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 Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 7  |  Issue : 1  |  Page : 38-40

Rifampicin-Induced Thrombocytopenia: A Rare Complication


Department of Respiratory Medicine, Sri Aurobindo Institute of Medical Sciences, Indore, Madhya Pradesh, India

Date of Web Publication18-Jan-2019

Correspondence Address:
Arun Chandelkar
Department of Respiratory Medicine, Sri Aurobindo Institute of Medical Sciences, Indore, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jacp.jacp_8_18

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  Abstract 

Extensive clinical experience has shown that rifampicin is well tolerated, but on rare occasions, it can cause life-threatening adverse reactions such as acute renal failure and thrombocytopenia. Throbocytopenia is mostly encountered with isoniazid and pyrazinamide. Rifampicin is an essential component of the treatment regimen for tuberculosis. We are reporting a case of rifampicin-induced thrombocytopenia which was being treated for pulmonary tuberculosis. The physician treating tuberculosis patients must be aware of this rare life-threatening complication.

Keywords: Rifampicin, thrombocytopenia, tuberculosis


How to cite this article:
Dosi R, Chandelkar A, Jain A, Motiwale S, Joshi P, Jain P. Rifampicin-Induced Thrombocytopenia: A Rare Complication. J Assoc Chest Physicians 2019;7:38-40

How to cite this URL:
Dosi R, Chandelkar A, Jain A, Motiwale S, Joshi P, Jain P. Rifampicin-Induced Thrombocytopenia: A Rare Complication. J Assoc Chest Physicians [serial online] 2019 [cited 2019 Oct 18];7:38-40. Available from: http://www.jacpjournal.org/text.asp?2019/7/1/38/250473


  Introduction Top


Most antitubercular drugs are relatively safe, but serious reactions are also not uncommon. Thrombocytopenia is one of the uncommon but potentially fatal adverse effects seen with certain antitubercular drugs, including rifampicin.[1] Rifampicin is a crucial drug in the treatment regimens for tuberculosis.

Adverse reaction to rifampicin is less on daily regimens but is relatively common with intermittent regimen.[2] These include cutaneous syndrome, abdominal syndrome, flu-like syndrome, respiratory syndrome, and increased transaminases.[3] Adverse reactions due to rifampicin are either dose related or allergic. Apart from its minor side effects like nausea, vomiting, and abdominal discomfort, very rarely it can cause life-threatening acute renal failure or thrombocytopenia.[4]

To identify the offending agent in a patient taking several medications, it poses a challenging clinical problem.[5],[6] Confirmation of drug-induced thrombocytopenia at the time of initial presentation is not often possible as tests for drug-dependent antiplatelet antibodies are not available in most laboratories.[2] Discontinuation of suspected drug leading to resolution of thrombocytopenia provides a strong evidence of drug-induced thrombocytopenia.[7] Rifampicin-induced thrombocytopenia was first reported in 1970.[7],[8] It is usually reversible if detected early with high index of suspicion and treated appropriately.


  Case Report Top


A 45-year-old male presented to our center with the complain of high-grade fever, cough with expectoration, loss of appetite from 1 month, and was found sputum positive. The patient had a history of taking anti tubercular therapy (ATT) for 1 month in November 2016 for sputum-positive pulmonary tuberculosis and was lost to follow-up; cartridge based nucleic acid amplification test (CBNAAT) was sent and Mycobacterium Tuberculosis (MTB) was detected with rifampicin sensitive. On examination, his vitals were stable, and post-tussive crepitations were present in left upper zone. So ATT was started under dots CAT II. His initial complete blood count (CBC) was within normal limit and platelet count was 3.51 Lacs. Renal and liver function test were within normal limits. He tolerated the treatment and was discharged on dots CAT II.

After 2 months of treatment, the patient presented with epistaxis, hemoptysis, and petechial eruption all over his trunk; his platelet count was found 3000/mm3, and rest investigation was within normal limit. The ATT was stopped, and transfuse with fresh frozen plasma and platelet-rich plasma, after 7 days patient platelet count, became normal and stabilize. His bleeding time and clotting time were 2 and 4.5 min, respectively. Rest all investigation was performed to rule out other causes of thrombocytopenia. Dengue profile and anti nuclear antibody (ANA) profile was negative. Bone marrow smear examination revealed megakaryocytic hyperplasia. Reticulocyte count was 0.3%. Peripheral smear showed normocytic normochromic red blood cell (RBC) and decreased platelet count. After ruling out other causes of thrombocytopenia, we planned to start an ATT with single-drug challenge at a time. The treatment was initiated with isoniazide and then pyrazinamide with a gap of 7 days added; lastly, rifampicin was added at dose of 450 mg/day, but this again resulted in thrombocytopenia (30,000/mm3) on the third day after starting rifampicin, and the drug was stopped; platelet count became normal (225,000/mm3) after 6 days without any supportive treatment; challenge with rifampicin was again given with low dose of 150 mg to the regimen and plan to gradually increase the dose once tolerated, but the platelet count decreased to 10,000/mm3 on lower dose only. The rifampicin was stopped, and during the follow-up, the platelet count became normal. Rifampicin was subtracted from regimen, and the patient was discharge on isoniazide, pyrazinamide, ethambutol, and streptomycin and had no further thrombocytopenia during remaining period of therapy. There were no clinical or laboratory abnormalities during follow-up examinations.


  Discussion Top


Tuberculosis Research Centre, Chennai, reported only a single case of rifampicin-induced thrombocytopenia among over 8000 patients treated for tuberculosis over 30 years.[9],[10]

Thrombocytopenia can occur with all primary antitubercular drugs. In case of isoniazid, it occurs as hematological reaction.[11] There are reports of ethambutol[12] and pyrazinamide[13]-induced thrombocytopenia, perhaps by immunological mechanism.

The causes of thrombocytopenia include viral infections, immune disorders, collagen vascular diseases, lymphoproliferative disorders, and drugs.[14] Other drugs known to cause thrombocytopenia are quinine, quinidine, chloroquine, sulfonamides, tolbutamide, chlorothiazide, digoxin, penicillamine, amphotericin B, sedatives, anticonvulsants, methyldopa, aspirin, etc.[8] The drugs causing thrombocytopenia lead to either suppression of platelet production or immunological platelet destruction; most drugs induced thrombocytopenia by latter mechanism, and the platelets are damaged by complement activation following the formation of drug–antibody complex. The best proof of drug-induced etiology is the prompt rise in the platelet count when suspected drug is discontinued.[7]

Serious adverse reactions due to rifampicin, which are immune complex mediated, are mostly encountered during intermittent therapy or when there is a gap in treatment.[15],[16] It has been postulated that with daily administration of rifampicin, there is neutralization of any antibody formed, and the immune complexes are continuously removed without causing any allergic reaction.[2] Discontinuation of treatment allowed sufficient quantity of platelets to build up during drug-free interval, so that when rifampicin is readministered, an intense reaction ensues.[16]

The mechanism hypothesized is that in the presence of the drug, the immune complexes nonspecifically adsorb to the platelet membrane, causing platelet damage and rapid removal from the circulation.[7],[17] The binding epitope of the Immunoglobulin G (IgG) antibody was found in the glycoprotein Ib/IX complex which is the target in rifampicin-induced immune thrombocytopenia.[18]

Incidence of thrombocytopenia occurred from 1st to 14th month of therapy of rifampicin.

Although restarting ATT therapy in a patient suspected to have drug-induced thrombocytopenia, it is prudent to start with three drugs that are not given previously including one parentral agents (aminoglycoside or polypeptide) and two oral agents that are safe, when life-threatening adverse drug reaction has occurred.[6] Cross-reactivity is not expected between different drugs or among stereo isomers due to high specificity of the reaction.[6] Platelet counts should be monitored regularly, and platelets should be transfused to maintain levels above 20,000/mm3. Corticosteroids are of no benefit in drug-induced thrombocytopenia.[6] However, in patients with severe thrombocytopenia, they may be administered as the diagnosis may be difficult to distinguish from other causes of thrombocytopenia due to similar clinical features. Offending drug should not be reused as only a minute quantity of drug is needed to set up subsequent immune reaction.[19]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Garg R, Gupta V, Mehra S, Singh R, Prasad R. Rifampicin induced thrombocytopenia. Indian J Tuberc 2007;54:94-6.  Back to cited text no. 1
    
2.
Bassi L, Perna G, Silvestri LG. Antibodies against rifampicin in patients with tuberculosis after discontinuation of daily treatment. Am Rev Respir Dis 1976;114:1189-90.  Back to cited text no. 2
    
3.
Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN et al. American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of tuberculosis. Am J Respir Crit Care Med 2003;167:603-62.  Back to cited text no. 3
    
4.
Friedman LN. Chemotherapeutic agents for mycobacterial infections. In: Tuberculosis: Current concepts and treatment. 2nd ed. Boca Raton, Florida: CRC Press LLC; 2001. pp 301-32.  Back to cited text no. 4
    
5.
Wazny LD, Ariano RE. Evaluation and management of drug induced thrombocytopenia in the acutely ill patients. Pharmacotherapy 2000;20:292-307.  Back to cited text no. 5
    
6.
Pedersen-Bjergaard U, Andersen M, Hansen PB. Drug induced thrombocytopenia: Clinical data on 309 cases and the effect of corticosteroid therapy. Eur J Clin Pharmacol 1997;52:183-9.  Back to cited text no. 6
    
7.
Blajchman MA, Lowry RC, Petil JE, Stradling P. Rifampicin induced immune thrombocytopenia. BMJ 1970;3:24-6.  Back to cited text no. 7
    
8.
Ferguson GC. Rifampicin and thrombocytopenia. BMJ 1971;3:638.  Back to cited text no. 8
    
9.
Banu Rekha VV, Adhilakshmi AR, Jawahar MS. Rifampicin-induced acute thrombocytopenia. Lung India 2005;22:122-4.  Back to cited text no. 9
    
10.
Verma A, Singh A, Chandra A, Kumar S, Gupta R. Rifampicin-induced thrombocytopenia. Indian J Pharmacol 2010;42:240.  Back to cited text no. 10
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11.
Ross JD, Horne NW. Drugs used in chemotherapy. In: Horne NW, editor. Modern drug treatment of tuberculosis. 1st Indian ed. New Delhi: Oxford University Press 1992. pp 1-17.  Back to cited text no. 11
    
12.
Prasad R, Mukerji PK. Rifampicin induced thrombocytopenia. Indian J Tuberc 1989;36:44.  Back to cited text no. 12
    
13.
Jain VK, Vardhar H, Prakash OM. Pyrazinamide induced thrombocytopenia. Tubercle 1988;69:217-8.  Back to cited text no. 13
    
14.
Robbins SL, Kumar V, Cotran RS. Diseases of red cells and bleeding disorders. In: Robbins pathological basis of diseases. 4th ed. Philadelphia: W.B. Saunders Co. 1989. pp 657-702.  Back to cited text no. 14
    
15.
Poole G, Stradling P, Worrledge S. Potential serious side effects of high-dose twice-weekly rifampicin. BMJ 1971;3:343-7.  Back to cited text no. 15
    
16.
Hong Kong Tuberculosis Treatment Services/Brompton Hospital/British Medical Research Council. A controlled trial of daily and intermittent rifampicin plus ethambutol in the retreatment of patients with pulmonary tuberculosis. Results up to 30 months. Tubercle 1975;56:179-89.  Back to cited text no. 16
    
17.
Marcus AJ. The Cecil textbook of medicine. 16th ed. Philadelphia: W.B. Saunders Co. 1982. p p 983.  Back to cited text no. 17
    
18.
Pereira J, Hidalgo P, Ocqueteau M, Blacutt M, Marchesse M, Nien Y et al. Glycoprotein Ib/IX complex is the target in rifampicin induced immune thrombocytopenia. Br J Haematol 2000;110:904-10.  Back to cited text no. 18
    
19.
Das S, Roy A, Maiti A. Rifampicin induced thrombocytopenia. Indian J Dermatol 2006;51:222.  Back to cited text no. 19
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