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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 2  |  Page : 205-208

Occurrence of Venous Thromboembolism in Hospitalized Patients with Tuberculosis in Saudi Arabia: A Retrospective Cohort Study


1 Department of Surgery, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
2 Department of Pathology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia

Date of Web Publication29-May-2020

Correspondence Address:
Talal A Altuwaijri
Department of Surgery, King Saud University, 37, P. O. Box: 7805, Riyadh 11472
Kingdom of Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_28_20

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  Abstract 


Background: The purpose of this study was to assess the risk of venous thromboembolism (VTE) and the potential need for thromboprophylaxis in patients with tuberculosis (TB). Methods: A total of 103 patients who underwent treatment for TB at the King Khalid University Hospital in Riyadh between February 2015 to May 2018, the percentage of patients diagnosed with TB who developed VTE was assessed. This was a retrospective cohort study conducted at King Khalid University Hospital in Riyadh. Fisher's exact test was used to analyze the categorical variables.P < 0.05 was considered statistically significant. Results: Our data showed the prevalence of VTE in TB patients to be 2.93% (3/103). VTE occurred irrespective of the type of TB (pulmonary and/or extrapulmonary). All TB patients with VTE showed no significant association with factors such as human immunodeficiency virus coinfection, malignancy, and multidrug-resistant TB. Conclusion: Our study showed that TB patients in Saudi Arabia may be at a higher risk for developing VTE and should be carefully monitored as potential candidates for additional thromboprophylaxis; further studies are recommended to establish more reliable assessment and recommendations.

Keywords: Human immunodeficiency virus infection, multidrug resistant, Saudi Arabia, tuberculosis, venous thromboembolism


How to cite this article:
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

How to cite this URL:
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 [serial online] 2020 [cited 2020 Jul 9];9:205-8. Available from: http://www.ijmyco.org/text.asp?2020/9/2/205/285225




  Introduction Top


Tuberculosis (TB), one of the oldest known human diseases, remains a worldwide health crisis, especially in developing countries.[1] Infections caused by Mycobacterium tuberculosis are endemic in the Kingdom of Saudi Arabia.[2],[3] According to the World Health Organization, the annual incidence rate of TB in Saudi Arabia in 2018 was ten in 100,000 people.[1]

Venous thromboembolism (VTE), which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), has an annual incidence rate of 0.1% in the general population,[4],[5],[6] and is a potentially fatal disease if left untreated. The annual incidence rate of VTE in Saudi Arabia was estimated at approximately 0.08% in 2015, which was similar to the estimated global rate.[7] Virchow's triad describes three broad groups of factors that contribute to thrombosis – blood hypercoagulability, endothelial injury, and venous stasis. Hypercoagulability is known to be a crucial risk factor for the development of spontaneous VTE.

Hematological disturbances in TB patients may favor the development of a hypercoagulable state.[4],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] Although the incidence of VTE in the general population is small, several studies have suggested that patients with TB are predisposed to VTE.[5],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21] Therefore, it is important to identify TB patients for appropriate thromboprophylaxis to prevent complications from VTE.

Although TB is widespread in Saudi Arabia, the correlation between TB and VTE in the Saudi population has not been previously investigated. The purpose of this study was to assess the risk of VTE and the potential need for thromboprophylaxis in TB patients in Saudi Arabia. We aimed to explore the correlation between TB and VTE in the local population and specifically focused on whether the risk of developing VTE was associated with TB disease severity, human immunodeficiency virus (HIV) coinfection, or concurrent malignancy in patients with TB.


  Methods Top


Study patients

Ethical approval for the study was obtained from the King Saud University (Chairperson: Dr. Abdulrahman Alsultan; Project # E-19-3656; Approval number: 10/0220/IRB; Date of approval: March 05, 2019). Informed consent was not required due to the retrospective nature of the study. A retrospective cohort study was conducted on 103 patients who tested positive for acid-fast bacilli staining and M. tuberculosis cultures in King Khalid University Hospital (Riyadh, Saudi Arabia) from February 2015 to May 2018.

We performed a chart review of all patients who developed a VTE event (DVT and/or PE). A VTE event was presumed to be related to TB if it occurred within 6 months of TB diagnosis.[4] All VTE events were confirmed by Duplex ultrasound, computerized tomography, or ventilation–perfusion scans. Information regarding the timing of TB and DVT/PE diagnosis, HIV status, personal history of malignancy, multidrug-resistant TB (MDR-TB), TB location (pulmonary vs. extrapulmonary TB), disseminated TB (military or spread to more than one organ), and the use of therapeutic anticoagulation were recorded. The exclusion criteria were as follows: postsurgical patients; patients <18 years old; patients with atypical nontuberculous Mycobacterial infection, latent TB, or thrombophilia; patients on anticoagulant therapy (Vitamin K antagonists or low-molecular-weight heparin) before TB diagnosis; and patients who developed a VTE event ≥6 months after TB diagnosis.

Statistical analysis

Data were analyzed using SPSS version 22.0 software (IBM Corporation, Armonk, New York, USA). Categorical variables, such as gender (male or female), VTE (yes or no), HIV status (positive or negative), malignancy (yes or no), MDR-TB (yes or no), disseminated TB (yes or no), and location of TB (pulmonary, extrapulmonary, or a combination of both) were expressed as percentages. Fisher's exact test was used to analyze the categorical variables. P < 0.05 was considered statistically significant.


  Results Top


Patient characteristics

[Table 1] shows the demographic characteristics of a total of 103 patients with TB. The mean age of the patients was 46.90 years. The majority of patients were Saudi and males (77.7% and 68%, respectively). The majority of the study patients had pulmonary TB (48.54%), 25.24% had disseminated TB (military or >1 organ), and 6.8% showed concurrent malignancy. Only one of the 103 patients with TB was positive for HIV, and none had MDR-TB [Table 2].
Table 1: Demographic data of tuberculosis patients (n=103)

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Table 2: Characteristics of tuberculosis patients (n=103)

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Prevalence of venous thromboembolism in tuberculosis patients

As shown in [Table 2], the prevalence of VTE among TB patients was 2.91% (3/103). Two of the three TB patients with VTE were female, [Table 3] and one of these three patients showed disseminated TB. The TB patients with VTE showed no specific bias toward a particular location of TB – one patient showed pulmonary TB, one showed extrapulmonary TB, and the other showed both pulmonary and extrapulmonary TB [Table 3]. The development of VTE in all three patients was almost coincident with the time of TB diagnosis. The timeline of TB and VTE diagnoses in the three patients was as follows: (1) patient #9: TB diagnosis in September 2017, DVT diagnosis in September and October 2017, and PE diagnosis in September 2017; (2) patient #59: TB diagnosis in June 2015, PE diagnosis in May 2015, and no DVT; and (3) patient #82: TB diagnosis in September 2017, DVT diagnosis in September 2017, and no PE.
Table 3: Correlation of venous thromboembolism with tuberculosis patient characteristics

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Association of venous thromboembolism with patient characteristics

[Table 3] shows the comparison between TB patients with and without VTE with regard to gender, HIV status, malignancy, MDR-TB, disseminated TB, and location of TB (pulmonary, extrapulmonary, or both). None of the TB patients with VTE showed HIV coinfection, malignancy, or MDR-TB. We observed no statistically significant differences between TB patients with and without VTE for all the assessed characteristics.


  Discussion Top


VTE, a term referring to blood clots in the veins, includes DVT and PE and is a potentially fatal disease. VTE by itself has an annual incidence rate of 0.1% in the general population.[4],[5],[6] However, several studies have shown higher instances of VTE in patients suffering from TB. Therefore, TB is considered a significant risk factor for the development of VTE. Our retrospective analysis showed the prevalence of VTE (2.91%) in patients with TB in Saudi Arabia. This result is similar to the VTE prevalence rates observed in the previous studies[15],[22] and reinforces that TB is a pertinent risk factor for VTE.

Severe TB can result in a hypercoagulable state.[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] The mechanisms for VTE in TB patients may involve all three aspects of the Virchow's triad. First, hypercoagulability (elevated plasma fibrinogen, impaired fibrinolysis coupled with decreased levels of antithrombin III, and reactive thrombocytosis) is thought to favor the development of DVT in pulmonary TB.[8],[9],[13] Second, venous stasis (pooling of blood due to local venous compression by enlarged lymph nodes or immobility due to compromised respiration) in TB patients may also increase the risk of blood clots.[20] Finally, endothelial dysfunction (endothelial injury caused by TB or the use of rifampicin) may induce clotting.[13],[23]

TB progression may also induce pro-inflammatory cytokines that stimulate the synthesis of coagulating proteins in the liver.[24] In our study, the TB patients with VTE did not show any specific bias toward pulmonary or extrapulmonary locations of TB. They also did not show a bias toward developing either PE or DVT. This suggests that the mechanism of VTE development in TB patients may predominantly be due to systemic hypercoagulability rather than due to localized factors. Our results are consistent with those of the previous studies.[15],[25] Future research with larger sample sizes may help reveal the exact mechanisms that cause hypercoagulability in TB patients.

In a previous study by Robson et al., 33 out of 35 patients with pulmonary TB developed DVT 7 days after TB diagnosis, and the other two patients presented DVT at the time of TB diagnosis.[9] In our study, two of the three patients developed VTE soon after TB diagnosis, and in one patient, the VTE event had preceded TB diagnosis. Together, these results suggest that it is crucial to monitor patients for VTE as soon as TB is diagnosed. Turken et al. showed that patients with active pulmonary TB exhibited hematological conditions prone to hypercoagulability but showed marked improvement after just 1-month of anti-TB therapy.[8] Therefore, consideration of thromboprophylaxis along with anti-TB therapy should help minimize the complications caused by VTE in TB patients.

In this study, we assessed whether the risk of VTE occurrence in TB patients was exacerbated by TB disease severity or by other known risk factors of TB or VTE. Cancer is a powerful risk factor for VTE.[26] It is known to be associated with a 4.1-fold increase in the risk of thrombosis,[27] and VTE is a leading cause of death in cancer patients.[28] TB is often associated with other chronic infections such as HIV. In fact, coinfection of HIV is known to be a strong risk factor for the progression of TB disease severity.[29] MDR-TB is a severe form of the disease characterized by resistance to the potent anti-TB drugs, isoniazid and rifampicin.[30] The MDR-TB rate in Saudi Arabia is about 4.4% in TB patients, which is similar to the global rate.[31] We found that none of the above factors – tumor malignancy, HIV coinfection, or multidrug resistance – showed an association with VTE occurrence in TB patients. Our results differ from those of a previously published study that showed a high risk of VTE (>5%) in HIV coinfected TB patients.[5] In our study, only one TB patient (without VTE) had HIV coinfection, which was possibly due to our lower sample size compared with the previous study (103 vs. 750 patients). Future analysis with larger sample groups may address whether HIV coinfection indeed increases the risk of VTE in TB patients.


  Conclusions Top


In Saudi Arabia, patients with TB may be showing a higher risk of developing VTE. Therefore, it is important to monitor TB patients and consider them for additional thromboprophylaxis to avoid the serious complications of VTE; further studies are recommended to establish more reliable assessment and recommendations.

Acknowledgements

The authors would like to thank Mr. Ahmad H. Al-Sharqawi for providing statistical assistance in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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