1) Minor hemorrhagic events that were greater than historical controls included: genitourinary and hematuria (11.6%), controls (0.8%); decreased hemoglobin and hematocrit (10.4%), controls (0%); groin bleeding (5.4%), controls (3.1%); hemoptysis (2.9%), controls (0.8%); and brachial bleeding (2.4%), controls (0.8%)(Prod Info argatroban IV injection aqueous solution, 2011).

1) CASE SERIES: Excessive anticoagulation (aPTT > 95 seconds) was reported in 4 out of 11 post-cardiothoracic surgery patients receiving argatroban infusion for heparin-induced thrombocytopenia. In 3 patients, argatroban was initiated at the recommended starting dose of 2 mcg/kg/min; in 1 patient therapy was initiated at 1 mcg/kg/min. All 4 patients had relatively normal hepatic function. Argatroban was withheld from each patient for a period of time, then restarted at rates ranging from 0.15 to 1.3 mcg/kg/min to maintain therapeutic anticoagulation. Clearance of argatroban after discontinuation also appeared delayed (Reichert et al, 2003)
2) CASE REPORT: Elevated aPTT persisted despite hemodialysis in a 54-year-old woman with a history of prosthetic mitral valve replacement who was admitted for anasarca secondary to renal failure. The patient was started on argatroban 2.0 mcg/kg/min to prevent valve thrombosis and stroke. She developed bleeding from an antecubital vein and the argatroban infusion was withheld, but the INR and aPTT remained elevated for 56 hours despite 3 sessions of dialysis (de Denus & Spinler, 2003).

1) CASE REPORT: An 82-year-old woman, with a history of atrial fibrillation, congestive heart failure, coronary artery disease, hypertension, and hyperlipidemia, presented to the emergency department with generalized weakness, dizziness, and decreased appetite approximately 1 week after beginning dabigatran 150 mg twice daily. The patient also experienced nausea and an episode of vomiting, possibly due to gastroenteritis, on the day of presentation. Other medications that the patient was taking included carvedilol, simvastatin, furosemide, and amiodarone. Laboratory data revealed serum creatinine and BUN concentrations of 1.78 mg/dL and 40 mg/dL, respectively (baseline 1 week prior to presentation was 1 mg/dL and 20 mg/dL, respectively), INR of 7.25, and a partial thromboplastin time (PTT) of 135 seconds. Fibrinogen level was less than 80 mg/dL, D-dimer level was less than 150 ng/dL, and thrombin time was greater than 120 seconds, indicative of excessive anticoagulation. Dabigatran therapy was withheld and the coagulopathy resolved over the next 4 days. After restarting dabigatran at 75 mg twice daily and administration of IV fluids, the patient's serum creatinine and BUN concentrations were 1.20 mg/dL and 26 mg/dL, respectively, and her INR and PTT improved to 1.49 and 40.8 seconds, respectively. It is believed that dabigatran toxicity was secondary to the development of acute renal insufficiency, possibly resulting from dehydration due to gastroenteritis, and concomitant administration of amiodarone, leading to an increase in dabigatran plasma concentrations (Fountzilas et al, 2013).
2) CASE REPORT: A 66-year-old man developed hypotension (80/40 mmHg), bradycardia (60 bpm), and worsening coagulopathy (INR 11.4 International Units (reference range 0.8 to 1.1 international units), aPTT 156.9 sec (reference range 25 to 37 sec), thrombin time greater than 240 sec (reference range, 15 to 21 sec), after intentionally ingesting 9 g dabigatran as well as metoprolol, amlodipine, olmesartan, and moxonidine. With supportive care and continuous veno-venous hemodiafiltration (CVVHDF) for 32 hours, the patient recovered without sequelae (Chiew et al, 2014).
3) CASE REPORT: An 85-year-old man with a history of type 2 diabetes, ischemic heart disease, and chronic renal failure was hospitalized with rectal bleeding and severe anemia. Medications included a 6-month history of dabigatran 110 mg once daily for atrial fibrillation. His estimated glomerular filtration rate (eGFR) at the time of dabigatran initiation was 35 mL/min. Based on the eGFR, the recommended dosage regimen is 75 mg twice daily; however, dabigatran is contraindicated with eGFR's less than 30 mL/min. Initial laboratory data included a hemoglobin level of 5.9 g/L and the patient received 2 units of packed red blood cells and 1 unit of fresh frozen plasma (FFP). On the second day of hospitalization, the patient had a hemoglobin level of 8.3 g/dL, a serum creatinine of 4.8 mg/dL with a corresponding eGFR of 11.5 mL/min, an INR of 2.47, an activated partial thromboplastin time (APTT) of 2.48, a thrombin time (TT) of 369 seconds (ratio 23.4), an ecarin chromogenic assay (ECA) of 597 ng/mL, and a diluted thrombin time (dTT) of 520 ng/mL. Treatment included an additional unit of FFP, 2 continuous veno-venous hemodiafiltration sessions (a total of 20 hours) and 2 intermittent hemodialysis sessions, resulting in gradual decreases in coagulation parameters (Montaruli et al, 2015).
4) CASE REPORT: An 81-year-old man, with a history of atrial fibrillation, hypertension, macular degeneration, and moderate renal insufficiency (creatinine clearance of 52 mL/min), intentionally ingested 1650 mg of dabigatran (15 110-mg capsules). Laboratory data at admission (approximately 150 minutes post-ingestion) revealed an activated partial thromboplastin time (aPTT) of 79 seconds (normal 23 to 37 seconds), an INR of 3.3, a serum creatinine of 1.33 mg/dL, and a creatinine clearance of 44 mL/min. The patient showed no signs of acute bleeding. With conservative supportive treatment, including gastric lavage and activated charcoal decontamination, and administration of fresh frozen plasma, IV fluids, and furosemide, his coagulation parameters gradually improved, and he was discharged four days later without complications (Mumoli et al, 2015).

1) CASE REPORT: Diagnostic allergy testing was performed on a 44-year-old woman following a delayed hypersensitivity reaction (erythema, pruritus and infiltrated plaques) to certoparin-sodium. Intradermal patch testing for lepirudin was initially negative in all cases. Fifteen minutes following a subcutaneous provocation test with lepirudin (0.2 mg), the woman developed erythema and edema at the injection site. A biopsy of the injection site taken 2 hours later revealed focal fibrin deposition, extensive extravasation of erythrocytes and vessel wall edema (Jappe et al, 2002).

1) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

1) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
2) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).