Faculty Opinions recommendation of Perioperative treatment of hemophilia A patients: blood group O patients are at risk of bleeding complications.

Author(s):  
Ravindra Sarode
2016 ◽  
Vol 14 (3) ◽  
pp. 468-478 ◽  
Author(s):  
H. C. A. M. Hazendonk ◽  
J. Lock ◽  
R. A. A. Mathôt ◽  
K. Meijer ◽  
M. Peters ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 962-962
Author(s):  
Jean-Louis H. Kerkhoffs ◽  
Rinie J. van Wordragen-Vlaswinkel ◽  
Jeroen C.J. Eikenboom ◽  
Anneke Brand

Abstract Introduction: Central venous catheters are frequently used in hematooncological patients for the administration of chemotherapy, antibiotics and parenteral feeding. Despite low platelet counts, observed in this category of patients, catheter related thrombosis (VTE), with the need for anticoagulant therapy, still occurs in 9.7% of the patients. Treatment of this complication in our institute consists of the removal of the catheter and anti-coagulant therapy, consisting of conventional heparin or low molecular weight heparin. Although solely based on expert opinion, the generally accepted platelet transfusion threshold of 10 x 109/l is raised to 20 – 40 x 109/l. In our institute a trigger of 30 x 109/l is used. We investigated whether this trigger policy is effective in the prevention of bleeding complications. Methods: We performed a case-control study to study bleeding complications and threshold policy. From 1 February 2000 to 1 May 2005 we reviewed medical records of patients, admitted at the hematology department of the Leiden University Medical Center. A total of 22 patients were identified having thrombosis confirmed by ultrasound or phlebography. The database of a recently performed clinical trial in our institution was used to select a control group. Thirty-one controls were selected, matched for age, gender, diagnosis and treatment. For each patient, we calculated the days at risk of bleeding, i.e. days of thrombocytopenia with or without anti-coagulant therapy and recorded bleeding complications, platelet and red cell transfusions from the medical charts. Statistical analysis was performed using SPSS. Results: There were no significant differences between patients with or without VTE in regard to age, gender, diagnosis and treatment. The number of days at risk of bleeding for patients without VTE was 511 days and for VTE group 239 days. The table shows the number of bleeding complications, the mean platelet count, the mean platelet transfusion threshold and the number of platelet and red cell transfusions. Both univariate as multivariate analysis (including age, gender, diagnosis, treatment and VTE-status) showed a significant effect of the existence of VTE on the occurrence of bleeding complications. The Odds’ ratio of bleeding in the VTE group compared to the non-VTE group was 2.9 (CI 95: 1.7 – 5.0; p = 0.0002). More then 95% of the bleeding complications consisted of WHO grades I and II. No lethal bleeding was observed. Discussion: Patients experiencing (catheter-related) venous thrombosis treated with anticoagulant therapy during a period of thrombocytopenia showed an increased risk of bleeding complications, despite a higher platelet transfusion threshold. Whether steering between Scylla and Charibdis can be facilitated by raising the platelet transfusion threshold remains to established. Study outcome No VTE VTE p value n = number Days at risk 511 239 n bleeding complications per day at risk 0.05 0.13 0.0002 mean platelet count (10E9/l) +/− SD 28 +/− 16 38 +/− 17 < 0.0001 mean platelet transfusion threshold (10E9/l) +/− SD 12 +/− 9 28 +/− 12 < 0.0001 n platelet transfusions per day at risk 0.35 0.49 0.0003 n red cell transfusions per day at risk 0.34 0.41 0.073


2020 ◽  
Vol 120 (10) ◽  
pp. 1395-1406 ◽  
Author(s):  
Iris Garcia-Martínez ◽  
Nina Borràs ◽  
Marta Martorell ◽  
Rafael Parra ◽  
Carme Altisent ◽  
...  

AbstractThe pharmacokinetic (PK) response of severe hemophilia A (HA) patients to infused factor VIII (FVIII) shows substantial variability. Several environmental and genetic factors are associated with changes in FVIII plasma levels and infused FVIII PK. Based on the hypothesis that factors influencing endogenous FVIII can affect FVIII PK, the contribution of single-nucleotide variants (SNVs) in candidate genes was investigated in 51 severe HA patients. The effects of blood group, F8 variant type, von Willebrand factor antigen and activity levels, age, and weight were also explored. The myPKFiT device was used to estimate individual PK parameters, and SNVs and clinically reportable F8 variants were simultaneously analyzed in an Illumina MiSeq instrument, using the microfluidics-based Fluidigm Access Array system. The contribution of SNVs to FVIII half-life and clearance was addressed by robust regression modeling, taking into account other modulators. In line with previous studies, we provide robust evidence that age, body weight, and blood group, as well as SNVs in ABO and CLEC4M, participate in the variability of FVIII PK in HA patients. Main results: each copy of the rs7853989 (ABO) allele increases FVIII half-life by 1.4 hours (p = 0.0131) and decreases clearance by 0.5 mL/h/kg (p = 5.57E-03), whereas each additional rs868875 (CLEC4M) allele reduces FVIII half-life by 1.1 hours (p = 2.90E-05) and increases clearance by 0.3 mL/h/kg (p = 1.01E-03). These results contribute to advancing efforts to improve FVIII replacement therapies by adjusting to each patient's PK profile based on pharmacogenomic data. This personalized medicine will decrease the burden of treatment and maximize the benefits obtained.


TH Open ◽  
2021 ◽  
Vol 05 (01) ◽  
pp. e84-e88
Author(s):  
Krishnan Shyamkumar ◽  
Jack Hirsh ◽  
Vinai C. Bhagirath ◽  
Jeffrey S. Ginsberg ◽  
John W. Eikelboom ◽  
...  

Abstract Introduction Dose adjustment based on laboratory monitoring is not routinely recommended for patients treated with rivaroxaban but because an association has been reported between high drug level and bleeding, it would be of interest to know if measuring drug level once could identify patients at risk of bleeding who might benefit from a dose reduction. Objective This study was aimed to investigate the reliability of a single measurement of rivaroxaban level to identify clinic patients with persistently high levels, defined as levels that remained in the upper quintile of drug-level distribution. Methods In this prospective cohort study of 100 patients with atrial fibrillation or venous thromboembolism, peak and trough rivaroxaban levels were measured using the STA-Liquid Anti-Xa assay at baseline and after 2 months. Values of 395.8 and 60.2 ng/mL corresponded to the 80th percentile for peak and trough levels, respectively, and levels above these cut-offs were categorized as high for our analyses. Results Among patients with a peak or trough level in the upper quintile at baseline, only 26.7% (95% confidence interval [CI]: 10.9–52.0%), and 13.3% (95% CI: 2.4–37.9%), respectively, remained above these thresholds. Conclusion Our findings do not support the use of a single rivaroxaban level measurement to identify patients who would benefit from a dose reduction because such an approach is unable to reliably identify patients with high levels.


BJA Education ◽  
2021 ◽  
Vol 21 (3) ◽  
pp. 84-94
Author(s):  
T. Ashken ◽  
S. West

2021 ◽  
pp. emermed-2020-210622
Author(s):  
Laura Goodwin ◽  
Helen Nicholson ◽  
Maria Robinson ◽  
Adam Bedson ◽  
Sarah Black ◽  
...  

BackgroundTranexamic acid (TXA) is an antifibrinolytic drug used to prevent bleeding. It was introduced as an intervention for post-traumatic haemorrhage across emergency medical services (EMS) in the UK during 2012. However, despite strong evidence of effectiveness, prehospital TXA administration rates are low. This study used the theoretical domains framework (TDF) to identify barriers and facilitators to the administration of TXA to trauma patients by EMS providers (paramedics) in the UK.MethodsInterviews were completed with 18 UK paramedics from a single EMS provider organisation. A convenience sampling approach was used, and interviews continued until thematic saturation was reached. Semistructured telephone interviews explored paramedics’ experiences of administering TXA to trauma patients, including identifying whether or not patients were at risk of bleeding. Data were analysed inductively using thematic analysis (stage 1). Themes were mapped to the theoretical domains of the TDF to identify behavioural theory-derived barriers and facilitators to the administration of TXA to trauma patients (stage 2). Belief statements were identified and assessed for importance according to prevalence, discordance and evidence base (stage 3).ResultsBarriers and facilitators to paramedics’ administration of TXA to trauma patients were represented by 11 of the 14 domains of the TDF. Important barriers included a lack of knowledge and experience with TXA (Domain: Knowledge and Skills), confusion and restrictions relating to the guidelines for TXA administration (Domain: Social/professional role and identity), a lack of resources (Domain: Environmental context and resources) and difficulty in identifying patients at risk of bleeding (Domain: Memory, attention and decision processes).ConclusionsThis study presents a behavioural theory-based approach to identifying barriers and facilitators to the prehospital administration of TXA to trauma patients in the UK. It identifies multiple influencing factors that may serve as a basis for developing an intervention to increase prehospital administration of TXA.


Blood ◽  
2019 ◽  
Vol 134 (11) ◽  
pp. 880-891 ◽  
Author(s):  
Laura L. Swystun ◽  
Kenichi Ogiwara ◽  
Orla Rawley ◽  
Christine Brown ◽  
Ilinca Georgescu ◽  
...  

Abstract Factor VIII (FVIII) pharmacokinetic (PK) properties show high interpatient variability in hemophilia A patients. Although previous studies have determined that age, body mass index, von Willebrand factor antigen (VWF:Ag) levels, and ABO blood group status can influence FVIII PK, they do not account for all observed variability. In this study, we aim to describe the genetic determinants that modify the FVIII PK profile in a population of 43 pediatric hemophilia A patients. We observed that VWF:Ag and VWF propeptide (VWFpp)/VWF:Ag, but not VWFpp, were associated with FVIII half-life. VWFpp/VWF:Ag negatively correlated with FVIII half-life in patients with non-O blood type, but no correlation was observed for type O patients, suggesting that von Willebrand factor (VWF) half-life, as modified by the ABO blood group, is a strong regulator of FVIII PK. The FVIII-binding activity of VWF positively correlated with FVIII half-life, and the rare or low-frequency nonsynonymous VWF variants p.(Arg826Lys) and p.(Arg852Glu) were identified in patients with reduced VWF:FVIIIB but not VWF:Ag. Common variants at the VWF, CLEC4M, and STAB2 loci, which have been previously associated with plasma levels of VWF and FVIII, were associated with the FVIII PK profile. Together, these studies characterize the mechanistic basis by which VWF clearance and ABO glycosylation modify FVIII PK in a pediatric population. Moreover, this study is the first to identify non-VWF and non-ABO variants that modify FVIII PK in pediatric hemophilia A patients.


1979 ◽  
Author(s):  
J.J.F. Belch ◽  
G.D.O. Lowe ◽  
J.G. Pollock ◽  
C.D. Forbes ◽  
C.R.M. Prentice

In a randomised double-blind controlled trial 24 patients undergoing elective aortic bifurcation graft surgery received subcutaneous calcium heparin (2, 500 u preoperatively then 5,000 u 12 hourly or 7 days) and 25 control patients received saline injections. All patients received the routine dose of intravenous sodium heparin intraoperatively. The trial was terminated because of excess bleeding complications in patients on subcutaneous heparin (8 vs. 1, p<0.05). Deep venous thrombosis was diagnosed by 125I-fibrinogen scanning in 8 control patients and 3 patients on heparin (p>0.05). In this group of patients the risk of bleeding due to subcutaneous heparin appeared to outweigh the benefit of thrombotic prophylaxis.


2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
L. Testa ◽  
G. G. L. Biondi Zoccai ◽  
M. Valgimigli ◽  
R. A. Latini ◽  
S. Pizzocri ◽  
...  

Thienopyridines are a class of drug targeting the platelet adenosine diphosphate (ADP) 2 receptor. They significantly reduce platelet activity and are therefore clinically beneficial in settings where platelet activation is a key pathophysiological feature, particularly myocardial infarction. Ticlopidine, the first of the class introduced to clinical practice, was soon challenged and almost completely replaced by clopidogrel for its better tolerability. More recently, prasugrel and ticagrelor have been shown to provide a more powerful antiplatelet action compared to clopidogrel but at a cost of higher risk of bleeding complications. Cangrelor, a molecule very similar to ticagrelor, is currently being evaluated against clopidogrel. Considering the key balance of ischemic protection and bleeding risk, this paper discusses the background to the development of prasugrel, ticagrelor, and cangrelor and aims to characterise their risk-benefit profile and possible implementation in daily practice.


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