What you need to know about migraine in Hughes syndrome patients.

BACKGROUND: Headache, often migrainous, is common in patients with antiphospholipid antibodies, whether or not they meet Sydney criteria for a definite diagnosis of Hughes syndrome. Migraine may be a harbinger of stroke in this patient population and even refractory migraine may be highly responsive to antithrombotic therapy in this clinical context. PURPOSE: To summarize what is known to date about managing this important manifestation of the immune-mediated hypercoagulable Hughes syndrome. RESULTS: We provide a suggested management algorithm for refractory headache in this unique patient population. CONCLUSION: Most neurologists don't see or recognize many aPL-positive patients in their practice, so hematologists and rheumatologists who see these patients should recognize that refractory headache may be a manifestation of their immune-mediated hypercoagulable disorder and understand that the potential risks of not addressing this issue may be high.

Catchment sourcing urban pesticide pollution using constructed wetlands in Melbourne, Australia.

A survey of 111 urban constructed stormwater wetlands (median watershed area = 86.8 ha) was conducted to identify the major pesticides present and to determine their major catchment sources (residential, industrial, commercial, sporting ovals) and associations with catchment imperviousness. Melbourne, Australia, has separate stormwater and sewerage systems and these wetlands are designed to treat urban stormwater. To maximise the pesticides that could be detected, three types of passive samplers (POCIS, Chemcatcher® SDB-XC and Chemcatcher® C18) were deployed, along with collection of fine sediments. A total of 231 pesticides were screened using these methods. Pesticides that were detected in >5 % of wetlands were checked to determine their registered use in urban areas using an Australian government database (PubCris). Twenty-five pesticides were detected in >5 % of wetlands: 4 pesticides were associated with non-urban land uses (agriculture and forests), another 4 pesticides had no known registered use in urban areas and 17 were associated with urban areas. The pesticides associated with urban areas were the herbicides simazine, diuron, metolachlor, bromacil, propyzamide and paclobutrazol, the fungicides tebuconazole, propiconazole, metalaxyl, trifloxystrobin, iprodione and carbendazim and the insecticides fipronil, bifenthrin, chlorantraniliprole, thiamethoxam and permethrin. Atrazine was also detected in 59 % of wetlands but has not been registered for urban uses in Australia since 2010. It's presence in Melbourne may be due to legacy issues or aerial transportation from rural areas where it's still widely used in crop cultivation. Generally, the major urban catchment source of pesticides is from residential areas (particularly fipronil and simazine), most likely in wood preservatives, paints and from weed or insect control. Many of these widely used pesticides were correlated with increased catchment imperviousness. Some pesticides (bromacil and imidacloprid) were correlated with commercial premises and chlorantraniliprole was correlated with the presence of sporting ovals in the catchment. No pesticides were specifically correlated with industrial areas. The use of passive samplers and fine sediments, in conjunction with detailed land use mapping of stormwater wetland catchments is very effective and efficient in monitoring and sourcing pesticide contamination in urban environments.

Dosing considerations in the use of the direct oral anticoagulants in the antiphospholipid syndrome.

WHAT IS KNOWN AND OBJECTIVES: At least four prospective trials have been initiated investigating the direct oral anticoagulants in the antiphospholipid syndrome. Preliminary reports have supported their use in patients with a history of venous thrombosis and a target INR of 2-3, but there have also been reports of failure of these agents in the antiphospholipid syndrome. The objective is to present a case report that illustrates there may be important dosing issues when considering the use of these agents in patients with the antiphospholipid syndrome. CASE SUMMARY: A 50-year-old woman with the antiphospholipid syndrome, manifesting clinically with recurrent pyoderma gangrenosum-like leg ulcers, was treated with apixaban, resulting in improved ulcer healing. For insurance purposes, she was switched to rivaroxaban with worsening of the ulcers which again improved when apixaban was resumed. WHAT IS NEW AND CONCLUSION: Despite a similar half-life, pharmacokinetics and pharmacodynamics, the manufacturer-recommended maintenance dosing of apixaban is twice daily and rivaroxaban once daily. We believe this difference in recommended dose accounts for the differential clinical response noted in the present case report and that twice daily dosing and a larger daily dose of these agents may be more efficacious in potent hypercoagulable disorders, such as the antiphospholipid syndrome.

Immediate remote ischemic postconditioning after hypoxia ischemia in piglets protects cerebral white matter but not grey matter.

Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. Our aim was to assess whether RIPostC is protective following cerebral hypoxia-ischemia in a piglet model of neonatal encephalopathy (NE) using magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry. After hypoxia-ischemia (HI), 16 Large White female newborn piglets were randomized to: (i) no intervention (n = 8); (ii) RIPostC - with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (n = 8). RIPostC reduced the hypoxic-ischemic-induced increase in white matter proton MRS lactate/N acetyl aspartate (p = 0.005) and increased whole brain phosphorus-31 MRS ATP (p = 0.039) over the 48 h after HI. Cell death was reduced with RIPostC in the periventricular white matter (p = 0.03), internal capsule (p = 0.002) and corpus callosum (p = 0.021); there was reduced microglial activation in corpus callosum (p = 0.001) and more surviving oligodendrocytes in corpus callosum (p = 0.029) and periventricular white matter (p = 0.001). Changes in gene expression were detected in the white matter at 48 h, including KATP channel and endothelin A receptor. Immediate RIPostC is a potentially safe and promising brain protective therapy for babies with NE with protection in white but not grey matter.

New horizons for newborn brain protection: enhancing endogenous neuroprotection.

Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade.

Black and minority ethnic pharmacists' treatment in the UK: A systematic review.

BACKGROUND: Pharmacists from black and minority ethnic (BME) backgrounds represent a significant proportion of the United Kingdom (UK) pharmacy profession. While there is evidence that BME doctors may be discriminated against in employment and regulatory practices, little is known about the treatment of BME pharmacists. OBJECTIVES: To identify published evidence on the disproportionate treatment in employment and regulatory practices of BME pharmacists in the UK. Evidence was sought in four specific domains: recruitment (into the profession); progression; retention (within sector and profession) and regulation. METHODS: The following databases were searched: Pubmed, Embase, Scopus, International Pharmaceutical Abstracts, SIGLE and Google Scholar. Inclusion criteria were: English language only, published between 1993 and 2014 and reporting UK-based findings. RESULTS: The search strategy identified 11 pertinent items; 6 peer-reviewed articles, 2 published reports, 2 conference papers and one PhD thesis. In employment practices, there was some evidence that BME pharmacists are over-represented among owners and under-represented amongst senior management in the community sector. BME pharmacists reported more difficulties in getting their first job. BME pharmacists were over-represented in disciplinary processes but there was no evidence of disproportionate treatment in the outcomes of inquiries. CONCLUSION: Only a small number of studies have been published in this area, and the evidence of disproportionate treatment of BME pharmacists is equivocal. Further research is needed to better understand the role of ethnicity in recruitment, retention, progression and regulation.

The relationships among work stress, strain and self-reported errors in UK community pharmacy.

BACKGROUND: Changes in the UK community pharmacy profession including new contractual frameworks, expansion of services, and increasing levels of workload have prompted concerns about rising levels of workplace stress and overload. This has implications for pharmacist health and well-being and the occurrence of errors that pose a risk to patient safety. Despite these concerns being voiced in the profession, few studies have explored work stress in the community pharmacy context. OBJECTIVES: To investigate work-related stress among UK community pharmacists and to explore its relationships with pharmacists' psychological and physical well-being, and the occurrence of self-reported dispensing errors and detection of prescribing errors. METHOD: A cross-sectional postal survey of a random sample of practicing community pharmacists (n = 903) used ASSET (A Shortened Stress Evaluation Tool) and questions relating to self-reported involvement in errors. Stress data were compared to general working population norms, and regressed on well-being and self-reported errors. RESULTS: Analysis of the data revealed that pharmacists reported significantly higher levels of workplace stressors than the general working population, with concerns about work-life balance, the nature of the job, and work relationships being the most influential on health and well-being. Despite this, pharmacists were not found to report worse health than the general working population. Self-reported error involvement was linked to both high dispensing volume and being troubled by perceived overload (dispensing errors), and resources and communication (detection of prescribing errors). CONCLUSIONS: This study contributes to the literature by benchmarking community pharmacists' health and well-being, and investigating sources of stress using a quantitative approach. A further important contribution to the literature is the identification of a quantitative link between high workload and self-reported dispensing errors.

Exposure to estrogenic chemicals induces ectopic expression of vtg in the testis of rainbowfish, Melanotaenia fluviatilis.

Vitellogenin (Vtg) is the major egg-yolk precursor protein in oviparous organisms normally synthesised only in mature females. In males and juveniles, the vtg gene, although present, is silent, but its hepatic expression may be activated by xenoestrogens. Surprisingly, its induction and potential consequences in non-hepatic tissues remain unexplored. Here we test the hepatic and testicular response of vtg expression in adult male rainbowfish Melanotaenia fluviatilis exposed to either 1, 3, 5 µg/L 17ß-estradiol or 100, 500 µg/L 4-n-nonylphenol for 24-96 h. Significant increase in the expression level of vtg mRNA in the liver and testes of exposed males was observed. The early (24 h), sensitive and reliable detection of the vtg induction using qPCR demonstrates the assay's robustness to monitor xenobiotic exposure particularly in smaller fish like rainbowfish, an emerging indicator species. Whilst, the ectopic induction of vtg mRNA in testes suggests a more complex Vtg pathway.

CCL3 induced migration occurs independently of intracellular calcium release.

The molecular signalling pathway of cell migration and whether it can occur independently of the release of intracellular calcium is still not completely understood. Therefore we investigated here the molecular mechanisms of CCL3 induced cell migration and the importance of intracellular calcium for chemotaxis in more detail. We show that CCL3 induced cell migration is dependent on activation of PLC. Several PKC inhibitors block the release of intracellular calcium independently of CCL3 activation and do not affect cell migration. This confirms that the release of intracellular calcium is not necessary for chemotaxis towards CCL3 and that PKC inhibitors should be used with caution in calcium release assays.

Early primary breast cancer in the elderly - pattern of presentation and treatment.

INTRODUCTION: The incidence of primary breast cancer in elderly patients is increasing. However, little is known about their biological profile and most appropriate clinical management, as most studies have been conducted in the younger population. This study aimed to identify a profile of characteristics in elderly women with operable primary breast cancer and investigate the dynamics influencing the treatment decision-making process. METHODS: A review of 268 consecutive female patients >70 years of age, diagnosed with early operable primary breast cancer (<5 cm) over a 30-month period at the Nottingham Breast Institute, was conducted. Age, co-morbidity, cancer characteristics, treatment offered and undertaken, and reason for patient choice were recorded and analysed. RESULTS: The median age was 78 (range 70-100) years. In our study, 82% of the patients had one or more co-morbidities, with 34% of them having three or more co-morbidities. The commonest pathological diagnosis (from needle core biopsies) was invasive ductal carcinoma of no special type (76%) with histological grade 2 (64%). Majority of them were oestrogen receptor (ER)-positive (84%) and had a high histochemical (H)-score (83% with H-score >200). Most of the patients (60%) underwent primary surgical management, of which 45.4% received breast-conserving surgery. Among the patients who had breast-conserving surgery, 68% of them received adjuvant radiotherapy. When offered genuine choice in treatment options, most patients chose non-operative treatment. Patients who underwent non-operative treatment were on average seven years older and had significantly more co-morbidities than those who had surgery. CONCLUSION: The elderly population evidently have demographic and cancer characteristics distinct from their younger counterparts, with less patients receiving surgical management. Further work is underway to correlate this with their clinical outcomes and to examine the factors behind the treatment decision-making process.

Biological profile of oestrogen receptor positive primary breast cancers in the elderly and response to primary endocrine therapy.

Aromatase inhibitors have been shown to be superior to Tamoxifen in several settings. It is unclear whether this superiority extends to their use as primary endocrine therapy in elderly patients with early operable primary breast cancer. Biological characteristics of the tumours may aid in selecting the most suitable agent. Primary endocrine therapy with Anastrozole in 64 women >70 years with oestrogen receptor alpha-positive (ERalpha+) breast cancer was compared to that in 84 treated with Tamoxifen during the same period. Biomarkers were assessed by immunohistochemistry on diagnostic core biopsies. There was no significant difference between the two groups (Anastrozole vs Tamoxifen) in terms of clinical benefit rates at 6 months (97% vs 100%) or median progression free survival (16.5 vs 22.5 months). There were no withdrawals due to adverse events from Anastrozole, compared to four with Tamoxifen. 46%, 99%, 8% and 5% of all patients were positive for progesterone receptor, ERbeta2, HER2 and EGFR, respectively, and 64% of patients had a moderate Ki-67 index. Positive HER2 status (18 vs 21 months, p=0.003) and moderate Ki-67 index (17.5 vs 23 months, p=0.042) were associated with significantly shorter progression free survival. Results thus far show that primary endocrine therapy with Anastrozole in elderly patients with early operable ERalpha+ breast cancer is similar to Tamoxifen in terms of efficacy, but appears to be associated with less adverse events leading to withdrawals. In this population, ERalpha+ breast cancer also appears to have a less aggressive biological profile favouring better hormone sensitivity.

Heparin-induced thrombocytopenia: diagnosis and management.

Heparin-induced thrombocytopenia (HIT) is an immune reaction in response to platelet factor 4-heparin complexes, which results in increased platelet activation and thrombocytopenia beginning on the 4th-5th day after heparin exposure induced by IgG antibody production. Platelet activation can lead to arterial thrombosis, but more commonly platelet microparticle formation contributes to venous thrombosis. Accurate diagnosis of HIT is based on the presence of clinical features, including a 50% fall in platelet count, appropriate timing of thrombocytopenia, development of new thrombosis despite thrombocytopenia and heparin therapy, and the absence of a more likely cause of thrombocytopenia. Documentation of an anti-PF4-heparin antibody is necessary, but is not sufficient to make the diagnosis since antibody formation occurs in a variety of clinical settings without the development of thrombocytopenia or thrombosis. Once HIT is suspected or confirmed, all forms of heparin should be discontinued and an alternative form of anticoagulation should be administered until the platelet count recovers. Treatment options include intravenous administration of argatroban, lepirudin, and bivalirudin; subcutaneous administration of fondaparinux has also been described. Warfarin therapy, if indicated, should be avoided until platelet recovery. Re-exposure to heparin can be avoided by use of alternative anticoagulants for most circumstances. Heparin-induced thrombocytopenia (HIT) has been the focus of increasing attention over the past 15-20 years. As interventions for HIT are developed, there is a need to accurately diagnose the condition, which can be challenging especially in severely ill patients.

The U.S. Thrombosis and Hemostasis Centers pilot sites program.

Venous thromboembolism (VTE) is a common disorder associated with significant morbidity and mortality. Despite important advances in understanding the etiology of VTE, delivery of care to patients with thrombosis and thrombophilia is frequently incomplete and highly variable. A comprehensive model of health care has been used successfully to treat and prevent complications for people with hemophilia and other chronic disorders. The effectiveness of an integrated healthcare model for patients with all coagulation disorders has yet to be evaluated. The Division of Hereditary Blood Disorders of the Centers for Disease Control and Prevention (CDC) is collaborating with eight Thrombosis and Hemostasis Centers (pilot sites) to provide health-related services and conduct research directed toward the reduction or prevention of complications of thrombosis and thrombophilia. The initial objectives of the collaboration are to (1) determine the efficacy of integrated multidisciplinary care and prevention services for people with hemostatic disorders, (2) assess unmet needs for service delivery and identify outreach strategies to improve access to care, (3) develop effective messages aimed at disease management and prevention, and (4) foster the development of training programs to enhance provider skills for the delivery of patient care. To address these objectives, the investigators and CDC have developed and implemented a web-based patient registry to follow prospectively service allocation and patient outcomes. Funding for the program began in October 2001. All eight funded centers are affiliated with U.S. medical schools. Principal investigators at the centers are hematologists (five adult, two pediatric) or cardiologists. Faculty in obstetrics-gynecology, surgery, and multiple other specialties are integral to the model of care at the centers. Other critical components at the centers are clinical laboratory services, training programs, research networks, and education and outreach programs. From August 2003 to March 2006, over 2,600 patients were enrolled in the registry, accounting for a total of more than 5,000 visits to the centers. Immediate goals of the data collection at the centers are to characterize patients receiving care at centers and document the state of health services provided. Long-term goals are to evaluate prospectively clinical outcomes for patients receiving multidisciplinary care and prevention services at centers. The network of data collection across centers will facilitate future collaborative clinical and epidemiologic investigations and enhance collective expertise in hemostasis and coagulation disorders.

Contribution of the Na+-K+-2Cl- cotransporter NKCC1 to Cl- secretion in rat OMCD.

In rat kidney the "secretory" isoform of the Na+-K+-2Cl- cotransporter (NKCC1) localizes to the basolateral membrane of the alpha-intercalated cell. The purpose of this study was to determine whether rat outer medullary collecting duct (OMCD) secretes Cl- and whether transepithelial Cl- transport occurs, in part, through Cl- uptake across the basolateral membrane mediated by NKCC1 in series with Cl- efflux across the apical membrane. OMCD tubules from rats treated with deoxycorticosterone pivalate were perfused in vitro in symmetrical HCO/CO2-buffered solutions. Cl- secretion was observed in this segment, accompanied by a lumen positive transepithelial potential. Bumetanide (100 microM), when added to the bath, reduced Cl- secretion by 78%, although the lumen positive transepithelial potential and fluid flux were unchanged. Bumetanide-sensitive Cl- secretion was dependent on extracellular Na+ and either K+ or NH, consistent with the ion dependency of NKCC1-mediated Cl- transport. In conclusion, OMCD tubules from deoxycorticosterone pivalate-treated rats secrete Cl- into the luminal fluid through NKCC1-mediated Cl- uptake across the basolateral membrane in series with Cl- efflux across the apical membrane. The physiological role of NKCC1-mediated Cl- uptake remains to be determined. However, the role of NKCC1 in the process of fluid secretion could not be demonstrated.

Primary care. Diverted traffic.

A trial scheme in which patients with common self-limiting conditions are offered a consultation with a community pharmacist instead of a GP has been taken up by more than a quarter of eligible patients. The pharmacists prescribe from a formulary agreed in consultation with GPs and the health authority. Pharmacists receive a payment for the consultation whether or not a prescription is dispensed.

Slow desorption of PCBs and chlorobenzenes from soils and sediments: relations with sorbent and sorbate characteristics.

The kinetics of slow desorption were studied for four soils and four sediments with widely varying characteristics [organic carbon (OC) content 0.5-50%, organic matter (OM) aromatic content (7-37%)] for three chlorobenzenes and five polychlorinated biphenyls (PCBs). Slowly and very slowly desorbing fractions ranged from 1 to 50% (slow) and 3 to 40% (very slow) of the total amount sorbed, and were observed for all compounds and all soils and sediments. In spite of the wide variations in sorbate K(OW) (factor 1000) and sorbent characteristics, the rate constants of slow (k(slow), around 10(-3) h(-1)) and very slow (k(very slow), 10(-5)-10(-4) h(-1)) desorption appeared to be rather constant among the sorbates and sorbents (both within a factor of 5). There was a good correlation (r(2) above 0.9) between the distribution over the slow, very slow and rapid sediment fractions and log K(OC), indicating that sorbate hydrophobicity may be important for this distribution. No correlation could be found between sorbent characteristics [OC, N, and O in the organic matter, polarity index C/(N+O), OC aromaticity as determined by CP-MAS (13)C-NMR] and slow desorption parameters (slowly/very slowly desorbing fractions+corresponding rate constants). The absence of (1) a correlation between k(slow) and k(very slow), respectively, and OC content, and (2) the narrow range of k(slow) and k(very slow) values, indicates that intra-OM diffusion is not the mechanism of slow or very slow desorption, because on the basis of this mechanism it would be expected that increasing OC content would lead to longer diffusion pathlengths and, consequently, to smaller rate constants. In addition, it was tested whether differential scanning calorimetry would reveal a glass transition in the soils/sediments. In spite of the sensitivity of the equipment used (changes in heat flow in the micro-Watt range were measurable), a glass transition was not observed. This means that activation enthalpies of slow desorption can be calculated from desorption measurements at various temperatures. In the present study these values ranged from 60 to 100 kJ/mol among the various soils and sediments studied.

In rat tIMCD, NH4+ uptake by Na+-K+-ATPase is critical to net acid secretion during chronic hypokalemia.

The purpose of this study was to determine the magnitude of Na+ pump-mediated NH4+ uptake in the terminal inner medullary collecting duct (tIMCD) at K+ and NH4+ concentrations observed in vivo in the inner medullary interstitium of normal and in K+-restricted rats. Interstitial K+ and NH4+ concentrations in the terminal half of the inner medulla were taken to be 10 and 6 mM in K+-restricted rats, but 30 and 6 mM in K+-replete rats. In tubules from K+-restricted rats, when perfused at a K+ concentration of 10 mM, addition of ouabain to the bath reduced total bicarbonate flux (JtCO2) by 40% and increased intracellular pH (pHi), indicating significant NH4+ uptake by the Na+-K+-ATPase. In tubules from K+-restricted rats, JtCO2 was reduced with increased extracellular K+. At a K+ concentration of 30 mM, ouabain addition neither reduced JtCO2 nor increased pHi in tubules from rats of either treatment group. In conclusion, in the tIMCD from hypokalemic rats, 1) acute changes in extracellular K+ concentration modulate net acid secretion, and 2) Na+ pump-mediated NH4+ uptake should be an important pathway mediating transepithelial net acid secretion in vivo.

Advice provided in British community pharmacies: what people want and what they get.

OBJECTIVES: This study explored advice-giving behaviour in community pharmacies in order to understand the nature and process of pharmaceutical consultations and consumers' views of the advice-giving role. METHOD: An ethnographic research strategy was used, combining patient interviews with non-participant observation of interactions between consumers and pharmacy staff. One week was spent in each of 10 pharmacies. RESULTS: The study demonstrated that the advice given in a community pharmacy is almost wholly focused on product recommendation and use. Advice-giving varies according to whether consultations concern prescription or non-prescription medicines. When the latter are involved, advice-giving is mostly consumer-led. Consumers' major 'need' for pharmacy services appears to be for information about the effectiveness of products they buy, whilst pharmacists and pharmacy assistants concentrate on providing advice on the safety of medicines. CONCLUSION: The notion of pharmacists as general health advisors does not appear to be shared by the public and may be at odds with how the public view and use pharmacies. Protocols to guide staff may be improved by including the consumer perspective. Most consumers have previous experience of their ailments and use pharmacies as one of several resources available to them to treat their minor illness, having made their own diagnosis and assessment before entering the pharmacy. The scope for giving new advice is therefore limited. The broader role of community pharmacies merits further attention.

Altered hemostasis in pulmonary hypertension.

Pulmonary hypertension is characterized by increased pressure in the pulmonary circulation and, in some cases, inflammation. Significant vascular remodeling occurs in response to these stresses and histopathology demonstrates in-situ thrombosis in a significant number of cases. Elevated shear stresses and inflammation, based on in-vitro data, would be expected to enhance platelet activation and aggregation/adhesion, increase release of von Willebrand factor, increase tissue factor expression, downregulate surface thrombomodulin with diminished thrombin inactivation and decreased protein C activation, and alter fibrinolytic factors with a net loss of fibrinolysis. Data from animal and human studies of pulmonary hypertension provide evidence for increased platelet activation, decreased platelet survival, increased release of von Willebrand factor antigen without an increase in activity, decreased soluble thrombomodulin and a net loss of fibrinolytic activity with excessive release of plasminogen activator inhibitor-1. These changes may result in in-situ thrombosis, which may occur as an inciting event of pulmonary hypertension, or as a consequence of other initiating factors. Chronic anticoagulation has been used in pulmonary hypertension based on observations of increased survival. However, the direct link between altered coagulation and the development or persistence of pulmonary hypertension awaits confirmation.