scholarly journals 302. Using Antiphospholipid Antibody Presence as an Additional Biomarker to Identify COVID-19 Positive Patients with High Risk for Thrombosis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S257-S257
Author(s):  
Jennifer R Hewlett ◽  
Jing Du ◽  
M Sung Lee ◽  
Gavin McLeod ◽  
Herbert Archer
Keyword(s):  
High Risk ◽  
Antiphospholipid Antibodies ◽  
Oral Anticoagulants ◽  
High Risk Group ◽  
Nucleic Acid Amplification ◽  
Antiphospholipid Antibody ◽  
Therapeutic Anticoagulation ◽  
Increased Risk ◽  
Risk For Thrombosis ◽  
D Dimer

Abstract Background Patients who are hospitalized with Coronavirus 2019 (COVID-19) are known to have increased risk for thrombosis. Several mechanisms have been proposed for increased thrombogenesis, including antiphospholipid antibodies (APLs). We sought to better understand the relationship between a commonly used marker of thrombosis, D-dimer, and antiphospholipid antibodies in relation to thrombosis in COVID-19. Methods This was a single-center prospective cohort study. Participants were adults admitted to the hospital with COVID-19 between March and December of 2020. Included patients required a positive COVID-19 nasopharyngeal nucleic acid amplification testing (NAAT), coagulation studies, and regular assessment of D-dimer levels. Patients who were excluded were pregnant adults, use of oral anticoagulants prior to admission, and absence of a positive COVID-19 nasopharyngeal NAAT. We tested 52 patients for antiphospholipid antibodies (APLs), including lupus anticoagulant (LA), anti-beta-2 glycoprotein antibodies (B2GP), and anti-cardiolipin antibodies (aCL). The endpoint for analysis was hospital discharge or development of a confirmed thrombosis. Results Twenty-nine of fifty-two patients (55.7%) with COVID-19 had non-negative APLs. Of these patients, twenty-seven (93.1%) had non-negative aCLs, the majority of which were IgM antibodies. There was a total of 7 thrombotic events in our cohort. The sensitivity of D-dimer alone was 85% and the sensitivity of APLs alone was 71%. In patients with an intermediate D-dimer level (i.e., greater than 2 milligrams per liter (mg/L) but less than 5 mg/L), the addition of non-negative APLs increased the sensitivity of D-dimer to 100%. In patients with a high D-dimer (i.e., greater than 5), the combined sensitivity of D-dimer and APLs was 60%. Out of the 7 thrombotic events in our cohort, two patients had negative APLs, however both patients had a D-dimer of greater than 5 mg/L. Conclusion The use of APLs can assist in risk-stratifying patients in an intermediate-risk D-dimer group to consider prophylactic anticoagulation if APLs are negative and to consider therapeutic anticoagulation if APLs are non-negative. In the high-risk group (i.e., a D-dimer greater than 5 mg/dL), a therapeutic anticoagulation approach may be more appropriate. Disclosures All Authors: No reported disclosures

scholarly journals Modified IMPROVE VTE Risk Score and Elevated D-Dimer Identify a High Venous Thromboembolism Risk in Acutely Ill Medical Population for Extended Thromboprophylaxis

TH Open ◽  
2020 ◽  
Vol 04 (01) ◽  
pp. e59-e65 ◽  
Author(s):  
Alex C. Spyropoulos ◽  
Concetta Lipardi ◽  
Jianfeng Xu ◽  
Colleen Peluso ◽  
Theodore E. Spiro ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Risk Score ◽  
Lower Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Cutoff Score ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
D Dimer

AbstractAn individualized approach to identify acutely ill medical patients at increased risk of venous thromboembolism (VTE) and a low risk of bleeding to optimize the benefit and risk of extended thromboprophylaxis (ET) is needed. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk score has undergone extensive external validation in medically ill patients for in-hospital use and a modified model was used in the MARINER trial of ET also incorporating an elevated D-dimer. The MAGELLAN study demonstrated efficacy with rivaroxaban but had excess bleeding. This retrospective analysis investigated whether the modified IMPROVE VTE model with an elevated D-dimer could identify a high VTE risk subgroup of patients for ET from a subpopulation of the MAGELLAN study, which was previously identified as having a lower risk of bleeding. We incorporated the modified IMPROVE VTE score using a cutoff score of 4 or more or 2 and 3 with an elevated D-dimer (>2 times the upper limit of normal) to the MAGELLAN subpopulation. In total, 56% of the patients met the high-risk criteria. In the placebo group, the total VTE event rate at Day 35 was 7.94% in the high-risk group and 2.83% for patients in the lower-risk group. A reduction in VTE was observed with rivaroxaban in the high-risk group (relative risk [RR]: 0.68, 95% confidence interval [CI]: 0.51–0.91, p = 0.008) and in the lower-risk group (RR: 0.69, 95% CI: 0.40 -1.20, p = 0.187). The modified IMPROVE VTE score with an elevated D-dimer identified a nearly threefold higher VTE risk subpopulation of patients where a significant benefit exists for ET using rivaroxaban.

The Risk of Recurrent Venous Thromboembolism in Patients with and without Factor V Leiden

1997 ◽  
Vol 77 (04) ◽  
pp. 624-628 ◽  
Author(s):  
Sabine Eichinger ◽  
Ingrid Pabinger ◽  
Andreas Stümpfien ◽  
Mirko Hirschl ◽  
Christine Bialonczyk ◽  
...  
Keyword(s):  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Factor V Leiden ◽  
Multicenter Trial ◽  
Observation Time ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Factor V ◽  
Increased Risk ◽  
Recurrent Vte

SummaryThromboprophylaxis with oral anticoagulants up to six months is established in patients after a first venous thromboembolic event (VTE). The risk of recurrent VTE is still considerable thereafter, and it is uncertain whether some patients might benefit from extended anticoagulation. We performed a prospective, multicenter trial (4 thrombosis centers) and evaluated in 380 patients with a first or recurrent VTE (patients with a deficiency of antithrombin, protein C, protein S or plasminogen; cancer; or an antiphospholipid antibody syndrome were excluded) the risk of recurrence after discontinuation of secondary thromboprophylaxis with oral anticoagulants. It was the aim of the study to evaluate whether patients with factor V Leiden are at an increased risk of recurrent VTE. 112 (29.5%) patients were carriers of factor V Leiden (26.9% heterozygous, 2.6% homozygous). After a median observation time of 19.3 months the overall recurrence rate of VTE was 9.9%. Recurrent deep vein thrombosis and/or pulmonary embolism occurred in 26 of 268 patients without factor V Leiden (9.7%) and in 10 of 112 patients with factor V Leiden (8.9%). The probability of recurrent VTE two years after discontinuation of oral anticoagulants was 12.4% (95% Cl 7.8-17) in patients without factor V Leiden and was 10.6% (95% Cl 3.8-17.4) in carriers of the mutation. This difference was statistically not significant. Patients with factor V Leiden are not at a higher risk of recurrent VTE within two years after discontinuation of oral anticoagulants than patients without factor V Leiden. Balancing the risk of recurrent VTE and bleeding from oral. anticoagulants, patients with factor V Leiden are not likely to benefit from oral anticoagulant therapy extended beyond six months.

Mortality in offspring of mothers with psychotic disorder

2007 ◽  
Vol 38 (8) ◽  
pp. 1203-1210 ◽  
Author(s):  
J. Suvisaari ◽  
L. Häkkinen ◽  
J. Haukka ◽  
J. Lönnqvist
Keyword(s):  
High Risk ◽  
General Population ◽  
Psychotic Disorder ◽  
Psychotic Disorders ◽  
Suicide Attempts ◽  
Risk Group ◽  
High Risk Group ◽  
Suicide Mortality ◽  
Increased Risk ◽  
Maternal Suicide

BackgroundPrevious studies suggest that offspring of mothers with psychotic disorders have an almost two-fold higher mortality risk from birth until early adulthood. We investigated predictors of mortality from late adolescence until middle age in offspring of mothers with psychotic disorders.MethodThe Helsinki High-Risk Study follows up offspring (n=337) of women treated for schizophrenia spectrum disorders in mental hospitals in Helsinki before 1975. Factors related to mortality up to 2005 among offspring of these mothers was investigated with a survival model. Hazard rate ratios (HRR) were calculated using sex, diagnosis of psychotic disorder, childhood socio-economic status, maternal diagnosis, and maternal suicide attempts and aggressive symptoms as explanatory variables. The effect of family was investigated by including a frailty term in the model. We also compared mortality between the high-risk group and the Finnish general population.ResultsWithin the high-risk group, females had lower all-cause mortality (HRR 0.43, p=0.05) and mortality from unnatural causes (HRR 0.24, p=0.03) than males. Having themselves been diagnosed with a psychotic disorder was associated with higher mortality from unnatural causes (HRR 4.76, p=0.01), while maternal suicide attempts were associated with higher suicide mortality (HRR 8.64, p=0.03). Mortality in the high-risk group was over two-fold higher (HRR 2.44, p<0.0001) than in the general population, and remained significantly higher when high-risk offspring who later developed psychotic disorders were excluded from the study sample (HRR 2.30, p<0.0001).ConclusionsOffspring of mothers with psychotic disorder are at increased risk of several adverse outcomes, including premature death.

Triple positive antiphospholipid antibody profile in outpatients with tests for lupus anticoagulants

2015 ◽  
Vol 53 (1) ◽  
Author(s):  
Paul Froom ◽  
Enas Saffuri-Elias ◽  
Orit Rozenberg ◽  
Mira Barak
Keyword(s):  
Antiphospholipid Antibody ◽  
Test Results ◽  
Serum Igg ◽  
Increased Risk ◽  
Antibody Positivity ◽  
Normal Functional ◽  
Single Positive ◽  
Antibody Profile ◽  
Risk For Thrombosis ◽  
Test Result

AbstractA triple positive antiphospholipid (aPL) antibody profile [two positive serum IgG aPL antibodies along with one positive functional plasma lupus anticoagulant (LAC) test result] is associated with an increased risk for thrombosis, whereas patients with single positive test results may have little to no increased risk. The frequency of triple positivity in outpatients with various combinations of LAC test results is unclear.We extracted from our database all LAC test results [dilute Russell viper venom times (dRVVT) and silica clotting times (SCT)] that had concomitant serum IgG aPL testing [both serum anti βThere were 3195 patients without a prolonged prothrombin time. Double antibody positivity was found in 1% (31/2955) of those with normal functional LAC test results, in 16.0% (31/81) of those with a positive dRVVT, in 12.7% (10/79) of those with a positive SCT, and in 56.3% (45/80) of those with both tests positive (p<0.001). A triple positive aPL antibody profile was found in 28.3% (68/240) of those with at least one positive LAC test result.We conclude that 28% of patients with elevated LAC tests have a triple positive aPL antibody profile and patients with two positive LAC tests have a higher prevalence of a triple positive profile than do those with one positive LAC test result.

People at risk of schizophrenia

1999 ◽  
Vol 174 (6) ◽  
pp. 547-553 ◽  
Author(s):  
Ann Hodges ◽  
Majella Byrne ◽  
Elizabeth Grant ◽  
Eve Johnstone
Keyword(s):  
At Risk ◽  
High Risk ◽  
Social Isolation ◽  
High Risk Group ◽  
Control Group ◽  
Psychiatric Interview ◽  
Increased Risk ◽  
Sample Characteristics ◽  
And Gender ◽  
Disordered Speech

BackgroundThe Edinburgh High-Risk Study is designed to explore the underlying pathogenesis of schizophrenia.AimsTo establish the sample characteristics of the first 100 subjects in this study of young adults at risk of schizophrenia for genetic reasons, and to compare them with appropriate controls.MethodDetails of the recruitment of the first 100 high-risk subjects aged 16–25 years into a prospective Scotland-wide study are given. Subjects and 30 age- and gender-matched normal controls were interviewed using the PSE, SADS-L and SIS and an unstructured psychiatric interview.ResultsSome significant differences emerged between the high-risk group and the control group, namely in previous psychiatric history (31 v. 6.3%), forensic contacts (19 v. 3.1%) and delinquent behaviour (20 v. 3.1%). There were also differences in some parameters from the SIS: childhood social isolation, interpersonal sensitivity, social isolation, suicidal ideation, restricted affect, oddness and disordered speech.ConclusionsThese differences may represent increased risk of developing schizophrenia although their true significance will not be revealed until the cohort has been followed through the at-risk years.

scholarly journals Associations between childhood trauma, bullying and psychotic symptoms among a school-based adolescent sample

2008 ◽  
Vol 193 (5) ◽  
pp. 378-382 ◽  
Author(s):  
Ian Kelleher ◽  
Michelle Harley ◽  
Fionnuala Lynch ◽  
Louise Arseneault ◽  
Carol Fitzpatrick ◽  
...  
Keyword(s):  
Domestic Violence ◽  
High Risk ◽  
Childhood Trauma ◽  
Psychotic Disorders ◽  
Traumatic Events ◽  
High Risk Group ◽  
Traumatic Experiences ◽  
Psychotic Symptoms ◽  
High Risk Population ◽  
Increased Risk

BackgroundChildren and adolescents who report psychotic symptoms appear to be at increased risk for psychotic disorders in adulthood – a putative ‘symptomatic’ high-risk group. However, little research has investigated whether those in this high-risk population have increased rates of exposure to traumatic events in childhood, as seen in patients who have a psychotic illness.AimsTo examine whether adolescents with psychotic symptoms have an increased rate of traumatic experiences.MethodPsychiatric interviews were carried out with 211 adolescents aged between 12 and 15 years and their parents as part of a population-based study. The interview enquired about a number of early traumatic events including physical and sexual abuse, exposure to domestic violence and bullying.ResultsFourteen adolescents (6.6% of those interviewed) reported experiencing at least one psychotic symptom. Adolescents who reported psychotic symptoms were significantly more likely to have been physically abused in childhood, to have been exposed to domestic violence and to be identified as a bully/victim (that is, both a perpetrator and victim of bullying) than those who did not report such symptoms. These findings were not confounded by comorbid psychiatric illness or family history of psychiatric history.ConclusionsOur findings suggest that childhood trauma may increase the risk of psychotic experiences. The characteristics of bully/victims deserve further study.

The Glasgow whipple risk score to predict pancreas-specific complications after pancreaticoduodenectomy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 394-394
Author(s):  
Lavanniya Kumar Palani Velu ◽  
Vishnuvardhan Chandrabalan ◽  
Ross Carter ◽  
Colin McKay ◽  
Donald McMillan ◽  
...  
Keyword(s):  
High Risk ◽  
Serum Amylase ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Prolonged Stay ◽  
Increased Risk ◽  
Clinically Significant ◽  
Serum Crp

394 Background: Pancreas-specific complications (PSC), comprising postoperative pancreatic fistula, post-pancreatectomy haemorrhage, and intra-abdominal collections, are drivers of morbidity following pancreaticoduodenectomy (PD). Intra-operatively derived pancreatic gland texture is a major determinant of postoperative PSC. We have previously demonstrated that a postoperative day 0 (PoD0) serum amylase ≥ 130 IU/L is an objective surrogate of pancreatic texture, and is associated with PSC. We sought to refine the PSC risk prediction model by including serial measurements of serum C-reactive protein (CRP). Methods: 230 consecutive patients undergoing PD between 2008 and 2014 were included in the study. Routine serum investigations, including amylase and CRP were performed from the pre-operative day. Receiver operating characteristic (ROC) curve analysis was used to identify a threshold value of serum CRP associated with clinically significant PSC. Results: 95 (41.3%) patients experienced a clinically significant PSC. ROC analysis identified post-operative day 2 (PoD2) serum CRP of 180 mg/L as the optimal threshold (P=0.005) associated with clinically significant PSC, a prolonged stay in critical care (P =0.032), and a relaparotomy (P = 0.045). Patients with a PoD0 serum amylase ≥ 130 IU/L who then developed a PoD2 serum CRP ≥ 180 mg/L had a higher incidence of postoperative complications. Patients were categorised into high, intermediate and low risk groups based on PoD0 serum amylase and PoD2 serum CRP. Patients in the high risk group (PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l) had significantly higher incidence of PSC, a return to theatre, prolonged lengths stay (all P≤ 0.05) and a four-fold increase in perioperative mortality compared patients in the intermediate and low risk groups (7 deaths in the high risk group versus 2 and nil in the intermediate and low risk groups respectively). Conclusions: A high risk profile, defined as PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l, should raise the clinician’s awareness of the increased risk of clinically significant PSC and a complicated postoperative course following pancreaticoduodenectomy.

scholarly journals Melanoma Prognostic Model Using Tissue Microarrays and Genetic Algorithms

2009 ◽  
Vol 27 (34) ◽  
pp. 5772-5780 ◽  
Author(s):  
Bonnie E. Gould Rothberg ◽  
Aaron J. Berger ◽  
Annette M. Molinaro ◽  
Antonio Subtil ◽  
Michael O. Krauthammer ◽  
...  
Keyword(s):  
Genetic Algorithm ◽  
High Risk ◽  
Proportional Hazards ◽  
Risk Group ◽  
High Risk Group ◽  
Hazard Ratio ◽  
Stage Ii ◽  
Primary Tumors ◽  
Increased Risk ◽  
Clinicopathologic Parameters

PurposeAs a result of the questionable risk-to-benefit ratio of adjuvant therapies, stage II melanoma is currently managed by observation because available clinicopathologic parameters cannot identify the 20% to 60% of such patients likely to develop metastatic disease. Here, we propose a multimarker molecular prognostic assay that can help triage patients at increased risk of recurrence.MethodsProtein expression for 38 candidates relevant to melanoma oncogenesis was evaluated using the automated quantitative analysis (AQUA) method for immunofluorescence-based immunohistochemistry in formalin-fixed, paraffin-embedded specimens from a cohort of 192 primary melanomas collected during 1959 to 1994. The prognostic assay was built using a genetic algorithm and validated on an independent cohort of 246 serial primary melanomas collected from 1997 to 2004.ResultsMultiple iterations of the genetic algorithm yielded a consistent five-marker solution. A favorable prognosis was predicted by ATF2 ln(non-nuclear/nuclear AQUA score ratio) of more than –0.052, p21WAF1nuclear compartment AQUA score of more than 12.98, p16INK4Aln(non-nuclear/nuclear AQUA score ratio) of ≤ −0.083, β-catenin total AQUA score of more than 38.68, and fibronectin total AQUA score of ≤ 57.93. Primary tumors that met at least four of these five conditions were considered a low-risk group, and those that met three or fewer conditions formed a high-risk group (log-rank P < .0001). Multivariable proportional hazards analysis adjusting for clinicopathologic parameters shows that the high-risk group has significantly reduced survival on both the discovery (hazard ratio = 2.84; 95% CI, 1.46 to 5.49; P = .002) and validation (hazard ratio = 2.72; 95% CI, 1.12 to 6.58; P = .027) cohorts.ConclusionThis multimarker prognostic assay, an independent determinant of melanoma survival, might be beneficial in improving the selection of stage II patients for adjuvant therapy.

scholarly journals Evaluation of Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in the Oncology Population

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5026-5026
Author(s):  
Jessica Hedvat ◽  
Christina Howlett ◽  
James K. McCloskey ◽  
Ruchi Jain
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Cancer Patients ◽  
Bleeding Episode ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Package Insert ◽  
Increased Risk ◽  
Clinically Significant ◽  
Risk For Bleeding

Abstract INTRODUCTION: Anticoagulant management of cancer-associated thrombosis is challenging since this patient population is concurrently at an increased risk for bleeding. The use of direct oral anticoagulants [(DOACs) dabigatran, rivaroxaban, apixaban] is not recommended for the treatment of venous thromboembolism (VTE) in cancer patients since there is limited data in this patient population. Despite limited evidence for use, DOACs are commonly prescribed due to ease of administration and lack of required laboratory monitoring. The objective of this study was to evaluate the practice and safety patterns of the DOACs when used for VTE treatment in the oncology population at Hackensack University Medical Center (HackensackUMC). METHODS: This study was a retrospective chart review of adult cancer patients treated at HackensackUMC who received dabigatran, rivaroxaban, or apixaban for the treatment of VTE. The protocol was reviewed and approved by the Institutional Review Board. Patients were identified through a computer generated report of the DOACs which included patients on all inpatient adult oncology floors at HackensackUMC from January 2013 to October 2015. Patients were included in this study if they were 18 years of age or older, admitted to an oncology floor, receiving a DOAC for VTE treatment for at least 48 hours, and had active cancer. Patients were excluded from this study if they were receiving hemodialysis or receiving a DOAC exclusively for the indication of atrial fibrillation. The primary outcomes of this study included the percentage of patients who were receiving a DOAC dosage consistent with that of the package insert and the percentage of patients who experienced clinically significant bleeding. The secondary outcomes of this study included the percentage of patients who had their DOAC held for thrombocytopenia and high risk procedures. Descriptive statistics were used to analyze study outcomes. RESULTS: Of the 126 patients screened, 39 patients were included. Thirty-five patients were on rivaroxaban and 4 patients were on apixaban (Table 1). Ten of 39 patients (26%) were not receiving a DOAC dosage consistent with that of the package insert. Of these 10 patients identified, the majority were receiving a lower DOAC dose than is recommended in the package insert. Our assumption is that these patients received a lower than recommended dose due to concerns for increased risk of bleeding. No patients experienced clinically significant bleeding. Four of 39 patients (10%) experienced a minor bleeding episode, all of which were gastrointestinal and/or genitourinary bleeds (Table 2). Four of 14 thrombocytopenic patients (29%) did not have their DOAC dose held for thrombocytopenia (none of which experienced a bleeding episode). All patients had their DOACs appropriately held for all procedures. CONCLUSION: Increased education and awareness on manufacturer recommended dosing of DOACs is warranted for oncology prescribers. Despite the increased risk for bleeding in cancer patients, no clinically significant bleeding events were identified in our patient cohort. To our knowledge, this is the first study to evaluate the use of DOACs for VTE treatment in patients with cancer at a high risk for bleeding. This data suggests that the use of DOACs may be safe to use for VTE treatment in the oncology population. This study may provide foundation for larger, randomized, controlled trials to determine whether DOACs should be used for VTE treatment in cancer patients. Disclosures Howlett: Eisai: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Sandoz: Honoraria; Teva: Speakers Bureau. McCloskey:Ariad: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau.

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