Inverse relationship between the severity of gingivitis and platelet reactivity in stable angina pectoris.
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Publications and source records attributed to P Järemo.
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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.
BACKGROUND: The aim of this study was to compare Chlamydia pneumoniae IgG and the extent of coronary atherosclerosis. METHODS: We investigated 92 patients with stable angina pectoris who underwent coronary angiography to assess chest pain. Before angiography, C. pneumoniae IgG was analyzed. The number of major coronary arteries (1-3) having at least one diameter narrowing (>/=50%) stenosis was determined. The patients were divided into two groups of equal size, according to C. pneumoniae IgG levels. One group included individuals with C. pneumoniae IgG levels exceeding 46 enzyme-immuno-units (EIU)/L and the other consisted of subjects with IgG concentrations below 46 EIU/L. RESULTS: Subjects with higher antibody concentrations had a more severe disease. The number of diseased arteries was 2.1+/-0.8 (S.D.) and 1.4+/-0.6 (S.D.) for the two groups, respectively. The difference is highly significant (p<0.0001). CONCLUSIONS: This study suggests a causative relationship between C. pneumoniae IgG and the degree of coronary atherosclerosis. It does not, however, prove causality.
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 gradient in a plasma-free milieu containing EDTA that binds soluble Ca(2+). 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 Ca(2+) 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.
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 micromol L-1) employed as platelet activating agents. Soluble P-selectin was used as a marker of platelet activity. RESULTS: When using 1.7 micromol 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 micromol 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.
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.
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<0.001). In addition, increased neutrophil counts (P<0.001), elevated monocyte counts (P<0.001), enhanced myeloperoxidase (P<0.001) and interleukin 6 (P<0.001) levels were demonstrated. We failed to show elevated soluble P-selectin. Compared to individuals with ST-segment elevations and low platelet density (less than or = 1.058 kg/l), patients having peak platelet densities >1.058 kg/l displayed lower neutrophil counts (P<0.01) and decreased interleukin 6 levels (P<0.01). Furthermore, we demonstrate that individuals with higher inflammatory response at the MI had higher neutrophil (r = 0.6; P<0.01) and higher monocyte counts (r = 0.6; P<0.001) at recovery. CONCLUSION: W 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.
BACKGROUND: This study evaluated whether it is possible to estimate the severity of pre-eclampsia through in vitro measurements of platelet and granulocyte parameters. EXPERIMENTAL PROTOCOL: Eighteen pre-eclamptic women in the third-trimester of pregnancy and 11 women in the third-trimester of normal pregnancies were included in the study. Three to 12 months after delivery, 15 patients with pre-eclampsia and all the subjects with normal pregnancies were re-examined. Before delivery, peak platelet density was determined using a specially designed apparatus. Before and 3-12 months after delivery the following were measured: platelet counts, mean platelet volume and neutrophil and monocyte counts. Furthermore, circulating P-selectin, interleukin-6 and myeloperoxidase were determined to estimate platelet, monocyte and granulocyte activities, respectively. RESULTS: Compared to their results after delivery, pre-eclamptic females demonstrated lower platelet counts (P < 0.001) and raised mean platelet volumes (P < 0.01). Both pre-eclamptic women (P < 0.01) and normal pregnancies (P < 0.05) demonstrated elevated soluble P-selectin at pregnancy. Then pre-eclamptic women had advanced neutrophil counts (P < 0.01) but normal pregnancies showed a similar phenomenon (P < 0.001). Interleukin-6 remained normal during pregnancy. Plasma myeloperoxidase levels were lower both in pre-eclampsia (P < 0.05) and in normal pregnancies (P < 0.001). In pre-eclampsia elevated blood pressure was related to higher mean platelet volumes (P < 0.05). Furthermore, a group of pre-eclamptic females whose platelets had disturbed density distribution displayed elevated mean platelet volumes (P < 0.01). CONCLUSIONS: The present work demonstrates considerable platelet alterations in pre-eclampsia. We failed to show granulocyte involvement in the pathogenesis of the disease. Severe pre-eclampsia is related to elevated mean platelet volumes. The latter parameter is associated with disturbed density distribution. It appears possible to estimate disease severity from measurements of platelet density and volume.
The study investigates platelet concentrates (PCs) contaminated with Staphylococcus epidermidis. The work was conducted using 12 pairs of PCs. Light transmission through the PCs was observed over 7 days. Immediately after preparation, one PC was inoculated with Staphylococcus epidermidis (17-43 colony forming units (CFU)/ ml) and the other served as a non-contaminated control. In the contaminated PCs the CFU/ml and swirling were determined on days 1, 3 and 7. In all PCs determination of pH and the extent of shape change (ESC) was carried out on days 3 and 7. All contaminated PCs had visible swirling on day 3 but they contained 2.0 X 10 4 to 9.0 X 10 8 CFU/ml. pH (P=0.05) and ESC (P<0.05) then were slightly lower. On day 7, eight of 12 of the contaminated PCs failed to display transmission changes despite deranged analytical results and impaired swirling. During early storage the contaminated units had unimpaired swirling and only slightly impaired in vitro quality. They appear to be difficult to identify in the routine.
This study aims to compare platelet density in myeloproliferative disorders (essential thrombocythemia (ET) and polycythemia vera (PV)) with platelet density of healthy subjects. Platelet density peaks were determined using a specially designed apparatus for scanning light transmission variations along test tubes containing density-separated platelets. Eighteen patients with myeloproliferative disorders (nine ET and nine PV) were compared with a control group consisting of 12 healthy volunteers. Compared with healthy volunteers, patients with myeloproliferative disorders had significantly lower platelet peak density ( P< 0.001). It is concluded that determination of peak platelet density may be a useful tool for excluding ET and PV. A high platelet density peak makes a clonal disorder less likely and a low density peak would confirm the suspicion.
This study aims to relate the duration of light transmission changes (LTCs) through platelet concentrates (PCs) to the results of a panel analytical procedures, many of which have correlated with platelet in vivo viability. LTCs of 16 PCs stored in P1-732 containers were studied over 10 d. On d 1, platelet counts and total PC ATP content were determined. On d 7, determination of the following parameters was carried out: pH, bicarbonate, the rate of oxygen consumption, the dispersion of the size distribution, the total platelet ATP content, the extent of shape change (ESC), the osmotic reversal reaction and extracellular lactate dehydrogenase (LDH) level. In addition, the rate of lactate production was determined over storage. A second series consisting of 18 PCs stored in P1-146 containers was monitored over 7 d. Mean platelet volume (MPV) was determined on d 3 and 7 and ESC was analysed on d 3. LTCs correlated significantly with pH, bicarbonate, the rate of oxygen consumption, increased platelet size distribution and decreased ESC. In addition, significant correlations were found when comparing LTCs with MPV(s). This study demonstrates that LTCs are closely related to parameters reflecting platelet metabolism.
OBJECTIVE: The present study investigates platelet density and mean platelet volume (MPV) in active inflammatory bowel disease (IBD). EXPERIMENTAL PROTOCOL: 27 patients with IBD (18 ulcerative colitis and 9 Crohn's disease) were compared to 12 healthy volunteers. 18 subjects had active disease. Platelet counts and mean platelet volume (MPV) were determined. Thereafter, platelets were separated according to density on a linear preformed Percoll gradient. A computerized device was employed for scanning transmission variations and thus the platelet distribution in the gradient and the platelet peak were identified. RESULTS AND CONCLUSIONS: Subjects with active IBD had greater platelet density (p = 0.02) and lower MPVs (p < 0.001). These findings may indicate augmented platelet granule content. The study also demonstrates that a low MPV is associated with active IBD.
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 performed 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 x 10(12)/l the ratio beta-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.
BACKGROUND: The study examines Pall Pl-50 platelet filters with respect to their influence on some biochemical properties of platelet concentrates. MATERIAL AND METHODS: Ten pairs of pooled platelet preparations, each consisting of 3 platelet concentrates, were studied. On day 1, one of the preparations was filtered and the other served as an identical non-filtered control. Immediately after filtration platelet counts, the levels of desarginated activated complement factor 3 (C3a), extracellular levels of lactate dehydrogenase (LDH) and extracellular and total concentrations of platelet factor 4 (PF4) were determined in both concentrates. After 5 days sterility testing and determination of extracellular levels of PF4 and LDH were performed. RESULTS: Extracellular concentrations of PF4 and C3a decreased immediately after filtration (p < 0.01). Furthermore, Pall Pl-50 filters caused cellular instability reflected by an increased release of PF4 (p < 0.01) during subsequent storage. CONCLUSION: Platelet concentrates filtered with Pall Pl-50 would not appear suitable for storage.
In the present work a computerised method for continuous monitoring of light transmission through platelet packs was evaluated. On series (Series 1) of 50 platelet concentrates was studied over a 5-day period, and thereafter the pH, extracellular lactate dehydrogenase (LDH) and platelet factor 4 (PF4) in the concentrates were determined. A second series (Series 2) of 52 concentrates was also monitored over 5 days, and thereafter the pH, extracellular LDH and intracellular concentrations of ATP, ADP and AMP were determined. 11 and 14 of the concentrates of Series 1 and 2, respectively, demonstrated long lasting transmission increases (> or = 3.0 days). In the total of 102 platelet concentrates 34 were observed to have late (< 1.0 day) or no transmission increase. It is concluded, that the present optical method identifies both a group of platelet concentrates having long lasting transmission increases and a group consisting of platelet concentrates having late or no transmission increase. Compared to the latter concentrates preparations with long lasting transmission changes demonstrated significant biochemical alterations. These observations could be applicable in the quality control of platelet concentrates.
The present study compares some properties of platelet concentrates, i.e. their ability to transmit light and the degree of platelet lysis and the deterioration of the platelet membrane glycoprotein Ib (GPIb). Extracellular levels of glycocalicin and lactate dehydrogenase (LDH) served as indicators for the proteolytic cleavage of GPIb and platelet lysis, respectively. The light transmission of 16 platelet apheresis concentrates was monitored continuously during storage using a specially designed apparatus. Determination of platelet counts and extracellular glycocalicin levels was carried out on day 1. In addition, after 7 days of storage extracellular concentrations of LDH and glycocalicin were determined. After 7 days highly significant correlations were found both when comparing light transmission changes and extracellular glycocalicin levels (r = 0.78; p < 0.001) and when comparing light transmission changes and extracellular concentrations of LDH (r = 0.83; p < 0.001).
The present study examined biochemical storage lesions in 58 buffy coats (BCs) intended as the raw material for platelet concentrates. The work was conducted in three series; the aims were to investigate: (a) the storage quality of BCs obtained from the routine production (series I), (b) whether improvement in platelet quality could be achieved by continuous agitation during storage (series II), and (c) whether macroscopic aggregate formation indicates platelet damage (series III). Series I and II consisted of 20 BCs each. Series III compared ten BCs with visible clumping with eight BCs not demonstrating macroscopic aggregates. In series I and II platelet counts and platelet factor 4 (PF4) release were determined after 1, 3, 5, and 24 h; lactate dehydrogenase (LDH) extracellular activity was measured after 1 and 24 h. In addition, in series I elastase concentrations were analyzed after 3, 5, and 24 h. Finally, in series III extracellular beta-thromboglobulin (beta-TG) levels were determined after 18-24 h. Low platelet counts, most likely reflecting the presence of aggregate formation, were found in 20% of the BCs (series I); in this series a total of 25% demonstrated increasing platelet counts, together with elevated PF4 and elastase, over the study period. Significant biochemical storage lesions were found after 5 and 24 h of storage. The study also demonstrated that continuous agitation during storage does not improve platelet quality (series II) and that BCs demonstrating visible clumping (series III) had augmented levels of extracellular beta-TG (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of the present study was to investigate how four different filters, i.e. Imugard IG500 (Terumo, Japan), Miropore (Miramed, Italy), Pall P1-100 (Pall, USA) and Sepacell P1-10A (Asahi, Japan) affect some biochemical properties of platelet concentrates. The work was conducted using 42 pairs of platelet concentrates. After 2 days of storage, one of the preparations was filtered and the other served as an unfiltered control. Immediately after filtration, determination of the platelet count, desarginated activated complement factor 3 (C3a des arg) and the extracellular and total concentrations of platelet factor 4 (PF4) and lactate dehydrogenase (LDH) were carried out on both these platelet concentrates. After an additional storage period of 3 d, extracellular concentrations of PF4 and LDH were determined on both concentrates. A significant decrease of extracellular PF4 concentration was found immediately after filtration when Pall P1-100 and Imugard IG500 were used. During the 3-d storage after filtration, the concentrates filtered with Imugard IG500 and Pall P1-100 demonstrated significantly higher platelet lysis as compared to the unfiltered controls. It is concluded that the present work demonstrates storage instability after filtration with Imugard IG500 and Pall P1-100. Therefore, platelet concentrates filtered with these filters would not appear to be suitable for storage.