UNINTENTIONAL PEDIATRIC SUPERWARFARIN EXPOSURES: DO WE REALLY NEED A PROTHROMBIN TIME?

Mullins ME, Brands CL, Daya MR. Pediatrics 2000 Feb;105(2):402-4.

OBJECTIVE. To determine whether routine follow-up coagulation studies are useful in children with accidental exposures to rodenticides containing superwarfarin compounds.

DESIGN. Retrospective review of poison center charts involving pediatric superwarfarin exposures occurring in two 2-year periods.

SETTING. An American Association of Poison Control Centers-certified regional poison control center with an annual call volume of 55 000 calls per year from a 2-state area with a combined population of 4 million people.

OUTCOME MEASURES. Prothrombin times and/or international normalized ratios and reported clinical signs of excessive anticoagulation after exposure.

RESULTS. Of 542 children in 4 years of data collection, follow-up prothrombin times and/or international normalized ratios measurements did not detect any significant coagulation abnormalities. No child developed bleeding complications. No child required or received antidotal treatment with vitamin K.

CONCLUSION. Normal preschool-aged children with unintentional acute exposures to superwarfarin rodenticides do not require any routine follow-up laboratory studies and do not require any medical intervention.

A PROSPECTIVE STUDY OF ACUTE, UNINTENTIONAL, PEDIATRIC SUPERWARFARIN INGESTIONS MANAGED WITHOUT DECONTAMINATION.

Ingels M, et al. Ann Emerg Med 2002 Jul;40(1):73-8.

STUDY OBJECTIVE: We determine the incidence of clinically important bleeding in children with superwarfarin rodenticide ingestions not treated with gastrointestinal decontamination or prophylactic vitamin K.

METHODS: We prospectively studied patients younger than 6 years of age who reported to our poison center with acute unintentional superwarfarin ingestions. Patients who received gastrointestinal decontamination or prophylactic vitamin K were excluded. Forty-eight- to 96-hour prothrombin time or international normalized ratio (INR) blood tests were recommended, and telephone contact was attempted at least 3 days after ingestion.

RESULTS: A total of 595 consecutive patients were enrolled during the 16-month study period. Fifty patients were excluded: 8 who were known to have ingested 1 pellet or less; 25 who received activated charcoal; 15 who were treated with induced emesis; and 2 who received prophylactic vitamin K. The resulting study group contained 545 patients. Eighty-two patients were lost to follow-up. Follow-up was obtained for 463 patients, including 222 by telephone contact alone, 62 by 48- to 96-hour INR, and 179 by both methods. None of the patients had clinically important coagulopathy. Two patients had an INR of 1.5 or greater (1.5 and 1.8) without symptoms. Single nosebleeds were reported in another 2 patients with normal 48-hour INRs. Another child had a small amount of blood crusted in the nose with no other symptoms and no laboratory work available. One child with a normal 48-hour INR had blood-streaked stools that were thought to be caused by an anal fissure.

CONCLUSION: Children with acute unintentional superwarfarin ingestions of less than 1 box may be managed without gastric decontamination or prophylactic vitamin K. Laboratory testing for coagulopathy should be reserved for cases involving clinically evident bleeding abnormalities.

PROSPECTIVE STUDY OF THE OUTCOMES OF AMBULATORY PATIENTS WITH EXCESSIVE WARFARIN ANTICOAGULATION.

Hylek EM, et al. Arch Intern Med 2000 Jun 12;160(11):1612-7.

BACKGROUND: Warfarin sodium therapy is highly effective in preventing thromboembolism. Its major toxic effect is hemorrhage, the risk of which increases with the international normalized ratio (INR). Data on the rate of major hemorrhage and the rate of INR decay after an episode of excessive anticoagulation therapy would help guide management of elevated INRs in the outpatient setting.

METHODS: We prospectively followed up outpatients in an anticoagulant therapy unit from April 24, 1995, through March 1, 1996. Study patients had to be taking warfarin for longer than 1 month and have an INR target range of 2.0 to 3.0. Consecutive outpatients with an INR greater than 6.0 were identified and compared with a randomly selected concurrent set of patients whose INR was in the target range. Major hemorrhage was defined as fatal, intracranial, or requiring hospitalization and transfusion of at least 2 U of blood.

RESULTS: One hundred fourteen patients with INRs greater than 6.0 were identified and compared with 268 patients with INRs in the target range. None of the patients had clinically apparent bleeding at the time of the INR measurement, and none received phytonadione (vitamin K1). Patients did not differ significantly in age, sex, indication, or duration of warfarin therapy. Ten patients with an INR greater than 6.0 (8.8%; 95% confidence interval, 4.3%-15.5%) sought medical attention for abnormal bleeding, and 5 of these experienced a major hemorrhage during 14-day follow-up (4.4%; 95% confidence interval, 1.4%-9.9%) compared with none of the patients with an in-range INR (P<.001). Thirty-three percent of patients with INRs greater than 6.0 had INRs less than 4.0 within 24 hours, 55% within 48 hours, 73% within 72 hours, and nearly 90% within 96 hours of temporary discontinuation of warfarin therapy.

CONCLUSIONS: Outpatients with INRs greater than 6.0 face a significant short-term risk of major hemorrhage. Randomized trials are needed to determine the net benefit of preventive treatment with phytonadione.

COMMENTS: While there were a few complications in this prospective study, it should be noted that they occurred when the INR has already dropped to the normal ranges for the treatment.