ArticlePDF Available

Immune Thrombocytopenia in Tuberculosis: Causal or Coincidental?

  • July 2014
  • Journal of Global Infectious Diseases 6(3):128-31
DOI:10.4103/0974-777X.138512
Authors:
Gopalakrishnan Srividya
Gopalakrishnan Srividya
Gopalakrishnan Srividya
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Gopalakrishna Pillai Syamala Nikhila
Gopalakrishna Pillai Syamala Nikhila
Gopalakrishna Pillai Syamala Nikhila
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Adusumilli Venkatakrishna Kaushik
Adusumilli Venkatakrishna Kaushik
Adusumilli Venkatakrishna Kaushik
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Kuppusamy Jayachandran
Kuppusamy Jayachandran
Kuppusamy Jayachandran
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Download full-text PDF
Read full-text
Download citation

Abstract

Immune thrombocytopenia is a relatively rare hematological manifestation in tuberculosis. We report two cases of immune thrombocytopemia, one in sputum positive pulmonary tuberculosis and the other in miliary tuberculosis. Antituberculous drugs and immunosuppressive therapy corrected the thrombocytopenia in both patients. Our case reports stress that tuberculosis should be considered during the evaluation of immune thrombocytopenia, and also highlights the safety of immunosuppressive therapy during active tuberculosis along with antituberculous drugs.
Available via license: CC BY-NC-SA
Content may be subject to copyright.
128 Journal of Global Infectious Diseases / Jul-Sept 2014 / Vol-6 / Issue-3
INTRODUCTION
Tuberculosis (TB) is a major communicable disease
in both developing and developed countries. The
incidence is on the rise due to multidrug-resistant
bacilli and Human Immunodefi ciency Virus (HIV). As
of 2012 India has the highest incidence of the disease
with an estimated 2.2 million cases, accounting for
26% of the global incidence according to the World
Health Organization statistics.[1] A wide spectrum
of hematological manifestations has been observed
in TB, with thrombocytopenia being common in
miliary TB and thrombocytosis in pulmonary TB.[2]
Thrombocytopenia in TB is usually non-immunological,
due to pancytopenia following bone marrow infi ltration.
Newly diagnosed immune thrombocytopenia in TB is
rare and only 27 cases have been reported so far. We
describe immune thrombocytopenia in two patients with
active pulmonary TB and miliary TB, both of whom
recovered completely with immunosuppressants and
antituberculous therapy (ATT).
Immune Thrombocytopenia in Tuberculosis: Causal
or Coincidental?
Gopalakrishnan Srividya, Gopalakrishna Pillai Syamala Nikhila, Adusumilli
Venkatakrishna Kaushik, Kuppusamy Jayachandran
Department of Medicine, PSGIMSR, Peelamedu, Coimbatore, Tamil Nadu, India
CASE REPORTS
Case 1
The fi rst case is about a 16-year-old boy who presented with
high grade fever and cough with mucoid expectoration for
10 days. Examination revealed petechiae over the patient’s
chest and upper arms. There was no lymphadenopathy or
hepatosplenomegaly.
Hemogram showed low platelets (10,000/ cu.mm) and
erythrocyte sedimentation rate (ESR) of 42 mm/h.
Peripheral smear showed severe thrombocytopenia and
no myeloid cells. High resolution computed tomography
(HRCT) of lungs showed a cavity in the right upper
lobe with surrounding consolidation [Figures 1 and 2].
Sputum for acid fast bacilli (AFB) was positive, and culture
grew Mycobacterium TB. Ultrasound of the abdomen was
normal. Bone marrow aspirate showed normocellular
marrow, normal maturation of erythroid and myeloid
precursors and increased megakaryocytes [Figure 3]. No
hemophagocytic cells were seen. Bone marrow culture for
AFB was sterile. Renal function tests, liver function tests,
serum fi brinogen, D-dimer, and serum procalcitonin were
all within the normal limits. Direct Coombs test, serological
tests for Hepatitis B virus, Hepatitis C virus, HIV and
antinuclear antibodies were negative.
Immune thrombocytopenia is a relatively rare hematological manifestation in tuberculosis. We report two cases of immune
thrombocytopemia, one in sputum positive pulmonary tuberculosis and the other in miliary tuberculosis. Antituberculous drugs and
immunosuppressive therapy corrected the thrombocytopenia in both patients. Our case reports stress that tuberculosis should
be considered during the evaluation of immune thrombocytopenia, and also highlights the safety of immunosuppressive therapy
during active tuberculosis along with antituberculous drugs.
Key words: Immune thrombocytopenia, Miliary tuberculosis, Pulmonary tuberculosis
ABSTRACT
Address for correspondence:
Dr. Gopalakrishnan Srividya, E-mail: srinarayanaa@yahoo.co.in
Access this article online
Quick Response Code:
Website:
www.jgid.org
DOI:
10.4103/0974-777X.138512
CASE REPORT
[Downloaded free from http://www.jgid.org on Thursday, January 26, 2023, IP: 207.230.120.10]
Journal of Global Infectious Diseases / Jul-Sept 2014 / Vol-6 / Issue-3 129
Srividya, et al.: Thrombocytopenia in tuberculosis
A diagnosis of sputum positive pulmonary TB
with possible immune thrombocytopenic purpura
was made and ATT was begun including Isoniazid,
Ethambutol, Pyrazinamide (Rifampicin excluded
due to thrombocytopenia, Levofloxacin included).
Immunosuppressive therapy was also begun with 1 g
of intravenous pulse methylprednisolone for 3 days
followed by 40 mg of oral prednisolone once daily.
After an initial positive platelet response, platelet counts
began to drop. Hence intravenous immunoglobulin was
begun (total of 60 g given over 3 days) which led to an
improvement in platelet counts. Patient was discharged
on ATT and oral prednisolone. Prednisolone was tapered
over 6 weeks and stopped. After completion of ATT,
patient’s sputum was negative for AFB, chest X-ray
showed clearing of the shadows and platelet counts
were in the normal range.
Case 2
A 19-year-old female patient was admitted with a
1 month history of low grade intermittent fever and
cough with scanty sputum. Initially she had fever and
thrombocytopenia (60,000/cu.mm) which was evaluated
elsewhere and attributed to viral infection. She was
referred to our hospital with continuous low grade
fever and serial persistent thrombocytopenia (40,000/
cu.mm and 48,000/cu.mm). She never had any bleeding
tendencies. She appeared ill. Systemic examination was
normal.
Hemogram showed thrombocytopenia (42,000/cu.mm)
and ESR of 46 mm/h. Peripheral blood smear showed
thrombocytopenia and morphologically normal platelets.
Repeated blood cultures were negative. Sputum AFB was
negative. Secondary causes for thrombocytopenia were
ruled out as in the previous case.
Chest X-ray posteroanterior and HRCT of the chest
showed miliary mottling [Figure 4]. Meanwhile, the
patient developed altered sensorium and headache.
Tuberculous meningitis was suspected clinically.
Computed tomography of the brain showed mildly
dilated lateral ventricles with obstruction. Cerebrospinal
fl uid analysis showed features of tuberculous meningitis
(increased protein, increased cell count with lymphocytic
predominance and increased adenosine deaminase
of 15 IU/L, normal value <10 IU/L). Bone marrow
showed megakaryocytosis and ill-defi ned granulomas
with normal maturation of erythroid and myeloid
precursors [Figure 5]. Bone marrow smear was negative
for AFB and culture was sterile.
Figure 1: Computed tomography of chest shows irregular thick walled
cavitary lesion with surrounding air space consolidation in the right
upper lobe with ground glass opacity in the posterior segment of right
upper lobe
Figure 2: High resolution computed tomography of chest shows air
space consolidation in right upper lobe with ground glass opacity in
the posterior segment of right upper lobe
Figure 3: Bone marrow aspirate showing immature hypolobulated form
of megakaryocytes-white block arrow (Giemsa stain, magnifi cation
×400)
[Downloaded free from http://www.jgid.org on Thursday, January 26, 2023, IP: 207.230.120.10]
130 Journal of Global Infectious Diseases / Jul-Sept 2014 / Vol-6 / Issue-3
Srividya, et al.: Thrombocytopenia in tuberculosis
A diagnosis of miliary TB with immune thrombocytopenia
was made. ATT including Isoniazid, Rifampicin, Ethambutol
and Pyrazinamide was begun along with intravenous
dexamethasone 4mg twice daily. The patient improved
clinically and was discharged with ATT and prednisolone
1 mg/kg/day. Prednisolone was tapered over 3 months and
stopped. After completion of ATT, chest X-ray was clear
and platelet counts were within normal range. Temporal
profi le of case 1 and case 2 [Table 1].
DISCUSSION
TB has various organ system involvements including the
hematological system. Hematological manifestations of TB
include anemia, leukocytosis, leucopenia, thrombocytosis,
or thrombocytopenia among others.[2] Thrombocytosis is
commonly seen in pulmonary TB and thrombocytopenia
in miliary TB.[2] Thrombocytopenia in TB may occur
owing to defective platelet production in the context
of pancytopenia due to bone marrow infiltration,
histiophagocytosis, thrombotic thrombocytopenic purpura,
disseminated intravascular coagulation, immune mediated
platelet destruction or as an adverse effect of therapy with
rifampicin and isoniazid.[3]
Immune thrombocytopenia is an acquired autoimmune
disorder characterized by isolated thrombocytopenia with
peripheral blood platelet count <100,000/cu.mm, with
or without mucocutaneous bleeding.[4] It is a diagnosis of
exclusion. Isolated thrombocytopenia has been reported
in 23-43 % of patients with disseminated TB.[5] Immune
thrombocytopenia in TB is rare and very few cases have
been reported so far.[6-9] These patients presented with
constitutional symptoms, cough with hemoptysis and few
with mucosal bleeding.
The mechanism of TB-related immune thrombocytopenia
is not clear. One theory is that antiplatelet antibodies may
be produced by activation of a clone of B-lymphocytes by
Mycobacterium TB.[10] Another is, Mycobacterium TB may share
antigen with platelets leading to antiplatelet antibody.[11]
The patient in Case 1 had constitutional symptoms
attributable to TB and petechiae with isolated
thrombocytopenia. The patient in Case 2 had persistent
Table 1: Temporal profi le of the patients before and after treatment
Time frame Case 1 Time frame Case 2
Platelet count
(cells/cu.mm)
Treatment Platelet count
(cells/cu.mm)
Treatment
Day of admission 10,000 Platelet transfusion Day of admission 42,000 —
Day 2 13,000 Platelet transfusion. ATT started Day 3 40,000 ATT
Day 4 8000 ATT with intravenous steroids (methyl
prednisolone)
Day 5 40,000 ATT with steroids (injection dexa-
methasone) for TB meningitis
Day 7 20,000 ATT with oral steroids (prednisolone) Day 7 75,000 ATT with steroids
Day 8 10,000 Intravenous immunoglobulin Day 10 78,000 ATT with steroids
Day 11 42,000 Discharged with ATT and oral steroids Day 12 78,000 Discharged with ATT and oral steroids
Follow-up — 3 months 240,000 Steroids stopped. ATT continued Follow-up — 3 months 190,000 Steroids stopped. ATT continued
Follow-up — 6 months 282,000 ATT completed Follow-up — 6 months 320,000 ATT completed
ATT: Antituberculous therapy; TB: Tuberculosis
Figure 4: High resolution computed tomography of lung shows miliary
pattern in bilateral lung fi elds with few coalescent larger nodules
Figure 5: Bone marrow biopsy showing epithelioid granuloma (H and E,
magnifi cation ×400)
[Downloaded free from http://www.jgid.org on Thursday, January 26, 2023, IP: 207.230.120.10]
Journal of Global Infectious Diseases / Jul-Sept 2014 / Vol-6 / Issue-3 131
Srividya, et al.: Thrombocytopenia in tuberculosis
isolated thrombocytopenia during episodes of fever,
and miliary TB was diagnosed based on histological
and radiological evidence. Normocellular marrow with
megakaryocytosis indicates peripheral thrombocytopenia.
Secondary causes for immune thrombocytopenia such as
drugs, infections, autoimmune conditions and malignancy
were ruled out in both cases. Even though granulomas
were seen in the bone marrow of the second patient, the
absence of pancytopenia excludes bone marrow infi ltration
as the cause of thrombocytopenia. The immunological
basis of thrombocytopenia is evident from the response to
steroids and intravenous immunoglobulin. Normalization
of platelet counts after completion of ATT suggests TB
as the etiology of the thrombocytopenia.
The other cases reported so far have also received similar
treatment with steroids, intravenous immunoglobulin and
ATT. Tests to detect antiplatelet antibodies were unavailable.
CONCLUSION
TB-related immune thrombocytopenia is a rare
hematological manifestation of a common disease. It
may be treated with immunosuppressants along with
ATT. TB should be considered as a cause of immune
thrombocytopenia in endemic areas and more research is
needed to elucidate the pathogenesis of TB-related immune
thrombocytopenia.
ACKNOWLEDGEMENT
We sincerely acknowledge Dr. T.Saravanan, MD, Professor
of Medicine, Dr. A. Murali, MD, Professor of Medicine and
Dr. Dhanya Ramachandran, MBBS, Junior Resident for editing
the manuscript and Dr. Kanmani, MD, Asst. Professor of
Pathology for providing the images.
REFERENCES
1. Annex 2 country profi les. Global Tuberculosis Report, Geneva: WHO: 2013.
p. 122. Available from: http://www.who.int/tb/publications/global_report/
en/ [Accessed 2013 Oct 26].
2. Kashyap R, Chaudhary VP. Haematological manifestations of tuberculosis.
In: Sharma SK, Mohan A, editors. Tuberculosis, New Delhi: Jaypee Brothers
Medical Publishers (P) Ltd.; 2006. p. 370-9.
3. Ali R, Ozkalemkas F, Ozçelik T, Ozkocaman V, Ozan U, Kimya Y, et al. Idiopathic
thrombocytopenic purpura in pregnancy: A single institutional experience with
maternal and neonatal outcomes. Ann Hematol 2003;82:348-52.
4. Liebman HA, Pullarkat V. Diagnosis and management of immune
thrombocytopenia in the era of thrombopoietin mimetics. Hematology
Am Soc Hematol Educ Program 2011;2011:384-90.
5. Boots RJ, Roberts AW, McEvoy D. Immune thrombocytopenia complicating
pulmonary tuberculosis: Case report and investigation of mechanisms.
Thorax 1992;47:396-7.
6. Ursavas A, Edigar D, Ali R, Koprucuoglu D, Bahcetepe D, Kocamaz G,
et al. Immune thrombocytopenia associated with pulmonary tuberculosis.
J Infect Chemother 2010;16:42-4.
7. Ghobrial MW, Albor noz MA. Immune thrombocytopenia: A rare presenting
manifestation of tuberculosis. Am J Hematol 2001;67:139-43.
8. Kalra A, Kalra A, Palaniswamy C, Vikram N, Khilnani GC, Sood R. Immune
thrombocytopenia in a challenging case of disseminated tuberculosis: A case
report and review of the literature. Case Rep Med 2010; 2010:pii: 946278.
9. Dagaonkar RS, Udwadia ZF. Disseminated tuberculosis with immune
thrombocytopenic purpura. Lung India 2012;29:63-5.
10. Jurak SS, Aster R, Sawaf H. Immune thrombocytopenia associated with
tuberculosis. Clin Pediatr (Phila) 1983;22:318-9.
11. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J
Med 2002;346:995-1008.
How to cite this article: Srividya G, Nikhila GS, Kaushik AV,
Jayachandran K. Immune thrombocytopenia in tuberculosis: Causal or
coincidental?. J Global Infect Dis 2014;6:128-31.
Source of Support: Nil. Confl ict of Interest: None declared.
[Downloaded free from http://www.jgid.org on Thursday, January 26, 2023, IP: 207.230.120.10]
... A proposed hypothesis describes an immune destruction of platelets through circulating antiplatelet antibodies, which are probably produced by an abnormal stimulation of B lymphocytes by Mycobacterium tuberculosis. [5][6][7]9 Other causes of thrombocytopenia, besides mycobacterial bone marrow infiltration, are histiophagocytosis, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, the immune type (present in this case), and the secondary to adverse effects of anti-TB drugs, especially rifampicin and isoniazid. 7 Bleeding is the most common manifestation of ITP, especially of mucosae and gastrointestinal tract. ...
... [5][6][7]9 Other causes of thrombocytopenia, besides mycobacterial bone marrow infiltration, are histiophagocytosis, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, the immune type (present in this case), and the secondary to adverse effects of anti-TB drugs, especially rifampicin and isoniazid. 7 Bleeding is the most common manifestation of ITP, especially of mucosae and gastrointestinal tract. ...
Immune Thrombocytopenic Purpura, a rare manifestation of active tuberculosis: Case report
Article
Full-text available
  • Aug 2020
Tuberculosis is currently considered a public health issue worldwide. Although a large number of hematological disorders related to tuberculosis have been described, immune thrombocytopenic purpura in patients with active tuberculosis is very rare but must be considered in a patient with no other evident cause. Tuberculosis is currently considered a public health issue worldwide. Although a large number of hematological disorders related to tuberculosis have been described, immune thrombocytopenic purpura in patients with active tuberculosis is very rare but must be considered in a patient with no other evident cause.
View
... The mechanism of isolated thrombocytopenia in tuberculosis is believed to be immune-mediated, through antiplatelet antibodies as mycobacterium TB may share antibodies with platelets or platelet-associated immunoglobulin G, which are generated by proliferating lymphocytes as a part of the immune response to infection. Most of the hematological abnormalities, including pancytopenia, have been noted to respond to ATT [3][4][5]. Thrombocytopenia in TB may occur owing to defective platelet production in the context of pancytopenia due to bone marrow infiltration, histiophagocytosis, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, immunemediated platelet destruction or as an adverse effect of therapy with rifampicin and isoniazid [4,6]. Henceforth a patient with newly- diagnosed thrombocytopenia should be evaluated for symptoms associated with disorders causing secondary ITP. ...
... Most of the hematological abnormalities, including pancytopenia, have been noted to respond to ATT [3][4][5]. Thrombocytopenia in TB may occur owing to defective platelet production in the context of pancytopenia due to bone marrow infiltration, histiophagocytosis, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, immunemediated platelet destruction or as an adverse effect of therapy with rifampicin and isoniazid [4,6]. Henceforth a patient with newly- diagnosed thrombocytopenia should be evaluated for symptoms associated with disorders causing secondary ITP. ...
Disseminated tuberculosis with severe immune thrombocytopenia
Article
Full-text available
  • Feb 2019
Immune thrombocytopenia is an autoimmune condition with increased platelet destruction. Immune thrombocytopenic purpura is an uncommon and rare manifestation of tuberculosis. A search of the literature available on TB-associated ITP identified only around 50 cases published between 1964 and 2016. We present an uncommon and interesting case of severe isolated immune thrombocytopenia secondary to bilateral tubercular cervical lymphadenopathy and pott's spine in 26 year old Indian male. Due to severe thrombocytopenia patient was managed with IVIg and steroids along with anti tubercular therapy. Early diagnosis and treatment with Anti tubercular therapy is important for effective control of bleeding manifestations.
View
... We reviewed all cases based on these case definitions to only include cases with 'highly suggestive' and 'suggestive' causality in our analysis. Of the 50 cases identified, 34 were included in our review: 22 (44%) were categorised under 'highly suggestive causality of ITP and TB' and 12 (24%) were categorised under 'suggestive causality of ITP and TB' ( Table 2); 13 (26%) were categorised under 'possible association of ITP and TB', 4,8,11,16,17,21,23,24,34 and 3 (6%) were categorised under 'unlikely causality of ITP and TB'. 12,18,22 Gender was evenly distributed (females n ¼ 18, males n ¼ 15, one case unknown); age ranged from 4 to 74 years (median 30, interquartile range [IQR] 22-50.5). ...
... Nonetheless, immune-modulatory therapy may be necessary to achieve PC normalisation. 23 ITP secondary to TB has been considered a very rare event. It is likely that the true number of cases with ITP secondary to TB is actually higher; many cases may remain undetected, especially in asymptomatic patients and in areas without a routinely available laboratory infrastructure. ...
Immune thrombocytopenia secondary to tuberculosis: A case and review of literature
Article
Full-text available
  • Apr 2017
  • INT J TUBERC LUNG D
Immune thrombocytopenia (ITP) is an auto-immune condition that results in isolated thrombocytopenia associated with possibly lethal haemorrhage. In its secondary form, ITP can be triggered by many infectious and non-infectious conditions. Secondary ITP associated with tuberculosis (TB) has rarely been described in the literature. We report on a 22-year-old patient presenting with hypermenorrhoea and petechiae due to ITP secondary to tuberculous lymphadenitis. Normalisation of thrombocytopenia was only achieved after initiation of anti-tuberculosis treatment following failure of thrombocyte substitution and immune-modulatory treatment. A search of the literature available on TB-associated ITP identified 50 cases published between 1964 and 2016.We reviewed all cases using suggested case definitions on the likelihood of association between ITP and TB. A broad spectrum of TB sites was reported to be associated with ITP, and anti-tuberculosis treatment was the most effective therapy for platelet count normalisation. Time from initiation of anti-tuberculosis treatment to platelet count recovery ranged from 2 days to 3 months. In endemic regions, TB should be considered as an underlying cause of ITP. Early diagnosis of TB and initiation of anti-tuberculosis treatment appears crucial for rapid platelet count recovery, and can reduce the risks associated with long-term immunosuppression, transfusions and the time at risk for haemorrhage.
View
... The diagnosis of tuberculosis was initially dismissed since severe thrombocytopenia aggravating TB is unusual, making early detection difficult, and tuberculosis accompanied by secondary ITP is regarded extremely rare. 8,14,23 Many secondary ITP cases caused by tuberculosis are treated with anti-tuberculosis drugs and corticosteroids, resulting in a platelet increase that lasts anywhere from a few days to three months. Within two weeks of starting prednisolone and one week of starting ATT, our patient's platelets improved. ...
Is It a Coincidence or Secondary Immune Thrombocytopenic Purpura? A Case of an 11-Year-Old Male Patient at Hawassa University Comprehensive Specialized Hospital, Hawassa, Sidama, Ethiopia
Article
Full-text available
  • Mar 2022
Background: Isolated thrombocytopenia with normal levels of other cell lines in the absence of other reasons is referred to as "immune thrombocytopenic purpura" (ITP). Tuberculosis has been associated with a variety of hematologic abnormalities, although severe thrombocytopenia and tuberculosis presenting as immune thrombocytopenic purpura are extremely uncommon. Case presentation: We discuss a case of an 11-year-old male adolescent who came with epistaxis and petechial rash lasting one day, as well as severe thrombocytopenia. Following the clinical diagnosis of ITP, the patient was started on prednisone, transfused with platelets, and later started on antituberculosis (ATT) after confirmation of tuberculosis. The patient had a satisfactory response during the course of treatment, and the platelet level was fully recovered after 6 months. Conclusion: Tuberculosis (TB) should be recognized as a cause of immunological thrombocytopenia in tuberculosis-endemic areas. Our patient's platelet count improved after 1 week of ATT and 2 weeks of prednisolone, and it was entirely restored after 6 months of ATT treatment. Unfortunately, there are no clear guidelines for treating TB-related immune thrombocytopenia or determining the cause of TB-related immune thrombocytopenia. Tuberculosis-induced ITP resolves with the ATT, even though more investigation is warranted.
View
... antibodies produced by the activation of Blymphocytes by mycobacterium TB or mycobacterium TB sharing the antigen with platelets leading to antiplatelet antibody are the possible mechanisms [2]. TB infection stimulates suppressor monocyte activity together with reduction of T-lymphocytes and purified protein derivative of tuberculin may be a nonspecific B-lymphocyte stimulator. ...
Immune thrombocytopenic purpura and tuberculosis: a rare association with management implications
Article
Full-text available
  • Jan 2019
Immune thrombocytopenia is a rare hematological manifestation associated with tuberculosis (TB). A 68-year-old postmenopausal woman was admitted to our hospital with fever and headache for 3 months and lower limb petechial rash since 1 day. She was evaluated and diagnosed to have central nervous system TB. She also had isolated thrombocytopenia and elevated platelet-associated IgG antibodies with a normal bone marrow study. Steroids combined with anti-TB drugs corrected thrombocytopenia and cured TB. We describe a rare hematological manifestation associated with TB and its management to make the readers aware of such unusual presentations of TB.
View
Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity
Article
Full-text available
  • Jun 2023
Introduction: During infection, bone marrow (BM) hematopoiesis is reprogrammed toward myeloid cell production, a mechanism named emergency myelopoiesis. In addition to replenishing myeloid cells, emergency myelopoiesis has been linked to trained immunity, a process that allows enhanced innate immune responses to secondary challenges. Although hematopoietic alterations during tuberculosis (TB) have been described and Mycobacterium tuberculosis may colonize the BM, studies using the mouse model of infection and the laboratory reference strain M. tuberculosis H37Rv have demonstrated limited emergency myelopoiesis and trained immunity. Methods: To further address this issue, we aerosol-infected C57BL/6 mice with high doses of the hypervirulent M. tuberculosis isolate HN878 and monitored alterations to the BM. This experimental model better resembles the human blood immune signature of TB. Results and discussion: We found increased frequencies of lineage-Sca-1 + cKit + (LSK) cells and the granulocyte/macrophage progenitor (GMP) population. At the mature cell level, we observed an increase of monocytes and neutrophils in the blood and lung, likely reflecting the increased BM myeloid output. Monocytes or monocyte-derived macrophages recovered from the BM of M. tuberculosis HN878-infected mice did not show signs of trained immunity, suggesting an uncoupling of emergency myelopoiesis and trained immunity in the BM. Surprisingly, M. tuberculosis HN878-induced emergency myelopoiesis was not fully dependent on IFNg, as mice lacking this cytokine and infected under the same conditions as wild-type mice still presented BM alterations. These data expand our understanding of the immune response to M. tuberculosis and raise awareness of pathogen strain-imposed differences to host responses.
View
Tuberculosis with immune thrombocytopenia Case reports and review of the literature
Article
Full-text available
  • Mar 2021
Rationale Immune thrombocytopenia (ITP) is a platelet disorder that is caused by antibodies against platelet cells. ITP can be either primary or secondary. One of the secondary causes of ITP is infectious diseases. Tuberculosis (TB) has been reported as a rare cause of secondary ITP. We report 3 cases of TB that were associated with ITP with favorable response to therapy. We also compared these cases with similar published cases in the literature. Patient concerns The first case was an Ethiopian female who presented with cough, fever, night sweats, and weight loss and was found to have isolated thrombocytopenia without manifestations. The second case was a Nepalese man who presented with mucocutaneous bleeding and respiratory symptoms. The third case was for a Nepalese male who presented with mucocutaneous bleeding without pulmonary symptoms but with lymphadenopathy on chest imaging. Diagnoses The first and second cases were diagnosed as pulmonary TB based on positive acid-fast Bacillus smear and PCR from the sputum. In the third case, mediastinal lymph node biopsy came positive for TB PCR and culture was consistent with extrapulmonary TB. ITP diagnosis was established in the 3 cases after ruling out other causes of thrombocytopenia. Interventions The first case received intravenous immunoglobulin and anti-tubercular treatment (ATT). The second case received ATT followed by prednisolone. The third case was started on intravenous Immunoglobulin and prednisolone; ATT was added after the diagnosis of TB was established later. Outcomes All the cases achieved a good response to the treatment with normalization of platelets count. Lessons It is important to consider TB as 1 of the causes of secondary ITP, especially in countries with a high TB burden. In our literature review, we found that ITP-specific therapy alone was not effective in treating ITP associated with TB; almost all the cases required ATT for achieving good platelet response.
View
PPE2 protein of Mycobacterium tuberculosis affects myeloid hematopoiesis in mice
Article
  • Dec 2020
  • IMMUNOBIOLOGY
Irregularity in hematopoiesis is noted in humans during tuberculosis. However, influence of mycobacterial protein(s) on bone marrow hematopoiesis is not fully understood. In this study, we have demonstrated the role of a mycobacterial protein, PPE2 (Rv0256c) in suppressing hematopoiesis during infection. PPE2 belongs to PPE (proline-proline-glutamine) family of mycobacterial proteins which are well known for hijacking host machineries for better survival inside host. In the present study, we have shown that mice infected with Mycobacterium smegmatis expressing PPE2 (M. smeg-PPE2) had a marked reduction in cells of myeloid lineage in bone marrow and peripheral blood along with altered bone marrow phenotype. Bone marrow of M. smeg-PPE2-infected mice showed an overall hypo-cellularity with an increase in population of immature cells, along with reduction in mature cell population. Higher number of M. smeg-PPE2 bacilli was observed in bone-marrow, lung, liver and spleen of mice as compared to the control mycobacteria (M. smeg-pVV16). M. smeg-PPE2-infected mice also showed higher expression of IFN-γ than those infected with M. smeg-pVV16. We conclude that PPE2 affects bone-marrow hematopoiesis of myeloid cells, probably by increasing IFN-γ levels, both locally and systemically, thus favoring the bacilli to establish a positive infection.
View
Case 37-2020: A 35-Year-Old Man with Lymphadenopathy and Petechiae
Article
  • Nov 2020
A 35-year-old man was admitted to the hospital with lymphadenopathy and thrombocytopenia (platelet count, 0 per microliter). Four months earlier, painless lymphadenopathy had developed in the groin area; a biopsy specimen of an enlarged lymph node showed necrosis, fibrosis, and inflammation but no malignant cells. A diagnostic procedure was performed.
View
Immune thrombocytopenia associated with tuberculosis - A case report
Article
Full-text available
  • Nov 2020
Tuberculosis can involve the hematological system and cause anemia, leucopenia, leukocytosis, thrombocytopenia, and thrombocytosis. Immune thrombocytopenia related to tuberculosis is rare. We present a case of a 54 years old male patient who was evaluated for isolated asymptomatic thrombocytopenia discovered on routine laboratory investigations. Work up was positive for disseminated tuberculosis. The patient responded to a tapering dose of steroids and anti-tuberculous medications with significant and persistent platelet count improvement.
View
Disseminated tuberculosis with immune thrombocytopenic purpura
Article
Full-text available
  • Jan 2012
Tuberculosis has a variety of hematological manifestations. Immune thrombocytopenic purpura is an uncommon manifestation of tuberculosis. We present a case of disseminated tuberculosis with isolated thrombocytopenia. While TB granulomas in the bone marrow can themselves cause hematological abnormalities, persistent thrombocytopenia refractory to anti-TB therapy may be ITP associated with TB.
View
Diagnosis and Management of Immune Thrombocytopenia in the Era of Thrombopoietin Mimetics
Article
Full-text available
  • Dec 2011
  • Hematology
The recognition of that patients with Immune Thrombocytopenia (ITP) have functional thrombopoietin deficiency and decreased platelet production due to immune-mediated megakaryocytic injury has challenged the traditional view of this disease as predominantly a disorder of antibody-mediated platelet destruction. The therapy of chronic refractory ITP has been transformed by the approval of the thrombopoietin minetics, romiplostim and eltrombopag, which have shown remarkable efficacy in randomized trials. The use of these agents earlier in the disease course after failure of corticosteroid therapy remains controversial. In this article, we review the current data on the efficacy and safety of thrombopoietin receptor agonists and discuss other therapies as well as diagnostic work up of ITP.
View
Immune Thrombocytopenia in a Challenging Case of Disseminated Tuberculosis: A Case Report and Review of the Literature
Article
Full-text available
  • Jan 2010
Mycobacterium tuberculosis (MTB) continues to predominate the cause of morbidity, and mortality in the developing world. The disease affects all the organ systems, and presents in various pathologic disease states. We report an uncommon manifestation of this rather common infectious disease in a 19-year-old male. Immune-mediated thrombocytopenia occurring as a consequence of the tuberculosis infection itself is an exceedingly rare occurrence, and at the time of writing of this paper, only 15 such published reports exist in the English literature so far.
View
Immune thrombocytopenia complicating pulmonary tuberculosis: Case report and investigation of mechanisms
Article
Full-text available
  • Jun 1992
Immune thrombocytopenia and pulmonary tuberculosis presented concurrently in a 20 year old Thai man as a bleeding diathesis. Intravenous immunoglobulin rapidly corrected the thrombocytopenia. Immunofluorescence and immunoblot studies with platelets and mycobacteria showed the presence of platelet surface membrane IgG.
View
Immune Thrombocytopenic Purpura
Article
Full-text available
  • Apr 2002
  • NEW ENGL J MED
Immune thrombocytopenic purpura, which may lead to bleeding, is typically caused by antibodies directed against the platelet glycoprotein IIb/IIIa complex. Since the management of the disorder is different for children and adults, the authors of this up-to-date review provide separate sections on the two age groups. Along with advances in management, they also discuss the current understanding of pathophysiology and, in particular, the way in which autoantibodies against platelets are generated.
View
Immune thrombocytopenia associated with pulmonary tuberculosis
Article
  • Feb 2010
  • J Infect Chemother
Many hematological abnormalities, such as pancytopenia, anemia, and leukocytosis, can be associated with tuberculosis (TB). Immune thrombocytopenic purpura (ITP) is an extremely rare event in TB. We report a 46-year-old male patient who was admitted to hospital with a history of weight loss, combined with hemoptysis, fever, cough, sputum, general malaise, and night sweats. Physical examination revealed a body temperature of 38.8 °C, and petechiae distributed over the lower extremities. Laboratory findings were as follows: erythrocyte sedimentation rate, 84 mm/h; white blood cells, 7070/mm3; hemoglobin, 11.7 g/dl; and platelet count, 4000/mm3. On Ziehl-Neelsen stain of sputum, acid-fast bacilli were observed. Antituberculosis therapy was started, together with prednisolone, 0.5 mg/kg per day, from the day of admission. He was treated successfully with the steroid and antituberculous drugs.
View
Immune Thrombocytopenia Associated with Tuberculosis
Article
  • May 1983
Thrombocytopenia associated with Mycobacterium tuberculosis infection developed concurrently in a mother and son. Antiplatelet antibodies were demonstrated in the serum of both patients. It is suggested that this and possibly other hematologic complications associated with tuberculosis are immune mediated.
View
Immune thrombocytopenia: A rare presenting manifestation of tuberculosis
Article
  • Jun 2001
We report the case of a 49 year-old male who presented with immune thrombocytopenia (ITP)-induced epistaxis and generalized purpura. During the same hospitalization the patient was also found to have clinical, microbiological, histological, and roentgenographic evidence of disseminated mycobacterial tuberculosis (TB). The hematological and infectious abnormalities, which did not respond to high-dose intravenous corticosteroids and immune globulin (IVIg), resolved after anti-tuberculous treatment. Herein we review the characteristics of this rarely documented association.
View
Significance of Haematological Manifestations in Patients with Tuberculosis
Article
  • Sep 2001
  • J Assoc Phys India
Tuberculosis is a major public health problem in India. Haematological changes associated with tuberculosis have been incompletely investigated. To the best of our knowledge, there is no comprehensive study assessing the haematological abnormalities in these patients from the Indian subcontinent. In the present study, we have compared peripheral blood and bone marrow findings in patients with disseminated/miliary tuberculosis (DTB/MTB) as well as pulmonary tuberculosis (PTB). An attempt has also been made to assess the effect of antituberculosis therapy on the haematologic abnormalities. Thirty two patients with disseminated/miliary tuberculosis and 23 patients with pulmonary tuberculosis were prospectively studied to determine the various haematological manifestations in tuberculosis and the effect of antituberculosis therapy. All patients received standard antituberculosis treatment. They were subjected to a detailed haemogram including peripheral blood examination, which was repeated on completion of antituberculosis therapy. Bone marrow aspiration and biopsy was also done in all patients before starting antituberculosis treatment. Normocytic normochromic anaemia was the most common abnormality observed in all the groups and subgroups (DTB/MTB 84%, PTB 86%). Other haematological abnormalities of the white blood cells include leucopenia (DTB/MTB 25%, PTB 0%; p < 0.02), neutropenia (DTB/MTB 22%, PTB 0%; p < 0.04), lymphocytopenia, monocytopenia, leukocytosis, neutrophilia, lymphocytosis and monocytosis. Pancytopenia was observed only in patients with disseminated/miliary tuberculosis (p < 0.05). Thrombocytopenia was more common in patients with disseminated/miliary tuberculosis (p < 0.007), whereas thrombocytosis was more common in patients with pulmonary tuberculosis (p < 0.04). The patients of disseminated/miliary tuberculosis with granulomas in the bone marrow had certain significant differences as compared to patients without granulomas. These patients showed severe anaemia, peripheral monocytopenia and bone marrow histiomonocytosis. The haemogram reverted to normal with antituberculosis therapy in these patients. In view of the varied haematological abnormalities observed in patients with tuberculosis in this part of the world, it is concluded that the differential diagnosis of tuberculosis should be entertained in patients with varied haematological disorders.
View
Idiopathic thrombocytopenic purpura in pregnancy: A single institutional experience with maternal and neonatal outcomes
Article
  • Jul 2003
We observed 13 pregnant women of 70 females with idiopathic thrombocytopenic purpura (ITP) from January 1992 through September 2002. Thirteen mothers with ITP gave birth to twelve babies and two fetuses died. One of the pregnancies produced twins. Seven of the cases were diagnosed with ITP before pregnancy and six during pregnancy. One of the thirteen pregnancies was complicated by preeclampsia, one by ablatio placentae, and one by intrauterine death. Seven mothers received corticosteroid treatment, four high-dose immunoglobulin therapies, and one underwent splenectomy in the second trimester of gestation. At the time of delivery six mothers had normal platelet counts and seven had low platelet counts. Nine deliveries were by vaginal route and four were by cesarean section. Eleven infants were born with normal platelet counts and one was thrombocytopenic at the time of delivery. No infant showed any clinical signs of hemorrhage and there were no neonatal complications. Two fetuses died; one of them because of ablatio placentae and the other was intrauterine dead. In conclusion, ITP in pregnancy requires the management of two patients, the mother and her baby; hence, the close collaboration of a multidisciplinary group composed of a hematologist, obstetrician, anesthesiologist, and neonatologist is essential.
View