Influence of platelet size on outcome after myocardial infarction

doi:10.1016/0140-6736(91)92719-I

The Lancet

Volume 338, Issue 8780, 7 December 1991, Pages 1409-1411

https://doi.org/10.1016/0140-6736(91)92719-I Get rights and content

Abstract

Although platelet characteristics have an important influence on ischaemic heart disease, the nature of the association of platelet size and platelet count with death and reinfarction after an index heart attack is unknown. Mean platelet volume (MPV), a determinant of platelet reactivity, was measured in 1716 men six months after myocardial infarction (MI). Deaths and recurrent ischaemic heart disease events were then assessed at two years. MPV was greater in 126 men who had a further ischaemic event (fatal or non-fatal) than in the 1590 men who had no further Ml (p<0·001). In addition, the MPV was larger in men who died than in those who did not (p<0·001). There was no difference in platelet count between these groups. When analysed by quartiles, consistent trends of increasing age-adjusted relative odds of death and recurrent ischaemic events were noted for MPV. MPV did not correlate with known ischaemic heart disease risk factors such as blood pressure, blood lipids, fibrinogen, white cell count, or plasma viscosity. We believe that MPV is a further independent risk factor for recurrent Ml.

References (25)

Jf Martin et al.
The biological significance of platelet volume: its relationship to bleeding time, platelet thromboxane B₂ production and megakaryocyte nuclear DNA concentration
Thromb Res
(1983)
Cb Thompson et al.
Platelet size does not correlate with platelet age
Blood
(1983)
Ml Burr et al.
Effect of changes in fat, fish, and fibre intakes on death and myocardial infarction: diet and reinfarction trial (DART)
Lancet
(1989)
Tw Meade et al.
Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study
Lancet
(1986)
Jj Walker et al.
Can platelet volume predict progressive hypertensive disease in pregnancy?
Am J Obstet Gynecol
(1989)
Steering Committee of the Physicians' Health Study Research Group
final report on the aspirin component of the ongoing physicians' study
N Engl J Med
(1988)
randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction
Lancet
(1988)
Jf Martin et al.
Changes in volume and density of platelets in myocardial infarction
Br Med J
(1983)
Am Gladwin et al.
Identification of mRNA for PDGF B-chain in human megakaryocytes isolated using a novel immunomagnetic separation method
Br J Haematol
(1990)
Ea Trowbridge et al.
Platelet production in myocardial infarction and sudden cardiac death
Thromb Haemost
(1984)

Sd Kristensen et al.

The bleeding time is inversely related to megakaryocyte nuclear DNA content and size in man

Thromb Haemost

(1988)

Pc Milner et al.

Shortened bleeding time in acute myocardial infarction and its relation to platelet mass

Br Med J

(1985)

Cited by (473)

Platelet and immune signature associated with a rapid response to the BNT162b2 mRNA COVID-19 vaccine
2022, Journal of Thrombosis and Haemostasis
A rapid immune response is critical to ensure effective protection against COVID‐19. Platelets are first‐line sentinels of the vascular system able to rapidly alert and stimulate the immune system. However, their role in the immune response to vaccines is not known.
To identify features of the platelet‐immune crosstalk that would provide an early readout of vaccine efficacy in adults who received the mRNA‐based COVID‐19 vaccine (BNT162b2).
We prospectively enrolled 11 young healthy volunteers (54% females, median age: 28 years) who received two doses of BNT162b2, 21 days apart, and we studied their platelet and immune response before and after each dose of the vaccine (3 and 10 ± 2 days post‐injection), in relation to the kinetics of the humoral response.
Participants achieving an effective level of neutralizing antibodies before the second dose of the vaccine (fast responders) had a higher leukocyte count, mounted a rapid cytokine response that incremented further after the second dose, and an elevated platelet turnover that ensured platelet count stability. Their circulating platelets were not more reactive but expressed lower surface levels of the immunoreceptor tyrosine‐based inhibitory motif (ITIM)‐coupled receptor CD31 (PECAM‐1) compared to slow responders, and formed specific platelet‐leukocyte aggregates, with B cells, just 3 days after the first dose, and with non‐classical monocytes and eosinophils.
We identified features of the platelet‐immune crosstalk that are associated with the development of a rapid humoral response to an mRNA‐based vaccine (BNT162b2) and that could be exploited as early biomarkers of vaccine efficacy.
Bone marrow NLRP3 inflammasome-IL-1β signal regulates post-myocardial infarction megakaryocyte development and platelet production
2021, Biochemical and Biophysical Research Communications
Platelet plays an important role in the progression of atherosclerosis. Recently it has been reported that myocardial infarction (MI) triggers megakaryopoiesis and thrombopoiesis in the bone marrow and leads to increased circulating platelets, which might contribute to the aggravation of atherosclerosis. However, the underlying mechanisms remain unclear. Here, we analyzed post-MI bone marrow tissue and found that MI induced an upregulation of bone marrow NOD-like Receptor Protein 3 (NLRP3) and subsequent secretion of IL-1β, an essential stimulator of megakaryopoiesis. Targeting NLRP3 using a specific inhibitor MCC950 reduced bone marrow IL-1β expression. Using bone marrow whole-mount immunofluorescence staining combined with flow cytometry, we demonstrated that MCC950 reduced megakaryocyte cellularity and maturity, and effectively attenuated the excessive platelet production after MI. Importantly, mice subjected to MI treated with MCC950 showed a higher survival rate compared with the only MI group. Taken together, this study shows that bone marrow NLRP3-IL-1β signal regulates megakaryocyte development and platelet production after myocardial infarction. It provides a new hint that pharmacological inhibition of NLRP3 might become a potential therapeutic approach for controlling excessive thrombopoiesis after MI.
Combined effects of plasma von Willebrand factor and platelet measures on the risk of incident venous thromboembolism
2021, Blood
Plasma von Willebrand factor (VWF) and platelet reactivity are risk factors for venous thromboembolism (VTE), and VWF can promote hemostasis by interaction with platelets. In this study, we explored the combined effects of plasma VWF and platelet measures on the risk of incident VTE. A population-based nested case-control study with 403 cases and 816 controls was derived from the Tromsø Study. VWF, platelet count and mean platelet volume (MPV) were measured in blood samples drawn at baseline. Odds ratios (ORs) with 95% confidence intervals (CIs) for VTE were estimated across VWF tertiles, within predefined MPV (<8.5, 8.5-9.5, and ≥9.5 fL) and platelet count (<230, 230-299, and ≥300 ×10⁹/L) strata. Here, participants with VWF levels in the highest tertile and with MPV ≥9.5 fL had an OR of 1.98 (95% CI, 1.17-3.36) for VTE compared with those in the lowest VWF tertile and with MPV <8.5 fL in the age- and sex-adjusted model. In the joint exposure group, 48% (95% CI, 15-96) of VTEs were attributable to the biological interaction between VWF and MPV. Similarly, individuals with VWF in the highest tertile and platelet count ≥300 × 10⁹/L had an OR of 2.91 (95% CI, 1.49-5.67) compared with those with VWF in the lowest tertile and platelet count <230 × 10⁹/L, and 39% (95% CI, −2 to 97) of VTEs in the joint exposure group were explained by the interaction. Our results suggest that platelet reactivity and platelet count interact biologically with high plasma VWF, resulting in an increased risk for incident VTE.
Platelet bound complement split product (PC4d) is a marker of platelet activation and arterial vascular events in Systemic Lupus Erythematosus
2021, Clinical Immunology
Platelet-bound complement activation products (PC4d) are associated with thrombosis in Systemic Lupus Erythematosus (SLE). This study investigated the effect of PC4d on platelet function, as a mechanistic link to arterial thrombosis. In a cohort of 150 SLE patients, 13 events had occurred within five years of enrollment. Patients with arterial events had higher PC4d levels (13.6 [4.4–24.0] vs. 4.0 [2.5–8.3] net MFI), with PC4d 10 being the optimal cutoff for event detection. The association of arterial events with PC4d remained significant after adjusting for antiphospholipid status, smoking, and prednisone use (p = 0.045). PC4d levels correlated with lower platelet counts (r = −0.26, p = 0.002), larger platelet volumes (r = 0.22, p = 0.009) and increased platelet aggregation: the adenosine diphosphate (ADP) concentration to achieve 50% maximal aggregation (EC₅₀) was lower in patients with PC4d 10 compared with PC4d < 10 (1.6 vs. 3.7, p = 0.038, respectively). These results suggest that PC4d may be a mechanistic marker for vascular disease in SLE.
Biomarker association with cardiovascular disease and mortality – The role of fibrinogen. A report from the NHANES study
2021, Thrombosis Research
While fibrinogen is a known cardiovascular disease (CVD) risk marker, its quantitative input to mortality risk is a topic of debate.
We investigated the contribution of fibrinogen, among that of other biomarkers, to prevalent CVD and incident CVD mortality in 4487 participants of the US National Health and Nutrition Examination Survey (NHANES). Participants were observed for a median period of 14 years, resulting in more than 58,000 person-years.
At baseline 551 participants had CVD and during follow up, 1339 all-cause deaths occurred, 321 (24%) of which were due to CVD. Hierarchical cluster analysis and principal component analysis (PCA) were performed to derive clusters of association between biomarkers. Next, structural equation modelling was performed to investigate the association of these clusters with baseline CVD and all-cause and CVD mortality during follow-up. Mediation analysis was used to determine which biomarkers played a mediatory role between prevalent CVD and future mortality. Fibrinogen clustered with C-reactive protein only and was associated with CVD at baseline (p < 0.0001) and with all-cause (p < 0.001) and CVD (p < 0.001) mortality at follow-up. Only fibrinogen (4.7%), followed by gamma-glutamyl transferase (GGT) (3.5%) and uric acid (2.3%) were identified as possible mediators between CVD status and all-cause mortality, with fibrinogen (3.2%) and GGT (3.1%) the only mediators between CVD status and CVD mortality.
This data shows that fibrinogen is not only cross-sectionally associated with CVD, but also contributes to all-cause and CVD mortality at follow-up. It furthermore appears to mediate the association between prevalent CVD and both all-cause and CVD mortality.
Principal component analysis of routine blood test results with Parkinson's disease: A case-control study
2021, Experimental Gerontology
This study aimed to explore the association of routine blood test values and blood cell ratios with the risk or severity of Parkinson's disease (PD). The medical records of 453 PD patients and 436 controls were retrospectively reviewed. The severity of PD was quantified by the modified Hoehn-Yahr (HY) scale. We performed principal component analysis (PCA) of significant values/ratios and used logistic regression analysis to explore the relationship between principal components (PCs) and the risk of PD. Spearman correlation and ordinal logistic regression analyses were performed to explore the relationship between indicators and the severity of PD. The PCA generated 9 PCs, which contributed to 90.86% of the total variance. Logistic regression analysis revealed positive associations of PC2 (a measure monocyte ratios) and PC6 (a measure of platelet ratios and volume) and negative associations of PC1 (a comprehensive measure of lymphocyte, eosinophil, neutrophil, and red blood cell values), PC4 (a measure of red blood cell values), and PC7 (a measure of red blood cell values and platelet volume) with the risk of PD. However, we observed no associations of variables with the severity of PD. In conclusion, PCA reduced the dimensionality of the data. Peripheral blood disorders may be associated with PD.

View all citing articles on Scopus

View full text

ORIGINAL ARTICLESInfluence of platelet size on outcome after myocardial infarction

Abstract

Thromb Res

Blood

Lancet

Lancet

Am J Obstet Gynecol

final report on the aspirin component of the ongoing physicians' study

N Engl J Med

randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction

Lancet

Changes in volume and density of platelets in myocardial infarction

Br Med J

Identification of mRNA for PDGF B-chain in human megakaryocytes isolated using a novel immunomagnetic separation method

Br J Haematol

Platelet production in myocardial infarction and sudden cardiac death

Thromb Haemost

The bleeding time is inversely related to megakaryocyte nuclear DNA content and size in man

Thromb Haemost

Shortened bleeding time in acute myocardial infarction and its relation to platelet mass

Br Med J

ORIGINAL ARTICLES
Influence of platelet size on outcome after myocardial infarction