Clinical Review

Man, 82, With New-Onset Headaches

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An 82-year-old man presented to his primary care provider complaining of headaches for the past week. At the time of presentation, he reported persistent, nonthrobbing pain behind his right eye. Previously, he had experienced pain on the top and right side of his head.

The patient denied any recent visual changes. His last eye examination had taken place four weeks earlier. He was prescribed new eyeglasses, but he had not yet filled the prescription. He denied having symptoms of transient ischemic attack or stroke. He denied any nasal drainage, fever, or chills and reported no prior history of headaches. For the current headache, he had been taking acetaminophen intermittently and said it provided some relief.

The patient’s prior diagnoses included type 2 diabetes, hypertension, dyslipidemia, gout, metabolic syndrome, osteoarthritis, leg edema, and atrial fibrillation. His current medications were allopurinol, diltiazem, glipizide, hydrochlorothiazide, rosiglitazone, valsartan, vardenafil, and warfarin.

His most recent international normalized ratio (INR), measured five days earlier, was 3.34. Fifteen days earlier, however, his INR had been measured at 4.6.

The patient described himself as active, riding his bicycle 50 miles each week. He denied using tobacco but admitted to having “a couple of cocktails” before dinner each evening. He was a widower who lived alone. He owned an advertising company and was involved in its day-to-day operation.

On examination, the patient was alert and oriented. He had an irregularly irregular heart rate with a controlled ventricular response. Cranial nerves II through XII were intact. No papilledema was noted.

The patient was given a diagnosis of headaches of unknown etiology. He was told that he could continue using acetaminophen and was scheduled for head CT with and without contrast the following day.

CT revealed a 2.3-cm, right-sided subacute (mixed-density) subdural hematoma (SDH) with midline shift of 1.8 cm (see Figure 1). The patient’s provider was notified of the CT results, and the patient was sent directly from radiology to the emergency department. His INR was 2.7. The patient was given a partial dose of recombinant factor VIIa (rFVIIa), then emergently transferred to another facility for neurosurgical care.

Upon his arrival there, the patient was noted to be drowsy but oriented, without any focal neurologic deficits. The dose of rFVIIa was completed, and he was given 5 mg of vitamin K. He underwent an emergency craniotomy for clot evacuation. Intraoperatively, his INR was measured at 1.5, and he was given two units of fresh frozen plasma (FFP) to further reverse his coagulopathy.

Repeat head CT the following morning revealed nearly complete removal of the clot, with reexpansion of the brain (see Figure 2). The patient’s INR was 1.1. Additional doses of FFP or rFVIIa were deemed unnecessary. The patient recovered and was discharged from the hospital four days after his surgery. When he was seen at the clinic one month later, he had no neurologic deficits. Head CT was found stable with only a thin rim of residual subdural fluid noted (see Figure 3). He was followed as an outpatient with serial head CTs until all the subdural fluid completely resolved. At that time, he was allowed to restart warfarin.

Discussion
Use of anticoagulation therapy will become increasingly common as our population ages. While anticoagulants are important for preventing thromboembolic events that may result from use of mechanical heart valves, atrial fibrillation, and other conditions, their use is not without risk. The most significant and potentially lethal complication is hemorrhage.

Warfarin-Associated Hemorrhage
In patients who take warfarin, hemorrhage can occur in a variety of areas—most commonly, cerebral and gastrointestinal sites, the nose, the airways, the urinary tract, muscle, and skin.1,2 The site of hemorrhage that carries the highest risk of mortality and morbidity is cerebral.3-5 Among anticoagulated patients experiencing intracranial hemorrhage, a fourfold to fivefold increase in mortality has been reported.6 Among study patients who experienced intracranial hemorrhages while taking warfarin, only 14% were able to return to living independently.4

Excessive Anticoagulation
Recent studies have led to the conclusion that excessive anticoagulation, not anticoagulation targeting specific therapeutic levels, is associated with major bleeding events.7,8 In a review of 2,460 patients from 2000 to 2003 at Brigham and Women’s Hospital in Boston, Fanikos et al8 found that 83% of major bleeding events occurred in patients with an INR exceeding 3.0.

In addition, excessive anticoagulation has been associated with increased morbidity and mortality.5,9,10 Pieracci et al9 found that among patients who experienced a traumatic intracranial hemorrhage with an INR exceeding 3.5, the mortality rate was nearly 75%.

Intracranial Hemorrhage
Subdural hematoma is one of the most common types of intracranial hemorrhage. SDHs are classified based on radiographic findings and age. Acute SDHs are those less than three days old, subacute (mixed-density) SDHs are three to 20 days old, and chronic SDHs (CSDHs) are at least 21 days old.

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