Measurement of prethrombotic markers in the assessment of acquired hypercoagulable states

Hypercoagulable states can be detected by measuring activation peptides, enzyme-inhibitor complexes, and fibrin/fibrinogen degradation products, which are markers of hemostatic activation. A series of these prethrombotic markers has been evaluated in the elderly, pregnancy, diabetes and acute myocardial infarction patients (n=30 in each group) as well as in hematologic malignancies (n=42). The parameters assayed were: prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complexes (TAT), fibrinopeptide A (FPA), plasmin-alpha2 antiplasmin complexes (PAP) and D-Dimer. Results were compared with those obtained in a group of 30 healthy subjects. We found a significant increase of F1+2, TAT and FPA in elderly (p<0.05), acute myocardial infarction (AMI) (p<0.01), hematologic malignancies (p<0.01), and pregnancy (p<0.0001), indicating a marked clotting activation. Diabetic patients under strict metabolic control only presented a moderate increase of TAT (p<0.05), suggesting a slight activation. We also observed a highly significant elevation of PAP and D-Dimer in elderly (p<0.001), AMI (p<0.0001), and malignancy (p<0.0001), indicating an activation of the fibrinolytic system. The combination of selected fibrinolytic and coagulation measurements is useful for the detection of a hypercoagulable state in conditions characterized by a risk of thrombosis

Does desmopressin acetate reduce blood loss after surgery in patients on cardiopulmonary bypass?

It has been suggested that desmopressin acetate (DDAVP) administration reduces blood loss after cardiac surgery. We have investigated the effect of DDAVP administration in a double-blind, randomized, prospective trial including 100 patients placed on cardiopulmonary bypass during surgery. Fifty patients received 0.3 micrograms/kg DDAVP and 50 patients received a placebo administered in a 50 ml saline solution over 15 min when cardiopulmonary bypass had been concluded. Results showed no significant differences either in total blood loss per square meter (458 +/- 206 ml in the DDAVP group vs 536 +/- 304 ml in the placebo group) or in necessity for red cell transfusions (1642 +/- 705 ml in the DDAVP group vs 1574 +/- 645 ml in the placebo group) in the first 72 hr after surgery. Only intraoperative blood loss per square meter was significantly lower (p less than .02) in the DDAVP group (131 +/- 106 ml) as compared with the placebo group (193 +/- 137 ml). The prolongation of bleeding time and the decrease of factor VIII:C and factor VIII:von Willebrand factor 90 min after treatment were significantly lower (p less than .001) in the DDAVP group as compared with the placebo group. We conclude that the administration of DDAVP in patients placed on cardiopulmonary bypass during surgery does not reduce total blood loss and is only effective in reducing intraoperative bleeding

Clotting activation and impairment of fibrinolysis in malignancy

Different coagulation and fibrinolysis parameters were investigated in 149 patients with metastatic and non-metastatic tumours and results were compared with those obtained in a healthy population. Results showed a significant increase of thrombin-antithrombin complexes, fibrinopeptide A (FPA) and fibrin monomers in the group of patients (p less than 0.001). There was also a significant prolongation of euglobulin lysis time (p less than 0.005) and an increase of plasminogen activator inhibitor activity (p less than 0.0001), fibrinogen degradation products (p less than 0.001), and D-dimer (p less than 0.05) in the group of patients as compared to controls; FPA levels were also increased in patients with metastases (p less than 0.005). This study demonstrates clotting activation, at the level of fibrinogen to fibrin conversion, and impairment of fibrinolysis in patients with malignancy

Fibrinogen Sevilla, a congenital dysfibrinogenemia characterized by an abnormal monomer aggregation and a defective plasmin lysis

A dysfibrinogenemia (fibrinogen Sevilla) was detected in a 64-yr-old woman with no previous history of hemorrhagic diathesis or thrombosis. Thrombin and reptilase times were prolonged. The aggregation of fibrin monomers showed a prolonged latency time with a defective slope although fibrinopeptide release and clot stabilization were found to be normal. Plasmin proteolysis was abnormal with a much slower plasmic degradation in patient's purified fibrinogen. By chromatofocussing the patient's fibrinogen showed an abnormality in pattern elution with a second peak eluting at a pH slightly more basic than the normal one (pH 5.5). Likewise, the isoelectrofocussing of purified non-reduced patient's fibrinogen in agarose gel showed an abnormal distribution in its focussed bands, especially in a group which focussed in a pI-interval between 5.20-5.85. By two-dimensional electrophoresis we did not find any abnormality in the fibrinogen-reduced chains. These results could indicate that the abnormal monomer aggregation, as well as the defective plasmin lysis, could be due to conformational aspects of fibrinogen rather than to structural defects

First record of Palaemon macrodactylus Rathbun, 1902 (Decapoda, Palaemonidae) in the western Mediterranean

The Mediterranean Sea is one of the world’s hotspots for marine bio-invasions. Most invasions are first documented based on an initial record of occasional adult captures. However, reports of larval stages could indicate that there is an adult population that is reproducing and therefore well established in the area. The spread of the oriental shrimp, Palaemon macrodactylus, from its native estuarine waters of southeast Asia to new regions worldwide is well documented. We report the first record of this species in the Mediterranean based on the presence of its larval stages in plankton samples. Decapod larvae were collected in five offshore plankton surveys performed off the Balearic Islands (western Mediterranean), and zoeae III and VI of the oriental shrimp were found among them. Taking into account the duration of the successive developmental stages, and the hydrodynamic characteristics of the study area, these larvae were most probably spawned by adult populations not yet documented. The larvae were found in marine waters despite the fact that adults usually inhabit brackish waters. Our study is a good example of how plankton studies can help to detect larval stages of invasive species before the adult populations are detectedPublicado

Long-term ecological research of aquatic ecosystem at Guadalquivir estuary (1997-2014): community structure and food web

A long term ecological research program (LTER) is developed monthly at the Guadalquivir estuary since 1997. Inter- and intra-specific euryhalinity differences both in prey and predators seem to determine spatial species distribution at this important nursery area: the less euryhaline species (marine recruits) tends to occur at physiologically more favourable salinities (lower osmotic stress and mortality risk); whereas most euryhaline species (estuarine species) occurred at ecologically more favourable salinities (lower inter-specific competition and predation). Likewise, inter-specific differences in spawning periods cause certain temporal segregation of those marine recruits using the estuary. High spatiotemporal coincidence of prey (mainly mysids and copepods) density peaks with that of their predators suggests food availability as a key factor in the estuarine nursery function. According to their distribution, the estuarine stretch situated seaward from the 5 isohaline position is mainly used as a nursery ground, principally during warm period (T > 15 °C). Thus, human management of the freshwater input to the estuary (from a 110 km upstream dam) modifies the nursery ground extent due to seaward/upstream displacements of the estuarine salinity gradient. During droughts, this freshwater control may also lead to a partial loss of the estuarine nursery function due to a decrease of prey availability linked to extremely high-turbidity events

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Study on the distribution of different species of Aristeus and Solenocera (Crustacea: Decapoda: Penaeoidea) along the African coast, based on the speciments from stock assessment cruises.

El estudio y seguimiento de la actividad pesquera es una herramienta de gran utilidad de cara a lograr su sostenibilidad, así como para maximizar su aprovechamiento, especialmente en aquellas zonas donde la escasa información disponible podría dar lugar a una gestión inadecuada y por lo tanto a un impacto importante sobre los recursos. La composición de especies de interés económico puede variar a lo largo del tiempo, por lo que resulta fundamental tener un conocimiento del conjunto de los organismos que de alguna manera, forman parte o son influidos por la actividad pesquera. El presente estudio se centra en dos géneros de crustáceos (Aristeus y Solenocera) con una presencia importante en las capturas que los buques pesqueros realizan en los caladeros incluidos en el área de estudio. Ésta abarca la costa atlántica africana, así como la costa de Mozambique, y las costas atlántica y mediterránea españolas. Se han estudiado más de 300 ejemplares pertenecientes a los citados géneros, tanto desde el punto de vista morfológico como molecular, con el objetivo principal de aportar información nueva sobre la distribución de las especies, así como delimitar más claramente los límites de sus distribuciones

Inherited haemorrhagic disease with abnormal prothrombin consumption

The propositus is a 4-year-old boy who presented with a history of excessive bleeding after surgical procedures as well as haematomas and epistaxis. The defect in haemostasis consisted in an anomaly of the prothrombin consumption tests as the only abnormality while all the other conventional coagulation and fibrinolysis tests as well as platelet function tests were normal. The father of the propositus had no previous history of excessive bleeding but was found to have an abnormal prothrombin consumption index. The reaction to prothrombin conversion, normal at onset, slowed down to less than normal and did not reach completion until 24 h. The in vivo studies suggest that the effect does not act on the interaction between platelet phospholipid and plasma. The factor II dosage and the electrophoretic mobility of prothrombin of the plasma were normal; nevertheless when studying the purified prothrombin by means of crossed immunoelectrofocusing there appeared an anomaly of pI. This result suggests the possible existence of an abnormal prothrombin molecule responsible for a slow prothrombin conversion