tPA for Stroke: The Story of a Controversial Drug

By Justin A. Zivin MD PhD and John Galbraith Simmons
tPA for Stroke: The Story of a Controversial Drug

tPA has been one of the most controversial drugs ever. Originally used and approved in the 1980s for heart attack, its relatively high cost provided grist for stories of Big Pharma greed and unethical collusion between doctors and drug marketers. When it came to stroke, such suspicion bolstered obstinate skepticism and disbelief even while, time and again, research has showed that the drug works. To be effective, tPA for stroke must be administered within 4.5 hours after symptoms start — and in any event, the sooner the better.

“Julie, are you all right?”

Sitting next to her, Steve Kondonijakos had heard her talking on the
phone.

“Yes, I’m fine. Why?”

It was September 30, 2004. At 26, Julie was an associate media director with four years in interactive advertising at Organic, Inc., a digital marketing firm on Market Street in San Francisco. She was Italianate, pretty and bright, serious and self-possessed, slender and blue-eyed with an oval face and a cascade of dark brown curls. Recently she had gotten engaged. Now the left side of her body just stopped working. Her arm flopped uselessly on the desk.

Fear and anxiety rapidly suffused the workplace. Steve and Eric sought the attention of Julie’s younger sister, Erica. She worked at Organic, too, just cubicles away.

No sooner had she asked, “What’s wrong?” than she noticed Julie’s hand, uncontrolled and weirdly curled.

Nobody said “stroke.” Steve, whose grandfather had suffered one a dozen years earlier, refrained from alarming Erica, and kept quiet. But Erica herself recognized something about her sister’s gnarled hand. She was reminded of their grandmother, who had been confined to a wheelchair for the past 14 years. Same hand. Erica didn’t say “stroke,” either.

Word spread. Everybody in the office gathered around Julie’s desk. Each voiced a different solution. Perhaps it was epilepsy, fatigue, or low blood sugar. Julie herself did not seem too distressed. She was calm and her arm flopped and her words came out distorted. She was not in pain.

Stroke is an ancient disease and inspires fear and trembling. That the word went unsaid in the offices of Organic that afternoon was in its own way tragic, reflecting a common and collective reluctance to face one of life’s most dangerous events. Stroke newly afflicts almost three quarters of a million people each year in the United States alone.

Yet in Julie’s case, a quickened sense of mortal danger prevailed over inevitable appeals to let’s-wait-and-see. Spurred by Erica’s sense of urgency, co-workers called 911....

Ray Crawford, a pleasant, mustachioed former fireman, was the paramedic who led the emergency medicine team. He kneeled beside Julie.

“Thanks for coming,” she said. “But I feel fine. I’m not exactly sure why you’re here but thanks for taking care of me.”

Julie saw Ray was in his mid- to late forties, of average build with reddish-blond hair. She did not see his mustache. Where his face ought to be she saw only a blur. The same was true, in fact, of her co-workers. She knew each by voice and physical outline, but just now she could not make out their faces. Everyone, it seemed, was faceless.

“Let’s take you in,” said Ray gently, betraying no alarm, “just in case.” In Ray’s own mind, as they placed Julie on the gurney and rolled her outside and lifted her into the ambulance, there was no doubt. Her slurred speech and failed left side, not to say insouciance and bewilderment, made this case transparent.

“I am very concerned,” he said, taking Erica aside. “It looks like your sister had or is having a stroke.”

Erica felt rising panic, but Ray warned her to keep a poker face. A spike in Julie’s blood pressure would not help."The only one that needs to know the reality,” said Ray, “is you.”...

California rules laid down that, unless patients make other demands, paramedics must take them to the nearest emergency facility. Paramedics are paid to transport, not diagnose. But that late afternoon on Market Street, Ray Crawford did exactly that. He diagnosed.

Ray made a point of treating patients the way he would his own family.

Before taking off in the ambulance, he told Erica quietly, “Listen, if this were me, I would take her to UCSF,” the University of California, San Francisco Medical Center. It was not the nearest emergency department. Two others, at San Francisco General and at St. Francis Memorial Hospital, were closer, each just a mile and a few minutes away. UCSF was five miles away — and this was rush hour.

“We’re going to have to pass almost every hospital in the city to get there.”

But Ray knew UCSF was obtaining official certification as a stroke center. Whatever that meant, he knew that at least there would be a neurologist on duty who could ensure that Julie received tPA if she was eligible — and it looked like she was. This would not be the case elsewhere. The nearer emergency rooms might not even risk treating Julie but transfer her, losing precious time. Ray knew that lost minutes cost huge numbers of brain cells.

Erica deferred to his advice.

Once Julie was in the rig and they were off, Ray alerted the hospital — calling twice, then a third time. He emphasized the woman was young and a candidate for therapy. To prime the stroke team, he adopted an urgent tone. Ray had a philosophy about this. “You know which cases to jump up on your pedestal and bark about, and which to let slide. You don’t get your panties in a knot. You don’t get upset about non-acute ones.”

At 6:45 that evening, about 90 minutes after her first symptoms, the emergency room staff injected Julie with tPA through the IV that Ray Crawford had started in the ambulance 40 minutes earlier. tPA is freshly mixed for each patient, and the dose is based on body weight. Apart from that, it is a simple injection and intravenous drip.

When her family left her that night, Julie was paralyzed on one side of her body; her speech was slurred and her thinking aff ected. Doctors assessed her with a score of 11 on the National Institutes of Health Stroke Scale, which is borderline severe.

Theoretically, any outcome was possible. She could be expected to improve a little or a lot, or recover completely. She might further decline, then stabilize at some level of disability; or she could sustain yet another stroke and die. Seemingly spontaneous recoveries from stroke do occur, but for Julie that prospect, by 8 o’clock that evening, was long past.