1/18/22, 5:46 PM Ranitidine-induced thrombocytopenia: A rare drug reaction

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Indian J Pharmacol. 2011 Feb; 43(1): 76–77. PMCID: PMC3062128

doi: 10.4103/0253-7613.75676 PMID: 21455428

Ranitidine-induced thrombocytopenia: A rare drug reaction

Amit V Bangia, Narendra Kamath, and Vidushi Mohan

Abstract
H2 antagonist ranitidine causing thrombocytopenia is a rare drug phenomenon. Here we present a case
of 55 year old female of pustular psoriasis who presented with fever and vomiting. Patient. was started
on roxithromycin, iv ondensetron, paracetamol and iv ranitidine. Complete blood count revealed
neutrophilia with normal blood picture. However repeat investigations showed falling WBC and
platelet count. After excluding other causes of pancytopenia we concluded that ranitidine was the cause
for this atypical drug reaction, more so when the blood picture improved within 72 hrs of ranitidine
withdrawal.

Keywords: Ranitidine, thrombocytocytopenia, adverse drug reaction

Introduction
Thrombocytopenia due to H2 receptor antagonist is a rare but known phenomenon. Only 29 cases of
H2 receptor antagonist (ranitidine and cimiteidine) induced thrombocytopenia have been reported so
far. Though ranitidine and cimetidine belong to the same class of drugs, cross-reactivity between them
is not conclusive. Platelet count typically falls from 75 to 80% of the normal value on exposure to the
drug and returns to normal after drug withdrawal. Ranitidine is able to cause thrombocytopenia by an
idiosyncratic reaction associated with an increase in platelet-induced immunoglobulins and its later
clearance by the phagocytic system. The diagnosis of this critical condition is based on clinical
suspicion and is a diagnosis of exclusion, probably life saving in critical patients.

Case Report
A 55-year-old female, a case of pustular psoriasis, presented with multiple pustules over extremities,
associated with fever and vomiting. Routine hemogram on admission revealed WBC count of 4900
cells/mm3 (N: 71, L: 23, E: 5, B: 1) and platelet count of 1.95 × 109/dL. Hb was 10 g%. Patient was
started on roxithromycin 150 mg BD, paracetomol 500 mg BD, IV ranitidine 50 mg BD and IV
ondansetron. Blood investigations repeated after 2 days revealed thrombocytopenia with platelet count
of 75 × 109/dL, WBC count of 3000 cells/mm3 with neutropenia and Hb 9.4 g%. Important causes of
pancytopenia like malaria, leptospirosis (this being an endemic area), dengue, autoimmune disorders,
and sepsis were ruled out. Repeat blood picture showed further fall in platelet count to 30,000 × 109/dL
and WBC count to 1700 cells/mm3; however, there was no spontaneous bleeding. Bleeding time,
clotting time and INR were normal. With other causes ruled out convincingly and the patient being
clinically asymptomatic, it was concluded that a drug may be the possible cause of thrombocytopenia.
Ranitidine-induced thrombocytopenia in critically ill patients has been reported. The drug was

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1/18/22, 5:46 PM Ranitidine-induced thrombocytopenia: A rare drug reaction

immediately withdrawn and after 48 hours a significant improvement in the blood picture was noticed
with Hb 9.6 g%, WBC count of 4500 cells/mm3 and platelet count of 75 × 109/dL. The patient had an
uneventful recovery and was discharged a week later with normal blood counts.

Discussion
Several drugs have been implicated in causing acute immunologically mediated thrombocytopenia.
[1,2] There are three possible mechanisms by which a drug causes decrease in platelet count: failure of
production by bone marrow, immune destruction and platelet aggregation in circulating blood.[3]
Antibodies that bind to normal platelets in the presence of drug have been strongly implicated for drugs
like cinchona, quinine and sulfa drugs.[4–7] However, in the case of H2 receptor antagonists,
demonstration of drug associated antibodies (complement fixation, antiglobulin consumption tests and
tests involving the release of platelets 11Cr or P173) is usually unsatisfactory[3] and diagnosis is based
on clinical suspicion. In our case, to confirm the causality of ranitidine leading to thrombocytopenia,
we applied the WHO-UMC system for standardized case causality assessment,[8] which suggested a
“certain relationship” between ranitidine and thrombocytopenia though we could not subject the patient
to a rechallenge. Drug-induced thrombocytopenia usually takes weeks or months to appear but may
appear within 12 hours of drug intake in a sensitized individual.[9–11] Typically, the platelet count falls
to 80% of the normal and thrombocytopenia may be associated with neutropenia and anemia. In our
case, there was pancytopenia which significantly improved after withdrawal of ranitidine. Literature
shows that this rare drug reaction due to H2 receptor antagonist (ranitidine) is more common in
critically ill patients (patients admitted in ICU). Hence, precaution should be taken to put these patients
on other medication for ulcer prophylaxis.

In conclusion, in cases of severe thrombocytopenia in critically ill patients, a pharmacological cause

must be suspected, including H2 receptor blockers. Other alternate drug regimens for prophylaxis of
stress ulcer should be considered.

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