Primary Hemostasis Research Articles

PWE-007 When to use hemospray? a single centre experience: Abstract PWE-007 Table 1

Introduction Hemospray is an inorganic nanopowder produced by Cook Medical and is licensed in Europe and Canada for the management of nonvariceal upper gastrointestinal bleed (NVUGIB). The powder adheres to liquid and forms a coagulum which concentrates clotting factors and stimulates the internal clotting cascade. There are numerous reports of successful haemostasis with hemospray, some reporting success rates of 85%.1However, the knowledge of which lesion is most suitable for hemospray use remains unclear. We report our experience at Guys and St Thomas’ NHS trust to establish the lesions most likely to benefit from hemospray either as a primary intervention or an add-on strategy. Method A retrospective review of endoscopic procedures that required hemospray was performed and the data was extracted from our endoscopy reporting system between December 2013 and February 2015 (14 months). We identified 32 patients who received hemospray, and excluded 2 where hemospray was applied blindly and the bleeding lesion was missed. The primary outcome was achieving primary haemostasis. Cases where primary haemostasis was not achieved or bleeding recurred requiring further endoscopic or radiological intervention were considered unsuccessful. Results The 30 procedures were divided according to the procedure performed. 1. Procedure induced bleeding: 9/30 (7 post Barrett’s endoscopic mucosal resection (EMR), 1 post gastric polypectomy and 1 iatrogenic bleed post nasojejunal tube insertion). 2. NVUGIB: 17/30. 3. Enteroscopy small bowel bleed: 2/30. 4. Colonoscopy: 2/30. Primary haemostasis was achieved in 80%, of which 10% required further endoscopic procedure or interventional radiological intervention ([Table 1][1]). The coagulum was not seen on second endoscopy. View this table: Abstract PWE-007 Table 1 Conclusion Hemospray provides good hemostasis for post procedure, in particular post EMR bleed, as a single agent or where coagulation alone failed. Bleeding from Forrest 1b, 2a and 2b responded well to hemospray as a second modality, or single modality when the lesion was inaccessible. Forrest 1a had a poor response to hemospray and all cases required further endotherapy or interventional radiology. Further evidence is required to establish the value of hemospray in colonic and variceal bleed. Disclosure of interest None Declared. Reference 1. Smith et al . Hemospray application in nonvariceal upper gastrointestinal bleeding: results of the survey to Evaluate the application of hemospray in the luminal tract. J Clin Gastroenterol. 2014 Nov-Dec;48(10):e89-92 [1]: #T1

PTU-031 Hemospray use for the management of acute bleeding from upper gastrointestinal cancer: the russells hall experience

<h3>Introduction</h3> Cancer of the upper gastrointestinal tract accounts for approximately 4% of acute upper gastrointestinal bleeding (UGIB) related admissions. The treatment of malignancy related bleeding is challenging due to the diffuse and widespread nature of bleeding. Hemospray (Cook Medical, Winston-Salem, North Carolina, USA), an inorganic haemostatic powder that allows a wide area of therapeutic coverage. To date little is known of its use in tumour related UGIB. The aim of this study was to assess feasibility and effectiveness of Hemospray in the treatment and palliation of malignancy related upper GI bleeding. <h3>Method</h3> Retrospective analysis of all malignancy related UGIB treated with Hemospray at Russells Hall Hospital. Patients were identified from the endoscopy database. Patient demographics, Hemospray use and the use of other therapeutic modalities were collected. Outcomes including primary haemostasis, rebleeding and mortality were obtained. <h3>Results</h3> Hemospray use was identified in 15 patients, on 19 occasions (range 1–3 per patient), with malignancy related UGIB. Mean patient age was 71 years, range 43–96 years; male gender 66.6% (n = 10). Mean haemoglobin on presentation was 72 ± 17 g/L and mean urea 10.9 ± 6.6 mmol/L. The bleeding was diffuse and widespread ooze in all cases. The tumour site was oesophageal 40% (n = 6), gastric 26.7% (n = 4) and duodenal 33.3% (n = 5). Hemospray was used as the primary haemostatic treatment on 89.5% of occasions (n = 17). On 2 occasions adrenaline was used first line. Primary haemostasis was achieved in 95% of cases (n = 18). In 1 patient the Hemospray delivery system failed; in this case Endoclot was used successfully. The median procedure duration was 18 min (range 9–50 min). The 7 day and 30 day rebleeding rate was 10.5% (n = 2) and 15.8% (n = 3) respectively. None of the patients required surgery or radiological intervention to arrest the bleeding. There were no documented complications of Hemospray therapy. Mortality was 5% (n = 1) and 16% (n = 3) at 7 and 30 days respectively. There were no bleeding related deaths; death was due to the underlying condition in all patients. Average length of stay was 19 days (range 3–101 days); excluding the outlier of 101 days the average length of stay was 9 days (range 3–27). One patient with gastric cancer had Hemospray applied on 3 occasions which palliated bleeding for approximately 2 months duration each time. <h3>Conclusion</h3> Overall Hemospray appears to be an effective haemostatic therapy for malignancy related UGIB and should be considered as a primary therapeutic modality in this setting. It may be used as a bridge to more definitive therapies such as radiotherapy or drug therapy (e.g. thalidomide, chemotherapy). <h3>Disclosure of interest</h3> None Declared.

PWE-032 Hemospray for acute upper gastrointestinal bleeding – a single centre experience

Introduction Upper gastrointestinal bleeding (UGIB) is the commonest medical emergency managed by the Gastroenterologists. Despite of familiarisation with a variety of medical and endoscopic strategies to treat underlying aetiologies, rebleeding and mortality rates remain high. A novel agent, known commercially as Hemospray, has recently been licensed for use in non-variceal upper gastrointestinal bleeding (NVUGIB). Method The aim of this study was to assess the effectiveness of Hemospray therapy, either as primary endotherapy, or as part of salvage endotherapy in NVUGIB, when conventional measures to achieve haemostasis were deemed insufficient. All patients treated with Hemospray at University Hospital Birmingham, since its introduction to the Unit in 2013, were retrospectively identified using the Unisoft endoscopy database. Data on the indications for Hemospray use, and application in conjunction with other therapeutic modalities were collected. Outcomes including mortality, primary haemostasis and re bleeding rates were analysed. Results Hemospray was applied in 48 patients with NVUGIB (median age 63 years, 70% male). Four patients had Hemospray used on more than one occasion. Causes of bleeding included peptic ulcer disease 29/48 patients (60.5%), other non variceal upper GI pathology 13/48 (27%) and post variceal banding oesophageal ulcers 6/48 (12.5%). Hemospray was used as primary endotherapy in 42/48 patients (87.5%), achieving initial haemostasis in 40/42 cases (95%). 6/48 patients (12.5%) received Hemospray as salvage therapy following a rebleed after treatment with standard primary therapy. Rebleeding within 7 days occurred in 4/42 patients (9.5%); two of them received Hemospray as monotherapy. 30-day mortality in this patient cohort was 9/48 (19%). There were no documented complications of Hemospray therapy. Conclusion Hemospray is a safe and effective endoscopic therapy in achieving initial haemostasis, both as primary and salvage therapy, and either as monotherapy or in combination with other endoscopic modalities in a wide variety of upper GI pathologies, including post variceal banding oesophageal ulcers. We have found this to be a useful adjunct in the management of NVUGIB when conventional techniques have failed. However, further studies are needed to define its cost-effectiveness in the acute hospital setting. Disclosure of interest None Declared.

The effectiveness of low-dose desmopressin in improving hypothermia-induced impairment of primary haemostasis under influence of aspirin - a randomized controlled trial.

BackgroundMild hypothermia (34–35 °C) increases perioperative blood loss. Our previous studies showed that desmopressin could have in vitro beneficial effects on hypothermia-induced primary haemostasis impairment. In this study, we investigate the in vitro effects of desmopressin on hypothermia-induced primary haemostasis impairment under the influence of aspirin in healthy volunteers.MethodsSixty healthy volunteers were randomly allocated to taking aspirin 100 mg or placebo for three days. On the sixth day blood samples were taken before and after the injection of desmopressin (1.5 microgram or 5 microgram) or normal saline subcutaneously. Measurements including Platelet Function Analyzer (PFA-100®) closure times, plasma von Willebrand Factor antigen, haemoglobin and platelet levels were made at 32 °C and 37 °C respectively.ResultsCollagen/epinephrine closure time (EPICT) was significantly prolonged by 21.13 % (95 %CI 2.34–39.74 %, p = 0.021) in aspirin group at 37 °C. While hypothermia alone prolonged both collagen/adenosine diphosphate (ADPCT) and EPICT by 17.63 % (95 %CI 13.5–20.85 %, p < 0.001) and 8.0 % (95 %CI 6.38–10.04 %, p = 0.024) respectively, addition of aspirin only further prolonged EPICT by 19.9 % (95 %CI 3.32–36.49 %, p = 0.013). In aspirin group, desmopressin 1.5 microgram and 5 microgram significantly reduced ADPCT to below baseline levels at 37 °C (p = 0.025 and <0.001 respectively), whereas reduction in EPICT was seen with desmopressin 5 microgram (p =0.008). The effect was less pronounced at 32 °C, with a significant reduction in EPICT obtained with a dosage of 5 microgram only (p = 0.011).ConclusionIt was shown that aspirin could further potentiate the hypothermia-induced closure time prolongations. Low dose desmopressin (1.5 microgram) reduced PFA-100® closure times towards baseline. A higher dosage (5 microgram) further reduced the closure times below baseline. Therefore low dose desmopressin (1.5 microgram) might have the potential to correct hypothermia-induced primary haemostasis impairment under the influence of aspirin during the perioperative period.Trial registrationClinicalTrials.gov: NCT01382134

Peripherally inserted central catheter placement in patients with coagulation disorders: A retrospective analysis.

To assess the safety of peripherally inserted central venous catheter (PICC) placement in patients with altered and uncorrected coagulation parameters or receiving antiplatelet therapy. Medical charts of all patients with major primary and secondary hemostasis disorders, combined hemostasis disorders or on antiplatelet therapy and who had undergone non-tunneled PICC placement from December 2009 to December 2013, were retrospectively reviewed. A hemostatic disorder was defined as a platelet count (PC)≤50×10(9)/L, an international normalized ratio (INR) ≥ 2, or an activated partial thromboplastin time (aPTT)≥66s, alone or in combination. Underlying hemostasis disorders were not corrected and antiplatelet therapy was not interrupted before PICC placement in any patient. 4, and 5-Fr single and dual lumen PICCs were used. A total of 378 PICCs were placed in 271 patients (180 men and 91 women; mean age=62±13.4years; range, 18-93 years)) with coagulation disorders. Eighty-nine (23%) PICCs were placed in patients who were receiving antiplatelet therapy (aspirin, clopidogrel, rivaroxaban). Thrombocytopenia was noted in 269PICC placements (71%). Among these patients, 23 had disseminated intravascular coagulation. Prolonged INR and aPTT were observed in 42 procedures (11.1%). PICC placement was achieved in all patients, with a mean number of 1.14 attempts. Peripheral venous access was obtained through the basilic and the brachial vein respectively in 295 (79.1%) and 83 (20.9%) of patients. The placements were performed by residents and fellows in 108 (28.5%) and 270 (71.5%) procedures, respectively. No early or late complications were reported after any procedure. No accidental puncture of the brachial artery occurred. In patients with severe primary and secondary hemostasis disorders, combined hemostasis disorders or on antiplatelet therapy, PICC placement is a feasible and safe procedure and does not require correction of coagulation parameters or discontinuation of antiplatelet therapy.

Platelet-type von Willebrand Disease: Diagnostic Challenges. Flaws and Pitfalls Experienced in the THROMKID Quality Project.

Primary haemostasis defects comprise von Willebrand disease (VWD) and platelet disorders (PD). Although presenting with mild to moderate bleeding tendency in most cases, severe bleeding and blood loss may occur unexpectedly in trauma and surgery. Diagnosis of VWD and PD often remains difficult owing to the wide spectrum of clinical and laboratory manifestations. Platelet-type von Willebrand disease (PT-VWD) is frequently misdiagnosed as type 2B VWD. Discrimination between type 2B VWD and PT-VWD is crucial as treatment differs. A literature review revealed difficulties in diagnostic work-up and choice of optimal treatment of PT-VWD. Guidelines favour the therapeutic use of platelet concentrates. A telephone survey of diagnostic practice with regard to type 2B VWD/PT-VWD was conducted. The prevalence and incidence of type 2B and PT-VWD remained unclear, but PT-VWD may be underestimated. An international study estimated that PT-VWD constitutes up to 15% of the total number of patients diagnosed with type 2B VWD. Our survey confirmed difficulties with diagnosis and showed that some centres did not exclude PT-VWD in type 2B patients. Some authors emphasize that genetic testing is the gold standard for diagnosis, but functional testing allows immediate diagnosis. Due to the important therapeutic implications we suggest that type 2B VWD be confirmed by genetic testing and that in case of a negative result PT-VWD should be excluded. PT-VWD should be excluded in all suspected cases of type 2B. PT-VWD should be treated with platelet concentrates.

The Platelet Function Analyser (PFA)-100 and von Willebrand disease: a story well over 16 years in the making.

The Platelet Function Analyser (PFA)-100 and von Willebrand disease: a story well over 16 years in the making.

The role of hemospray in the endoscopic treatment of non variceal upper gastrointestinal bleeding; initial experiences in a tertiary centre gastroenterological unit

Introduction: Early endoscopic diagnosis and endoscopic haemostasis are essential tasks in cases with acute upper gastrointestinal bleeding (UGIB). Hemospray is a novel modality in endoscopic treatment of UGIB. The aim of our retrospective analyses was to evaluate the role and efficacy of Hemospray treatment in acute upper non variceal bleeders referred to our tertiary centre gastroenterological and endoscopy unit. Method: Hemospray as an endoscopic haemostatic modality is available in our unit since June 2013. Hemospray powder was sprayed via a 7 or 10 French catheter inserted through the endoscope channel targeting the actively bleeding points. Hemospray was used either as a rescue therapy after failed primary endotherapies or as a first choice intervention. Results: In 20 months period a total of 271 acute UGIB patients were admitted to our department with a mean age of 66.9 ± 13.7. At the emergency endoscopy in 66 patients gastrooesohageal varices or portal gastropathies were detected as bleeding sources. Gastroduodenal ulcers were found in 115 patients and in 90 cases the bleeding originated from other sources like Mallory-Weiss tear, erosive oesophagitis, angiodysplasia. Endoscopic therapy was performed in 56.6% out of the non variceal upper gastrointestinal bleeders (116/205). Combined endotherapies were done in 62 cases while endoscopic monotherapies were performed in 54 cases. In 10 severly bleeding patients Hemospray was used in a total of 11 settings. Hemospray therapy was necessary in 5 cases because of failed primary hemostatic efforts and in other 5 cases Hemospray was used as a first line therapy. In 10 cases out of all non variceal UGIB patients was necessary to act with of Hemospray (4.9%). Out of all endoscopic therapies Hemospray was used as rescue activity in 9.5% of patients (11/116). Primary haemostasis was achieved 9 out of the 10 Hemospray cases. Conclusions: Hemospray endotherapy may support the chance of primary hemostasis in severe acute upper GI bleeders in about one out of every twenty patients. Hemospray rescue therapy proved to be useful in nearly 10% of all endoscopic haemostatic efforts in our practice.

Endoscopic Suturing for Ulcer Exclusion in Patients With Massively Bleeding Large Gastric Ulcer

Bleeding peptic ulcer is one of the most important causes for hospitalization worldwide. Though endoscopic hemostasis is the current standard of treatment for bleeding peptic ulcers, ulcer rebleeding remained a chief cause of mortality.1Chiu P.W. et al.Clin Gastroenterol Hepatol. 2009; 3: 311-316Abstract Full Text Full Text PDF Scopus (88) Google Scholar One of the important strategies to improve outcomes for bleeding peptic ulcers is to prevent rebleeding. Indeed, endoscopic features for ulcers with high risk of rebleeding include ulcers larger than 2 cm, actively bleeding and those located at posterior duodenal bulb or high lesser curvature.2Johnston J.H. et al.Gastroenterology. 1987; 92: 1101-1108Abstract Full Text PDF PubMed Scopus (111) Google Scholar With the use of high-dose intravenous proton pump inhibitors (PPI), those who developed rebleeding after PPI infusion were patients with significant perioperative risks, high proportion of comorbidities, as well as older age which rendered them high-risk surgical candidates.3Elmunzer B.J. et al.Am J Gastroenterol. 2008; 103: 2625-2632Crossref PubMed Scopus (119) Google Scholar A prototype endoscopic suturing device had been investigated for the safety and efficacy in achieving hemostasis among massively bleeding gastric ulcers.4Chiu P.W. et al.Dig Surg. 2009; 26: 243-248Crossref PubMed Scopus (16) Google Scholar This is an initial report on the clinical application of surgical ulcer exclusion using endoscopic suturing for large bleeding gastric ulcer. The Apollo Overstitch is an endoscopic suturing system which consists of a cap-based suturing system with a curved suture arm extending from one of the dual channels and the anchor exchange system extending from the same channel. The handle to control the suture plication system was mounted onto the shaft of a double-channel endoscope (Olympus 2T100 scope, Olympus Co Ltd, Hong Kong). The Overstitch system attached to the double-channel endoscope was introduced into the stomach through an overtube. The bleeding ulcer was first located with an ordinary single-channel endoscope. Endoscopic suturing begins with the needle first driving through the distal edge of the bleeding ulcer. After closing the curved needle driver, the detachable needle should be grasped by the anchor exchange and detached from the needle driver. After opening the needle driver, the endoscope with Overstitch should be moved away from the distal ulcer edge. The needle should be placed back in the needle driver by the anchor exchange. The needle should then be driven over the proximal edge of the ulcer and the procedure repeated until the 2 edges of the ulcer can be pulled together. The needle anchor should be dropped, while the anchor exchange is replaced by the cinching device which passes along the 2 ‘O’ polypropylene suture. After passage of the cinch to ulcer edge, the polypropylene suture should be tightened against the end of the cinch. The cinch is then closed to cut the stitch and release the plug to tighten the suture, and the ulcer should be excluded from an intragastric high acidity environment to stop current bleeding and prevent rebleeding. Three patients received endoscopic ulcer exclusion for a massively bleeding gastric ulcer. This video shows endoscopic suturing for ulcer exclusion in an actively bleeding gastric ulcer. The patient was a 78-year-old man who presented with passage of tarry stool for 3 days; upper endoscopy showing a 2 cm large gastric ulcer at angular incisura with visible vessel. There was active bleeding from visible vessel (Figure 1). The Overstitch device was introduced through an overtube. The first suture plication was performed over the superior edge of the ulcer. After exchange of the anchor, the second suture plication was performed over the inferior ulcer edge. This process was continued until a figure of eight suture was formed over the ulcer. The anchor was then dropped and the suture was tightened with the cinching device. The ulcer was excluded with adequate hemostasis (Figure 2). The patient had no clinical evidence of rebleeding, and a repeated endoscopy in 72 hours confirmed secure closure of the ulcer.Figure 2Ulcer exclusion achieved after tightening of overstitch.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Surgical exclusion of bleeding ulcer is a conventional treatment for prevention of further bleeding through suture closure of the ulcer and excluding it from intragastric acidity. This is the first technological report on clinical application of endoscopic surgical suturing for ulcer exclusion. The success of endoscopic ulcer exclusion will lead to improvement in primary endoscopic hemostasis, and theoretically excluding the ulcer from acid to prevent further bleeding. The ulcer exclusion shall be a better method to prevent rebleeding compared with adjunctive high-dose proton pump inhibitor infusion or prophylactic angiographic embolization. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI0NDRlMDkxM2NmMGRhNGUwNGJiZDFkODUyMjRjMjQxYyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjgxMzYwNDY3fQ.XXJzrp-6yqa5X_Fxu-t93ZJmJ4gGt5KEIICkg-xZWs2P9QUVTwPcWU5BIAoyY161WQqS9Xoq2xlMpMeFIa03TVHD9haMAQ-SBed6va3cMQtozXytNgaNMojGDSQwMA4hN2-dG7kGlLfGkDlU3dV9Oi0epZaZBfhQIxkNVWPYU76Fm68LSNLJ7_1G29qT5DlWZrSOHsW10o5dkts0yBD9W0Bc9PUUOiJX1P41J4-g2lAv77tNCIPyZNrVzhbQnAt1xIYBD1YAb1HHnXEHF1q2P_ISMMsqrfBJmW0OLGH8PblHrNNDwqnDn3pnyRIekdVxovny7vwoogxhrPzxLQT2mw Download .mp4 (43.03 MB) Help with .mp4 files Video 1

Laboratory testing for platelet function disorders.

Platelet function testing is both complex and labor intensive. A stepwise approach to the evaluation of patients with suspected platelet disorders will optimize the use of laboratory resources, beginning with an appropriate clinical evaluation to determine whether the bleeding is consistent with a defect of primary hemostasis. Bleeding assessment tools, evaluation of platelet counts, and review of peripheral blood cell morphology can aid the initial assessment. For patients requiring further laboratory testing, platelet aggregometry, secretion assays, and von Willebrand factor assays are the most useful next steps and will direct further specialized testing including flow cytometry, electron microscopy, and molecular diagnostics. Guidelines and recommendations for standardizing platelet function testing, with a particular focus on light transmission aggregometry, are available and can provide a template for clinical laboratories in establishing procedures that will optimize diagnosis and assure quality results. This review outlines an approach to platelet function testing and reviews testing methods available to clinical laboratories.

Long Term Stability Evaluation of Prostacyclin Released from Biomedical Device through Turbiscan Lab Expert.

Therapeutic guidelines indicate prostacyclin as the first line of treatment in inflammation and vascular diseases. Prostacyclins prevent formation of the platelet plug involved in primary hemostasis by inhibiting platelet activation and, combined with thromboxane, are effective vasodilators in vascular damage.Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease II guidelines indicates prostacyclins; in particular, Iloprost, as the first therapeutic option for treating peripheral arterial disease. However, therapeutic efficacy of Iloprost has witnessed several drawbacks that have occurred in patients receiving repeated weekly administration of the drug by intravenous infusions. Adverse reactions arose under perfusion with Iloprost for 6 h and patient compliance was drastically decreased. Biomedical devices could provide a suitable alternative to overcome these drawbacks. In particular, elastomeric pumps, filled with Iloprost isotonic solution, could slowly release the drug, thus decreasing its side effects, representing a valid alternative to hospitalization of patients affected by peripheral arterial disease. However, the home therapy treatment of patients requires long-term stability of Iloprost in solution-loaded elastomeric pumps.The aim of this work was to investigate the long-term stability of Iloprost isotonic solution in biomedical devices using Turbiscan technology. Turbiscan Lab Expert (L’Union, France) predicts the long-term stability of suspensions, emulsions and colloidal formulations by measuring backscattering and transmission of particulates dispersed in solution. The formulations were evaluated by measuring the variation of physical-chemical properties of colloids and suspensions as a function of backscattering and transmission modifications. In addition, the release profile of Iloprost isotonic solution from the biomedical device was evaluated.

Human platelets and their capacity of binding viruses: meaning and challenges?

Blood platelets are first aimed at ensuring primary hemostasis. Beyond this role, they have been acknowledged as having functions in the maintenance of the vascular arborescence and, more recently, as being also innate immune cells, devoted notably to the detection of danger signals, of which infectious ones. Platelets express pathogen recognition receptors that can sense bacterial and viral moieties. Besides, several molecules that bind epithelial or sub-endothelial molecules and, so forth, are involved in hemostasis, happen to be able to ligate viral determinants, making platelets capable of either binding viruses or even to be infected by some of them. Further, as platelets express both Fc-receptors for Ig and complement receptors, they also bind occasionally virus-Ig or virus-Ig-complement immune complexes. Interplays of viruses with platelets are very complex and viral infections often interfere with platelet number and functions. Through a few instances of viral infections, the present review aims at presenting some of the most important interactions from pathophysiological and clinical points of view, which are observed between human viruses and platelets.

Clinical outcomes of nonvariceal upper gastrointestinal bleeding in Kosova

The aim was to determine the sociodemographic and etiologic factors, endoscopic accuracy, treatment efficiency and clinical outcome of patients with nonvariceal upper gastrointestinal system bleeding in Kosova. We retrospectively evaluated patients who had applied to our Gastroenterology Department between January 2006 and December 2010. There were 460 eligible cases with mean age 56.85+16.18 years, while male /female ratio was 2.71/1. The greatest occurrence was at age group of 60-69 years (27.1 %). The most common clinical symptom was melena (62.6%). Comorbid diseases were present in 57, 6% of the patients. The percentage of patients using acetylsalicylic acid and /or other non-steroidal anti-inflammatory drugs was 43.7%. Five point two percent were using anticoagulants. Peptic ulcer was the main cause of bleeding (82.2%) and most of them were Forrest III (41.6%). Endoscopic treatment was performed in 90 patients, primary hemostasis was achieved in 96.7% while rebleeding developed in 10% of these patients. The average length of hospital stay was 9.29+5.58 (1-35) days. Rebleeding was reported in 4.1% of all patients while the overall mortality rate was 5.7%. Age over 60 years, previous history of gastrointestinal bleeding, treatment with anticoagulants, low hemoglobin values at presentation (<7 g/dL), hematemesis, Forrest class, localization of lesion of bleeding, comorbidities, tachycardia, transfusion requirement>2 unit, type of treatment and time of endoscopy were predictors of poor outcome in study present.

Procoagulant platelets and the pathways leading to cell death.

Platelets are critical mediators of thrombosis and hemostasis. In response to agonist, platelets aggregate to form a thrombus via ligand binding of the glycoprotein IIb/IIIa receptor. However, activated platelets are heterogeneous in nature and a subset of platelets stimulated by strong agonists support the assembly of the coagulation complexes. It is proposed that these "procoagulant" platelets have a unique role in hemostasis and thrombosis as the link between primary and secondary hemostasis, localizing the thrombin burst required for fibrin formation to micro-domains within the platelet thrombus. Loss of procoagulant potential leads to bleeding while an increase is linked with propensity to thrombosis. While many features of the procoagulant platelet are known, the exact nature of the procoagulant platelet remains controversial. It is noted that many of the morphological and biochemical features of procoagulant platelets are also features of the cyclophilin D necrosis pathway. This review will focus on the distinct roles of platelet subpopulations, the identity of the procoagulant platelet, and the potential role of the cell death pathways in regulating platelet procoagulant response.

Is diabetes a hypercoagulable state? A critical appraisal.

Diabetes mellitus (DM), a chronic disease with an increasing incidence and prevalence worldwide, is an established risk factor for arterial cardiovascular, cerebrovascular and peripheral vascular diseases including acute myocardial infarction, stroke and peripheral artery disease. On the other hand, its role as independent risk factor for venous thromboembolism (VTE) and for cardioembolic stroke or systemic embolism (SE) in patients with atrial fibrillation (AF) is more conflicting. Venous and arterial thromboses have traditionally been regarded as separate diseases, but recent studies have documented an association between these vascular complications. Cardiovascular risk factors may contribute to unprovoked VTE, and VTE may be an early symptomatic event in patients at high cardiovascular risk, including diabetic patients. Compelling evidences suggest that DM is associated with a higher risk of development and progression of AF. Furthermore, in AF patients with a coexisting DM the risk of cardioembolic stroke/SE appeared increased. Thus, DM has been included as one of the items of the CHADS2 score and of the subsequent CHA2DS2-VASc score that have been developed to assess the arterial tromboembolic risk of AF patients. Such a high incidence of thromboembolic events observed in these clinical subsets may be attributable to the DM-related prothrombotic state due to a number of changes in primary and secondary hemostasis. Although of potential clinical interest, unfortunately, to date, no study has properly evaluated the effects of drugs used to control blood glucose levels on the risk of venous thromboembolism and arterial cardioembolic events in patients with DM.

Extracorporeal membrane oxygenation induces short-term loss of high-molecular-weight von Willebrand factor multimers.

High-molecular-weight (HMW) von Willebrand factor (vWF) multimers are crucial for primary hemostasis. Increased shear stress from ventricular assist devices can provoke premature degradation of HMW vWF multimers. Whether similar loss of vWF multimers occurs during extracorporeal membrane oxygenation (ECMO) is not clear. We conducted a prospective observational study in a clinical cohort of patients who required ECMO for intractable cardiac and/or respiratory failure. The primary end point was the quantity and quality of HMW vWF multimer bands before, during, and after ECMO support. To investigate further changes in primary hemostasis, we also measured vWF antigen activity (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), and factor VIII in 38 patients who required ECMO support before initiation of ECMO (baseline), after 24 and 48 hours on ECMO, and 24 hours after termination of ECMO therapy. Compared with baseline, vWF:Ag and vWF:RCo decreased after 24 hours of ECMO (mean ± SD, vWF:Ag, 307% ± 152% to 261% ± 138%, P = 0.002; vWF:RCo 282% ± 145% to 157% ± 103%, P < 0.0001) and remained lower during ongoing support (vWF:Ag 265% ± 128%, P = 0.025; vWF:RCo 163% ± 94%, P < 0.0001). After termination of ECMO, vWF:Ag was greater than baseline (359% ± 131%, P = 0.004) and vWF:RCo was similar to baseline levels (338% ± 142%, P = 0.046). Compared with baseline, the calculated vWF:RCo/vWF:Ag ratio decreased after 24 hours on support (0.96 ± 0.23 to 0.61 ± 0.17, P ≤ 0.0001) and remained lower during 48 hours on ECMO (0.63 ± 0.18, P ≤ 0.0001). After termination of ECMO support (0.94 ± 0.19, P = 0.437), values rapidly returned to baseline. The number of HMW vWF multimers (n) decreased from baseline after 24 hours on ECMO (21 ± 1.4 to 14 ± 1.8, P ≤ 0.0001) and after 48 hours on ECMO (15 ± 2.1, P ≤ 0.0001). Twenty-four hours after termination of ECMO support, HMW vWF multimeric pattern had returned to baseline values (21 ± 1.8, P = 0.551). Loss of HMW vWF multimer bands occurred in patients undergoing ECMO support and resolved after the termination of ECMO. Although not detectable with coagulation screening tests, a vWF:RCo/vWF:Ag ratio <0.7 during ECMO was highly indicative for loss of HMW vWF multimers. Our findings may at least in part explain increased bleeding tendency during ECMO therapy. Administration of vWF concentrates may support restoration of primary hemostasis in patients with relevant bleeding during ECMO support.

Effect of Puumala hantavirus infection on human umbilical vein endothelial cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release.

Puumala virus (PUUV) infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs) we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor (TF) expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVEC and subsequently specifically to PUUV virus particles. Infection of HUVEC with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1) compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased TF expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.

Effects of chronic administration of valproic acid to epileptic patients on coagulation tests and primary hemostasis.

Valproic acid (VPA) is an antiepileptic drug that has been associated with impaired hemostasis and increased risk for postsurgical bleeding. However, the published reports provide controversial results. We measured parameters of primary hemostasis in VPA-treated patients with epilepsy, focusing on adenosine nucleotide-dependent platelet responses, which play a central role in primary hemostasis. We enrolled 20 cases (epileptic patients receiving treatment with VPA) and 20 controls (12 epileptic patients receiving treatment with drugs different from VPA and 8 healthy subjects). Measurements included prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, platelet function analyzer (PFA)-100 closure times, plasma von Willebrand factor levels, platelet content of ADP, ATP, and serotonin (all stored in platelet dense granules), and platelet shape change and aggregation induced by ADP and other platelet agonists, including the ATP analog α,β-methylene-ATP. The plasma concentration of VPA was in the therapeutic range in 17 patients and slightly above the upper limit in 3 patients. There were no statistically significant differences in any of the studied parameters in cases versus controls. Our thorough controlled study failed to show that chronic treatment with VPA induces significant abnormalities of coagulation and primary hemostasis. Therefore, VPA, when present in the circulation in the therapeutic range, does not impair hemostasis.

Platelet function analyser (PFA-100) results and von Willebrand factor deficiency: a 16-year 'real-world' experience.

The platelet function analyser (PFA-100) is a biological tool designed to explore primary haemostasis. This system has thus been widely demonstrated as reliable in detecting von Willebrand factor (VWF) deficiency. However, most studies were based on patients benefitting from regular medical care and accurate diagnosis, and it would seem probable that the results were somewhat optimistic, and do not reflect its performances in 'real-world' situations. We have chosen to study the reliability of PFA-100 for screening VWF ristocetin cofactor (VWF:RCo) deficiency. We retrospectively analysed the results (n=6431) of 4027 patients referred to our centre between October 1997 and June 2013 and in whom PFA-Epi, PFA-ADP, and VWF:RCo activity had been evaluated. We studied the influence of blood group on the results and the performances of each method in a subgroup of 213 patients with genetically confirmed von Willebrand disease. We have shown that the PFA-100 system, in our experience, constitutes an excellent screening test for detecting VWF:RCo deficiency, whatever the clinical situation, in 'real-world' conditions. The negative predictive value (NPV), the positive predictive value, the sensitivity and the specificity were respectively: 0.98, 0.51, 0.98 and 0.40. When values adjusted for blood group are used, NPV and sensitivity are inferior to those using normal values which have not been adjusted for blood group. We have shown the PFA-100 method to be more efficient in screening for VWF deficiency than the VWF:RCo technique.

Haemostatic function and biomarkers of endothelial damage before and after RBC transfusion in patients with haematologic disease.

Transfusion of red blood cells (RBC) is beneficial for the patient but can also be harmful, as randomized trials have demonstrated increased infection rates, bleeding and mortality. The study aim was to investigate the response of the vascular system (the haemostatic function and the endothelium) to RBC transfusion. Blood was sampled from patients with various transfusion-dependent haematologic diseases before 1 and 24 h after RBC transfusion. Primary and secondary haemostasis was evaluated by whole-blood impedance aggregometry (Multiplate) and by thromboelastography (TEG). Samples were analysed by ELISA for biomarkers reflecting endothelial activation and damage (sICAM-1, syndecan-1, sThrombomodulin (sTM), sVE-Cadherin), platelet activation (sCD40L) and inflammation (hsCRP). A total of 58 patients were enrolled in the study. Median age was 71 years. Compared to before transfusion, patients had slightly reduced coagulability 1 h after RBC transfusion, assessed by TEG. However, transfusion of older RBC products (>14 days) was associated with increased coagulability (all P < 0·05). The level of syndecan-1 increased slightly 24 h after transfusion (median 12·4 (IQR 9-23) vs. 13·2 (9-25) ng/ml, P < 0·01), indicating increased glycocalyx degradation. Overall, RBC transfusion was associated with reduced coagulability and endothelial glycocalyx degradation. Transfusion of older RBCs was however associated with increased coagulability. The changes observed were small to moderate and the clinical relevance of these findings should be investigated in larger studies.