Inverse relationship between erythrocyte size and platelet reactivity in elderly

Abstract

Previous work indicates that erythrocytes (RBCs) accumulate β-amyloid X-40 (Aβ₄₀) in individuals with Alzheimer disease (AD) and to a lesser extent in healthy elderly. The toxin damages RBCs and increases their mean corpuscular volume (MCV). Furthermore, AD platelets demonstrate lower reactivity. This study investigated interactions between RBCs and platelets. Older individuals with moderate hypertension (n = 57) were classified into two groups, depending on MCV in whole blood: The MCV^high group comprised individuals with higher MCV (n = 27; 97 ± 3(SD) fl) and MCV^low group had relatively lower MCV (n = 30; 90 ± 3(SD) fl). Flow cytometry was used to determine platelet reactivity, i.e., the surface binding of fibrinogen after provocation. Adenosine diphosphate (ADP) and a thrombin receptor-activating protein (TRAP-6) were used as agonists. Subsequently, blood cells were divided according to density into 17 subfractions. Intra-RBC Aβ₄₀ content was analyzed and in all platelet populations surface-bound fibrinogen was determined to estimate platelet in vivo activity. We found Aβ₄₀ inside RBCs of approximately 50% of participants, but the toxin did not affect MCV and platelet reactivity. In contrast, MCV associated inversely with platelet reactivity as judged from surface-attached fibrinogen after ADP (1.7 μmol/L) (p < 0.05) and TRAP-6 provocation (57 μmol/L (p = 0.01) and 74 μmol/L (p < 0.05)). In several density fractions (nos. 3, 4, 8, 11–13 (p < 0.05) and nos. 5–7 (p < 0.01)) MCV linked inversely with platelet-attached fibrinogen. In our community-dwelling sample, enhanced MCV associated with decreased platelet reactivity and lower in vivo platelet activity. It resembles RBCs and platelet behavior in AD-type dementia.

Keywords:

• Alzheimer´s disease
• β-amyloid
• elderly
• erythrocytes
• fibrinogen
• mean corpuscular volume
• platelet activity
• platelet density
• platelet reactivity

Sources of funding

“Konung Gustav V:s och Drotttning Viktorias Frimurarstiftelse” and Hultman´s Foundation provided generous grants. The Åhlen’s Foundation and the Gun and Bertil Stohne’s Foundation made important donations. The Swedish Alzheimer Foundation, the “Stiftelsen för Gamla Tjänarinnor,” and Magnus Bergvall’s Foundation contributed financially. The work was further supported by Pfizer AB, Sweden; the Swedish Board for Health and Welfare and the County Council of Östergötland, Sweden.

Disclosure of conflicts of interest

None declared.

Additional information

Funding

“Konung Gustav V:s och Drotttning Viktorias Frimurarstiftelse” and Hultman´s Foundation provided generous grants. The Åhlen’s Foundation and the Gun and Bertil Stohne’s Foundation made important donations. The Swedish Alzheimer Foundation, the “Stiftelsen för Gamla Tjänarinnor,” and Magnus Bergvall’s Foundation contributed financially. The work was further supported by Pfizer AB, Sweden; the Swedish Board for Health and Welfare and the County Council of Östergötland, Sweden.