Haganbagge3564

Due to poor initial prognosis further treatment of the facial malignancy was not feasible. However, initial, early postnatal, excisional surgery provided a prolonged and better quality of life for the patient and family. Hemophilia A, an X-linked recessive bleeding disorder, is caused by mutations of F8 gene. In about 2% hemophilia A patients, no exonic mutation of F8 gene was found. We aimed to identify deep intronic mutations of F8 gene. We reanalyzed the next-generation sequencing data of six hemophilia A patients with negative F8 variant in either coding region or splice site. Deep intronic F8 c.5999-27A>G variant (NM_000132.3) was found in two unrelated moderate hemophilia A patients from different region, and one patient's mother was mild hemophilia A patient. Splice site prediction algorithms showed no impact of this variant on F8 mRNA splicing of exon 19, including Human Splicing Finder 3.1, NNSPLICE 0.9, NetGene2, and Transcript-inferred Pathogenicity score. Exonic splicing enhancer was predicted by ESEfinder, and no difference was found between the wild type and mutant sequence. The branch point predicted by SVM-BPfinder suggested that F8 c.5999-27A>G variant may disrupt the branch point in intron 18 and affect the acceptor site splicing of F8 exon 19. Sanger sequencing of F8 cDNA from peripheral blood mononuclear cells confirmed that F8 c.5999-27A>G variant caused F8 exon 19 skipping in proband and his mother. Skewed X chromosome inactivation was found in another X chromosome of this mother, combined with F8 c.5999-27A>G variant in trans. In conclusion, our study suggests that deep intronic F8 c.5999-27A>G variant may be responsible for F8 exon 19 skipping and lead to moderate hemophilia A. Systematic reanalysis of next-generation sequencing data could promote the diagnostic yields. Pulmonary embolism typically occurs from deep venous thrombosis (DVT). However, not always a DVT can be identified, and 'in situ' generation of pulmonary embolism has been considered, referred to in the literature as 'De novo pulmonary embolism' (DNPE). The objective of the study is to assess risk factors, comorbidities, clinic characteristics and long-term evolution of patients with pulmonary embolism in the absence of an identified source. Retrospective study of 280 patients with pulmonary embolism, 190 pulmonary embolisms with DVT group and 90 (32%) pulmonary embolism without DVT (DNPE group), admitted to an Internal Medicine Department of a tertiary hospital from January 2012 to December 2015. In the DNPE group, segmental and subsegmental arteries were more frequently affected (P = 0.01). As compared with pulmonary embolisms with DVT group older age, female sex, sedentary lifestyle, diabetes mellitus, arterial hypertension, heart failure, respiratory infections and chronic obstructive pulmonary disease (COPD) were significantly more frequent in DNPE. In multivariate analysis, respiratory infection [odds ratio (OR) 12.2, P  less then  0.0001], COPD (OR 8.7, P  less then  0.0001) and female sex (OR 3.0, P = 0.003) were independently associated risk factors. Long-term mortality (median follow-up 15 months) was also higher in DNPE group (34 vs. 16%, P = 0.01). De novo pulmonary embolism occurred in 32% of cases of pulmonary embolisms and was more frequent in female and COPD patients or those with respiratory infections as compared with pulmonary embolisms in which DVT was identified as a source of embolism. The aim of this study was to elucidate the molecular defects in a Chinese family with dysfibrinogenemia. The fibrinogen activity was measured by the one-stage clotting method. The fibrinogen antigen was measured with immunoturbidimetry. The fibrinogen gene was amplified by PCR with direct sequencing. Suspected mutation was confirmed by reverse sequencing. Bioinformatics and model analysis were used to study the conservatism and harm of the mutation. The proband had a history of menorrhagia. Study showed fibrinogen activity at 0.35 g/l and fibrinogen antigen at 2.05 g/l. Sequencing analysis detected a heterozygous c.1178T>C missense mutation in exon 9 of FGG gene resulting in p.IIe367Thr. The bioinformatics and model analysis indicated that the IIe367Thr mutation may disrupt the activation of the fibrinogen. We detected a novel IIe367Thr missense mutation in the FGG. To our knowledge this is causative mutation has not been reported so far. To analyze the causative gene and the molecular pathogenesis in a pedigree with compound hereditary coagulation factor V deficiency. Routine blood coagulation indexes and factor V antigen (FVAg) were detected by the one-stage clotting method and ELISA. Function of the mutant protein was evaluated by the method Calibrated Automated Thrombogram (CAT). The factor V gene was amplified by PCR with direct sequencing. The possible impact of the mutations were analyzed by bioinformatics tools. The proband's factor V activity and FVAg were reduced to 3 and 6%. Gene sequencing revealed compound heterozygous mutations c.911G>A (Gly276Glu) in exon 6 and c.5343C>G (Ser1781Arg) in exon 16. The thrombin generation test showed that the mutant protein markedly decreased thrombin. Bioinformatics indicated that mutations were deleterious. The compound heterozygous mutations Gly276Glu and Ser1781Arg were responsible for the decrease of factor V activity and FVAg, of which Ser1781Arg was first reported in the world. Women with inherited bleeding disorders (IBDs) are reported to have higher rates of primary and secondary postpartum haemorrhage (PPH), even with optimal haemostatic management. We evaluated whether women with IBD have higher odds of PPH compared with those without, when controlled for mode of delivery with a control group of women without IBDs. The obstetric experiences and outcomes of all women with IBD delivering at a tertiary centre between 2008 and 2017, were compared with matched controls (1  1). Obstetric care was provided according to national guidelines to both women with IBD and controls. Primary PPH was defined as estimated blood loss at least 500 ml. There were 46 completed pregnancies in women with IBD 16 haemophilia A carriers, eight haemophilia B carriers, eight factor XI deficiency patients and 14 von Willebrand disease patients (type 1 = 6; type 2 = 8). No peripartum haemostatic treatment was received by carriers of haemophilia A or B. There were 74 control pregnancies. Women with IBD had higher odds of primary PPH, in a model controlling for mode of anaesthesia (adjusted odds ratio 5.30, 95% confidence interval 1.02-27.59, P = 0.048). Carriers of haemophilia A had a higher, statistically nonsignificant, odds for primary PPH than controls (adjusted odds ratio 6.85, confidence interval 0.77-60.73, P = 0.084). An increase in primary PPH was observed in women with IBD, particularly in haemophilia A, despite management according to guidelines. These results warrant further investigation and consideration should be given as to which factor levels to target. We aimed to investigate how prosthetic valve thrombosis (PVT) affects brain natriuretic peptide (BNP) levels and how BNP changes following thrombolytic therapy. The study included 70 consecutive patients with left-sided mechanical PVT who received thrombolytic therapy. The patients were divided into two groups, namely obstructive thrombus (n = 42) and nonobstructive thrombus (NOT, n = 28). BNP levels of patients were assessed before and after thrombolytic therapy. BNP levels were higher in obstructive thrombus group than NOT group in whole study population, in patients with mitral PVT and in patients with aortic PVT [325.0 (189.5-496.0) vs. 84.0 (44.5-140.0), P  less then  0.001, 323.0 (193-449.0) vs. 59.0 (37.0-131.0), P  less then  0.001 and 321.0 (132.0-525.0) vs. 99.0 (60.5-173.0), P  less then  0.001]. BNP levels were positively correlated with transmitral and transaortic mean gradients, and negatively correlated with mitral valve area (r 0.374, P = 0.013; r 0.432, P = 0.035 and; r -0.642, P  less then  0.001, respectively). BNP values above 165 pg/ml may predict the presence of obstructive thrombus with a sensitivity of 88.0%, and a specificity of 79.0% (AUC = 0.928, 95% confidence interval 0.871-0.986, P  less then  0.001). Following thrombolytic therapy, BNP levels (pg/ml) significantly decreased from 325.0 (189.5-496.0) to 137.0 (101.7-224.5), P  less then  0.001, in all patients with obstructive thrombus, from 323.0 (193.0-449.0) to 129.0 (98.0-223.0), P  less then  0.001, in patients with only mitral obstructive thrombus and from 321.0 (132.0-525.0) to 181.0 (99.0-217.5), P  less then  0.001, in patients with only aortic obstructive thrombus. BNP levels are significantly higher in prosthetic valve patients with obstructive thrombus than in those with NOT and decrease in patients with obstructive thrombus after thrombolytic therapy. A cut off value of BNP of at least 165.0 pg/ml was found to discriminate obstructive thrombus from NOT. Bleeding among critically ill paediatric haematology/oncology (CIPHO) patients leads to significant morbidity and mortality. Recombinant activated factor VII (rFVIIa) has shown some benefits in previous reported off-label use when conventional therapies have failed. However, data in CIPHO are lacking. We retrospectively studied (2006-2014) the efficacy and outcomes in CIPHO patients younger than 21 years who received at least one rFVIIa dose for bleeding in the ICU. Of 39 patients, the majority had leukaemia (59%), bone marrow transplantation (77%) and a life-threatening bleed (80%) with most common site being pulmonary haemorrhage (44%). Most needed invasive mechanical ventilation (87%) or vasopressor support (59%). After rFVIIa administration, 56% had cessation or decreased bleeding. Packed red blood cell transfusion requirements decreased significantly 48-72 h after rFVIIa administration. Lower baseline prothrombin time and more rFVIIa doses were related to bleeding control. A favourable response was associated with higher survival (55% in responders versus 18% in nonresponders, P = 0.019). Overall, bleeding-related mortality was 37.5%, highest in pulmonary haemorrhage. Two patients had thromboembolic events. Use of rFVIIa for CIPHO patients appears to be well tolerated with low adverse events. Despite half of the patients having a favourable response of cessation or decrease in bleeding after rFVIIa administration, mortality was high. These findings highlight the need for prospective studies to evaluate interventions to improve outcomes in this population. Platelets play a pivotal role in controlling hemorrhaging from vessels of the human body. The impairment of platelets may lead to the development of bleeding manifestations. ULK-101 in vivo Unraveling the precise defects of platelets by means of suitable laboratory methods paves the way for the effective control and management of platelet disorders. Choosing the most appropriate approach for the detection of platelet disorders may be difficult for a researcher or clinical internist when faced with ordering a platelet-function test. The aim of the current study was to provide a user-friendly overview of the advantages and disadvantages of the available detection systems. To reach this goal, 11 commonly used methods of studying platelet activity were evaluated and compared in detail. A literature search, with no time or language limitations, was conducted in Google Scholar and Medline. All publications published before June 2019 were analyzed. The following laboratory methods were compared number and size of platelets, bleeding time, clot retraction time, platelet function assay 100 & 200, Rapid platelet function assay, flow cytometry, light transmission aggregometry, multiple electrode aggregometry, 96-well plate aggregometry, cone and plate(let) analyzer (Impact-R), and Plateletworks (single platelet counting system).