Prognostic importance of biomarkers associated with haemostatic, vascular and endothelial disturbances in acute coronary syndrome patients in relation to kidney function.

BACKGROUND: Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction. METHODS: Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox regression were used to study their association with the composite outcome of myocardial infarction, ischemic stroke, heart failure or death. Interaction with eGFR strata above or below 60 ml/min/1.73 m2 was tested. RESULTS: Tissue factor, proteinase-activated receptor, soluble urokinase plasminogen activator surface receptor (suPAR), thrombomodulin, adrenomedullin, renin, and angiotensinogen correlated inversely with eGFR and were selected for the Cox regression. Mean follow-up was 5.2 years during which 428 events occurred. Adrenomedullin, suPAR, and renin were independently associated with the composite outcome. Adrenomedullin showed interaction with eGFR strata (p = 0.010) and was associated with increased risk (HR 1.88; CI 1.44-2.45) only in patients with eGFR ≥60 ml/min/ 1.73 m2. CONCLUSIONS: Adrenomedullin, suPAR, and renin were associated with the composite outcome in all. Adrenomedullin, involved in endothelial protection, showed a significant interaction with renal function and outcome, and was associated with the composite outcome only in patients with preserved kidney function.

Do Gene Polymorphisms Play a Role in Newborn Hyperbilirubinemia?

Objectives: Polymorphisms of the uridine-diphospho-glucuronosyltransferase 1A1 (UGT1A1) gene, hepatic solute carrier organic anion transporter 1B1/B3 (SLCO1B1/3) gene, and glutathione S-transferase (GST) gene have been associated with significant hyperbilirubinemia in some populations. This study aims to determine whether the variation of UGT1A1, SLCO1B1/3 and GST genes play an important role in neonatal hyperbilirubinemia in Turkish newborn infants. Methods: The study included 61 idiopathic hyperbilirubinemia cases, 28 prolonged jaundice cases, and 41 controls. Ten common polymorphisms in four genes involved in bilirubin metabolism were examined. Polymerase chain reaction-restriction fragment length polymorphism method was used to detect variants of those genes. Results: No association was found between the variants of UGT1A1 at nt 211, the SLCO1B1 gene at nt 388, 463, 521, 1463, the SLCO1B3 gene at nt 334, 727+118, 1865+19721, and the GST gene at nt 313, 341, and neonatal hyperbilirubinemia. There was no difference between the case and control groups in terms of allele frequencies of these genes (except SLCO1B3 at nt 334) (p>0.05 in all comparisons). The presence of the G allele of the SLCO1B3 at nt 334 variant gene seemed to protect from jaundice in infants with idiopathic hyperbilirubinemia. Conclusion: These gene polymorphisms currently studied do not seem to modulate the risk of hyperbilirubinemia in Turkish newborn infants.

Antiphospholipid antibodies in patients with myocardial infarction with and without obstructive coronary arteries.

BACKGROUND: Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA). OBJECTIVES: To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C-protein C inhibitor (APC-PCI) complex. METHODS: Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case-control study. Autoantibodies (IgA/G/M) targeting cardiolipin and ß2 glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC-PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay. RESULTS: Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-ß2 glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC-PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients. CONCLUSIONS: aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability-measured by increased levels of the APC-PCI complex-were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system.

Altered Vascular Reactivity to Circulating Angiotensin II in Familial Hypercholesterolemia.

ABSTRACT: We have previously shown increased vascular reactivity to angiotensin (Ang) II in familial combined hyperlipidemia. However, this has not been well studied in familial hypercholesterolemia (FH), a condition with incipient endothelial dysfunction. This study aimed to examine microvascular and macrovascular responses to Ang II in FH. Therefore, we investigated the effects of a 3-hour infusion of Ang II on blood pressure and forearm skin microvascular function in 16 otherwise healthy patients with FH and matched healthy controls. Skin microvascular hyperemia was studied by laser Doppler fluxmetry during local heating. Microvascular resistance was determined by the ratio of mean arterial pressure to microvascular hyperemia. Macrovascular reactivity was assessed by changes in brachial blood pressure. Compared with the controls, the FH group had increased baseline systolic blood pressure (127 ± 14 vs. 115 ± 12 mm Hg; P = 0.02), while systolic blood pressure responses were similar (+24 ± 9 vs. +21 ± 7 mm Hg; P = 0.26) after 3 hours of Ang II infusion. At baseline, there were no group differences in microvascular hyperemia or resistance. However, after 3 hours of Ang II infusion, heat-induced microvascular hyperemia was less pronounced in FH (126 ± 95 vs. 184 ± 102 arbitrary units; P = 0.01), while microvascular resistance during heat-induced hyperemia was increased (1.9 ± 0.9 vs. 0.9 ± 0.8, P = 0.01), as compared to controls. Both these responses were further pronounced 1 hour after stopping Ang II. In conclusion, despite similar blood pressure responses to Ang II in the FH group and controls, microvascular dilatation capacity was impaired in the FH group, indicating endothelial dysfunction. These findings and increased microvascular resistance may lead to hypertension and microvascular complications in FH.

Endovascular Relining of Chronically Occluded Infrainguinal Venous Bypass Grafts.

BACKGROUND: Treatment of chronically occluded infrainguinal venous bypass grafts in patients presenting with recurrent chronic limb threatening limb ischemia (CLTI) represent a clinical challenge. Recent case reports have suggested the use of endovascular recanalization techniques without preceding thrombolysis. This study assesses feasibility and mid-term outcomes of this technique. RESULTS: A retrospective review of 5 consecutive patients (3 men, 2 women, mean age 70 ± 5 years) presenting with chronic venous bypass graft occlusion and recurrence of CLTI during 1 year was performed. Patients were treated with relining of the bypass grafts. Patients were followed up at median 26 (6-36) months. All patients were treated successfully with restoration of flow in the grafts using recanalization and relining technique without thrombolysis. In 4 patients, a Viabahn stentgraft (SG) was used with the addition of interwoven nitinol stents (INS) in 3. In 1 patient, the graft was treated with INS without the addition of a stentgraft. No peripheral embolization was encountered during the procedures. One patient occluded the relined grafts after 6 months. The remaining 4 grafts were all patent at 24-month follow-up. A total of 6 reinterventions (in 3 patients) were performed to reach 80% secondary patency. CONCLUSIONS: This case series demonstrate feasibility and promising mid-term results, from relining of chronically occluded infra-inguinal venous bypass grafts using stent grafts, interwoven and bare-metal stents without preceding thrombolysis. The technique could be an alternative treatment option in the treatment of these challenging cases.

2D perfusion-angiography during endovascular intervention for critical limb threatening ischemia - A feasibility study.

PURPOSE: Two-dimensional perfusion angiography is a new method to quantify and evaluate tissue perfusion during endovascular intervention. The aim was to evaluate time-patterns and dynamics of contrast arrival and distribution before and after endovascular intervention in patients with critical limb threatening ischemia. METHODS: Data were collected from 37 patients with critical limb threatening ischemia due to infra-inguinal occlusive disease having a successful endovascular procedure. two-dimensional perfusion angiography was used as a post-processing software with analysis of numeric parameters related to arrival and distribution patterns of contrast. RESULTS: Thirty-three patients were successfully analysed whereas four patients were excluded due to motion artefacts. All patients were successfully treated with recanalization of the superficial femoral, popliteal, below the knee-vessels or a combination. Short-term improvement at 30-day follow-up was noted both clinically and by ankle-brachial index and toe pressure measurements. A significant reduction in contrast arrival time between pre-and post-angioplasty runs was noted as measured by arrival time median 3.2 and interquartile range (2.5-4.2) vs. 2.6 (1.6-3.4) and time-to-peak 4.1 (3.6-5.0) vs. 3.1 (2.3-3.9) p = 0.009. An increased wash-in rate was also observed 18.3 (12.6-21) vs. 30.1 (22-30.5) p = 0.001 between pre-and post-angioplasty runs. CONCLUSIONS: The use of perfusion angiography for evaluation of foot-circulation during endovascular interventions provides new information regarding quantitative assessment of contrast inflow before and after endovascular intervention without the need for extra contrast or runs. No selective catheterisation is necessary. The technique is easily adopted in a clinical setting. Further studies are necessary to create robust clinical endpoints.

Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilization with fresh respectively frozen-thawed embryo transfer: Nationwide cohort study.

BACKGROUND: The assisted reproductive technique in vitro fertilization (IVF) is associated with an increased risk of venous thromboembolism (VTE) and pulmonary embolism (PE) during the first trimester. OBJECTIVES: To compare the incidence of VTE and PE during the first trimester of IVF pregnancies using fresh or frozen-thawed embryo transfer to that during natural pregnancies. PATIENT/METHODS: Nationwide Swedish registry-based cohort study of women who gave birth (n = 902 891) at the age of 15-50 years to their first child from the 1st of January 1992 until the 31st of December 2012. Exposure groups were IVF with fresh respectively frozen-thawed embryo transfer. Incidences of VTE and PE were calculated, and time-varying hazard ratios estimated for all trimesters after fresh respectively frozen-thawed embryo transfer IVF and compared to natural conception. RESULTS AND CONCLUSION: Women giving birth after fresh embryo transfer IVF had a more than eightfold increased incidence of venous thromboembolism (hazard ratio [HR] 8.96, 95% CI 6.33 to 12.67) and pulmonary embolism during the first trimester, (HR 8.69, 95% CI 3.83 to 19.71) compared to women giving birth after natural conception. The incidence of VTE in women giving birth after frozen-thawed embryo transfer was not increased during the first trimester. To conclude, fresh embryo transfer IVF was associated with a significantly increased incidence of VTE and PE during the first trimester. These results suggest that frozen-thawed embryo transfer could be a preferred method of IVF with a minimised maternal risk.

Assays of fibrin network properties altered by VKAs in atrial fibrillation - importance of using an appropriate coagulation trigger.

Atrial fibrillation (AF) is a prothrombotic condition, involving increased thrombin generation and fibrinogen concentrations. Vitamin K antagonists (VKAs) prevent arterial thromboembolism if optimal anticoagulation is achieved by individualised drug doses, assessed by determining the Prothrombin time-related International Normalized Ratio (Pt-INR). There is evidence that formation of tight-laced fibrin networks is pathogenic in prothrombotic diseases. This study was performed among AF patients, to test whether long-term treatment with VKAs affects the structure of fibrin networks, and whether the effect is altered by employing different coagulation triggers: exogenous thrombin (1 IU/ml), 10 pM tissue factor (TF) or a commercial Pt-INR reagent (containing 400-fold more TF). In the thrombin-based method, fibrin network porosity (scanning electron microscopy) and liquid permeability (flow measurements) correlated inversely to fibrinogen concentrations, while positive correlations to the degree of anticoagulation were shown with the Pt-INR reagent. In the method with 10 pM TF, the two above relationships were detected, though the influence of Pt-INR was more profound than that of fibrinogen concentrations. Moreover, greater shortening of clot lysis time (CLT) arose from more permeable clots. As a coagulation trigger, 10 pM TF vs exogenous thrombin or the Pt-INR reagent is more informative in reflecting the in vivo process from thrombin generation to fibrin formation. Since fibrin network permeability rose in parallel to elevations of INR and shortening of CLT in AF patients, antithrombotic effects on prevention of thrombotic complications may be achieved from impairment of thrombin generation, resulting in formation of permeable clots susceptible to fibrinolysis.

Impaired endothelium-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes.

AIMS: The present study investigated the effects of lipid-lowering therapy with atorvastatin on skin microvascular function in patients with type 1 diabetes and dyslipidaemia. METHODS: Twenty patients received daily treatment with atorvastatin 80 mg or placebo during 2 months in a randomised, double-blind, cross-over study. Forearm skin microcirculation was investigated with laser Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity, respectively. Various biochemical markers of endothelial function were also investigated. RESULTS: Endothelium-dependent microvascular reactivity decreased during atorvastatin (p < 0.001), showing a significant treatment effect compared with placebo (p = 0.04). Atorvastatin treatment was also associated with increased haemoglobin A1C levels from 7.45% to 7.77% (p = 0.008). CONCLUSIONS: The present study shows impaired endothelium-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes, thus implicating a risk for deterioration of microvascular function during such therapy in these patients.

A novel WT1 gene mutation in a newborn infant diagnosed with Denys-Drash syndrome.

Denys-Drash syndrome (DDS) is a rare disorder characterized by glomerulopathy, genital abnormalities and predisposition to Wilms' tumor. It is associated with constitutional Wilms'tumor suppressor 1 (WT1) gene mutations, in which the majority being missense mutations in the zinc-finger region. Here, we present a newborn with DDS, associated with a novel heterozygous missense mutation, p.Asp396His, on exon 9 of WT1.

High-dose aspirin is required to influence plasma fibrin network structure in patients with type 1 diabetes.

OBJECTIVE: Patients with type 1 diabetes form a less permeable fibrin network, which could contribute to their increased risk of cardiovascular disease (CVD). Low-dose aspirin treatment is the standard in the management of CVD; however, the effect seems reduced in patients with diabetes. We investigated the effects of low- and high-dose aspirin treatment on fibrin network formation in patients with type 1 diabetes (primary aim) and the possible interaction between the treatment effects of aspirin on fibrin network permeability and glycemic control in these patients (secondary aim). RESEARCH DESIGN AND METHODS: Forty-eight patients (24 subjects with good [HbA(1c) <7.4%] and 24 subjects with poor [HbA(1c) >8.4%] glycemic control) were randomly assigned to treatment with 75 or 320 mg/day aspirin during 4 weeks in a crossover fashion. A 4-week washout period separated the treatment periods. The plasma fibrin network was assessed by determination of the permeability coefficient (K(s)). RESULTS: Treatment with 75 mg aspirin did not influence fibrin network permeability (K(s)). However, K(s) increased significantly during treatment with 320 mg aspirin (P = 0.004), and a significant treatment effect was seen compared with treatment with 75 mg aspirin (P = 0.009). The increase in K(s) during high-dose aspirin treatment was significant in patients with poor glycemic control (P = 0.02), whereas K(s) only tended to increase in patients with good glycemic control (P = 0.06). CONCLUSIONS: A high dose of aspirin is required to influence fibrin network permeability in patients with type 1 diabetes. The observed lack of effect with low-dose aspirin may contribute to aspirin treatment failure in diabetes.

Effects on fibrin network porosity of anticoagulants with different modes of action and reversal by activated coagulation factor concentrate.

Orally available direct thrombin inhibitors (DTI) and direct activated factor X inhibitors (DFXaI) may replace vitamin K antagonists in patients needing long-term anticoagulant treatment. We investigated the influence on the fibrin network of anticoagulants with different modes of action: AR-H067637 (DTI), the active metabolite of AZD0837, apixaban (DFXaI), fondaparinux (indirect FXaI) and warfarin. Counteraction of the anticoagulant effect by FEIBA(®) (Factor Eight Inhibitor Bypass Activity) was also investigated. Tissue factor, phospholipids and calcium were used to initiate coagulation in human platelet poor plasma. The permeability constant (Ks), reflecting the amount of buffer passing through the coagulum, was calculated and the fibrin network was visualized by 3D confocal microscopy. Warfarin (International Normalized Ratio 2-3) increased Ks in plasma by 28-50% compared with control. 'Therapeutic' plasma concentrations of AR-H067637 (0·3-0·6 µmol/l), apixaban (0·2-0·4 µmol/l) and fondaparinux (0·1-0·3 µmol/l) increased Ks by 72-91%, 58-76% and 36-53% respectively. Addition of FEIBA(®) totally reversed the warfarin effect but only partially reversed effects of the other anticoagulants at concentrations that increased Ks by 50% or more. Fibrin network observed with 3D confocal microscopy agreed well with the permeability results. In conclusion, all examined anticoagulants rendered the fibrin network more porous. FEIBA(®) reversed the increased permeability in warfarin plasma but had only partial effects on the other anticoagulants.

Long-term effects of an expanded cardiac rehabilitation programme after myocardial infarction or coronary artery bypass surgery: a five-year follow-up of a randomized controlled study.

OBJECTIVE: To investigate the long-term effect of expanded cardiac rehabilitation on a composite end-point, consisting of cardiovascular death, myocardial infarction or readmission for cardiovascular disease, in patients with coronary artery disease. DESIGN: Single-centre prospective randomized controlled trial. SETTING: University hospital. SUBJECTS: Two hundred and twenty-four patients with acute myocardial infarction or undergoing coronary artery by-pass grafting. INTERVENTION: Patients were randomized to expanded cardiac rehabilitation (a one-year stress management programme, increased physical training, staying at a 'patient hotel' for five days after the event, and cooking sessions), or to standard cardiac rehabilitation. MAIN MEASURES: Data on cardiovascular death, myocardial infarction, readmission for cardiovascular disease and days at hospital for cardiovascular reasons were obtained from national registries of the Swedish National Board of Health and Welfare. RESULTS: The primary end-point occurred in 121 patients altogether (54%). The number of cardiovascular events were reduced in the expanded rehabilitation group compared with the standard cardiac rehabilitation (53 patients (47.7%) versus 68 patients (60.2%); hazard ratio 0.69; P =0.049). This was mainly because of a reduction of myocardial infarctions in the expanded rehabilitation group. During the five years 12 patients (10.8%) versus 23 patients (20.3%); hazard ratio 0.47; P =0.047 had a myocardial infarction. Days at hospital for cardiovascular reasons were significantly reduced in patients who received expanded cardiac rehabilitation (median 6 days) compared with standard cardiac rehabilitation (median 10 days; P =0.02). CONCLUSION: Expanded cardiac rehabilitation after acute myocardial infarction or coronary artery bypass grafting reduces cardiovascular morbidity and days at hospital for cardiovascular reasons.

ADAMTS13 and von Willebrand factor concentrations in patients with diabetes mellitus.

The von Willebrand factor (VWF) is elevated in patients with diabetes mellitus and degraded by a metalloprotease, ADAMTS13. We hypothesized that this elevation is due to a decreased function of ADAMTS13. Thus, we investigated ADAMTS13 in patients with diabetes mellitus without and with peripheral artery occlusive disease (PAOD). When treating the latter group with dalteparin, VWF is reported to increase significantly, and we therefore measured ADAMTS13 also in these patients. VWF antigen and ADAMTS13 antigen and activity concentrations were measured in patients with diabetes mellitus but without PAOD (diabetes mellitus; n = 23) and with diabetes mellitus and PAOD (diabetes mellitus + PAOD; n = 65) before and after treatment with dalteparin or placebo. In the diabetes mellitus group, concentration of VWF antigen was significantly higher, whereas that of ADAMTS13 activity was significantly lower than in the healthy controls. In the diabetes mellitus along with PAOD group, VWF antigen was significantly higher, but ADAMTS13 antigen or activity did not differ significantly from those of healthy controls. The ADAMTS13 activity/antigen ratio was lower than in controls only in the diabetes mellitus patient group. VWF antigen increased significantly during dalteraprin treatment, whereas ADAMTS13 activity and antigen remained unchanged. Only patients with diabetes mellitus had significantly lower concentrations of ADAMTS13 activity in plasma than controls, although the diabetes mellitus along with PAOD had a more pronounced VWF antigen elevation than diabetes mellitus patients, illustrating a possible link between ADAMTS13 and microangiopathy in diabetes mellitus patients. The increase in VWF antigen concentration during treatment with dalteparin does not seem to be due to changes in ADAMTS13.

Elevations in soluble CD40 ligand in patients with high platelet aggregability undergoing percutaneous coronary intervention.

High aggregatory responses despite antiplatelet treatment is associated with an increased risk of thrombotic complications following percutaneous coronary intervention (PCI). In the present study, we investigated the relationship between platelet aggregatory responses to ADP and the release of CD40L (sCD40L): an immunomodulatory compound involved in atherothrombosis - in patients undergoing PCI. ADP-induced platelet aggregation, sCD40L and soluble P-selectin (sP-selectin) were determined before and 24 h after PCI, in samples from 52 patients receiving aspirin and thienopyridines. Platelet aggregation to ADP above the median was defined as 'high aggregation', and aggregation below the median as 'low aggregation'. Data below are medians and interquartile ranges. Patients with 'high platelet aggregability' had a significantly higher increase in both sCD40L (Delta-values: 0.78 (-0.19-3.18) vs. -0.65 (-2.10-0.00) ng/ml, P = 0.002) and sP-selectin (Delta-values: 8.0 (-2.00-16.00) vs. 4.50 (-13.00-0.50) ng/ml, P = 0.001) compared with patients with 'low platelet aggregability'. In a multivariate linear regression analysis adjusted for clinical characteristics and type of preintervention therapy, the only independent predictors of sCD40L and sP-selectin were platelet aggregation to ADP before PCI (P < 0.001) and the combination of platelet aggregation to ADP before PCI and urgency of PCI (P < 0.001). Circulating CD40L is more markedly increased after PCI in patients with high ADP-induced platelet aggregation.

The effects of cervical headgear with an expanded inner bow in the permanent dentition.

In this study, the effects of cervical headgear (CHG) use on the transverse dimension of the maxillary dental arch were evaluated in patients in the permanent dentition. Thirteen girls and 12 boys (mean age: 13.41 +/- 0.52 years) with a bilateral full cusp Class II molar relationship comprised the study group. Fifteen girls and 10 boys with a Class I normal occlusion comprised the controls. In the treatment group, CHG with an expanded inner bow was used for a mean period of 11.2 +/- 5.6 months. The headgear was used for molar distalization and the force magnitude was 196.1 cN. After CHG treatment, the patients underwent non-extraction fixed orthodontic treatment for 14.1 +/- 2.5 months. During this period, the control group received regular dental check-ups. Dental casts obtained at the beginning (T1) and end (T2) of headgear use and at the end of orthodontic treatment (T3) and posteroanterior cephalograms taken at T1 and T2 were evaluated. A Student's t-test was used for intergroup comparison at T1, T2, and T3 and a Mann-Whitney U-test with a Bonferroni correction for comparison of treatment/observation changes. At T2, intercanine (0.96 +/- 0.56 mm), interpremolar (1.6 +/- 0.55 mm for the first premolar, 1.74 +/- 0.65 mm for the second premolar), and intermolar (2.31 +/- 0.75 mm) widths increased, while the distance between the intersection of the zygomatic process and the maxillary alveolar process on the right (JR) and left (JL) did not change. Fixed orthodontic treatment did not have any effect on any of the measurements. With the intentional expansion of the inner bow of CHG, the amount of maxillary dental arch expansion achieved in the permanent dentition was statistically significant (P < 0.017).

Platelet dysfunction in patients with severe traumatic brain injury.

Coagulopathy is a common phenomenon in traumatic brain injury (TBI) and a major contributor to a poor outcome. Thrombocytopenia is a strong negative prognostic factor in TBI, but bleeding tendency can be present even with a normal platelet count. We investigated platelet function in patients with TBI by means of modified thromboelastography (i.e., platelet mapping [TEG-PM]). Four groups were studied: (1) patients with severe isolated TBI (n = 20), (2) patients with general trauma without TBI (the ICU group, n = 10), (3) patients with chronic alcohol abuse (n = 7; as alcohol abuse is common in patients with TBI), and (4) healthy volunteers (n = 10). We measured platelet counts in venous blood (Plt), Ivy bleeding time, standard TEG parameters, and platelet responses to arachidonic acid (AA) and adenosindiphosphate (ADP), using TEG-PM. TBI patients had a lower Plt (180 +/- 68 x 10(9) ; mean +/- SD) and a longer bleeding time (674 +/- 230 sec) than healthy controls, (256 +/- 43 x 10(9), p < 0.01) and (320 +/- 95 sec, p < 0.005), respectively. TBI patients had dramatically lower platelet responses to AA (0-86%, mean 22%) compared to healthy controls (57-89%, mean 73%), the ICU group (4-75%, mean 49%), and the alcohol abusers (17-88%, mean 64%; p < 0.001). Responses to ADP did not differ significantly between the groups. Patients with low responsiveness to AA at admittance to the hospital were likely to develop bleeding complications later. Patients with TBI develop platelet dysfunction, which most likely contributes to bleeding complications. The observed platelet dysfunction appears to involve the cyclooxygenase pathway. TEG-PM analysis can be used to identify patients with a high risk of bleeding complications.