scholarly journals Signal for a Different Risk of Thrombosis Between Eltrombopag and Romiplostim

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2170-2170
Author(s):  
Thi Thanh Loan N'Guyen ◽  
Maryse Lapeyre-Mestre ◽  
François Montastruc ◽  
Jean-Louis Montastruc ◽  
Guillaume Moulis
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Risk Factor ◽  
Oral Contraceptive ◽  
Venous Thrombosis ◽  
Cerebrovascular Accident ◽  
Arterial Thrombosis ◽  
Increased Risk ◽  
Pharmacovigilance Database ◽  
Venous Thromboses

Abstract Introduction:Eltrombopag and romiplostim are two thrombopoietin receptor agonists (TPO-RAs) marketed for the treatment of immune thrombocytopenia (ITP). Thrombotic events have been reported with both drugs. Whether there exists a differential risk of thrombosis between the two TPO-RAs is unknown. Indeed, there exist pharmacological arguments to sustain a differential risk: i) the two drugs have different structures and different sites of action: romiplostim is an Fc-peptide fusion protein binding to the extracellular TPO receptor domain, while eltrombopag is a small non-peptide molecule that binds to a transmembrane site of the TPO receptor; ii) consequently the intracellular signaling pathways activated by TPO-RAs are not strictly identical in vitro; iii) in clinical practice, a patient who stops a given TPO-RA due to inefficacy, adverse drug reaction (ADR) or important platelet fluctuations can be efficiently rechallenged with the other TPO-RA; and iv) a disproportionality study carried out in the French PharmacoVigilance Database suggested a signal for a different pattern of ADRs between the two drugs. The aim of this study was to assess whether there exists a signal for a different risk of thrombosis, arterial thrombosis, venous thrombosis, ischemic stroke (IS) and myocardial infarction (MI) between romiplostim and eltrombopag. Methods:We carried out a disproportionality analysis (case/non-case method) in the World Health Organization PharmacoVigilance Database (VigiBase®). We selected all the adverse drug reaction (ADR) reports with exposure to eltrombopag or romiplostim between 01 January 2011 and 31 December 2013. Cases were all reports of thrombosis, identified thanks to validated standardized queries and checked by two independent investigators. Non-cases were all other reports. We searched an exposure to eltrombopag (versus romiplostim) in cases and in non-cases, allowing the calculation of Reporting Odds Ratios (RORs). All analyses were adjusted on thrombotic risk factors recorded in the database: age, gender, indication, exposure to oral contraceptive, danazol, polyvalent immunoglobulins, and other pro-thrombotic drugs. We conducted two sensitivity analyses: one restricted to cases and non-cases reported by physicians, and one including the reports of "cerebrovascular accident" among the cases. Results: Out of 2 733 224 ADR reports colligated in VigiBase®during the study period, 4714 were included in the study. TPO-RA indication was ITP in 96.6% of the reports. We found 598 cases of thrombosis: 203 arterial thromboses (94 IS and 110 MI) and 324 venous thrombosis. Among the 324 venous thromboses, 131 (40.4%) were pulmonary embolisms, 45 (13.9%) portal thromboses, and 17 (5.2%) cerebral venous thromboses were found. In multivariate analyses, there was an increased risk of thrombosis (ROR=1.46; 95% CI [1.18-1.82]) and venous thrombosis (ROR=1.46; 95% CI [1.10-1.94]) with eltrombopag. There was no statistically significant difference between the two TPO-RAs regarding arterial thrombosis (ROR=1.29; 95% CI [0.89-1.87]), IS (ROR=1.28; 95% CI [0.79-2.05]) and MI (ROR=1.53; 95% CI [0.96-2.43]). Age was independently associated with the risk of thrombosis. Female gender was a risk factor for venous thrombosis (ROR=1.55; 95% CI [1.16-2.06]); in contrast, it was a protective factor for arterial thrombosis (ROR=0.65; 95% CI [0.44-0.94]) and MI (ROR=0.55; 95% CI [0.34-0.90]). Exposure to oral contraceptive was also an independent risk factor for venous thrombosis (ROR=3.45; 95% CI [1.20-9.90]). Exposure to IVIg was associated with MI (ROR=2.13; 95% CI [1.23-3.68]). When we restricted to ADRs reported by physicians, all ROR measures were slightly increased (overall thrombosis: ROR=2.07; 95% CI [1.60-2.69]; venous thrombosis: ROR=2.02; 95% CI [1.44-2.83]), reaching significance for arterial thrombosis (ROR=1.58; 95% CI [1.01-2.48]) and IS (ROR=2.00; 95% CI [1.16-3.44]). Inclusion of the 45 reports of "cerebrovascular accident" did not influence the results (data not shown). Conclusions: This study suggests a signal for an increased risk of thrombosis with eltrombopag compared to romiplostim, that must be confirmed by population-based pharmacoepidemiological studies. Disclosures No relevant conflicts of interest to declare.

Polymorphisms in the protein C gene as risk factor for venous thrombosis

2009 ◽  
Vol 101 (01) ◽  
pp. 62-67 ◽  
Author(s):  
Carine Doggen ◽  
Hans Vos ◽  
Pieter Reitsma ◽  
Frits Rosendaal ◽  
Elisabeth Pomp
Keyword(s):  
Oral Contraceptive ◽  
Venous Thrombosis ◽  
Protein C ◽  
Contraceptive Use ◽  
Factor V Leiden ◽  
Factor V ◽  
Thrombotic Risk ◽  
Control Subjects ◽  
Oral Contraceptive Use ◽  
Increased Risk

SummaryProtein C is an important inhibitor of blood coagulation. We investigated the effect of two polymorphisms within the promoter region of the protein C gene (C/T at position 2405 and A/G at position 2418) on risk of venous thrombosis and on plasma protein C levels. In addition the combined effect of the two polymorphisms with factor V Leiden and oral contraceptive use was investigated. Previous studies on these polymorphisms were small and were not able to investigate synergistic effects. In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), protein C levels were determined in 2,043 patients with venous thrombosis and 2,857 control subjects, and the two polymorphisms in 4,285 patients and 4,863 control subjects. The CC/GG genotype was associated with the lowest protein C levels. Compared to carriers of the TT/AA genotype – a genotype associated with higher protein C levels – the risk of venous thrombosis in CC/GG carriers was 1.3-fold increased (95% confidence interval 1.09–1.48). The combination of factor V Leiden with the CC/GG genotype led to a 4.7-fold increased risk, compared to non-carriers with the TT/AA genotype. Oral contraceptive use together with the CC/ GG genotype resulted in a 5.2-fold increased risk. In conclusion, the CC/GG genotype is associated with lower levels of protein C and an elevated risk of venous thrombosis compared to the TT/AA genotype. There is no clear synergistic effect of the CC/ GG genotype with factor V Leiden or oral contraceptive use on thrombotic risk.

scholarly journals Antiphospholipid antibodies and thrombosis: association with acquired activated protein C resistance in venous thrombosis and with hyperhomocysteinemia in arterial thrombosis

2004 ◽  
Vol 92 (12) ◽  
pp. 1312-1319 ◽  
Author(s):  
Jeannine Kassis ◽  
Carolyn Neville ◽  
Joyce Rauch ◽  
Lambert Busque ◽  
Erika Chang ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Complete Blood Count ◽  
Tertiary Care ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Activated Protein C Resistance ◽  
Increased Risk

SummaryAlthough antiphospholipid antibodies (aPL) are associated with thrombosis, it is not known who with aPL is at higher risk for thrombosis. It was the aim of this cross-sectional study to investigate how thrombophilic factors contribute to venous or arterial thrombosis in aPL-positive individuals. In outpatient test centres at two tertiary care hospitals, two hundred and eight (208) persons requiring aPL testing were matched by age, gender and centre to 208 persons requiring a complete blood count. Persons were classified as aPL-positive (having anticardiolipin, lupus anticoagulant and/or anti-β2-glycoprotein I antibodies) or aPL-negative. Several thrombophilic factors were studied using logistic regression modelling. Results showed that the aPL-positive group had three-fold more events (37%) than the aPL-negative group (12%). In unadjusted analyses, clinically important associations were observed between factor V Leiden and venous thrombosis, hyperhomocysteinemia and arterial thrombosis, and activated protein C resistance (APCR) and venous thrombosis (OR, 95% CI = 4.00, 1.35-11.91; 4.79, 2.03-11.33; and 2.03, 1.03-3.97, respectively). After adjusting for recruitment group, persons with both APCR and aPL had a three-fold greater risk (OR, 95% CI = 3.31, 1.30-8.41) for venous thrombosis than those with neither APCR nor aPL. Similarly, after adjusting for hypertension, family history of cardiovascular disease, gender and recruitment group, persons with both hyperhomocysteinemia and aPL had a five-fold increased risk (OR, 95% CI = 4.90, 1.37-17.37) for arterial thrombosis compared to those with neither risk factor. In conclusion, APCR phenotype and hyperhomocysteinemia are associated with a higher risk of venous and arterial thrombosis, respectively, in the presence of aPL.

scholarly journals Aripiprazole as a risk factor for impulse control disorders: a systematic review

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S300-S301
Author(s):  
Benjamin Williams ◽  
Benjamin Williams ◽  
Kishen Neelam ◽  
Saumya Singh
Keyword(s):  
Systematic Review ◽  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Dopamine Agonist ◽  
Impulse Control ◽  
Bipolar Affective Disorder ◽  
Impulse Control Disorders ◽  
Risk Of Bias ◽  
Potential Association ◽  
Increased Risk

AimsAripiprazole is an anti-psychotic medication widely used for bipolar affective disorder and depression. It's primary mechanism of action is as a partial dopamine agonist. Aripiprazole's effect on dopamine signalling in the mesolimbic and mesocortical pathways may lead to impulse control disorders, as seen with other dopamine agonist medications. Aripiprazole is often chosen by prescribers because of its favourable side effect profile. There is a need to synthesise the available epidemiological literature on the potential association between aripiprazole use and impulse control disorders. This is needed to inform patients and prescribers of the best available evidence regarding this potential association. Our aim is to conduct a systematic review of the available non case-study evidence on the potential association between aripiprazole and impulse control disorders.MethodDatabases were searched using MEDLINE, PsychINFO, EMBASE, Cochrane Clinical Trials and Web of science. All studies from no earliest date to December 2020 were included; adult patients with a severe and enduring mental illness prescribed antipsychotic medication were included. Cinician diagnosis, structured interview diagnosis, and interviewer or self-completion questionnaires were used to measure prevalence. The study designs included were experimental designs, cohort study, cross-sectional survey and administrative databases. Exclusion criteria being those with traumatic brain injury, psychosis secondary to autoimmune, iatrogenic, chromosomal or metabolic disorder, those with Learning disability or Autistic Spectrum disorders. studies with majority of participants <18yrs. Those who were on other antipsychotic medications in addition to Aripiprazole, were excluded. To ensure quality assurance, we used ROBINS-I tool and GRADE assessment to measure the risk of bias.Result240 records were retrieved, 187 after duplicates were removed. 8 full text articles were assessed for eligibility, of which 4 were included in the qualitative synthesis. 2 studies were analyses of spontaneous adverse drug reaction reporting systems and 2 of health insurance claims databases. All 4 studies found aripiprazole to be associated with greater risk of impulse control disorders. The single study which compared directly with other antipsychotics had a much smaller effect size. Study heterogeneity precluded meta-analysis. All studies were at high risk of bias. The quality of evidence is very low.ConclusionThe available evidence is consistent with the existing warnings regarding increased risk of impulse control disorders in patients prescribed aripiprazole. Clinicians may wish to monitor for this adverse drug reaction. Further research which can account for potential confounders, examines specific impulse control disorders and which is less susceptible to detection and ascertainment biases is required.

A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1311-1318 ◽  
Author(s):  
Beatrice Saposnik ◽  
Jean-Luc Reny ◽  
Pascale Gaussem ◽  
Joseph Emmerich ◽  
Martine Aiach ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Healthy Subjects ◽  
Protein C ◽  
Temporal Stability ◽  
Soluble Form ◽  
Cell Protein ◽  
Increased Risk ◽  
Phenotypic Groups ◽  
Candidate Risk Factor

Abstract The endothelial cell protein C (PC) receptor (EPCR) facilitates PC activation by the thrombin-thrombomodulin complex. A soluble form of this receptor (sEPCR) found in plasma inhibits both activated PC (aPC) activity and PC activation by competing for PC with membrane-associated EPCR. Elevated sEPCR levels are found in approximately 20% of healthy subjects, but the mechanisms underlying this interindividual variability are unknown. We measured sEPCR levels in 100 healthy male volunteers, and observed 2 phenotypic groups of subjects. The temporal stability of sEPCR levels suggested genetic control. Extensive analysis of the EPCR gene in these subjects revealed 13 polymorphisms in complete linkage disequilibrium; these defined 3 haplotypes, 1 of which (A3) was strongly associated with high sEPCR levels. The high constitutive sEPCR levels observed in A3 haplotype carriers might reduce the efficiency of the PC system and predispose these subjects to venous thrombosis. By studying 338 patients with venous thrombosis and 338 age- and sex-matched healthy subjects, we found that the A3 haplotype was overrepresented in the patients. In multivariate analysis, subjects carrying the A3 haplotype had an increased risk of thrombosis (odds ratio [OR] = 1.8; P = .004). Thus, the A3 haplotype, which is associated with elevated plasma sEPCR levels, is a candidate risk factor for venous thrombosis.

The Risk of Intrauterine Growth Restriction (IGR) Is Increased by Risk Determinants of Arterial Thrombosis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2145-2145
Author(s):  
Andrea Gerhardt ◽  
Nadja Howe ◽  
Jan S. Krussel ◽  
Hans G. Bender ◽  
Rudiger E. Scharf ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Significant Risk ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Lipoprotein A ◽  
G20210a Mutation ◽  
Risk Determinants ◽  
Risk Association

Abstract Background: As previously shown, the risk of cardiovascular disease is higher after a maternal placental syndrome, especially in the presence of fetal compromise. The HPA1-b allele of the ß3 subunit of the essential platelet integrin Alphallbbeta3 is a risk factor for increased platelet thrombogenicity, leading to arterial vascular occlusion also triggered by inflammatory endothelial alterations. We performed a case-control study to assess hereditary risk factor for arterial thrombosis in addition to the known risk determinants for venous thrombosis as risk determinants for fetal IGR. Materials and Methods: 121 women with severe fetal IGR (defined by birth weight below the 5th- percentile for gestational age and sex) and 300 normal women were evaluated. Women with other reasons of IGR (history of venous thrombosis, fetal loss, and preeclampsia, neonatale immunthrombocytopenia) were excluded. The fetuses were born alive after the 24th week of gestation. Results: A significant risk association could be shown for the HPA-1b/1b genotype OR 3.1 (95%CI 1.2–8.8), increased levels of lipoprotein (a) (&gt;0.2g/l) OR 1.7 (95%CI 1.0–2.9), increased levels of fibrinogen (&gt;median 284mg/dl) OR 2.8 (95%CI 1.8–4.4) increased levels of FVIII:C (&gt;median 147%) OR 1.7 (95%CI 1.1–2.7), and increased levels of von-Willebrand-factor antigen (vWF-Ag) (&gt;median 129%) OR 2.7 (95%CI 1.1–2.7). The combination of risk determinants led to a further increase in risk (e.g. HPA-1b allele, increased lipoprotein (a) and vWF-Ag OR 14.0) There was no significant risk association for factor V Leiden G1691A OR 1.3 (95% CI 0.7–2.81), and prothrombin G20210A mutation. OR 2.0 (95% CI 0.6–6.5) Conclusions: Increased platelet thrombogenicity via interaction with an inflammatory vascular process and/or via plasma levels of components of hemostasis/receptor ligands appear to be more important in women with IGR than the established risk determinants for venous thrombosis. Pharmacological control of the observed platelet thrombogenicity in patients at risk may be of clinical relevance. In consequence, it will be of importance to examine whether the critical subgroup of patients can benefit from prevention with specific antiplatelet agents.

scholarly journals Incidence, Type, and Management of Venous and Arterial Thrombosis during Ibrutinib Treatment

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3148-3148
Author(s):  
Elizabeth Kander ◽  
Qiuhong Zhao ◽  
Tracy Wiczer ◽  
John C. Byrd ◽  
Jennifer A. Woyach ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
B Cell ◽  
Cumulative Incidence ◽  
Antineoplastic Agent ◽  
Antiplatelet Agents ◽  
Lymphocytic Leukemia ◽  
Bleeding Events ◽  
B Cell Malignancies ◽  
Increased Risk ◽  
Venous Thromboses

Abstract BACKGROUND: Ibrutinib is an irreversible inhibitor of BTK in the B-cell receptor signaling cascade and is widely used to treat chronic lymphocytic leukemia (CLL) and other B-cell malignancies. Ibrutinib also inhibits the tyrosine kinase Tec in platelets, which may be one of the mechanisms of its bleeding toxicity. This makes concomitant use of anticoagulation (AC) or antiplatelet agents challenging, which is a common delimma as many patients taking ibrutinib are elderly and have increased risks of venous and arterial thromboses. The incidence of thrombosis in patients taking ibrutinib is unknown, and we hypothesized that the risk of thrombosis may be reduced during ibrutinib treatment. Therefore, we conducted a single-institution retrospective cohort study to determine the incidence and type of both arterial and venous thromboses during ibrutinib treatment and their management. METHODS: We reviewed medical records of all patients treated with ibrutinib for a hematological malignancy at the Ohio State University between 6/1/2010 and 3/31/2016. Baseline patient and disease characteristics were captured at time of starting ibrutinib. All thrombotic events occurring at any time during treatment with ibrutinib and within three days of its discontinuation were recorded. Time to thrombosis was calculated from the date of starting ibrutinib to the date of thrombosis or censored at the last assessment date, treating discontinuation of ibrutinib or death prior to thrombosis as competing risks. The cumulative incidence of thrombosis was estimated and the Fine and Gray regression models accounting for competing riskes were used to examine the association between patient characteristics and risk of thrombosis. RESULTS: The cohort included 565 patients. Median age was 65 (range 23->89) years and 70.3% (397/565) were men. The majority of patients had CLL (73.6%, 416/565). Other diagnoses included mantle cell lymphoma (9.9%, 56/565), indolent B-cell malignancies (8.1%, 46/565), and aggressive lymphomas (8.3%, 47/565). Median number of prior treatments was 3 (range 0-18) and 6.5% (37/565) of patients were treatment naïve. Prior to ibrutinib, 144 of 565 patients (25.5%) had a history of thrombosis. Sixty-four (11.3%, 64/565) patients had only venous thromboses, 66 (11.7% 66/565) had only arterial thromboses, and 14 patients had both. Concurrently with ibrutinib, 193 (34.2%) patients received antiplatelet agents, 16 (2.8%) patients received AC, and 31 (5.5%) patients received both. Total ibrutinib exposure for the cohort was 1,429 person-years with a median exposure of 2.39 (range 0-7.36) years per patient. A second antineoplastic agent was given with ibrutinib in 30.8% (174/565) of cases, including an immunomodulatory drug in 24 (4.2%, 24/565) patients. During ibrutinib treatment, 22 of 565 (3.9%) patients experienced 24 acute thrombotic events, mostly arterial (Table 1). The incidence of thrombosis was 1.7 (95% CI 1.1-2.5) per 100 person-years of ibrutinib exposure. Of the venous thromboses, 87.5% (7/8) were deep vein thromboses and developed at a median of 7.5 (range 0.5-75.3) months after starting ibrutinib. Of the arterial thromboses, the majority were acute cerebrovascular accidents (37.5%, 6/16) and developed at a median of 27.4 (range 0.4 - 56.6) months after starting ibrutinib. Thrombosis treatment is summarized in Table 1. After thrombosis, ibrutinib was discontinued or held in the majority of cases (75%, 18/24). One patient developed a recurrent thrombosis while on ibrutinib and AC. There were six bleeding events, 3 major (based on ISTH criteria) and 3 minor: all were taking ibrutinib and most were on AC (2 patients on antiplatelet, 1 on AC, 2 on both, 1 on neither). On univariable analysis, the only factors associated with significant (p<0.05) and substantial (HR >2) increased risk of venous thrombosis were prior venous (HR 4.73, CI: 1.06-21.11) and arterial (HR 15.66, CI: 3.07-79.87) thromboses. Antiplatelet use was not significantly associated with either thrombus type. CONCLUSIONS: The cumulative incidence of thrombosis during ibrutinib treatment was low (1.7 per 100 person-years), with the majority being arterial. Prior thrombosis was associated with increased venous thrombosis risk. There are more bleeding than thrombotic complications after patients develop thromboses on ibrutinib, and optimal treatment strategies for this population requires further investigation. Disclosures Kander: AstraZeneca: Consultancy. Wang:Daiichi Sankyo: Consultancy, Other: Travel.

scholarly journals Neutrophil-to-Lymphocyte Ratio (NLR) Is a Risk Factor for Venous Thrombosis in Polycythemia Vera

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1499-1499
Author(s):  
Alessandra Carobbio ◽  
Alessandro Vannucchi ◽  
Paola Guglielmelli ◽  
Giuseppe Gaetano Loscocco ◽  
Ayalew Tefferi ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Polycythemia Vera ◽  
Board Of Directors ◽  
Arterial Thrombosis ◽  
Research Funding ◽  
Multivariate Model ◽  
Advisory Committees ◽  
Thrombotic Risk ◽  
Lymphocyte Ratio

Abstract Background. The tendency towards thrombosis in myeloproliferative neoplasms (MPNs) is linked to the JAK2-mutant clone which leads to hypercellularity and functional interplay between abnormal erythrocytes, platelets, leukocytes and dysfunctional endothelium. The resulting cell activation that also involves stromal cells in their microenvironment, has been shown associated with chronic, systemic, subclinical pro-inflammatory state, and has been implicated in the pathogenesis of thrombosis in MPN. Neutrophil to lymphocyte ratio (NLR) is a novel inflammatory marker found to be associated with the severity and prognosis of cardiovascular diseases but there is little evidence for its prognostic significance in MPN. We investigated whether NLR could predict the onset of arterial and venous thrombosis in polycythemia vera (PV). Methods. Subjects of this study were 1508 patients included in the ECLAP trail with NLR evaluation available. In addition to standard statistical methods, we used proportional hazards additive models (GAM) as they can provide an excellent fit in the presence of nonlinear relationships, for the prediction of total, arterial and venous thrombosis as smooth functions with cubic splines of different blood parameters. Results. After a median follow-up of 2.76 years, 169 thrombotic events (10.3%) were objectively diagnosed and analyzed: 87 arterial (MI, Stroke, TIA, PAT) and 88 venous thrombosis (DVT±PE, superficial thrombophlebitis). In univariate analysis, arterial thrombosis was associated with age (p=0.003) and previous thrombosis, especially if arterial (p&lt;0.001), and with the presence of at least one cardiovascular risk factor (p=0.009). No association between baseline platelet and leukocyte counts and NLR with arterial events was found. Conversely, in venous thrombosis, beside age (p=0.039) and history of venous thrombosis (p&lt;0.001), additional risk factors were low hemoglobin (p=0.039) and increasing values of NLR (p=0.002) resulting from a simultaneous increase of neutrophils (p=0.002) and to a decrease of absolute number lymphocytes (p=0.002).To predict outcomes, we tested total leukocytes, neutrophils, lymphocytes, platelets and NLR by GAM to evaluate their trend in continuous scale of thrombotic risk. A significant association between the risk of venous thrombosis and the progressive lower counts of lymphocytes (p=0.002) emerged, leading to increase the NLR values (p=0.005). However, given the greater precision of the NLR estimates and the markedly wide confidence interval of lymphocyte counts estimates, NLR was used in multivariate model. Conversely, neither absolute values of neutrophils and lymphocytes nor NLR were found associated with arterial events.In multivariate model, adjusted for age, gender and treatments at baseline, the risk of venous thrombosis was independently associated with previous venous events (HR=5.48, p ≤0.001) and NLR values ≥5 -the best cut-off resulted applying the Liu's method (HR=2.13, p=0.001). NLR effect for total venous thrombosis was not modified by excluding superficial venous thrombosis (HR=2.90, p=0.001) in a sensitivity analysis. Older age (i.e., ≥65 years, HR=1.88, p=0.005) and previous arterial thrombosis (HR=1.92, p=0.003) retained the prognostic statistical significance for arterial thrombosis.Our learning cohort findings, indicating a correlation between NLR values and venous thrombosis, have been validated in two Italian independent external cohorts (Florence, n=282 and Rome, n=173) of contemporary PV patients (Figure 1). Conclusions. The NLR is an inexpensive and easily accessible test compared to other inflammatory markers. We found that NLR-alone is an independent predictor of venous thrombosis and could be included in a new scoring system. In addition to guiding the stratification of thrombotic risk, these data confirm that inflammation is a relevant target of antithrombotic therapy in PV. Figure 1 Figure 1. Disclosures Vannucchi: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Barbui: AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Severe Hypoalbuminemia Increases the Risk of Thrombocytopenia in Critically Ill Adult Patients Receiving Teicoplanin

2019 ◽  
Vol 18 (2) ◽  
pp. 153-157 ◽  
Author(s):  
Md Jahidul Hasan ◽  
Raihan Rabbani ◽  
Sitesh C Bachar
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Observational Study ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Albumin Level ◽  
Adult Patients ◽  
Normal Blood ◽  
Drug Of Choice ◽  
Increased Risk

Teicoplanin is a drug of choice for treating infections by gram positive microorganisms. Teicoplanininduced thrombocytopenia is an adverse drug reaction found in critically ill patients receiving teicoplanin. The aim of this observational study was to analyze the increased risk of occurring teicoplanin-induced thrombocytopenia in patients with severe hypoalbuminemia than the patients having normal blood-albumin level. A 5-month long study was conducted in an adult-ICU department on 42 critically ill adult patients. In this study, 17 (40.48%, n=42) patients developed teicoplanin-induced thrombocytopenia and among them, 14 patients (60.87%, n=23) were suffering from severe hypoalbuminemia during the initiation of teicoplanin therapy. All the events were normalized within 48 hours after discontinuing the teicoplanin. In this study, we found that teicoplanin-induced thrombocytopenia is one of the most common adverse drug reaction developed in critically ill adult patients and concurrent severe hypoalbuminemia may enormously increase the risk of this adverse drug reaction. Dhaka Univ. J. Pharm. Sci. 18(2): 153-157, 2019 (December)

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