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Immobilization of blood coagulant factor VII on polycaprolactone membrane through polydopamine grafting

Gopal R, Md Shakhih MF, Sahalan M, Lee TC, Hermawan H, Sivalingam S, et al.

Colloids Surf B Biointerfaces, 2023 Aug;228:113390.
PMID: 37315506 DOI: 10.1016/j.colsurfb.2023.113390

Postoperative bleeding following cardiac surgeries is still an issue that deranges the medical resources and cost. The oral and injection administrations of blood coagulation protein, Factor VII (FVII), is effective to stop the bleeding. However, its short half-life has limited the effectiveness of this treatment and frequent FVII intake may distress the patients. Instead, incorporating FVII into synthetic biodegradable polymers such as polycaprolactone (PCL) that is commonly used in drug delivery applications should provide a solution. Therefore, this study aimed to immobilize FVII on PCL membranes through a cross-linkage polydopamine (PDA) grafting as an intermediate layer. These membranes are intended to provide a solution for cardiac bleeding in coagulating blood and sealing the sutured region. The membranes were evaluated in terms of its physio-chemical properties, thermal behavior, FVII release profile and biocompatibility properties. The ATR-FTIR was used to analyze the chemical functionalities of the membranes. Further validation was done with XPS where the appearances of 0.45 ± 0.06% sulfur composition and C-S peak have confirmed the immobilization of FVII on the PCL membranes. The cross-linked FVIIs were viewed in spherical immobilization on the PCL membranes with a size range between 30 and 210 nm. The surface roughness and hydrophilicity of the membranes were enhanced with a slight shift of melting temperature. The PCL-PDA-FVII0.03 and PCL-PDA-FVII0.05 membranes, with wide area of FVII immobilization released approximately only 22% of FVII into the solution within 60 days period and, it is found that the PCL-PDA-FVIIx membranes projected the Higuchi release model with non-Fickian anomalous transport. While the cytotoxic and hemocompatibility analyses showed advance cell viability, identical coagulation time and low hemolysis ratio on the PCL-PDA-FVIIx membranes. The erythrocytes were viewed in polyhedrocyte coagulated structure under SEM visualization. These results validate the biocompatibility of the membranes and its ability to prolong blood coagulation, thus highlighting its potential application as cardiac bleeding sealant.

Matched MeSH terms: Coagulants*
Treatment of landfill leachate by using lateritic soil as a natural coagulant

Syafalni, Lim HK, Ismail N, Abustan I, Murshed MF, Ahmad A

J Environ Manage, 2012 Dec 15;112:353-9.
PMID: 22964042 DOI: 10.1016/j.jenvman.2012.08.001

In this research, the capability of lateritic soil used as coagulant for the treatment of stabilized leachate from the Penang-Malaysia Landfill Site was investigated. The evaluation of lateritic soil coagulant in comparison with commercialized chemical coagulants, such as alum, was performed using conventional jar test experiments. The optimum pH and coagulant dosage were identified for the lateritic soil coagulant and the comparative alum coagulant. It was found that the application of lateritic soil coagulant was quite efficient in the removal of COD, color and ammoniacal-nitrogen content from the landfill leachate. The optimal pH value was 2.0, while 14 g/L of lateritic soil coagulant was sufficient in removing 65.7% COD, 81.8% color and 41.2% ammoniacal-nitrogen. Conversely, the optimal pH and coagulant dosage for the alum were pH 4.8 and 10 g/L respectively, where 85.4% COD, 96.4% color and 47.6% ammoniacal-nitrogen were removed from the same leachate sample. Additionally, the Sludge Volume Index (SVI) ratio of alum and lateritic soil coagulant was 53:1, which indicated that less sludge was produced and was an environmentally friendly product. Therefore, lateritic soil coagulant can be considered a viable alternative in the treatment of landfill leachate.

Matched MeSH terms: Coagulants/chemistry*
Fulltext Rurioctocog alfa pegol PK-guided prophylaxis in hemophilia A: results from the phase 3 PROPEL study

Klamroth R, Windyga J, Radulescu V, Collins PW, Stasyshyn O, Ibrahim HM, et al.

Blood, 2021 04 01;137(13):1818-1827.
PMID: 33150384 DOI: 10.1182/blood.2020005673

Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs ≥1% has shown to be efficacious with an acceptable safety profile in people with hemophilia A (PwHA). The PROPEL trial compared safety and efficacy of 2 target FVIII troughs in PwHA aged 12 to 65 years, with severe disease, annualized bleeding rate ≥2, and previous FVIII treatment. PwHA were randomized to 12 months' pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1% to 3% (reference arm) or 8% to 12% (elevated arm); first 6 months was treatment-adjustment period. The primary endpoint was absence of bleeds during the second 6 months, analyzed using multiple imputations (full analysis set [FAS]). In the 1% to 3% and 8% to 12% arms, respectively, point estimates (95% confidence interval) of proportions of PwHA with zero total bleeds were 42% (29% to 55%) and 62% (49% to 75%) in FAS (N = 115; P = .055) and 40% (27% to 55%) and 67% (52% to 81%) in per-protocol analysis set (N = 95; P = .015). Dosing frequency and consumption varied in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA; serious AEs in 7/115 (6%) PwHA, including 1 treatment-related in 8% to 12% arm (transient anti-FVIII inhibitor). There were no deaths, serious thrombotic events, or AE-related discontinuations. PK-guided prophylaxis was achievable and efficacious in both arms. No new safety signals were observed in the 8% to 12% arm. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and emphasize the importance of personalized treatment. This trial was registered at www.clinicaltrials.gov as #NCT02585960.

Matched MeSH terms: Coagulants/adverse effects; Coagulants/pharmacokinetics; Coagulants/therapeutic use*
Fulltext Vulcanisation and coagulant dipping of epoxidised natural rubber latex

Dazylah Darji, Ma'zam Md Said

Pertanika Journal of Science & Technology, 2010;18(2):-.
MyJurnal

Epoxidised Natural Rubber (ENR) is now a commercially available polymer produced by chemical modification of natural rubber. Currently, three types of ENR are commercially available, and these are ENR 10, ENR 25, and ENR 50 with 10%, 25%, and 50% mol epoxidation, respectively. Studies on prevulcanisation of ENR 50 and postvulcanisation of the latex films were carried out. The objective of this study was to develop ENR 50 that could be dipped easily in coagulant dipping solution to produce dipped products. Several attempts were made by compounding prevulcanised ENR 50 at various sulphur levels ranging from 0.5 to 3.0 pphr. Using suitable coagulant dipping systems, ENR 50 film could be formed despite the high contents of non-ionic surfactant. It was found that the tensile strength of prevulcanised ENR 50 film decreased with the increase in the sulphur level. The results show that as level of sulphur increased, M300 also increased to an optimum value of 1.5 pphr of sulphur. For the postvulcanised ENR 50 film, however, the tensile strength increased and then decreased with the increasing sulphur level. Meanwhile M300 increased with the increasing postvulcanization time and sulphur level. The postvulcanisation of ENR 50 film seems to be a more effective way of increasing tensile properties than by prevulcanisation of ENR 50.

Matched MeSH terms: Coagulants
Fulltext Snake Venom Proteomics, Immunoreactivity and Toxicity Neutralization Studies for the Asiatic Mountain Pit Vipers, Ovophis convictus, Ovophis tonkinensis, and Hime Habu, Ovophis okinavensis

Tan CH, Palasuberniam P, Tan KY

Toxins (Basel), 2021 07 23;13(8).
PMID: 34437385 DOI: 10.3390/toxins13080514

Snakebite envenomation is a serious neglected tropical disease, and its management is often complicated by the diversity of snake venoms. In Asia, pit vipers of the Ovophis species complex are medically important venomous snakes whose venom properties have not been investigated in depth. This study characterized the venom proteomes of Ovophis convictus (West Malaysia), Ovophis tonkinensis (northern Vietnam, southern China), and Ovophis okinavensis (Okinawa, Japan) by applying liquid chromatography-tandem mass spectrometry, which detected a high abundance of snake venom serine proteases (SVSP, constituting 40-60% of total venom proteins), followed by phospholipases A2, snake venom metalloproteinases of mainly P-III class, L-amino acid oxidases, and toxins from other protein families which were less abundant. The venoms exhibited different procoagulant activities in human plasma, with potency decreasing from O. tonkinensis > O. okinavensis > O. convictus. The procoagulant nature of venom confirms that consumptive coagulopathy underlies the pathophysiology of Ovophis pit viper envenomation. The hetero-specific antivenoms Gloydius brevicaudus monovalent antivenom (GbMAV) and Trimeresurus albolabris monovalent antivenom (TaMAV) were immunoreactive toward the venoms, and cross-neutralized their procoagulant activities, albeit at variably limited efficacy. In the absence of species-specific antivenom, these hetero-specific antivenoms may be useful in treating coagulotoxic envenomation caused by the different snakes in their respective regions.

Matched MeSH terms: Coagulants/analysis; Coagulants/immunology; Coagulants/toxicity
A comparative study of the biological properties of some venoms of snakes of the genus Bothrops (American lance-headed viper)

Tan NH, Ponnudurai G

Comp. Biochem. Physiol., B, 1991;100(2):361-5.
PMID: 1799979

1. The hemorrhagic, procoagulant, anticoagulant, phosphodiesterase, alkaline phosphomonoesterase, 5'-nucleotidase, hyaluronidase, arginine ester hydrolase, phospholipase A, L-amino acid oxidase and protease activities of 26 samples of venoms from 13 species of Bothrops were determined, and the Sephadex G-75 gel filtration patterns for some of the venoms also examined. 2. The results show that while there are considerable individual variations in the biological activities of many of the Bothrops venoms tested, there are some common characteristics at the genus and species levels. 3. The differences in the biological properties of the Bothrops venoms tested can be used for the differentiation of most Bothrops species examined.

Matched MeSH terms: Anticoagulants/chemistry; Coagulants/chemistry
Once-weekly prophylactic treatment vs. on-demand treatment with nonacog alfa in patients with moderately severe to severe haemophilia B

Kavakli K, Smith L, Kuliczkowski K, Korth-Bradley J, You CW, Fuiman J, et al.

Haemophilia, 2016 May;22(3):381-8.
PMID: 26823276 DOI: 10.1111/hae.12878

Limited data are available on optimal prophylaxis regimens of factor IX (FIX) replacements for patients with haemophilia B.

Matched MeSH terms: Coagulants/adverse effects; Coagulants/therapeutic use*
Efficacy and safety of long-acting recombinant fusion protein linking factor IX with albumin in haemophilia B patients undergoing surgery

Négrier C, Abdul Karim F, Lepatan LM, Lienhart A, López-Fernández MF, Mahlangu J, et al.

Haemophilia, 2016 Jul;22(4):e259-66.
PMID: 27333467 DOI: 10.1111/hae.12972

INTRODUCTION: Recombinant factor IX fusion protein (rIX-FP) has been developed to improve the pharmacokinetic (PK) profile of factor IX (FIX), allowing maintenance of desired FIX activity between injections at extended intervals, ultimately optimizing haemophilia B treatment.
AIM: To determine the efficacy and safety of rIX-FP in the perioperative setting.
METHODS: Subjects were adult and paediatric patients with severe to moderately severe haemophilia B (FIX ≤ 2%) participating in three Phase III clinical trials and undergoing a surgical procedure. PK profiles were established prior to surgery for each patient. Haemostatic efficacy was assessed by the investigator for up to 72 h after surgery. Safety measurements during the study included adverse events and inhibitors to FIX. FIX activity was monitored during and after surgery to determine if repeat dosing was required.
RESULTS: Twenty-one, both major and minor, surgeries were performed in 19 patients. Haemostatic efficacy was rated as excellent (n = 17) or good (n = 4) in all surgeries. A single preoperative dose maintained intraoperative haemostasis in 20 of 21 surgeries. Nine major orthopaedic surgeries were conducted in eight patients with a mean of 7 (range: 6-12) rIX-FP injections during surgery and the 14-day postoperative period. Median rIX-FP consumption for orthopaedic surgeries was 87 IU kg(-1) preoperatively and 375 IU kg(-1) overall. No subject developed inhibitors to FIX or antibodies to rIX-FP.
CONCLUSION: Recombinant factor IX fusion protein was well tolerated and effectively maintained haemostasis during and after surgery. Stable FIX activity was achieved with a prolonged dosing interval and reduced consumption compared to conventional or currently available long-acting recombinant FIX.
KEYWORDS: albumin fusion proteins; factor IX; haemophilia B; orthopaedic surgery; recombinant fusion proteins

Matched MeSH terms: Coagulants/therapeutic use*
Recombinant long-acting glycoPEGylated factor IX (nonacog beta pegol) in haemophilia B: assessment of target joints in multinational phase 3 clinical trials

Negrier C, Young G, Abdul Karim F, Collins PW, Hanabusa H, Colberg T, et al.

Haemophilia, 2016 Jul;22(4):507-13.
PMID: 26936227 DOI: 10.1111/hae.12902

BACKGROUND: The paradigm(™) 2 and 4 phase 3 clinical trials investigated the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in previously treated haemophilia B patients.
AIM: These post hoc analyses investigated the bleeding patterns in target joints.
METHODS: Patients randomized to 40 or 10 IU kg(-1) once weekly prophylaxis who had at least one target joint were included. Baseline demographics and disease-specific data were collected. Bleeding patterns were assessed, and an International Society on Thrombosis and Haemostasis (ISTH) definition of target joints was used.
RESULTS: A total of 67% and 8% of patients in the 40 and 10 IU kg(-1) arm, respectively, did not experience target joint bleeds during the paradigm(™) 2 trial. Twenty-four target joints were recorded in each prophylaxis arm at baseline. During the paradigm(™) 2 trial, no bleeds were reported in 17 (71%) and 7 (29%) target joints in the 40 and 10 IU kg(-1) arms respectively. All target joint bleeds in the 40 IU kg(-1) once weekly prophylaxis arm were controlled with a single injection of 40 IU kg(-1) nonacog beta pegol. By the latest ISTH definition, 90% and 58% of target joints in the 40 and 10 IU kg(-1) arms, respectively, were no longer considered target joints at the end of the paradigm(™) 2 trial. At the end of the paradigm(™) 4 extension trial, all target joints in the 40 IU kg(-1) arm were no longer considered target joints.
CONCLUSION: Routine prophylaxis with 40 IU kg(-1) once weekly nonacog beta pegol has the potential for effective management of target joint bleeds in haemophilia B patients.

Matched MeSH terms: Coagulants/therapeutic use*
A comparative study of the biological properties of venoms of some old world vipers (subfamily viperinae)

Tan NH, Ponnudurai G

Int. J. Biochem., 1992 Feb;24(2):331-6.
PMID: 1733799

1. The hemorrhagic, procoagulant, anticoagulant, phosphodiesterase, hyaluronidase, alkaline phosphomonoesterase, 5'-nucleotidase, arginine ester hydrolase, phospholipase A, L-amino acid oxidase and protease activities of 30 samples of venoms from nine species (12 taxa) of the old world vipers (Subfamily Viperinae) including snakes from the genera Bitis, Causus, Cerastes, Echis, Eristicophis and Pseudocerastes, were determined and the Sephadex G-75 gel filtration patterns for some of the venoms were also examined. 2. Examination of the biological properties of the venoms of the Viperinae tested indicates the presence of common venom biological characteristics at the various phylogenic levels. 3. Venoms of most species of the Viperinae examined exhibited characteristic biological properties at the species level, and this allows the differentiation of the Viperinae species by differences in their biological properties. 4. Particularly useful for this purpose, are the effects of venom on kaolin-cephalin clotting time of platelet poor rabbit plasma and the Sephadex G-75 gel filtration pattern and arginine ester hydrolase activity of the venom.

Matched MeSH terms: Anticoagulants; Coagulants
Vitrectomy for breakthrough bleeding in age related macular degeneration and polypoidal choroidal vasculopathy in a Malaysian Hospital

Bastion, M.L.C., Amelah, M.A.Q., Wong, H.S.

Journal of Surgical Academia, 2012;2(2):21-26.
MyJurnal

This study aimed to review the risk factors and clinical outcomes of patients undergoing pars planar vitrectomy (PPV) for breakthrough bleeding (BTB) from age related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). We performed a retrospective review of medical records of 346 patients operated by the vitreoretinal unit at Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Kuala Lumpur, Malaysia from January 2008 - June 2011. We found eight eyes of 8 patients with AMD/IPCV-related BTB who underwent PPV. Mean age of patients was 64.4 years (range 41-80 years) with 5 males. Five were Chinese. Duration of symptoms ranged from days to months. Four patients were on anti-coagulants. Two had history of prior photodynamic therapy. There were five cases of PCV, of which three were macular in location. All three cases of AMD were macular. Intraoperative intravitreal ranibizumab injection was given in three cases and two had combined vitrectomy and cataract extraction. All cases reported improvement in visual acuity with four cases achieving 6/60 or better post operatively including two cases of extramacular PCV achieving 6/9 vision. Mean follow-up was 60 weeks. Postoperative complications included retinal tear and detachment in one case, reattached on reoperation. Six patients had a history of hypertension including one individual with stroke. Our small series indicates a predominance of Chinese individuals with BTB. Usage of anticoagulants and hypertension may be a predisposing factor. Better visual prognosis occurs with extramacular lesions which tend to be of PCV type.

Matched MeSH terms: Anticoagulants; Coagulants
A comparative study of the biological properties of krait (genus Bungarus) venoms

Tan NH, Ponnudurai G

Comp Biochem Physiol C Comp Pharmacol Toxicol, 1990;95(1):105-9.
PMID: 1971550

1. The intravenous median lethal doses (LD50), protease, phosphodiesterase, alkaline phosphomonoesterase, L-amino acid oxidase, acetylcholinesterase, phospholipase A, 5'-nucleotidase, hyauronidase and anticoagulant activities of fourteen samples of venoms from the four common species of krait (Bungarus caeruleus, Bungarus candidus, Bungarus multicinctus and Bungarus fasciatus) were examined. 2. The results indicate that even though there are individual variations in the biological properties of the krait venoms, interspecific differences in the properties can be used for differentiation of the venoms from the four species of Bungarus. Particularly useful for this purpose are the LD50's and the contents of 5'-nucleotidase and hyaluronidase of the venoms.

Matched MeSH terms: Anticoagulants; Coagulants

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