Factor VIII Levels After Stroke May Flag Recurrent Events

Caroline Helwick

October 18, 2013

NEW ORLEANS — Patients with acute ischemic stroke (AIS) who have elevated factor VIII levels (in excess of 150%) may be at increased risk for recurrent thrombotic events, and these recurrent events are associated with high rates of death and disability, a new study shows.

"We think elevated factor VIII is a marker for thrombosis. Two out of 3 of our patients have elevated factor VIII levels," said senior investigator Sheryl Martin-Schild, MD, PhD, director of the Stroke Program at Tulane University Hospital and Clinic, New Orleans, Louisiana. "We don't know what it means and we don't know what to do with this information. Is it an epiphenomenon for the patient's stroke? A marker of clot burden, which would then be a marker for size of stroke, which would be marker of stroke severity? We don't yet know."

Elevated plasma levels of factor VIII, which is common in AIS, have been associated with a heightened risk for both venous and arterial thrombotic events. Both high factor VIII level and recurrent thrombotic events are linked to poor outcomes in patients with AIS, but the relationship between elevated factor VIII and additional thrombotic events during hospitalization for AIS has not been previous investigated, Dr. Martin-Schild and her team noted.

They presented their findings here at the American Neurological Association (ANA) 2013 Annual Meeting. The first author was Brittany M. Gouse, a medical student and research intern for the Stroke Program at Tulane.

Elevated Factor VIII

The investigators identified 206 patients with AIS in the Stroke Program registry from 2008 to 2012. Of these, 132 (64.1%) had elevated factor VIII at admission.

New thrombotic events occurred in more patients with elevated factor VIII than in patients with normal levels: 9.8% vs 2.7% (P = .0583). This association remained after adjustment for stroke severity (odds ratio [OR], 3.18; P = .14), although without statistical significance.

Patients with new thrombotic events had higher factor VIII levels and significantly higher rates of death and major disability, the results showed.

Table. Outcomes in Patients With and Without In-Hospital Thrombotic Event

Outcome No Thrombotic Event (n = 191) (%) Any New Thrombotic Event (n = 15) (%) P Value
Death 1.6 13.3 .0048
Discharge mRS 0 to 4 96.8 60.0 <.0001
Discharge mRS > 4 3.2 40.0 <.0001

mRS = modified Rankin scale.

 

The researchers also reported that patients with AIS who have elevated factor VIII had a trend toward increased risk for acute kidney injury: OR 1.82 (P = .0878).

Glomerular filtration rate was significantly lower and peak serum creatinine was higher in patients with elevated factor VIII than in those with normal levels. Factor III was positively associated with admission-to-peak creatinine (P = .0022), reported Dominique J. Monlezun, an MD/PhD candidate at Tulane.

What Does It Mean?

Patients with high factor VIII levels were more often black and had higher baseline glucose, lower hematocrit, higher inflammatory markers, and lower baseline glomerular filtration rates compared with patients with normal factor VIII.

"There were too many factors to adjust for in a study of this size," said Dr. Martin-Schild, who is now spearheading a larger study that will adjust for multiple factors.

Preliminary data from that study has shown that of 21 recurrent thrombotic events during hospitalization, 18 occurred in patients with elevated factor VIII, vs only 3 in those with normal levels, a statistically significant difference (P = .02). "The significance held after adjusting for baseline stroke severity," she noted.

"We are now looking at predictors of persistently elevated factor VIII at 3 months, and whether it resolves. We are learning what things need to be factored in for a larger study. We want to determine if we can distinguish between patients who will have persistent elevations versus those that resolve, and whether this matters, as well as determine the best treatment for these patients," she told Medscape Medical News.

Patients with elevated factor VIII might best be treated with a direct thrombin inhibitor, "which makes sense to me since it works in the part of the cascade that drives the conversion from prothrombin to thrombin," she suggested. "These are pilot studies whose intent is, down the line, to answer the question of how to optimize medical management of patient with persistently elevated factor VIII so that recurrent thrombotic events could be prevented."

Tzu-Ching (Teddy) Wu, MD, director of Telemedicine at the University of Texas at Houston, told Medscape Medical News that he found the study "very intriguing."

"By knowing up front whether a patient has elevated factor VIII, we can potentially predict who is going to be at high risk for a recurrent thrombotic event," he said. "We don't routinely measure factor VIII levels in all patients, but this practice could be expanded if it proves to significantly impact outcome and choice of treatment. It could affect our interventions — whether we simply give aspirin or something stronger. It could make a big difference."

Dr. Martin-Schild, Ms. Gouse, and Mr. Monlezun have disclosed no relevant financial relationships.

American Neurological Association (ANA) 2013 Annual Meeting. Abstracts #S422 and #S433. Presented October 13, 2013.

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