Coroner’s Inquest into the Death of an Elderly Patient on AntiCoagulation Therapy

CASE SUMMARY

A 77 year old woman died six weeks after admission to a Long Term Care Home (LTCH). The reported cause of death was bilateral subdural hematomas as a consequence of anticoagulation therapy with a contributing factor of pneumonia.

Concerns over the monitoring of anticoagulation therapy led the coroner’s jury to refer the case to the Geriatric and Long Term Care Review Committee to assist the Office of the Chief Coroner in the investigation. The Committee’s recommendations to several institutions are highlighted following the review of the case.

CASE HISTORY

The patient was admitted to the LTCH from her private residence on December 1, 2015. She had several co-morbid conditions which are listed in Appendix A. Medications at the time of admission to the LTCH are listed in Appendix B. The admitting physician conducted an admission history and physical which noted that she was treated with warfarin for atrial fibrillation. An admission INR and creatinine were ordered. The INR was reported as 2.7 which was within normal limits for a therapeutic range of 2-3 for atrial fibrillation. The creatinine level was 157 with an eGFR of 27. The patient had difficulty settling into her new environment. She became less ambulatory and ate poorly as a result of the transition.
While in the acute care hospital, the INR level was found to be significantly elevated at 10 (normal range 2-3). The patient was treated with Vitamin K and Octiplex. A CT scan of the head revealed bilateral extensive subdural hematomas. She was admitted to the ICU and subsequently placed on comfort measures until her death on January 13, 2016.

Summary of Events Leading to Hospital Admittance

DISCUSSION

The Committee’s review reflected that no regular monitoring of the INR was ordered by the physician upon admission to the LTCH. It was also noted that this was not flagged by the staff or pharmacist.
Factors that affect the dose-response relationship between warfarin dose and INR include the following:

• Nutritional status, including vitamin K intake,
• Activity level,
• Infections and hypermetabolic states,
• Drug interactions,
• Smoking and alcohol use,
• Renal, hepatic, and cardiac function, and
• Genetic variation.
  

Acute illnesses, especially infections and gastrointestinal episodes, may alter anticoagulation through effects on dietary vitamin K intake, warfarin metabolism, and medication interactions. Monitoring intervals are generally increased in any patient with an infection requiring antibiotic therapy. One of the ways antibiotics contribute to variability in the INR is by reducing intestinal vitamin K synthesis. This may occur through the disruption of intestinal microflora and effects on the hepatic CYP2C9 or other cytochrome P-450 isoforms. Other drug interactions, such as the use of as needed acetaminophen, may also play a role in INR variation.

The patient experienced several of these contributing factors during her stay at the LTCH. Warning signs for excessive anticoagulation include petechiae, excessive bruising and hematuria. Despite warning signs being noted, no reassessment of the INR was ordered. Although the LTCH had an electronic medical record with standard admission order sets, there were no automatic orders for INR monitoring or monitoring of other drugs that may have required adjustment to achieve therapeutic levels.

Appendix A: Patient Conditions

• polycystic kidney disease with acute decompensation requiring transient dialysis
• chronic obstructive pulmonary disease (COPD)
• previous smoker
• spinal stenosis
• dyslipidemia
• stable adrenal mass
• partial thyroidectomy with hypothyroidism
• osteoporosis
• paroxysmal atrial fibrillation
• right vertex calcified brain lesion (stable)
• transient ischemic attack (TIA)
• severe pulmonary hypertension
• dependent edema with chronic venous stasis
• dementia

Appendix B: Patient Medications as Indicated

Scheduled Medications:

• warfarin 2.5 mg daily
• metoprolol 100 mg bid
• furosemide 80 mg daily
• escitalopram 10 mg daily
• donepezil
• memantine
• digoxin 0.0625 mg daily
• calcitriol 0.25 mcg daily
• rosuvastatin 20 mg hs
• bisacodyl 10 mg daily
• ferrous fumarate 300 mg daily
• tiotropium 18 mcg inhaled qam
• fluticasone/salmeterol 250/50 inhaled bid
• vitamin D 1000 units daily

PRN Medications:

• risperidone 0.5 mg q12h prn
• salbutamol 2 inhalations q4h prn
• acetaminophen
• dextromethorphan
• dimenhydrinate
• guaifenesin
• sennosides
• aluminum hydroxide
• fleet enemas

REFERENCES

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2. Ansell J, Hirsh J, Poller L, et al. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:204S.
3. Juurlink DN. Drug interactions with warfarin: what clinicians need to know. CMAJ 2007; 177:369.
4. Hylek EM, Heiman H, Skates SJ, et al. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA 1998; 279:657.
5. Clark NP, Delate T, Riggs CS, et al. Warfarin interactions with antibiotics in the ambulatory care setting. JAMA Intern Med 2014; 174:409.