Activated Recombinant Factor VII (rFVIIa/NovoSeven®) in the Treatment of Bleeding Complications Following Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1135-1135 ◽  
Author(s):  
Benjamin Brenner ◽  
Markus Pihusch ◽  
Andrea Bacigalupo ◽  
Jeff Szer ◽  
Mario von Depka Prondzinski ◽  
...  
Keyword(s):  
Adverse Events ◽  
Initial Dose ◽  
Factor Vii ◽  
Bleeding Complications ◽  
Controlled Study ◽  
Severe Bleeding ◽  
Trial Period ◽  
Hematopoietic Stem ◽  
Coagulation Parameters ◽  
Transfusion Requirements

Abstract HSCT is a common treatment of hematological or oncological disorders. Many HSCT-associated complications, including prolonged aplasia, infection and graft-versus-host disease (GVHD) predispose to bleeding, resulting in increased morbidity and mortality. Platelet concentrates, fresh frozen plasma, antifibrinolytic agents or prothrombin complex concentrates are often ineffective. Although licensed for use in hemophilia pts with inhibitors, rFVIIa has been reported to be effective for the treatment of bleeding related to thrombocytopenia, thrombasthenia and other coagulation disorders. We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of rFVIIa in treatment of bleeding from days 2 to 180 after HSCT (F7BMT-1360 trial). Patients received rFVIIa (40, 80, 160 μg/kg) or placebo every 6h for 36h and were followed up for 96h after the initial dose. Exclusion criteria were recent thromboembolic events, atherosclerotic disease, DIC, thrombotic microangiopathy, venoocclusive disease and active AML (M3, M4, M5). The primary efficacy endpoint was the change in bleeding from 0h to 38h after initial dose. Secondary endpoints were transfusion requirements, change of coagulation parameters, and adverse events (AEs). One hundred patients (64 m; 36 f; 97 allogeneic; 3 autologous; 67 PBSC; 30 bone marrow; 2 cord blood; 1 unknown) with moderate or severe bleeding were included (38 lower GI; 26 hemorrhagic cystitis; 14 upper GI; 7 pulmonary; 1 intracerebral; 14 other). 80 μg/kg rFVIIa was effective, however no significant reduction in bleeding was seen at 160 μg/kg. There were no differences in transfusion requirements and changes in coagulation parameters across dose groups. Thirteen serious adverse events (SAEs) were reported within the trial period; there was no apparent drug or dose-related trend in the type or number of SAEs. One thromboembolic SAE (catheter thrombosis, 160 μg/kg) was observed within the trial period (2 days after last dosing) and two thromboembolic SAEs (cerebral infarction, 80 μg/kg; myocardial infarction, 40 μg/kg) were reported 4 and 14 days after last dosing. In this first controlled study on the use of rFVIIa after HSCT we found a significant effect of 80 μg/kg rFVII versus the standard hemostatic treatment. The diversity of the hemostatic disturbances and the heterogeneity of the patient population may have contributed to the lack of an increasing effect with increased dose. No safety issues were identified. Further trials with higher numbers of patients should focus upon optimizing the dose regimen of rFVIIa and on severe bleeding complications Bleeding status 38h after initial dose Treatment Gp N Stopped Decreased Unchanged/worse Cumulative odds ratio 97.1% CI p All data based on ITT. p<0.029 considered sig. Overall treatment effect: p=0.003. *Status unknown for 2 pts Placebo 22 5 (23%) 8 (36%) 9 (41%) 1.00 - - 40μg/kg 20 6 (30%) 4 (20%) 10 (50%) 0.94 [0.24; 3.64] 0.923 80μg/kg 26 14 (54%) 7 (27%) 5 (19%) 4.20 [1.05; 16.84] 0.021 160μg/kg 30 4 (13%) 9 (30%) 17 (57%) 0.54 [0.16; 1.83] 0.269 Total 98* 29 (30%) 28 (29%) 41 (42%) - - -

Thoracal Carcinoma Surgery in FVII Deficient Patient Managed with rFVIIa.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4073-4073
Author(s):  
Kerstin Erdlenbruch ◽  
Bernhard Stephan ◽  
Tamam Bakchoul ◽  
Joachim Schenk ◽  
Gerhard Pindur
Keyword(s):  
Adverse Events ◽  
Thoracic Surgery ◽  
Clinical Course ◽  
Bleeding Complications ◽  
Substitution Therapy ◽  
Regular Control ◽  
Transfusion Requirements ◽  
Safe Side ◽  
Thoracic Cancer ◽  
Fvii Deficiency

Abstract Introduction: In patients with congenital FVII deficiency and positive bleeding history surgical procedures should be covered by an sufficient substitution therapy of FVII concentrate. For the first three postoperative days trough level of at least >0,2U are recommended. We report haemostasis management of a complex thoracic surgery procedure in a 14 year old boy with FVII deficiency and diagnosis of a mucoepidermoid bronchogenic carcinoma of the left upper lobe. Extended thoracic surgery without extra corporal circulation was performed as a lobectomy of the left upper lobe including extended preparation of lymphnodes. Preoperative Lab: Platelets 285000/μl, INR 1,6, aPTT 28s, fibrinogen 239 mg/dl, FVII 0.33IU Because of positve bleeding anamnesis, the extended surgical procedure and possibility of further extension of the planned procedure we decide to cover surgery by factor treatment to be on the safe side though FVII activity was 0.33IU. Because of virus safety and safety profile we decide to give rFVIIa (NovoSevenR) as bolus injections. Frequency of treatment was chosen according to regular lab controls and clinical course. Haemostasis management during surgery: Preoperative rFVIIa dosage: 30 μg/kg BW, given immediately before skin cut as a bolus. Intraoperativly was no significant bleeding and no transfusion requirements though it was a complex and extended procedure. Haemostasis management postoperatively: Regular control of FVII activity and Hb was done every 6 hours to decide if substitution therapy is required. In the early phase after surgery FVII activity remained >1.0 IU, so additional factor treatment was not necessary. Hb remained stable in normal range. 24h after surgery FVII activity fell to 0.16IU. Substitution was done with dosage of 15μg/kgBW rFVIIa as a bolus (NovoSevenR). Frequency: once daily, duration: 2 days Clinical course: no bleeding complications. For remove of drainges a last bolus of 30μg/kg was given. Residual FVII activity: >0,2IU in all regular controls during the first three days. Figure 1: thromboplastin time, F VII activity and tFVIIa substitution in the course of time Figure 1:. thromboplastin time, F VII activity and tFVIIa substitution in the course of time Results: Bleeding/Transfusion requirements: No bleeding complications or wound healing complications occurred, no blood products has been transfused. Adverse events: no adverse events, no thrombembolic events and no inhibitor development. Conclusions: Regular control of FVII activity and clinical bleeding signs led to an efficient use of factor concentrates. rFVIIa given as bolus in FVII deficiency seem to be a save and efficient therapy for haemostasis management in complex thoracic cancer surgery.

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 ◽  
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.

A Randomized Placebo Controlled Phase II Trial of Prevention of Severe Oral Mucositis Using Single Dose Velafermin in Patients Receiving Myeloablative Therapy and Autologous Hematopoietic Stem Cell Transplant (AHSCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 615-615 ◽  
Author(s):  
Michael W. Schuster ◽  
J. Mehta ◽  
E.K. Waller ◽  
R.M. Rifkin ◽  
I. Micallef ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Oral Mucositis ◽  
Interim Analysis ◽  
Safety Information ◽  
Study Drug ◽  
Controlled Study ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Safety And Efficacy

Abstract Oral mucositis (OM) is a commonly occurring side effect in patients (pts) undergoing AHSCT. Velafermin, recombinant human fibroblast growth factor-20, is under investigation for the prevention of severe OM. Previous studies demonstrated that velafermin at 30 mcg/kg was well tolerated and was effective in reducing the incidence of severe mucositis. The primary objective of this multicenter, randomized, double-blind, placebo controlled study was to confirm safety and efficacy of 30 mcg/kg velafermin for prevention of severe OM incidence (grade 3/4 OM based on the WHO grading system). The secondary objective was to evaluate safety and efficacy of 10 and 60 mcg/kg doses to better define the therapeutic range. Pts were randomized to receive placebo or velafermin at 30, 10 or 60 mcg/kg in a 3:3:1:1 ratio 24–36 hrs after stem cell infusion. Randomization was stratified by study center and OM risk factors identified from the previous placebo controlled study in a similar population including conditioning regimen and body mass index (BMI ≥30). Pts with multiple myeloma or lymphoma (≥18 y.o.) receiving ≥2X106 /kg CD34+ cells following chemotherapy with or without Total Body Irradiation (TBI) were eligible. OM status and safety data were collected for 30 days post treatment while mortality and disease progression were followed for 1 yr. An interim analysis by a data monitoring committee (DMC) was planned to assess safety and efficacy after 50% of pts completed the 30 day treatment period. A total of 390 pts who received melphalan (200 mg/m2) (n=239), BEAM (n=129), TBI (n=15), or other (n=7) were randomized and 384 pts were treated. The study drug was well tolerated in general and no pts discontinued study due to drug-related adverse events. There were 93 serious adverse events (SAEs) in 78 (20%) pts and no drug-related death was reported. Five infusion-related SAEs were reported including vasovagal episode (2), syncope (2), and anaphylactoid reaction (1). All 5 episodes occurred on the day of study drug infusion and resolved on the same day with no sequelae. Based on review of the results from the interim analysis, which included safety and efficacy data from 200 pts, the DMC recommended that the study continue to completion as planned. The last pt has completed the 30 day study period. The un-blinded results of the OM efficacy endpoints from velafermin treated groups or placebo as well as 30-day safety information from all pts will be reported.

scholarly journals Randomized controlled study of ECP with methoxsalen as first-line treatment of patients with moderate to severe cGVHD

2019 ◽  
Vol 3 (14) ◽  
pp. 2218-2229 ◽  
Author(s):  
Madan Jagasia ◽  
Christof Scheid ◽  
Gérard Socié ◽  
Francis Ayuketang Ayuk ◽  
Johanna Tischer ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase 1 ◽  
Standard Of Care ◽  
Response Assessment ◽  
Controlled Study ◽  
First Line ◽  
Serious Adverse Events ◽  
Hematopoietic Stem ◽  
Intention To Treat ◽  
First Line Therapy

Abstract The investigation of extracorporeal photopheresis (ECP) plus standard of care (SoC) (SoC+ECP) in chronic graft-versus-host disease (cGVHD) within prospective, randomized clinical studies is limited, despite its frequent clinical use. This phase 1/pilot study was the first randomized, prospective study to investigate ECP use as first-line therapy in cGVHD, based on the 2015 National Institutes of Health (NIH) consensus criteria for diagnosis and response assessment. Adult patients with new-onset (≤3 years of hematopoietic stem cell transplantation) moderate or severe cGVHD were randomized 1:1 to 26 weeks of SoC+ECP vs SoC (corticosteroids and cyclosporine A/tacrolimus) between 2011 and 2015. The primary endpoint was overall response rate (ORR), defined as complete or partial response, at week 28 in the intention-to-treat population (ITT). Other outcomes included quality of life (QoL) measures and safety. Sixty patients were randomized; ITT included 53 patients (SoC+ECP: 29; SoC: 24). Week 28 ORR was 74.1% (SoC+ECP) and 60.9% (SoC). Investigator-assessed ORR was 56.0% (SoC+ECP) and 66.7% (SoC). Patients treated with SoC experienced a decline in QoL over the 28-week study period; QoL remained unchanged in SoC+ECP patients. Most frequent treatment-emergent adverse events (TEAEs) in SoC+ECP patients were hypertension (31.0%), cough (20.7%), dyspnea (17.2%), and fatigue (17.2%). Seventeen patients (SoC+ECP: 8; SoC: 9) experienced 35 serious adverse events (SAEs). No TEAEs or SAEs were considered related to the ECP instrument or methoxsalen. The encouraging short-term results of this study could inform the design of subsequent studies. This trial was registered at www.clinicaltrials.gov as #NCT01380535.

scholarly journals IVMP+IVIG raises platelet counts faster than IVIG alone: results of a randomized, blinded trial in childhood ITP

2020 ◽  
Vol 4 (7) ◽  
pp. 1492-1500
Author(s):  
Manuel Carcao ◽  
Mariana Silva ◽  
Michele David ◽  
Robert J. Klaassen ◽  
MacGregor Steele ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Adverse Events ◽  
Immune Thrombocytopenia ◽  
Controlled Study ◽  
Severe Bleeding ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Platelet Counts ◽  
Life Threatening ◽  
Blinded Trial

Abstract Children with immune thrombocytopenia (ITP) rarely suffer from life-threatening bleeds (eg, intracranial hemorrhage). In such settings, the combination of IV methylprednisolone (IVMP) with IV immune globulin (IVIG) is used to rapidly increase platelet counts (PCs). However, there are no controlled data to support using combination therapy over IVIG alone. We conducted a randomized, double-blind, placebo-controlled study to evaluate the rapidity of the PC increment and associated adverse events (AEs) between 2 regimens: A (IV placebo) and B (IVMP 30 mg/kg), both given over 1 hour, followed in both cases by IVIG (Gamunex 10%) 1 g/kg over 2-3 hours in children 1-17 years old with primary ITP and PCs <20 × 109/L in whom physicians had decided to treat with IVIG. Thirty-two children (ages: median, 8 years; range, 1.2-17.5 years) with a mean baseline PC of 9.2 × 109/L participated. Eighteen were randomized to regimen A and 14 to regimen B. By 8 hours after initiating therapy, 55% of all children had a PC ≥20 × 109/L (no group difference). By 24 hours, mean PCs were 76.9 × 109/L (B) vs 55 × 109/L (A) (P = .06; P = .035 when adjusted for intergroup differences in patient ages). No patient experienced severe bleeding/unexpected severe AEs. There were statistically fewer IVIG-related headaches in the group receiving combination therapy (P = .046). Our findings show a rapid response to IVIG with/without steroids and provide evidence to support the use of IVMP+IVIG in life-threatening situations. This trial was registered at www.clinicaltrials.gov as #NCT00376077.

Anticoagulation in addition to dual antiplatelet therapy has no impact on long-term follow-up after endovascular treatment of (sub)acute lower limb ischemia

VASA ◽  
2019 ◽  
Vol 48 (4) ◽  
pp. 321-329
Author(s):  
Mariya Kronlage ◽  
Erwin Blessing ◽  
Oliver J. Müller ◽  
Britta Heilmeier ◽  
Hugo A. Katus ◽  
...  
Keyword(s):  
Endovascular Treatment ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Limb Ischemia ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
Short Term ◽  
Long Term Follow Up

Summary. Background: To assess the impact of short- vs. long-term anticoagulation in addition to standard dual antiplatelet therapy (DAPT) upon endovascular treatment of (sub)acute thrombembolic occlusions of the lower extremity. Patient and methods: Retrospective analysis was conducted on 202 patients with a thrombembolic occlusion of lower extremities, followed by crirical limb ischemia that received endovascular treatment including thrombolysis, mechanical thrombectomy, or a combination of both between 2006 and 2015 at a single center. Following antithrombotic regimes were compared: 1) dual antiplatelet therapy, DAPT for 4 weeks (aspirin 100 mg/d and clopidogrel 75 mg/d) upon intervention, followed by a lifelong single antiplatelet therapy; 2) DAPT plus short term anticoagulation for 4 weeks, followed by a lifelong single antiplatelet therapy; 3) DAPT plus long term anticoagulation for > 4 weeks, followed by a lifelong anticoagulation. Results: Endovascular treatment was associated with high immediate revascularization (> 98 %), as well as overall and amputation-free survival rates (> 85 %), independent from the chosen anticoagulation regime in a two-year follow up, p > 0.05. Anticoagulation in addition to standard antiplatelet therapy had no significant effect on patency or freedom from target lesion revascularization (TLR) 24 months upon index procedure for both thrombotic and embolic occlusions. Severe bleeding complications occurred more often in the long-term anticoagulation group (9.3 % vs. 5.6 % (short-term group) and 6.5 % (DAPT group), p > 0.05). Conclusions: Our observational study demonstrates that the choice of an antithrombotic regime had no impact on the long-term follow-up after endovascular treatment of acute thrombembolic limb ischemia whereas prolonged anticoagulation was associated with a nominal increase in severe bleeding complications.

scholarly journals Restrictive transfusion strategy for critically injured patients (RESTRIC) trial: a study protocol for a cluster-randomised, crossover non-inferiority trial

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e037238
Author(s):  
Mineji Hayakawa ◽  
Takashi Tagami ◽  
Hiroaki IIjima ◽  
Daisuke Kudo ◽  
Kazuhiko Sekine ◽  
...  
Keyword(s):  
Emergency Department ◽  
Severe Bleeding ◽  
Transfusion Strategy ◽  
Ethical Guidelines ◽  
Restrictive Transfusion ◽  
Cluster Randomised ◽  
Transfusion Requirements ◽  
Injured Patients ◽  
Restrictive Transfusion Strategy ◽  
Rbc Transfusion

IntroductionResuscitation using blood products is critical during the acute postinjury period. However, the optimal target haemoglobin (Hb) levels have not been adequately investigated. With the restrictive transfusion strategy for critically injured patients (RESTRIC) trial, we aim to compare the restrictive and liberal red blood cell (RBC) transfusion strategies.Methods and analysisThis is a cluster-randomised, crossover, non-inferiority trial of patients with severe trauma at 22 hospitals that have been randomised in a 1:1 ratio based on the use of a restrictive or liberal transfusion strategy with target Hb levels of 70–90 or 100–120 g/L, respectively, during the first year. Subsequently, after 1-month washout period, another transfusion strategy will be applied for an additional year. RBC transfusion requirements are usually unclear on arrival at the emergency department. Therefore, patients with severe bleeding, which could lead to haemorrhagic shock, will be included in the trial based on the attending physician’s judgement. Each RBC transfusion strategy will be applied until 7 days postadmission to the hospital or discharge from the intensive care unit. The outcomes measured will include the 28-day survival rate after arrival at the emergency department (primary), the cumulative amount of blood transfused, event-free days and frequency of transfusion-associated lung injury and organ failure (secondary). Demonstration of the non-inferiority of restrictive transfusion will emphasise its clinical advantages.Ethics and disseminationThe trial will be performed according to the Japanese and International Ethical guidelines. It has been approved by the Ethics Committee of each participating hospital and The Japanese Association for the Surgery of Trauma (JAST). Written informed consent will be obtained from all patients or their representatives. The results of the trial will be disseminated to the participating hospitals and board-certified educational institutions of JAST, submitted to peer-reviewed journals for publication, and presented at congresses.Trial registration numberUMIN Clinical Trials Registry; UMIN000034405. Registered 8 October 2018.

scholarly journals Efficacy and safety associated with the infusion speed of intravenous immunoglobulin for the treatment of Kawasaki disease: a randomized controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Saori Fukui ◽  
Mitsuru Seki ◽  
Takaomi Minami ◽  
Kazuhiko Kotani ◽  
Kensuke Oka ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Adverse Events ◽  
Intravenous Immunoglobulin ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Link Type ◽  
Cell Counts ◽  
Infusion Speed ◽  
Ivig Administration

Abstract Background High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10–24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds. Methods This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration. Results A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p < 0.01). Conclusion The efficacy and safety of IVIG administered over 12 h (double speed) were similar to those administered over 24 h (reference speed). Trial registration University Hospital Medical Information Network (UMIN000014665). Registered 27 July 2014 – Prospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000017058

scholarly journals Phenotyping of CYP 4501A2 Activity by Total Overnight Salivary Caffeine Assessment (TOSCA) in Patients on Warfarin Treatment: A Cross-Sectional Study

2017 ◽  
Vol 24 (6) ◽  
pp. 928-935 ◽  
Author(s):  
Giovanni Tarantino ◽  
Domenico Capone ◽  
Paola Contaldi ◽  
Adriana Gianno ◽  
Mosca Teresa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Drug Concentration ◽  
Ethical Issues ◽  
Single Point ◽  
Warfarin Dose ◽  
Individual Variability ◽  
Bleeding Complications ◽  
Close Monitoring ◽  
Cross Sectional ◽  
Warfarin Sodium

Warfarin is an oral anticoagulant, commonly used for primary and secondary prevention of venous and arterial thromboembolic events. The drug is characterized by narrow therapeutic index, widespread individual variability in clinical response, and high rates of adverse events, particularly bleeding complications. For these reasons, a close monitoring of the dosage, using the frequent assessment of coagulation status by means of International Normalized Ratio value, is mandatory. Warfarin is metabolized by hepatic cytochrome P-450. High CYP 450 activity may lead to low drug concentration and requires high warfarin doses to reach efficacy; conversely, low CYP 450 activity is responsible for high drug concentration and needs for low doses to avoid potential toxicity risks. The major isoforms of CYP involved in the metabolism of warfarin sodium are CYP1A2 (for the R-warfarin) and CYP2C9 (for the S-warfarin). The probes for testing CYP1A2 are phenacetin and caffeine while for CYP2C9 tolbutamide. Although S-warfarin has major activity, it was decided to exclude its phenotyping for ethical issues, being mandatory to use a drug (tolbutamide). Instead, it was chosen to test the 1A2 isoform, as the activity of the latter isoform could be investigated by using caffeine contained in the caffeinated beverages. Specifically, a single-point concentration of salivary caffeine (total overnight salivary caffeine assessment [TOSCA]) after an overnight period of the caffeinated beverages abstinence was utilized. In the present study, 75 nonsmoker patients regularly receiving warfarin sodium were enrolled. The results have showed a significant association of the warfarin dose with TOSCA values (coefficient = –0.15, standard error = 0.04, 95% confidence interval = –0.24 to –0.06, t = –3.23, P = .002). In conclusion, the phenotyping of CYP1A2 by TOSCA could be useful, if further proven, to help manage patients on warfarin in order to lessen severe adverse events.

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