Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Veno occlusive disease (VOD) is a frequent complication of allogenic bone marrow transplantation (BMT) for which no predictive blood markers are available. 39 patients grafted for severe aplastic anemia (18), and leukemia (21) were prospectively studied. Of the 39 patients, 5 leukemic patients, but no aplastic patients developed VOD. In all the 5 patients with VOD complications we demonstrated a decrease in factor VII and in protein C before the clinical onset of the disease and before any changes in hepatic enzymes were observed. This decrease is the earliest sign of hepatic involvement by the VOD suggesting that the determination of Factor VII and protein C can be used as a prediction test to identify the patients who are at risk of developing VOD after transplantation. In addition, a toxicity of the endothelial cells was suggested by the observed increase in von Willebrand factor and in Serum Angiotensin Converting Enzyme. Signs of endothelial toxicity was more pronounced in leukemic than in aplastic patients.
 ...
PMID:Liver veno-occlusive disease after bone marrow transplantation changes in coagulation parameters and endothelial markers. 132 36

We tested an in vitro system simulating bleeding time reported by Kratzer et al. Primary hemostasis was studied perfusing an artificial vessel with citrated blood under a constant pressure of 40 mmHg, measuring the blood volume perfused (bleeding volume) and the time until blood flow stopped (bleeding time). The artificial vessel consists of a glass capillary simulating arteriole and a filter covered with collagen type I to provide a surface for the adhesion of platelets. The bleeding volume (mean +/- SD microliters) was 317.7 +/- 93.8 in controls (n = 19), 487.3 +/- 242.1 in idiopathic thrombocytopenic purpura (n = 9), 666.8 +/- 224.1 in aplastic anemia and paroxysmal nocturnal hemoglobinuria (n = 4), greater than 820 in von Willebrand's disease (n = 3), 231.0 +/- 74.5 in hemophilia A (n = 3), 499.0 +/- 269.4 in liver cirrhosis (n = 6), and 457.7 +/- 229.0 in myeloproliferative disorders (n = 11). When citrated blood was applied to this system after incubation with monoclonal antibodies (MoAb) to von Willebrand factor or platelet membrane glycoprotein Ib (GPIb), bleeding volume was significantly increased while no effects were observed after incubation with MoAb to GPIIb/IIIa, factor VIII: CAg and factor XIIIa. These data suggest that in vitro model of primary hemostasis could be used for not only diagnosing bleeding disorders although 'time' is not reliable, but also investigating the mechanisms of hemostasis.
 ...
PMID:[Bleeding time and volume in vitro by THROMBOSTAT]. 231 3

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

There is some clinical evidence that cyclosporine A (CyA) is associated with thrombotic complications of bone marrow and renal transplantation. We investigated plasma concentrations of lipoprotein(a) [Lp(a)], a potentially atherothrombotic lipoprotein, and hemostatic and vascular status in ten patients with aplastic anemia receiving CyA, eleven patients not taking it, and 38 age-matched healthy controls. Patients receiving CyA had significantly higher concentrations of plasma fibrinogen (P < 0.05), prothrombin fragment 1 + 2 (F1 + 2; P < 0.05), plasminogen activator inhibitor-1 (PAI-1; P < 0.05), and von Willebrand factor antigen (P < 0.05) than did patients not taking CyA. Plasma concentrations of Lp(a) were higher in CyA-treated patients than those not receiving it (P < 0.05) or healthy controls (P < 0.05). The difference in the Lp(a) concentration between controls and patients who did not receive CyA-treatment was not significant. Our results suggest that hypercoagulability is likely to occur during CyA therapy. Further, the presence of high concentrations of Lp(a) may accelerate the process of atherosclerosis and increase thrombotic events in patients receiving long-term CyA.
 ...
PMID:Hypercoagulability and high lipoprotein(a) levels in patients with aplastic anemia receiving cyclosporine. 889 50

Twenty-eight adolescents with menorrhagia by pictorial blood loss assessment chart (PBAC) criteria were investigated for underlying hemostatic defect. CBC, ABO blood group, bleeding time, APTT, PT, TT FVIII:C, VWF:Ag, RiCoF and platelet aggregation study were evaluated. Six patients (21.4%) were addressed with underlying hemostatic defect. Of these, severe aplastic anemia (n=1) and thrombotic thrombocytopenicpurpura (n=1) were identified in 2 patients with low platelets after an initial CBC. Four patients with prolonged bleeding time demonstrated inherited hemostatic defect: von Willebranddisease (VWD) type 3 (n=1), Glanzmann thrombasthenia (n=1) and Bernard-Soulier syndrome (n=2). Median PBAC score of patients with hemostatic defect was significantly higher than that of patients with unknown cause of menorrhagia (436.5 vs. 251.3, p = 0.01). After the exclusion of six patients with well-identified bleeding risks, isolated abnormal platelet aggregation response to adrenaline was detected in 11 (50%) adolescents using platelet aggregation study. No significant difference of median PBAC score was noted among patients with and without evidence of this impaired responsiveness to adrenaline. In addition, the authors also found an abnormal platelet aggregation with adrenaline stimulant in 15 (75%) among 20 healthy female controls who had no history of bleeding diathesis. No significant difference infrequency of abnormal platelet aggregation to adrenaline was observed between affected cases and controls. In summary, an impaired responsiveness of platelets to adrenaline in the present study is insufficient to support its risk of bleeding. On the contrary, the simple test such as CBC and bleeding time revealed a worthy contribution to investigate coexisting coagulopathy in adolescents with menorrhagia.
 ...
PMID:Hemostatic defects in Thai adolescents with menorrhagia. 2046 86