Red blood cell transfusion in southern Finland from 2011 to 2016: a quality audit.

OBJECTIVES: The current trends in RBC use and pre- and post-transfusion Hb levels were analysed to improve practice and to provide international comparison. BACKGROUND: Indications for RBC transfusion have changed with growing scientific evidence. The lowest acceptable haemoglobin (Hb) level has decreased, and transfusing single units instead of pairs has become the new standard. Evidence-based guidelines and patient blood management (PBM) programmes increase clinician awareness of rational RBC use. In Finland, however, no formal PBM programme has been established to date. METHODS: The study was registry-based, retrospective and observational. All RBC transfusions for adult patients from 2011 to 2016 in the southern region of Finland were analysed. RESULTS: RBC usage decreased from 34·9 to 27·5 units per 1000 population (P < 0·001). The percentage of single-unit transfusions increased from 57·9 to 66·7%, and the median pre- and post-transfusion Hb levels decreased from 8·4 to 8·2 g dL-1 (P < 0·001) and 9·9 to 9·6 g dL-1 (P < 0·001), respectively. The proportion of transfusions with pre-transfusion Hb ≥ 9·0 g dL-1 decreased during the study period but remained high, being 29·5% in 2011 and still 25·2% in 2016. CONCLUSIONS: Consumption of RBCs has decreased despite aging population and increasing healthcare performance demands. The results indicate more rational and evidence-based RBC use. Nevertheless, the transfusion rate and pre- and post-transfusion Hb are still sufficiently high to enable more restrictive transfusion practice.

Health effects of reduced occupational sedentary behaviour in type 2 diabetes using a mobile health intervention: a study protocol for a 12-month randomized controlled trial-the ROSEBUD study.

BACKGROUND: Short-term trials conducted in adults with type 2 diabetes mellitus (T2DM) showed that reducing sedentary behaviour by performing regular short bouts of light-intensity physical activity enhances health. Moreover, support for reducing sedentary behaviour may be provided at a low cost via mobile health technology (mHealth). There are a wide range of mHealth solutions available including SMS text message reminders and activity trackers that monitor the physical activity level and notify the user of prolonged sitting periods. The aim of this study is to evaluate the effects of a mHealth intervention on sedentary behaviour and physical activity and the associated changes in health in adults with T2DM. METHODS: A dual-arm, 12-month, randomized controlled trial (RCT) will be conducted within a nationwide Swedish collaboration for diabetes research in primary health care. Individuals with T2DM (n = 142) and mainly sedentary work will be recruited across primary health care centres in five regions in Sweden. Participants will be randomized (1:1) into two groups. A mHealth intervention group who will receive an activity tracker wristband (Garmin Vivofit4), regular SMS text message reminders, and counselling with a diabetes specialist nurse, or a comparator group who will receive counselling with a diabetes specialist nurse only. The primary outcomes are device-measured total sitting time and total number of steps (activPAL3). The secondary outcomes are fatigue, health-related quality of life and musculoskeletal problems (self-reported questionnaires), number of sick leave days (diaries), diabetes medications (clinical record review) and cardiometabolic biomarkers including waist circumference, mean blood pressure, HbA1c, HDL-cholesterol and triglycerides. DISCUSSION: Successful interventions to increase physical activity among those with T2DM have been costly and long-term effectiveness remains uncertain. The use of mHealth technologies such as activity trackers and SMS text reminders may increase awareness of prolonged sedentary behaviour and encourage increase in regular physical activity. mHealth may, therefore, provide a valuable and novel tool to improve health outcomes and clinical management in those with T2DM. This 12-month RCT will evaluate longer-term effects of a mHealth intervention suitable for real-world primary health care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04219800 . Registered on 7 January 2020.

Serial measurements of plasma homocysteine levels in early and late phases of ischemic stroke.

High plasma levels of homocysteine (Hcy) may predispose to ischemic stroke (IS), but results of previous studies have been conflicting. We decided to determine in IS patients whether their Hcy levels are elevated, whether levels vary at different time points following stroke, whether levels are associated with stroke severity, outcome, recurrence, etiology, infarct volume, or risk factors, and whether levels are correlated with hemostatic factors or C-reactive protein values. We measured plasma Hcy levels in 102 consecutive IS patients on admission and at 1 week, 1 month, and 3 months after stroke and once in 102 control subjects. Hemostatic factors were measured in 55 patients. Compared with controls, plasma Hcy levels in patients were significantly lower on admission but not at later time points, with levels increasing by week and remaining at this level for 3 months. Hcy levels showed a positive correlation with age and a negative correlation with Mini-Mental State Examination (MMSE) scores. Plasma Hcy levels inversely correlated with plasminogen activator inhibitor type-1. Decreased Hcy levels on admission may reflect the strength of the acute-phase response rather than a pathogenetic event. The negative correlation between Hcy levels and MMSE scores is more probably age-related than stroke-related.

Flow cytometric detection of residual disease in acute leukemia by assaying blasts co-expressing myeloid and lymphatic antigens.

A method employing CD45-gating of blast cells was evaluated for the flow cytometric detection of residual disease in CD19- and myeloid antigen-positive acute leukemia in morphologic remission. In the normal bone marrow, CD45-gating identified at least three populations of immature cells, one of which appeared to retain a minute fraction of CD19- and CD13/33-antigen co-expressing cells. In acute leukemia, CD45 expression separated the blast cell population from the normal marrow cell populations. In the majority of patients with CD19- and myeloid antigen-positive acute leukemia, subpopulations of blast cells with this mixed phenotype were detected during morphologic remission.

Flow cytometric analysis of glutathione-S-transferase-pi in acute leukemia.

Increased expression of glutathione-S-transferase isoenzyme pi (GST-pi) may account for drug resistance and treatment failure in hematologic malignancies when alkylating agents like cyclophosphamide, chlorambucil, busulfan and melphalan, or doxorubicin are used. We have studied the expression of GST-pi in peripheral blood lymphocytes of healthy blood donors. In peripheral and bone marrow lymphocytes/blasts of patients with other diseases than hematologic malignancies, and of patients with acute leukemia by using flow cytometry. We studied bone marrow cells of 35 patients diagnosed as having acute leukemia at initial presentation, 16 patients in the refractory stage, 20 in morphological remission and 15 controls. None of the samples obtained in remission contained more GST-pi-positive cells than the controls, whereas 51% of the samples obtained at diagnosis and 56% of those obtained in the refractory stage were GST-pi-positive. The mean proportion of GST-pi-positive cells in the lymphocyte/blast cell gate of bone marrow cells of controls was 2.6% and of patients with acute leukemia studied at diagnosis 16.6%, respectively. We analyzed the samples also for P-glycoprotein expression. There was a significant positive association between GST-pi and P-glycoprotein expression in acute leukemia.

Fresh frozen plasma reduces thrombin formation in newborn infants.

BACKGROUND: Newborn infants undergoing intensive care are at risk of bleeding and thrombotic complications. Fresh frozen plasma (FFP) is used in hope of preventing these complications, despite poorly defined effects on the coagulation system and lack of proven clinical efficacy. OBJECTIVES AND METHODS: We prospectively evaluated coagulopathy and the effect of standardized amount of FFP transfusion (10 mL kg-1 + 4 mL in 2 h) on various coagulation markers in 33 newborn infants during the first 24 h of intensive care. RESULTS: Increased levels of prothrombin fragment F1+2, thrombin-antithrombin complexes (TAT), and d-dimer were found prior to the transfusion in 97%, 81%, and 100% of the patients, respectively. FFP transfusion was associated with a decrease in F1+2 level in 26/32 (81%) of the patients. The extent of F1+2 decrease correlated with the pretransfusion F1+2 level (R = 0.65, P < 0.0001). The patient series was divided into two groups according to increasing pretransfusional F1+2 level: Group 1 (preFFP F1+2 > or = 2.35 nm, n = 16), Group 2 (F1+2 <2.35 nm, n = 16). In Group 1, F1+2 decreased on average 1.58 nm (P < 0.01) from the baseline during FFP transfusion but no significant change in the level of F1+2 during the transfusion was observed in Group 2. Pretransfusional levels of individual factors or prothrombin time (PT) did not correlate with the FFP-associated decrease in F1+2 level. CONCLUSIONS: In the patients with the highest pretransfusional thrombin formation, FFP had an acute thrombin-reducing effect. Pretransfusion thrombin generation markers, rather than PT or individual pro- and anticoagulants, may be helpful in identifying the patient who will have measurable coagulational effects induced by FFP.

Relation of inflammation to vascular function in patients with coronary heart disease.

Endothelium plays a pivotal role in the regulation of vascular relaxation. Inflammation may in turn induce endothelial dysfunction and thus increase the risk of atherothrombosis. We investigated 31 men with angiographically verified coronary heart disease, aged 57. 7+/-5.3 years, in regard to endothelium-dependent, acetylcholine-induced, and to endothelium-independent, sodium nitroprusside-induced vasodilatation in the forearm vasculature by strain-gauge plethysmography. Logistic regression analysis served to determine the relation between forearm vascular function and the inflammatory factors measured, concentration of C-reactive protein, subtypes of peripheral blood T-lymphocytes, and other factors potentially affecting endothelial function (lipoprotein and glucose levels). Concentration of C-reactive protein was an independent determinant of endothelium-dependent vascular function (P<0.001 for low dose acetylcholine, P=0.01 for high dose acetylcholine). Other determinants of endothelium-dependent vascular dysfunction were CD8-lymphocytes expressing ICAM-1 (P=0.001), antibodies to oxidized low-density lipoprotein (P<0.001), and body weight (P=0.007). The present data showed an association between inflammatory risk factors linked to atherothrombosis and endothelial dysfunction in coronary heart disease patients. It is possible that endothelial dysfunction in coronary heart disease patients is related to the chronic inflammation or infection coexisting with atherosclerosis.

Determination of anti-IgA antibodies with a flow cytometer-based microbead immunoassay (MIA).

A flow cytometer-based microbead immunoassay (MIA) was employed to detect anti-IgA antibodies in patients with IgA deficiency. 3 microns latex particles were coated with purified IgA and serum anti-IgA antibodies of the IgG class were detected with FITC-conjugated anti-human IgG. Antibodies against three different IgA preparations were tested from 22 patients samples as well as 20 controls and compared with a conventional enzyme-linked immunosorbent assay (ELISA) and a passive hemagglutination assay (HA). There was a very close correlation between the results obtained with the MIA and the ELISA assay and between MIA and the HA. Because of the low intra-assay variation and good linearity of the assay, the analysis of one single serum dilution was sufficient to determine the anti-IgA level of a patient and no titration series was required. We conclude that MIA is a satisfactory alternative method for routine anti-IgA antibody determinations. For laboratories already equipped with a flow cytometer the assay is cost effective.

Diagnostic significance of indium-111 granulocyte scintigraphy in febrile patients.

Sixty-eight patients with fever of unknown origin, 32 patients with postoperative fever, and 26 patients with therapy-resistant fever after bacteremia were investigated with [111In] granulocyte scintigraphy for the detection of abscesses. The results showed that the value of [111In]granulocyte scintigraphy in the detection of infectious foci vary in these three types of febrile conditions. The overall sensitivity and specificity were 86.5% and 87.8%, respectively. We observed, however, a relatively low predictive value of a positive result in the fever of unknown origin group (73.1%), and also a low predictive value of a negative result in the bacteremia group (66.7%). The C-reactive protein (CRP) levels in patients with a true-positive scintigram were significantly (p less than 0.001) higher than in patients with a true-negative scintigram. There was also a significant positive correlation (p less than 0.01) between the serum CRP concentration and the intensity of the granulocyte accumulations. There was no correlation between the peripheral leukocyte count or the erythrocyte sedimentation rate (ESR) and the intensity of the granulocyte uptake. Therefore CRP, but not the leukocyte count or ESR, appears useful for selecting the patients who benefit most from granulocyte scintigraphy.

Splenic dynamics of indium-111 labeled platelets in idiopathic thrombocytopenic purpura.

Splenic dynamics of 111In-labeled platelets and platelet-associated IgG in 33 patients with idiopathic thrombocytopenic purpura (ITP) were studied. Two half-lives were calculated for the biexponential splenic time-activity curve after i.v. injection of 111In-labeled platelets. There was no difference in the mean half-life of the rapid component of the splenic curve (ST1) when patients with negative or slightly positive platelet suspension immunofluorescence test (PSIFT) were compared to those with strongly positive PSIFT (3.0 +/- 0.7 min vs. 3.6 +/- 0.4, p greater than 0.05). Mean half-life of the slow component of the splenic curve (ST2) was found to be longer in patients with a strongly positive than a negative or weakly positive PSIFT (26 +/- 5 min vs. 13.2 +/- 1.0 min, p less than 0.01). It seems that determination of the two components of the splenic time-activity curve provides a useful method for studying platelet kinetics in ITP.

Flow cytometric analysis of terminal deoxynucleotidyl transferase. A simplified method.

The authors evaluated a new cell membrane permeabilization method for the flow cytometric detection of terminal deoxynucleotidyl transferase (TdT). In this method, gradient-separated leukocytes or unseparated blood or bone marrow cells were incubated in a commercially available diethylene glycol-based red blood cell lysing solution, which not only lyses red blood cells, but also permeabilizes leukocyte cell membranes; the light scattering properties of the cells are retained. The validity of the current method was demonstrated by the good concordance of the findings with previously published data as follows: (1) practically identical results were obtained when an established method for cell permeabilization was used in parallel on the same samples; (2) the proportion of TdT-positive cells in normal peripheral blood was negligible; (3) the proportion of TdT-positive cells in normal bone marrow averaged 1%, and a significant portion of TdT-positive cells in normal bone marrow expressed CD10 and CD34; and (4) TdT-positive cell populations were seen with the expected frequencies in various types of leukemia. This method for TdT flow cytometry provides significant advantages over previously used methods and is especially suitable for TdT detection in routine laboratories.

Platelet splenic transit times in idiopathic thrombocytopenic purpura. Compartmental vs. non-compartmental model.

Platelet splenic transit times following injection of autologous or homologous 111In-labeled platelets were studied in 42 patients with idiopathic thrombocytopenic purpura. The transit times were determined by two methods from the splenic time-activity curves recorded with a gamma camera: closed two-compartmental model and non-compartmental model (deconvolution analysis). By compartmental analysis the mean splenic transit time for platelets was 6.3 +/- 0.3 min (mean +/- S.E.) and by non-compartmental analysis 7.6 +/- 0.4 min for all cases studied. The mean splenic transit time for autologous platelets was significantly (p less than 0.001) shorter (5.1 +/- 0.3 min) in patients with platelet-associated IgG (measured by platelet suspension immunofluorescence test) than in those with no autoantibodies (7.1 +/- 0.4 min), when the compartmental model was employed. There was no significant difference between mean transit times for autologous platelets in antibody positive and negative patients when deconvolution analysis was applied, but the residue of the splenic transfer function was lower for antibody positive than negative patients (7.2 +/- 1.0% vs. 11.7 +/- 1.6%, p less than 0.05). It is concluded that in idiopathic thrombocytopenic purpura the presence of platelet-associated autoantibodies expands the splenic platelet pool and reduces recirculation of platelets.

Variability in platelet responses to collagen--comparison between whole blood perfusions, traditional platelet function tests and PFA-100.

The purpose of this study was to determine if the results obtained in platelet function tests and whole blood perfusions are associated with those in platelet function analyser (PFA)-100. We used collagen type I monomers and fibrils to analyse the distinct roles of glycoprotein (GP) Ia/IIa and other collagen receptors in flowing blood under a high shear rate (1600/s) and in aggregation studies. Also, anticoagulation [citrate vs. D-phenylalanyl-1-prolyl-1 arginine chloromethyl ketone (PPACK)] was varied to enhance the functions of GP Ia/IIa, since it has been shown that the cation-poor environment of citrated blood impairs GP Ia/IIa-dependent platelet recruitment. Large interindividual variability (45-fold) was detected in deposition of platelets in whole blood perfusions over collagen monomers, whereas this variation was only fourfold in fibrils. In PFA, this variation was reduced to 2.5-fold. However, platelet deposition on monomers is associated with epinephrine-enhanced PFA (r=-.49, P<.03), whereas platelet deposition on fibrils is correlated with adenosine diphosphate (ADP)-enhanced PFA (r=-.47, P<.05), suggesting a distinct synergism between epinephrine and monomers (GP Ia/IIa) as well as ADP with fibrils (other collagen receptors). Donors with 807 C/C polymorphism of GP Ia (n=14) had longer lag phase in aggregation experiments compared with C/T (n=7) both by monomers and fibrils (P<.04), but these polymorphisms with their mild impact on GP Ia/IIa activity did not markedly differ in other tests. In conclusion, the results obtained in perfusion studies and PFA experiments correlated, but PFA fails to reveal the large-scale variability related to collagen-induced platelet responses.

Haemostatic disturbances in burned patients during early excision and skin grafting.

Bleeding is a major problem during early excision of burned skin. Therefore, 13 severely burned adult patients operated on during the first week after the trauma were studied. Blood loss was replaced with crystalloids, colloids and packed red cell concentrates (PRC). After ten infused PRCs, four fresh frozen plasma (FFP) units were given and thereafter one FFP unit with one PRC unit. Arterial blood samples were drawn before anaesthesia (SO), during operation after every four units of PRC transfusion (S1-4), 4 h postoperatively (S5) and on the first postoperative morning (S6). Prothrombin time (%) and activated partial thromboplastin time (s) were abnormal before operation (median values 67%, range 22-99% and 44 s, range 30-86 s, respectively). Prothrombin time decreased during operation and reached the critical level for normal haemostasis at S2. Thrombelastography showed decreased clot formation rate and impaired fibrin platelet interaction peri- and postoperatively. Fibrinogen and factor VIII activity were high preoperatively (median 6.1 g/l and 253%) and the critical values for normal haemostasis were not reached. Burned patients have a consumption coagulopathy which, in combination with haemodilution during operation, results in a clinically significant deficiency of coagulation factors II, VII and X, in spite of reactive elevation of coagulation factor VIII and fibrinogen.

Endothelial release of tissue-type plasminogen activator and ischemia-induced vasodilatation are linked in patients with coronary heart disease.

Dysfunction in the vascular endothelium disturbs blood flow and predisposes individuals to atherosclerosis. Deteriorated fibrinolysis may further enhance the risk for atherothrombosis. We investigated 14 healthy volunteers and 24 patients with coronary heart disease. Endothelium-dependent (acetylcholine- and ischemia-induced) and endothelium-independent (nitroprusside-induced) vasodilatation in the forearm vasculature were studied using strain-gauge plethysmography, and the fibrinolytic system measured as the response of tissue plasminogen activator (t-PA) to provocation testing (20 min venous occlusion; VOT). When acetylcholine-induced vasodilatation was measured, endothelium-dependent vasodilatation differed between groups: those with coronary heart disease had a median value of 8.5 ml/min per 100 g tissue (25th to 75th percentile 4.8-10.3), compared with 11.6 ml/min per 100 g tissue (7.3-15.5) among healthy volunteers (P = 0.03). However, ischemia-induced vasodilatation showed no difference between the groups [26.8 (22.7-35.0) versus 29.1 (25.6-30.7) ml/min per 100 g tissue, respectively, NS]. Levels of t-PA after VOT also showed no difference between the groups [21.5 (16.5-31.9) versus 20.4 (11.8-31.5) ng/ml, respectively, NS]. Results of ischemia tests and levels of t-PA after VOT correlated only in patients with coronary heart disease (r = 0.5, P = 0.015), and not in healthy volunteers. We observed a positive correlation between endothelium-dependent vasodilatation function and endothelial release of t-PA. This indicates that the same mechanism that results in defective ischemia-induced endothelial relaxation in patients with coronary heart disease may also result in suppressed fibrinolytic capacity, thus making such patients more prone to atherothrombosis.

Association between high antistaphylolysin and teichoic acid antibody titres with rheumatic syndromes.

To analyse which rheumatic syndromes are associated with serological evidence of recent Staphylococcus aureus infection, we studied retrospectively 44 adult patients, gathered between 1979-1990, having an acute arthritis syndrome or an exacerbation in their chronic rheumatic disease and simultaneously a high antistaphylolysin (ASTA > 4,0) and/or high teichoic acid antibody titre (TAA > 8). Patients with septic arthritis or endoprosthetic infections were not included. 25 patients had arthritis/arthralgia associated with a known rheumatic disease, 9 patients had reactive arthritis and 8 patients had arthralgia. The frequency of HLA-B27 in tested patients was significantly higher in the whole patient group than in the healthy Finnish population (43% v 14%, p < 0.001). It is concluded that high ASTA and/or TAA titres are associated with various acute rheumatic syndromes including reactive arthritis.

Plasminogen activator inhibitor-1 in patients with ischemic stroke.

Low fibrinolytic activity may increase the risk of thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of the fibrinolytic system. We examined the PAI-1 levels in patients with ischemic stroke. Plasma levels of PAI-1 were measured using enzyme-linked immunosorbent assay (ELISA) in 55 consecutive patients (age 60.2 +/- 11.4, 40 males and 15 females) with ischemic stroke. The PAI-1 assessments as well as neurological examinations using validated stroke scales were conducted at admission and 1 week, 1 month, and 3 months after stroke. Sex- and age-matched controls (+/- 4 years) underwent plasma PAI-1 measurement once. Etiology of the stroke was classified using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. All pertinent stroke risk factors were recorded. All patients were contacted 3 years after stroke for recurrent vascular thrombotic disease. The plasma PAI-1 levels were 17.2 +/- 7.8 IU at admission, 11.2 +/- 9.2 IU at 1 week, 14.4 +/- 7.9 IU at 1 month, and 17.8 +/- 7.8 IU at 3 months among patients and 11.8 +/- 9.5 IU among controls (p values are < .002, .7, .12, and < .0005, respectively). As a rule, the neurological scores did not show a correlation to the PAI-1 levels. Presence of diabetes, hypertension, obesity, smoking, anticoagulant treatment, and sleep apnea did not affect the PAI-1 levels at any time point. Females had slightly higher PAI-1 levels. Age was a strong determinant for PAI-1 levels being higher in younger patients at every sampling time point (p values .02, .02, .02, and .03 respectively). The etiology of the ischemic stroke did not have an impact on PAI-1 levels. In 16 patients recurrent thrombosis had occurred. The high PAI-1 levels at admittance may reflect either an acute phase response or a chronic state. Normalized levels at 1 week and 1 month may be due to hospital diet, antithrombotic medication, weight loss, active physical therapy, and better care for diabetes. PAI-1 levels at 3 months after stroke did not predict recurrent thrombosis.