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DESCRIPTION
Ticlopidine hydrochloride (Ticlid) is an oral antithrombotic medication that inhibits platelet function.
FORMS AND USES
- It is used for prevention of stroke, myocardial infarction, or complications from sickle cell disease (250 mg orally twice a day).
- It is also used to maintain vascular graft patency.
TOXIC DOSE
Ingestion of 10 g in an adult may result in life-threatening hemodynamic instability and coagulopathy.
PATHOPHYSIOLOGY
- Ticlopidine prolongs bleeding time by irreversibly inhibiting aggregation for the life of the platelet.
- Minimal effects can be demonstrated within 6 hours, and peak platelet inhibitory effects occur in 3 to 5 days.
EPIDEMIOLOGY
Poisoning is uncommon.
CAUSES
- Severe poisoning is usually the result of suicidal ingestion.
- Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.
DRUG AND DISEASE INTERACTIONS
- The safety of combining ticlopidine with other anticoagulants, such as aspirin or coumadin, is controversial, and the practice is generally not recommended.
- Serum levels of phenytoin and theophylline are often increased by ticlopidine.
PREGNANCY AND LACTATION
FDA Pregnancy Category B. Animal studies indicate no fetal risk and there are no controlled human studies, or animal studies show an adverse fetal effect but well-controlled studies in women do not.
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DIFFERENTIAL DIAGNOSIS
Toxic causes of coagulopathy include brodifacoum, warfarin, or other anticoagulants.
SIGNS AND SYMPTOMS
Cardiovascular
Large overdose may cause agitation, hypotension, and tachycardia.
Gastrointestinal
- Nausea, vomiting, and diarrhea are common.
- Cholestatic jaundice has occurred during therapy.
Hematologic
- In overdose, spontaneous bleeding may develop.
- Reversible neutropenia may develop during therapy using ticlopidine.
- Thrombocytopenic thrombotic purpura has been reported during therapy using ticlopidine.
Fluids and Electrolytes
Metabolic acidosis results from large overdose.
Neurologic
Agitation, CNS depression, and seizures may develop.
PROCEDURES AND LABORATORY TESTS
Essential Tests
No tests may be needed in asymptomatic patients.
Recommended Tests
- Serum elecrolytes, glucose, BUN, and creatinine in symptomatic patients to assess acidosis and renal function.
- Arterial blood gas in symptomatic patients to assess acid-base status.
- Coagulation studies and serum liver enzymes are used to assess toxicity.
- ECG, serum acetaminophen and aspirin levels in overdose setting to detect occult ingestion.
Not Recommended Tests
Drug levels in the serum are not typically available and do not correlate well with clinical effects.
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- Treatment should focus on control of seizures, correction of electrolyte abnormalities, and replacement of coagulation factors in patients with bleeding.
- Dose and time of exposure should be determined for all substances involved.
DIRECTING PATIENT COURSE
The health-care professional should call the poison control center when:
- Severe or persistent effects develop.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
The patient should be referred to a health-care facility when:
- Suicide or homicide attempt is possible.
- Toxic effects develop.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
Admission Considerations
Patients who develop major toxicity (seizures, metabolic acidosis, coagulopathy, spontaneous hemorrhage) should be admitted.
DECONTAMINATION
Out of Hospital
Emesis should be induced with ipecac within 1hour of ingestion for alert pediatric or adult patient if health-care evaluation will be delayed.
In Hospital
- Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1hour of a large ingestion or if serious effects are present.
- One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.
ANTIDOTES
There is no specific antidote for ticlopidine poisoning.
ADJUNCTIVE TREATMENT
- Seizures should be controlled using a benzodiazepine, followed by phenobarbitol in resistant cases.
- Blood components should be replaced as needed.
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PATIENT MONITORING
- Blood count should be monitored, including differential at baseline and every 2 weeks during the first 3 months of therapy to monitor for neutropenia and thrombocytopenia.
- Liver function tests should be considered in any patient in whom liver dysfunction is suspected.
- Complete recovery is anticipated unless sequelae of acidosis or hemorrhage develop.
DISCHARGE CRITERIA/INSTRUCTIONS
- From the emergency department. Asymptomatic patients may be discharged after a 6-hour observation period, decontamination, and psychiatric evaluation, if needed.
- From the hospital. Patient may be discharged when toxic effects resolve.
Section Outline:
ICD-9-CM 964.2Poisoning by agents primarily affecting blood constituents: anticoagulants.
See Also: SECTION II, Seizures chapter.
RECOMMENDED READING
Farver DK, Hansen LA. Delayed neutropenia with ticlopidine. Ann Pharmacother 1994;28:1344-1346.
Horowitz RS, et al. Cardiopulmonary instability, mental status changes and hemorrhage associated with overdose of ticlopidine. Vet Hum Toxicol 1993;35:344.
Author: Robert E. Vander Leest
Reviewer: Richard C. Dart