Safety and Efficacy of Protamine Administration for Prevention of Bleeding Complications in Patients Undergoing TAVR

Objective: To analyze safety and efficacy of single-dose ketorolac after primary palatoplasty (PP). Design: Consecutive cohort of patients undergoing PP, comparing to historical controls. Setting: A large academic children’s hospital. Patients, Participants: A consecutive cohort of 111 patients undergoing PP (study n = 47) compared to historical controls (n = 64). Interventions: All patients received intraoperative acetaminophen, dexmedetomidine, and opioids while the study group received an additional single dose of ketorolac (0.5 mg/kg) at the conclusion of PP. Main Outcome Measures: Safety of ketorolac was measured by significant bleeding complications and need for supplementary oxygen. Efficacy was assessed through bleeding, Face Legs Activity Cry Consolability (FLACC) scale, and opioid dose. Results: Length of stay was similar for both groups (control group 38.5 hours [95% CI: 3.6-43.3] versus study group 37.6 hours [95% CI: 31.3-44.0], P = .84). There were no significant differences in all postoperative FLACC scales. The mean dose of opioid rescue medication measured as morphine milligram equivalents did not differ between groups ( P = .56). Significant postoperative hemorrhage was not observed. Conclusions: This is the first prospective study to evaluate the safety and efficacy of single-dose ketorolac after PP. Although lack of standardization between study and historical control groups may have precluded observation of an analgesic benefit, analysis demonstrated a single dose of ketorolac after PP is safe. Further investigations with more patients and different postoperative regimens may clarify the role of ketorolac in improving pain after PP.

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Risk factors for bleeding in pediatric post-cardiotomy patients requiring ECLS

Perfusion ◽

10.1177/0267659109346667 ◽

2009 ◽

Vol 24 (3) ◽

pp. 191-197 ◽

Cited By ~ 3

Author(s):

Kathryn Nardell ◽

Gail M Annich ◽

Jennifer C Hirsch ◽

Cathe Fahrner ◽

Pat Brownlee ◽

...

Keyword(s):

Risk Factors ◽

Blood Loss ◽

Blood Product ◽

Life Support ◽

Extracorporeal Life Support ◽

Bleeding Complications ◽

Excessive Bleeding ◽

Surgical Exploration ◽

Platelet Counts ◽

Protamine Administration

Background/Objective: There is limited literature documenting bleeding patterns in pediatric post-cardiotomy patients on extracorporeal life support (ECLS). This retrospective review details bleeding complications and identifies risk factors for bleeding in these patients. Methods: Records from 145 patients were reviewed. Patients were divided into excessive (E) and non-excessive (NE) bleeding groups based on blood loss. Results: Excessive bleeding occurred predominantly from 0-6h. Longer CPB duration (NE=174±8min; E=212±16; p=0.02) and lower platelet counts (NE=104.8±50K; E=84.3±41K; p=0.01) were associated with excessive bleeding during the first 6h (p=0.005). Use of intraoperative protamine with normal platelets was associated with decreased bleeding from 7-12h post-ECLS (p=0.002). Most mediastinal exploration occurred >49h post-ECLS, with decreased bleeding post-exploration in E patients. Conclusions: The majority of pediatric post-cardiotomy ECLS bleeding occurs early after support initiation. Longer CPB time and thrombocytopenia increased bleeding 0-6h post-ECLS. Since early bleeding may be coagulopathic in origin, an approach to minimize bleeding includes protamine administration and aggressive blood product replacement with target platelet counts of 100-120K. Surgical exploration should follow if additional hemostasis is necessary.

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The Administration of Fondaparinux in Strongly Suspected Heparin-Induced Thrombocytopenia (HIT): Further Evidence of Its Safety and Efficacy, and Need for a Controlled Randomized Study.

Blood ◽

10.1182/blood.v114.22.1072.1072 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1072-1072

Author(s):

Franco Piovella ◽

Stefano Barco ◽

Marisa Barone ◽

Chiara Beltrametti ◽

Mara De Amici

Keyword(s):

Unfractionated Heparin ◽

Bleeding Complications ◽

Controlled Study ◽

Severe Bleeding ◽

Minor Bleeding ◽

Heparin Induced Thrombocytopenia ◽

Safety And Efficacy ◽

Coronary Syndrome ◽

Platelet Number ◽

The Mean

Abstract Abstract 1072 Poster Board I-94 Introduction: Heparin-induced thrombocytopenia (HIT), alone or associated with thrombosis (HITT), may develop during anticoagulant treatment with unfractionated heparin (UFH) or low-molecular weight heparin (LWMH). Fondaparinux is a selective inhibitor of coagulation factor Xa which apparently does not react with anti-PF4/heparin antibodies in in vitro testing. Methods: From january 2005 to december 2007 we treated 44 patients who had strong suspect of HIT (12 patients) or HITT (32 patients, of whom 12 had both DVT and PE). Of these, 30 patients were previously exposed to unfractionated heparin (UFH) for major cardiac surgery. The remaining patients were admitted to medical or general surgery wards. In the 32 patients who developed HITT, we applied therapeutic dosages of fondaparinux, i.e. 7.5 mg QD or lower, in accordance with their bleeding risk. The remaining patients were treated with prophylactic dosages of fondaparinux, i.e. 2.5 mg QD. Switch to warfarin was performed as soon as possible. The mean of our patients 4T's score was 6.2, corresponding to high risk patients; the mean of anticorpal optical density (GTI Enhanced®) was 1.4; the mean platelet number was 45 × 109/L. Results: All patients but four showed sustained normalization of the platelet number. All patients but four showed a significant reduction of their thromboembolic burden. No death related to severe bleeding was recorded. Two episodes of major bleeding were recorded in post-surgical patients (4,5%); 4 episodes of minor bleeding were recorded (9,1%). Four patients underwent dialysis during fondaparinux without bleeding complications. One patient developed acute coronary syndrome during treatment with fondaparinux. Nine patients did not survive (20,5%), with a key role of primitive diseases (i.e. sepsis) causing delay in the diagnostic process of HIT (four of them had a diagnosis of HIT with a mean delay of 7 days). In 16 patients submitted to therapeutic dosages of fondaparinux, anti-PF4/heparin antibody titers were followed over time showing a constant decrease: in one case antibody levels did not decrease up to 6 months after stopping both heparin and fondaparinux. Thirty patients were easily switched from fondaparinux to VKAs without problems in reaching the appropriate INR target. Conclusions: This report provides further evidence supporting the safety and efficacy of fondaparinux in the treatment of HIT and underlines the importance of an early diagnosis. However, it shows the need of a randomized controlled study between fondaparinux and a registered comparator drug. Disclosures: Piovella: GlaxoSmithKline: Honoraria, Speakers Bureau; Bayer: Honoraria, Speakers Bureau; Boehringer Ingelheim: Honoraria, Speakers Bureau. Off Label Use: fondaparinux in the treatment of heparin-induced thrombocytopenia.

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Safety and efficacy of retreating follicular non-Hodgkin’s lymphoma (NHL) with 90Y ibritumomab tiuxetan

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17528 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17528-17528 ◽

Cited By ~ 3

Author(s):

J. Shah ◽

D. Harrough ◽

W. Saville ◽

J. Mueh ◽

J. Lister ◽

...

Keyword(s):

Platelet Count ◽

Growth Factor ◽

External Beam Radiotherapy ◽

Bleeding Complications ◽

Hematologic Toxicity ◽

Ibritumomab Tiuxetan ◽

Safety And Efficacy ◽

Secondary Myelodysplastic Syndrome ◽

The Mean ◽

Mean Time

17528 Background: There is no data regarding safety and efficacy of treating follicular NHL patients with a second course of 90Y ibritumomab tiuxetan (Zevalin). Methods: Patients with follicular NHL who received 2 courses of Zevalin therapy were identified nationally, and data was retrospectively collected. Results: 10 patients (pts) (mean age 62.5 years, 48–91) were identified. Prior to the first Zevalin, all pts received chemotherapy (mean 2.4 courses, 1–5), 3/10 auto-PBSCT, and 4/10 external beam radiotherapy(ebRT). After the initial course of treatment, the mean time to nadir for the anemia was 7.9 weeks (wks)(4–13), neutropenia was 6.7 wks (4–10); and thrombocytopenia was 5.2 wks (4–8). 1 pt required growth factor support and transfusions; 2 had an incomplete recovery of platelet count at 23 and 30 wks (76,000 and 126,000/μl). Hematologic toxicity and grades are in the table below. Prior to the second course of Zevalin 2 pts received ebRT, 1 received 131I tositumomab, and 3 received chemotherapy (1–5 regimens). The median time to the second Zevalin course was 613 days (183–1,300). After the second course of Zevalin, the mean time to nadir for the anemia was 8.2 wks (2–25); neutropenia was 6.7 wks (4–10); and thrombocytopenia was 5.5 wks (4–7). 4/10 pts required growth factor support, 2 required transfusions, 3 had incomplete recovery of platelet count and early progression, 2 pts had a maximum recovery of their platelet count at 29 and 40 wks (143,000 and 144,000/μl). There were no infectious or bleeding complications with either course of Zevalin. No secondary myelodysplastic syndrome or acute leukemia were reported. Conclusions: Retreating patients with follicular NHL with a second course of Zevalin is tolerable with substantial evidence of clinical efficacy. This data warrants further evaluation of Zevalin retreatment in a clinical trial. [Table: see text] [Table: see text]

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Safety and Efficacy of Enoxaparin Compared With Unfractionated Heparin for Venous Thromboembolism Prophylaxis in Hemodialysis Patients

Hospital Pharmacy ◽

10.1177/0018578717724799 ◽

2017 ◽

Vol 52 (9) ◽

pp. 623-627 ◽

Cited By ~ 5

Author(s):

Melissa S. Green ◽

Katie B. Tellor ◽

Amanda R. Buckallew

Keyword(s):

Venous Thromboembolism ◽

Unfractionated Heparin ◽

Bleeding Complications ◽

Secondary Outcome ◽

Renal Elimination ◽

Minor Bleeding ◽

Safety And Efficacy ◽

Vte Prophylaxis ◽

Medically Ill ◽

Medically Ill Patients

Background: Enoxaparin, a low-molecular-weight heparin approved for prophylaxis in patients at risk for venous thromboembolism (VTE), offers several advantages compared with unfractionated heparin (UFH). Enoxaparin is primarily excreted through renal elimination and is currently not recommended in patients receiving hemodialysis (HD) due to potential increased bleeding complications. To date, there are limited safety and efficacy data supporting the use of enoxaparin in this patient population for VTE prophylaxis. Objective: The aim of this study was to compare the safety and efficacy of enoxaparin with UFH for deep venous thromboembolism (DVT) prophylaxis in medically ill HD patients. Methods and Results: This retrospective cohort study examined medically ill patients who received HD and were concomitantly prescribed enoxaparin or UFH for at least 2 consecutive days for VTE prophylaxis. A total of 225 patients (150 received UFH and 75 received enoxaparin) were evaluated in chronological order. The primary outcome was a composite of major, clinically relevant nonmajor, and minor bleeding based on International Society on Thrombosis and Haemostasis bleeding definitions. The secondary outcome was the occurrence of a confirmed thrombotic event. Baseline characteristics were similar between the cohorts. One patient in each cohort had a documented bleed (UFH = 0.7%, enoxaparin = 1.3%, P > .05) during the admission assessed; however, neither bleed was related to the prophylactic agent utilized. No patients developed a VTE during the index hospitalization. Conclusions: This study demonstrates that enoxaparin may be as safe and effective as UFH for VTE prophylaxis in medically ill patients receiving HD.

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Full-length sucrose-formulated recombinant factor VIII for treatment of previously untreated or minimally treated young children with severe haemophilia A

Thrombosis and Haemostasis ◽

10.1160/th03-10-0643 ◽

2005 ◽

Vol 93 (03) ◽

pp. 457-467 ◽

Cited By ~ 73

Author(s):

Joan Gill ◽

Chantal Rothschild ◽

Marilyn Manco-Johnson ◽

Jeanne Lusher ◽

Elke Kellermann ◽

...

Keyword(s):

Young Children ◽

Factor Viii ◽

Full Length ◽

Recombinant Factor Viii ◽

Bleeding Complications ◽

Adverse Event Rate ◽

Haemophilia A ◽

Severe Haemophilia ◽

Safety And Efficacy ◽

Mean Values

SummaryThe safety and efficacy of a full-length sucrose-formulated recombinant factor VIII product (rFVIII-FS; KogenateFS; Kogenate Bayer) was evaluated in previously untreated (PUPs) and minimally treated (MTP) patients with severe haemophilia A (FVIII < 2%). Patients (37 PUPs; 24 MTPs) aged 0.1–25.7 months were treated with rFVIII-FS for a cumulative of 9,141 exposure days (EDs), median 114 EDs (range 4–478), on prophylactic or on-demand therapy. Eighty-nine percent of all treated bleeding episodes were successfully treated with 1 (74%) or 2 (15%) infusions. Clinical response to first infusion for each bleeding episode was rated as ‘excellent’ in 58%, or ‘good’ in 33%, of all cases. Recombinant FVIII-FS was used in 27 surgical procedures, mainly catheter implantations, which were all conducted without bleeding complications. FVIII recovery mean values (~2%/kg/ IU) were as expected for any licensed FVIII concentrate. FVIII neutralizing antibody formation was 15% (9/60). Aside from inhibitor formation, three adverse events were rated as ‘at least possibly drug-related’ for a total drug-related adverse event rate of 0.14%. No viral seroconversions were observed. Overall, excellent safety and efficacy were demonstrated with rFVIII-FS for therapy of young children with severe haemophilia A.

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The safety and efficacy of use of low-molecular-weight heparin in pediatric neurosurgical patients

Journal of Neurosurgery Pediatrics ◽

10.3171/2015.1.peds14489 ◽

2015 ◽

Vol 16 (3) ◽

pp. 329-334 ◽

Cited By ~ 9

Author(s):

David D. Gonda ◽

Jared Fridley ◽

Sheila L. Ryan ◽

Valentina Briceño ◽

Sandi K. Lam ◽

...

Keyword(s):

Molecular Weight ◽

Subcutaneous Administration ◽

Pediatric Neurosurgery ◽

Antiplatelet Agents ◽

Bleeding Complications ◽

Low Molecular Weight ◽

Minor Bleeding ◽

Safety And Efficacy ◽

Neurosurgical Patients ◽

Venous Thromboembolic Events

OBJECT Low-molecular-weight heparins (LMWHs), mainly enoxaparin, offer several advantages over standard anticoagulation therapies such as unfractionated heparin and warfarin, including predictable pharmacokinetics, minimal monitoring, and subcutaneous administration. The purpose of this study was to determine the safety and efficacy of LMWHs in pediatric neurosurgical patients. METHODS A retrospective study was performed with patients 18 years old or younger who were admitted to the Pediatric Neurosurgery Service at Texas Children's Hospital and treated with LMWH for either therapeutic or prophylactic purposes between March 1, 2011, and December 30, 2013. Demographic and clinical features and outcomes were recorded. RESULTS LMWH was administered for treatment of venous thromboembolic events (VTEs) in 17 children and for prophylaxis in 24 children. Clinical resolution of VTEs occurred in 100% (17 of 17) of patients receiving therapeutic doses of LMWH. No patient receiving prophylactic doses of LMWH developed a new VTE. Major or minor bleeding complications occurred in 18% (3 of 17 children) and 4% (1 of 24 children) of those receiving therapeutic and prophylactic doses, respectively. All 4 patients who experienced hemorrhagic complications had other bleeding risk factors—i.e., coagulopathies and antiplatelet medications. CONCLUSIONS LMWH seems to be safe and efficacious for both management and prophylaxis of VTEs in pediatric neurosurgery. However, pediatric practitioners should be aware of higher risk for bleeding complications with increasing doses of LMWH, especially in patients with preexisting bleeding disorders or concurrent use of antiplatelet agents.

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Design and rationale of a randomized, double-blind, placebo-controlled, Phase 2/3 study to evaluate the safety and efficacy of dociparstat sodium (DSTAT) in adults with acute lung injury associated with severe COVID-19

10.21203/rs.3.rs-52289/v1 ◽

2020 ◽

Author(s):

Joseph A. Lasky ◽

Jyotsna Fuloria ◽

Marion E. Morrison ◽

Randall Lanier ◽

Odin Naderer ◽

...

Keyword(s):

Mechanical Ventilation ◽

Critical Care ◽

Standard Of Care ◽

Bleeding Complications ◽

Continuous Measure ◽

Phase 2 ◽

Double Blind ◽

Safety And Efficacy ◽

Double Blind Placebo ◽

Critical Care Units

Abstract Background: The COVID-19 Global Pandemic caused by the novel coronavirus, SARS-CoV-2, and the consequent morbidity and mortality attributable to progressive hypoxemia and subsequent respiratory failure, threaten to overrun hospital critical care units globally. New agents that can address the hyperinflammatory “cytokine storm” and hypercoagulable pathology seen in these patients may be a promising approach to treat patients, minimize hospital stays, and ensure hospital wards and critical care units are able to operate effectively. Dociparstat sodium (DSTAT) is a glycosaminoglycan derivative of heparin with robust anti-inflammatory properties, including the potential to address underlying causes of coagulation disorders with substantially reduced risk of bleeding complications compared to commercially available forms of heparin. Methods: This study is a randomized, double-blind, placebo-controlled, Phase 2/3 trial to determine the safety and efficacy of DSTAT added to standard of care versus placebo, in adults with COVID-19 who require hospitalization and supplemental oxygen therapy. The Phase 2 portion will enroll 12 participants in each of two dose escalating cohorts, to confirm the safety of DSTAT in this population. Following a data monitoring committee review of the data, an additional 50 participants will be enrolled. Contingent upon positive results, the Phase 3 portion of the study will enroll approximately 450 participants randomized 1:1 to DSTAT or placebo. The primary endpoint, agreed on by the US FDA, is the proportion of participants who survive and do not require mechanical ventilation through day 28. Discussion: Advances in standard of care regimens and the recent emergency use authorization of remdesivir and positive data with dexamethasone, has likely contributed to an increasing proportion of patients who are surviving without the need for mechanical ventilation. Therefore, examining the time to improvement of NIAID score will be essential to provide a more continuous measure of drug effect on recovery. Additional analysis of other endpoints, including supportive biomarkers (e.g., IL-6, HMGB1, soluble RAGE, D-dimer) will be performed at the conclusion of Phase 2 to further define the effect of DSTAT in patients hospitalized with COVID-19 infection. Trial Registration: ClinicalTrials.gov identifier NCT04389840, Registered 13 May 2020, https://clinicaltrials.gov/ct2/keydates/NCT04389840

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Retrospective 12-Year Study of the Safety and Efficacy of Transcatheter Arterial Embolization for Managing Bleeding Complications Following Hip Surgery

CardioVascular and Interventional Radiology ◽

10.1007/s00270-013-0772-2 ◽

2013 ◽

Vol 37 (6) ◽

pp. 1464-1468 ◽

Cited By ~ 2

Author(s):

Hongtao Cheng ◽

Ji Hoon Shin ◽

Hyun Ki Yoon ◽

Jooae Choe ◽

Gi Young Ko ◽

...

Keyword(s):

Transcatheter Arterial Embolization ◽

Arterial Embolization ◽

Hip Surgery ◽

Bleeding Complications ◽

Safety And Efficacy

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Prevalence of Contraindications to Entering a DVT Prophylaxis Trial in Medical Admissions.

Blood ◽

10.1182/blood.v106.11.2247.2247 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2247-2247

Author(s):

Robert G. Lerner ◽

Tushar M. Shah

Keyword(s):

Medical Center ◽

Academic Medical Center ◽

Tertiary Care ◽

Control Treatment ◽

Bleeding Complications ◽

General Medical Service ◽

Computer Assisted ◽

Safety And Efficacy ◽

Dvt Prophylaxis ◽

At Home

Abstract Studies have revealed that many patients developing deep vein thrombosis (DVT) during a hospitalization have not received any prior DVT prophylaxis despite a lack of medical contraindications. Many measures have been proposed to increase the use of DVT prophylaxis, including computer assisted reminders, standing admission orders, educational activities, etc. Another measure to increase the use of DVT prophylaxis has been to study special patient populations and extended duration of DVT prophylaxis. We present the prevalence of contraindications to the use of a low-molecular-weight-heparin (LMWH) prophylaxis regimen that we encountered in screening patients for admission to a clinical trial of DVT prophylaxis using LMWH with extended treatment at home after discharge. From November 2002 through July 2005 patients admitted to the general medical service of a major tertiary care academic medical center were screened for trial eligibility. Of 4388 patients screened only 19 (0.4%) were eligible for the trial. Of the 4369 patients excluded, 1072 (25%) were not confined to bed and were not felt to need DVT prophylaxis. Individuals under the age of 40 [1305 (30%)] were considered to be at low risk and thus not in need of DVT prophylaxis. An abnormal baseline laboratory value (either creatinine, platelet count or prothrombin time) precluded LMWH treatment in 687 patients (16%). There were 534 patients (12%) who already had an indication for full dose anticoagulation and were excluded. Active bleeding or a pre-existing bleeding disorder was present in 136 patients (3%). There were 276 patients (6%) with a history of recent surgery who were either considered high risk for bleeding complications or were already receiving DVT prophylaxis or treatment, and 109 patients (2.5%) who were judged by themselves or the medical staff to be unable to self-inject the LMWH at home. Individuals expected to die before completion of the trial [21 (0.5%)] were excluded. Miscellaneous exclusions such as demented or comatose patients unable to give consent, surgical or trauma patients admitted to a medical unit or need for an invasive procedure accounted for an additional 229 individuals (5%) of the total. Figure Figure These results do not reflect any lack of adherence to guidelines in the use of DVT prophylaxis at our institution, rather they indicate that the study design included criteria strict enough to restict eligibility to very few individuals. Strict eligibility criteria serve to limit a trial to those individuals most likely to show safety and efficacy of the study drug and avoid diluting the results with groups in which safety and efficacy might not be better than the control treatment. The limitation of that strategy is that the results may not be generalizable to a larger population. Labelling, marketing and treatment decisions based on this and other trials require a knowledge of the generalizability of the data. This in turn requires a knowledge of the inclusion and exclusion criteria and screening data. Based upon this experience we would recommend that screening data be made available when studies are eiither registered or published.

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