Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1832526 (PCC)
 5,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two prothrombin complex concentrates, Auto-Factor IX and Proplex, have been reported to be effective in controlling bleeding in hemophilic patients with factor VIII inhibitors. A third PCC, Konyne, was used to treat 64 bleeding episodes (130 infusions) in five hemophilic patients with factor VIII inhibitors. Prompt control of bleeding was observed in each instance with doses of 15 to 100 units of factor IX/kg; no complications were encountered. Konyne resulted in in vivo and in vitro shortening of the partial thromboplastin time of patients with factor VIII inhibitors, but the mechanism of action is unknown. If further studies confirm the efficacy and safety of PCC in the treatment of such patients, its use for this purpose could lead to significant saving of factor VIII concentrates.
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PMID:Prothrombin complex concentrate (Konyne) in the treatment of hemophilic patients with factor VIII inhibitors. 124 80

PCC's were isolated either by adsorption to DEAE-Sephadex A-50 (particle size 40-120 microns; Pharmacia Uppsala) or by adsorption to Molselect DEAE-50 (particle size 100-320 microns; Reanal Budapest) from human citrated plasma after separation of factor VIII by cryoprecipitation. The two products obtained (without heparin) were both compared by in vitro (NAPTT, TGt50) and in vivo (venous stasis) model in rats acc. to WESSLER) tests. The agent prepared by adsorption to DEAE-Sephadex A-50 showed a significantly higher thrombogenicity than that prepared by Molselect DEAE-50. ED50 values for thrombus formation to amounted 15 Factor IX U/kg for the first product and to 210 factor IX U/kg for the second.
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PMID:[Thrombogenicity of prothrombin complex concentrates]. 171 62

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 1.2 mg/1,000 IU 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 degrees 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 log10 of vesicular stomatitis virus and more than 4.3 log10 of sindbis virus within 1 and 2 h of treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Properties of a highly purified human plasma factor IX:c therapeutic concentrate prepared by conventional chromatography. 261 59

We describe our experience with radical prostatectomy in a patient with hemophilia B. whose factor IX activity was 7% and partial thromboplastin time was 55.9 sec. A total of 43,000 units of factor IX concentrate (PCC) was given perioperatively for 2 weeks. No abnormal hemorrhage was noted. An algorithm for perioperative management of hemophilia B patient is discussed.
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PMID:[Radical prostatectomy in a patient with hemophilia B]. 747 42

Among 117 cases of hemophilia, there were 7 hemophilia A and 2 hemophilia B with factor VIII and factor IX inhibitors diagnosed at the Department of Pediatrics, Siriraj Hospital, Bangkok, Thailand. The overall incidence of hemophilia with inhibitors was 7.7%. Eight cases (6 hemophilia A. 2 hemophilia B) were severe hemophilia and 1 moderate hemophilia A. The average age of the inhibitor detection was about 5 years. Of the 9 cases, 7 had high inhibitor titers and 2 had low inhibitor titers. The frequency of bleeding problems before and after inhibitor detection were not different. The bleedings included hemarthrosis, mucosal bleed, hematoma, oozing from wound, hematuria and intracranial hemorrhage. The treatment of hemarthrosis in hemophilia A with low inhibitor titers was the combination of short course of prednisolone and single large dose factor VIII. In high inhibitor titer patients with acute hemarthrosis (both hemophilia A and hemophilia B), the treatment consisted of prednisolone short course and single high dose of PCC. For bleeding control in both high and low inhibitor titer with mucosal bleeds, oozing from wounds, central nervous system bleeding and hematuria, the combination was used of high dose factor VIII or factor IX for 2 days, and tranexamic acid, prednisolone, cyclophosphamide were required. In life-threatening hemorrhage and surgical operation, plasmapheresis and large dosage factor VIII or factor IX were the treatment of choice. All supportive measures were also important in every case of mucosal bleeds, wounds and surgical operations. The result of treatment revealed one death from massive intracranial hemorrhage and 8 survivals, with joint contracture in 2 cases. All still have inhibitor detected, but in low titer.
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PMID:Hemophilia with factor VIII and factor IX inhibitors, incidence, bleeding problems and management. 788 49

A prospective cross-over study was carried out on 19 patients with haemophilia B. comparing the pharmacokinetics of a purified factor IX concentrate prepared by metal chelate affinity chromatography (9MC) with a conventional three-factor prothrombin complex concentrate (9A). The highly purified factor IX concentrate was shown to have a half-life comparable to the PCC; the in vivo recovery of the purified concentrate was significantly greater than that of the complex (P < 0.01). The 20% change in the value of the International Standard for Factor IX Concentrate, introduced in 1988, might have been expected to lower the recovery values. However, the in vivo recovery for both concentrates was somewhat higher than reported previously, particularly in the older literature. In nine patients, serial assays for fibrinopeptide A, prothrombin fragment F1+2 and thrombin-antithrombin complexes (TAT) were performed to assess the potential thrombogenicity of the two concentrates. Evidence was obtained that there was significantly less activation of coagulation following administration of purified factor IX (9MC), as compared to the activation that occurred after the PCC.
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PMID:A cross-over pharmacokinetic and thrombogenicity study of a prothrombin complex concentrate and a purified factor IX concentrate. 798 19

The pharmacokinetic profile, the thrombogenicity and the virus safety of Preconativ, a PCC subjected both to virus removal procedure and dry-heat treatment were studied. Preconativ is produced from plasma pool, negative both for HBsAg and for antibodies to HIV. To further reduce the risk of virus transmission, the manufacturing process includes hydrophobic gel chromatography and dry-heat treatment at +68 degrees C for 48 hours. Nine patients with hemophilia B participated in a single dose, pharmacokinetic study. The decay curves of factor IX clotting activity were evaluated by model-independent methods. The Clearance and the Mean Residence Time were very similar to those previously reported for untreated PCC. The Volume of Distribution Area and In Vivo Recovery resulted inversely correlated and respectively larger and smaller than those of untreated PCC. A slight fall in platelet count and Antithrombin III level and an increase of Beta-Thromboglobulin and Fibrinopeptide A concentration were found, indicating a clear-cut activation of the coagulation process during the first hours following Preconativ administration. Seven patients (2 of the ones enrolled in the pharmacokinetic study) were completely fulfilling the SSC-ISTH criteria for virus safety prospective study. The follow up of these patients did not show any transaminases elevation or seroconversion against HBV, HCV or HIV. These findings did not change over a 3-5 year follow up in 3 out of 7 patients, repeatedly infused with Preconativ.
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PMID:Pharmacokinetics, thrombogenicity and safety of a double-treated prothrombin complex concentrate. 821 85

Inhibitor formation is a serious complication, occurring in 24-52% of patients with haemophilia A and in 1.5-3% of patients with haemophilia B. Low-titre inhibitors can easily be overcome and do not represent a treatment challenge. They are treated with increased doses of factor concentrate. However, high-titre inhibitors may still cause death from haemorrhage in this population. Optimal treatment of acute, life-threatening haemorrhage in patients with factor VIII inhibitors includes either porcine factor VIII or human factor VIII in high doses since, with both modalities, circulating factor levels are achievable. If the inhibitor titres are too high, plasmapheresis may be warranted. For routine joint bleeds, PCC or aPCC can be administered at home with variable success. For patients with factor IX inhibitors treatment options are more limited. If the haemorrhage is life-threatening, plasmapheresis should be done to decrease the inhibitor and high doses of pure factor IX administered either by continuous infusion or bolus. Attainment of levels of > 20% should be attempted. New clinical options, such as rFVIIa, may emerge. For both groups of patients, IT should be started as soon as the inhibitor is discovered and its behaviour characterized. Unfortunately, no standard regimen for IT exists and the treater will have to choose whichever schedule he/she feels is the most appropriate.
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PMID:Inhibitors in congenital haemophilia. 880 May 8

Melagatran is the active form of the oral, direct thrombin inhibitor, H 376/95, that is under evaluation in clinical trials for the prevention and treatment of thromboembolism. In this study, a single dose, calculated on body weight basis, of antifibrinolytic treatment, factor VIIa, factor VIII with and without von Willebrand factor (vWF), factor IX, activated (APCC) or nonactivated (PCC) prothrombin complex concentrates was given intravenously to rats and rabbits, in an attempt to reverse the prolonged bleeding time during intensive anticoagulation with melagatran (2 micromol/kg/h). The doses used were at or above human therapeutic doses. The cutaneous tail bleeding time in the rat, as well as the ear incision bleeding time and cuticle bleeding time, and the blood loss in the rabbit were used for evaluation of the hemostatic effects of these agents. In vivo Feiba (APCC) and Prothromplex-T (PCC) shortened the prolonged cutaneous bleeding times in rats (P<.05); Feiba and Autoplex (APCC) shortened the cutaneous bleeding times in rabbits (P<.05). In contrast, Prothromplex-T prolonged bleeding times and blood loss in the rabbits (P<.05). Ex vivo Feiba, Autoplex and NovoSeven (rF VIIa) significantly (P<.05) shortened the prolonged whole blood clotting time (WBCT). Prothromplex-T significantly prolonged WBCT, activated clotting time (ACT) and activated partial thromboplastin time (APTT). Feiba, Autoplex, and Prothromplex-T increased thrombin generation measured as increased thrombin-antithrombin complex (TAT) formation. In conclusion, APCCs were found to be the most effective agents for reversing bleeding time induced by a very high plasma concentration of melagatran. APCC and recombinant activated factor FVII (rF VIIa) effectively shortened the prolonged WBCT. Thus, stimulating thrombin generation with the use of APCC may counteract the anticoagulant effect observed with a very high dose of a thrombin inhibitor.
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PMID:Effects of agents, used to treat bleeding disorders, on bleeding time prolonged by a very high dose of a direct thrombin inhibitor in anesthesized rats and rabbits. 1122 39