Patients with cerebral small vessel disease (SVD) can present as isolated lacunar infarction or with diffuse white matter changes, with the imaging appearance of leukoaraiosis. Endothelial dysfunction, which can lead to breakdown of the blood-brain barrier, impaired cerebral autoregulation and prothrombotic changes, is believed to be important in mediating disease. Circulating levels of intercellular adhesion molecule 1 (ICAM1), thrombomodulin (TM), tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are markers of endothelial activation and damage, and may provide insights into disease pathogenesis or differences between phenotypes. We therefore measured these markers in a prospective series of patients with lacunar stroke. One hundred and ten white Caucasian patients with previous lacunar stroke and 50 community control subjects were studied. Markers of endothelial function were measured on venous blood samples. Patients were classified on brain imaging into two groups: isolated lacunar infarction (n = 47) and ischaemic leukoaraiosis, defined as a clinical lacunar stroke and leukoaraiosis on brain imaging (n = 63). The number of lacunes and severity of leukoaraiosis were also scored on MRI. ICAM1, TM and TFPI were elevated in cerebral SVD subjects compared with controls (P

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Hypofibrinogenemia and inadequate heparin reversal are 2 important factors contributing to clot strength and perioperative hemorrhage after pediatric CPB. TEG may be a useful tool for predicting and guiding early treatment of mediastinal bleeding in this group.

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SummaryThe pathogenic mechanism underlying the prothrombotic tendency of Hughes’ or antiphospholipid syndrome (APS) has not been elucidated. Numerous procoagulant mechanisms have been tested including platelet activation, monocyte tissue factor (TF) expression and endothelial cell (EC) activation. There is some evidence for the latter from studies on cultured human umbilical vein endothelial cells (HUVEC). Incubation with antiphospholipid antibodies (aPL) induces EC activation in vitro. We investigated whether there was evidence of EC perturbation in vivo using enzyme-linked immunosorbant assays (ELISAs) for soluble markers of EC dysfunction. Serum and plasma were collected from controls and patients with primary APS and ELISAs performed to quantify soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), endothelin-1 (ET-1), von Willebrand factor (vWF) and soluble tissue factor (sTF). In addition, soluble p-selectin (p-selectin) and vascular endothelial growth factor (VEGF) were measured: the former as a marker of platelet activation, the latter as a potential mediator of TF expression. No significant differences in the levels of blood-borne soluble markers were detected between the patient and control groups except for VEGF and sTF, patients having significantly higher levels of VEGF and sTF than controls (p <0.05). These results suggest plasma soluble tissue factor and VEGF may play a role in the pathogenesis of thrombosis in APS, although the cell of origin of these molecules remains unclear.

Summary. Background: Pre-eclampsia (PET) and/or fetal growth restriction (FGR) remain a major cause of maternal and fetal morbidity and mortality. In pregnancy, fibrinolysis is controlled by the maternal endothelium and placenta, both of which are central to the pathogenesis of PET/FGR. Clinically, uterine artery Doppler screening at 23 weeks is used to predict PET/FGR. An abnormal uterine artery Doppler finding is defined as early diastolic bilateral uterine artery notching (BN) in the waveform. However, about 50% of mothers with BN do not develop PET/FGR. Objectives: We investigated fibrinolytic changes and uterine artery Doppler findings in the second trimester, and related them to pregnancy outcome; in particular assessing whether fibrinolytic markers could discriminate between normal and abnormal outcome in mothers with BN. Patients/methods: Plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), plasminogen activator inhibitor-2 (PAI-2), plasmin-a 2 antiplasmin (PAP), D-dimers and markers of endothelial dysfunction were measured with Doppler ultrasound at 23 weeks. Results: Those with BN had decreased PAP and D-dimer levels, and raised PAI-1 and thrombomodulin levels. Mothers with BN and PET/FGR had significantly increased t-PA levels and reduced PAI-2 levels. Conclusions: BN at 23 weeks of gestation is associated with increased PAI-1 levels. Within the BN group, mothers who developed PET/FGR had increased t-PA levels and decreased PAI-2 levels, although there was no net change in fibrinolysis as measured by D-dimer levels. No single fibrinolytic marker is helpful in determining pregnancy outcome in those with BN, but t-PA and PAI-2 are worthy of study in a multifactorial algorithm.

SummaryThis study aimed to estimate the diagnostic utility of biomarkers for suspected venous thromboembolism (VTE) in pregnancy and the puerperium. Research nurses/midwives collected blood samples from 310 pregnant/postpartum women with suspected pulmonary emboli (PE) and 18 with diagnosed deep vein thrombosis (DVT). VTE was diagnosed using imaging, treatment and adverse outcome data. Primary analysis was limited to women with conclusive imaging (36 with VTE, 247 without). The area under the curve (AUC) for each biomarker was: activated partial thromboplastin time 0·669 (95% confidence interval 0·570–0·768), B‐type natriuretic peptide 0·549 (0·453–0·645), C‐reactive protein 0·542 (0·445–0·639), Clauss fibrinogen 0·589 (0·476–0·701), D‐Dimer (by enzyme‐linked immunosorbent assay) 0·668 (0·561–0·776), near‐patient D‐Dimer 0·651 (0·545–0·758), mid‐regional pro‐atrial natriuretic peptide 0·524 (0·418–0·630), prothrombin fragment 1 + 2 0·562 (0·462–0·661), plasmin‐antiplasmin complexes 0·639 (0·536–0·742), prothombin time 0·613 (0·508–0·718), thrombin generation lag time 0·702 (0·598–0·806), thrombin generation endogenous potential 0·559 (0·437–0·681), thrombin generation peak 0·596 (0·478–0·715), thrombin generation time to peak 0·655 (0·541–0·769), soluble tissue factor 0·531 (0·424–0·638) and serum troponin 0·597 (0·499–0·695). No diagnostically useful threshold for diagnosing or ruling out VTE was identified. In pregnancy and the puerperium, conventional and candidate biomarkers have no utility either for their negative or positive predictive value in the diagnosis of VTE.

Summary. Deep vein thrombosis (DVT) remains common in patients with acute ischemic stroke (AIS) receiving aspirin and graded compression stockings (considered standard thromboprophylaxis in the UK), most events occurring in patients with Barthel indices (BI) of £ 9 (Ôsevere strokeÕ) around the time of admission. In the absence of data indicating improved clinical outcomes with use of low-dose anticoagulant thromboprophylaxis, we evaluated the hypothesis that plasma D-dimers (D-d) might be a valuable initial screening test for proximal DVT (PDVT), facilitating selective use of imaging. One hundred and two unselected AIS-patients receiving aspirin/graded compression stockings thromboprophylaxis were screened for DVT using magnetic resonance direct thrombus imaging, a highly accurate noninvasive technique which directly visualizes thrombus. D-d (VIDAS and IL test D-d assays) were measured on recruitment and at weekly intervals. Median D-d were significantly higher throughout the study in patients with severe stroke who developed PDVT vs. those with severe stroke not developing PDVT, differences being most marked around day 9. Depending on the discriminatory threshold used, a single D-d measurement at this time in patients with severe-AIS allowed identification of a subgroup with 50% prevalence of PDVT. Sensitivity of these strategies for PDVT was 67-83%, at a cost of imaging 22-30% of the entire cohort of patients. A single measurement of BI around the time of admission and D-d level at day 9 in AIS-patients receiving aspirin/graded compression stockings thromboprophylaxis allows identification of a subgroup containing a substantial proportion of all PDVTs who could be selectively imaged.