Assessment of Chromolena odorata potential ability of hemostasis in patients with and without Haemophilia A Inhibitors

Haemophilia is a chronic bleeding illness that causes several difficulties in the patient's daily life in various aspects. Inhibitor development is presently the most important treatment complication observed in patients with hemophilia. Treatment modalities of Haemophilia A with either plasma or recombinant FVIII regimes results in the development of inhibitors and the risk of complications in patients. Hence, newer treatment strategies involving innovative hemostatic therapy are warranted for better management of hemophilia patients. The aim and objective of this study was to assess the efficacy of Chromolena odorata mediated hemostasis in patients with hemophilia A inhibitors. It was a cohort study constituting 147 clinically diagnosed hemophilic A patients. All the patients underwent treatment with FVIII A regimes (specific or multiple). The severity of hemophilia and clotting time was assessed by standard FVIII and aPTT assays, respectively. Modified Bethesda assay method was used to detect FVIII inhibitors. The hemostatic capacity of Chromolena odorata was evaluated by pooling the patient’s plasma with Chromolena extract concentrate. Younger age group (15-30) were more prevalent (56.4%) among hemophilia pathogenesis. Hemarthrosis was the significant co-morbidity observed in 58.5% of patients. Majority of the patients (72.7%) were diagnosed with severe hemophilia A. We identified 10 clinically evident patients to possess inhibitors for FVIII. Evaluation of Chromolena odorata hemostatic potential showed the improvement of clotting capacity with optimal concentrations of extract in patients with inhibitors. The findings of the study revealed the hemostatic properties of Chromolena odorata that can be recommended in the treatment strategies of Haemophilia patients.

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Differences in presentation and management patterns in patients with hepatocellular carcinoma (HCC): Data from HCC registry in Asia.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.229 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 229-229

Author(s):

Pierce K. H. Chow ◽

Lequn Li ◽

Jiangtao Li ◽

Fan Jia ◽

Hee-Jee Wang ◽

...

Keyword(s):

South Korea ◽

Treatment Strategies ◽

Cancer Staging ◽

Treatment Modalities ◽

First Line ◽

Real World Data ◽

First Line Therapy ◽

Target Sample Size ◽

Common Cancer ◽

Younger Age

229 Background: HCC is the 6th most common cancer worldwide with > 70% of cases in Asia. There is limited real-world data on the diagnosis, treatment modalities, outcomes and treatment costs in HCC. Methods: The HCC Registry in Asia (AHCC08) is a multi-country longitudinal cohort study of HCC patients diagnosed between 2013 and 2019. Target sample size is 2500 from 9 geographies: China, Singapore, South Korea, Japan, Taiwan, Australia, New Zealand, Hong Kong, and Thailand. We present initial data on diagnosis, etiology, stage at presentation, and treatment modalities of HCC from China [CN] (5 centers), Singapore [SG] (3 centers), South Korea [SK] (4 centers), and Japan [JP] (2 centers). Results: 657 patients (436 CN; 102 SG; 85 SK; 34 JP) were evaluated in August 2018. Patients from China were diagnosed at a younger age, while patients from Japan were diagnosed at an older age (mean age 51 years CN; 67 years SG; 58 years SK; 68 years JP). The highest proportion of regular alcohol drinkers were from Japan (16% CN; 21% SG; 24% SK; 50% JP) and occasional drinkers from China (20% CN; 17% SG; 12% SK; 15% JP). 77% had Hepatitis B across the 5 geographies, with the highest incidence in China (93%), followed by South Korea (68%). 27% were diagnosed using AASLD/APASL imaging criteria, with the highest utilization in Singapore (66% AASLD; 80% APASL) and South Korea (64% AASLD; 20% APASL). Later-stage patients (according to Barcelona Clinic Liver Cancer staging guidelines) were more predominant in Japan (Stage C: 28% CN, 16% SG, 8% SK, 41% JP; Stage D: 0.5% CN, 0% SG, 1% SK, 3% JP). Relatively few radiofrequency ablations were carried out as the first-line therapy across the 5 geographies (2% CN; 5% SG; 2% SK; 0% JP). In China, liver resection was preferred in first-line HCC treatment (65% CN vs 28% SG, SK, and JP aggregated), followed by loco-regional (27% CN vs 7% SG, SK, and JP aggregated) and systemic therapy (2% CN vs 10% SG, SK, and JP aggregated). Conclusions: There is considerable variation in presentation and management patterns between the 5 geographies. These data will benefit policymakers, companies and clinicians in improving policies and developing treatment strategies for HCC. (ClinicalTrials.gov: NCT03233360).

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Helixate®Nexgen in the Treatment of Patients with Hemophilia A: A Long-Term Pharmacovigilance Surveillance.

Blood ◽

10.1182/blood.v106.11.4091.4091 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4091-4091

Author(s):

Sabine Haertel ◽

Claudia Zacharias ◽

Hans-Herrmann Brackmann ◽

Zimmermann Roland ◽

Lenk Harald

Keyword(s):

Large Scale ◽

Hemophilia A ◽

Chinese Hamster ◽

Treatment Modalities ◽

Good Tolerability ◽

Safety Parameters ◽

Recombinant Fviii ◽

Set Up ◽

Observation Period

Abstract Comprehensive large-scale pharmacovigilance surveillances are very effective tools to collect data on products in the post authorization period. The evaluation presented here was set up to assess the long-term efficacy, safety and tolerability of the recombinant FVIII concentrate, Helixate®NexGen (in the US: Helixate®FS). Sixty-five hemophilia centers in Germany, Austria, Italy, France, and Sweden are participating in this ongoing international project. Previously untreated (PUP) and previously treated patients (PTP) at any age suffering from hemophilia A treated with Helixate®NexGen were eligible for the surveillance. Based on the standard schedule preferred at the centers, patients are routinely screened every 3 to 12 months. At these visits, the following parameters, as used routinely for these patients, were documented (non-interventional design): overall clinical response, pharmacokinetics, occurrence of bleedings, adverse drug reactions including the incidence of inhibitors, other laboratory safety parameters, coagulation parameters, relevant concomitant diseases, and medication. To determine the level of exposure, treatment modalities with Helixate®NexGen, including average factor consumption per month and exposure days are recorded. One hundred and ten patients have been included into the investigation up to now; data from 104 patients were available for this interim analysis including 2 PUPs. The median age was 25 years (range: 8 months – 68 years). One patient suffered from mild, eleven from moderate, and 89 from severe hemophilia A; in three patients the information on severity was missing. Most of the patients were treated prophylactically (92%, at least one infusion per week). Exposure to Helixate®NexGen during the pharmacovigilance ranged between 5 and 703 days. A total of 112 bleedings were documented during the observation period, with a range of 0 to 20 bleedings per patient per year. Efficacy of Helixate®NexGen was assessed as good or excellent in 97% of all cases. There were no cases of inhibitor development during the 2-year observation period, especially no cases of inhibitors when patients were switched from products produced in Chinese hamster ovary (CHO) cells to Helixate®NexGen, which is produced in baby hamster kidney (BHK) cells. The good tolerability of Helixate®NexGen was further supported by the fact that there were no other relevant side effects documented. In summary this pharmacovigilance supports the good tolerability and good/excellent efficacy data of Helixate®NexGen.

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Transperitoneal hernioplasty in a patient with severe hemophilia A on preventive treatment with emicizumab

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2021-20-3-116-124 ◽

2021 ◽

Vol 20 (3) ◽

pp. 116-124

Author(s):

S. A. Shutov ◽

K. I. Danishyan ◽

O. V. Shcherbakova ◽

L. A. Gorgidze ◽

P. A. Batrov ◽

...

Keyword(s):

Hemophilia A ◽

Preventive Treatment ◽

Perioperative Period ◽

Severe Hemophilia ◽

Surgical Interventions ◽

Perioperative Bleeding ◽

Laparoscopic Hernioplasty ◽

Thrombotic Complications ◽

Hemostatic Therapy ◽

Recombinant Fviii

Performance of surgical interventions in patients with severe hemophilia A on emicizumab requires the development of a protocol for the perioperative period management. Objective. To present the first experience of laparoscopic hernioplasty, hemostatic therapy and laboratory monitoring in a patient with severe hemophilia A on emicizumab. A transperitoneal hernioplasty was performed in a 31-year-old patient with severe hemophilia A on emicizumab. The patient received hemostatic therapy with recombinant FVIII for 5 days. Laboratory parameters (detection of FVIII via chromogenic and clotting methods, thromboelastography, determination of aPTT and FVII inhibitor titer) were monitored for 8 days. For a complete postoperative hemostasis, a significantly smaller amount of FVIII concentrate was required due to the lower frequency of administrations compared to similar surgical interventions in patients with severe hemophilia A who did not receive prophylactic therapy with emicizumab. According to thromboelastrography data, not a single episode of hypercoagulation was recorded. Emicizumab monotherapy can maintain adequate hemostasis during surgical procedures associated with a potentially low risk of perioperative bleeding in patients with hemophilia A. In other situations, the use of standard doses of FVIII concentrate concomitantly with emicizumab makes it possible to control hemostasis during postoperative period without the risk of thrombotic complications. The patient has signed a consent to the use of information, including photos, for research purposes and in publications.

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Prevalence of Inhibitors in a Population of 3435 Hemophilia Patients in France

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648507 ◽

1992 ◽

Vol 67 (06) ◽

pp. 600-602 ◽

Cited By ~ 85

Author(s):

Y Sultan ◽

Keyword(s):

Hemophilia A ◽

Hemophilia B ◽

Study Group ◽

Cooperative Study ◽

Population Prevalence ◽

French Study ◽

Number Of Patients ◽

High Incidence ◽

Recombinant Fviii ◽

High Responders

SummaryA cooperative study between the 37 centers of the French Hemophilia Study Group was undertaken to establish the prevalence of inhibitor patients in the French hemophilia population. The prevalence reported in the literature varies widely from 3.6% to 17.5%. Some of the studies are dealing with a small number of patients and inhibitor patients are reported either to the total number of hemophiliacs or to the severely affected ones. The French study provided information concerning 3,435 hemophiliacs and showed a prevalence of 6.2% for the overall population. Prevalence of inhibitors was found to be 7% in the population of hemophilia A patients and 12.8% in the population of severely affected ones. The prevalence of inhibitors in the population of hemophilia B patients was 2% and 4% in the population of severely affected hemophilia B patients. The cooperative study also showed that 47.5% of inhibitors are detected before 10 years of age and that 82% of inhibitor patients are high responders. Analysis of inhibitor detection in patients under the age often showed that there was a peak in the population of 2 years old children. Although not comparable to the present study the high incidence of inhibitors with ultrapurified and recombinant FVIII reported in previously untransfused patient may be borne in mind.

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A Multicenter Pharmacosurveillance Study for the Evaluation of the Efficacy and Safety of Recombinant Factor VIII in the Treatment of Patients with Hemophilia A

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665410 ◽

1997 ◽

Vol 78 (05) ◽

pp. 1352-1356 ◽

Cited By ~ 45

Author(s):

Emel Aygören-Pürsün ◽

Inge Scharrer ◽

Keyword(s):

Factor Viii ◽

Hemophilia A ◽

Parvovirus B19 ◽

Subjective Evaluation ◽

Recombinant Factor Viii ◽

Fviii Inhibitor ◽

Previously Treated Patients ◽

Previously Treated ◽

Bleeding Episodes ◽

Recombinant Fviii

SummaryIn this open multicenter study the safety and efficacy of recombinant factor VIII (rFVIII) was assessed in 39 previously treated patients with hemophilia A (factor VIII basal activity ≤15%).Recombinant FVIII was administered for prophylaxis and treatment of bleeding episodes and for surgical procedures. A total of 3679 infusions of rFVIII were given. Efficacy of rFVIII as assessed by subjective evaluation of response to infusion and mean annual consumption of rFVIII was comparable to that of plasma derived FVIII concentrates. The incremental recovery of FVIII (2.4 ± 0,83%/IU/kg, 2.12 ± 0.61%/IU/kg, resp.) was within the expected range. No clinical significant FVIII inhibitor was detected in this trial. Five of 16 susceptible patients showed a seroconversion for parvovirus B19. However, the results are ambiguous in two cases and might be explained otherwise in one further case. Thus, in two patients a reliable seroconversion for parvovirus B19 was observed.

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New Trends and Developments in Patients with Severe Aortic Stenosis – Towards Optimal Treatment?

European Cardiology Review ◽

10.15420/ecr.2009.5.2.81 ◽

2009 ◽

Vol 5 (2) ◽

pp. 81 ◽

Cited By ~ 2

Author(s):

Martijn WA van Geldorp ◽

Johanna JM Takkenberg ◽

Ad JJC Bogers ◽

A Pieter Kappetein ◽

◽

...

Keyword(s):

Aortic Stenosis ◽

Severe Aortic Stenosis ◽

Surgical Techniques ◽

Treatment Strategies ◽

Tissue Doppler ◽

Doppler Imaging ◽

Treatment Modalities ◽

Diagnostic Tools ◽

Number Of Patients ◽

Transcatheter Valve

Over the next few decades the number of patients diagnosed with aortic stenosis is expected to rise as the population ages and the use of several diagnostic tools expands. This will result in a growing need for both medical and surgical treatment and stimulate the development of new diagnostic and surgical techniques. This article briefly describes the prevalence, pathogenesis and clinical presentation of patients with aortic stenosis and focuses on developments in diagnostic tools, treatment strategies and treatment modalities: the use of echocardiography, tissue Doppler imaging, stress testing and biomarkers is discussed, as well as timing of surgery and the role microsimulation can play in prosthesis selection. Furthermore, newly developed transcatheter valve implantation techniques and their possible role in treating ‘inoperable’ or ‘elderly’ patients are discussed.

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Common Genetic Variants in ABO and CLEC4M Modulate the Pharmacokinetics of Recombinant FVIII in Severe Hemophilia A Patients

Thrombosis and Haemostasis ◽

10.1055/s-0040-1714214 ◽

2020 ◽

Vol 120 (10) ◽

pp. 1395-1406 ◽

Cited By ~ 1

Author(s):

Iris Garcia-Martínez ◽

Nina Borràs ◽

Marta Martorell ◽

Rafael Parra ◽

Carme Altisent ◽

...

Keyword(s):

Blood Group ◽

Half Life ◽

Robust Regression ◽

Hemophilia A ◽

Illumina Miseq ◽

Activity Levels ◽

Severe Hemophilia ◽

Single Nucleotide Variants ◽

Common Genetic Variants ◽

Recombinant Fviii

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.

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Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

Journal of Clinical Medicine ◽

10.3390/jcm10132803 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2803

Author(s):

Carolin Czauderna ◽

Martha M. Kirstein ◽

Hauke C. Tews ◽

Arndt Vogel ◽

Jens U. Marquardt

Keyword(s):

Clinical Care ◽

Treatment Options ◽

Treatment Strategies ◽

Specific Treatment ◽

Growth Factor Receptor ◽

Treatment Modalities ◽

Precision Oncology ◽

Recurrence Rates ◽

Isocitrate Dehydrogenase 1 ◽

Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

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