RANITIDINE-INDUCED THROMBOCYTOPENIA IN SEVERE BURN PATIENTS. A PROPOS OF ONE CASE

Ann. Medit. Burns Club - vol. VIII - n. 3 - September 1995

RANITIDINE-INDUCED THROMBOCYTOPENIA IN SEVERE BURN PATIENTS. A PROPOS OF ONE CASE

Pérez del Caz M.D.*, Terrén J.*, De la Rubia J.**, Codîna J.*, Safont J.*, Mirabet V.*

* Departamento de Cirugia Plàstica y Quemados, Hospital Universitarlo La Fe, Valencia, Spain
** Servicio de Hematologia, Hospital Universitario La Fe

SUMMARY. We present a case of thromboeytopenia induced by H2 antagonists (ranitidine) in a 55% TBSA burned patient. This is a relatively rare cause of thromboeytopenia and we were unable to find other cases among burn patients in the literature. We describe the cli nical evolution and how discontinuation of ranitidine improved the platelet disease.

Introduction

Thromboeytopenia is present when the platelet count in peripheral blood is <150 x 101/1. Drugs are able to decrease the platelet count by three mechanisms: failure of production by the marrow, immune destruction, or platelet aggregation in circulating blood. Ranitidine treatment is usual in the management of bum patients. As an H2-antagonist it prevents Curling's disease and gastrointestinal haemorrhage. Ranitidine is able to cause immunological platelet destruction by an idiosyncratic reaction which is distinguished by the increase of platelet-associated immunoglobulins and the later clearance of platelets by the phagocytic system, Ranitidine, like other drugs, acts as both antigen and hapten, binding to the plasmatic or membrane proteins. Antigen-antibody complexes are then formed that adhere to the platelets and facilitate their destruction.'

Case report

A 60-year-old Caucasian man, with no pathological antecedents of interest, was admitted to the burn centre with deep bums (55% TBSA) and respiratory injury. On admission the full blood count, peripheral blood film, and coagulation screen were normal. The platelet count was 225 x 10M. Treatment was routine: fluid loss replacement with Ringer's lactate, oxygen therapy, analgesia with pethidine HCI, low molecular heparin (enoxapa~ rin), and ranitidine (100 mg/day i.v.). On day 2 (Table I) there was a din-finution in the platelet count (89 x 109/1), without bleeding, and a decreased Quick index (52%). We suspected disseminated intravascular coagulation (DIC) and we began to give fresh-frozen plasma and vitamin K. The thromboeytopenia deteriorated however (30 x 109 platelets/]), without any other important abnormalities. We performed an abdominal ecography, which showed no changes in the spleen. There were no signs of bleeding or infection. On day 6 we initiated platelet transfusion (6 units per day) without any rise in the platelet count. On the contrary, the platelet count remained at about 5 x 109/1 for several consecutive days (Table I).
In view of the evolutive characteristics and the severe thromboeytopenia with no substitutive effect of the platelet transfusion, a drug-related thromboeytopenia was suspected. There was no change in the initial treatment. Bearing in mind the known association of H2 antagonists with thromboeytopenia we decided to discontinue ranitidine on day ten. Forty-eight hours later, and with no more platelet transfusions, the platelet count increased (48 x 101/1) and four days later was 147 x 101/1. The following week the count was up to normal values (250 x 101/1).

Discussion

Drug-induced thromboeytopenia appears about 12 hours after the drug has been taken if previously there has been sensitivization by previous exposure. If not, the interval will be weeks or months after first exposure. Most patients present severe thromboeytopenia with purpura, and sometimes neutropenia and/or haemolytic anaemia, with fever, joint pain and rash. The degree of thrombocytopenia would not usually cause purpura, but its association with antiplatelet aggregation treatment by aspirin and dipyridamole probably leads to this condition.' Diagnostics requires a high index of suspicion. It is necessary to have a detailed history of drug exposure. Laboratory demonstration of drug-associated antibodies (cornplement-fixation, antiglobulin consumption tests, tests involving the release of platelets' 11Cr or P173) is usually unsatisfactory.' An in vivo test is too dangerous and must be ruled out.' The platelets increase in number after drug discontinuation in about one week.
Characteristically, in the bum patient, the blood platelet count begins to fall soon after burning and continues to fall for a day or two, when the lowest counts are found, occasionally reaching almost thrombocytopenic values during the subsequent one to three weeks (of the order of 50 x101/1). Subsequently the counts rise, becoming normal and then supranormal after about a week. The initial fall in platelet count appears to be related to the severity of the bum. The other coagulation factors and measurements of the coagulation system (PT and PTT) are normal . A review of the literature shows that ranitidine-induced thromboeytopenia is relatively rare2,1,1,1 and this is the first case reported in an extensive bum. We must make a differential diagnosis from other causes of thrombocytopenia: infections, sepsis, DIC, and haemorrhage.
In conclusion, in cases of severe thromboeytopenia (<50 x 101 platelets/1) we must suspect a pharmacological cause. The possibility of ranitidine-induced thrombocytopenia must be borne in mind in a bum patient with no evidence of organic causes.

RESUME. Nous présentons un cas de thrombopénie causé par des antagonistes H2 (ranitidine) dans un patient atteint de brûlures en 55% de la surface corporelle. Cette cause de thrombopénie est relativement rare et nous n'avons pas trouvé aucun autre cas dans la littérature des brûlés. Nous décrivons l'évolution clinique et comment l'interruption du traitement avec ranitidine améliorait la maladie des plaquettes.

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