Platelets: The unsung heroes in the battle against tuberculosis – A comprehensive review of platelet indices as diagnostic beacons and pathophysiological players

INTRODUCTION

Tuberculosis (TB) remains a significant global health challenge, necessitating improved diagnostic and prognostic tools. In recent years, there has been growing interest in the role of platelets in TB pathogenesis and their potential as diagnostic and prognostic markers. This review aims to explore the relationship between platelet indices and TB, focusing on their potential diagnostic and prognostic value, as well as their role in the pathophysiology of the disease.

PLATELET INDICES: AN OVERVIEW

Platelet indices are parameters that provide information about platelet production, destruction, and activation. The main platelet indices discussed in TB research include:

1. Platelet count (PLT): The total number of platelets per unit volume of blood.

2. Mean platelet volume (MPV): The average size of platelets in a blood sample.

3. Platelet distribution width (PDW): A measure of the variation in platelet size.

4. Plateletcrit (PCT): The volume percentage of platelets in blood.

ALTERATIONS IN PLATELET INDICES IN TB

Numerous studies have reported significant changes in platelet indices in TB patients compared to healthy controls and patients with other respiratory conditions:

1. PLT: Thrombocytosis (elevated PLT) is frequently observed in active TB. Sahin et al. found thrombocytosis in 44% of pulmonary TB (PTB) patients, with a mean PLT of 384.5 ± 122 × 10³/μL in TB patients, compared to 304.4 ± 88.3 × 10³/μL in pneumonia patients and 253.78 ± 55 × 10³/μL in healthy controls,^[1,2] as shown in Table 1. Renshaw and Gould also reported an association between thrombocytosis and Mycobacterium tuberculosis infection.^[3]

2. MPV: Findings on MPV have been inconsistent across studies. Sahin et al. found no significant difference in MPV between TB patients, pneumonia patients, and healthy controls.^[1] However, Tozkoparan et al. reported higher MPV values in active TB patients compared to those with inactive TB and healthy controls^[4] [Table 1]. A recent study by Xu et al. suggested that MPV could be a potential diagnostic marker for comorbidity of TB and diabetes mellitus.^[5]

3. PDW: PDW has been found to be significantly higher in PTB patients compared to healthy controls. Sahin et al. reported PDW values of 14.7 ± 2.0% in TB patients [Table 1 and Figure 1], higher than pneumonia patients, and healthy controls.^[1,2]

4. PCT: PCT has been reported to be significantly higher in TB patients compared to controls and patients with pneumonia. Sahin et al. found PCT values of 0.33 ± 0.09% in TB patients [Table 1 and Figure 1], higher than pneumonia patients, and healthy controls.^[1,2]

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Figure 1:

Comparison of platelet indices in various patient groups (Sahin et al., 2012) TB: Tuberculosis, MPV: Mean platelet volume, PDW: Platelet distribution width.

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These indices were measured by ABX Pentra 120 (Impedance and Optical, Minnesota, USA) device by Sahin et al.^[1,2] and Coulter Model-S-Plus automatic counter (Coulter Electronics, Hialeah, FL, USA) with standard calibration and quality control procedures by Tozkoparan et al.^[4]

DIAGNOSING TB AND DIFFERENTIATING IT FROM PNEUMONIA AND OTHER INFECTIONS

For diagnosing TB, Sahin et al.^[1,2] and Tozkoparan et al.^[4] used chest radiography and sputum examination. Sputum smears for acid fast bacilli were prepared by ZN stain and mycobacterial cultures were carried out using Lowenstein– Jensen media and a radiometric BACTEC TB 460 system. When sputum smears were negative or insufficient, bronchoalveolar lavage through fiberoptic bronchoscopy was carried out for smear preparation and Mycobacterium culture. Diagnosis of active PTB was confirmed by positive M. tuberculosis culture. Patients who exhibited no culture growth were excluded, even if they had clinical and radiological improvement after anti-tuberculous treatment and were accepted as having active TB. Inactive PTB was diagnosed when patients had a negative culture result, and radiographic lesions attributable to sequel PTB that showed no change during at least a 3-month follow-up period.

Patients other than those with active PTB comprised the non-tuberculous (non-TB) group as controls, including patients with inactive PTB. Patients with pneumonia in the non-TB group formed a subgroup representing non-TB patients with an acute phase response. Diagnostic criteria for pneumonia were as follows: Symptoms and signs of pyrexia, cough (productive or non-productive), dyspnea, pleuritic chest pain, and auscultatory findings (altered breath sounds, crepitations, and/or localized rales) corresponding to an acute infiltrate on a chest radiograph that was cleared by antibiotic therapy.

PATHOPHYSIOLOGICAL MECHANISMS

The alterations in platelet indices observed in TB patients can be attributed to several pathophysiological mechanisms:

DIAGNOSTIC AND PROGNOSTIC VALUE OF PLATELET INDICES IN TB

The observed changes in platelet indices in TB patients have led researchers to investigate their potential diagnostic and prognostic value:

Monitoring treatment response

Akpan et al. investigated hemostatic indices, including PLT, as markers for monitoring PTB treatment.^[11] They found that these indices could be useful in assessing treatment efficacy. Awodu et al. also reported changes in hemorheological variables during TB therapy.^[12] Tozkoparan et al.^[4] reported the changes in platelet indices after antitubercular treatment [Figure 2].

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Figure 2:

Platelet indices before and after ATT (Tozkoparan et al., 2007) ATT: Antitubercular treatment, MPV: Mean platelet volume, PDW: Platelet distribution width.

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CHALLENGES AND LIMITATIONS

While the evidence supporting the use of platelet indices in TB is growing, several challenges and limitations should be considered:

FUTURE DIRECTIONS

1. Large-scale, multi-center studies to validate and refine cutoff values for different populations and clinical scenarios.

2. Longitudinal studies to assess the dynamics of platelet indices throughout the course of TB treatment and their correlation with treatment outcomes.

3. Mechanistic studies to further elucidate the role of platelets in TB pathogenesis and immune response.

4. Exploration of combined biomarker panels that incorporate platelet indices with other established and emerging TB biomarkers.

5. Investigation of platelet indices in pediatric TB, as suggested by the recent study by Hilda et al.^[10]

6. Further research on the potential of MPV as a marker for TB-diabetes comorbidity, as proposed by Xu et al.^[5]

7. Exploration of the relationship between platelet indices and TB-associated coagulation abnormalities, building on the work of Turken et al. and others.^[9,18]

8. Investigation of the potential therapeutic implications of modulating platelet function in TB, considering their role in immune modulation and granuloma formation.^[8]

CONCLUSION

Platelet indices have emerged as promising diagnostic and prognostic markers for TB, offering potential advantages in terms of cost-effectiveness and rapid results. Significant alterations in PLT, MPV, PDW, and PCT have been observed in TB patients, reflecting the complex interplay between platelets and the immune system during infection. These changes not only contribute to our understanding of TB pathogenesis but also open new avenues for clinical applications.

However, challenges persist, including lack of specificity and measurement variability across different clinical settings. To address these limitations, future research should focus on large-scale, multi-center studies to validate and refine cutoff values for diverse populations. Longitudinal studies exploring the dynamics of platelet indices throughout TB treatment could provide valuable insights into their prognostic value. In addition, investigating combined biomarker panels that incorporate platelet indices with other established TB markers may enhance diagnostic accuracy.

Further exploration of the mechanistic role of platelets in TB immunity and granuloma formation could potentially lead to novel therapeutic approaches, highlighting the broader implications of this field of study.