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Thrombocytopenia Causes

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1. Lusutrombopag for treating thrombocytopenia in people with chronic liver disease needing a planned invasive procedure

Lusutrombopag for treating thrombocytopenia in people with chronic liver disease needing a planned invasive procedure Lusutrombopag for treating thrombocytopenia in people with chronic liver disease needing a planned invasive procedure T echnology appraisal guidance Published: 8 January 2020 www.nice.org.uk/guidance/ta617 © NICE 2020. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and-conditions#notice-of- rights).Y Y our responsibility our responsibility (...) equality of opportunity and to reduce health inequalities. Commissioners and providers have a responsibility to promote an environmentally sustainable health and care system and should assess and reduce the environmental impact of implementing NICE recommendations wherever possible. Lusutrombopag for treating thrombocytopenia in people with chronic liver disease needing a planned invasive procedure (TA617) © NICE 2020. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms

2020 National Institute for Health and Clinical Excellence - Technology Appraisals

2. Immune thrombocytopenia

Immune thrombocytopenia Immune thrombocytopenia - Symptoms, diagnosis and treatment | BMJ Best Practice You'll need a subscription to access all of BMJ Best Practice Search  Immune thrombocytopenia Last reviewed: February 2019 Last updated: March 2019 Summary Immune thrombocytopenia (ITP), also known as immune thrombocytopenic purpura, is defined as an autoimmune haematological disorder characterised by isolated thrombocytopenia in the absence of an identifiable cause. Typically found (...) immune thrombocytopenia (ITP) is a haematological disorder characterised by isolated thrombocytopenia (platelet count <100 × 10⁹/L [<100 × 10³/microlitre]) in the absence of an identifiable cause. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. http://bloodjournal.hematologylibrary.org/cgi/content/full

2019 BMJ Best Practice

3. Timely diagnosis and treatment of neonatal alloimmune thrombocytopenia caused by anti HPA-3a antibody: A case report. Full Text available with Trip Pro

Timely diagnosis and treatment of neonatal alloimmune thrombocytopenia caused by anti HPA-3a antibody: A case report. Neonatal alloimmune thrombocytopenia (NAIT) caused by anti HPA-3a antibody is rare, and the clinical features of the syndrome are not specific.A male infant was noted to be irritable and physical examination revealed the presence of petechiae and bruising on the right arm and thigh after born.Platelet antibodies were investigated using the monoclonal antibody-specific (...) immobilization of platelet antigens (MAIPA) assay, platelet genotyping (HPA 1-17) was performed by polymerase chain reaction technique with sequence-specific primers (PCR-SSP). The HPA genotype of the newborn was HPA-3a/b, while that of his mother and his father were HPA-3b/b and HPA-3a/a, respectively. The sera of newborn contained antibody against the platelet of newborn's father. The HPA antibody of the newborn was identified as anti HPA-3a. The newborn was confirmed as a patient of NAIT caused by anti

2019 Medicine

4. TUBB1 dysfunction in inherited thrombocytopenia causes genome instability. (Abstract)

TUBB1 dysfunction in inherited thrombocytopenia causes genome instability. Inherited thrombocytopenia is a genetically heterogeneous disease characterized by varying degrees of thrombocytopenia and risk of haematological malignancy, and the genetic cause of many cases remains unknown. We performed whole-exome sequencing of a family with thrombocytopenia and myeloid malignancy and identified a novel TUBB1 variant, T149P. Screening of other thrombocytopenia pedigrees identified another TUBB1

2019 British journal of haematology

5. Germline mutations in the transcription factor IKZF5 cause thrombocytopenia. (Abstract)

Germline mutations in the transcription factor IKZF5 cause thrombocytopenia. To identify novel causes of hereditary thrombocytopenia, we performed a genetic association analysis of whole-genome sequencing (WGS) data from 13,037 individuals enrolled in the NIHR BioResource, including 233 cases with isolated thrombocytopenia. We found an association between rare variants in the transcription factor (TF)-encoding gene IKZF5 and thrombocytopenia. We report five causal missense variants in or near (...) controls. Comparison of RNA-seq data from platelets, monocytes, neutrophils and CD4+ T-cells from three cases and 14 healthy controls showed 1,194 differentially expressed genes (DEGs) in platelets but only four DEGs in each of the other blood cell types. In conclusion, IKZF5 is a novel transcriptional regulator of megakaryopoiesis and the eighth transcription factor associated with dominant thrombocytopenia in humans.Copyright © 2019 American Society of Hematology.

2019 Blood

6. Immunodeficiency, autoimmune thrombocytopenia and enterocolitis caused by autosomal recessive deficiency of PIK3CD-encoded phosphoinositide 3-kinase δ. Full Text available with Trip Pro

Immunodeficiency, autoimmune thrombocytopenia and enterocolitis caused by autosomal recessive deficiency of PIK3CD-encoded phosphoinositide 3-kinase δ. Copyright © 2019, Ferrata Storti Foundation.

2019 Haematologica

7. Peripheral serotonin causes dengue-induced thrombocytopenia through 5HT<sub>2</sub> receptors. (Abstract)

Peripheral serotonin causes dengue-induced thrombocytopenia through 5HT2 receptors. Dengue virus (DENV) is the most prevalent vector-borne viral pathogen, infecting millions of patients annually. Thrombocytopenia, a reduction in circulating platelet counts, is the most consistent sign of DENV-induced disease, independent of disease severity. However, the mechanisms leading to DENV-induced thrombocytopenia are unknown. Here, we show that thrombocytopenia is caused by serotonin (...) , derived from mast cells (MCs), which are immune cells that are present in the perivascular space and a major peripheral source of serotonin. We show that during DENV infection, MCs release serotonin, which prompts platelet activation, aggregation and enhanced phagocytosis, dependent on 5HT2A receptors. MC-deficiency in mice or pharmacological inhibition of MCs reversed thrombocytopenia. Furthermore, reconstitution of MC-deficient mice with wild-type MCs, but not MCs lacking serotonin synthesis due

2019 Blood

8. Prenatal Management of Pregnancies at Risk of Fetal Neonatal Alloimmune Thrombocytopenia (FNAIT)

access Please review our and check box below to share full-text version of article. I have read and accept the Wiley Online Library Terms and Conditions of Use. Shareable Link Use the link below to share a full-text version of this article with your friends and colleagues. Copy URL Share a link - FNAIT is suspected in a neonate with thrombocytopenia for which there is no other medical cause identified. In mild to moderately affected neonates, FNAIT typically resolves in the first week of life without (...) Prenatal Management of Pregnancies at Risk of Fetal Neonatal Alloimmune Thrombocytopenia (FNAIT) Prenatal Management of Pregnancies at Risk of Fetal Neonatal Alloimmune Thrombocytopenia (FNAIT) - Regan - - BJOG: An International Journal of Obstetrics & Gynaecology - Wiley Online Library By continuing to browse this site, you agree to its use of cookies as described in our . Search within Search term Search term RCOG Scientific Impact Paper Free Access Prenatal Management of Pregnancies

2019 Royal College of Obstetricians and Gynaecologists

9. Lusutrombopag - to prevent excessive bleeding in adults with thrombocytopenia due to long-standing liver disease

EMEA/H/C/004720 Lusutrombopag Shionogi (lusutrombopag) An overview of Lusutrombopag Shionogi and why it is authorised in the EU What is Lusutrombopag Shionogi and what is it used for? Lusutrombopag Shionogi is a medicine used to prevent excessive bleeding in adults with thrombocytopenia due to long-standing liver disease. Patients with thrombocytopenia have reduced number of platelets (components in the blood that help it to clot), which can cause excessive bleeding. The medicine is for use (...) Lusutrombopag - to prevent excessive bleeding in adults with thrombocytopenia due to long-standing liver disease Official address Domenico Scarlattilaan 6 ? 1083 HS Amsterdam ? The Netherlands An agency of the European Union Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 © European Medicines Agency, 2019. Reproduction is authorised provided the source is acknowledged. EMA/889817/2018

2019 European Medicines Agency - EPARs

10. Diagnosis and management of heparin?induced thrombocytopenia: a consensus statement from the Thrombosis and Haemostasis Society of Australia and New Zealand HIT Writing Group

, Simon McRae, Leonardo Pasalic, Chee Wee Tan, Christopher M Ward and Beng H Chong Med J Aust 2019; 210 (11): . || doi: 10.5694/mja2.50213 Published online: 17 June 2019 Topics Abstract Introduction: Heparin‐induced thrombocytopenia (HIT) is a prothrombotic disorder that occurs following the administration of heparin and is caused by antibodies to platelet factor 4 and heparin. Diagnosis of HIT is essential to guide treatment strategies using non‐heparin anticoagulants and to avoid unwanted (...) Diagnosis and management of heparin?induced thrombocytopenia: a consensus statement from the Thrombosis and Haemostasis Society of Australia and New Zealand HIT Writing Group Diagnosis and management of heparin‐induced thrombocytopenia: a consensus statement from the Thrombosis and Haemostasis Society of Australia and New Zealand HIT Writing Group | The Medical Journal of Australia mja-search search Use the for more specific terms. Title contains Body contains Date range from Date range

2019 MJA Clinical Guidelines

11. Heparin-induced thrombocytopenia

and medications that cause thrombocytopenia history of recent surgery or trauma features consistent with recent venous or arterial thromboembolic event (e.g., PE, DVT, stroke, MI) necrosis at heparin injection site(s) absence of bleeding signs of adrenal haemorrhagic necrosis acute systemic reaction signs of venous limb gangrene recent heparin exposure (within past 100 days) recent orthopaedic or cardiovascular surgery female sex Diagnostic investigations FBC Warkentin (4Ts) Probability Scale HIT antigen (...) Heparin-induced thrombocytopenia Heparin-induced thrombocytopenia - Symptoms, diagnosis and treatment | BMJ Best Practice You'll need a subscription to access all of BMJ Best Practice Search  Heparin-induced thrombocytopenia Last reviewed: February 2019 Last updated: May 2018 Summary A severe drug reaction to heparin that can lead to life- and limb-threatening venous and/or arterial thromboembolism. Diagnosis requires the combination of a compatible clinical picture and laboratory confirmation

2018 BMJ Best Practice

12. Assessment of thrombocytopenia

a reduced production of platelets in the bone marrow, increased clearance, or sequestering of platelets in the spleen. Epidemiology The causes of thrombocytopenia are diverse, making epidemiological generalisations difficult. However, immune thrombocytopenia (ITP) is typically an illness of young women. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168-186. http (...) Assessment of thrombocytopenia Assessment of thrombocytopenia - Differential diagnosis of symptoms | BMJ Best Practice You'll need a subscription to access all of BMJ Best Practice Search  Assessment of thrombocytopenia Last reviewed: February 2019 Last updated: June 2018 Summary Thrombocytopenia is defined as a low circulating platelet count (<150,000 per microlitre). Platelet life span is normally approximately 5 days, with continual renewal. True thrombocytopenia results from either

2018 BMJ Best Practice

13. Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia. Full Text available with Trip Pro

Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia. People with a low platelet count (thrombocytopenia) often require lumbar punctures or an epidural anaesthetic. Lumbar punctures can be diagnostic (haematological malignancies, subarachnoid haematoma, meningitis) or therapeutic (spinal anaesthetic, administration of chemotherapy). Epidural catheters are placed for administration of epidural (...) anaesthetic. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to lumbar punctures and epidural anaesthesia, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to these procedures varies significantly from country to country. This indicates significant uncertainty among clinicians regarding the correct management of these patients. The risk of bleeding appears to be low

2018 Cochrane

14. Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia Full Text available with Trip Pro

Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia Germline mutations in the ubiquitously expressed ACTB, which encodes β-cytoplasmic actin (CYA), are almost exclusively associated with Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF). Here, we report six patients with previously undescribed heterozygous variants clustered in the 3'-coding region of ACTB. Patients present with clinical features distinct from BWCFF, including mild developmental disability, microcephaly (...) , and thrombocytopenia with platelet anisotropy. Using patient-derived fibroblasts, we demonstrate cohort specific changes to β-CYA filament populations, which include the enhanced recruitment of thrombocytopenia-associated actin binding proteins (ABPs). These perturbed interactions are supported by in silico modeling and are validated in disease-relevant thrombocytes. Co-examination of actin and microtubule cytoskeleton constituents in patient-derived megakaryocytes and thrombocytes indicates that these β-CYA

2018 Nature communications

15. Ovarian teratoma: yet another cause of immune thrombocytopenia Full Text available with Trip Pro

Ovarian teratoma: yet another cause of immune thrombocytopenia A hematologic disorder occurred simultaneously with an ovarian cystic teratoma in a young woman. The blood disorder was a severe thrombocytopenia, with no spontaneous remission, or improvement after steroids tapering. To date, this is the second report in literature of immune thrombocytopenia associated with an ovarian teratoma, completely resolving following surgical excision of the ovarian teratoma. This case may suggest

2018 International journal of women's health

16. Author Correction: Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia Full Text available with Trip Pro

Author Correction: Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia The original version of this Article contained an error in Figure 4. In panel i, the lower CYA and α-SMA images were inadvertently inverted. This has been corrected in both the PDF and HTML versions of the Article.

2018 Nature communications

17. Sphingolipid dysregulation due to lack of functional KDSR impairs proplatelet formation causing thrombocytopenia. Full Text available with Trip Pro

Sphingolipid dysregulation due to lack of functional KDSR impairs proplatelet formation causing thrombocytopenia. Sphingolipids are fundamental to membrane trafficking, apoptosis and cell differentiation and proliferation. KDSR or 3-keto-dihydrosphingosine reductase is an essential enzyme for de novo sphingolipid synthesis, and pathogenic mutations in KDSR result in the severe skin disorder erythrokeratodermia variabilis et progressiva-4. Four of the eight reported cases also had (...) thrombocytopenia but the underlying mechanism has remained unexplored. Here we expand upon the phenotypic spectrum of KDSR deficiency with studies in two siblings with novel compound heterozygous variants associated with thrombocytopenia, anemia and minimal skin involvement. We report a novel phenotype of progressive juvenile myelofibrosis in the propositus, with spontaneous recovery of anemia and thrombocytopenia in the first decade of life. Examination of bone marrow biopsies showed megakaryocyte

2018 Haematologica

18. Successful use of ofatumumab in two cases of early-onset juvenile SLE with thrombocytopenia caused by a mutation in protein kinase C δ. Full Text available with Trip Pro

Successful use of ofatumumab in two cases of early-onset juvenile SLE with thrombocytopenia caused by a mutation in protein kinase C δ. We previously described an endogamous Pakistani kindred in whom we identified a novel homozygous missense mutation in the PRKCD gene encoding for protein kinase C δ (PKCδ) as a cause of monogenic systemic lupus erythematosus (SLE). PKCδ has a role in the negative regulation of B cells. Given the nature of the disease, a logical targeted therapeutic approach (...) in these patients is B cell depletion. Indeed, the 3 siblings all had a marked clinical response and resolution of symptoms with rituximab, although 2 of the siblings had severe reactions to rituximab thus precluding further treatment with this. We therefore describe the first successful use of ofatumumab for this rare form of monogenic SLE.All three affected siblings presented with SLE before the age of 3-years with lethargy, intermittent fever, thrombocytopenia, cutaneous involvement, alopecia

2018 Pediatric Rheumatology

19. A novel CYCS mutation in the α-helix of the CYCS C-terminal domain causes non-syndromic thrombocytopenia. (Abstract)

A novel CYCS mutation in the α-helix of the CYCS C-terminal domain causes non-syndromic thrombocytopenia. We report a patient with thrombocytopenia from a Japanese family with hemophilia A spanning four generations. Various etiologies of thrombocytopenia, including genetic, immunological, and hematopoietic abnormalities, determine the prognosis for this disease. In this study, we identified a novel heterozygous mutation in a gene encoding cytochrome c, somatic (CYCS, MIM123970) using whole (...) expression and functional defects in the mitochondrial respiratory chain, indicating that the loss of function of cytochrome c underlies thrombocytopenia. The clinical features of known CYCS variants have been reported to be confined to mild or asymptomatic thrombocytopenia, as was observed for the patient in our study. This study clearly demonstrates that thrombocytopenia can result from CYCS loss-of-function variants.© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

2018 Clinical Genetics

20. T-448, a specific inhibitor of LSD1 enzyme activity, improves learning function without causing thrombocytopenia in mice. (Abstract)

T-448, a specific inhibitor of LSD1 enzyme activity, improves learning function without causing thrombocytopenia in mice. Dysregulation of histone H3 lysine 4 (H3K4) methylation has been implicated in the pathogenesis of several neurodevelopmental disorders. Targeting lysine-specific demethylase 1 (LSD1), an H3K4 demethylase, is therefore a promising approach to treat these disorders. However, LSD1 forms complexes with cofactors including growth factor independent 1B (GFI1B), a critical (...) regulator of hematopoietic differentiation. Known tranylcypromine-based irreversible LSD1 inhibitors bind to coenzyme flavin adenine dinucleotide (FAD) and disrupt the LSD1-GFI1B complex, which is associated with hematotoxicity such as thrombocytopenia, representing a major hurdle in the development of LSD1 inhibitors as therapeutic agents. To discover LSD1 inhibitors with potent epigenetic modulation and lower risk of hematotoxicity, we screened small molecules that enhance H3K4 methylation

2018 Neuropsychopharmacology

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