Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

avWD is a rare entity that is primarily associated with lymphoproliferative disorders, most commonly with multiple myeloma, lymphoma, and the myeloproliferative diseases. Various pathogenetic mechanisms have been postulated. The most commonly seen is antibodies directed against the FVIII complex, resulting in either its accelerated destruction or its accelerated clearance by the reticuloendothelial system. There may be immunoadsorption of the FVIII complexes onto the clones of malignant cells, as has been reported in several cases, or proteolysis may be causing the peripheral destruction of the FVIII complex. Lastly, as seen in hypothyroidism, global decrease in production of the multimers also results in avWD. The treatment, in general, should be aimed at controlling the underlying disorder and at stopping any life-threatening hemorrhage. The treatment includes any or all of the following: DDAVP, cryoprecipitate, FVIII concentrates, extracorporeal immunoadsorption, and chemotherapy as needed to control the underlying disorders. The screening tests that will allow for the detection of the avWD include measurement of the bleeding time, the FVIII:C, FVIII:vWF, and the FVIII:RCoF. FVIII:C inhibitors can be demonstrated by mixing the patient plasma with normal plasma. A normal prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) are expected. Clinically, these patients present with mucosal bleeding, and in avWD tend to have an association with lymphoproliferative malignancies. They tend to be elderly patients with no prior history of bleeding diathesis and to have negative family histories for coagulopathies. Further study of these patients is warranted, because this disorder appears to have a multifactorial etiology. Increasing our understanding of avWD may increase our understanding of congenital vWD, thus allowing us to more effectively treat all patients with von Willebrand's disease.
...
PMID:Acquired von Willebrand's disease. 145 20

Ageing does not bring with it any major changes in the coagulation or fibrinolytic proteins or platelets. It does bring a greater burden of disease, with less reserves, and so when haemorrhage occurs in the elderly it has more serious consequences. The cause of a bleeding diathesis can usually be determined after a careful history, and examination of the patient followed by simple tests--the platelet count, blood film, bleeding time, prothrombin time, partial thromboplastin time, thrombin time, fibrin degradation products and the euglobulin clot lysis time. Other confirmatory tests, assays and inhibitor titres, will seal the diagnosis. Treatment is mainly directed at removing the underlying cause, if possible, and remedying the defect, with platelet transfusion, fresh frozen plasma or factor concentrates. These treatments will not be effective where there is an inhibitor or antibody present; steroids, splenectomy (for ITP), plasma exchange or immunosuppression are needed. Two major advances have occurred in the early 1980s. One has been the introduction of high-dose intravenous immunoglobulin in the management of ITP, although worries remain about thrombotic events in elderly patients. The other is the spreading use of DDAVP, originally introduced for von Willebrand's disease and mild haemophilia, and now finding a role in uraemia and with cardiopulmonary bypass. Drugs are a significant and potentially preventable cause of bleeding in the elderly. The most frequent problems arise with anticoagulants. The risk of interactions increase with the number of other medications which are prescribed.
...
PMID:Bleeding and coagulation disorders in the elderly. 332 49

The prolonged partial thromboplastin time observed in the plasma of a 36 year old asymptomatic man was related to the reduced prekallikrein activities (coagulant; antigenic; and amidolytic) and the absence of coagulant and immunologic activities of high molecular weight kininogen (HMWKg). The patient's plasma also exhibited impaired surface-mediated fibrinolysis and impaired generation of kallikrein. The coagulation defect was identified as the "Fitzgerald trait". The levels of CH50, C2, C4 and C-1 inactivator were normal. Venous occlusion in the patient gave rise to a normal release of extrinsic plasminogen activator from the vascular endothelium. The administration of DDAVP led to a FVIII/VWF response which was similar to that obtained in healthy subjects. No alteration could be observed in the contact phase proteins after DDAVP administration.
...
PMID:New congenital deficiency of high molecular weight kininogen and prekallikrein (Fitzgerald trait). Study of response to DDAVP and venous occlusion. 363 67

Desmopressin acetate 0.3 microgram/kg was given intravenously to nine patients with chronic liver disease and to a further six such patients in a double blind controlled study versus placebo. Desmopressin acetate significantly shortened the bleeding time compared with basal values in both groups and compared with placebo. There was also a significant decrease in partial thromboplastin time (but not prothrombin time) and significant increases in factor VIII and its components, von Willebrand factor and ristocetin cofactor activity, but not in factors VII, IX, X, XI, or XII. Increased fibrinolysis could be blocked by concomitant administration of tranexamic acid. No important side effects were seen. The multimer pattern of von Willebrand factor was studied for the first time in chronic liver disease. It was normal, but after administration of desmopressin acetate the percentage of multimers of higher molecular weight increased significantly. This may be an important mechanism in the shortening of the bleeding time in cirrhosis, as has been shown in uraemia and other conditions after administration of desmopressin acetate. Desmopressin acetate may be useful in correcting defects in primary haemostasis in chronic liver disease.
...
PMID:Desmopressin and bleeding time in patients with cirrhosis. 393 77

Von Willebrand's disease (vWD) is the most common inherited bleeding disorder. Typical clinical features such as bleeding after surgery or trauma might suggest the disease. We present a series of 24 patients with vWD treated between 1989 and 1992. Diagnosis was confirmed by a reduction in plasma factor VIII antigen concentration, reduction of ristocetin cofactor activity and reduced factor VIII activity. Seventeen of the patients underwent surgery (7 adenoidectomies, 8 tonsillectomies, 2 paranasal sinus operations) and received preoperative stimulation of von Willebrand factor (vWF) using DDAVP. This resulted in a rapid increase in plasma vWF concentration from an average of 56% before stimulation to 190% of the normal value after stimulation. A reduction of partial thromboplastin time from an average of 44.4 seconds to 34.4 seconds was observed following DDAVP. No bleeding complications or other side-effects occurred. Preoperative stimulation of vWF using DDAVP proved to be a safe method to reduce the risk of bleeding in patients with vWD undergoing surgery.
...
PMID:[Von Willebrand syndrome--risk of hemorrhage in ENT interventions in childhood]. 806 Apr 55

We report a family with a combined factor VII Padua defect and von Willebrand's disease (vWd). The propositus is a 9-year-old child with a moderate bleeding tendency who appeared to be heterozygous for both factor VII Padua and type I vWd. The diagnosis of factor VII Padua was based on a normal factor VII antigen and factor VII activity which was low with rabbit brain thromboplastin but normal with ox brain thromboplastin. Type I vWd was diagnosed because of a concomitant decrease of von Willebrand factor antigen (vWf:Ag) and vWf ristocetin-cofactor activity (vWf:RCoF), associated with the presence of vWf multimers of all sizes in plasma and platelets. The parents were not consanguineous but came from the same isolated river Piave valley in North Eastern Italy where the factor VII Padua defect was first described. The father had the factor VII Padua defect but was clinically asymptomatic in accordance with the heterozygous state. The propositus's mother had type I vWd and was mildly symptomatic. The propositus' sisters, who were clinically asymptomatic, were both heterozygotes for factor VII Padua. The infusion of DDAVP normalized the factor VIII/vWf pattern in all patients. In the propositus, in contrast to the mother and normal subjects, showed a more rapid clearance both of vWf and factor VIII. The same pattern, albeit to a lesser degree, was also observed in the father.
...
PMID:First report of combined factor VII Padua defect and von Willebrand's disease due to casual association of the two defects. 845 48

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
...
PMID:Screening and diagnosis of coagulation disorders. 882 61

In our patients, haemophilia A was observed in German shepherd dogs and Siberian huskies. Frequently occurring clinical symptoms were excessive bleeding from the gums, when getting adult teeth, and haematomas in the regions of the proximal hindleg, the knee joint as well as the chest or abdominal wall, respectively. The activated partial thromboplastin time (aPTT) as a screening test of the intrinsic coagulation system reflects sensitively also a mildly reduced factor VIII:C activity which may be present for example during substitution therapy. Therefore, the aPTT is well suited for screening for haemophilia A. In haemophilic dogs suffering from hypovolaemic shock due to a considerable acute blood loss, besides the aPTT also the prothrombin time and partly the platelet number were beyond the respective reference range due to loss and consumption of coagulation factors and thrombocytes. For substitution therapy, fresh frozen plasma was used in the first line. Administered at a dose of 15 or 20 ml/kg BW, it caused an increase of factor VIII:C activity by 20 or 33%, respectively. 24 hours after the end of infusion the mean of the remaining activity increase in comparison with the value measured immediately after substitution was 27%. The fast, biphasic elimination of factor VIII:C in some cases required a repeated application until clinical recovery. Desmopressin acetate given at a dose of 1 microgram/kg KGW intravenously or subcutaneously to two dogs each did not cause a distinct increase of the factor VIII:C activity, and is, therefore, not an efficacious supplementary therapy to substitution therapy in haemophilic dogs.
...
PMID:[Hemophilia A in the dog: symptoms, blood coagulation analysis and treatment]. 900 37

As in adults, desmopressin (DDAVP) can be used in children for prophylaxis of bleeding and to stop bleeding in many hereditary and acquired bleeding disorders. DDAVP is the treatment of choice in children with mild hemophilia and type 1 von Willebrand's disease (vWD). It is effective in some variants of vWD and in many patients with platelet function defects. It reduces the bleeding diathesis of children with uremia and drug-induced bleeding complications. In any case, a test dose of DDAVP has to be given to the patient to predict the hemostatic effect before relying on this drug for treatment. The response can be measured by shortening of the bleeding time (BT) and of partial thromboplastin time (PTT), indicating a rise of Factor (F) VIII or von Willebrand factor (vWF). Side effects such as facial flushing, transient headache, increased pulse rate, and drop in systolic blood pressure are mild and transient. They can be minimized when the dose is not exceeding 0.3 microg/kg body weight, and the infusion lasts at least 20 to 30 minutes. The strong antidiuretic action of DDAVP has some potential problems that are negligible in adults and older children when water intake is restricted. In infants and small children under the age of 18 months, however, DDAVP should be used with caution and with close surveillance in order to prevent water intoxication and electrolyte imbalance. The danger is increased when the patients receive parenteral fluid substitution. The advantages of DDAVP include the reduction in the use of plasma factor concentrates, thereby minimizing the danger of immunological or infectious complications, as well as the considerable reduction of costs realized by treatment with this form of medication. Fortunately, it can be applied successfully in the most frequent hereditary bleeding disorder, namely vWD type 1.
...
PMID:Desmopressin (DDAVP) in bleeding disorders of childhood. 1006 51

We tested the response to desmopressin (1-deamino-cys-8-D-arginine-vasopressin; DDAVP) in four patients with haemophilia B [factor IX (F IX) at diagnosis 1.4-5%]. The activated partial thromboplastin time (aPTT) was significantly shortened in all patients. Although there was an up to 1.4-fold increase in F IX levels in three patients, maximal F IX activity remained below 10%. Much more prominent were the increases in F VIII (three- to fourfold), in von Willebrand factor antigen (VWF:Ag; 2.5-fold) and particularly in VWF collagen-binding activity (VWF:CBA; fivefold). These changes were reflected by the prophylactic efficacy of DDAVP for dental surgery. After pretesting, DDAVP could be a useful drug for reducing the need for plasma products for prevention of minor surgical bleeding in patients with mild to moderate haemophilia B.
...
PMID:DDAVP (desmopressin; 1-deamino-cys-8-D-arginine-vasopressin) treatment in children with haemophilia B. 1155 8


1 2 Next >>

---