Platelets

Background and Purpose— Tirofiban is a highly selective, fast-acting nonpeptide glycoprotein IIb/IIIa platelet receptor antagonist with a short half-life time. Glycoprotein IIb/IIIa antagonists are effective for the treatment of acute coronary syndromes proven in large clinical trials. Safety and efficacy in patients with ischemic stroke are uncertain. This was addressed in the Safety of Tirofiban in acute Ischemic Stroke (SaTIS) trial. Methods— Two hundred sixty patients with acute ischemic stroke were randomized in a placebo-controlled, prospective, open-label treatment, blinded outcome reading multicenter trial. Subjects with a National Institutes of Health Stroke Scale between 4 and 18 received intravenously either tirofiban or placebo within 3 to 22 hours after symptom onset for 48 hours. The primary end point was the rate of cerebral bleeding as measured in follow-up CT scans 2 to 7 days after inclusion. The secondary end point was clinical efficacy within 1 week (National Ins...

Venous thromboembolism (VTE) is a significant cause of mortality in patients with lung cancer. Despite the availability of a wide range of anticoagulants to help prevent thrombosis, thromboprophylaxis in ambulatory patients is a challenge due to its associated risk of haemorrhage. As a result, anticoagulation is only recommended in patients with a relatively high risk of VTE. Efforts have been made to develop predictive models for VTE risk assessment in cancer patients, but the availability of a reliable predictive model for ambulate patients with lung cancer is unclear. We have analysed the latest information on this topic, with a focus on the lung cancer-related risk factors for VTE, and risk prediction models developed and validated in this group of patients. The existing risk models, such as the Khorana score, the PROTECHT score and the CONKO score, have shown poor performance in external validations, failing to identify many high-risk individuals. Some of the newly developed an...

BACKGROUND: Whether high-ratio resuscitation (HRR) provides patients with survival advantage remains controversial. We hypothesized a direct correlation between HRR infusion rates in the first 180 minutes of resuscitation and survival. STUDY DESIGN: This was a retrospective analysis of massively transfused trauma patients surviving more than 30 minutes and undergoing surgery at a level 1 trauma center. Mean infusion rates (MIR) of packed red blood cells (PRBC), fresh frozen plasma (FFP), and platelets (Plt) were calculated for length of intervention (emergency department [ED] time þ operating room [OR] time). Patients were categorized as HRR (FFP:PRBC > 0.7, and/or Plts: PRBC > 0.7) vs low-ratio resuscitation (LRR). Student's t-tests and chi-square tests were used to compare survivors with nonsurvivors. Cox proportional hazards regression models and Kaplan-Meier curves were generated to evaluate the association between MIR for FFP:PRBC and Plt:PRBC and 180-minute survival. RESULTS: There were 151 patients who met criteria: 121 (80.1%) patients survived 180 minutes (MIR:PRBC 71.9 mL/min, FFP 92.0 mL/min, Plt 3.5 mL/min) vs 30 (19.9%) who did not survive (MIR:PRBC 47.3 mL/min, FFP 33.7 mL/min, Plt 1.1 mL/min), p ¼ 0.43, p < 0.0001 and p < 0.011, respectively. A Cox regression model evaluated PRBC rate, FFP rate, and Plt rate (mL/min) as mortality predictors within 180 minutes to assess if they significantly affected survival (hazard ratios 1.01 [p ¼ 0.054], 0.97 [p < 0.0001], and 0.75 [p ¼ 0.01], respectively). Another model used stepwise Cox regression including PRBC rate, FFP rate, and Plt rate (hazard ratios 1.00 [p ¼ 0.85], 0.97 [p < 0.0001], and 0.88 [p ¼ 0.24], respectively), as well as possible confounding variables. CONCLUSIONS: This is the first study to examine effects of MIRs on survival. Further studies on the effects of narrow time-interval analysis for blood product resuscitation are warranted.

Platelet aggregation may be an important factor in the feasibility of transcatheter laser angioplasty. The in vitro effects of increasing doses of CO, laser irradiation on platelet number, function, and surface ultrastructure were examined. Results indicated a progressive doseresponse reduction of both platelet number and function following laser irradiation. By scanning electron microscopy the irradiated platelets showed dose-related changes in pseudopods as well as progressive damage of the cell membrane.

Upon stimulation with agonists, platelets express CD40 ligand (CD40L), a transmembrane protein implicated in the initiation and progression of atherosclerotic disease. We have recently discovered that oxidative stress plays a major role in platelet CD40L expression. In this study, we sought to determine whether vitamin C, a known antioxidant, is able to influence platelet CD40L expression. In vitro experiments were done by stimulating platelets with collagen in the presence or absence of vitamin C (50-100 AM) or vehicle as control. An in vivo study was done in 10 healthy subjects who were randomized to intravenous infusion of placebo or 1 g vitamin C for 45 min in a crossover design. At the end of infusion platelet CD40L and O 2-were measured. The in vitro study demonstrated that vitamin C dose dependently inhibited platelet CD40L expression without affecting agonist-induced platelet aggregation. In subjects treated with placebo no changes of platelet CD40L and O 2-were observed; conversely, vitamin C infusion caused a significant and parallel decrease of platelet O 2-(À70%, P b 0.001) and CD40L (À68%, P b 0.001). Platelet aggregation was not modified by either treatment. This study suggests that water-soluble antioxidants, which scavenge superoxide radicals, may reduce platelet CD40L expression.

Objective: Vivax malaria is common in Pakistan. We carried out this study to determine the effects of this infection on blood counts and the impact of splenomegaly on these results.
Methods: This was a retrospective observational study carried out at 1 Mountain Medical Battalion, Bagh, Azad Kashmir. Old medical records of all patients admitted with vivax malaria from Jan 2010 to Oct 2012 were scrutinized. The presence or absence of a palpable spleen and the results of complete blood counts and platelet counts measured at the time of admission were noted down. Anaemia was defined as Hb<13g/dl in men, leukopenia as total leukocyte count (TLC)<4000/µl and thrombocytopenia as platelets count <150000/µl. Data was analysed with STATA version 12.1. The results of haematology parameters were compared amongst patients with splenomegaly and the rest.
Results: Anaemia was seen in 22.15%, neutropenia in 23.49% and thrombocytopenia in 90.60% of the 149 male patients having a mean age of 27.54±5.11 years. The differences in mean blood counts and the number of patients with haematological abnormalities in the two groups were statistically insignificant.
Conclusion: Since the blood counts are not affected by presence or absence of splenomegaly, mechanisms other than hypersplenism are important.

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The clinical use of platelet-rich plasma (PRP) is based on the increase in the concentration of growth factors and in the secretion of proteins which are able to maximize the healing process at the cellular level. Since PRP is an autologous biologic material, it involves a minimum risk of immune reactions and transmission of infectious and contagious diseases, and it has been widely used for the recovery of musculoskeletal lesions. Despite the great potential for applicability, the implementation of the therapeutic employment of PRP as a clinical alternative has become difficult, due to the lack of studies related to the standardization of the techniques and/or insufficient description of the adopted procedures. Therefore, it is required establish standard criteria to be followed for obtaining a PRP of high quality, as well as a larger number of studies which should establish the proper concentration of platelets for the different clinical conditions. In this context, the purpose of this review is to discuss some methodological aspects used for achieving the PRP, as well as to discuss the bioactive properties of PRP, and to point out its therapeutic use in different fields of regenerative medicine.

Atherosclerosis is a chronic inflammatory condition of the blood vessel wall that can lead to arterial narrowing and subsequent vascular compromise. Although there are a variety of open and endovascular procedures used to alleviate the obstructions caused by atherosclerotic plaque, blood vessel instrumentation itself can lead to renarrowing of the vessel lumen through intimal hyperplasia, wound contracture, or a combination of the two. While the cell types involved in both atherosclerosis and vessel renarrowing after surgical intervention are largely characterized, current research has shown that components of the extracellular matrix are also important in the pathogenesis of the aforementioned processes. One such component is hyaluronic acid (HA). The objective of this review, therefore, is to examine the involvement of HA in these pathologic processes.

Background: Acquired Glanzmann's thrombasthenia (aGT) is a rare hemorrhagic disorder caused by autoantibodies, alloantibodies, or paraproteins directed against platelet GPIIb/IIIa. Its diagnosis requires several laboratory assays and mixing tests, which are complex and time consuming. We describe here a new case of aGT and compare different tests for the detection of GPIIb/IIIa-blocking autoantibodies.

The factors controlling the lifespan of platelets both in vivo and in vitro are poorly understood. What is known is that platelet aging in vivo leads to a reduction in the platelets' responsiveness to physiological agonists and that younger platelets are more haemostatically active than older ones. Under in vitro and ex vivo conditions platelets also lose function and ultimately die for reasons that are unclear, by mechanisms that share some similarity with those used by nucleated cells for programmed cell death. The consequences of platelet death in vitro include the formation of a novel platelet-platelet interaction that occurs between dead but not viable platelets and the shedding of the collagen receptor, GPVI and CD42b, a component of the von Willebrand receptor complex. Both of these phenomena appear to be regulated by metalloproteinase activity. In addition to these observations it is becoming increasingly clear that platelets execute a novel form of programmed cell death in response to agonists such as collagen and thrombin suggesting that their death is intimately associated with effective haemostasis. Finally, platelets must be removed from circulation. It is unclear how senescent platelets are removed, but monocyte-macrophages are an important determinant of thrombus resolution possibly due to the phagocytosis of effete, activated platelets.

Our aim was to describe the treatment of iatrogenic previable premature rupture of membranes with the intra-amniotic injection of platelets and cryoprecipitate (amniopatch). STUDY DESIGN: Patients with iatrogenic previable premature rupture of membranes and without evidence of intra-amniotic infection underwent transabdominal intra-amniotic injection of platelets and cryoprecipitate through a 22-gauge needle. The study was approved by the Institutional Review Board of St Joseph's Hospital in Tampa, Florida, and all patients gave written informed consent. RESULTS: Seven patients with iatrogenic preterm premature rupture of membranes underwent placement of an amniopatch. Membrane sealing was verifiable in 6 of 7 patients. Three patients had iatrogenic preterm premature rupture of membranes after operative fetoscopy, 3 cases were after genetic amniocentesis, and 1 was after diagnostic fetoscopy. Three pregnancies progressed well, with restoration of the amniotic fluid volume and no further leakage. Two patients had unexplained fetal death despite successful sealing. One case of bladder outlet obstruction had no further leakage, but oligohydramnios persisted and did not allow unequivocal documentation of sealing. One patient miscarried from twin-twin transfusion, but the amniotic cavity was sealed. CONCLUSIONS: Iatrogenic preterm premature rupture of membranes can be treated effectively with an amniopatch. The technique is simple and does not require knowledge of the exact location of the defect. Unexpected fetal death from the procedure may be attributable to vasoactive effects of platelets or indigo carmine. Although the appropriate dose of platelets and cryoprecipitate needs to be established, the amniopatch may mean that iatrogenic preterm premature rupture of membranes no longer needs to be considered a devastating complication of pregnancy. (Am J Obstet Gynecol 1999;181:744-9.)

Conclusion: Using Alaris CC/GP infusion pumps had no influence on the cellular, functional, and phenotypic in vitro properties of platelets.

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Sn-Bi solders may be applied for electronic applications where low-temperature soldering is required, i.e., sensitive components, step soldering and soldering LEDs. In spite of their potential to cover such applications, the mechanical response of soldered joints of Sn-Bi alloys in some cases does not meet the strength requirements due to inappropriate resulting microstructures. Hence, careful examination and control of as-soldered microstructures become necessary with a view to pre-programming reliable final properties. The present study aims to investigate the effects of solidification thermal parameters (growth rate -V L and cooling rate -Ṫ L ) on the microstructure of the Sn-52 wt.%Bi solder solidified under unsteady-state conditions. Samples were obtained by upward directional solidification (DS), followed by characterization through metallography and scanning electron microscopy (SEM). The microstructures are shown to be formed by Sn-rich dendrites decorated with Bi precipitates surrounded by a complex regular eutectic mixture, with alternated Bi-rich and Sn-rich phases. Experimental correlations of primary (λ 1 ), secondary (λ 2 ), tertiary (λ 3 ) dendritic and eutectic spacings (λ coarse and λ fine ) with cooling rate and growth rate are established. Two ranges of lamellar eutectic sizes were determined, described by two experimental equations λ = 1.1 V L −1/2 and λ = 0.67 V L −1/2 . The onset of tertiary branches within the dendritic array along the Sn-52 wt.%Bi alloy DS casting is shown to occur for cooling rates lower than 1.5°C/s.

Understanding the physiology of fluid distribution within the human body is fundamental to the practice of anaesthetists and intensivists of all grades. There is a necessity to recognize the range of actions and consequences of the commonly infused intravenous fluids if safe patient care is to be provided. There are many historical and on-going trials surrounding fluid therapy and it is important for the physician to keep up to date with current guidelines.

Injury to the hamstring muscle complex (HMC) is extremely common in the athletic community. Anatomical and functional aspects of the HMC predispose it to injury, including the fact that the muscles cross two joints and undergo eccentric contraction during the gait cycle. Injury most commonly occurs at the muscle tendon junction but may occur anywhere between the origin and insertion. Complete hamstring avulsions require early surgical repair. The principal indication for imaging is in a triage role to rule out or confirm proximal hamstring avulsion. Acute onset and chronic posterior thigh and buttock pain may relate to pathology at the hamstring origin or muscle tendon junction that can be readily defined on magnetic resonance imaging or, less frequently, ultrasound. Some cases of buttock and thigh pain may relate to spinal pathology. In the elite athlete there is an increasing emphasis on optimizing the rehabilitation process after hamstring injury, to minimize the absence from sports and improve the final outcome. Imaging has a role in confirming the site of injury and characterizing its extent, providing some prognostic information and helping plan treatment. There is increasing interest in the use of growth factors to accelerate healing after muscle and tendon injury. Animal studies have demonstrated clear benefits in terms of accelerated healing. There are various methods of delivery of the growth factors, all involving the release of growth factors from platelets. These include plasma rich in platelets and autologous blood. Clinical studies in humans are very limited at this stage but are promising. At present the World Anti-Doping Authority bans the intramuscular administration of these agents. Other percutaneous injection therapies include the use of Actovegin and Traumeel S and antifibrotic agents.

Platelets are especially well known for their thrombotic role. However, besides their role on stopping bleeding, platelets contribute for several mechanisms and steps in wound healing and tissue repair, such as inflammation, angiogenesis, cells proliferation, and differentiation.
The potential of platelets to be used therapeutically to assist in wound repair led researchers around the world to look at platelet-based products and their capacity to promote tissue regeneration, in vitro and in vivo. In this chapter, we will discuss the main growth factors present in platelet granules that affect tissue regeneration. In addition, we will consider how platelet-derived products, such as those obtained from platelet-rich plasma (PRP), can be used to enhance tissue regeneration. We will review the applications of this knowledge in clinical
trials, and in vivo models, as well as discussing the capacity for platelet products to substitute for classical components of media for in vitro cell culture.

Las plaquetas fueron el último de los elementos formes de la sangre en ser descubierto. Durante el siglo XIX, numerosos observadores reportaron la presencia en la sangre de corpúsculos más pequeños que los glóbulos rojos y los glóbulos blancos. Friederich Arnold (1803-1890), fue el primer anatomista en reconocer e ilustrar plaquetas en 1845. En 1862 Max Schultze (1825-1874), describió ciertos corpúsculos incoloros que tendían a agruparse, y los llamó "pequeños elementos". Giulio Bizzozero (1841-1901), aisló plaquetas de los trombos e identificó a la hemostasia y a la trombosis como procesos análogos. En 1886, Eberth y su asistente observaron que la estasis sanguínea llevaba al depósito de las plaquetas sobre el endotelio formando un "trombo rojo", fenómeno al que denominó "metamorfosis viscosa" de las plaquetas. En 1906, James Homer Wright (1869-1928), descubrió, que los megacariocitos daban lugar a las plaquetas. A lo largo de los últimos 60 años Hellem, Hovig, Owren, Ardlie y Kloeze caracterizaron a los agonistas y antagonistas junto con sus receptores en la membrana plasmática de las plaquetas, el análisis de los mecanismos moleculares implicados en la transducción de la señal y, sobre todo, la introducción en la medicina de tratamientos antiplaquetarios dirigidos a la prevención primaria y secundaria de desórdenes aterotrombóticos.

Understanding the physiology of fluid distribution within the human body is fundamental to the practice of anaesthetists and intensivists of all grades. There is a necessity to recognize the range of actions and consequences of the commonly infused intravenous fluids if safe patient care is to be provided. There are many historical and on-going trials surrounding fluid therapy and it is important for the physician to keep up to date with current guidelines.

The platelet receptor glycoprotein (GP)Ib-IX-V complex plays a dominant role in the first steps of platelet adhesion and arterial thrombus formation. Through its interaction with the multimeric plasma protein von Willebrand factor (VWF), which is bound to the damaged subendothelial structures, GPIb-IX-V tethers the platelets from the flowing blood thereby slowing them down. This step is a prerequisite for the collagen receptors to participate in firm adhesion resulting in the formation of a first platelet layer which is the basis for further thrombus formation. Recently, other ligands for GPIb-IX-V besides the extensively studied VWF have been identified, such as : -thrombin, coagulation factor XII (FXII), high molecular weight kininogen (HMWK), factor XI (FXI), integrin Mac-1 and P-selectin. In this review, the interaction of GPIb-IX-V with its different ligands is described and the anticipated or demonstrated in vivo effects are discussed.

Background The involvement of platelets in the pathogenesis of diabetic vascular complications is supported by several studies. Type 1 diabetic (T1D) platelets show increased adhesiveness and aggregation related to a modification of nitric oxide synthase activity. Moreover, different cell types from diabetic patients showed a decreased membrane Na + /K + -ATPase activity, which might be involved in diabetic complications. The aim of this study was to investigate whether T1D at onset is able to induce alterations of platelet physicochemical and functional properties and whether these changes are affected by hyperglycaemia.

Resuscitation of a severely traumatised patient with the administration of crystalloids, or colloids along with blood products is a common transfusion practice in trauma patients. The determination of this review article is to update on current transfusion practices in trauma. A search of PubMed, Google Scholar, and bibliographies of published studies were conducted using a combination of key-words. Recent articles addressing the transfusion practises in trauma from 2000 to 2014 were identified and reviewed. Trauma induced consumption and dilution of clotting factors, acidosis and hypothermia in a severely injured patient commonly causes trauma-induced coagulopathy. Early infusion of blood products and early control of bleeding decreases trauma-induced coagulopathy. Hypothermia and dilutional coagulopathy are associated with infusion of large volumes of crystalloids. Hence, the predominant focus is on damage control resuscitation, which is a combination of permissive hypotension, haemorrhage control and haemostatic resuscitation. Massive transfusion protocols improve survival in severely injured patients. Early recognition that the patient will need massive blood transfusion will limit the use of crystalloids. Initially during resuscitation, fresh frozen plasma, packed red blood cells (PRBCs) and platelets should be transfused in the ratio of 1:1:1 in severely injured patients. Fresh whole blood can be an alternative in patients who need a transfusion of 1:1:1 thawed plasma, PRBCs and platelets. Close monitoring of bleeding and point of care coagulation tests are employed, to allow goal-directed plasma, PRBCs and platelets transfusions, in order to decrease the risk of transfusion-related acute lung injury.

Vascular injury leads to formation of a structured thrombus as a consequence of platelet activation and aggregation, thrombin and fibrin formation, and trapping of leukocytes and red cells. This review summarises current evidence for heterogeneity of platelet responses and functions in the thrombus-forming process. Environmental factors contribute to response heterogeneity, as the platelets in a thrombus adhere to different substrates, and sense specific (ant)agonists and rheological conditions. Contraction of platelets and interaction with fibrin and other blood cells cause further response variation. On the other hand, response heterogeneity can also be due to intrinsic differences between platelets in age and in receptor and signalling proteins. As a result, at least three subpopulations of platelets are formed in a thrombus: aggregating platelets with (reversible) integrin activation, procoagulant (coated) platelets exposing phosphatidylserine and binding coagulation factors, an...

Platelet secretion not only drives thrombosis and haemostasis, but also mediates a variety of other physiological and pathological processes.  The ubiquitous SNARE machinery and a number of accessory proteins have been implicated in regulating secretion in platelets.  Although several platelet SNAREs have been identified, further members of the SNARE family may help fine-tune platelet secretion.  In this study I identified expression of t-SNAREs VTI1A, VTI1B (Qb SNAREs) and STX8 (Qc SNARE) in human and mouse platelets.  Those ‘novel’ SNAREs were able to interact with each other and previously reported SNAREs VAMP8 (R-SNARE) and STX11 (Qa SNARE), thus suggesting existence of a secondary SNARE complex in addition to the widely accepted SNAP23-VAMP8-STX11 complex.  In following mouse studies, whereas neither gene was found to
be essential for α-granule or lysosome secretion, Stx8-/- platelets showed a significant defect in dense granule secretion and aggregation, that was most pronounced at intermediate concentrations of agonists.  Addition of exogenous ADP could rescue the aggregation defect but failed to restore dense granule secretion, suggesting the defect lies in the ‘primary’ secretory pathway.  Pretreatment with P2Y receptors antagonists reduced secretion and aggregation to the same extent in WT and Stx8-/- platelets, suggesting that the ADP-driven positive feedback mechanism was not defective in Stx8-/- platelets.  In addition, STX8 was found to play a role in regulating pro-coagulant activity suggesting novel roles for SNAREs in platelets.  Neither Vti1a-/- nor Vti1b-/- showed any
significant defects, suggesting complementarity between those homologues in
platelets.  STX8 therefore specifically contributes to dense granule secretion and
represents another member of a growing family of genes that play distinct roles
in differentially regulating granule release from platelets.  Taken together, data
presented in this Thesis not only provides first evidence of an additional SNARE complex present in platelets but also suggests novel roles for SNAREs in regulation of thrombosis and haemostasis

Type 2 diabetes mellitus induces a number of cardiovascular disorders, including platelet hyperactivity and hyperaggregability, which is associated to an increased oxidant production and abnormal cytosolic Ca 2+ mobilization. In the present study, we have investigated the eVect of cinnamtannin B-1 obtained from bay wood on oxidants production, Ca 2+ mobilization and aggregation in platelets from type 2 diabetic donors. Pretreatment of platelets with cinnamtannin B-1 reversed the enhanced oxidants production and Ca 2+ mobilization, including Ca 2+ entry, evoked by thapsigargin plus ionomycin or thrombin, observed in platelets from diabetic subjects, so that in the presence of cinnamtannin B-1 Ca 2+ entry was similar in platelets from healthy and diabetic subjects. In addition, cinnamtannin B-1 reduced thrombin-induced aggregation in platelets from type 2 diabetic subjects. We conclude that cinnamtannin B-1 exerts an eVective antioxidant action in platelets from patients with type 2 diabetes mellitus and reverses the enhanced Ca 2+ mobilization and hyperaggregability.

Objective: To determine the accuracy of thrombocytopenia as a diagnostic marker for malaria. Study Design: Cross-sectional study. Place and Duration of Study: Department of Medicine, 1 Mountain Medical Battalion (Bagh, Azad Kashmir) from July to September 2013. Methodology: Adult patients presenting with a short history of fever without any localizing symptoms or signs were included. Exclusion criteria included patients with fever of > 7 days duration, those in whom an underlying diagnosis could be easily confirmed on the basis of history and physical examination, those on antibiotics/ antimalarials or antiplatelet agents and patients with Dengue fever. Platelet counts in venous whole blood samples were analysed with Sysmex KX-21 Haematology analyzer. Thick and thin peripheral blood smears were then prepared and examined for malarial parasites. Diagnosis of malaria was established on the basis of smear findings. Results: There were 245 patients in total. Out of the 109 patients with thrombocytopenia, 61 had vivax malaria. Platelets count was normal in 136 patients, including 4 with vivax malaria. Falciparum malaria was not seen in any patient. All cases with malaria were uncomplicated. Various measures of accuracy thus calculated were sensitivity 93.85%, specificity 73.33%, positive predictive value 55.96%, negative predictive value 97.06%, positive likelihood ratio of 3.52, negative likelihood ratio of 0.08, diagnostic odds ratio 41.94 and diagnostic accuracy of 78.78%. Conclusion: Thrombocytopenia has an excellent sensitivity and a very good specificity for vivax malaria. Normal platelet counts provide very strong evidence against malaria as the etiology of fever without a focus.

L~~crobacillu.s rhurnnosus CC is an experimentally and clinically well documented probiotic used in different dairy products. The present study aimed to investigate the safety aspects of Lactobtrcillus rhmnno.su.s GG, particularly with respect to platelet aggregation, the initiating event in thrombosis. Platelet rich plasma was separated from the blood of healthy volunteers, and the effects of Luctnbucillus rhumnosus GG (ATCC _5_?103), Lactobacillus rhnmrwsus (ATCC 74hY) uncl Entermoccus fiwcium T2Lh in different dilutions on spontaneous. ADP-and adrenaline-induced aggregation were tested. The bacteria did not influence spontaneous aggregation. Only EnterococcLlsfilecium T2L6 enhanced the adrenaline-induced aggregation, with a less clear effect on ADP-induced aggregation.

a b s t r a c t a r t i c l e i n f o When platelet numbers are low or when their function is disabled, the risk of bleeding is high, which on the one hand indicates that in normal life vascular damage is a rather common event and that hence the role of platelets in maintaining a normal hemostasis is a continuously ongoing physiological process. Upon vascular injury, platelets instantly adhere to the exposed extracellular matrix resulting in platelet activation and aggregation to form a hemostatic plug. This self-amplifying mechanism nevertheless requires a tight control to prevent uncontrolled platelet aggregate formation that eventually would occlude the vessel. Therefore endothelial cells produce inhibitory compounds such as prostacyclin and nitric oxide that limit the growth of the platelet thrombus to the damaged area. With this review, we intend to give an integrated survey of the platelet response to vascular injury in normal hemostasis.

Upon activation, platelets secrete more than 300 active substances from their intracellular granules. Platelet dense granule components, such as ADP and polyphosphates, contribute to haemostasis and coagulation, but also play a role in cancer metastasis. α-Granules contain multiple cytokines, mitogens, pro- and anti-inflammatory factors and other bioactive molecules that are essential regulators in the complex microenvironment of the growing thrombus but also contribute to a number of disease processes. Our understanding of the molecular mechanisms of secretion and the genetic regulation of granule biogenesis still remains incomplete. In this review we summarise our current understanding of the roles of platelet secretion in health and disease, and discuss some of the hypotheses that may explain how platelets may control the release of its many secreted components in a context-specific manner, to allow platelets to play multiple roles in health and disease.

Background: LCn-3PUFA comprised of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) offer cardioprotection involving a decrease in coagulant activity; however, the evidence is equivocal. We have previously demonstrated that the acute (24 h) effects and chronic (4 weeks) effects of LCn-3PUFA supplementation on platelet aggregation in human subjects are sex specific. This study investigated the mechanisms of the sex-dependent effects of LCn-3PUFA with 4 weeks supplementation of EPA-rich vs. DHA-rich oils on procoagulant and platelet activity in healthy subjects. Design: A double-blinded, placebo-controlled randomised trial was conducted in 94 healthy adults: male (n=41) and female (n=53). Platelet coagulation parameters including factors I, II, V, VII, VIII, IX, X, vWF:Ag and endogenous thrombin potential were measured at baseline and 4 weeks postsupplementation with EPA-rich or DHA-rich oil capsules. Results: We have previously reported that platelet aggregation is specifically reduced by supplementation with EPA in males and DHA in females. This sexspecific effect was also observed for decreases in plasma levels of Factor II (−7.9±3.8%, P=.026), Factor V (−6.5±4.5%, P=.022) and vWF:Ag (−7.3±2.1%, P=.034) and was most pronounced in males supplemented with EPA. In contrast, DHA-mediated reduction in platelet aggregation in females was not accompanied by any significant changes in the coagulation parameters tested. Conclusion: Significant interactions between sex and specific LCn-3PUFA exist to reduce procoagulant activity differentially in males vs. females and could have profound effects on managing risk of thrombotic disease.

Las Enfermedades Cardiovasculares son la principal causa de muerte en el mundo. Junto con los esfuerzos en disminuir los factores de riesgo cardiovascular, se recurre a diversos medicamentos para disminuir la morbimortalidad asociada a estas enfermedades, entre otros fármacos se utilizan, antihipertensivos, antidiabéticos, hipolipimiantes y antiagregantes plaquetarios. Dada la participación de las plaquetas, tanto en las etapas precoces de la aterogénesis como en la trombosis arterial, el uso de antiagregantes plaquetarios es muy relevante en la prevención primaria y secundaria de las trombosis arteriales. Los antiagregantes plaquetarios son utilizados en prevención primaria y secundaria de ECV. En esta revisión, se abordan diversos aspectos relativos a los antiagregantes, especialmente mecanismo de acción y riesgos asociados al uso durante los últimos 10 años. Como fuente bibliográfica se utilizó principalmente www.pubmed.com; y los términos utilizados en la búsqueda fueron: antiagregantes plaquetarios, aspirina, dipiridamol, clopidogrel, abciximab, entre otros; luego se buscaron los textos completos de los artículos que interesaban y además se utilizaron algunos libros de hematología.

Upon activation by extracellular matrix components or soluble agonists, platelets release in excess of 300 active molecules from intracellular granules. Those factors can both activate further platelets and mediate a range of responses in other cells. The complex microenvironment of a growing thrombus, as well as platelets' roles in both physiological and pathological processes, require platelet secretion to be highly spatially and temporally regulated to ensure appropriate responses to a range of stimuli. However, how this regulation is achieved remains incompletely understood. In this review we outline the importance of regulated secretion in thrombosis as well as in ‘novel’ scenarios beyond haemostasis and give a detailed summary of what is known about the molecular mechanisms of platelet exocytosis. We also discuss a number of theories of how different cargoes could be released in a tightly orchestrated manner, allowing complex interactions between platelets and their environment.

Dengue infection is the fastest spreading mosquito borne disease in the world. More than 2.5billion people spread over more than 100 countries are at risk. Thrombocytopenia is a key clinical feature and around 500,000 people annually develop the more severe form of this infection known as severe dengue (Dengue Haemorrhagic Fever/ Dengue Shock Syndrome). Platelets are key in the pathogenesis of severe dengue. Platelets have a cardinal role in 159 ,(158)Lai CY, Tsai WY, Lin SR, Kao CL, Hu HP, King CC, Wu HC, Chang GJ, Wang WK Antibodies to envelope glycoprotein of dengue virus during the natural course of infection are predominantly cross-reactive and recognize epitopes containing highly conserved residues at the fusion loop of domain II. J Virol 2008; 82:6631-6643 160 Rajamanonmani R, Nkenfou C, Clancy P, Yau YH, Shochat SG, Sukupolvi-Petty S, Schul W, Diamond MS, Vasudevan SG, Lescar J On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes.