• Users Online: 409
  • Home
  • Print this page
  • Email this page


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 11  |  Issue : 1  |  Page : 83-87

Investigation of two general venous thromboembolism risk-stratification models in predicting venous thromboembolic events in TB patients


1 Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Virology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Date of Submission22-Dec-2021
Date of Decision30-Dec-2021
Date of Acceptance08-Feb-2022
Date of Web Publication12-Mar-2022

Correspondence Address:
Mojdeh Azimi
National Research Institute for Tuberculosis and Lung Diseases, Masih Daneshvari Hospital, Darabad Ave, Bahonar roundabout, Tehran
Iran
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_252_21

Rights and Permissions
  Abstract 


Background: Tuberculosis (TB) remains an infectious disease with a high prevalence worldwide and represents a major public health concern. It is known that TB causes a hyper-coagulable state due to its infective nature. Thus, patients are prone to higher incidence rates of venous thromboembolism (VTE) in comparison with the general population. Although there are many risk assessment models (RAMs) that estimate the risk of VTE incidence in the general population, none have been proven to show significant prognostic value in early and accurate VTE prediction among TB patients. This study aims to investigate the accuracy of general RAMs in prediction of VTE incidence in the population of TB-positive patients. Methods: The following survey is a retrospective study among patients afflicted with TB, in whom VTE had occurred either during or at the onset of admission. A total number of 865 smear-positive TB cases were recorded in hospital in a 7-year timespan, among which a total sum of 37 patients (67.6% males, age: 56.19 ± 20 years) experienced at least one episode of thromboembolic incidence. We nominated Padua and Geneva RAMs and calculated the scores with regard to their inpatient hospital records. Results: Of 865 adult hospitalized smear-positive TB patients, 37 patients happened to develop VTE in the course of infection, after excluding the unacceptable data. The incidence of VTE was calculated at 4.27%. Of all VTEs, 73% turned out to be deep venous thromboembolism (DVT), 18.9% were pulmonary thromboembolism (PTE), and 8.1% of patients developed both DVT and PTE during the course of disease. Among all cases, 32.4% revealed Geneva score equivalent or >3. It conveys the meaning that these patients were at greater risk for VTE development and were indicated to receive prophylactic medication. Similarly, Padua model was capable of predicting 29.7% cases scoring >4, which is alarming for elevated VTE probability. 21.6% of TB patients, who had developed VTE during the course of their disease eventually passed away. Conclusion: Our statistics show minimal positive predictive value for Padua and Geneva RAMs, which are seemingly in sharp contrast with the excellent validation of these models verified by numerous surveys in general population. This fact could be attributable to failing to consider TB, or in general chronic infections, as independent indicators of VTE incidence. These findings indicate the need for revising the presenting RAMs or establishing a separate RAM for VTE prediction in TB patients, resembling the VTE risk assessment model for cancer patients.

Keywords: Tuberculosis, validation study, venous thromboembolism


How to cite this article:
Sharif-Kashani B, Azimi M, Tabarsi P, Sadr M, Shirzadi S. Investigation of two general venous thromboembolism risk-stratification models in predicting venous thromboembolic events in TB patients. Int J Mycobacteriol 2022;11:83-7

How to cite this URL:
Sharif-Kashani B, Azimi M, Tabarsi P, Sadr M, Shirzadi S. Investigation of two general venous thromboembolism risk-stratification models in predicting venous thromboembolic events in TB patients. Int J Mycobacteriol [serial online] 2022 [cited 2022 May 25];11:83-7. Available from: https://www.ijmyco.org/text.asp?2022/11/1/83/339516




  Introduction Top


Tuberculosis (TB) is a chronic infectious disease with relatively high prevalence in the Middle East. It is still considered as one of the main mortality contributors and accounts for over 8 million new cases and about 2 million deaths annually.[1],[2] Although all age groups are at risk, the frequency of TB appears to be highest in the 34–45-year age group, with an increased incidence in the elderly.[3]

Deep vein thrombosis and pulmonary embolism collectively referred to as venous thromboembolism (VTE), constitute a major global burden of disease.[4] Even until recently, the data supporting the benefits of thromboprophylaxis in general medical patients were scarce, however, numerous studies have now verified positive role of anticoagulant therapy in reduction of VTE incidence.[5] Although several risk factors result in VTE, no specific risk factor can be identified in a third to half of VTE events and VTE is categorized as unprovoked in these cases.[6]

It is now known that infections in general, and TB in specific, could result in thromboembolic events through different mechanisms,[7],[8] for instance local invasion, extra pressure on veins, and blood stasis.[9] As a result, they would eventually lead to a hypercoagulable state.[10] On the other hand, some medications used in the treatment of TB (such as Rifampicin) are proven to have thrombotic effects, as they reduce the level of plasma antithrombotic agents.[7],[11] It is estimated that about 0.7% of all TB patients would experience VTE during the course of their disease.[12] The risk for VTE increases with disease severity and exacerbations. Hence, hospitalized patients should be considered for thromboprophylaxis administration. This link is considerable enough that some articles point to the need for VTE screening in every TB patient to minimize its adverse effects.[13],[14]

Early initiation of anti-TB treatment along with anticoagulant therapy can prevent the potentially fatal complication of the disease. Low-molecular-weight heparins are safer and require minimal monitoring. The overall morbidity and mortality may also be decreased if the condition is timely diagnosed and managed properly.[15],[16]

Diverse risk stratification models have been designed to estimate the probability of VTE incidence among all hospitalized patients and their validity has been assessed in specific studies.[17] Among many present risk-assessment models for prediction of VTEs Padua score and Geneva score have been proven to be capable of predicting the risk for VTEs acceptably,[18],[19] though their effectiveness has not been frequently tested among specific populations such as TB patients. Given the fact that our center is a tertiary referral hospital for TB patients in the middle-east region and the accumulation of smear-positive TB patients is uniquely elevated at this center, we aimed to analyze the predictive value for these models in the mentioned population. With respect to the potentially fatal nature of VTE and the economic and mental burden of this complication on patients and the health-care system, trying to predict possible probability of its development seems indispensable.


  Methods Top


In the current research, we devised an observational study among patients diagnosed with TB in Masih Daneshvari Hospital, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), a tertiary TB and lung center in Tehran, Iran.

Objectives

  • To evaluate the positive predictive value and credibility of general risk-assessment models (in specific Geneva and Padua scores), in the population of TB affected patients
  • To elucidate whether or not decision-making based on general risk-assessment models is suitable in the situation of TB for VTE treatment or starting prophylactic medications.


Selection of the study participants and inclusion criteria

Data were collected from a retrospective sample of the newly diagnosed smear-positive TB patients in a 7-year timespan, from March 2011 to September 2018.

We included all adult beings (18 or more) at the onset of TB diagnosis from the records of NRITLD and studied their following inpatient records, screening admissions due to thromboembolic accidents. Any patient with the experience of at least one episode of Thromboembolic event either during or at the onset of admission was enrolled in the study.

Exclusion criteria

Patients with presentations of extrapulmonary TBs and thromboembolic events other than pulmonary thromboembolism (PTE) and deep venous thromboembolism (DVT) were excluded from our study.

Recordings containing missing or distorted data were completely excluded, indeed.

Sample size

The total number of Tb patients who experience VTEs is exceptionally small in the general hospitals and we lack studies with a focus on VTE in TB patients that evaluate VTE prediction and risk-assessment models. With respect to the fact that NRITLD is a referral hospital with cases from all around the middle-east and the region is endemic for TB, we aimed to enroll all of the cases, which met the criteria to yield precise outcomes as much as possible.

Data presentation and statistical analysis

Of 865 adult hospitalized smear-positive TB patients, after excluding the unacceptable data, 37 patients were included (67.6% males, age 56.19 ± 20 years, 18.9% Afghan immigrants).

Considering the limitations of hospital data recordings, we found out two risk-stratification models suitable, which could be measured precisely from hospital's records in a retrospective study. The two nominated models were Padua and Geneva scores. An archive survey including these risk assessment models (RAMs) was conducted to assess the risk of VTE incidence thereafter and the scores were calculated based on following tables [Table 1] and [Table 2].
Table 1: Padua score details

Click here to view
Table 2: Geneva score details

Click here to view


Padua score equivalent or more than 4 and Geneva score equivalent or >3 were considered as high risk for thromboembolic events.

As TB is subcategorized as a chronic infection, we did not calculate any score for that, neither did we consider TB as a known hypercoagulable state in scoring.

The data underwent statistical analysis with SPSS software (Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp).

Diagnosis of venous thromboembolisms

DVT was diagnosed by Doppler sonography from visualization of an intraluminal thrombus in deep vein, accompanied with reduced compressibility.

PTE was diagnosed by means of IV contrast computed tomography scanning presented with one or several low attenuation areas that partly or completely filled the lumen of an opacified vessel.


  Results Top


Of 865 adult hospitalized smear-positive TB patients, after excluding the unacceptable data, 37 patients were recorded with at least one episode of VTE during their course of infection. The incidence of VTE was 4.27% in our study. Twenty-seven percent had previous history of VTE. Of all VTEs, 73% were diagnosed DVT, 18.9% suffered from PTE, and 8.1% developed both DVT and PTE embolic events. The score for both Geneva and Padua models was calculated before the development of the first embolic event for these selected cases. Among all cases, 32.4% revealed Geneva score equivalent or >3, which is to say these patients were considered as high risk for future embolic events. Furthermore, 29.7% of all cases revealed Padua score equivalent or >4 for whom thromboprophylaxis was indicated as well. 21.6% of TB patients, who had developed VTE during the course of their disease, passed away [Table 3].
Table 3: Results

Click here to view



  Discussion Top


It has been demonstrated before that the risk for VTE increases in acute infections, and as the survey by Dentan et al. outlined, the prevalence of VTE among patients with TB was reported 2.07%.[10]

The incidence rate of VTE venous thromboembolic events reported in our study is 4.27%, which is significantly greater in comparison with that of Ambrosseti et al. in Italy (0.6%)[12] and the study in Ryadt (2.93%)[20] and >previous studies that were performed in NRITLD center (0.94% and 2.8%).[9],[21] This could possibly be attributable to the short follow-up period after diagnosis of TB in the Italian survey. It should be noted that our study design did not limit the incidence of VTE to specifically 1 month after diagnosis of TB, to observe the additional imposed risk following the chronic infection, in the whole duration of affliction. In addition, this could be helpful in assessing the necessary duration of thromboprophylaxis period, after the onset of TB in further researches.

The fact that strikes the most is the number of young adults who developed venous thromboembolic events with no other specific risk factor (8 out of 37 people-21.6%). This has been mentioned in other studies as well (Gupta A, Epaulard O, Purayil NK, Huang L)[16],[22],[23],[24] and could be suggestive of the independent role of TB as a single risk factor. Although many studies have been designed to compare risk stratification models in generally admitted patients, not many similar studies have investigated the accuracy of present RAMs in TB patients. The most similar study that has investigated the RAMs among general population is Nendaz et al. s'[25] that includes 1487 admitted patients in a prospective cohort study and investigates the positive predictive values of each model. Genava score had predicted 962 patients as high risk that 3.2% of them had developed VTE and 516 were assessed as low risk that 0.6% of them had developed VTE as well. Padua score indeed had predicted 3.5% of high-risk population to develop VTE in contrast with 1.1% of low-risk population, which shows the acceptable predictive value of these models in general population. Another recent study by Arpaia et al.[18] in 2020 focused on the validation of Padua predicting score and reported a respective sensitivity and specificity of 0.97 and 0.21 with the negative likelihood ratio being 0.15.

The outcome of these statistics proved that both Padua and Geneva score favorably predict the chance of VTE development and mortality in general population. This conflict in findings could be secondary to underestimation of the role of chronic infections, specifically TB, as independent indicators of VTE incidence. Considering the number of cases, mild difference between positive predictive values of the two models does not seem to be significant. In fact, we suggest that like many other chronic conditions, a specific risk stratification model should be revised to assess the chance of VTE development in TB patients.

This suggestion is congruent with the recent meta-analysis paper on the global epidemiology of VTE in patients with active TB, which also demonstrated a similar outcome.[26] Danwang et al. reported an elevated risk of VTE in active TB patients and suggested a cost-effective preventive strategy to curb the dreadful burden of VTE in the mentioned population.


  Conclusion Top


The findings of our study show that the mentioned RAMs were not capable of predicting the incidence of thromboembolic events precisely; therefore, it is mandatory to consider TB as an independent risk factor for VTE incidence and perhaps a specific version of risk stratification should be revised for TB patients, resembling Khorana VTE risk assessment model,[27] for cancer patients. There is no need to further mention that regarding the limitations of the archive survey, only two RAMs were assessed in this study, thus performing prospective studies, assessing other VTE scores would be convenient.

Ethical clearance

Institutional ethics committee permission was obtained before the commencement of the study (IR.SBMU.MSP.REC.1395.686). The anonymity of study participants was ensured. Considering the retrospective nature of the study, the ethical committee waived off the need for informed patient consent.

Limitation of the study

As the study was performed retrospectively, we had limited choice for selecting and comparing various models, for many of the scoring items could not be assessed solely based on the patients' records and needed bedside evaluation. Therefore, designing a prospective study and calculating the scores of various risk-assessment models would be beneficial in achieving more precise results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
World Health Organization. Global Tuberculosis Report 2016. Geneva: World Health Organization; 2016. Available from: http://www.who.int/iris/handle/10665/250441. [Last accessed on 2019 Nov 01]  Back to cited text no. 1
    
2.
Babamahmoodi F, Alikhani A, Yazdani Charati J, Ghovvati A, Ahangarkani F, Delavarian L, et al. Clinical epidemiology and paraclinical findings in tuberculosis patients in north of Iran. Biomed Res Int 2015;2015:381572.  Back to cited text no. 2
    
3.
Ng BH, Andrea YL, Nuratiqah NA, Faisal AH, Low HJ. Clots in tuberculosis. Med J Malaysia 2021;76:953-5.  Back to cited text no. 3
    
4.
Di Nisio M, van Es N, Büller HR. Deep vein thrombosis and pulmonary embolism. Lancet 2016;388:3060-73.  Back to cited text no. 4
    
5.
Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:S152-84.  Back to cited text no. 5
    
6.
Azdaki N, Moezi S, Farzad M. Pulmonary tuberculosis: A differential diagnostic priority in unprovoked deep venous thrombosis patients with haemoptysis. Pan Afr Med J 2018;29:57.  Back to cited text no. 6
    
7.
Goncalves IM, Alves DC, Carvalho A, do Ceu Brito M, Calvario F, Duarte R. Tuberculosis and venous thromboembolism: A case series. Cases J 2009;2:9333.  Back to cited text no. 7
    
8.
Lau A, Sligl W, Sun K, Barrie J, Long R. Incidence and significance of venous thromboembolism in critically ill pulmonary tuberculosis patients. Eur Respir J 2020;56:2001753.  Back to cited text no. 8
    
9.
Sharif-Kashani B, Bikdeli B, Moradi A, Tabarsi P, Chitsaz E, Shemirani S, et al. Coexisting venous thromboembolism in patients with tuberculosis. Thromb Res 2010;125:478-80.  Back to cited text no. 9
    
10.
Dentan C, Epaulard O, Seynaeve D, Genty C, Bosson JL. Active tuberculosis and venous thromboembolism: Association according to international classification of diseases, ninth revision hospital discharge diagnosis codes. Clin Infect Dis 2014;58:495-501.  Back to cited text no. 10
    
11.
Naithani R, Agrawal N, Choudhary VP. Deep venous thrombosis associated with tuberculosis. Blood Coagul Fibrinolysis 2007;18:377-80.  Back to cited text no. 11
    
12.
Ambrosetti M, Ferrarese M, Codecasa LR, Besozzi G, Sarassi A, Viggiani P, et al. Incidence of venous thromboembolism in tuberculosis patients. Respiration 2006;73:396.  Back to cited text no. 12
    
13.
Sharma D, Sethi P, Yadav A. To study the clinico-radiological profile of patients of pulmonary tuberculosis with deep vein thrombosis. Int J Mycobacteriol 2021;10:26-30.  Back to cited text no. 13
[PUBMED]  [Full text]  
14.
Ha H, Kim KH, Park JH, Lee JK, Heo EY, Kim JS, et al. Thromboembolism in Mycobacterium tuberculosis infection: Analysis and literature review. Infect Chemother 2019;51:142-9.  Back to cited text no. 14
    
15.
Keramidas G, Gourgoulianis KI, Kotsiou OS. Venous thromboembolic disease in chronic inflammatory lung diseases: Knowns and unknowns. J Clin Med 2021;10:2061.  Back to cited text no. 15
    
16.
Gupta A, Dixit R. Pulmonary tuberculosis: A neglected risk factor for deep venous thrombosis. Int J Mycobacteriol 2017;6:184-6.  Back to cited text no. 16
[PUBMED]  [Full text]  
17.
Venous thromboembolism in critically ill patients: Risk stratification and prevention. In: Critical Care Update. New Delhi, India: Jaypee Brothers Medical Publishers; 2019. p.135–140.  Back to cited text no. 17
    
18.
Arpaia GG, Caleffi A, Marano G, Laregina M, Erba G, Orlandini F, et al. Padua prediction score and IMPROVE score do predict in-hospital mortality in internal medicine patients. Intern Emerg Med 2020;15:997-1003.  Back to cited text no. 18
    
19.
Robert-Ebadi H, Mostaguir K, Hovens MM, Kare M, Verschuren F, Girard P, et al. Assessing clinical probability of pulmonary embolism: Prospective validation of the simplified Geneva score. J Thromb Haemost 2017;15:1764-9.  Back to cited text no. 19
    
20.
Altuwaijri TA, Alhindi GK, Al-Qattan NM, Alkharashi SK, Somily AM, Altoijry AH. Occurrence of venous thromboembolism in hospitalized patients with tuberculosis in Saudi Arabia: A retrospective cohort study. Int J Mycobacteriol 2020;9:205-8.  Back to cited text no. 20
[PUBMED]  [Full text]  
21.
Marjani M, Tabarsi P, Baghaei P, Shamaei M, Biani PG, Mansouri D, et al. Incidence of thromboembolism in hospitalized patients with tuberculosis and associated risk factors. Arch Clin Infect Dis 2012;7:56-9.  Back to cited text no. 21
    
22.
Epaulard O, Foote A, Bosson JL. Chronic infection and venous thromboembolic disease. Semin Thromb Hemost 2015;41:644-9.  Back to cited text no. 22
    
23.
Purayil NK, Sirajudeen J, Al Arbi KM, Baghi MA, Zahid M. Venous thromboembolism: An unusual presentation of pulmonary tuberculosis. Cureus 2021;13:e14092.  Back to cited text no. 23
    
24.
Huang L, Yin C, Gu X, Tang X, Zhang X, Hu C, et al. Severe pulmonary tuberculosis complicated with insidious pulmonary thromboembolism: A case report and literature review. J Thromb Thrombolysis 2020;49:644-50.  Back to cited text no. 24
    
25.
Nendaz M, Spirk D, Kucher N, Aujesky D, Hayoz D, Beer JH, et al. Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit assessment of thromboembolic risk and prophylaxis for medical patients in Switzerland (ESTIMATE). Thromb Haemost 2014;111:531-8.  Back to cited text no. 25
    
26.
Danwang C, Bigna JJ, Awana AP, Nzalie RN, Robert A. Global epidemiology of venous thromboembolism in people with active tuberculosis: A systematic review and meta-analysis. J Thromb Thrombolysis 2021;51:502-12.  Back to cited text no. 26
    
27.
Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: The Protecht score. Intern Emerg Med 2012;7:291-2.  Back to cited text no. 27
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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
Methods
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed422    
    Printed16    
    Emailed0    
    PDF Downloaded30    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]