Rationale

According to literature, the inflammatory response and platelets are associated with coronary heart disease mortality. In this study, we examine if similar relationships exist after acute cerebral infarctions.

Design

Between 2005 and 2007, individuals (n = 61) hospitalized with acute stroke were investigated 2.1 ± .3 (SD) days after hospital admission. After 9.3 ± .7 (SD) years, 29 patients (age 79 ± 8 [SD]; 12 women) had died. They were compared with survivors (age 69 ± 9 [SD]; 9 women) with respect to inflammatory parameters and platelet features such as activity and reactivity.

Results and conclusion

Inflammation and platelets at the acute event do not forecast long-term survival of stroke sufferers

Objective

Platelets may well be significant in the pathogenesis of cerebral infarction. Platelets vary substantially according to gender. The scope of our current work is to establish if female and male stroke sufferers differ regarding platelet reactivity.

Patients and methods

73 Consecutive individuals stricken by acute ischemic cerebral infarction (31 females, 42 males) participated. All stroke subtypes were included. Platelet counts was determined electronically. Platelet reactivity i.e. the presence of surface-bound fibrinogen following provocation was analyzed with a flow cytometer. ADP (1.7 μmol/L) and a thrombin receptor agonist (TRAP-6) (57 μmol/L) were the agonists used.

Results

Female stroke sufferers had higher platelet counts (p = 0.013) but their platelets were less reactive. The p values were (p = 0.038) and (p = 0.016) for ADP and TRAP-6, respectively.

Conclusion

The current study demonstrates that women suffering acute cerebral infarction have less reactive platelets. It is concluded that gender affects platelets. Our study indicates that it may be beneficial to individualize platelet inhibition of stroke sufferers according to gender.

Introduction: Alzheimers disease (AD) is a progressive form of dementia characterized by an increase in the toxic substance beta-amyloid in the brain. Platelets display a substantial heterogeneity with respect to density. They further contain a substantial amount of beta-amyloid precursor protein. Platelets take up and store serotonin (5-HT) that plays an important role in the pathogenesis of severe depression. The current study aims to investigate platelet serotonin content in different platelet density populations. Material and methods: The study involved 8 patients (age 70 +/- 8 (SD) years) (3 females/5 males) with moderate AD. 6 healthy elderly subjects (age 66 +/- 9 (SD) years) (3 females/3 males) served as controls. The platelet population was divided into 17 subpopulations according to density, using a linear Percoll (TM) gradient. Platelets were counted in all fractions. After cell lysis an ELISA technique was employed to determine the 5-HT content in each platelet subfraction. Results: The two study groups did not differ significantly regarding platelet distribution in the gradients, but AD sufferers have a significantly higher 5-HT content (p less than 0.05) in the lighter platelet populations. Discussion: AD-type dementia proved to be associated with lighter platelets containing more 5-HT. It is possible that platelets from AD patients release less 5-HT. It is speculated that AD synapses are affected in a manner comparable to platelets, which could explain why 5-HT reuptake inhibitors are less effective in AD dementia.

BACKGROUND:

The current study investigates circulating eosinophils and neutrophils in Alzheimer's (AD) type dementia with respect to density (kg/L). The existence of β-amyloid plaques in the brain is a feature of AD. Sporadic scientific reports indicate that the disease affects circulating neutrophils. In contrast, numerous publications investigate inflammatory reactions in AD brains. Locally, the plaques evoke a substantial inflammatory response involving activated microglia and astrocytes.

METHODS:

Subjects with probable AD (n = 39) were included and compared with elderly individuals (n = 22) lacking apparent memory problems. We sampled 10 mL venous blood in citrate. Granulocytes were separated according to density in linear Percoll™ gradients. Subsequently, the gradients were divided into density subfractions (n = 16). In every fraction, determination of eosinophil and neutrophil counts was carried out.

RESULTS:

AD sufferers displayed less granulocytes in fractions nos. 13-15 containing light cells. For these fractions, the P-values proved to be (P < 0·001; not significant; P = 0·03) and (P = 0·01; P = 0·01; not significant), for eosinophils and neutrophils, respectively.

CONCLUSIONS:

The present work describes that less circulating light granulocytes are a feature of AD demented individuals. It is to hypothesize that it is a sign of impaired granulocyte turnover and cell damage. It is concluded that AD affects inflammatory cells in the periphery and that the behaviour of granulocytes in dementia is worthwhile further studies.

Stroke is worldwide a leading cause of death and disability. Its etiology is regarded as heterogeneous. Platelets are implicated in its pathophysiology, but our understanding of their specific role is incomplete. Only sparse and conflicting information exists about platelet reactivity and activity in acute stroke. Some scientists take the view that platelets activate in conjunction with acute cerebral infarctions. Others put forward evidence corroborating the contrary notion. Increased soluble P-selectin as a sign of platelet and/or endothelial activity seems to be a feature of the disease. The latter point of view is opposed by other researchers. Due to these conflicting opinions, this study is devoted to platelet characteristics in acute cerebral infarctions. We studied subjects (n = 72; age 74 +/- 10(SD) years; 31 females) having acute stroke. As controls served atrial fibrillation (AF) patients (n = 58; age 69 +/- 7(SD) years; 12 females) subject to electrical cardioversion, a flow cytometer was put to use for measuring platelet reactivity and activity. After agonist provocation, both platelet bound P-selectin and fibrinogen were employed as estimates of platelet reactivity. Dilutions of a thrombin-receptor-activating peptide (TRAP-6) (74 and 57 mmol/l) (P-selectin and fibrinogen) and ADP (8.5 and 1.7 mmol/l) (fibrinogen only) were put to use as platelet agonists. Membrane-bound P-selectin without agonist stimulation served as a measure of in vivo platelet activation. Soluble P-selectin, as determined from a commercial ELISA, was used to assess platelet and/or endothelial activity. In acute stroke neither platelet-bound P-selectin nor fibrinogen after stimulation, i.e. reactivity, differed from AF controls. In contrast, lower platelet activity as judged from surface attached and circulating P-selectin without agonist stimulation proved to be a feature of cerebral infarctions. The p-values were p < 0.001 and p < 0.01, respectively. It is concluded that acute stroke is not associated with platelet reactivity platelets circulate less activated during the disease. It is evident that the mechanisms reflecting platelet reactivity and activity being investigated in this study play minor roles in stroke pathophysiology. New powerful platelet inhibitory drugs are currently introduced. To avoid major bleeding studies on platelet, behavior in acute stroke are necessary before including these medications in stroke treatment protocols.

Objective. Knowledge concerning the neurobiological importance of platelets in Alzheimers disease (AD) is sparse. P-selectin, which is located together with beta-amyloid precursor proteins in platelet alpha-granules, is also found in endothelial cells. Upon activation, P-selectin is relocated to cell surfaces where it acts as a receptor. Subsequently, the protein is cleaved from the membrane, to then be circulated. We investigated P-selectin behavior in AD dementia. Methods. We recruited 23 persons diagnosed moderate AD and 17 healthy elders without obvious memory problems. Circulating P-selectin was analyzed using an ELISA technique and flow cytometry was used to measure surface-bound P-selectin. The latter measure was carried out without provocation (platelet activity) and after in vitro agonist stimulation (platelet reactivity). A thrombin-receptor activating peptide (TRAP-6) (74 mu mol/L)) was used as a platelet agonist. Results. Soluble P-selectin was augmented in AD (p = 0.019) but platelet membrane-attached P-selectin did not differ from controls. AD diagnosis was associated with less surface-bound P-selectin after provocation. Significant results were obtained when 74 mu mol/L TRAP-6 was used as a platelet agonist (p = 0.0008). Conclusion. This study describes apparently paradoxical P-selectin reactions in moderate AD. While soluble P-selectin was higher in the disease group, membrane-attached P-selectin without agonist stimulation was no different between the disease and control groups. In contrast, AD was linked to lower platelet reactivity. The current findings encourage further research into this P-selectin paradox and its relevance for AD and, perhaps, other types of dementia as well.

Platelets contain a substantial quantity of amyloid-precursor protein (APP) and β-amyloid. However, despite the large importance of APP and β-amyloid to dementia, little is known about platelets in sporadic Alzheimer dementia (AD). Furthermore, platelet heterogeneity influences human pathology and has been described to affect the progression of AD. This study investigated AD platelets with respect to density diversity and in vivo activity associated with density sub-fractions. We included 39 AD patients and used, as controls, 22 elderly individuals without apparent memory disorder. A continuous Percoll™ gradient covering the density span 1.04–1.09 kg/l provided the basis to divide platelets of whole blood into density fractions (n = 16). All platelet populations were evaluated accordingly. Platelet counts were determined electronically. A flow-cytometer was put to use to measure surface-bound fibrinogen as a measure of platelet in vivo activity. Samples obtained from patients diagnosed with sporadic AD contained platelets (fractions numbers 4–16) that circulated with significantly less surface-bound fibrinogen, i.e., their platelet activation in vivo was reduced, compared with controls. In particular, highly significant differences (p < 0.001) were obtained for the six less dense platelet populations (fractions numbers 11–16) when comparing sporadic AD with controls. In contrast, the densest AD platelets in fractions numbers 1–3 did not differ significantly from control cells with respect to in vivo platelet-bound fibrinogen. It is concluded that sporadic AD is characterized by lower density platelet populations that, while circulating, exhibited reduced activation. The clinical significance of this finding is unclear but these results suggest the importance of platelet heterogeneity in dementia as a topic for further investigation.

BACKGROUND: The impact of atrial fibrillation (AF) upon platelet reactivity has not been investigated.

METHODS: Subjects were 33 individuals with AF who consented to elective electrical cardioversion (ECV) immediately before ECV determination of surface-bound fibrinogen after stimulation i.e. platelet reactivity was carried out. A flow cytometer was employed. ADP (1.7 and 8.5mumol/L) and a thrombin receptor activating peptide (54 and 74mumol/L) were used as agonists. The analyses were repeated after 26+/-8(SD) months.

RESULTS: Compared to day 1 subjects with AF (n=18) had a trend towards lower platelet reactivity at study end. It reached significance when using 1.7mumol/L ADP. In contrast, after 26+/-8(SD) months sinus rhythm (SR) (n=15) was associated with significant lower reactivity with all agonists.

CONCLUSION: After 26+/-8(SD) months patients returning with AF had higher platelet reactivity than those who remained with SR.

Essential thrombocythemia (ET) is characterized by high platelet counts and a slightly increased bleeding risk. Why severe hemorrhage does not occur more frequently is not known. Variations of platelet density (kg/l) depend mainly on cell organelle content in that high-density platelets contain more alpha and dense granules. This study compares ET patients (n = 2) and healthy volunteers (n = 2) with respect to platelet density subpopulations. A linear Percoll gradient containing prostaglandin E(1) was employed to separate platelets according to density. The platelet population was subsequently divided by density into 16 or 17 subpopulations. Determination of platelet counts was carried out. In each density fraction, platelet in vivo activity, i.e. platelet-bound fibrinogen, was measured using a flow cytometer. To further characterize platelet subpopulations, we determined intracellular concentrations of CD40 ligand (CD40L) and P-selectin in all fractions. Patients and controls demonstrated similar density distributions, i.e. 1 density peak. High-density platelets had more surface-bound fibrinogen in conjunction with signs of platelet release reactions, i.e. with few exceptions they contained less CD40L and P-selectin. Peak density platelets showed less surface-bound fibrinogen. These platelets contained less CD40L and P-selectin than nearby denser populations. The light platelets had more surface-bound fibrinogen than peak platelets together with elevated concentrations of CD40L. In ET, the malignant platelet production could exist together with platelets originating from normal megakaryocytes. It is also possible that clonal megakaryocytes produce platelets covering the entire density span. The 'normal' density distribution offers a tenable explanation as to why serious bleedings do not occur more frequently.