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Drug induced thrombocytopenia

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https://www.readbyqxmd.com/read/28815933/an-%C3%AE-iib-%C3%AE-3-antagonist-prevents-thrombosis-without-causing-fc%C3%AE-riia-mediated-thrombocytopenia
#1
Yu-Ju Kuo, Ying-Ru Chen, Chun-Chieh Hsu, Hui-Chin Peng, Tur-Fu Huang
BACKGROUND: Thrombocytopenia, a common side effect of Arg-Gly-Asp (RGD)-mimetic antiplatelet drugs, is associated with drug-dependent antibodies (DDAbs) that recognize conformation-altered integrin αIIb β3 . OBJECTIVE: To explore the correlation between αIIb β3 binding epitopes and induction of DDAb binding to conformation-altered αIIb β3 , we examined whether two purified disintegrins TMV-2 and TMV-7 with distinct binding motifs that have different effects on induction of αIIb β3 conformational change and platelet aggregation in the presence of AP2, an IgG1 inhibitory monoclonal antibody (mAb) raised against αIIb β3 ...
August 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28799436/immunotherapy-based-approaches-in-myelofibrosis
#2
Lucia Masarova, Srdan Verstovsek, Hagop Kantarjian, Naval Daver
Aberrant regulation of the immune system with up-regulation of pro-inflammatory cytokines contributes to disease pathophysiology in myelofibrosis (MF). Therapeutic options for MF associated anemia, thrombocytopenia, and bone marrow fibrosis remain limited. Areas covered: This review focuses on immune based therapies in MF, including immunomodulatory imide drugs (IMiDs), interferons, monoclonal antibodies and targeted agents (SL-401), and checkpoint inhibitors. Published literature was reviewed using available databases (PubMed, Cochrane, Scopus) and web pages (clinicaltrials...
August 11, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28789610/management-of-refractory-bleeding-post-cardiopulmonary-bypass-in-an-acute-heparin-induced-thrombocytopenia-type-ii-renal-failure-patient-who-underwent-urgent-cardiac-surgery-with-bivalirudin-angiox-%C3%A2-anticoagulation
#3
Kimberly Hassen, Maria R Maccaroni, Haytham Sabry, Smitangshu Mukherjee, Shankari Serumadar, Inderpaul Birdi
Acute heparin-induced thrombocytopenia (HIT) patients present a myriad of anticoagulation management challenges, in clinical settings where unfractionated heparin (UFH) is the traditional drug of choice. UFH use in cardiac surgery is a known entity that has been subject to rigorous research. Research has, thus, led to its unparalleled use and the development of well-established protocols for cardiac surgery. In comparison to UFH, bivalirudin use for acute HIT patients requiring urgent cardiac surgery with cardiopulmonary bypass (CPB) is still in its infancy...
August 1, 2017: Perfusion
https://www.readbyqxmd.com/read/28782406/severe-sunitinib-induced-myelosuppression-in-a-patient-with-a-cyp-3a4-polymorphism
#4
Nirav D Patel, Kanishka Chakrabory, Garrett Messmer, Koyamangalath Krishnan, John B Bossaer
Sunitinib, an oral vascular endothelial growth factor receptor, is a first-line option for metastatic renal cell carcinoma and widely used in clinical practice. Despite the proven benefit of sunitnib in metastatic renal cell carcinoma, patients may suffer from a variety of adverse events including hypertension, fatigue, hypothyroidism, hand-foot skin reactions, rash, depigmentation, and myelosuppression. Myelosuppression is usually mild, transient and resolves during the two weeks at the end of each cycle where no drug is taken...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28782250/meropenem-induced-immune-thrombocytopenia-and-the-diagnostic-process-of-laboratory-testing
#5
Rong Huang, Guang-Qing Cai, Jun-Hua Zhang, Feng-Xia Liu, Jin-Qi Ma, Hong Liu, Xin-Min Nie, Rong Gui
BACKGROUND: Drug-induced immune thrombocytopenia (DITP) is a serious, life-threatening clinical syndrome, the diagnosis of which is consistently difficult. In this report, we present a case of DITP caused by meropenem that was confirmed by laboratory tests. CASE REPORT: A 59-year-old male patient developed severe thrombocytopenia 8 days after the administration of meropenem and cefoperazone-sulbactam. After other causes were ruled out, DITP was suspected. Drug-induced platelet (PLT) antibodies were detected by enzyme immunoassay, flow cytometry, and monoclonal antibody immobilization of PLT antigens (MAIPA)...
August 7, 2017: Transfusion
https://www.readbyqxmd.com/read/28774273/thrombotic-microangiopathy-associated-with-valproic-acid-toxicity
#6
Sean A Hebert, Timothy P Bohan, Christian L Erikson, Rita D Swinford
BACKGROUND: Thrombotic microangiopathy (TMA) is a serious, sometimes life-threatening disorder marked by the presence of endothelial injury and microvascular thrombi. Drug-induced thrombotic microangiopathy (DI-TMA) is one specific TMA syndrome that occurs following drug exposure via drug-dependent antibodies or direct tissue toxicity. Common examples include calcineurin inhibitors Tacrolimus and Cyclosporine and antineoplastics Gemcitabine and Mitomycin. Valproic acid has not been implicated in DI-TMA...
August 3, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28725494/apixaban-for-treatment-of-confirmed-heparin-induced-thrombocytopenia-a-case-report-and-review-of-literature
#7
Daniel E Ezekwudo, Rebecca Chacko, Bolanle Gbadamosi, Syeda Batool, Sussana Gaikazian, Theodore E Warkentin, Jo-Ann I Sheppard, Ishmael Jaiyesimi
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening condition caused by the binding of platelet-activating antibodies (IgG) to multimolecular platelet factor 4 (PF4)/heparin complexes because of heparin exposure. The by-product of this interaction is thrombin formation which substantially increases the risk of venous and/or arterial thromboembolism. Currently, only one anticoagulant, argatroban, is United States Food and Drug Administration-approved for management of HIT; however, this agent is expensive and can only be given by intravenous infusion...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28718268/oxymorphone-induced-thrombotic-microangiopathy-mimicking-atypical-haemolytic-uremic-syndrome
#8
Amibhen Gandhi, Saad Ullah, Shani Kotadia, Samer Nasser
Atypical Haemolytic Uremic Syndrome (aHUS) is a rare life threatening entity characterized by thrombocytopenia, haemolytic anaemia and renal dysfunction. It is a thrombotic microangiopathy related to genetic mutations in the alternate complement pathway and has a distinct pathophysiology which makes it harder to distinguish from other microangiopathies. We present a case of a 25-year-old male patient with history of polysubstance abuse who presented with chest pain and dyspnoea. He admitted to using injectable oxymorphone (Opana) two weeks before presentation...
April 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28712066/effect-of-ph-and-ionic-strength-on-the-binding-strength-of-anti-pf4-polyanion-antibodies
#9
Thi-Huong Nguyen, Andreas Greinacher
Antibodies against the chemokine platelet factor 4 (PF4) in complex with heparin cause the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). The current dilemma for laboratory diagnosis of HIT is that only about 50% of these antibodies are pathogenic, but the widely available enzyme immunosorbent assays (EIA), used for diagnosis in the clinical laboratory cannot differentiate between non-pathogenic- and pathogenic (platelet activating) antibodies. It would be highly desirable to improve diagnosis for HIT...
July 15, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28688202/influence-of-human-leukocyte-antigen-hla-alleles-and-killer-cell-immunoglobulin-like-receptors-kir-types-on-heparin-induced-thrombocytopenia-hit
#10
Jason H Karnes, Christian M Shaffer, Robert Cronin, Lisa Bastarache, Silvana Gaudieri, Ian James, Rebecca Pavlos, Heidi Steiner, Jonathan D Mosley, Simon Mallal, Joshua C Denny, Elizabeth J Phillips, Dan M Roden
OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT...
July 8, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28682499/high-dose-dexamethasone-or-all-trans-retinoic-acid-restores-the-balance-of-macrophage-toward-m2-in-immune-thrombocytopenia
#11
Q Feng, M Xu, Y Y Yu, Y Hou, X Mi, Y X Sun, S Ma, X Y Zuo, L L Shao, M Hou, X H Zhang, J Peng
Immune thrombocytopenia (ITP) is an autoimmune disorder. Deficiency of immune-tolerance in antigen-presenting cells (APCs) and cross-communication between APCs and T cells are involved in the pathogenesis of ITP. Macrophages can polarize into pro-inflammatory M1 or anti-inflammatory M2 phenotypes in response to different environmental stimuli, and possess diverse immunological functions OBJECTIVES: To investigate the imbalance of M1/M2 in ITP and whether high-dose dexamethasone (HD-DXM) or all-trans retinoic acid (ATRA) could restore this imbalance METHODS: Numbers of M1 and M2 in the spleens of ITP patients and patients with traumatic spleen rupture were analyzed by immunofluorescence...
July 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28680014/can-rivaroxaban-be-a-drug-of-choice-for-treating-heparin-induced-thrombocytopenia-in-a-patient-with-pulmonary-thromboembolism
#12
Marija Vavlukis, Irina Kotlar, Hajber Taravari, Lidija Poposka, Sasko Kedev
No abstract text is available yet for this article.
July 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28667459/clinical-pharmacokinetics-and-pharmacodynamics-of-panobinostat
#13
REVIEW
Mathilde Van Veggel, Elsbeth Westerman, Paul Hamberg
Histone deacetylase (HDAC) inhibitors cause an increase in acetylation that leads to an increase in DNA transcription and accumulation of different proteins, reducing cell proliferation and inducing cell death. Panobinostat is a first-in-line HDAC inhibitor approved for treating multiple myeloma in combination with bortezomib and dexamethasone. It is a pan-deacetylase inhibitor and therefore inhibits not only HDAC but also other deacetylases. The main mechanism of action of panobinostat is to inhibit HDAC, which causes cell cycle arrest and apoptosis, leading to it being an antineoplastic drug...
June 30, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28661475/protein-kinase-a-activation-by-the-anti-cancer-drugs-abt-737-and-thymoquinone-is-caspase-3-dependent-and-correlates-with-platelet-inhibition-and-apoptosis
#14
Natalia Rukoyatkina, Elke Butt, Hariharan Subramanian, Viacheslav O Nikolaev, Igor Mindukshev, Ulrich Walter, Stepan Gambaryan, Peter M Benz
Chemotherapy-induced thrombocytopenia is a common bleeding risk in cancer patients and limits chemotherapy dose and frequency. Recent data from mouse and human platelets revealed that activation of protein kinase A/G (PKA/PKG) not only inhibited thrombin/convulxin-induced platelet activation but also prevented the platelet pro-coagulant state. Here we investigated whether or not PKA/PKG activation could attenuate caspase-dependent apoptosis induced by the anti-cancer drugs ABT-737 (the precursor of navitoclax) and thymoquinone (TQ), thereby potentially limiting chemotherapy-induced thrombocytopenia...
June 29, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28660533/analysis-of-cytopenia-in-geriatric-inpatients
#15
G Röhrig, I Becker, K Pappas, M C Polidori, R J Schulz
BACKGROUND: Peripheral blood dyscrasias in older patients are repeatedly seen in geriatric clinical practice; however, there is substantial lack of data about the epidemiology, possible causes and treatment options in this patient group. Proton pump inhibitors (PPI) are extensively used in older patients and associated with leukopenia. The primary objective of this study was the assessment of encoded cytopenia prevalence in a geriatric patient cohort and the secondary objective was the assessment of putative causes and the analysis of PPI administration in patients with cytopenia...
June 28, 2017: Zeitschrift Für Gerontologie und Geriatrie
https://www.readbyqxmd.com/read/28655784/inhibition-of-megakaryocyte-differentiation-by-antibody-drug-conjugates-adcs-is-mediated-by-macropinocytosis-implications-for-adc-induced-thrombocytopenia
#16
Hui Zhao, Sara Gulesserian, Sathish Kumar Ganesan, Jimmy Ou, Karen Morrison, Zhilan Zeng, Veronica Robles, Josh Snyder, Lisa Do, Hector Aviña, Sher Karki, David R Stover, Fernando Doñate
Thrombocytopenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADCs), including AGS-16C3F, an ADC targeting ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3) and Trastuzumab emtansine (T-DM1). This study aims to elucidate the mechanism of action of ADC-induced thrombocytopenia. ENPP3 expression in platelets and megakaryocytes (MKs) was investigated and shown to be negative. The direct effect of AGS-16C3F on platelets was evaluated using platelet rich plasma following the expression of platelet activation markers...
June 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28652707/development-of-new-promising-antimetabolite-dfp-11207-with-self-controlled-toxicity-in-rodents
#17
Masakazu Fukushima, Kenzo Iizuka, Cheng Jin, Chun Zhang, Mei Hong, Kiyoshi Eshima
To reduce 5-fluorouracil (5-FU)-induced serious toxicities without loss of antitumor activity, we have developed DFP-11207, a novel fluoropyrimidine, which consists of 1-ethoxymethyl-5-fluorouracil (EM-FU; a precursor form of 5-FU), 5-chloro-2,4-dihydroxypyridine (CDHP; an inhibitor of 5-FU degradation), and citrazinic acid (CTA; an inhibitor of 5-FU phosphorylation). In vitro studies of DFP-11207 indicated that it strongly inhibited the degradation of 5-FU by dihydropyrimidine dehydrogenase (DPD) in homogenates of the rat liver, and also inhibited the phosphorylation of 5-FU by orotate phosphoribosyltransferase (OPRT) in tumor tissues in a similar magnitude of potency by CDHP and CTA, respectively...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28646408/a-mechanism-based-pk-pd-model-for-hematological-toxicities-induced-by-antibody-drug-conjugates
#18
Sihem Ait-Oudhia, Weiyan Zhang, Donald E Mager
Antibody-drug conjugates (ADCs) are complex drug platforms composed of monoclonal antibodies (mAbs) conjugated to potent cytotoxic drugs (payloads) via chemical linkers, enabling selective payload delivery to neoplastic cells, resulting in improved efficacy and reduced toxicity. Brentuximab vedotin (Adcetris®, SGN-35) and adotrastuzumab emtansine (Kadcyla®, T-DM1) are the two FDA-approved and commercially available ADCs, and both drugs exhibit ADC-related thrombocytopenia and neutropenia. A pharmacokinetic/pharmacodynamic (PK/PD) model for ADCs was developed to identify the analyte from each ADC that is most associated with the observed hematopoietic toxicities and to determine the role of the apparent in vivo payload release rate on the severity of thrombocytopenia and neutropenia...
June 23, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28638678/detailed-features-of-hematological-involvement-and-medication-induced-cytopenia-in-systemic-lupus-erythematosus-patients-single-center-results-of-221-patients
#19
Hava Üsküdar Teke, Döndü Üsküdar Cansu, Cengiz Korkmaz
OBJECTIVE: Systemic lupus erythematosus (SLE) may affect a number of systems, with the hematological system being one of the most common. Our aim is to determine the existence of cytopenia at diagnosis or during follow-up of our SLE patients as well as the associated factors. MATERIAL AND METHODS: A cohort of SLE patients that had been followed-up in the Department of Rheumotology from 1998 to 2015 was retrospectively assessed. Clinical and laboratory findings about the patients were recorded...
June 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28638161/argatroban-for-heparin-induced-thrombocytopenia-during-venovenous-extracorporeal-membrane-oxygenation-with-continuous-venovenous-hemofiltration
#20
Jonathan H Sin, Natasha D Lopez
Patients receiving extracorporeal membrane oxygenation (ECMO) are at risk of circuit thrombosis due to constant contact between blood and the extracorporeal components. Unfractionated heparin has traditionally been used in this setting as a systemic form of anticoagulation to prevent thrombosis of the circuit. However, if a patient develops heparin-induced thrombocytopenia (HIT), an alternative anticoagulant would be required while the patient is maintained on ECMO. Unfortunately, the pharmacokinetic changes induced by ECMO and critical illness may potentially affect optimal drug dosing...
June 2017: Journal of Extra-corporeal Technology
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