Heparin-induced thrombocytopenia (HIT)

2006 ◽  
Vol 95 (06) ◽  
pp. 967-981 ◽  
Author(s):  
Alex Gallus ◽  
Harry Magnani
Keyword(s):  
Platelet Count ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Case Reports ◽  
Cross Reactivity ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Fatal Adverse Events ◽  
Platelet Count Monitoring

SummaryClinical outcomes of 1,478 danaparoid treatment case reports for HIT (involving 1,418 patients) treated between 1982 and mid-2004 are analysed. Treatment in 1,291 episodes was for current HIT. Thromboembolism due to HIT was present in 39.4a%. The patients include 33 children and 32 pregnancies. Two hundred twenty-six patients required extra-corporeal circuit use for renal failure, 241 patients had a concomitant thrombophilic disorder, and 351 major operations were performed. Clinical outcomes were assessed during danaparoid treatment (range one day to 3.5 years) plus three months of follow-up. Of the danaparoid-treated patients 83.8a% survived; 63.7a% had no or minor adverse events and 20.1a% suffered serious non-fatal adverse events. New thromboses occurred during 9.7a% of treatment episodes, and 16.4a% of treatment episodes had an inadequate treatment response (i. e. developed one or more of the following: new/extended thrombosis, persistent/new platelet count reduction, unplanned amputation during treatment and follow-up). Major bleeding was reported in 8.1a% of treatment episodes. Clinical cross-reactivity of danaparoid (new/persistent platelet count reduction and/or new/extended thrombosis) was confirmed serologically in 23 of 36 patients with positive pretreatment serological danaparoid cross-reactivity and in 22 of 32 additional patients tested at the time of the new event, i. e. a total of 45 patients (3.2a%). Clinical outcomes of these case reports of patients given danaparoid because of suspected or confirmed HIT appear to be comparable with those reported by others who used direct thrombin inhibitors, especially when a sufficient danaparoid dosing intensity was used in patients with isolated HIT. Post-operative bleeding limits danaparoid use for cardiopulmonary by-pass surgery. Routine clinical and platelet count monitoring are required to minimise adverse reactions due to cross-reactivity.

scholarly journals Predictors of adverse prognosis in patients with infective endocarditis in a surgical referral center

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Scheggi ◽  
I Olivotto ◽  
N Ceschia ◽  
I Merilli ◽  
V Andrei ◽  
...  
Keyword(s):  
Renal Failure ◽  
Infective Endocarditis ◽  
Adverse Events ◽  
Ejection Fraction ◽  
Relapse Rate ◽  
Left Ventricular Ejection ◽  
All Cause Mortality ◽  
Fatal Adverse Events

Abstract Background Despite optimal medical and surgical treatment, mortality in infective endocarditis (IE) remains high. Aim of this study was to identify predictors of long term mortality for any cause, adverse event rate, relapse rate and valvular dysfunction at follow-up, in a high-volume surgical center. Methods We retrospectively analyzed 358 consecutive patients (127 women) admitted to our department with definite diagnosis of IE not device-related. IE occurred on native valves in 224 patients (63%); the infection involved the aortic valve in 192 (54%), mitral valve in 139 (39%) and tricuspid valve in 26 (7%). Overall 285 (80%) patients underwent surgery and 73 (20%) were treated conservatively, 38 due to absence of surgical indication and 35 due to refusal or prohibitive surgical risk. Long-term follow-up was obtained by structured telephone interviews. Primary endpoints were all-cause mortality, freedom from recurrent endocarditis, postoperative incidence of major adverse events (hospitalization for any cause, pace-maker implantation, new onset of atrial fibrillation, sternal dehiscence), worsening of left ventricular ejection fraction (LVEF) and valvular dysfunction. Results Mean age was 65 years (SD 15.2). Mean vegetation length was 8.9 mm (SD 7.6). Endocarditis was left-sided in 332 (93%). Average follow-up was 6 months. At univariable analysis, mortality was associated with female gender (p=0.031), age (p<0.001), higher EuroSCORE 2 (p<0.001), chronic renal failure (p<0.001), diabetes (p=0.002), brain embolism on presentation (p=0.05), double valve infection (p=0.008), low ejection fraction (p<0.001), paravalvular extension (p=0.031), prosthetic infection (p=0.018), exclusion from surgery if indicated (p<0.001), high procalcitonin levels (p=0.035); factors associated with a significantly lower mortality were streptococcal infection (p=0.04; OR 0.34) and early surgery (p=0.009, OR 0.55). At multivariable analysis independent predictors of all-cause mortality were lower EF, EuroSCORE2, procalcitonin levels and diabetes. Non-fatal adverse events were associated with renal failure (p 0.035, OR 2.8). Relapse rate was associated with S aureus infection (p=0.005, OR 3.8), right-sided endocarditis (p<0.001, OR 6.7) and drug abuse (p<0.001, OR 9.4). Conclusions The present study shows that low EF, EuroSCORE2, procalcitonin levels and diabetes are independent predictors of death in patients with IE. Non-fatal adverse events are more frequent in patients with renal failure. Relapse rate is higher in drug abusers. These informations may help personalize follow-up strategies after acute admission for IE. Funding Acknowledgement Type of funding source: None

scholarly journals Decreased Cytokine Plasma Levels and Changes in T-Cell Activation Are Associated With Hemodynamic Improvement and Clinical Outcomes After Percutaneous Mitral Commissurotomy in Patients With Rheumatic Mitral Stenosis

2021 ◽  
Vol 7 ◽  
Author(s):  
Vicente R. Silva ◽  
Eula G. A. Neves ◽  
Lívia S. Araújo Passos ◽  
Flávia Cristina de Melo ◽  
Andrea Teixeira-Carvalho ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
T Cell Activation ◽  
Plasma Levels ◽  
Mitral Stenosis ◽  
Cell Activation ◽  
Hemodynamic Improvement ◽  
Mitral Commissurotomy

Mitral stenosis (MS) is a consequence of rheumatic heart disease that leads to heart failure requiring mechanical intervention. Percutaneous mitral commissurotomy (PMC) is the treatment of choice for the intervention, and currently there are no soluble markers associated with hemodynamic improvement after PMC. This study aims to determine the changes in cytokine/chemokine plasma levels, as well as T cell activation after PMC, and to investigate their association with immediate hemodynamic improvement and clinical outcomes. Plasma samples from eighteen patients with well-defined MS who underwent PMC and 12 healthy controls were analyzed using BioPlex immunoassay. We observed that 16 out of the 27 (60%) molecules assessed were altered in patients' plasma pre-PMC as compared to control group. Of those, IL-1β, IL-12, IL-6, IL-4, PDGF, and CCL11 showed significant decrease after PMC. Stratifying the patients according to adverse outcome after a 28-month median follow up, we detected a significant reduction of IL-1β, IL-12, IL-6, IL-4, IFN-γ, CXCL-10, VEGF, FGF and PDGF post-PMC in patients without events, but not in those who presented adverse events during the follow-up. Patients with adverse outcomes had lower IL-10 pre-PMC, as compared to the ones without adverse events. In addition, the frequency of CD8+ activated memory cells was increased after PMC, while the frequency of CD4+ activated memory cells did not change. Our results show an association between the decrease of specific cytokines and changes in T cell activation with hemodynamic improvement post-PMC, as well as with long-term outcomes, suggesting their possible use as soluble markers for hemodynamic recovery after MS intervention.

scholarly journals SAT0525 EFFICACY AND SAFETY OF MZR FOR IgG4-RELATED DISEASE.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1219-1220
Author(s):  
S. Kawaai ◽  
S. Fukui ◽  
T. Nakai ◽  
G. Kidoguchi ◽  
H. Ozawa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Retention Rate ◽  
Case Reports ◽  
Efficacy And Safety ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Number Of Patients ◽  
Serum Igg4 ◽  
Over Time

Background:IgG4-Related Disease (IgG4RD) is known to cause multiple organ lesions with infiltration of IgG4-positive plasma cells, and patients often have relapses with tapering treatments despite an initial good response to glucocorticoids therapy. Mizoribine (MZR) is an immunosuppressant working as an inhibitor of purine synthesis, which mechanism of action is similar to mycophenolate mofetil. Data regarding the efficacy and safety of MZR on IgG4RD is limited although some previous case reports1showed effectiveness for IgG4RD.Objectives:This study aims to assess the efficacy and safety of MZR in patients with IgG4RD.Methods:We retrospectively reviewed charts of IgG4RD patients who used MZR between January 2004 and December 2019 at Immuno-Rheumatology Center in St. Luke’s International Hospital, Tokyo, Japan. We investigated basic demographics, involved organs, results of blood tests including IgG and IgG4 titer, and medications used including glucocorticoid and other immunosuppressants (IS). We followed IgG4 titer, dose of glucocorticoid, flare of disease and retention of MZR at the beginning, 6 and 12months after starting MZR. We compared changes in PSL (prednisolone) doses and IgG4 titers over time using Friedman test with Bonferroni correction. We also checked adverse events during follow up.Results:Twenty-two patients with IgG4RD who used MZR were included. Median age was 62 years old, and 15 (68.2%) patients are male. Lacrimal and salivary glands, pancreatitis and retroperitoneal fibrosis were common lesions. All patients were initially treated with glucocorticoids. Flare was observed in 5 (22.7 %) patients before initiation of MZR. The number of patients who continued MZR without flare are 19 (86.4 %) at 6 months, and 14 (73.7 %) at 12 months. IgG4 titer significantly declined at 6 and 12 months from baseline although significant consecutive decrease in PSL dose (Figure 1, 2). Liver dysfunctions are commonest adverse events (n=16, 72.7%) but mild (grade1; n=15, 68.2%) and most cases are apparently due to other reasons. Serious infection (SI) occurred in 3 (13.6%) patients in total follow up, however no SI were observed during 1 year after MZR treatment.Conclusion:MZR can be safely used in patients of IgG4RD with high retention rate, and seemed to have steroid-sparing effect. Prospective comparative studies are needed.References:[1]Nanke Y, Kobashigawa T, Yago T, Kamatani N, Kotake S. A case of Mikulicz’s disease, IgG4-related plasmacytic syndrome, successfully treated by corticosteroid and mizoribine, and then by mizoribine alone. Intern Med 49: 1449-1453, 2010.Table 1.Patient characteristics    Table 2.Disease and treatment status before and after initiation of MZR    Figure 1.Serum IgG4 level changesFigure 2.Changes in the PSL dose over timeDisclosure of Interests:None declared

Decreasing Adverse Drug Events Associated with Lepirudin and Argatroban for the Treatment of Heparin-Induced Thrombocytopenia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1787-1787 ◽  
Author(s):  
Molly McDaniel ◽  
Gerald A. Soff
Keyword(s):  
Case Reports ◽  
Significant Risk ◽  
Thrombin Inhibitors ◽  
Recommended Dose ◽  
Physician Education ◽  
Direct Thrombin Inhibitors ◽  
Poor Correlation ◽  
Close Monitoring ◽  
Heparin Induced Thrombocytopenia ◽  
The Mean

Abstract Purpose: Case reports, as well as our anecdotal experience, revealed frequently elevated activated partial thromboplastin time (aPTT) levels in some patients on the direct thrombin inhibitors (DTI) lepirudin and argatroban when dosed according to the FDA-approved guidelines in the Product Inserts. We analyzed our institution’s experience with these agents to determine if dosing guidelines need reconsideration. Methods: A retrospective chart review was conducted under the auspices of the pharmacy quality management team, with IRB approval. Cases were from the pharmacy database of all patients that received lepirudin or argatroban from September 2002 through March 2004. Sixty-six cases were identified and reviewed. Results: Patients were treated with the DTI for Heparin Induced Thrombocytopenia, with or without thrombosis (HIT, HITT), based on a decline of platelet count on heparin by 50% or to <100,000/uL (70%, n=46), and/or a positive HIPA ELISA (27%, n=18). 39 patients received lepirudin and 27 patients argatroban. The mean dose of the DTI which resulted in a therapeutic aPTT (55–80 sec) was calculated for each patient. The mean lepirudin dose resulting in therapeutic aPTT was 0.071 mg/kg/hr with 35 (90%) of patients requiring less than the recommended dose of 0.15mg/kg/hr. Only 4 (10%) patients had a mean dose at or above the recommended dose. 19 (49%) patients required 0.05 mg/kg/hr or lower. The mean argatroban dose resulting in therapeutic aPTT was 1.52 mcg/kg/min. 18 (67%) of patients required less than the recommended dose, 4 (15%) patients had a dose equal to the recommended, and only 5 (18%) had a mean dose above the recommended dose. aPTT levels were therapeutic or supratherapeutic a majority of the time in both groups, even though the dosing of the two DTI was overall lower than the recommended dosing. Furthermore, for many of the patients with both agents, there was a poor correlation between the dose of the DTI and the resulting aPTT, making it difficult to predict the resulting aPTT for a given dose adjustment of the DTI. Lastly, twenty occurrences of written prescription errors in five patients receiving argatroban were identified. These errors were due to the confusion between the dosing of argatroban as mcg/kg/min and not mg/kg/hr. The incorrect dose of argatroban was not dispensed to any patient. Conclusion: The DTI, Lepirudin and argatroban, used for HIT/HITT lack specific dosing titration guidelines, yet they require careful dosing and close monitoring for safe use. As with any acute anticoagulant, they carry a significant risk of life-threatening hemorrhage. Results of this study suggest that current dosing recommendations for both agents are too high, and that for safer use with lower risk of hemorrhage, the dosing guidelines need to be lowered. And while it is not likely that the prescribing errors for argatroban will be administered by pharmacy departments and nurses, the appropriateness of dosing the agent as mcg/kg/min as opposed to the more typical mg/kg/hr should be addressed, at least by greater physician education and possibly by altering the product insert. This study also supports that both lepirudin and argatroban should be considered high-alert medications requiring special attention by experienced clinicians.

Comparison of Clinical Outcomes in Patients with Heparin-Induced Thrombocytopenia Treated with Direct Thrombin Inhibitors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3942-3942 ◽  
Author(s):  
John L. Francis ◽  
Ranjeev Sandhu ◽  
Alane Drexler ◽  
John Dougherty
Keyword(s):  
Length Of Stay ◽  
Clinical Outcomes ◽  
Clinical Syndrome ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Efficacy And Safety ◽  
Platelet Factor ◽  
Platelet Recovery ◽  
Heparin Induced Thrombocytopenia ◽  
All Cause Mortality

Abstract Heparin-induced thrombocytopenia (HIT) is a clinical syndrome that has been reported to occur in 3–5% of patients treated with unfractionated heparin. If untreated, 36–50% of patients diagnosed with HIT develop life or limb-threatening thromboses. The occurrence of thrombosis, the most common serious complication of HIT, results in rates of amputation and death of 10–20% and 20–30% respectively. Thus, the desired clinical outcomes in patients with HIT are the prevention of thromboembolic complications, limb amputation, and death. The three direct thrombin inhibitors available in the U.S. are lepirudin, argatroban and bivalirudin. Lepirudin and argatroban have both been shown in clinical trials to significantly decrease the incidence of these complications in patients with HIT. Our institution also has experience with bivalirudin as treatment for HIT. We therefore sought to confirm whether all-cause mortality, length of stay, bleeding rate, time to platelet recovery, absolute change in platelet count following therapy, and percentage of therapeutic APTTs differed among patients treated with these agents at our institution. Data were collected by retrospective chart reviews, and from the Florida Hospital pharmacy computer system. Length of stay was calculated as the time to hospital discharge following the finding of a positive heparin-platelet factor 4 antibody test. For the purposes of comparison, the therapeutic range for APTT was taken as 50–90 seconds. As shown in the table, there were no statistically significant differences in any of the endpoints, when the efficacy and safety of the three direct thrombin inhibitors were compared. It therefore appears that within our institution, each of the direct thrombin inhibitors are equally efficacious and safe in treating the clinical syndrome of HIT, with similar outcomes with respect to length of stay, recovery of platelet counts, incidence of bleeding, and overall mortality. We conclude that selection of a direct thrombin inhibitor can be guided by the patient’s clinical status and organ function instead of efficacy and safety considerations. Drug n All-cause mortality (%) Length of stay (days) Bleeding (%) Time to platelet recovery (days) Therapeutic APTT (%) Lepirudin 7 28.5 11.0 28.5 5.3 70 Argatroban 20 30.0 15.1 20.0 5.2 65 Bivalirudin 24 25.0 18.7 25.0 5.4 74 P-value NS NS NS NS NS

scholarly journals Multiple Doses of Icatibant used during Pregnancy

2017 ◽  
Vol 8 (3) ◽  
pp. ar.2017.8.0210 ◽  
Author(s):  
Lauren W. Kaminsky ◽  
Theodore Kelbel ◽  
Fay Ansary ◽  
Timothy Craig
Keyword(s):  
Adverse Events ◽  
Literature Search ◽  
Medical Literature ◽  
Case Reports ◽  
Treatment Options ◽  
Multiple Treatment ◽  
Multiple Doses ◽  
Healthy Infants

Background Hereditary angioedema (HAE) is a life-long disease that often manifests by puberty. Treatment of attacks is essential to improve quality of life and to decrease morbidity and mortality. During pregnancy, treatment is limited because multiple treatment options, including icatibant, are not approved for use during pregnancy. Objective We report the outcomes of three pregnancies during which icatibant was used by a patient with HAE with normal C1-inhibitor for treatment of attacks. We also reviewed the literature for reports of icatibant use during pregnancy for outcomes and adverse events. Methods We report on a patient who treated herself with icatibant during three separate pregnancies. Postpartum follow-up verified the health of the mother and children. We also performed a complete literature search of medical literature data bases on icatibant use during pregnancy. Results The patient in our report administered multiple doses of icatibant during three pregnancies. The child born from the first pregnancy and the child from the third pregnancy were born at term and without congenital anomalies. The child from the second pregnancy was 1-month preterm. All three children were developmentally normal. The literature search identified two case reports and one abstract of limited icatibant use without adverse events during pregnancy in patients with HAE. These pregnancies resulted in the births of healthy infants. Conclusion From a search of the literature, three cases of icatibant use during pregnancy resulted in healthy infants. In addition, we report that from icatibant use in three separate pregnancies, one infant was born prematurely, but there were no birth defects. From follow-up, the children continued meeting developmental milestones. This report adds to the acquisition of knowledge for drug adverse events during postmarketing surveillance for icatibant use during pregnancy.

scholarly journals Bevacizumab Combined with Corticosteroids Does Not Improve the Clinical Outcome of Nasopharyngeal Carcinoma Patients With Radiation-Induced Brain Necrosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Honghong Li ◽  
Xiaoming Rong ◽  
Weihan Hu ◽  
Yuhua Yang ◽  
Ming Lei ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Nasopharyngeal Carcinoma ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
World Health ◽  
World Health Organization Quality ◽  
Brain Necrosis ◽  
Radiation Induced

ObjectiveOur aim was to compare the clinical outcomes of patients treated with bevacizumab combined with corticosteroids and those with bevacizumab monotherapy from a radiation-induced brain necrosis (RN) registry cohort (NCT03908502).MethodsWe utilized clinical data from a prospective RN registry cohort (NCT03908502) from July 2017 to June 2020. Patients were considered eligible if they had symptomatic RN after radiotherapy for nasopharyngeal carcinoma (NPC) and received bevacizumab (5 mg/kg, two to four cycles) with a minimum follow-up time of 3 months. The primary outcome was a 2-month response rate determined by MRI and clinical symptoms. Secondary outcomes included quality of life [evaluated by the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire] and cognitive function (evaluated by the Montreal Cognitive Assessment scale) at 2 months, RN recurrence during follow-up, and adverse events.ResultsA total of 123 patients (34 in the combined therapy group and 89 in the monotherapy group) were enrolled in our study with a median follow-up time of 0.97 year [interquartile range (IQR) = 0.35–2.60 years]. The clinical efficacy of RN did not differ significantly between patients in these two groups [odds ratio (OR) = 1.642, 95%CI = 0.584–4.614, p = 0.347]. Furthermore, bevacizumab combined with corticosteroids did not reduce recurrence compared with bevacizumab monotherapy [hazard ratio (HR) = 1.329, 95%CI = 0.849–2.079, p = 0.213]. The most common adverse events of bevacizumab were hypertension (17.89%), followed by nosebleed (8.13%) and fatigue (8.13%). There was no difference in grade 2 or more severe adverse events between the two groups (p = 0.811).InterpretationOur results showed that the treatment strategy of combining bevacizumab with corticosteroids did not lead to better clinical outcomes for RN patients with a background of radiotherapy for nasopharyngeal carcinoma.

scholarly journals 10-year clinical outcomes after radiofrequency catheter ablation for atrial fibrillation. A single center experience

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J.F Alderete Martinez ◽  
S Shizuta ◽  
F Yoneda ◽  
S Nishiwaki ◽  
M Tanaka ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Adverse Events ◽  
Confidence Interval ◽  
Clinical Outcomes ◽  
Radiofrequency Catheter Ablation ◽  
Rank Test ◽  
Log Rank Test

Abstract Background Radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) is becoming a routine procedure to treat patients with drug-refractory symptomatic AF. However, data regarding very long-term clinical outcomes is limited. The aim of the present study was to evaluate the 10-year clinical outcomes of patients who underwent RFCA for paroxysmal and persistent AF. Methods We retrospectively enrolled 503 consecutive patients (mean age 66,9±9,51 years; 71,6% male) who underwent RFCA for drug-refractory symptomatic AF between February 2004 and June 2011. Follow-up information was obtained using medical records and/or telephonic interviews with the patient, relatives and/or referring physicians. Results Among 503 patients enrolled in this study, 362 had paroxysmal atrial fibrillation (PAF) and 141 had persistent atrial fibrillation (PeAF) (72% and 28%, respectively). Mean follow-up was 8,84±3,05 years. The 10-year event-free rate for recurrent atrial tachyarrhythmia (AT) after the first procedure was 44,5% (49,4% for PAF vs 31,9% for PeAF; p=0,002 by log-rank test) and 81,9% after the last procedure (87,3% for PAF and 67,9% for PeAF; p≤0,001 by log-rank test). AT recurrence was observed most commonly during the first 12 months of the initial procedure (56%), with only 18% of them occurring after 60 months. Multivariate analysis revealed that persistent AF (hazard ratio=1,366; 95% confidence interval 1,058–1,76; p=0,017) and duration of AF &gt;5 years (hazard ratio=1,357; 95% confidence interval 1,064–1,732; p=0,005) were independent risk factors for AT recurrence. Regarding adverse events, there were 24 (4,8%) hospitalizations for acute decompensated heart failure, 20 (4%) ischemic strokes and 14 (2,8%) bleeding complications requiring hospital admissions. Patients taking oral anticoagulation and antiarrhythmic drugs at the end of the study accounted for 32,8% and 16,7% respectively. Conclusions RFCA for AF provided favorable results in terms of arrhythmia event-free survival in long-term follow-up with better results in patients with paroxysmal AF. Persistent AF and long-standing AF (beyond 5 years) were associated with AT recurrence. Despite the large number of patients who discontinued oral anticoagulation, thromboembolic adverse events were rare. FUNDunding Acknowledgement Type of funding sources: None.

Abstract 14733: Influence of High Risk Adrenergic Receptor Genotypes on Outcome in Infants With Single Ventricle

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ronand Ramroop ◽  
Dorin Manase ◽  
George Manase ◽  
Cory Simmons ◽  
Jane W Newburger ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Outcomes ◽  
Confidence Intervals ◽  
Adrenergic Receptor ◽  
Single Ventricle ◽  
Adverse Outcomes ◽  
Hospital Length Of Stay ◽  
Serious Adverse Events ◽  
Free Survival

Introduction: Variants in adrenergic receptor (ADR) genes are associated with adverse clinical outcomes in patients with heart failure. We evaluated the association of variants in ADR receptor genes with outcomes in infants with single ventricle lesions. Methods: Infants with single ventricle lesions participating in the Pediatric Heart Network Single Ventricle Reconstruction Trial (randomized to Norwood with modified Blalock-Taussig shunt versus right ventricle-pulmonary artery shunt) underwent genotyping for 4 single nucleotide polymorphisms (SNPs) in 3 ADR genes: ADRB1-A/G (rs1801252), ADRB1-C/G (rs1801253), ADRB2-C/G (rs1042714) and ADRA2A-C/T (rs553668). Linear and logistic regression, deviance tests, t-tests and F-tests were used to analyze association of genotype with clinical outcomes including hospital length of stay (LOS) at Norwood, occurrence of serious adverse events (SAE), and transplant-free survival during 14 months follow-up using a dominant model. Results: The study included 347 eligible patients (62% male; 83% white). The mean age at Norwood procedure was 6±3.6 days and median Norwood LOS was 8 days. During 14 months follow-up, 147 patients had SAEs, 94 patients died and 14 were transplanted. ADRB1 AA (rs1801252) genotype was associated with longer Norwood LOS. The difference in LOS between AA vs AG/GG was 7.99 days (confidence intervals, 0.27, 15.71; p=0.043). ADRA2A CC (rs553668) genotype was associated with higher odds of SAEs i.e. 103/216 (47.6%) in CC compared to 36/106 (34%) in CT/TT [Odds ratio 1.77 (confidence intervals, 1.09, 2.87), p=0.018]. Transplant-free survival was not different between genotype groups. Combined analysis of risk genotypes did not confer an additive risk of adverse outcomes. Conclusions: ADR genotypes known to cause adrenergic upregulation were associated with prolonged Norwood hospitalization and/or serious adverse events in infant single ventricles. This may be secondary to adverse effects of adrenergic overexpression on cardiac function and systemic hemodynamics. Analysis is ongoing to replicate these findings for utility as predictive markers for outcomes in infant single ventricles.

Bivalirudin in Patients with HIT or Clinically Suspected HIT.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 918-918 ◽  
Author(s):  
Luz M. Ramirez ◽  
Teresa L. Carman ◽  
Susan M. Begelman ◽  
Amjad AlMahameed ◽  
Douglas Joseph ◽  
...  
Keyword(s):  
Platelet Count ◽  
Renal Dysfunction ◽  
The United States ◽  
Heparin Therapy ◽  
Left Ventricular ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Suitable Alternative ◽  
Coronary Syndrome ◽  
History Of

Abstract Background: Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin and low molecular weight heparin therapy. All patients with HIT need treatment with a non-heparin anticoagulant. In the United States, two direct thrombin inhibitors are FDA-approved for patients with HIT: lepirudin and argatroban. Lepirudin is eliminated by the kidneys and is not ideal in patients with renal dysfunction. Argatroban is metabolized in the liver and should be used with caution in patients with hepatic insufficiency. Bivalirudin is approved for use in percutaneous coronary intervention and is under study for use in patients with HIT undergoing cardiopulmonary bypass. Bivalirudin has a short half-life (25 min) and is 20% metabolized via the kidneys and 80% by proteolytic cleavage. Methods: We are reporting our experience from a retrospective review of 42 patients with clinically suspected, laboratory-confirmed, or previously diagnosed HIT treated with bivalirudin. Results: Thirteen patients had a history of HIT; 9 were admitted for an interventional procedure or surgery. In 29 (69%) patients, HIT was suspected because of a fall in platelet count and/or thrombosis in the setting of current or recent heparin therapy. HIT was confirmed in 15/29 (51.7%) (Table). Bivalirudin was initiated by continuous intravenous infusion (range 0.03–0.2 mg/kg/h) and adjusted to an aPTT of 1.5–2.5 times patient baseline. The mean infusion rate was 0.1 mg/kg/h. The average duration of therapy was 7.8 (range 1–24) days. 7/42 (16.7%) of patients had overt bleeding and received ≥ 2 units of packed red blood cells during their hospitalization. There were three new thrombotic events: ischemic stroke (subtherapeutic aPTT), cephalic vein thrombosis, and left ventricular thrombus. There were no amputations and 5 patients died: 2 withdrawal of care, 1 MSOF, 1 respiratory failure, 1 disseminated intravascular coagulation. Conclusions: Our experience indicates that bivalirudin is a suitable alternative anticoagulant for patients with HIT or suspected HIT. The bleeding and thrombotic complications were deemed acceptable in our largely critically ill and postoperative patients. Class of patients No. of pts Indication for initial use of anticoagulation Mean platelet count (K/μL) at the time of bivalirudin initiation (Range) Renal dysfunction (RD) OR Liver dysfunction (LD) OR Both (RD&LD) ICU stay OR Required mechanical ventilation (MV) Multi-system organ failure (MSOF) OR Sepsis VTE = Venous Thromboembolism, Mech Valve = Mechanical Valve, ACS = Acute Coronary Syndrome, Afib = Atrial Fibrillation History of HIT 13 VTE 3, Intervention or Surgery 9, Other 1 172 (30–374) RD 23.1%, LD 0%, RD&LD 0% ICU 61.5%, MV 0% MSOF 7.7% Sepsis 0% Clinically suspected HIT 14 VTE 8, Mech Valve 1, ACS 4, Other 1 57.9 (7–115) RD 21.4%, LD 7.1%, RD&LD 7.1% ICU 85.7%, MV 42.9% MSOF 14.3% Sepsis 28.6% Confirmed HIT 15 VTE 3, Afib 2, ACS 4, Other 6 44.6 (10–107) RD 26.7%, LD 6.7%, RD&LD 13.3% ICU 86.7%, MV 53.3% MSOF 20% Sepsis 20%

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