DECEMBER 2013

TOXICOLOGY CASE OF THE MONTH:

CASE:

63yoF presents to the Emergency Department for her second time in a week complaining of epistaxis. On the first visit, she had packing placed. Bleeding was attributed to dry environment and changing weather. She was discharged home with Cephalexin. However, she returned to the ED 2 days later complaining not only of persistent epistaxis, but of hematuria and rectal bleeding. On further questioning, she admits to taking a “handful” of d-CON daily over the past 2 weeks as a suicide attempt.

PMH: Depression, HTN, no hematalogic disorders

Meds: Prozac, Amlodipine; no blood-thinning medications

All: NKDA

VS: 101/59125 16 99% RA 36.6

Exam remarkable for persistent epistaxis from L nare without a clear site of bleeding. Rectal exam notable for gross positive blood. No skin lesions (petechiae, purpura, ecchymosis).

Labs:

CBC: WBC 9.5, Hgb/Hct 9.2/27.9, Platelets 210

Chem: 132/4.2/95/26/55/0.8/110

LFTs wnl

INR: >15

Acetaminophen, Salicylate, EtOH undetectable

Applicable case questions:

1. What is the Toxicology differential diagnosis of bleeding?
2. What is d-CON?
3. Why should I be worried about it?
4. What is the toxic dose?
5. What are the clinical effects? What labs should I order?
6. What is the most appropriate management of rodenticide ingestions?

Answers:

1. What is the Toxicology differential diagnosis of bleeding?

• Note: this differential dose not include other causes that should be considered such as bleeding disorders, hepatic failure, DIC, ITP, TTP
• A lot of pharmacology but an important review – we see patients on may of these
• Warfarins and suprawarfarins (i.e. rodenticide)
• Direct thrombin inhibitors (ie Dabigatran/Pradaxa)
• Factor Xa inhibitors (ie Rivaroxaban (Xarelto)
• Anti-platelet agents
  • COX inhibitors (Aspirin)
  • ADP receptor inhibitors (Clopidogrel/Plavix, Prasugrel/Effient, Ticagrelor/Brilinta, Ticlopidine/Ticlid)
  • Glycoprotein IIB/IIA inhibitors: mostly IV use (Abciximab/Reopro, Eptifibatide/Integrilin, Tirofiban/Aggrastat)
  • Adenosine reuptake inhibitors (Dipyridamole/Persantine)
  • PDE inhibitors (Cilostazol/Pletal)

• Rattlesnake envenomation
• Arsenic toxicity (may have pancytopenia 1-2 weeks after acute ingestion, usually more leukopenia and anemia)

2. What is d-CON?

• Anticoagulant rodenticide – contains long-acting suprawarfarins
  • Brodifacoum is most common: this is what is in d-CON brand
  • Others: Diphacinone, bromadiolone, chlorophacinone, difenacoum, pindone, valone
  • Interesting fact: warfarin initially used for rat poison, however rats and mice became resistant

3. Why should I be worried about it?

• Like warfarin, suprawarfarins inhibit conversion of vitamin K to its active form: necessary to synthesize coagulation factors II, VII, IX, X, proteins C & S
• The duration of anticoagulation from a single dose of warfarin is usually 2 to 5 days
• Suprawarfarins may produce significant anticoagulation for weeks to months after a single ingestion

4. What is the toxic dose?

• Warfarin
  • Single small dose (10-20mg) will not cause serious toxicity
  • Chronic or repeated ingestion (i.e. 2mg/day) can cause significant anticoagulation

• Suprawarfarins:
  • Potential to have prolonged effects even after a single small ingestion
  • Large study of accidental suprawarfarin ingestion in children: no serious cases of ingestions less than 1 box
    • Ingels M, Lai C, et al. A prospective study of acute, unintentional, pediatric superwarfarin ingestions managed without decontamination.. Ann Emerg Med 2002;40(1):73-8.

5. What are the clinical effects? What labs should I order?

• Excessive anticoagulation
  • Warfarin: anticoagulation effects within 15 hours, lasts up to 5 days
    • Suprawarfarin: Anticoagulant effects usually delayed up to 2 days and may persist weeks to months
    • CBC, PT/INR, Type & Screen (if bleeding),
      • Toxicologists will order Brodifacoum levels to determine duration of therapy
      • If you ordered warfarin-dependent clotting factors, these will be decreased

• PTT, fibrinogen, liver enzymes, D dimer may help evaluatuation of other causes of bleeding if cause is unknown
• Acetaminophen, Salicylate levels – rule out coingestants

6. What is the appropriate management of d-CON ingestions?

• Most ingestions: accidental, by children
• Poison center recommends: send child to the hospital if they ingest greater than a box of d-CON or other rodenticide, otherwise can be observed at home
  • Parents can observe for bleeding clinically
  • Poison center recommends that these patients can have a follow up at PMD office – a normal PT/INR 48 hours after exposure rules out significant ingestion (Studies suggest that if patients have no clinically evident bleeding that this measure may be unnecessary)

• If patient comes to the ED just after this ingestion:
  • Activated charcoal
    • Appropriate conditions (recent exposure, normal mental status, not vomiting)
    • Not indicated if patient ingests less than 1 box
    • Labs will not give any information about toxicity but may establish baseline if there is concern for any underlying hematologic disorders
    • Do not give prophylactic Vitamin K (see below)

• Significant bleeding
  • Treat shock – pRBC transfusion
  • Vitamin K
    • Give if evidence of clinically significant anticoagulation
    • Do not give prophylactically for any ingestion: if this is the case, then the 48 hour PT/INR cannot be used to determine severity -  will need at least 5 days of monitoring
    • Be aware: patients with significant bleeding due to suprawarfarin toxicity need weeks to months of treatment with Vitamin K – poison center can help admitting physicians with dosing but large doses may be required (up to 800mg per day!)
    • FFP for non-life threatening bleeding
    • PCC’s for life-threatening bleeding if available, otherwise FFP
    • Management can be difficult if patient requires long-term anticoagulation (ie prosthetic valve) – can consider heparin for maintenance anticoagulation

CASE CLOSURE:

• Patient ultimately developed hemorrhagic shock in ED
• Was treated with Vitamin K and PCCs – INR decreased to 1.3 in ED
• Up to 5 the next day – still being treated with Vitamin K
• No further significant hemorrhage initial reversal

TAKE-HOME PEARLS:

• Classic toxicology teaching: “All things are poison and nothing is without poison: only the dose makes a thing not a poison.” –Paracelsus
• One box of d-CON or less: patients can be observed at home for signs of bleeding and follow up with PMD in 48H
  • +/- follow up INR in 2 days – recommended if bleeding
  • Activated charcoal if appropriate conditions and ingestion of at least 1 box
  • No prophylactic Vitamin K
  • FFP, PCC, Vitamin K for significant bleeding
  • Will require long term vitamin K treatment for suprawarfarin ingestions – poison center can help with this management