11.3%, respectively.[20] In our study, we found in 4.8%, 7.2%, and 12.1% of cases, respectively.

Hyperhomocysteinemia is associated with an increased risk of both arterial and venous thrombosis, but recurrence is not well documented. Various studies have shown/depicted high prevalence of hyperhomocysteinemia among DVT patients up to 18%–25%.[21],[22] In our study, it was the most common abnormality detected in 24.7%.

According to studies, the prevalence of heterozygous factor V Leiden mutation in DVT patients was found in 10%–19% cases, whereas its homozygous mutation was found in 1.5%–2% only.[23] Studies have suggested a slightly elevated risk of DVT recurrence with factor V Leiden mutations.[24] In our study, it was found in 9.1% of cases, but because of lack of facility, we could not classify into heterozygous and homozygous groups. Ghosh et al. in one study from India found LACs in 8.3% of DVT patients,[25] whereas we found in 3.6% of cases.

Recurrent rates in DVT patients are reported as 17.5% at 2 years and 24.6% at 5 years. Wicker has reported that patients testing positive for two or more defects have higher risk of recurrent thrombosis during their lifetime if not given extended anticoagulation.[26] We had 16.3% recurrence in our study.

DVT has 30% risk of PTS and 11.3% mortality in 10–20 years.[27],[28] In our study, we had 17 cases (10.2%) of PTS and 3 cases (1.2%) of PE. Two patients were successfully managed with conservative management, whereas one case with extensive PE succumbed.


  Conclusion Top


Many patients with DVT are at a substantial risk of recurrence. Although laboratory evaluation of thrombophilia is costly but it is essential for monitoring therapy in certain sets of high risk patients. However, it is important to balance the bleeding risks associated with extended anticoagulant therapy against the reduction in DVT recurrence when determining the duration of therapy. In our study we found prevalence of thrombophilia in about 50% of DVT patients who are <40 years, with unprovoked DVT or with recurrent DVT. Out of which hyperhomocysteinemia is the most common. But more studies including RCTs are required for further clarifications. Use of various clinical, laboratory, and imaging tests may be helpful in specific patients for better treatment decisions. Identification of an inherited thrombophilic condition is worth, and thrombophilia testing affects the overall standard clinical management of patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hull RD, Raskob GE, Hirsh J. Prophylaxis of venous thromboembolism. An overview. Chest 1986;89:374S-83S.  Back to cited text no. 1
    
2.
Gjores JE. The incidence of venous thrombosis and its sequelae in certain districts of Sweden. Acta Chir Scand Suppl 1956;206:1-88.  Back to cited text no. 2
    
3.
Cushman M, Tsai AW, White RH, Heckbert SR, Rosamond WD, Enright P, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: The longitudinal investigation of thromboembolism etiology. Am J Med 2004;117:19-25.  Back to cited text no. 3
    
4.
Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007;92:199-205.  Back to cited text no. 4
    
5.
Khor B, Van Cott EM. Laboratory evaluation of hypercoagulability. Clin Lab Med 2009;29:339-66.  Back to cited text no. 5
    
6.
Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: Prospective cohort study. Lancet 2003;362:523-6.  Back to cited text no. 6
    
7.
Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S, et al. Clinical guidelines for testing for heritable thrombophilia. Br J Haematol 2010;149:209-20.  Back to cited text no. 7
    
8.
Heit JA. Thrombophilia: Common questions on laboratory assessment and management. ASH Education Program Book 2007;2007:127-35.  Back to cited text no. 8
    
9.
Fowkes FJ, Price JF, Fowkes FG. Incidence of diagnosed deep vein thrombosis in the general population: Systematic review. Eur J Vasc Endovasc Surg 2003;25:1-5.  Back to cited text no. 9
    
10.
East AT, Wakefield TW. What is the optimal duration of treatment for DVT? An update on evidence-based medicine of treatment for DVT. Semin Vasc Surg 2010;23:182-91.  Back to cited text no. 10
    
11.
Barnes GD, Kanthi Y, Froehlich JB. Venous thromboembolism: Predicting recurrence and the need for extended anticoagulation. Vasc Med 2015;20:143-52.  Back to cited text no. 11
    
12.
Machin SJ. Pros and cons of thrombophilia testing: Cons. J Thromb Haemost 2003;1:412-3.  Back to cited text no. 12
    
13.
Martinelli I. Pros and cons of thrombophilia testing: Pros. J Thromb Haemost 2003;1:410-1.  Back to cited text no. 13
    
14.
Nakashima MO, Rogers HJ. Hypercoagulable states: An algorithmic approach to laboratory testing and update on monitoring of direct oral anticoagulants. Blood Res 2014;49:85-94.  Back to cited text no. 14
    
15.
Ho WK, Hankey GJ, Quinlan DJ, Eikelboom JW. Risk of recurrent venous thromboembolism in patients with common thrombophilia: A systematic review. Arch Intern Med 2006;166:729-36.  Back to cited text no. 15
    
16.
Liu HW, Kwong YL, Bourke C, Lam CK, Lie AK, Wei D, et al. High incidence of thrombophilia detected in Chinese patients with venous thrombosis. Thromb Haemost 1994;71:416-9.  Back to cited text no. 16
    
17.
Chen TY, Su WC, Tsao CJ. Incidence of thrombophilia detected in southern Taiwanese patients with venous thrombosis. Ann Hematol 2003;82:114-7.  Back to cited text no. 17
    
18.
Mishra MN, Bedi VS. Prevalence of common thrombophilia markers and risk factors in Indian patients with primary venous thrombosis. Sao Paulo Med J 2010;128:263-7.  Back to cited text no. 18
    
19.
Yohe S, Olson J. 38 Thrombophilia: Assays and interpretation. In: Laboratory Hematology Practice. 2012;492-8.  Back to cited text no. 19
    
20.
Bhattacharyya M, Kannan M, Chaudhry VP, Saxena R. Venous thrombosis: Prevalence of prothrombotic defects in north Indian population. Indian J Pathol Microbiol 2003;46:621-4.  Back to cited text no. 20
    
21.
Simioni P, Prandoni P, Burlina A, Tormene D, Sardella C, Ferrari V, et al. Hyperhomocysteinemia and deep-vein thrombosis. A case-control study. Thromb Haemost 1996;76:883-6.  Back to cited text no. 21
    
22.
Fermo I, Vigano' D'Angelo S, Paroni R, Mazzola G, Calori G, D'Angelo A. Prevalence of moderate hyperhomocysteinemia in patients with early-onset venous and arterial occlusive disease. Ann Intern Med 1995;123:747-53.  Back to cited text no. 22
    
23.
Rosendaal FR. Venous thrombosis: A multicausal disease. Lancet 1999;353:1167-73.  Back to cited text no. 23
    
24.
Sveinsdottir SV, Saemundsson Y, Isma N, Gottsäter A, Svensson PJ. Evaluation of recurrent venous thromboembolism in patients with Factor V Leiden mutation in heterozygous form. Thromb Res 2012;130:467-71.  Back to cited text no. 24
    
25.
Ghosh K, Shetty S, Madkaikar M, Pawar A, Nair S, Khare A, et al. Venous thromboembolism in young patients from western India: A study. Clin Appl Thromb Hemost 2001;7:158-65.  Back to cited text no. 25
    
26.
Prandoni P, Lensing AW, Cogo A, Cuppini S, Villalta S, Carta M, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1-7.  Back to cited text no. 26
    
27.
Zwicker J. Consultative Hemostasis and Thrombosis. Philiadelphia: WB Saunders CO; 2002.  Back to cited text no. 27
    
28.
Carrier M, Le Gal G, Wells PS, Rodger MA. Systematic review: Case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med 2010;152:578-89.  Back to cited text no. 28
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
   Abstract
  Introduction
   Materials and Me...
  Results
  Discussion
  Conclusion
   References
   Article Tables

 Article Access Statistics
    Viewed286    
    Printed4    
    Emailed0    
    PDF Downloaded42    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]