CASE SERIES |
https://doi.org/10.5005/jp-journals-11010-1148 |
Challenges and Triumphs: A Case Series of Drug-resistant Tuberculosis Management in Patients with Coagulation Disorders
Department of Respiratory Medicine, Velammal Medical College Hospital and Research Institute, Madurai, Tamil Nadu, India
Corresponding Author: Raghul Raj S, Department of Respiratory Medicine, Velammal Medical College Hospital and Research Institute, Madurai, Tamil Nadu, India, Phone: +91 7598305440, e-mail: s.raghulraj@gmail.com
Received: 09 April 2024; Accepted: 05 January 2025; Published on: 17 February 2025
ABSTRACT
Managing drug-resistant tuberculosis (MDR-TB) in patients with underlying coagulation disorders such as hemophilia and combined factor V and VIII deficiency presents significant challenges due to the risk of bleeding and potential drug-related complications. This case series details two unique instances of MDR-TB in such patients, exploring the complexities of treatment. Tuberculosis, known to induce a hypercoagulable state, can further complicate existing coagulation abnormalities. Using individualized shorter all-oral MDR-TB regimens alongside careful monitoring, both patients were successfully treated without severe bleeding episodes or deterioration in their coagulation profiles. This series highlights the importance of therapeutic approaches with close interdisciplinary collaboration to manage such cases effectively and improve patient outcomes.
Keywords: Case report, Coagulation disorders, Combined factors V and VIII deficiency, Hemophilia, Multidrug resistant tuberculosis
How to cite this article: S RR. Challenges and Triumphs: A Case Series of Drug-resistant Tuberculosis Management in Patients with Coagulation Disorders. Indian J Respir Care 2024;13(4):265–267.
Source of support: Nil
Conflict of interest: None
Patient consent statement: The author(s) have obtained written informed consent from the patient(s) for publication of the case report details and related images.
INTRODUCTION
India accounts for nearly 23% of global tuberculosis cases, with 9.6 million incident cases annually worldwide.1 The country had an estimated incidence of MDR/RR-TB of 1,19,000 (93,000–1,45,000) in 2021, according to the Global TB Report 2022.2 Pulmonary tuberculosis infection increases blood clotting while reducing clot-dissolving factors, resulting in hypercoagulability.3 While effective treatment regimens exist, managing TB in patients with underlying coagulation disorders presents unique challenges. Coagulation disorders, such as hemophilia and combined factor V and VIII deficiency, can complicate TB management due to the risk of bleeding complications and potential interactions with antituberculosis medications. Managing drug-resistant tuberculosis (MDR-TB) in patients with coagulation defects poses challenges due to potential hematological side effects from various anti-TB drugs, with limited literature documenting optimal management strategies.
CASE DESCRIPTION
Case 1
A 20-year-old male presented with low-grade fever with evening rise and cough with mucopurulent expectoration for 2 months. He was diagnosed with severe hemophilia B at 9 months of age, with a positive family history of the same among family members and used to receive factor VII as needed at the time of injuries. However, he never had any major bleeding manifestations requiring blood transfusion. Clinical examination findings included fever (101°F), tachycardia (110 bpm), respiratory rate (19/minute), and room air saturation (96%). Other system examinations were normal, and lab findings were unremarkable. The chest X-ray (Fig. 1) and high-resolution computed tomography (HRCT) thorax (Fig. 2) showed consolidation with cavitation in the right lower lobe. Sputum for cartridge-based nucleic acid amplification test (CBNAAT) indicated rifampicin-resistant TB, following which a shorter all-oral MDR-TB regimen was initiated according to Programmatic Management of Drug-Resistant Tuberculosis (PMDT) 2021 Indian guidelines. Intermittent factor VII injections were administered to manage the patient’s underlying coagulation disorder throughout the treatment course.
Fig. 1: Chest X-ray revealing right lower zone consolidation with right heart border silhouette sign
Fig. 2: HRCT thorax showing right lower lobe consolidation with cavitation
Case 2
A 36-year-old male with diabetes presented with a 2-month history of fever, weight loss, anorexia, productive cough, and recurrent mild streaky hemoptysis. He was diagnosed with combined factor V and VIII deficiency of mild severity since childhood, with a similar history among his sisters, and no major spontaneous bleeding episodes despite very low factor levels (<1%). His physical exam was unremarkable. Lab results, including complete blood count and liver and kidney function tests, were normal except for elevated activated partial thromboplastin time (aPTT) and international normalized ratio (INR) values, which were corrected with a vitamin K injection for 3 days and 4 units of fresh frozen plasma, respectively. On imaging, the chest radiograph (Fig. 3) showed right middle and lower zone consolidation. Rifampicin-resistant TB was diagnosed on sputum CBNAAT, following which a shorter all-oral MDR-TB regimen was initiated according to PMDT 2021 Indian guidelines and uneventfully completed without any worsening of the underlying coagulation disorder.
Fig. 3: Chest X-ray showing right mid and lower zone infiltration
DISCUSSION
Pulmonary TB-related extensive lung involvement causes a severe inflammatory reaction with activation of cytokines and interleukins, associated with a systemic hyperprocoagulant state.4
Currently, no direct evidence suggests that bedaquiline, linezolid, or any other standard TB drugs directly cause coagulation factor deficiencies. However, both drugs have known hematological side effects that may indirectly influence coagulation profiles.
Linezolid, a known cause of dose-dependent thrombocytopenia reported in 2.4–66% of patients, complicates TB management in those with coagulation disorders due to its myelosuppressive or immune-mediated effects. This risk is heightened by TB-induced hypercoagulability and factors such as prolonged use, renal impairment, or liver disease.5,7
Bedaquiline, while primarily known for its bactericidal properties, can also cause QT prolongation and has been linked to other adverse effects, though it is not typically associated with direct coagulation factor deficiencies.8
Both medications, along with other TB treatments, can impact hematological parameters, so close monitoring of blood counts and coagulation profiles is essential when they are used, especially in patients with preexisting coagulation disorders. This monitoring helps prevent complications such as bleeding or thrombosis, which may arise due to the combination of drug side effects and underlying coagulation abnormalities.
Both cases were treated with an 11-month shorter oral MDR-TB regimen, following the PMDT 2021 Indian guidelines. The regimen included bedaquiline (Bdq), levofloxacin (Lfx), clofazimine (Cfz), ethambutol (E), high-dose isoniazid (Hh), and ethionamide (Eto), avoiding the longer all-oral regimen to reduce the risk of hematological side effects associated with linezolid (Lzd).
In case 1, a single dose of factor VII was administered at baseline due to low levels and mild streaky hemoptysis. After the injection and upon treatment completion, follow-up factor VII levels were normal, and no further bleeding episodes occurred.
In case 2, baseline INR derangement was corrected with vitamin K injections, and subsequent monthly coagulation profiles remained normal throughout treatment without any bleeding complications.
Regular monthly monitoring was conducted, including complete blood counts with platelets, liver function tests, and coagulation profiles. Repeating coagulation factor assays at the end of treatment revealed normal levels, making further testing redundant as neither patient experienced bleeding during treatment.
CONCLUSION
Managing TB-related complications like hemoptysis in patients with coagulation disorders requires a team approach, involving pulmonologists, hematologists, and infectious disease specialists. This case series highlights the need for careful monitoring of bleeding symptoms and personalized treatment to ensure successful outcomes. Further studies are needed to refine treatment strategies for these complex cases.
ORCID
Raghul Raj S https://orcid.org/0009-0004-5004-0331
REFERENCES
1. Kaur G, Mundhe V, PUS et al. Pulmonary tuberculosis induced coagulation disorder: a case series. Int J Med Sci Curr Res Rev 2023;6(1):81–90. DOI: 10.5281/zenodo.7554959
2. Central TB Division Ministry of Health and Family Welfare, http://www.tbcindia.gov.in March 2023.
3. Suryakusumah L, Tabri NA, Saleh S, et al. Hemostatic parameters in pulmonary tuberculosis patients after intensive phase treatment. Caspian J Intern Med 2021;12(3):294–298. DOI: 10.22088/cjim.12.3.294
4. Toro AU, Ortega JG. Acquired hemophilia and tuberculosis: case report and literature review. Hematol Transfus Int J 2017;5(5):315–317. DOI: 10.15406/htij.2017.05.00135
5. Conradie F, Bagdasaryan TR, Borisov S, et al. Bedaquiline-pretomanid-linezolid regimens for drug-resistant tuberculosis. N Engl J Med 2022;387(9):810–823. DOI: 10.1056/NEJMoa2119430
6. Report of the Guideline Development Group Meeting on the use of bedaquiline in the treatment of multidrug-resistant tuberculosis. A review of available evidence. (2016). Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO.
7. Takahashi Y, Takesue Y, Nakajima K, et al. Risk factors associated with the development of thrombocytopenia in patients who received linezolid therapy. J Infect Chemother 2011;17(3):382–327. DOI: 10.1007/s10156-010-0182-1
8. Padmapriyadarsini C, Oswal VS, Jain CD, et al. Effectiveness and safety of varying doses of linezolid with bedaquiline and pretomanid in treatment of drug-resistant pulmonary tuberculosis: open-label, randomized clinical trial. Clin Infect Dis 2024:ciae388. DOI: 10.1093/cid/ciae388
________________________
© The Author(s). 2024 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.