INDICES> Re: Thrombocytopenia and TB Drugs

[marceg@ull.es]

The commonest haematological reaction reported to rifampicin is thrombocytopenic
purpura. The patient notices purpura, nose bleeds, or easy brusing, and the platelet
counr falls. But if treatment is stopped the count returns to normal in 36 hours.
The drug should never be given again to such patient. This effect occurs with
intermittent administration of the drug too. (Nariman S, Adverse reactions to drugs
used in the treatment of tuberculosis. Adverse Drug React. Acute Poisoning Rev.,
1988; 4: 207-27.)

But, in this case is possible this effect should be relationed with the other drugs.
In Meyler's Side Effects of Drugs, Leuenberg and Sonntag describe thrombocytopenia
(agranulocytosis, hemolytic anemia, sideroblastic anemia, pure red cell aplasia,
methemoglobinemia and eosinophilia) as haematological reactions of isoniazid. There
is a case report of bleeding disoder in a patient with Waldenstrom's
macroglobulinemia treated with isoniazid that developed an acquired coagulation
factor XIII inhibitor. Our Centre has received a case report of a 12 years old girl,
with Cemidon« (isoniazid, 300 mg/d). She developed hemolytic anemia after four
months of treatment, and returned to normal count after four weeks of stopped
treatment (she had also ANA, dsADN and Antihystone A +). There are also a single
case report of a patient with thrombocytopenia due to ethambutol, perhaps by an
immunological mechanism (Rabinovitz M, Pitlik SD, Haley J, et al. Ethambutol-induced
thrombocytopenia. Chest, 1982; 81: 765-6).

As you can't know which is the guilty drug, you can need an alternative treatment
without any of these that you used.
Goble MG, et al. reviewed 171 patients with pulmonary tuberculosis resistant to
isoniazid and rifampin (N Engl J Med, 1993; 323: 527-32), that you can use as
position. When possible, they administered three dugs not given previously,
including one parenteral agent (an aminoglycoside or polypeptide) and two oral
agents that met these criteria. The 171 patients received a median of four drgus.
Ethionamide, pyrazinamide, aminosalicylic acid (para-amino salicylate) and
cycloserine were given divided doses to increase drug tolerance. They describe a
great efforts to continue therapy even if adverse drug reactions other than those
considered life-theratening occurred. Patients usually remained in the hospital
until a series of sputum cultures remained negative for at least three months of
until treatment failure was evident after at least three months of therapy. The
median stay in the hospital was 7.3 months for patients whose treatment was
successful and 7.8 months to those whose treatment failed.
Drugs Tested and Dosages Administered (doses/kg from Conn's Current Therapy, 1998):
- Amikacin: 15 mg/kg of body weight, given intramuscularly 5 days a week until
cultures become negative, then 15 mg/kg 3 days a week until cultures have been
negative 6 months;
- Capreomycin: As above;
- Kanamycin: as above;
- Streptomycin: as above;
- Viomycin: as above;
- Cycloserine: 250 mg 3 to 4 times daily by mouth (15-20 mg/kg);
- Ethambutol: 25 mg/kg daily by mouth until cultures become negative, then 15 mg/kg
daily by mouth;
- Ethionamide: 250 mg 3 to 4 times daily by mouth (15-20 mg/kg);
- Isoniazid: 300 to 600 mg daily by mouth (5-10 mg/kg);
- Aminosalicylic acid: 3 g 4 times daily by mouth (150 mg/kg);
- Pyrazinamide: 1 g 3 times daily by mouth (20-35 mg/kg);
- Rifampin: 600 mg daily by mouth (10-20 mg/kg)

You don't say if your patient has some other complication, and we don't know if you
have access to these medicines or to do cultures... but, I hope that this should be
some useful information.

Marcelino Garc_a
Eduardo Fernßndez
Drug Surveillance and Therapeutic Information Centre. Canary Island.
Health Canary Service. Dpt. Pharmacology, School of Medicine. Univ. La Laguna


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