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  • 1.
    Järemo, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Eriksson, M.
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Platelets and acute cerebral infarction2013In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 24, no 5, p. 407-411Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    Järemo, Petter
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson-Franzen, Marie
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Platelets, gender and acute cerebral infarction2015In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, ISSN ISSN 1479-5876, Vol. 13, no 267Article in journal (Refereed)
    Abstract [en]

    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.

  • 3.
    Järemo, Petter
    et al.
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Eriksson-Franzen, Marie
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Oweling, Magnus
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Platelets and inflammatory parameters do not affect long-term survival after acute stroke. Journal of Stroke and Cerebrovascular Diseases,2016In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 25, no 8, p. 1936-1938Article in journal (Refereed)
    Abstract [en]

    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

  • 4.
    Järemo, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Fransson, Sven Göran
    Östergötlands Läns Landsting, Heart Centre, Department of Cardiology Thoracic Radiology. Linköping University, Faculty of Health Sciences.
    Milovanovic, Micha
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Logander, Elisabeth
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Richter, Arina
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Inverse relationship between platelet density and reactivity alterations at coronary angiography2001In: Haemostasis, ISSN 0301-0147, E-ISSN 1423-0038, Vol. 31, no 1, p. 55-60Article in journal (Refereed)
    Abstract [en]

    This work investigates relationships between platelet density and reactivity. 21 individuals subject to coronary angiography were studied. Peak platelet density was analyzed using a newly developed electronic device. The apparatus measures light transmission through test tubes containing density-separated platelets, thus allowing an estimation of the platelet distribution in the gradient. A flow cytometry technique was used for determining platelet reactivity after stimulating with ADP. Platelet counts, mean platelet volumes, peak platelet density and platelet reactivity were determined immediately before (day 1) and 24 h after cardiac catheterization (day 2). For all parameters changes during the day of angiography were compared with platelet density alterations. The subjects were divided into two groups according to density changes at angiography. Group 1 individuals showed density alterations (i.e. day 2 – day 1 value) ≥–8 × 10–5 kg/l. In contrast, group 2 subjects either displayed density changes <–8 × 10–5 kg/l or grossly disturbed platelet density patterns on day 2. Before angiography both groups had similar platelet counts and volumes. Then platelet reactivity when stimulating with ADP did not differ significantly between the two groups. After angiography, the number of fibrinogen-positive cells when stimulating with ADP rose by 6 ± 8% for group 2 patients. The corresponding figure for group 1 was –1 ± 6%. The difference was significant (p = 0.01). No such relationships were found when comparing density alterations and changes of platelet counts and volumes. We conclude that in this study platelet density alterations at coronary angiography are inversely related to variations of platelet reactivity.

  • 5.
    Järemo, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Buller, Caroline
    Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Winblad, Bengt
    Karolinska Institute, Huddinge, Sweden.
    Alzheimer's disease and granulocyte density diversity2013In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 43, no 6, p. 545-548Article in journal (Refereed)
    Abstract [en]

    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.

  • 6.
    Järemo, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Buller, Caroline
    Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, East County Primary Health Care.
    Winblad, Bengt
    Karolinska Institutet.
    Low-density platelet populations demonstrate low in vivo activity in sporadic Alzheimer disease2012In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 23, no 2, p. 116-120Article in journal (Refereed)
    Abstract [en]

    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.

  • 7.
    Järemo, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Buller, Caroline
    Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, East County Primary Health Care.
    Winblad, Bengt
    Karolinska Institute, Sweden .
    P-selectin paradox and dementia of the Alzheimer type: Circulating P-selectin is increased but platelet-bound P-selectin after agonist provocation is compromised2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 2, p. 170-174Article in journal (Refereed)
    Abstract [en]

    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.

  • 8.
    Järemo, Petter
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Richter, Arina
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Elevated platelet reactivity in stable angina pectoris without significant coronary flow obstruction2008In: Journal of Cardiovascular Medicine, ISSN 1558-2027, Vol. 9, no 2, p. 129-130Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    There are many different causes of angina pectoris without significant coronary flow obstruction in major coronary arteries. Examples include Prinzmetal angina and small vessel atherosclerotic disease.

    METHODS:

    We investigated individuals with stable angina pectoris subject to elective coronary angiography. To keep the study group as homogeneous as possible, patients with diabetes mellitus were excluded. Subjects with normal coronary angiograms (n = 13) or insignificant (< 50%) coronary flow obstruction(s) (n = 4) were grouped together. The remaining cohort (n = 96) with at least one significant (> or = 50%) flow obstruction in at least one major coronary artery served as controls.

    RESULTS:

    Before angiography, platelet activity in vitro on stimulation with a thrombin-receptor activating peptide (TRAP-6) (57 micromol/l and 74 micromol/l) and ADP (1.7 micromol/l and 8.5 micromol/l) was determined. Angina pectoris individuals without significant flow obstruction in major coronary arteries had enhanced platelet reactivity both when stimulated with TRAP-6 and ADP (P < 0.01 for both TRAP-6 concentrations and P < 0.05 for both ADP concentrations, respectively.

    CONCLUSIONS:

    It is concluded that angina pectoris without significant flow impediment in major epicardial arteries is associated with augmented platelet reactivity.

  • 9.
    Järemo, Petter
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Richter, Arina
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Letter: Elevated platelet density and enhanced platelet reactivity in stable angina pectoris complicated by diabetes mellitus type II2009In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 124, no 3, p. 373-374Article in journal (Other academic)
    Abstract [en]

    The prognosis of coronary heart disease (CHD) has changed for the better. Type II diabetes mellitus (T2DM) complicates CHD and is associated with less favorable prospects and higher rates of coronary recurrence.

    149 individuals below 75 years of age subject to elective coronary angiography to evaluate chest pain were consented. Patients were eligible if they did not have a history of rheumatic disease. 51 individuals treated medically for T2DM were compared with the remaining subjects (n = 98). Blood samples were obtained before elective coronary angiography.A special designed optical apparatus was used to analyze peak platelet density. Platelet bound fibrinogen after provocation reflecting the activation of the GPIIb-IIIa receptor i.e. platelet reactivity was determined with the use of a flow cytometer.

    T2DM is associated with augmented platelet density (p < 0.001).Diabetic platelets displayed enhanced reactivity when stimulating with higher concentrations ADP (8.5 μmol/l) (p < 0.01) and TRAP-6 (74 μmol/l) (p < 0.001).

    DTII patients with stable angina pectoris showed enhanced platelet density, augmented platelet reactivity and increased MPV. Platelets are more reactive in DTII. More aggressive platelets may offer a explanation as to why DTII has an impact upon the prognosis of CHD.

     

  • 10.
    Järemo, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, East County Primary Health Care.
    Buller, Caroline
    Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Post, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Winblad, Bengt
    Department of Neurobiology, Care Sciences and Society (NVS), KI-Alzheimer’s Disease Research Center, Karolinska Institute, Huddinge; Sweden.
    Alzheimer's disease is characterized by more low-density erythrocytes with increased volume and enhanced β-amyloid x-40 content2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 5, p. 489-492Article in journal (Other academic)
  • 11.
    Järemo, Petter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Milovanovic, Micha
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Social and Welfare Studies, Health, Activity, Care.
    Richter, Arina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Gender and stable angina pectoris: Women have greater thrombin-evoked platelet activity but similar adenosine diphosphate-induced platelet responses2005In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 94, no 1, p. 227-228Other (Other academic)
  • 12.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Platelets: with special reference to platelet density subpopulations, stable coronary heart disease and atrial fibrillation2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The current thesis was divided into two parts. Basic platelet research is the topic of the first section. The subsequent clinical part examines platelet reactivity in stable angina pectoris (AP) and in atrial fibrillation.

    Platelet heterogeneity was investigated in the first section (papers 1 and 2). The cells were separated according to density using linear Percoll™ (a density medium) gradients. The latter contained EDTA, prostaglandin E1 and theophylline to prevent platelet in vitro activity. The platelet population was then divided into density subpopulations (n = 16 - 20). Membrane attached fibrinogen was determined with a flow cytometer technique and used as a marker reflecting platelet in vivo activity. Platelet P-Selectin content was employed to estimate the quantity of platelet α-granules. Paper I examined healthy blood donors (n = 3). The second report (paper II) compared healthy volunteers (n = 2) and subjects with essential thrombocythemia (ET) (n = 2). The latter is a clonal disease being characterized by an excessive platelet production. Platelet counts were determined in all fractions. In manuscripts I and II determination of surface bound fibrinogen and intracellular P-Selectin was carried out in 12 and 16 platelet density fractions, respectively.

    High density platelets displayed more surface bound fibrinogen indicating in vivo activity. They also contained less P-Selectin. The latter finding implies platelet in vivo release reactions. Low density platelets circulated with more surface bound fibrinogen as well. Compared with peak density platelets, lighter cells contained more P-Selectin. ET was characterized by a similar platelet density pattern in that high and low density platelets displayed more surface bound fibrinogen. The similarity may explain why severe bleedings do not occur more frequently in ET. It is also obvious from the current thesis that the significance of platelet heterogeneity remains unclear and stimulates to further research. In particular, future work must involve more patients.

    The second part (papers III-VI) of the thesis was devoted to stable AP and atrial fibrillation. Determination of platelet reactivity i.e. platelet bound fibrinogen after stimulation was carried out in whole blood. A flow cytometer technique was employed (papers III-VI). Adenosine diphosphate (ADP) (1.7 and 8.5 μmol/L) and a thrombin-receptor activating peptide (TRAP-6) (57 and 74 μmol/L) were used as stimulating agents. Determination of peak platelet density (kg/L) was utilized as a further measure reflecting platelet reactivity (paper V). Surface bound and soluble P-Selectin were employed as platelet activity markers (paper VI).

    Gender differences with respect to platelet reactivity were investigated in paper III. Paper IV examined platelets in stable AP without significant coronary flow obstruction(s) as determined by coronary angiography. In a following study platelet reactivity was analysed in diabetes type II complicated by stable AP (paper V). Finally, long-term (more than 2 years) outcome of atrial fibrillation was related to platelet reactivity and activity (paper VI). In this study the subjects were investigated at the initial electrical cardioversion and the analysis were repeated after more than 2 years.

    Postmenopausal women with stable AP demonstrated more reactive platelets when stimulating with TRAP-6. They had higher platelet counts (paper III) as well. Stable AP without significant coronary flow obstruction(s) was associated with elevated platelet reactivity (paper IV). Diabetes type II was linked to higher peak platelet density and elevated platelet reactivity (paper V). Augmented platelet reactivity proved to be a feature of subjects remaining in atrial fibrillation more than 2 years after the electrical cardioversion (paper VI). In contrast, the irregular heart rhythm did not affect platelet activity.

    It is to assume that platelets at least partly are responsible for the sometimes atypical symptoms of females with stable AP. It is also conceivable to speculate that platelets contribute to chest pain in AP free from significant coronary flow obstruction(s). Theoretically, enhanced platelet reactivity could at least partly explain why diabetes type II affects the prognosis of coronary heart disease. The thesis further shows a possible theoretical link between atrial fibrillation, increased platelet reactivity and clot formation.

    List of papers
    1. Identification of low-density plate and elevated let populations with increased reactivity alpha-granule content
    Open this publication in new window or tab >>Identification of low-density plate and elevated let populations with increased reactivity alpha-granule content
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    2003 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 111, no 01-Feb, p. 75-80Article in journal (Refereed) Published
    Abstract [en]

    The present study examines biochemical and functional characteristics of platelet density subpopulations together with their ability to mobilise intracellular fibrinogen when activated. Platelets from three healthy volunteers were investigated. The total platelet population was separated according to density in a linear Percoll(TM) gradient in a plasma-free milieu containing EDTA that binds soluble Ca2+. Subsequently, platelets from each individual were divided according to density into 11 or 12 aliquots. In all fractions, we determined platelet count, intracellular P-selectin and the ADP-evoked platelet fibrinogen binding as a measure of platelet reactivity together with the platelet dense body content. The work demonstrates that platelets use stored intracellular fibrinogen when activated. It also shows that the platelet-fibrinogen binding can be initiated in a surrounding depleted of Ca2+ and fibrinogen. Moreover, the study demonstrates subpopulations of light platelets having increased reactivity and more alpha-granules but less dense bodies. The biological significance of the findings needs to be elucidated. (C) 2003 Elsevier Ltd. All rights reserved.

    Keywords
    platelets, platelet density, dense bodies, fibrinogen, P-selectin
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-46312 (URN)10.1016/j.thromres.2003.08.019 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2020-01-23
    2. Platelet Density Distribution in Essential Thrombocythemia
    Open this publication in new window or tab >>Platelet Density Distribution in Essential Thrombocythemia
    Show others...
    2010 (English)In: Pathophysiology of Haemostasis and Thrombosis, ISSN 1424-8832, E-ISSN 1424-8840, Vol. 37, no 1, p. 35-42Article in journal (Refereed) Published
    Abstract [en]

    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.

     

    Place, publisher, year, edition, pages
    Basel, Switzerland: S. Karger, 2010
    Keywords
    Essential thrombocythemia, Flow cytometry, Plateletactivity, Platelet density
    National Category
    Hematology
    Identifiers
    urn:nbn:se:liu:diva-59581 (URN)10.1159/000314964 (DOI)000208040900005 ()20484885 (PubMedID)
    Note

    Original Publication: Micha Milovanovic, Kourosh Lotfi, Tomas Lindahl, Claes Hallert and Petter Järemo, Platelet Density Distribution in Essential Thrombocythemia., Pathophysiology of Haemostasis and Thrombosis, 2010. http://dx.doi.org/10.1159/000314964 Copyright: Karger http://www.karger.com/

    Available from: 2010-09-29 Created: 2010-09-21 Last updated: 2017-12-12Bibliographically approved
    3. Gender and stable angina pectoris: Women have greater thrombin-evoked platelet activity but similar adenosine diphosphate-induced platelet responses
    Open this publication in new window or tab >>Gender and stable angina pectoris: Women have greater thrombin-evoked platelet activity but similar adenosine diphosphate-induced platelet responses
    2005 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 94, no 1, p. 227-228Other (Other academic)
    Publisher
    p. 227-228
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-48196 (URN)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12
    4. Elevated platelet reactivity in stable angina pectoris without significant coronary flow obstruction
    Open this publication in new window or tab >>Elevated platelet reactivity in stable angina pectoris without significant coronary flow obstruction
    2008 (English)In: Journal of Cardiovascular Medicine, ISSN 1558-2027, Vol. 9, no 2, p. 129-130Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    There are many different causes of angina pectoris without significant coronary flow obstruction in major coronary arteries. Examples include Prinzmetal angina and small vessel atherosclerotic disease.

    METHODS:

    We investigated individuals with stable angina pectoris subject to elective coronary angiography. To keep the study group as homogeneous as possible, patients with diabetes mellitus were excluded. Subjects with normal coronary angiograms (n = 13) or insignificant (< 50%) coronary flow obstruction(s) (n = 4) were grouped together. The remaining cohort (n = 96) with at least one significant (> or = 50%) flow obstruction in at least one major coronary artery served as controls.

    RESULTS:

    Before angiography, platelet activity in vitro on stimulation with a thrombin-receptor activating peptide (TRAP-6) (57 micromol/l and 74 micromol/l) and ADP (1.7 micromol/l and 8.5 micromol/l) was determined. Angina pectoris individuals without significant flow obstruction in major coronary arteries had enhanced platelet reactivity both when stimulated with TRAP-6 and ADP (P < 0.01 for both TRAP-6 concentrations and P < 0.05 for both ADP concentrations, respectively.

    CONCLUSIONS:

    It is concluded that angina pectoris without significant flow impediment in major epicardial arteries is associated with augmented platelet reactivity.

    Place, publisher, year, edition, pages
    Lippincott Williams & Wilkins, 2008
    Keywords
    angina pectoris; flow cytometry; platelets; platelet reactivity
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-44108 (URN)10.2459/JCM.0b013e3280c56d46 (DOI)18192803 (PubMedID)75552 (Local ID)75552 (Archive number)75552 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2014-01-07Bibliographically approved
    5. Letter: Elevated platelet density and enhanced platelet reactivity in stable angina pectoris complicated by diabetes mellitus type II
    Open this publication in new window or tab >>Letter: Elevated platelet density and enhanced platelet reactivity in stable angina pectoris complicated by diabetes mellitus type II
    2009 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 124, no 3, p. 373-374Article in journal, Letter (Other academic) Published
    Abstract [en]

    The prognosis of coronary heart disease (CHD) has changed for the better. Type II diabetes mellitus (T2DM) complicates CHD and is associated with less favorable prospects and higher rates of coronary recurrence.

    149 individuals below 75 years of age subject to elective coronary angiography to evaluate chest pain were consented. Patients were eligible if they did not have a history of rheumatic disease. 51 individuals treated medically for T2DM were compared with the remaining subjects (n = 98). Blood samples were obtained before elective coronary angiography.A special designed optical apparatus was used to analyze peak platelet density. Platelet bound fibrinogen after provocation reflecting the activation of the GPIIb-IIIa receptor i.e. platelet reactivity was determined with the use of a flow cytometer.

    T2DM is associated with augmented platelet density (p < 0.001).Diabetic platelets displayed enhanced reactivity when stimulating with higher concentrations ADP (8.5 μmol/l) (p < 0.01) and TRAP-6 (74 μmol/l) (p < 0.001).

    DTII patients with stable angina pectoris showed enhanced platelet density, augmented platelet reactivity and increased MPV. Platelets are more reactive in DTII. More aggressive platelets may offer a explanation as to why DTII has an impact upon the prognosis of CHD.

     

    Place, publisher, year, edition, pages
    Elsevier Ltd, 2009
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-59613 (URN)10.1016/j.thromres.2008.12.042 (DOI)19230957 (PubMedID)
    Available from: 2010-09-21 Created: 2010-09-21 Last updated: 2017-12-12Bibliographically approved
    6. Letter: Atrial fibrillation and platelet reactivity: in International Journal of Cardiology(ISSN 0167-5273)(EISSN 1874-1754)
    Open this publication in new window or tab >>Letter: Atrial fibrillation and platelet reactivity: in International Journal of Cardiology(ISSN 0167-5273)(EISSN 1874-1754)
    2010 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 145, no 2, p. 357-358Article in journal, Letter (Other academic) Published
    Abstract [en]

    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.

    Place, publisher, year, edition, pages
    Ireland: Elsevier, 2010
    Keywords
    Atrial fibrillation, Flow cytometry, platelet reactivity, platelet activity
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-59612 (URN)10.1016/j.ijcard.2010.02.030 (DOI)
    Note
    Original Publication: Micha Milovanovic, Elisabeth Fransson, Claes Hallert and Petter Järemo, Letter: Atrial fibrillation and platelet reactivity, International Journal of Cardiology, 2010. http://dx.doi.org/10.1016/j.ijcard.2010.02.030 Copyright: ElsevierAvailable from: 2010-09-29 Created: 2010-09-21 Last updated: 2017-12-12Bibliographically approved
  • 13.
    Milovanovic, Micha
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Eriksson, Kristoffer
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Winblad, Bengt
    Karolinska Institute, Sweden.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Primary Health Care in Norrköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Post, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Järemo, Petter
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Alzheimer and platelets: Low-density platelet populations reveal increased serotonin content in Alzheimer type dementia2014In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, no 15, p. 51-53Article in journal (Refereed)
    Abstract [en]

    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.

  • 14.
    Milovanovic, Micha
    et al.
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Fransson, Elisabeth
    Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Hallert, Claes
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Järemo, Petter
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Letter: Atrial fibrillation and platelet reactivity: in International Journal of Cardiology(ISSN 0167-5273)(EISSN 1874-1754)2010In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 145, no 2, p. 357-358Article in journal (Other academic)
    Abstract [en]

    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.

  • 15.
    Milovanovic, Micha
    et al.
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Fransson, Sven Göran
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Richter, Arina
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Järemo, Petter
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Inverse relationships between coronary blood flow obstruction and platelet reactivity in stable angina pectoris2005In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 16, no 3-4, p. 211-213Article in journal (Refereed)
    Abstract [en]

    This study investigates relationships between platelet reactivity and coronary blood flow obstruction in stable angina pectoris. Consented were 36 patients with single-vessel disease. The subjects were divided into two groups. One group (n = 14) had less severe (< = 80%) and the second group (n = 22) had severe coronary flow impairment (90%). Before elective coronary angiography platelet in vitro reactivity in venous whole blood was determined using a flow cytometry technique. A thrombin-receptor activating peptide (TRAP-6) (0.77 and 0.06 g/l) and ADP (8.5 and 1.7 µmol/l) were used to activate platelets. The number of fibrinogen positive cells (%) i.e., activated platelets after stimulation was employed as experimental parameter. Less severe flow obstruction was associated with more reactive platelets. When stimulating with 0.77 g/l TRAP-6 the number of activated platelets was 64 ± 15 (SD)%. The corresponding value for the group with severe flow obstruction was 40 ± 17(SD)%. The difference is significant (P < 0.001). 0.06 g/l TRAP-6 yielded similar results (P < 0.01). Also when using 8.5 µmol/l ADP to challenge platelets less severe flow obstruction was associated with enhanced reactivity (P < 0.01). 1.7 µmol/l ADP generated comparable results (P < 0.05). Thus, in stable angina pectoris coronary flow obstruction is inversely related to platelet reactivity.

  • 16.
    Milovanovic, Micha
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hallert, Claes
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Järemo, Petter
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Platelet Density Distribution in Essential Thrombocythemia2010In: Pathophysiology of Haemostasis and Thrombosis, ISSN 1424-8832, E-ISSN 1424-8840, Vol. 37, no 1, p. 35-42Article in journal (Refereed)
    Abstract [en]

    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.

     

  • 17.
    Milovanovic, Micha
    et al.
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Lysen, J.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Richter, Arina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Järemo, Petter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Identification of low-density plate and elevated let populations with increased reactivity alpha-granule content2003In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 111, no 01-Feb, p. 75-80Article in journal (Refereed)
    Abstract [en]

    The present study examines biochemical and functional characteristics of platelet density subpopulations together with their ability to mobilise intracellular fibrinogen when activated. Platelets from three healthy volunteers were investigated. The total platelet population was separated according to density in a linear Percoll(TM) gradient in a plasma-free milieu containing EDTA that binds soluble Ca2+. Subsequently, platelets from each individual were divided according to density into 11 or 12 aliquots. In all fractions, we determined platelet count, intracellular P-selectin and the ADP-evoked platelet fibrinogen binding as a measure of platelet reactivity together with the platelet dense body content. The work demonstrates that platelets use stored intracellular fibrinogen when activated. It also shows that the platelet-fibrinogen binding can be initiated in a surrounding depleted of Ca2+ and fibrinogen. Moreover, the study demonstrates subpopulations of light platelets having increased reactivity and more alpha-granules but less dense bodies. The biological significance of the findings needs to be elucidated. (C) 2003 Elsevier Ltd. All rights reserved.

  • 18.
    Milovanovic, Micha
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Nillsson, Ethel
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Järemo, Petter
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Relationships between platelets and inflammatory markers in rheumatoid arthritis2004In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 343, no 1-2, p. 237-240Article in journal (Refereed)
    Abstract [en]

    AIM OF THE STUDY: To investigate platelets and different inflammatory markers in conjunction with a substantial inflammatory reaction. We used individuals with active rheumatoid arthritis (RA) as an experimental cohort.

    METHODS: We selected 16 patients with active RA having at least one affected joint. On day 1, platelet and neutrophil counts together with C-reactive protein (CRP) were determined. We further analysed platelet volume (MPV) and plasma levels of thrombopoietin (TPO), P-selectin, myeloperoxidase and interleukin 6 (IL-6). After 2 years when all patients failed to show any swollen joints all analyses were repeated.

    RESULTS AND CONCLUSIONS: As expected platelet count, CRP and IL-6 were elevated in active RA. The measures correlated with each other thus reflecting the same characteristic of the inflammatory response. The neutrophil count, MPV and myeloperoxidase also mirror disease activity. They failed to correlate with other activity markers thus providing unique information. MPV and myeloperoxidase on day 1 correlated with recovery values. Therefore, they could be suitable to use when following the inflammatory reaction over a long period of time.

  • 19.
    Milovanovic, Micha
    et al.
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Nillsson, Ethel
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland.
    Järemo, Petter
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Relationships between platelets and inflammatory markers in rheumatoid arthritis2004In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 343, no 1-2, p. 237-240Article in journal (Refereed)
    Abstract [en]

    Aim of the study: To investigate platelets and different inflammatory markers in conjunction with a substantial inflammatory reaction. We used individuals with active rheumatoid arthritis (RA) as an experimental cohort. Methods: We selected 16 patients with active RA having at least one affected joint. On day 1, platelet and neutrophil counts together with C-reactive protein (CRP) were determined. We further analysed platelet volume (MPV) and plasma levels of thrombopoietin (TPO), P-selectin, myeloperoxidase and interleukin 6 (IL-6). After 2 years when all patients failed to show any swollen joints all analyses were repeated. Results and conclusions: As expected platelet count, CRP and IL-6 were elevated in active RA. The measures correlated with each other thus reflecting the same characteristic of the inflammatory response. The neutrophil count, MPV and myeloperoxidase also mirror disease activity. They failed to correlate with other activity markers thus providing unique information. MPV and myeloperoxidase on day 1 correlated with recovery values. Therefore, they could be suitable to use when following the inflammatory reaction over a long period of time.

  • 20.
    Milovanovic, Micha
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Primary Health Care in Norrköping.
    Harakka, PI
    Karolinska Institutet, Stockholm, Sweden.
    Post, C.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gerlde, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    High in vivo platelet activity in female fibromyalgia patients2016In: Journal of Biomedical Sciences, ISSN 2254-609X, Vol. 5, no 3:21, p. 1-5Article in journal (Refereed)
    Abstract [en]

    Introduction: Fibromyalgia (FMS) is a pain syndrome characterized by chronic widespread pain and hyperalgesia/allodynia. Many affected are women and risk factors are unidentified. Today, a certain number of set criteria of disease signs and symptoms must be met for the diagnosis to be made. These criteria are used because of the lack of reliable biomarkers or other medical examination. The current study examines if in vivo platelet activity varies between FMS and controls without FMS.

    Material and Methods: The study involves 24 females (age 38 + 9 (SD) years) with diagnosed FMS. 25 healthy females (age 50 + 12 (SD) years) without FMS served as controls. After sampling the whole platelet population was separated according to density with a linear Percoll™, into 17 density fractions. Platelet counts was carried out in all fractions using a routine cell counter. In addition, a flow cytometer was used to measure platelet bound fibrinogen without platelet agonist, reflecting in vivo platelet activity.

    Results: The study groups did not differ with respect to the distribution of platelets in the gradient. FMS sufferers demonstrated a significant higher platelet bound fibrinogen in most of the platelet density fractions. In particular, significant differences (p < 0.05) were obtained in fractions numbers 2-14 and 16. In difference, fractions numbers 1, 15 and 17 did not show any significant variance.

    Discussion: This is the first study to examine in vivo platelet activity in FMS. The results indicate that FMS is associated with elevated in vivo platelet activity compared to individuals without FMS. The clinical significance and the biochemical mechanisms regarding platelet heterogeneity are still uncertain. The results stimulate further research to elucidate the importance of platelet diversity in FMS

1 - 20 of 20
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