Prothrombin Complex Concentrates for Clinical Use

Chandra, S.; Brummelhuis, H.G.J.

doi:10.1159/000460659

Cited by 7 publications

(9 citation statements)

References 91 publications

(123 reference statements)

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“…Thrombotic dis orders and disseminated intravascular coagulation may be associated with high-dose use of PCC [3], possibly because of an overload of factors II:c, or X:c, activated factors IX, VII or X, and/or coagulant active phospholipids [4,5].…”

Section: Introductionmentioning

confidence: 99%

Properties of a Highly Purified Human Plasma Factor IX:c Therapeutic Concentrate Prepared by Conventional Chromatography

Burnouf¹,

Michalski²,

Goudemand³

et al. 1989

Vox Sanguinis

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We have characterized a highly purified (HP) factor IX concentrate intended for therapy of hemophilia B. The product has been prepared from pooled human plasma using a large-scale procedure combining three conventional chromatographic steps based on DEAE ion exchange and affinity on immobilized heparin. The specific activity of the product was 119±10 IU factor IX:c/mg protein (n = 15), corresponding to a purification factor of about 9,000. The concentrate was free of the vitamin K-dependent clotting factors II, VII and X and of proteins C and S. Most of the contaminants found in factor IX complex concentrate (PCC) were absent in this new product. High-molecular-weight kininogen, factors VIII, XI, XII or prekallikrein were not detected. There were no activated factors, such as factors IXa, and Xa, no thrombin and no phospholipids. Only two contaminants could be detected: C4 and inter-alpha-trypsin inhibitor (about 0.8 and 1.2mg/1,000IU factor IX:c, respectively). The purity of the product, as compared to PCC, was confirmed by sodium dodecylsulfate polyacrylamide gel electrophoresis, cellulose acetate electrophoresis, Grabar- Williams immunoelectrophoresis, and bidimensional immunoelectrophoresis. Thrombogenicity tests in rabbits revealed that the HP factor IX tested had a lower thrombogenic power than the PCC tested. The concentrate has been subjected to a 0.3% tri(n-butyl) phosphate-1% Tween 80 treatment for 6h at 25°C during its production to reduce or eliminate the risk of transmission of plasma-borne lipid-enveloped viruses. These conditions inactivated more than 3.8 log(10) of vesicular stomatitis virus and more than 4.3 log(10) of sindbis virus within 1 and 2 h of treatment, respectively. These data demonstrate that a highly purified therapeutic clotting factor IX concentrate can be prepared from human plasma by conventional chromatographic methods.

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Section: Introductionmentioning

confidence: 99%

Properties of a Highly Purified Human Plasma Factor IX:c Therapeutic Concentrate Prepared by Conventional Chromatography

Burnouf¹,

Michalski²,

Goudemand³

et al. 1989

Vox Sanguinis

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“…One unit of FFP approximately 100 ml was thawed in a 37~ waterbath, pH was adjusted to 7.0 with IM HCI and treated with dry DEAESephadex A50 gel (Pharmacia, Uppsala, Sweden) at 0.5g/I plasma and stirred for 30 minutes at room temperature to remove prothrombin complex (9). After 30 minutes the plasma was filtered through nylon net (40 pm mesh).…”

Section: F VIII Chromatographymentioning

confidence: 99%

Separation of antihemophilic factor VII from human plasma by column chromatography

Baikar¹,

Kamath²,

Vishwanathan³

et al. 2003

Indian J Clin Biochem

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TMAE-Fractogel 650 (M) (Trimethylaminoethyl) is an ion exchange medium can be used to capture factor Vlll (F VIII) directly from plasma. Previous reports have focused on the use of DEAE-Fractoge1650 (M) (Dimethylaminoethyl) ion exchange medium to capture F Vlll from cryoprecipitate and plasma. Our main objectives were (I) to standardise the purification of FVIII from human plasma by column chromatographic technique. (11) to study the recovery of FVIII activity in purified fraction at 18 -20~ process condition. (Ill) to study the effect of virucidal step on recovery of FVIII activity and (IV) to study the effect of lyophilisation on FVIII activity. In this report, Citrate Phosphate Dextrose (CPD) plasma was batch stirred with dry DEAE-Sephadex A50, filtered, diluted, loaded on to a column packed with TMAE-Fractogel and chromatographed. Most of the unwanted proteins flowed through the gel unadsorbed. Bound F VIII was eluted by increasing the ionic strength of the buffer. This purification step gave an overall 80% recovery from the plasma with a specific activity of 0.97 IU FVlll/mg protein. The purified F VIII fraction was made virus safe by employing the virucidal technique developed by New York Blood Centre (NYBC). There was 48.43% loss of FVIII activity in Virus inactivation treatment and the loss of FVIII activity in lyophilisation was 8.45% which is acceptable. This method of purification gave a higher yield of FVIII than cryoprecipitation, and is a promising alternative method to cryoprecipitation of F VIII.

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“…On the contrary, patients receiving fibrinogen, which is cur rently considered as a 'high risk' product [10], surprisingly did not show a significantly increased risk of developing PT hepatitis when compared to cases treated only with blood units from single donors. The high risk of non-A, non-B hepatitis connected with the use of the prothrombin-complex [7] or of factor IX concentrates [18] has been attrib uted to various factors and particularly to the use of large-pool preparations and to the impossiblity to apply virucidal heat treat ment, for the inactivation of these factors by heat [9], Our study shows that the hepatitis attack rate is very high in recipients of a single dose of prothrombin-complex, suggesting that the potential benefit of its clinical use should be carefully weighed against the risk on an individual basis, as recently recommanded by the World Health Organisation Expert Committee on Viral Hepatitis [17], Finally, acute non-A, non-B post-transfusion hepatitis had an asymptomatic and anicteric course in about two-thirds of our…”

Section: Risk Ofpt Hepatitis In Relation To Blood Volume and Blood Prmentioning

confidence: 99%

Prospective Study of Posttransfusion Hepatitis in Cardiac Surgery Patients Receiving only Blood or also Blood Products

Tremolada¹,

Chiappetta²,

Noventa³

et al. 1983

Vox Sanguinis

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The incidence, etiology and risk factors of posttransfusion (PT) hepatitis were evaluated in a prospective study of 297 consecutive open-heart surgery patients. PT hepatitis occurred in 63 (21.2%) patients with a significantly higher hepatitis attack rate in 51 recipients of commercial clotting factor concentrates (56.8%) compared to 246 recipients of blood units from single volunteer donors (13.8% p<0.001). Among the concentrates, Prothrombin- complex showed the highest relative hepatitis risk (24) while in patients receiving only blood, the incidence PT hepatitis was correlated with the blood volume transfused. Of the 63 patients with PT hepatitis, 2 (3%) had hepatitis B, 8 (13%) showed evidence of cytomegalovirus infection and 53 (84%) had non-A, non-B hepatitis. These results show that in Italy, as elsewhere, non-A, non-B PT hepatitis is frequent, particularly when commercial blood products are used.

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Prothrombin Complex Concentrates for Clinical Use

Cited by 7 publications

References 91 publications

Properties of a Highly Purified Human Plasma Factor IX:c Therapeutic Concentrate Prepared by Conventional Chromatography

Properties of a Highly Purified Human Plasma Factor IX:c Therapeutic Concentrate Prepared by Conventional Chromatography

Separation of antihemophilic factor VII from human plasma by column chromatography

Prospective Study of Posttransfusion Hepatitis in Cardiac Surgery Patients Receiving only Blood or also Blood Products

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