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)

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

In summary, while a great deal of information has accumulated concerning the properties and natural history of F VIII inhibitors, management remains frustrating and controversial. While bleeding episodes in those who are low responders can be treated with F VIII concentrates, treatment of bleeding in high responders is often much more difficult. Current therapeutic options include F VIII concentrates of human or porcine origin in high dosage, and PCC or APCC. The choice of treatment depends on the patient's current inhibitor concentration, the type and severity of bleeding, product availability, and the preference of the medical personnel involved. However, none of the available therapeutic modalities work as well as F VIII in a hemophiliac without an inhibitor. Perhaps more promising are the immune tolerance regimens that have been developed and are now being modified and fine tuned by a number of investigators. Such regimens have reportedly eradicated F VIII inhibitors in some hemophiliacs, and have converted others from high responders to low responders, in whom bleeding episodes can be effectively treated with conventional doses of F VIII. In contrast to the F VIII inhibitors developing in hemophiliacs, those developing in nonhemophiliacs can often be eradicated with corticosteroids or immunosuppressive drugs, either alone or in combination with F VIII. Not all respond to such approaches and serious hemorrhage may still occur. Treatment of bleeding episodes has included the use of human or porcine F VIII, APCC and, in two instances, DDAVP.
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PMID:Management of patients with factor VIII inhibitors. 298 Feb 69

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)
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PMID:Clinical patterns of hemophilic patients who develop inhibitors. 643 36

We have isolated the genes encoding 11 photosystem I (PSI) subunits from Synechococcus sp., from which this reaction center has been crystallized. The recombinant DNAs, including psaA, psaB, psaC, psaD, psaE, psaF, psaI, psaJ, psaK and psaL, were obtained by heterologous hybridization with probes from appropriate cDNAs or genes from spinach and Synechocystis sp. PCC 6803, or with synthetic oligodeoxyribonucleotides. Genes psaA/psaB, psaF/psaJ and psaL/psaI are each closely linked. The open reading frames predict polypeptides of 83 kDa (subunits Ia and Ib, encoded by genes psaA and psaB, respectively), 15.4 kDa (II, psaD), 17.7 kDa (III, psaF), 8.4 kDa (IV, psaE), 8.8 kDa (VII, psaC), 4.6 kDa (VIII, psaI), 4.8 kDa (IX, psaJ), 8.5 kDa (X, psaK) and 15.5 kDa (XI, psaL). A novel subunit (XII, psaM) was also identified. Subunits II, III, IV and VII seem to be peripheral, while the others seem to be intrinsic components of the reaction center. These data imply a striking similarity of cyanobacterial and eukaryotic PSI. All subunits studied are encoded by single-copy genes which seem to be transcribed into monocistronic (psaC, psaD, psaC, psaK) or dicistronic (psaA/psaB, psaF/psaJ, psaL/psaI) RNA species. Subunit III is translated as a 17.7-kDa precursor, including a transit peptide of 23 amino acid residues. This is consistent with its location in the thylakoid lumen.
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PMID:Genes encoding eleven subunits of photosystem I from the thermophilic cyanobacterium Synechococcus sp. 848 90

The spontaneous onset of autoantibodies against circulating factors, including factors II, V, VII, VIII, IX, XI, XII, and XIII, is a phenomenon of unclear causes. It may occur in patients with no underlying disease process or may be antedated by autoimmune diseases and malignancies. The antibodies are almost always IgG and are most commonly directed at F VIII. They generally present with a bleeding diathesis in patients with no history of prior bleeding events. The laboratory abnormalities vary depending on whether the inhibitor involves the intrinsic or extrinsic pathway of coagulation, and the laboratory studies may vary depending on the technique used. Supportive measures are used initially but are generally not completely effective. Supportive measures are followed by blood products, such as recombinant human F VIII, porcine F VIII, or PCC/aPCC. There are limitations to each of these, however. If bleeding is severe and high titers of inhibitors are present, plasma-pheresis may lead to a temporary decrease in the titer but is short-lived. Immunosuppressive therapy should ultimately be attempted to suppress further antibody production. Spontaneous remission may occur with some of the inhibitors, primarily postpartum or drug related, for reasons not fully understood.
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PMID:Autoimmune coagulation disorders. 915

Systematic evaluations of anemia, thrombocytopenia, and coagulopathy are essential to identifying and managing their causes successfully. In all cases, clinicians should evaluate RBC measurements alongside WBC and platelet counts and WBC differentials. Multiple competing factors may coexist; certain factors affect RBCs independent of those that affect WBCs or platelets. Ideally, clinicians should examine the peripheral blood smear for morphologic features of RBCs, WBCs, and platelets that provide important clues to the cause of the patient's hematologic disorder. Thrombocytopenia arises from decreased platelet production, increased platelet destruction, or dilutional or distributional causes. Drug-induced thrombocytopenias present diagnostic challenges, because many medicines can cause thrombocytopenia and critically ill patients often receive multiple medications. If they suspect type II HIT, clinicians must promptly discontinue all heparin sources, including LMWHs, without awaiting laboratory confirmation, to avoid thrombotic sequelae. Because warfarin anticoagulation induces acquired protein C deficiency, thereby exacerbating the prothrombotic state of type II HIT, warfarin should be withheld until platelet counts increase to more than 100,000/microL and type II HIT is clearly resolving. The presence of a consumptive coagulopathy in the setting of thrombocytopenia supports a diagnosis of DIC, not TTP-HUS, and is demonstrated by decreasing serum fibrinogen levels, and increasing TTs, PTs, aPTTs, and fibrin degradation products. Increasing D-dimer, levels are the most specific DIC parameter and reflect fibrinolysis of cross-linked fibrin. Elevated PTs or a PTTs can result from the absence of factors or the presence of inhibitors. Clinicians should suspect factor inhibitors when the prolonged PT or aPTT does not correct or only partially corrects following an immediate assay of a 1:1 mix of patient and normal plasma. In addition to factor inhibitors, antiphospholipid antibodies (e.g., lupus anticoagulant) can produce a prolonged aPTT that does not correct with normal plasma but is overcome by adding excess phospholipid or platelets. Paradoxically, a tendency to thrombosis, not bleeding, accompanies lupus anticoagulants and the antiphospholipid antibody syndrome. Transfusion of red blood cells, platelets, or plasma products is sometimes warranted, but clinicians must carefully weigh potential benefits against known risks. In critically ill patients, administering RBCs can enhance oxygen delivery to tissues. Among euvolemic patients who do not have ischemic heart disease, guidelines recommend a transfusion threshold of HGB levels in the range of 6.0 to 8.0 g/dL; patients who have HGB that is at least 10.0 g/dL are unlikely to benefit from blood transfusion. The use of rHuEPO to increase erythropoiesis offers an alternative to RBC transfusion, assuming normal, responsive progenitor cells and adequate iron, folate, and cobalamin stores. Future research should examine whether clinical outcomes from rHuEPO use in critically ill patients are important and cost-effective. Because platelets play an instrumental role in primary hemostasis, platelet transfusions are often important in managing patients who are bleeding or at risk of bleeding with thrombocytopenia or impaired platelet function. Platelet transfusions carry risks, and decisions to transfuse platelets must consider clinical circumstances. Most important, platelet transfusions are generally contraindicated if the underlying disorder is TTP or type II HIT, because platelet transfusion in these settings may fuel thrombosis and worsen clinical signs and symptoms. Plasma products can correct hemostasis when bleeding arises from malfunction, consumption, or underproduction of plasma coagulation proteins. Choice of plasma product for transfusion depends on clinical circumstances. FFP is the most commonly used plasma product to correct clotting factor deficiencies, particularly coagulopathies that are attributable to multiple clotting factor deficiency states as in liver disease, DIC, or warfarin anticoagulation. PCC or rFVIIa that is administered in small volumes may provide advantages over FFP when coagulopathies require quick reversal without risk of volume overload. Factor concentrates can replace specific factor deficiencies. Recombinant FVIIa bypasses inhibitors to factors VIII and IX and vWF. Use of rFVIIa in managing hemostatic abnormalities from severe liver dysfunction; extensive surgery, trauma, or bleeding; excessive warfarin anticoagulation; and certain platelet disorders requires further study to determine optimal and cost-effective dosing regimens. Recombinant activated protein C reduces mortality from severe sepsis that is associated with organ dysfunction in adults who are at high risk for death (APACHE scores of at least 25). In severe sepsis, levels of protein C decrease, as do fibrinogen and platelet levels. Because of its anticoagulant effect, however, drotrecogin alfa may induce bleeding. Guidelines for drotrecogin alfa use must take into account bleeding risks.
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PMID:Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. 1471 Jun 93