Year : 2014 | Volume
: 6 | Issue : 3 | Page : 93--94
State of the globe: Immune thrombocytopenia, an uncommon complication in tuberculosis
Department of Medicine, Medical College Kolkata, West Bengal, India
Department of Medicine, Medical College Kolkata, West Bengal
|How to cite this article:|
Paul R. State of the globe: Immune thrombocytopenia, an uncommon complication in tuberculosis.J Global Infect Dis 2014;6:93-94
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Paul R. State of the globe: Immune thrombocytopenia, an uncommon complication in tuberculosis. J Global Infect Dis [serial online] 2014 [cited 2021 Apr 19 ];6:93-94
Available from: https://www.jgid.org/text.asp?2014/6/3/93/138495
Tuberculosis (TB) has been associated with a variety of hematological abnormalities such as anemia, pancytopenia, leukopenia, myelofibrosis or the hemophagocytic syndrome.  Normochromic normocytic anemia or anemia of chronic disease with high erythrocyte sedimentation rate is the most common abnormality. These hematological alterations may be the first and only manifestation of TB. Platelet counts may change either way in TB. Although thrombocytosis is associated with pulmonary TB, thrombocytopenia is usually associated with disseminated or miliary TB.  The hematological changes often revert to normal with treatment of TB alone.
The etiology of this thrombocytopenia in TB may be
Bone marrow infiltration in disseminated TB.TB related disseminated intravascular coagulation.Generation of anti-platelet antibodies immune thrombocytopenia (ITP).Rifampicin induced thrombocytopenia.
To differentiate among these etiologies, bone marrow studies, blood coagulation parameters or a therapeutic trial may be needed.
ITP has been only rarely reported in TB. A 1995 study from the middle east reported only 1% incidence of ITP in TB patients.  Although TB itself is a precipitating factor for ITP, there are also some case reports where latent ITP was reactivated by TB.  Most of the cases have been reported from parts of Asia. In the current issue of this journal, Srividya et al have reported 2 cases of ITP in tuberculosis from India.  No age is immune from this complication, but it reported commonly in 3 rd and 4 th decades of life and more frequently in females. The exact cause of ITP in TB is not known. It is thought that there is some molecular mimicry between tubercular antigens and platelet membrane surface proteins.  The sensitized plasma cells secrete antibodies against the tubercular antigen, which cross react with the platelets and cause their destruction. Thus, especially in TB endemic regions like India, any patient presenting with new onset ITP should be screened for TB. This is because unless treatment of the underlying mycobacterial infection is done, the thrombocytopenia will not resolve with other immunosuppressive therapies alone. Furthermore, in TB patients with ITP, concomitant HIV infection must be ruled out as this is also a cause of thrombocytopenia.
ITP has been reported in pulmonary TB as well as tuberculous lymphadenitis, splenic abscess and disseminated forms of the disease.  Very rarely, knee joint TB has been associated with ITP.  However, in disseminated TB, bone marrow biopsy must be done to rule out infiltration by tuberculous granuloma before an immune cause is considered. Ghobrial and Albornoz have reported a case of tuberculous inguinal and abdominal lymphadenopathy that presented with severe bleeding manifestations and remained resistant to several courses of steroids and intravenous immunoglobulin (IVIg).  The thrombocytopenia in TB can be very severe and may present with disseminated purpura, epistaxis, hematuria or mucosal bleeding. ,, One potentially confusing situation is hemoptysis. TB patients may have hemoptysis due to the infection itself, or it may be the first manifestation of developing ITP also. Thus, if recurrent or severe hemoptysis occurs, platelet count of the patient should be checked.
According to the American Society of Hematology 2011 guidelines, ITP is diagnosed by isolated bleeding due to thrombocytopenia in the absence of organomegaly and with no evidence of alteration in other cell lines. In general, bone marrow examination or assay of anti-platelet antibodies is not needed to diagnose ITP if typical clinical features are present. However, all secondary causes of thrombocytopenia such as collagen vascular disease, drug induced disorders, malignancy and hepatic disorders must be ruled out before a diagnosis of ITP is made. If bone marrow examination is carried out in ITP, mild increase in all cell lines is seen, especially with an increase in size and number of megakaryocytes. , Bone marrow study in TB patients with ITP in some of the reported cases also revealed the same features. In general, anti-platelet antibodies are not routinely tested in suspected ITP cases. A study from Mumbai, India reported four cases of anti-platelet antibody positivity in TB cases.  ELISA was used to detect anti-platelet antibodies in this study. In that study, rifampicin was also associated with generation of these antibodies and discontinuation of Rifampicin led to complete disappearance of these antibodies.  Similar anti-platelet antibodies were also reported in other cases of TB with ITP. These reports tested the anti-protective antigen IgG antibody.
Treatment of ITP associated with TB consists of anti-tubercular therapy (ATT) along with steroids and/or IVIg.  Only immunosuppressive therapy will not resolve the condition. Although rifampicin has been implicated in causing thrombocytopenia in some cases, all the reported cases used four drug ATT including rifampicin without the aggravation of the condition. , IVIg has been used in the standard dose of 400 mg/kg/day for 5 days and prednisolone has been used in doses of 1-2 mg/kg/day orally. The exact mechanism of action of IVIg is still debated, but it is thought to suppress the production of anti-platelet antibodies and also inhibit Fc receptor mediated platelet phagocytosis. There is also accelerated anti-platelet antibody elimination. Usually platelet count starts to recover by 1-2 weeks.  Usually, the thrombocytopenia resolves completely by 2-3 months and review of literature did not reveal any case of persistent ITP after TB treatment.  The thrombocytopenia may recur for first 2 months as some of the mycobacteria may remain alive. The exact duration of the immunosuppressive therapy is not standardized and must be individualized according to hematological response of the patient. However, in most of the reported cases steroids were withdrawn in 1-2 months.
TB, once thought to be almost extinct in the developed world, has now come back in different forms all over the world. Hematological manifestations may be the only presentation of TB in some cases. Thrombocytopenia can be life-threatening in some cases and hence needs prompt treatment. However in TB associated ITP, unless ATT is also instituted the platelet count will continue to fluctuate. Hence, in endemic regions, physicians should always think of TB in a case of refractory ITP.
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