Drop in Platelet Count After TAVR Signals Poor Outcomes

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Patients who experience a decrease in platelet count following transcatheter aortic valve replacement (TAVR) are at increased risk of adverse events, according to a paper published in the June 1, 2013, issue of the American Journal of Cardiology. However, the exact mechanisms for the condition and its consequences are unclear.

Pascal Lim, MD, PhD, of University Hospital Henri Mondor (Creteil, France), and colleagues retrospectively studied 144 consecutive patients with severe symptomatic aortic stenosis who received the CoreValve device (Medtronic, Minneapolis, MN) between December 2007 and July 2011. Blood platelet count was measured at baseline and every day after TAVR until discharge, and outcomes were defined according to Valve Academic Research Consortium criteria.

Higher In-Hospital MACE Rates Seen

Before TAVR, blood platelet count averaged 216 x 10⁹/L ± 67 x 10⁹/L. All but 1 patient experienced a decrease in platelet count postprocedure, with the minimum platelet count averaging 170 x 10⁹/L ± 54 x 10⁹/L. Platelet count reached its nadir at 2.5 ± 1.1 days after TAVR.

Moderate thrombocytopenia (platelet count 50 x 10⁹/L to 150 x 10⁹/L) was seen in 90 patients (63%) and severe thrombocytopenia (platelet count < 50 x 10⁹/L) in 3 patients (2.5%). No patients were given platelet transfusions, though dual antiplatelet therapy was stopped in those with severe thrombocytopenia.

Divided into tertiles, platelet count decreases were 18 ± 7%, 33 ± 4%, and 55 ± 10% for groups 1, 2, and 3 respectively. Patients in group 3, the highest tertile, tended to have more complex procedures that were less apt to be successful (P = 0.009) and more likely to involve prosthesis displacement (P = 0.005), longer procedural times (P < 0.0001), longer x-ray times (P= 0.002), and greater contrast volume (P= 0.006) than those in groups 1 and 2.

The rate of in-hospital MACE (all-cause death, life-threatening and major bleeding, and stroke) was reduced for patients in group 1, who also showed trends for less in-hospital mortality and reduced bleeding. Those with the smallest decreases in platelet count had smaller hemoglobin loss and fewer red blood cell transfusions. Other outcomes during hospitalization were statistically similar among the 3 groups (table 1).

Table 1. In-hospital Outcomes by Decrease in Platelet Count

At 30 days, there was a reduction in the combined safety endpoint (all-cause mortality, major stroke, life-threatening bleeding, stage 3 acute kidney injury, periprocedural MI, major vascular complications, and repeat procedures for valve-related dysfunction ) in patients with smaller platelet count drops (8%, 8%, and 29% in tertiles 1-3; P = 0.004) and a trend toward lower mortality (2%, 8%, and 15% in tertiles 1-3; P = 0.08).

Multivariate analysis showed that the percent decrease in blood platelet count was the only predictor of in-hospital MACE (OR 1.67; 95% CI 1.05-2.67; P = 0.03).

Causes and Effects Uncertain

Platelet count decreases are not unique to TAVR, the researchers point out, noting that the phenomenon has also been observed after PCI and surgical aortic valve replacement. Previous studies have hinted that low-osmolar contrast agents may be partially responsible, as well as reactions to unfractionated heparin.

But in the current study, all patients received unfractionated heparin and most received antiplatelet medications, casting doubt on any connection between these drugs and platelet count, they say.

Instead, certain characteristics shared with aortic valve surgery may play a role, Dr. Lim and colleagues suggest. These include “endothelial damage caused by prosthesis implantation, fibrinogen binding on metallic armatures, and shear stress modifications due to prosthesis implantation,” they note, adding that “tissue injury during aortic valve implantation may play an important part in platelet activation,” which has been associated with worse outcomes.

Peter C. Block, MD, of Emory University School of Medicine (Atlanta, GA), agreed that the cause of platelet decreases is unclear.

“My sense of this is that if you put a lot of foreign body into the circulation, platelets when they [pass] by become activated,” he told TCTMD in a telephone interview. “Over a series of 100 circulations, the platelets just get extremely activated, and the spleen, liver, and lungs start picking them off because they’re activated platelets and not doing any good. So the platelet count goes down. I don’t know if any of that is true. It just makes sense to me that that might be happening.” Inflammatory response could also be the culprit, he added.

Clinicians who perform TAVR see this phenomenon regularly, Dr. Block said. But most patients have high enough baseline platelet counts that the decreases have little effect. In more severe cases, additional doses of antiplatelet medications may help platelet counts rise, he suggested, stressing that only anecdotal evidence supports that technique.

For prevention, the solution may be “better prostheses that are perhaps less irritating to the circulation and platelets,” Dr. Block proposed, adding that “because clinically 95% of the time it is a nonissue for us,” dedicated studies on this issue are unlikely.

In a telephone interview with TCTMD, Philippe Généreux, MD, of Columbia University Medical Center (New York, NY), said that platelet count decreases have been commonly reported for first-generation TAVR devices. However, it is unclear whether the decreases “are simply a marker of sicker patients or caused by the device per se,” he emphasized. “This needs to be better investigated before any conclusions can be drawn.”

Without knowing the cause, it is hard to know how best to deal with the condition, Dr. Généreux noted. The root cause of the decrease should be addressed first. In lieu of that, platelet transfusions may be considered, he said.

 

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Source:
Gallet R, Seeman A, Yamamoto M, et al. Effect of transcatheter (via femoral artery) aortic valve implantation on the platelet count and its consequences. Am J Cardiol. 2013;111:1619-1624.

 

 

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