[Isoniacid intoxication: correlation between blood level and coagulation status? (author's transl)]

Area of Science:

• Pharmacology
• Toxicology
• Hematology

Background:

• Isoniazid (INH) is a primary treatment for tuberculosis.
• Drug-induced liver injury (DILI) is a known but rare complication of INH therapy.
• Coagulation factor synthesis is liver-dependent.

Observation:

• A 1.10-year-old boy experienced intoxication after ingesting isoniazid.
• Immediate decreases in prothrombin and prolonged reduction in clotting factor VII were observed.
• Other coagulation factors and inhibitor activity remained unaffected.

Findings:

• The rapid decline in liver-dependent clotting factors suggests a dose-dependent hepatotoxic effect of INH.
• Factor VII reduction persisted for over 46 hours, significantly longer than INH's serum half-life (2.98 hours).
• No direct correlation was found between INH plasma levels and the observed liver injury.

Implications:

• The findings suggest that acetylated intermediates of INH, rather than the parent drug, may be responsible for its hepatotoxic potential.
• This highlights the importance of monitoring coagulation parameters in cases of isoniazid overdose.
• Further research into the specific mechanisms of INH-induced hepatotoxicity is warranted.