losartan-potassium and Hemorrhagic-Disorders

Anemia is a frequent complication of renal failure. As in anemias of other origin, the resulting tissular hypoxia is partially compensated by an increased production of 2,3-diphosphoglycerate in red cells and a shift to the right of the oxygen hemoglobin dissociation curve. Two mechanisms are implicated in this anemia: increased hemolysis and depressed production of red cells. Decreased production of erythropoietin is probably the cause of reduced erythropoiesis, but the role of uremic intoxication has not been unequivocally excluded. In the course of chronic hemodialysis, iron deficiency anemia and occasionally hypersplenism develop. It is noteworthy that blood requirements in anephric patients are two to three times greater than those of nonanephric hemodialyzed patients. Accordingly, bilateral nephrectomy should be restricted to carefully selected cases. At the present time, androgens seem to be the best treatment of renal anemia. Qualitative anomalies of platelets are the main factor responsible for uremic bleeding and are corrected by hemodialysis.

Topics: Anemia; Animals; Cell Survival; Erythrocytes; Erythropoiesis; Erythropoietin; Hematologic Diseases; Hemolysis; Hemorrhagic Disorders; Humans; Kidney Failure, Chronic; Kidney Transplantation; Renal Dialysis; Transplantation, Homologous; Uremia

Recombinant human erythropoietin may improve hemostasis of uremic patients by correcting anemia. However, a complete correction of renal anemia carries the risk of hypertension, encephalopathy, thrombosis, and hyperkalemia. Our aim was to establish the minimum level of packed cell volume (PCV) achieved with recombinant human erythropoietin that corrects the prolonged bleeding time in uremia. Twenty patients with chronic renal failure, anemia, and very prolonged bleeding time (greater than or equal to 15 minutes) were randomly allocated to erythropoietin or no specific treatment. The initial dose of erythropoietin was 50 U/kg intravenously (IV) three times a week. Every 4 weeks, the dose was increased by 25 U/kg until a normalization of bleeding time was achieved. Erythropoietin at a dose ranging from 150 to 300 U/kg/wk induced an increase in PCV to a range of 27% to 32% in all patients but one, and normalized bleeding time in all patients. A significant negative correlation (r = 0.898, P less than 0.001) was found between PCV and bleeding time measurements. Erythropoietin also significantly (P less than 0.01) increased values for red blood cell (RBC) distribution width (basal, 11.3 +/- 0.6; 12 weeks, 13.1 +/- 1.3). Platelet count and platelet function parameters did not significantly change. In untreated patients, no changes were recorded in all the parameters considered. These results establish in a controlled fashion that erythropoietin shortens bleeding time of uremic patients and indicate that a partial correction of renal anemia is enough to normalize bleeding time.

Topics: Adult; Aged; Bleeding Time; Erythropoietin; Female; Hematocrit; Hemorrhagic Disorders; Humans; Male; Middle Aged; Platelet Count; Prothrombin Time; Recombinant Proteins; Thromboxane B2; Uremia

We report here the interesting case of a 76-year-old man with severe proteinuria who was diagnosed with systemic mastocytosis accompanied by a clonal non-mast-cell lineage haematological disorder (a non-secretory plasma cell dyscrasia). This is a unique report of systemic mastocytosis with a non-secretory plasma cell dyscrasia and nephrotic syndrome. The pathophysiological relevance between these entities along with the probability of occult amyloidosis is discussed.

Topics: Aged; Amyloidosis; Anemia; Biopsy; Bone Marrow; Clone Cells; Coloring Agents; Congo Red; Darbepoetin alfa; Drug Therapy, Combination; Erythropoietin; Factor X Deficiency; Gingiva; Hemorrhagic Disorders; Histamine Antagonists; Humans; Male; Mastocytosis, Systemic; Nephrotic Syndrome; Paraproteinemias; Prednisone; Proteinuria; Splenectomy; Splenomegaly; Subcutaneous Fat

Impaired platelet function and a bleeding tendency are well-recognized complications of chronic renal failure. Because the fibrinogen receptor GPIIb-IIIa plays a central role in platelet aggregation and adhesion to the subendothelium, it was reasoned that a defect in this receptor may underlie the impaired platelet function in uremia. To test this hypothesis, the function of this receptor in the platelets of 11 uremic patients was studied. Aggregation studies were performed with flow cytometric techniques with anti-GPIIb-IIIa conformation-specific monoclonal antibodies (mAb) (anti-LIBS1 and anti-PMI-1). Antifibrinogen and antithrombospondin mAb were used to characterize fibrinogen binding to GPIIb-IIIa and the release of alpha-granules, respectively. Platelets from patients with chronic renal failure showed significantly decreased binding of conformation-dependent anti-LIBS1 mAb after ADP, phorbol myristate acetate, or RGD-peptide stimulation compared with normal controls, suggesting a defect related to the ability of the fibrinogen receptor to undergo a conformational change. Moreover, antifibrinogen and antithrombospondin binding to activated platelets were reduced in uremic patients, implying impairment of both ligand-binding and alpha-granule release. Hemodialysis partially restored GPIIb-IIIa function, which may account for the observed effects of this therapy in restoring platelet aggregation. These findings indicate that platelets of patients with chronic renal failure reveal an aggregation defect at least partially due to an intrinsic GPIIb-IIIa dysfunction and the presence of a putative uremic toxin that inhibits fibrinogen binding to GPIIb-IIIa.

Topics: Adenosine Diphosphate; Amino Acid Sequence; Antibodies, Monoclonal; Epitopes; Erythropoietin; Female; Fibrinogen; Flow Cytometry; Hemorrhagic Disorders; Humans; Kidney Failure, Chronic; Male; Molecular Sequence Data; Oligopeptides; Platelet Aggregation; Platelet Membrane Glycoproteins; Protein Binding; Protein Conformation; Recombinant Proteins; Renal Dialysis; Tetradecanoylphorbol Acetate

Topics: Acute Disease; Erythropoietin; Feeding and Eating Disorders; Heart Failure; Hemorrhagic Disorders; Humans; Hypertension; Peripheral Nervous System Diseases; Renin; Uremia; Vomiting