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[Isoniacid intoxication: correlation between blood level and coagulation status? (author's transl)]
Insights
Isoniazid (INH) intoxication in a child caused immediate drops in clotting factors, suggesting dose-dependent liver injury. This effect persisted longer than the drug
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.
Abstract:
In a 1,10 year old boy intoxication by isoniazid (INH) produced an initial fall of prothrombin and a prolonged fall of the clotting factor VII. The rest of the coagulation factors as well as the inhibitor activity remained uninfluenced. Since the decrease of the liver-dependent clotting factors occurred immediately after ingestion the apparently rare INH induced liver injury is considered as dose-dependent. On the other hand, however, since the serum half-life of INH amounted to 2,98 hours whereas the decrease of factor VII persisted over 46 hours and there appears to be no correlation between liver injury and INH plasma levels. This discrepancy may be attributable to the fact that only the acetylated intermediates of INH may have a hepatotoxic potential.