Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sensitive radioimmunoassay (RIA) for the fragment that is liberated from factor X when this zymogen is activated by factor VII/VIIa-tissue factor or factor IXa was developed. Antisera were raised in rabbits to a synthetic 15 amino acid peptide containing the COOH-terminal sequence of the activation fragment coupled to bovine serum albumin with glutaraldehyde. The reactivity of the antibody population obtained toward the factor X zymogen was negligible (less than 1/36,000 that of the activation peptide on a molar basis). However, because other plasma constituents contributed to a nonspecific basal signal in the RIA, a procedure by which the peptide could be reproducibly extracted from plasma was developed. The mean level of this species in normal individuals younger than the age of 40 was 66.4 pmol/L, and elevations up to 550 pmol/L were observed in patients with evidence of disseminated intravascular coagulation. The validity of these measurements of factor X activation is supported by the fact that the RIA signal migrates on reverse-phase high pressure liquid chromatography in a manner identical to that of the native peptide and can be quantitatively recovered. The mean concentration of the activation fragment was markedly decreased to 25.7 pmol/L in patients with hereditary factor VII deficiency (P = .0001 v normal controls), whereas the mean level in subjects with factor VIII deficiency was 61.1 pmol/L (P greater than .1 v normal controls). These data indicate that the basal (ie, in the absence of thrombosis or provocative stimuli) levels of FXP under in vivo conditions result mainly from the activity of the extrinsic pathway.
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PMID:Detection of factor X activation in humans. 280 45

Factor VIII molecular complex is included in the proteins of "acute inflammation", being changed not only in the congenital diseases - hemophilia A and Willebrand disease but also in a series of acquired diseases as various inflammatory processes, hypercoagulability, DIC syndrome, neoplasms. The studies carried out on Hodgkin's disease and non-Hodgkin lymphomas reveal that the changes in its separate activities (factor VIIIK and Willebrand antigen) are not unidirectional with the changes of fibrinogen level and cannot serve as an index of the activity of the process.
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PMID:[Changes in the factor VIII molecular complex in Hodgkin's disease and non-Hodgkin's lymphoma]. 311 78

The bleeding disorder of hemophilia A currently treated by replacement therapy of the missing coagulation factor, factor VIII, is frequently complicated by the development of neutralizing antibodies. The therapeutic potential of attenuated forms of the lipid-associated glycoprotein tissue factor, a known initiator of coagulation, was investigated as a factor VIII-by-passing activity. The protein moiety of tissue factor (Apo-TF) was partially purified and exhibited minimal procoagulant activity before relipidation in vitro. In pilot studies, Apo-TF injection into rabbits previously anticoagulated with an antibody to factor VIII was found to have a procoagulant effect. The efficacy of the material was further demonstrated when injection of Apo-TF in hemophilic dogs resulted in a normalization of the cuticle bleeding time. Little or no change in the blood parameters associated with disseminated intravascular coagulation was observed at lower doses, although mild to moderate effects were seen at higher doses. These data suggest a novel role for Apo-TF preparations as a potential therapeutic agent for hemophiliacs with antibodies to factor VIII once the potential thrombogenicity of such materials is evaluated.
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PMID:Factor VIII-bypassing activity of bovine tissue factor using the canine hemophilic model. 313 99

Eleven patients with chronic subdural hematoma (CSDH) with bleeding tendency (BT) were surgically treated in the last 12 years. To study the clinical problem of CSDH with BT, 11 surgical cases were divided into 3 groups, Group A; CSDH with primary BT (1 case of hemophilia A), Group B; CSDH with BT secondary to a basic disease (3 cases of leukemia, 2 cases of malignant tumor with DIC, 1 case of chronic renal failure and 1 case of liver cirrhosis), Group C; CSDH with BT by anticoagulants (warfarin) (2 cases of replacement of mitral valve, 1 case of A-C bypass). Evacuation of the hematoma was performed by means of one or two burr holes with irrigation of the hematoma cavity and a drainage tube was placed in the subdural space. The outcome was excellent in Groups A and C. In Group B, two patients with DIC due to gastric cancer and prostatic cancer died, and 3 patients with leukemia recovered dramatically from CSDH, but the poor course of the disease itself resulted in death. The outcome of other patients in Group B was excellent. Since CSDH with BT is often fatal, those patient had usually been treated conservatively. However, from this analysis, we stress that CSDH with BT should be surgically treated after checking the blood conditions carefully to determine whether or not the patient has need for surgery.
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PMID:[Chronic subdural hematoma with bleeding tendency; clinical analysis of 11 surgical cases]. 784 20

We describe a 39 years-old male hemophilia A patient with acquired immunodeficiency syndrome (AIDS) developing to disseminated intravascular coagulation (DIC) due to gastric carcinoma. He had been diagnosed as human immunodeficiency virus (HIV) sero-positive in 1990. Since then, he has been treated by the oral administration of zidovudine (AZT), dideoxyinosine (ddI) and intravenous administration of glycyrrhizin. In September 1990, he suddenly complained abdominal pain with bloody stool. His condition deteriorated in spite of our intensive treatment for DIC. He died of multiple organ failure (MOF) due to DIC. The autopsy findings showed gastric carcinoma, defined of signet ring cell carcinoma histopathologically. But neither opportunistic infection nor other cause of DIC were observed.
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PMID:[An autopsy case of AIDS with hemophilia A who died of DIC and gastrointestinal bleeding associated with gastric carcinoma (signet ring cell carcinoma)]. 796 58

After clinical assessment, pertinent history, and family history, the clinician often has a good idea concerning the cause of a patient's bleeding. The most appropriate laboratory tests can then be ordered. Routine screening tests include a complete blood cell count, platelet count, and evaluation of a peripheral blood sample, a prothrombin time, and an activated partial thromboplastin time. Thrombocytopenia may result from idiopathic thrombocytopenic purpura, disseminated intravascular coagulation, or, less commonly, acute leukemia, aplastic anemia, thrombotic thrombocytopenic purpura, or a particular drug that a patient is taking. Again, the patient's history, physical findings, and evaluation of a well-prepared peripheral blood smear will be helpful in determining the cause of the patient's thrombocytopenia. An isolated prolongation of the activated partial thromboplastin time may result from low levels of factors VIII, IX, or XI. A slightly prolonged activated partial thromboplastin time and a moderate decrease in factor VIII may reflect von Willebrand disease or the "carrier" state for hemophilia A. In women a greatly prolonged activated partial thromboplastin time and very low levels of factor VIII (< 3%) most often result from an acquired factor VIII inhibitor (autoantibody against factor VIII) or from severe (type III) von Willebrand disease. If von Willebrand disease is suspected (because of menorrhagia with or without other mucous membrane bleeding, a positive family history, and a prolonged activated partial thromboplastin time), more specific laboratory tests for this disease should be done. These include assays of factor VIII, von Willebrand factor antigen, von Willebrand factor activity (measured by the ristocetin cofactor assay), and template bleeding time. In von Willebrand disease the defect is in von Willebrand factor. The affected individual may have subnormal levels of structurally and functionally normal von Willebrand factor (this is called "classic" or type I von Willebrand disease) or may produce von Willebrand factor that is structurally and functionally abnormal (von Willebrand disease type 2). Individuals who inherit a gene for von Willebrand disease from both parents have severe (type 3) von Willebrand disease and will have extremely low levels (< 3%) of von Willebrand factor and factor VIII and will have a very prolonged bleeding time. In most populations type I disease is the most common form, whereas type 3 is the least commonly encountered form. It should be noted that levels of von Willebrand factor can be influenced by the patient's blood type (persons who have blood type AB have 60% to 70% higher levels than do persons who have blood type O) and can be elevated during pregnancy, stress, and hyperthyroidism. The two major functions of von Willebrand factor are to serve as a "bridge" between platelets and injury sites in blood vessel walls and to protect circulating factor VIII from rapid proteolytic degradation. Thus, if a patient has either too little or functionally abnormal von Willebrand factor, the bleeding time will be prolonged and factor VIII will be decreased (because it is not being protected by von Willebrand factor). It should be determined which type of von Willebrand disease a particular patient has because treatment depends on type. Multimeric analysis of von Willebrand factor can be done with use of sodium dodecyl sulfate gels, radiolabeled antibody to von Willebrand's factor, and autoradiography. This will allow visualization of the multimeric structure of von Willebrand factor. In type I disease all bands are present, whereas in the type 2 variants 2A and 2B no high-molecular-weight multimers are seen. Desmopressin acetate (which is available in parenteral form for intravenous use and in a highly concentrated intranasal spray formulation) is the treatment of choice for classic type I disease. The drug effects a rapid release of von Willebrand factor from endothelial cell stor
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PMID:Screening and diagnosis of coagulation disorders. 882 61

Inhibitors to factor VIII (FVIII) or IX (FIX) in patients with haemophilia A or B create a challenging problem for the treatment of these patients. Recombinant FVIIa (rFVIIa; NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) is a realistic treatment option, owing to its specific mode of action and lack of immunogenicity. This was a multicentre, open-label, compassionate-use trial in patients with severe haemophilia A (FVIII:C < 1%) or B (FIX:C < 1%) with inhibitors, acquired antibodies to FVIII or FIX, or FVII deficiency (FVII:C < 5%), for whom alternative therapies had failed or were contraindicated. Patients received rFVIIa treatment for life- or limb-threatening bleeding episodes or for coverage during essential surgery. The mean rFVIIa dose was approximately 90 microg kg-1 for haemophilia A/B and acquired inhibitor patients, and 25 microg kg-1 for FVII-deficient patients. Efficacy data for 67 treatment episodes (45 bleeding episodes, 22 surgical procedures) are presented; seven patients were treated for a concurrent serious bleeding episode and surgical procedure. At the end of treatment, rFVIIa was effective or partially effective in 85% of serious bleeding episodes. During surgery, bleeding was assessed as none or less than or equivalent to normal in 91% of surgical procedures; postoperatively, 91% of procedures were associated with no or minimal oozing. During 60 separate treatment episodes, 26 adverse events (22 nonserious, four serious) were reported in 15 patients, during 17 bleeding episodes or surgical procedures. Only 10 were considered as having a possible, probable, or unknown relationship with rFVIIa; of these, fever (n=2) and thrombophlebitis (n=3) were the most common. There was no evidence of disseminated intravascular coagulation. In conclusion, rFVIIa is an effective, well-tolerated treatment for serious bleeding episodes and bleeding associated with surgical procedures in patients with severe haemophilia A/B with inhibitors, acquired inhibitors, or FVII deficiency.
Haemophilia 1999 Jul
PMID:Recombinant factor VIIa for patients with inhibitors to factor VIII or IX or factor VII deficiency. 1046 79

Hemophilia A is the most severe of the inherited bleeding disorders. Otolaryngologists are frequently asked to assist in the care of a patient with this disorder who has intractable bleeding from sites in the head and neck. This disorder is transmitted in an X-linked recessive manner and results from factor VIII deficiency. Factor replacement therapy has contributed much to the management of acute bleeding episodes and the prevention of long-term sequelae in patients with hemophilia. A consequence of factor replacement therapy that occurs in as much as 16% of patients is the development of antibodies to the exogenous factor. These antibodies inactivate any supplemental factor VIII, resulting in continued bleeding despite attempts at replacement therapy. This poses an extremely challenging clinical problem because other standard therapies have had limited usefulness. Activated prothrombin complex has been shown to be efficacious in the treatment of patients with inhibitors. This has led to the production of factor VIII inhibitor bypassing activity (FEIBA), which contains activated forms of factors II, VII, IX, and X. The mechanism of action of this preparation remains unknown, but it seems to bypass the need for factor VIII in the clotting cascade. Factor VIII inhibitor bypassing activity is not as effective as factor VIII concentrates in patients with normally responsive hemophilia, and patients with low inhibitor levels may be given larger doses of factor VIII. Disseminated intravascular coagulation is most often mentioned as a potential complication of the administration of factor VIII inhibitor bypassing activity, although it has been rarely reported. Otolaryngologists should be familiar with this clinical phenomenon and understand its implications. Two patients with bleeding diatheses were recently treated at our institution.
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PMID:Manifestations of factor VIII inhibitor in the head and neck. 1055 99

To examine the safety profile of products used to treat inhibitor patients unresponsive to factor VIII, a review of published clinical experience was performed. The products evaluated were activated prothrombin complex concentrates (aPCCs), such as AUTOPLEX T, porcine factor VIII and recombinant activated factor VII (rVIIa). Safety characteristics included potential for transmission of infectious agents, anamnesis, thrombogenicity, thrombocytopenia and allergic reactions. While viral transmission has been virtually eliminated, the risk is theoretically higher with plasma-derived products such as aPCC and porcine factor VIII than with rVIIa, although contamination of cultured cells is a concern. Anamnesis occurs with aPCCs and porcine factor VIII, and may induce resistance to further therapy with porcine factor VIII. Thrombosis and disseminated intravascular coagulation are very infrequently reported in patients exposed to aPCCs and rVIIa, and never with porcine factor VIII. The latter is occasionally associated with thrombocytopenia, but this uncommonly limits treatment with this agent. Lastly, allergic reactions occur with about equal frequency with all products, but anaphylaxis is mainly a concern after administration of porcine factor VIII. In conclusion, products currently available are reasonably safe. Considerations such as efficacy, availability, ease of administration and cost must also be considered in making treatment choices.
Haemophilia 1999 Sep
PMID:Complications associated with the treatment of haemophiliacs with inhibitors. 1059 83

Haemophilia patients with inhibitors are treated for acute bleeding with prothrombin complex concentrates (PCCs) or activated prothrombin complex concentrates (aPCCs). Despite this therapy, patients with high-level inhibitors are at increased risk of developing devastating joint disease. This paper examines available information that supports the study of PCCs and/or aPCCs as prophylactic therapy for haemophilia patients with inhibitors. This strategy would require that PCCs or aPCCs be administered repetitively in a dose that is sufficient to prevent haemarthrosis without causing thrombogenic events, or causing anamnestic response in inhibitor titre. PCC doses ranging from 30 to 50 U kg-1 every other day for up to 8 months have resulted in subjective improvement both in bleeding associated with target joints and in the management of chronic joint inflammation. aPCC doses as low as 50-100 U kg-1 every other day have been useful in postsurgical prophylaxis. The risk of developing a myocardial infarction or clinically relevant disseminated intravascular coagulation is linked to total dosages of either PCCs or aPCCs greater than 200 U kg-1 day-1. It is uncertain what anamnestic response would result from prophylaxis, but with typical therapy the aPCCs cause such a response in only a small percentage of patients. Based on these findings, a clinical trial of these products used in doses of 50-100 U kg-1 every other day would appear to be warranted in patients who have permanent inhibitors and frequent joint bleeding.
Haemophilia 1999 Sep
PMID:Use of prothrombin complex concentrates and activated prothrombin complex concentrates as prophylactic therapy in haemophilia patients with inhibitors. 1059 85


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