Platelet PlA2 polymorphism enhances risk of neurocognitive decline after cardiopulmonary bypass. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.
BACKGROUND
Neurocognitive decline, often produced by atherosclerotic plaque embolization, remains a frequent complication of cardiopulmonary bypass. Plaque fragments may initiate local thrombosis, which, in turn, aggravates the embolic insult. Prothrombotic genetic factors may exacerbate this process. We investigated whether the PlA2 polymorphism of platelet GPIIIa, a prothrombotic risk factor in other cardiovascular settings, is associated with early neurocognitive decline after cardiopulmonary bypass.


METHODS
Neurocognitive changes were evaluated by the Mini-Mental State Examination administered preoperatively and on postoperative day 4 and the PlA genotype determined in 70 patients undergoing cardiopulmonary bypass.


RESULTS
Forty-nine patients were PlA1/A1, and 21 were PlA1/A2 or PlA2/A2. Fifty-two patients (74%) demonstrated post-cardiopulmonary bypass neurocognitive decline, of which 34 were PlA1/A1 and 18 were PlA1/A2 or PlA2/A2 Multivariate analysis revealed that the PlA2 genotype and baseline Mini-Mental State Examination were significantly associated with greater neurocognitive decline (decreased Mini-Mental State Examination scores, p = 0.036 and 0.024, respectively).


CONCLUSIONS
This study demonstrates a link between the PlA2 allele of platelet GPIIIa and more severe neurocognitive decline after cardiopulmonary bypass. Although the mechanism is unknown, it could represent exacerbation of platelet-dependent thrombotic processes associated with plaque embolism.
Mathew
J P
JP
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8051, USA.
Rinder
C S
CS
Howe
J G
JG
Fontes
M
M
Crouch
J
J
Newman
M F
MF
Phillips-Bute
B
B
Smith
B R
BR
D000368:Aged; D000483:Alleles; D016824:Antigens, Human Platelet / Q000235:genetics*; D002315:Cardiopulmonary Bypass; D005260:Female; D005838:Genotype; D006801:Humans; D039661:Integrin beta3; D002537:Intracranial Arteriosclerosis / Q000175:diagnosis / Q000235:genetics*; D020766:Intracranial Embolism / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011183:Postoperative Complications / Q000175:diagnosis*; D012307:Risk Factors
D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039661:Integrin beta3; C083451:human platelet antigen 1b