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  • 1.
    Järemo, Petter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Chlamydia pneumoniae is associated with elevated platelet activity in patients with acute myocardial infarction2002In: Svenskt kardiovaskulärt vårmöte,2002, 2002Conference paper (Other academic)
  • 2.
    Järemo, Petter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Chlamydia pneumoniae och aterioskleros i kranskärlen2003In: Svenskt kardiovaskulärt vårmöte,2003, 2003Conference paper (Other academic)
  • 3.
    Järemo, Petter
    Department of Clinical Chemistry, Örebro Medical Center Hospital, Örebro, Sweden.
    Computerised method for recording platelet density distribution1995In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 54, no 5, p. 304-309Article in journal (Refereed)
    Abstract [en]

    In the present study a computerized apparatus was employed for scanning light transmission variations along test tubes containing density-separated platelets. The device consists of a stepping motor, a stationary halogen lamp and a photopotentiometer connected to a personal computer. Anticoagulated whole blood was layered on a preformed continuous Percoll gradient having a density span from 1090 kg/l (bottom) to 1040 kg/l (top). After centrifugation at 3400g for 1.5 hours, high-density cells (i.e. erythrocytes) pass through to the bottom of the test tube and the lighter platelets remain in the gradient. The test tube is moved by the computer between the halogen lamp and the photopotentiometer. Transmission variations along the gradient were recorded and registered in the computer. Density markers beads were used as an internal standard and platelet peak density was determined. After perforating the test tube the gradient was divided into 45 aliquots. In all fractions determination of platelet counts and mean platelet volume was carried out. In addition, in the aliquots having a platelet count > 20 × 1012/l the ratio β-thromboglobulin per platelet was also determined. The platelet distribution in the gradient was illustrated graphically. A good agreement was found when comparing platelet distributions in the gradients and light transmission variations along the test tubes.

  • 4.
    Järemo, Petter
    Department of Internal Medicine, The Vrinnevi Hospital, Norrköping, Sweden.
    Evidence that Chlamydia pneumoniae affects platelet activity in patients with acute myocardial infarction and ST-segment elevations2001In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 33, no 10, p. 747-748Article in journal (Refereed)
    Abstract [en]

    This study concerns platelet activity at myocardial infarctions and possible relationships with Chlamydia pneumoniae seroreactivity. Fourteen patients with acute myocardial infarction and ST-segment elevations were enrolled. They all received thrombolytic therapy. The subjects were examined within 24 h after hospital admission (Day 1) and after 6 months of recovery. On Day 1, C. pneumoniae IgM antibody titres were analysed and on Day 1 and during recovery C. pneumoniae IgG and soluble P-selectin were determined. P-selectin was used to estimate platelet activation. C. pneumoniae IgM titres at the infarction were closely related to both Day 1 IgG titres (r = 0.6; p < 0.05) and to IgG levels after 6 months (r = 0.8; p < 0.01). These results indicate a possible reactivation of a chronic infection. C. pneumoniae IgM was related to platelet activation. The correlation coefficient was r = 0.7 (p < 0.01) when comparing IgM titres with Day 1 plasma P-selectin. A similar relationship was found when comparing IgM and recovery P-selectin (r = 0.8; p < 0.01). The pathogen appears to contribute to platelet responses occurring during myocardial infarctions with ST-segment elevations. It is concluded that an ongoing reactivation of a chronic infection is related to increased platelet activity.

  • 5.
    Järemo, Petter
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Platelets and the inflammatory response in coronary heart disease2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The thesis investigates a new invented computerised apparatus suitable for determining platelet density distribution and peak platelet density in undisturbed linear Percoll™ gradients. The device measures light transmission through test tubes containing density-separated platelets. The transmission reflects the distribution of platelets in the gradient. Coloured particles (density marker beads™) with known density are used as calibration. Consequently, the technique makes it possible to determine peak platelet density by comparing the position of the platelet peak in the gradient with the locations of the beads. The thesis describes the construction of the device and investigates its reliability (paper I). A subsequent article (II) compares platelet density alterations and changes of platelet reactivity as estimated from the ADP-evoked platelet fibrinogen binding. We examined individuals with stable angina pectoris (n=18) subject to coronary angiography. Sampling was carried out immediately before angiography and 24 hours thereafter. In a further study (paper III) platelet density was measured in patients having acute myocardial infarctions with ST-segment elevations (STEMI) (n=36). Platelet counts and volumes were also determined. Soluble P-selectin was used to assess platelet activity. The neutrophil and monocyte counts were used to estimate the inflammatory response. Myeloperoxidase and interleukin 6 (IL-6) were employed to quantify neutrophil and monocyte activity, respectively. All measures except platelet density were repeated after 6 months of recovery.

    The second part of the thesis (papers IV and V) investigates Chlamydia pneumoniae in coronary heart disease. Paper IV studies a cohort (n=92) with stable angina pectoris. C. pneumoniae IgG was compared with disease severity i.e. the number of diseased coronary arteries (1-3) as determined by coronary angiography. Determination of the following was carried out before angiography: C. pneumoniae IgG, neutrophil count, myeloperoxidase and IL-6. Article V examines if the organism affects platelet activity in acute STEMI (n=I4). In this study C. pneumoniae IgM and IgG together with soluble P-selectin were determined on day I. Except for IgM the measures were repeated after 6 months. Finally, in the last article (paper VI) individual heterogeneity of platelet inhibition after a clopidogrel-loading dose was explored. Platelet reactivity as estimated from the ADP-evoked platelet fibrinogen binding was determined before angiography, stenting and the clopidogrel load (day I). The analysis was repeated after 24 hours (day 2). The thesis demonstrates that the optical apparatus is technically reliable (paper I). Healthy individuals repeatedly have platelet density subpopulations as evidenced from additional transmission peaks (paper I). The subpopulations frequently display enhanced a-granule content as expected from their positions in the gradient (paper I). The second paper shows that platelet density alterations are inversely related to changes of platelet reactivity (paper II). Decreased platelet count and an elevated inflammatory response are features of acute STEMI (paper III). We demonstrate that some patients have substantial inflammatory reactions whereas others had lower inflammatory responses. The difference persisted in the recovery. Compared to subjects with higher platelet density, individuals with lower/disturbed density displayed more severe inflammatory characteristics (paper III). Manuscript IV shows that C. pneumoniae is associated to the severity of coronary atherosclerosis as estimated from to coronary angiography. Paper V reveals that elevated C. pneumoniae IgM at the acute STEMI is related to enhanced soluble P-selectin. Both parameters proved to be associated with IgG both at the MI and after 6 months of recovery (paper V). Thus, enhanced soluble P-selectin at the STEMI is associated with a reactivation of a chronic C. pneumoniae infection. Finally, the thesis shows a substantial individual heterogeneity of platelet inhibition after a clopidogrel load (paper VI). Some individuals had strong inhibition most likely susceptible to bleedings. Others had weak reactions after clopidogrel exposure indicating elevated risk for thrombotic events.

    List of papers
    1. Computerised method for recording platelet density distribution
    Open this publication in new window or tab >>Computerised method for recording platelet density distribution
    1995 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 54, no 5, p. 304-309Article in journal (Refereed) Published
    Abstract [en]

    In the present study a computerized apparatus was employed for scanning light transmission variations along test tubes containing density-separated platelets. The device consists of a stepping motor, a stationary halogen lamp and a photopotentiometer connected to a personal computer. Anticoagulated whole blood was layered on a preformed continuous Percoll gradient having a density span from 1090 kg/l (bottom) to 1040 kg/l (top). After centrifugation at 3400g for 1.5 hours, high-density cells (i.e. erythrocytes) pass through to the bottom of the test tube and the lighter platelets remain in the gradient. The test tube is moved by the computer between the halogen lamp and the photopotentiometer. Transmission variations along the gradient were recorded and registered in the computer. Density markers beads were used as an internal standard and platelet peak density was determined. After perforating the test tube the gradient was divided into 45 aliquots. In all fractions determination of platelet counts and mean platelet volume was carried out. In addition, in the aliquots having a platelet count > 20 × 1012/l the ratio β-thromboglobulin per platelet was also determined. The platelet distribution in the gradient was illustrated graphically. A good agreement was found when comparing platelet distributions in the gradients and light transmission variations along the test tubes.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84674 (URN)10.1111/j.1600-0609.1995.tb00690.x (DOI)
    Available from: 2012-10-17 Created: 2012-10-17 Last updated: 2017-12-07Bibliographically approved
    2. Inverse relationship between platelet density and reactivity alterations at coronary angiography
    Open this publication in new window or tab >>Inverse relationship between platelet density and reactivity alterations at coronary angiography
    Show others...
    2001 (English)In: Haemostasis, ISSN 0301-0147, E-ISSN 1423-0038, Vol. 31, no 1, p. 55-60Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Basel: S. Karger, 2001
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-74256 (URN)10.1159/000048045 (DOI)
    Available from: 2012-01-22 Created: 2012-01-22 Last updated: 2017-12-08Bibliographically approved
    3. Elevated inflammatory parameters are associated with lower platelet density in acute myocardial infarctions with ST-elevation
    Open this publication in new window or tab >>Elevated inflammatory parameters are associated with lower platelet density in acute myocardial infarctions with ST-elevation
    2000 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 100, no 6, p. 471-478Article in journal (Refereed) Published
    Abstract [en]

    Objective: Platelets and granulocytes play important roles in coronary disorders. We therefore, investigated platelet and granulocyte alterations in myocardial infarctions (MIs).

    Patients and study design: A total of 36 individuals having MI with raised ST-segments who were receiving thrombolytic therapy were studied. Sampling was carried out after thrombolysis within 24 h after hospital admission. After 3 to 6 months of recovery, 25 patients were reinvestigated. At the infarction, peak platelet density was determined using a special designed computerised apparatus. In addition, we did counts on platelets, neutrophils and monocytes. Moreover, plasma levels of soluble P-selectin, myeloperoxidase and interleukin 6 were determined to estimate the degree of platelet, neutrophil and monocyte activation, respectively. Peak platelet density was analysed at the MI. All other parameters were determined at the acute event and at recovery.

    Results: At the MI, compared to the recovery, platelet counts were lower (P<.001). In addition, increased neutrophil counts (P<.001), elevated monocyte counts (P<.001), enhanced myeloperoxidase (P<.001) and interleukin 6 (P<.001) levels were demonstrated. We failed to show elevated soluble P-selectin. Compared to individuals with ST-segment elevations and low platelet density (≤1.058 kg/l), patients having peak platelet densities >1.058 kg/l displayed lower neutrophil counts (P<.01) and decreased interleukin 6 levels (P<.01). Furthermore, we demonstrate that individuals with higher inflammatory response at the MI had higher neutrophil (r=.6; P<.01) and higher monocyte counts (r=.6; P<.001) at recovery.

    Conclusion: We conclude that MI is associated with an inflammatory response. However, a subgroup of patients having MI with ST-elevations and low peak platelet density was identified. Compared to subjects with higher platelet density, they had more severe inflammatory characteristics. The differences persisted during recovery.

    Keywords
    interleukin 6, myocardial infarction, neutrophil granulocytes, platelets, platelet density, P-selectin
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26960 (URN)10.1016/S0049-3848(00)00366-2 (DOI)11593 (Local ID)11593 (Archive number)11593 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. A significant relationship between Chlamydia pneumoniae seroreactivity and the severity of coronary atherosclerosis
    Open this publication in new window or tab >>A significant relationship between Chlamydia pneumoniae seroreactivity and the severity of coronary atherosclerosis
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background. Clinical evidence supporting a causal role of Chlamydia pneumoniae in the process of atherosclerosis is limited. It is also uncertain if the organism participates in the inflammatory response in stable angina pectoris. The current study investigates C. pneumoniae IgG and markers reflecting the inflammatory response in stable angina pectoris. The data were subsequently compared with the extent of coronary atherosclerosis.

    Setting. Department of Cardiology, Linköping University Hospital, Linköping, Sweden.

    Experimental protocol. We investigated 92 patients with stable angina pectoris subject to coronary angiography to assess chest pain Before angiography C. pneumoniae IgG, neutrophil count and plasma levels of myeloperoxidase and interleukin 6 were analysed. The number of major coronary arteries (1-3) having at least one diameter narrowing(=> 50%) stenosis was determined. The patients were divided into two equal sized groups according to C. pneumoniae IgG levels.

    Results. Subjects with higher antibody concentrations had a more severe disease. The number of diseased arteries was 2.1±0.8(SD) and 1.4±0.6(SD) for the two groups, respectively. The difference proved to he highly significant (p<0.0001). The groups did not differ with respect to inflammatory parameters.

    Conclusion. This study with 92 consented individuals with stable angina pectoris suggests a causative relationship between C. pneumoniae IgG seroreactivity and the degree of coronary atherosclerosis. It does not, however, prove causality. Thus, it is likely that C. pneumoniae participates in the progression of atherosclerosis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84675 (URN)
    Available from: 2012-10-17 Created: 2012-10-17 Last updated: 2012-10-17Bibliographically approved
    5. Evidence that Chlamydia pneumoniae affects platelet activity in patients with acute myocardial infarction and ST-segment elevations
    Open this publication in new window or tab >>Evidence that Chlamydia pneumoniae affects platelet activity in patients with acute myocardial infarction and ST-segment elevations
    2001 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 33, no 10, p. 747-748Article in journal (Refereed) Published
    Abstract [en]

    This study concerns platelet activity at myocardial infarctions and possible relationships with Chlamydia pneumoniae seroreactivity. Fourteen patients with acute myocardial infarction and ST-segment elevations were enrolled. They all received thrombolytic therapy. The subjects were examined within 24 h after hospital admission (Day 1) and after 6 months of recovery. On Day 1, C. pneumoniae IgM antibody titres were analysed and on Day 1 and during recovery C. pneumoniae IgG and soluble P-selectin were determined. P-selectin was used to estimate platelet activation. C. pneumoniae IgM titres at the infarction were closely related to both Day 1 IgG titres (r = 0.6; p < 0.05) and to IgG levels after 6 months (r = 0.8; p < 0.01). These results indicate a possible reactivation of a chronic infection. C. pneumoniae IgM was related to platelet activation. The correlation coefficient was r = 0.7 (p < 0.01) when comparing IgM titres with Day 1 plasma P-selectin. A similar relationship was found when comparing IgM and recovery P-selectin (r = 0.8; p < 0.01). The pathogen appears to contribute to platelet responses occurring during myocardial infarctions with ST-segment elevations. It is concluded that an ongoing reactivation of a chronic infection is related to increased platelet activity.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26961 (URN)10.1080/003655401317074545 (DOI)11594 (Local ID)11594 (Archive number)11594 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    6. Individual variations of platelet inhibition after loading doses of clopidogrel
    Open this publication in new window or tab >>Individual variations of platelet inhibition after loading doses of clopidogrel
    2002 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 252, no 3, p. 233-238Article in journal (Refereed) Published
    Abstract [en]

    Objective.  To investigate individual variations of platelet inhibition after clopidogrel-loading doses.

    Setting.  Department of Cardiology, Linköping University Hospital, Linköping, Sweden.

    Subjects.  Individuals with stable angina pectoris (n = 18) subject to percutaneous coronary interventions (PCI) and subsequent stenting were investigated.

    Methods and experimental protocol.  A 300-mg clopidogrel loading dose was administrated immediately after stenting (day 1) followed by an additional 75 mg clopidogrel after 24 h (day 2). The ADP-evoked platelet fibrinogen binding was analysed to estimate platelet reactivity immediately before angiography and on day 2. A flow cytometry technique was used with two ADP solutions (final concentrations 0.6 and 1.7 μmol L−1) employed as platelet activating agents. Soluble P-selectin was used as a marker of platelet activity.

    Results.  When using 1.7 μmol L−1 ADP to activate platelets four individuals had a strong inhibition (i.e. platelet reactivity <10% of the day 1-value day 2). In contrast, five patients demonstrated a weak inhibition (i.e. platelet reactivity >60% of the day 1-value day 2). Similar results were obtained when using 0.6 μmol L−1 ADP as a platelet-activating agent. Clopidogrel, however, fails to suppress platelet activity as estimated from soluble P-selectin.

    Conclusions.  Clopidogrel evoked platelet inhibition exhibits a considerable individual heterogeneity. Some individuals only had weak responses whereas others displayed strong platelet inhibition. The present flow cytometry technique appears suitable for identifying patients with abnormal reactions after clopidogrel exposure.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25248 (URN)10.1046/j.1365-2796.2002.01027.x (DOI)9687 (Local ID)9687 (Archive number)9687 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
  • 6.
    Järemo, Petter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Stora individuella variationer i effekten an klopidogrel2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. naArticle in journal (Other academic)
  • 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 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.

  • 8.
    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.

  • 9.
    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

  • 10.
    Järemo, Petter
    et al.
    Department of Internal Medicine, Vrinnevisjukhuset, Norrköping, Sweden.
    Hansson, G.
    Department of Internal Medicine, Vrinnevisjukhuset, Norrköping, Sweden.
    Nilsson, O.
    Department of Internal Medicine, Vrinnevisjukhuset, Norrköping, Sweden.
    Elevated inflammatory parameters are associated with lower platelet density in acute myocardial infarctions with ST-elevation2000In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 100, no 6, p. 471-478Article in journal (Refereed)
    Abstract [en]

    Objective: Platelets and granulocytes play important roles in coronary disorders. We therefore, investigated platelet and granulocyte alterations in myocardial infarctions (MIs).

    Patients and study design: A total of 36 individuals having MI with raised ST-segments who were receiving thrombolytic therapy were studied. Sampling was carried out after thrombolysis within 24 h after hospital admission. After 3 to 6 months of recovery, 25 patients were reinvestigated. At the infarction, peak platelet density was determined using a special designed computerised apparatus. In addition, we did counts on platelets, neutrophils and monocytes. Moreover, plasma levels of soluble P-selectin, myeloperoxidase and interleukin 6 were determined to estimate the degree of platelet, neutrophil and monocyte activation, respectively. Peak platelet density was analysed at the MI. All other parameters were determined at the acute event and at recovery.

    Results: At the MI, compared to the recovery, platelet counts were lower (P<.001). In addition, increased neutrophil counts (P<.001), elevated monocyte counts (P<.001), enhanced myeloperoxidase (P<.001) and interleukin 6 (P<.001) levels were demonstrated. We failed to show elevated soluble P-selectin. Compared to individuals with ST-segment elevations and low platelet density (≤1.058 kg/l), patients having peak platelet densities >1.058 kg/l displayed lower neutrophil counts (P<.01) and decreased interleukin 6 levels (P<.01). Furthermore, we demonstrate that individuals with higher inflammatory response at the MI had higher neutrophil (r=.6; P<.01) and higher monocyte counts (r=.6; P<.001) at recovery.

    Conclusion: We conclude that MI is associated with an inflammatory response. However, a subgroup of patients having MI with ST-elevations and low peak platelet density was identified. Compared to subjects with higher platelet density, they had more severe inflammatory characteristics. The differences persisted during recovery.

  • 11.
    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.

  • 12.
    Järemo, Petter
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Fransson, Sven Göran
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences.
    Richter, Arina
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Individual variations of platelet inhibition after loading doses of clopidogrel2002In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 252, no 3, p. 233-238Article in journal (Refereed)
    Abstract [en]

    Objective.  To investigate individual variations of platelet inhibition after clopidogrel-loading doses.

    Setting.  Department of Cardiology, Linköping University Hospital, Linköping, Sweden.

    Subjects.  Individuals with stable angina pectoris (n = 18) subject to percutaneous coronary interventions (PCI) and subsequent stenting were investigated.

    Methods and experimental protocol.  A 300-mg clopidogrel loading dose was administrated immediately after stenting (day 1) followed by an additional 75 mg clopidogrel after 24 h (day 2). The ADP-evoked platelet fibrinogen binding was analysed to estimate platelet reactivity immediately before angiography and on day 2. A flow cytometry technique was used with two ADP solutions (final concentrations 0.6 and 1.7 μmol L−1) employed as platelet activating agents. Soluble P-selectin was used as a marker of platelet activity.

    Results.  When using 1.7 μmol L−1 ADP to activate platelets four individuals had a strong inhibition (i.e. platelet reactivity <10% of the day 1-value day 2). In contrast, five patients demonstrated a weak inhibition (i.e. platelet reactivity >60% of the day 1-value day 2). Similar results were obtained when using 0.6 μmol L−1 ADP as a platelet-activating agent. Clopidogrel, however, fails to suppress platelet activity as estimated from soluble P-selectin.

    Conclusions.  Clopidogrel evoked platelet inhibition exhibits a considerable individual heterogeneity. Some individuals only had weak responses whereas others displayed strong platelet inhibition. The present flow cytometry technique appears suitable for identifying patients with abnormal reactions after clopidogrel exposure.

  • 13.
    Järemo, Petter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Milovanovic, M
    Lindahl, TL
    Richter, Arina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Elevated platelet reactivity in stable angina pectoris without significant coronary flow obstruction2005In: Svenskt kardiovaskulärt vårmöte,2005, 2005Conference paper (Other academic)
  • 14.
    Järemo, Petter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Milovanovic, M
    Richter, Arina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Gender and stable angina pectrois: women have greater thrombin-evoked platelet activity but similar ADP-induced platelet responses.2004In: The 10th Erfurt Conference on Platelets,2004, 2004Conference paper (Other academic)
  • 15.
    Järemo, Petter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Milovanovic, M
    Richter, Arina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    In stable angina pectoris females have more reactive platelets than males2004In: Svenskt kardiovaskulärt vårmöte,2004, 2004Conference paper (Other academic)
  • 16.
    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.

  • 17.
    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.

  • 18.
    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.

  • 19.
    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.

  • 20.
    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.

     

  • 21.
    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)
  • 22.
    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)
  • 23.
    Järemo, Petter
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Richter, Arina
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    A significant relationship between Chlamydia pneumoniae seroreactivity and the severity of coronary atherosclerosisManuscript (preprint) (Other academic)
    Abstract [en]

    Background. Clinical evidence supporting a causal role of Chlamydia pneumoniae in the process of atherosclerosis is limited. It is also uncertain if the organism participates in the inflammatory response in stable angina pectoris. The current study investigates C. pneumoniae IgG and markers reflecting the inflammatory response in stable angina pectoris. The data were subsequently compared with the extent of coronary atherosclerosis.

    Setting. Department of Cardiology, Linköping University Hospital, Linköping, Sweden.

    Experimental protocol. We investigated 92 patients with stable angina pectoris subject to coronary angiography to assess chest pain Before angiography C. pneumoniae IgG, neutrophil count and plasma levels of myeloperoxidase and interleukin 6 were analysed. The number of major coronary arteries (1-3) having at least one diameter narrowing(=> 50%) stenosis was determined. The patients were divided into two equal sized groups according to C. pneumoniae IgG levels.

    Results. Subjects with higher antibody concentrations had a more severe disease. The number of diseased arteries was 2.1±0.8(SD) and 1.4±0.6(SD) for the two groups, respectively. The difference proved to he highly significant (p<0.0001). The groups did not differ with respect to inflammatory parameters.

    Conclusion. This study with 92 consented individuals with stable angina pectoris suggests a causative relationship between C. pneumoniae IgG seroreactivity and the degree of coronary atherosclerosis. It does not, however, prove causality. Thus, it is likely that C. pneumoniae participates in the progression of atherosclerosis.

  • 24.
    Järemo, Petter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Richter, Arina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Neutrophils, smoking and coronary heart disease2003In: Heart, ISSN 1355-6037, E-ISSN 1468-201XArticle in journal (Other academic)
  • 25.
    Järemo, Petter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Starkhammar, C
    Östergötlands Läns Landsting, Public Dental Service.
    Lundström, Å
    Östergötlands Läns Landsting, Public Dental Service.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Richter, Arina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Inverse relationship between the severity of gingivitis and platelet reactivity in stable angina pectoris [6]2007In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 5, no 2, p. 422-423Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 26.
    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.

  • 27.
    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.

  • 28.
    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.

  • 29.
    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.

     

  • 30.
    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.

  • 31.
    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.

  • 32.
    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.

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