Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
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.
 ...
PMID:[Thrombogenicity of prothrombin complex concentrates]. 171 62

Hungary's health service (10 million pop.) needs about 2000 kg of albumin, 10 million units of Factor VIII 1-1,5 million units of Factor IX, and 3 million micrograms of anti D IgG a year. The plasma for these products is collected from volunteer blood donors and by plasmapheresis. 90% of the albumin is produced by the Cohn method. To study the efficiency of a new chromatographic plasma fractionation method (3), we installed an integrated system for the production of factor VIII, PCC, albumin and intravenous IgG. About 10% of the total albumin is produced using this system. The paper discusses the results of 3 years of experimentation with the chromatographic system. The problems of the method are also analysed in detail. PCC is now in clinical use, the albumin is under clinical trial and the clinical trial of the i.v. IgG will start soon.
 ...
PMID:Plasma fractionation in blood transfusion service. 311 12

During a 4-year national cooperative study of factor VIII inhibitors in patients with classic hemophilia, new inhibitors were identified in 31 of 1,306 patients without this finding on entry. The age of patients upon detection of an inhibitor ranged from 2-62 years with a median age of 16 years. The incidence of new inhibitors was 8 per 1000 patient-years of observation. In 29 patients baseline VIII:C was less than or equal to 0.03 units/ml; the other two patients had levels of 0.06 and 0.07 units/ml. Factor VIII:CAg was measured in entry samples of plasma from 27 subjects and generally corresponded to levels of VIII:C; the levels of VIII:CAg ranged from 0.01-0.11 units/ml in 9 cases and were less than 0.01 units/ml in the remaining 18. In no instance did an inhibitor develop without preceding exposure to infused VIII:C, appearing within 8-250 VIII:C exposure-days in all patients and within 75 exposure-days in 10 of 11 patients with maximum inhibitor values greater than 15 Bethesda units/ml. Development of an inhibitor could not be correlated with any of the following variables: bleeding tendency, intercurrent illness, drugs, and selected clinical laboratory tests including blood counts, liver enzymes, and immunoglobulins. On the basis of maximum activity and persistence of inhibitors, a spectrum of patterns could be identified. (1) In Group IA with 9 patients, inhibitors with maximum values greater than 15 Bethesda units/ml persisted throughout the remaining study period. (2) In Group IB with 2 patients with mild classic hemophilia, inhibitors with maximum values greater than 15 Bethesda units/ml disappeared despite varying continued exposure to VIII:C and PCC. (3) In Group IIA with 10 patients, inhibitors with maximum values less than or equal to 15 Bethesda units/ml persisted throughout the remaining study period. (4) In Group IIB with 3 patients, maximum values less than or equal to 15 Bethesda units/ml disappeared within 18 months despite varying continued exposure to VIII:C and PCC. (5) In Group III with 7 patients, an inhibitor with a value of less than 5 Bethesda units/ml was conclusively documented on a sing study period. (4) In Group IIB with 3 patients, maximum values less than or equal to 15 Bethesda units/ml disappeared within 18 months despite varying continued exposure to VIII:C and PCC. (5) In Group III with 7 patients, an inhibitor with a value of less than 5 Bethesda units/ml was conclusively documented on a sing study period.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Clinical patterns of hemophilic patients who develop inhibitors. 643 36

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.
 ...
PMID:Hemophilia with factor VIII and factor IX inhibitors, incidence, bleeding problems and management. 788 49

Alloantibodies occurring in hemophiliacs is a side effect or repeated treatment and represents a severe complication. The induction of immune tolerance using one of the lower dose regimens should be attempted as soon as it is feasible as regimens started soon after the inhibitor appears may have greater success in inducing tolerance. If the hemophiliac with inhibitor hemorrhages, PCC for aPCC should be the first line of therapy since these concentrates can be given in the home setting. If the hemorrhage is severe and the anti-porcine inhibitor titer is low, the patient should be infused in a clinic or hospital setting with porcine factor VIII using increasing doses to achieve a circulating factor VIII level. Entry into clinical trials, such as those using rFVIIa should be encouraged.
 ...
PMID:Inhibitors of factor VIII: detection and treatment. 788 76

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.
 ...
PMID:Inhibitors in congenital haemophilia. 880 May 8

A hemophilia A patient with high responder inhibitor had been treated by (activated) prothrombin complex concentrates (A) PCC and activated factor VII until the occurrence of intracranial bleeding at the age of 6 years. Since the inhibitor titer was decreased less than 1 Bethesda Units/ml, high dose of factor VIII was given followed by the infusions of factor VIII concentrates (100 units/kg) three times a week. In spite of previous episodes of anamnestic responses by factor VIII products before, the inhibitor titer did not increase and disappeared completely 6 months after the FVIII infusion therapy. The specific anti-factor VIII IgG subclasses of the inhibitor were IgG2 and IgG4. The inhibitor recognized both light and heavy chains. He have no bleeding episode for 6 months since the beginning of the prophylactic with factor VIII concentrates.
 ...
PMID:[Successful induction of immune tolerance and novel hemostatic effects in a hemophilia A with high-responder inhibitor by regular infusions of factor VIII]. 896 Jun 66

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.
 ...
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

Non-activated and activated prothrombin complex concentrates (PCC/aPCC) have been used successfully to treat bleeds in haemophilia patients with inhibitors, but most physicians do not consider these products as effective as factor VIII/IX (FVIII/IX) concentrates in non-inhibitor patients. Thus, surgical procedures in inhibitor patients have been performed reluctantly. We have performed 14 minor and five major surgical and invasive diagnostic procedures in eight patients with congenital haemophilia A and inhibitors and in two patients with acquired haemophilia. When a loading dose of 100 U kg-1 of FEIBA was given followed by 200 U kg-1 day-1 in three divided doses every 8 h for 3 days, and then, when the daily dose was tapered to 100-150 U kg-1, no severe or unexpected bleeding complications were observed. However, one adverse event was observed. A 69-year-old man who suffered a myocardial infarction the third postoperative day following sigmoidectomy was managed safely with opiate analgesia, nitrates and diuretics, and the continued use of FEIBA(R).
 ...
PMID:Activated prothrombin complex concentrate (FEIBA) treatment during surgery in patients with inhibitors to FVIII/IX. 1496 7


1 2 Next >>