deamino-arginine-vasopressin and Uremia

Uremic bleeding syndrome is a recognized consequence of renal failure and can result in clinically significant sequelae. Although the pathophysiology of the condition has yet to be fully elucidated, it is believed to be multifactorial. This article is a review of both the normal hemostatic and homeostatic mechanisms that operate within the body to prevent unnecessary bleeding, as well as an in-depth discussion of the dysfunctional components that contribute to the complications associated with uremic bleeding syndrome. As a result of the multifactorial nature of this syndrome, prevention and treatment options can include one or a combination of the following: dialysis, erythropoietin, cryoprecipitate, desmopressin, and conjugated estrogens. Here, these treatment options are compared with regard to their mechanism of action, and onset and duration of efficacy. An extensive review of the clinical trials that have evaluated each treatment is also presented. Lastly, we have created an evidence-based treatment algorithm to help guide clinicians through most clinical scenarios, and answered common questions related to the management of uremic bleeding.

Topics: Deamino Arginine Vasopressin; Erythropoietin; Estrogens, Conjugated (USP); Evidence-Based Medicine; Factor VIII; Fibrinogen; Hemorrhage; Humans; Practice Guidelines as Topic; Renal Dialysis; Renal Insufficiency; Uremia; von Willebrand Factor

Topics: Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Blood Coagulation Disorders; Blood Loss, Surgical; Cardiac Surgical Procedures; Contraindications; Deamino Arginine Vasopressin; Estrogens, Conjugated (USP); Hemorrhage; Hemostatics; Humans; Safety; Tranexamic Acid; Uremia

Topics: Blood Platelets; Combined Modality Therapy; Cryotherapy; Deamino Arginine Vasopressin; Endothelium, Vascular; Estrogens; Hemorrhage; Humans; Kidney Transplantation; Peritoneal Dialysis; Renal Agents; Renal Dialysis; Uremia; von Willebrand Factor

The pathogenesis, clinical manifestations, and management of uremic bleeding are discussed, and the role of pharmacologic intervention in the treatment of this disorder is emphasized. Care of the patient with uremia is frequently complicated by spontaneous, life-threatening bleeding episodes. Although not completely elucidated, this bleeding tendency may be associated with ineffective binding of the von Willebrand Factor (a component of factor VIII) to platelet membranes, acquired storage-pool deficiency, and anemia. Uremic patients may develop a number of clinical manifestations, including epistaxis, purpura, and bleeding from the gastrointestinal tract. Dialysis, while frequently effective for the short term, does not completely correct platelet dysfunction. Red-blood-cell transfusions may partially reduce bleeding time; however, their use places the patient at risk for viral infection. Cryoprecipitate is often used in acute situations because of its short onset of action. Desmopressin is likewise effective when an immediate effect is desired. Conjugated-estrogen therapy appears beneficial for patients in whom a long-lasting effect is desired. Management of uremic bleeding may include dialysis, red-blood-cell transfusions, cryoprecipitate, desmopressin, and conjugated estrogens. Adverse effects, particularly the risk of viral infection, as well as duration of action, must be considered in therapy selection.

Topics: Blood Transfusion; Deamino Arginine Vasopressin; Estrogens, Conjugated (USP); Hemorrhage; Humans; Renal Dialysis; Uremia

Renal insufficiency is associated with a bleeding tendency. Hemorrhagic manifestations are usually mild (i.e., ecchymoses or purpura) but can be severe in occasional patients who may have gastrointestinal tract or intracranial bleeding. Modern techniques for the management of uremia have definitely reduced the incidence of severe bleeding episodes in patients with renal failure, but hemorrhages still represent a major clinical problem, particularly for patients undergoing surgery or invasive procedures. Although the pathogenesis of uremic bleeding has not been completely elucidated, in the past 10 years a number of studies have contributed substantially to our knowledge of the cause of uremic bleeding tendency and have indicated new therapeutic strategies. The present review will focus mainly on modern concepts of the cause of uremic bleeding and will critically analyze the various therapeutic approaches.

Topics: Aspirin; Blood Platelet Disorders; Deamino Arginine Vasopressin; Estrogens; Hemorrhage; Humans; Uremia

Since the pressor and antidiuretic properties of the native hormone were characterized, chemists have been working to synthesize vasopressin analogues selective for particular biologic activities. Desmopressin has had the longest clinical track record. Subsequently, three more analogues have been formulated and have found specific clinical application. Their actions and uses are reviewed.

Topics: Blood Platelet Disorders; Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Diabetes Insipidus; Hemophilia A; Humans; Liver Cirrhosis; Uremia; von Willebrand Diseases

Topics: Anemia; Aspirin; Bleeding Time; Blood Platelets; Blood Transfusion; Cryoprotective Agents; Deamino Arginine Vasopressin; Erythrocyte Transfusion; Erythropoietin; Estrogens; Hemorrhage; Humans; Parathyroid Hormone; Platelet Adhesiveness; Platelet Aggregation; Thromboxane A2; Uremia; von Willebrand Factor

Desmopressin (1-deamino-8-D-arginine vasopressin, abbreviated DDAVP) is a synthetic analogue of the antidiuretic hormone L-arginine vasopressin. Because it can raise circulating levels of factor VIII coagulant activity (FVIII) and von Willebrand factor and shorten the prolonged bleeding time, DDAVP is established as a nontransfusional form of treatment for mild and moderate hemophilia and von Willebrand disease. Recently, DDAVP has also been purported to be useful for shortening the prolonged skin bleeding times that occur with uremia, cirrhosis, and platelet dysfunctions of various etiologies. Finally, there is evidence from controlled clinical trials that DDAVP can reduce blood loss and transfusion requirements for hemostatically normal individuals undergoing spinal fusion surgery and for patients undergoing cardiopulmonary bypass surgery. The purpose of this report is to review the therapeutic applications of DDAVP in congenital and acquired bleeding disorders and to discuss areas in which further basic and clinical research is needed.

Topics: Blood Coagulation Disorders; Deamino Arginine Vasopressin; Hemophilia A; Humans; Tachyphylaxis; Uremia; von Willebrand Diseases

At this time, when the acquired immunodeficiency syndrome, hepatitis, and other blood-borne diseases threaten patients, with bleeding disorders, who need treatment with blood products, it is rewarding to realize that a number of them can be safely and effectively treated through the stimulation of their own VIII:C and vWF production with desmopressin. Desmopressin is clinically useful for treatment of patients with moderate and mild hemophilia. The limits of the clinical indications are the nature of the bleeding episode, the resting factor level, the level that must be achieved, and the length of time the level must be maintained to manage any given bleeding episode. Desmopressin can be used more extensively to raise VIII:C in von Willebrand's disease, than in classic hemophilia, because fewer of the patients have the severe form of the disease that is unresponsive to desmopressin. VIII:C increases to about four times the resting values that can be expected in both hemophilia and von Willebrand's disease, but it must be kept in mind that the range of individual responses is large. Even though it is not easy to correct the prolonged bleeding time, particularly in patients with dysfunctional vWF, this drawback is of clinical importance for only a minority of cases. Use of desmopressin in acquired diseases of primary hemostasis has been proposed more recently, and our experience is more limited than for congenital bleeding disorders. Uremia is probably the most firmly established indication, because the bleeding time is often dramatically shortened by desmopressin, and hemorrhages can be stopped or prevented. The indications for the compound in liver cirrhosis and congenital and acquired platelet dysfunctions are promising but much less well-established. The mechanism of action of desmopressin is not well-known, and more work must be done to fill this important gap. This problem is not only of theoretical importance, because understanding of the mechanism of action of the compound should open up new perspectives into understanding the physiological mechanisms that regulate hemostasis. Many unclarified aspects of the mechanism of desmopressin action might be elucidated by using specific antagonists and also by using appropriate animal models. (Dogs and primates respond partially to desmopressin, but rats and rabbits do not respond at all).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Deamino Arginine Vasopressin; Factor VIII; Hemophilia A; Hemorrhagic Disorders; Humans; Uremia; von Willebrand Diseases

At a time when the acquired immunodeficiency syndrome as well as hepatitis and other blood-borne diseases are a threat to patients with bleeding disorders who need treatment with blood products, it is rewarding to realize that a number of these patients can be safely and effectively treated with their own desmopressin-stimulated F.VIII:C and vWF. Desmopressin is clinically useful for treatment of patients with moderate and mild hemophilia. The limits of the clinical indications are established by the nature of the bleeding episode, the resting factor level, the level that must be achieved, and the length of time the level must be maintained to manage any given bleeding episode. In von Willebrand disease, desmopressin can be used more extensively to raise F.VIII:C levels than in classic hemophilia, because fewer of the patients have the severe form of the disease that is unresponsive to desmopressin. Increases in the level of F.VIII:C of about four times the resting value can be expected both in hemophilia and von Willebrand disease, but it must be borne in mind that the range of individual responses is large. Even though it is not easy to correct the prolonged bleeding time, particularly in patients with dysfunctional vWF, this drawback is of clinical relevance only in a minority of cases. A role for the use of desmopressin in acquired diseases of primary hemostasis has been proposed more recently, and experience is more limited than in congenital bleeding disorders. Uremia is probably the most firmly established indication because it has been shown that the bleeding time is often dramatically shortened by desmopressin, and hemorrhages can be stopped or prevented before surgical procedures. The indications for use of the compound in liver cirrhosis and congenital and acquired platelet dysfunctions are promising but much less established from a clinical standpoint. The bulk of available clinical experience is based on intravenous administration. Intranasal and subcutaneous administration have been successfully attempted and might be more convenient in selected circumstances, such as home treatment and the stimulation of blood donors to provide more abundant supplies of F.VIII:C and vWF. However, the responses after intranasal administration are less predictable and consistent than after intravenous administration. Desmopressin has few troublesome side-effects. Mild facial flushing, a small increase in heart rate, and, more rarely, mild headache can occur t

Topics: Administration, Cutaneous; Administration, Intranasal; Amino Acid Sequence; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Endothelium; Factor VIII; Fibrinolysis; Hemophilia A; Hemostasis; Humans; Injections, Intravenous; Tachyphylaxis; Uremia; von Willebrand Diseases; von Willebrand Factor

Uremia is associated with platelet dysfunction and can cause a bleeding tendency resulting in a major bleeding event after an invasive procedure or surgery that may be aggravated by antiplatelet agents. We prospectively investigated the potential of desmopressin to improve platelet dysfunction and to lower bleeding risk after emergent invasive procedures in uremic patients taking antiplatelet drugs. Twenty-three patients were enrolled with a mean age of 60.2 ± 11.7 years. Baseline blood urea nitrogen and creatinine were 70.5 ± 29.4 and 10.02 ± 4.52 mg/dL, respectively. Twenty-one patients took aspirin. All patients were infused with desmopressin before their invasive procedures, which were a central catheter insertion for emergent hemodialysis in 13 patients, percutaneous nephrostomy in 7 patients, and angiography through arm or leg vessels in 3 patients. After desmopressin infusion, both the hematocrit and platelet count were slightly decreased without changes in prothrombin time or activated partial thrombin time. Collagen/epinephrine-closure time was significantly shortened from 252.7 ± 40.7 to 144.6 ± 51.0 s (p < 0.001). There were minimal bleeding in 20 patients and mild bleeding in 3 patients. None experienced severe bleeding event or required additional intervention for bleeding control. There were no adverse events including the decrease of serum sodium concentration. In conclusion, a single infusion of desmopressin before invasive procedures in uremic patients on antiplatelet drugs appeared to be well tolerated and improved platelet dysfunction measured by collagen/epinephrine-closure time.

Topics: Adult; Aged; Antidiuretic Agents; Blood Platelets; Deamino Arginine Vasopressin; Female; Humans; Male; Middle Aged; Nephrostomy, Percutaneous; Partial Thromboplastin Time; Platelet Aggregation Inhibitors; Platelet Count; Prospective Studies; Renal Dialysis; Uremia

Desmopressin decreases bleeding time in uremic patients. Although bleeding time is the most frequently used measure of global platelet function, this test has important disadvantages. In vitro closure time (CT) is a relatively new and efficient test of primary hemostasis. We designed a prospective randomized study to evaluate the effect of desmopressin on platelet function, as measured by in vitro CT, in uremic patients.. Forty-eight uremic patients, about to commence hemodialysis and with prolonged CT, were randomized to infusion with desmopressin (n = 24) or saline alone (n = 24). Complete blood count, prothrombin time, activated partial thrombin time, levels of plasma fibrinogen, von Willebrand factor (VWF), factor VIII (FVIII) and CT were measured before and 1 h after desmopressin or saline infusion.. Following desmopressin infusion, collagen/epinephrine and collagen/adenosine diphosphate CT were significantly shortened from 212 +/- 58 to 152 +/- 45 s (p = 0.01) and from 189 +/- 78 to 147 +/- 58 s (p = 0.012), respectively; levels of FVIII and VWF were significantly increased from 188 +/- 66 to 252 +/- 93% (p = 0.017) and from 113 +/- 9 to 121 +/- 9% (p = 0.043), respectively. There were no significant changes in the control group.. Desmopressin improved platelet dysfunction and increased the plasma concentrations of VWF and FVIII, suggesting that desmopressin may play a role in improving the bleeding tendency in uremic patients.

Topics: Adult; Aged; Aged, 80 and over; Blood Platelet Disorders; Blood Platelets; Deamino Arginine Vasopressin; Female; Hemostasis; Humans; Male; Middle Aged; Platelet Count; Prospective Studies; Time Factors; Uremia

The effect of 1 deamino-8-D-arginine vasopressin (DDAVP) on blood platelet serotonin and some parameters of haemostasis was investigated. DDAVP was administered intravenously in a dose of 0.4 micrograms/kg BW to 16 uraemic patients maintained on chronic haemodialysis in a double-blind crossover study compared with placebo. The bleeding time was significantly shortened after DDAVP administration from 21.3 +/- 8 minutes to 11.5 +/- 6 minutes (p less than 0.001). VIII: Ag increased from 239.1 +/- 94% to 473 +/- 293% (p less than 0.01). Euglobulin lysis time was shortened from 238 +/- 101 to 148 +/- 84 minutes (p less than 0.005). The platelet serotonin level was significantly reduced from 532 +/- 141 to 366 +/- 88 ng/10(9) platelets (p less than 0.02). There were no changes in haematocrit, platelet count, VIII: C levels and blood serotonin concentrations after DDAVP administration. In placebo group there were no changes in all investigated parameters. Our data indicate that DDAVP shortens prolonged bleeding time in uraemic probably by means of the serotonergic mechanism. Further studies are needed to confirm this suggestion.

Topics: Adult; Aged; Bleeding Time; Blood Coagulation Tests; Blood Platelets; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemostasis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Uremia

The intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) is used as a nontransfusional form of treatment in patients with congenital and acquired bleeding disorders, including patients with uremia associated with prolonged bleeding times. Since uremic patients experience minor bleeding episodes that might be self-managed at home (particularly epistaxis, gingival bleeding, and menorrhagia), we carried out a double-blind, placebo-controlled crossover study in nine uremics to evaluate whether the prolonged bleeding times could be shortened by subcutaneous injections of DDAVP. One hour after administration, the bleeding time was significantly shortened (P less than .01) and became normal in seven of nine patients. After 4 hr, the bleeding time was still shorter than baseline (P less than .01), but in only three patients was it still normal. There was no significant bleeding time change after placebo. When the same patients were treated with the same dose of DDAVP infused intravenously, the bleeding times were not significantly different from those measured after subcutaneous administration. Hence, subcutaneous DDAVP is an alternative method for short-term shortening of the bleeding time in uremia, at least as effective as intravenous DDAVP but with the possibility of self-administration by the patients at home.

Topics: Adult; Aged; Bleeding Time; Deamino Arginine Vasopressin; Female; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Platelet Function Tests; Uremia

In a randomized double-blind cross-over trial we gave either 1-deamino-8-D-arginine vasopressin or placebo to 12 patients with uremia, hemorrhagic tendencies, and prolonged bleeding times. After vasopressin infusion, all patients had shortened bleeding times, with the effect lasting for at least four hours in most cases. Platelet count, platelet cyclic AMP levels, platelet retention on glass beads, plasma fibronectin, serum thromboxane B2 and residual prothrombin, hematocrit, and plasma osmolarity were unchanged after vasopressin. A consistent post-infusion increase in factor VIII coagulant activity and, to a lesser extent, in factor VIII-related antigen and ristocetin cofactor accompanied the shortening of bleeding time. In addition, vasopressin induced the appearance in plasma of larger von Willebrand-factor multimers than those present in the resting state. The compound was given to nine additional patients with acute or chronic renal failure and prolonged bleeding times, before major surgery or renal biopsy. In these patients, shortening of the bleeding time was associated with normal hemostasis. Our findings indicate that 1-deamino-8-D-arginine vasopressin can be used for temporary correction of bleeding time and may prevent surgical bleeding in patients with uremia.

Topics: Adult; Antigens; Arginine Vasopressin; Bleeding Time; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Factor VIII; Female; Fibrinogen; Hemorrhage; Humans; Male; Middle Aged; Platelet Function Tests; Postoperative Complications; Random Allocation; Uremia; von Willebrand Factor

Topics: Biopsy; Deamino Arginine Vasopressin; Hemorrhage; Humans; Hyponatremia; Kidney; Uremia

Recombinant activated factor VII (rFVIIa) is approved for prevention and treatment of bleeding in hemophilia patients with inhibitors to FVIII (hemophilia A) or IX (hemophilia B), patients with congenital and acquired hemophilia and in patients with FVII deficiency or Glantzmann thrombasthenia (last indication is approved only in Europe). Off-labeled, the drug has been prescribed for prevention, or treatment of bleeding in severe hepatic disease, neonatal coagulopathies, high-risk surgical procedures, trauma, thrombocytopenia and platelet function disorders, as well as for urgent reversal of oral anticoagulation. Here we report a case of a 53-year-old female patient with delayed graft function after kidney transplantation, who had kidney biopsy complicated with prolonged bleeding. After unsuccessful treatment with desmopressin, the patient was treated with rFVIIa and the bleeding stopped immediately. Only few anecdotal reports of use of rFVIIa for treatment of bleeding in uremic patients have been published thus far. To our knowledge, this is the first case that describes use of rFVIIa for management of bleeding as a complication of renal biopsy in a uremic patient in the early kidney posttransplantation period.

Topics: Biopsy; Deamino Arginine Vasopressin; Drug Administration Schedule; Factor VIIa; Female; Hemorrhage; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Recombinant Proteins; Uremia

Topics: Cerebral Hemorrhage; Deamino Arginine Vasopressin; Fatal Outcome; Female; Humans; Middle Aged; Postoperative Complications; Renal Agents; Subdural Space; Thrombocytopenia; Uremia

Topics: Administration, Intranasal; Adolescent; Adult; Bleeding Time; Blood Coagulation; Child; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Hemorrhage; Humans; Renal Agents; Treatment Outcome; Uremia

Desmopressin (DDAVP) 0.3 micrograms/kg was infused in 20 uremic patients with prolong bleeding time. Prior to infusion, the uremic patients had a reduced level of tissue plasminogen activator (t-PA), normal levels of von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (vWF:RCo) and elevated level of factor VIII coagulant activity (FVIII:C). Patients with lower hematocrit or t-PA levels tended to have a longer bleeding time. One hour after DDAVP infusion, the bleeding time was shortened significantly. This improvement was significant in all patient groups irrespective of the high or low initial levels of factor VIII complex components. Plasma levels of FVIII:C, vWF:Ag, vWF:RCo and t-PA all increased significantly. The magnitude of increase in these factors, however, was not significantly correlated with the extent of bleeding time shortening. The multiple regression model for predicting the extent of bleeding time shortening suggested only two variables, viz initial bleeding time and posttreatment FVIII:C activity to be of significance. The present results indicate that the hemostatic response to DDAVP is uniform in uremic patients, regardless of whether the initial activities of factor VIII complex components are high or low. Posttreatment FVIII:C activity appears to play a significant role in the hemostatic action of DDAVP. Furthermore, a depressed fibrinolytic activity was generally observed to concur with the hemostatic defect in uremic patients.

Topics: Adolescent; Adult; Deamino Arginine Vasopressin; Female; Fibrinolysis; Hemostasis; Humans; Infusions, Intravenous; Male; Middle Aged; Renal Agents; Renal Dialysis; Uremia

Topics: Adult; Aged; Antithrombin III; Blood Coagulation; Deamino Arginine Vasopressin; Enzyme-Linked Immunosorbent Assay; Humans; Middle Aged; Protein C; Protein S; Renal Agents; Uremia

This study is designed to evaluate the clinical outcome of uremic bleeding treated with DDAVP. DDAVP was given intravenously in nine ESRD patients who had undergone A/V fistula surgery and showed oozing of the operation site for more than one hour.. Hemostasis was observed by removing the blood from the wound site with a piece of filter paper for 3 hours after DDAVP administration. vWF, t-PA antigen, t-PA activity, total fibrinolytic activity in euglobulin fraction, fibrinopeptide A and FDP were measured before and after DDAVP administration.. Cessation of the oozing did not occur within 3 hours after DDAVP administration in all of the cases. vWF levels and t-PA antigen were significantly increased after DDAVP administration peaked at 30 min for vWF and 60 min for t-PA antigen. t-PA activity increased in 6 cases and euglobulin fibrinolytic activity increased in 7 cases, respectively. These values fell towards pre-administration levels 120 min after the administration. There was no difference in fibrinopeptide A levels before and after DDAVP administration. FDP became positive in 4 cases after DDAVP administration.. DDAVP increased both vWF and t-PA levels and cessation of the oozing from post-operative AV-fistula wounds did not occur within 3 hours after DDAVP administration in all of the cases. These results suggest that the effect of DDAVP should be reassessed in the treatment of uremic bleeding.

Topics: Adult; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostasis; Humans; Male; Middle Aged; Tissue Plasminogen Activator; Uremia; von Willebrand Factor

Topics: Adult; Biopsy; Blood Transfusion; Deamino Arginine Vasopressin; Humans; Kidney Transplantation; Male; Nephrostomy, Percutaneous; Plasma; Renal Agents; Thrombelastography; Uremia

The effects of azotemia on von Willebrand factor (vWf) plasma concentration, structure, and function were studied by utilizing canine models for both uremic bleeding and type I vWf deficiency (vWd). Seventy-five percent to 80% renal mass reduction in eight mixed-breed dogs induced marked azotemia (blood urea nitrogen [BUN] 103 +/- 7 mg/dl [mean +/- SEM]; creatinine 5.8 +/- 1 mg/dl) and prolonged mean buccal mucosal bleeding time (BMBT) from 1.8 +/- 0.2 minutes to 7.0 +/- 0.4 minutes. The mean vWf plasma concentration increased from 0.88 +/- 0.11 U/ml to 1.26 +/- 0.14 U/ml. The pre- and postsurgical sodium dodecyl sulfate-agarose gel electrophoresis multimeric patterns were similar in all dogs. Administration of cryoprecipitate from pooled azotemic mixed-breed dog plasma to five Doberman pinschers with type I vWd increased the mean plasma vWf from 0.14 +/- 0.01 U/ml to 0.48 +/- 0.04 U/ml and decreased the BMBT from 7.1 +/- 0.6 minutes to 3.14 +/- 0.09 minutes. After renal mass reduction, five type I vWd Dobermans developed marked azotemia (BUN 79 +/- 8.6 mg/dl; creatinine 3.7 +/- 0.6 mg/dl) and prolonged BMBT (16.1 +/- 3.6 minutes). Findings in the eight azotemic mixed-breed dogs indicated that (1) vWf plasma levels were normal to increased in azotemic dogs; (2) vWf structure and multimeric distribution were not altered in canine azotemia; and (3) vWf was functional when placed in a non-azotemic environment. The prolongation of the BMBT in azotemic vWd dogs indicated that factors other than alteration of vWf function were responsible for the prolonged BMBT in canine azotemia.

Topics: Animals; Bleeding Time; Blood; Chemical Precipitation; Cold Temperature; Deamino Arginine Vasopressin; Dogs; Fibronectins; Hemostasis; Osmolar Concentration; Reference Values; Uremia; von Willebrand Factor

DDAVP, an analog of vasopressin, has been shown to have hemostatic activity. Although it has been used clinically to control bleeding, there have been very few attempts to characterize this agent in experimental animals. We describe a new animal model which is fast, reliable and inexpensive, and which may be used to screen novel analogs of the peptide. Under sodium pentobarbital anesthesia, rats were bilaterally nephrectomized and implanted with indwelling intravenous cannulae. The next day they were re-anesthetized, a standardized cut was made in the tail and the tail was allowed to bleed into warm isotonic saline (25 ml). After 10 min., the tail was removed from the saline and the blood loss was measured either by laser nephelometry or by colorimetric analysis. DDAVP was then injected intravenously and the rat was allowed to rest quietly for 30 min., after which time a second incision was made in the tail and blood loss again measured for 10 min. Unlike bleeding time which was highly variable, blood loss proved to be a reliable index of the hemostatic activity. Thus we were able to demonstrate that DDAVP reduced blood loss in the uremic rats, whereas it was without effect in intact rats.

Topics: Animals; Bleeding Time; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Rats; Reproducibility of Results; Uremia

Haemorrhagic diathesis is a serious complication of uraemia. Desmopressin is known to shorten prolonged bleeding time in uraemia but mechanism of the haemostatic action of this drug remains still unknown. The aim of the work was to study the effect of desmopressin on some haemostatic parameters in relation to plasma and platelet serotonin. Desmopressin was administered i.v. to 33 haemodialysed patients (age range 27-66 years) in a dose of 0.4 microgram/kg b.w., 90 minutes after desmopressin infusion bleeding time became significantly shorter (p < 0.001) and correlated with the shortening of the euglobulin clot lysis time (r = -0.43, p < 0.05). Tissue plasminogen activator activity increased (p < 0.01) and its inhibitor (PAI) activity decreased (p < 0.001) after desmopressin infusion. A correlation between the fall in platelet serotonin content and changes in tissue plasminogen activator and PAI activities was found (r = 0.55, p < 0.01 respectively). A rise in plasma serotonin concentration was observed. In vitro desmopressin inhibited 14C serotonin uptake in a dose-dependent manner. After 2 hours of platelet incubation with desmopressin in a concentration of 4 ng/ml 16% of 14C serotonin was released. A possibility of serotoninergic mechanism in the haemostatic action of desmopressin is suggested.

Topics: Adult; Aged; Blood Platelets; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Hemorrhagic Disorders; Hemostasis; Humans; Middle Aged; Serotonin; Tissue Plasminogen Activator; Uremia

The effect of desmopressin (DDAVP) on protein C (PC) and PC inhibitors was investigated in 7 uremic predialysis patients, 7 hemodialysis patients and 7 controls. Significant decrease in PC activity was observed in all groups after DDAVP administration. Desmopressin did not influence PC antigen and two well-known PC inhibitors, plasminogen activator inhibitor-3 and alpha 1-antitrypsin. Thus, it is suggested that DDAVP-induced decrease in PC activity is not related to the changes in PC inhibitors; further studies are needed to clarify the precise mechanisms of the effect of DDAVP on PC in uremia.

Topics: Adult; alpha 1-Antitrypsin; Antigens; Blood Coagulation; Deamino Arginine Vasopressin; Hemorrhage; Humans; Middle Aged; Plasminogen Inactivators; Protein C; Renal Dialysis; Uremia

Topics: Animals; Blood Coagulation; Blood Platelets; Deamino Arginine Vasopressin; Male; Rats; Rats, Wistar; Serotonin; Uremia

Topics: Adult; Aged; Amino Acid Sequence; Blood Platelets; Deamino Arginine Vasopressin; Female; Humans; Male; Middle Aged; Molecular Sequence Data; Plasminogen Inactivators; Serotonin; Tissue Plasminogen Activator; Uremia

Bleeding times, von Willebrand activities, and platelet retentions were examined before and following d-DAVP in 13 uremic patients. Shortening of the bleeding time from 16.6 +/- 2.2 (SEM) to 6.8 +/- 0.7 min was seen in six patients. However, bleeding times remained greater than or equal to 20 min in the remaining seven individuals. The only baseline parameter that correlated with response to d-DAVP was the amount of blood loss (mg/min) during the bleeding time test. Responders had normal blood loss values averaging 6.2 +/- 1.5 mg/min. By contrast, these values were elevated in 6/7 of the non-responders and averaged 28.4 +/- 5.9 mg/min (P = 0.01). Von Willebrand activities increased following d-DAVP in the responders but not in the non-responders. Platelet retention was uniformly low in all patients and improved from 21.0 +/- 7.0% to 75.0 +/- 7.9% (P = less than 0.001) following d-DAVP in responders but not non-responders. To further define the retention abnormality in uremia, the two-stage platelet retention assay was performed prior to d-DAVP. Most of the patients (9/12) had both first- and second-phase abnormalities. Therefore, the retention defect in uremia appears to be more complex than that seen in von Willebrand's disease (2nd phase abnormality only). Nevertheless, d-DAVP seems to improve platelet rheology in uremic individuals whose von Willebrand activities increase with d-DAVP.

Topics: Adult; Aged; Aged, 80 and over; Bleeding Time; Blood Platelets; Cell Adhesion; Deamino Arginine Vasopressin; Humans; Middle Aged; Rheology; Uremia; von Willebrand Factor

Topics: Benzamidines; Blood Transfusion; Deamino Arginine Vasopressin; Gabexate; Guanidines; Hemorrhage; Heparin; Humans; Kidney Failure, Chronic; Molecular Weight; Protease Inhibitors; Renal Dialysis; Uremia

The qualitative platelet disorder of uraemia results in decreased primary haemostatic capacity which can result in significant blood loss during invasive procedures. Treatments of the disorder tend to be empirical and include measures such as aggressive dialysis, conjugated oestrogens, and use of DDAVP. Improvement in platelet function is typically monitored by repeated bleeding times. The variability of the bleeding time is an all too recognized limitation of its usefulness. We report here the case of a 35-year old male with end stage renal disease who presented with intractable bleeding secondary to peptic ulcer disease and haemorrhagic gastritis. Platelet function tests including bleeding time, platelet aggregation studies, and clot retraction measurements were monitored before and after intravenous administration of DDAVP (0.3 microgram/kg). The bleeding time which had been 8 min before DDAVP did not change. Platelet aggregation studies revealed improved aggregation by both collagen and adenosine diphosphate. Clot retraction forces were dramatically enhanced after DDAVP. Pre-DDAVP clots containing 72 x 10(9) platelets per 1 and 1 g fibrinogen per 1 produced 90 dynes/cm2 of force at 800 s post-thrombin addition. Identical clots formed with blood drawn 2 h post-DDAVP produced 750 dynes/cm2. The DDAVP dose was repeated after 8 h with obvious slowing of blood loss. The marked effect of DDAVP on clot retraction may allow monitoring of DDAVP therapy utilizing this technique.

Topics: Adenosine Diphosphate; Adult; Bleeding Time; Blood Platelet Disorders; Clot Retraction; Collagen; Deamino Arginine Vasopressin; Humans; Male; Platelet Aggregation; Uremia

Topics: Deamino Arginine Vasopressin; Factor VIII; Fibrinogen; Hemorrhage; Humans; Uremia

Topics: Administration, Intranasal; Administration, Topical; Antifibrinolytic Agents; Deamino Arginine Vasopressin; Hemophilia A; Hemorrhage; Hemorrhagic Disorders; Hemostatics; Humans; Injections, Subcutaneous; Liver Cirrhosis; Surgical Procedures, Operative; Uremia; von Willebrand Diseases

A more concentrated desmopressin (DDAVP) preparation (40 micrograms/ml), which required small injection volumes (less than 1 ml), was studied in a double-blind trial in 10 healthy volunteers, 12 patients with haemophilia A, and 8 patients with uraemic bleeding. DDAVP was administered by subcutaneous injection at a dose of 0.4 micrograms/kg body weight. In healthy subjects, peak levels of DDAVP ranging from 480 to 638 pg/ml were reached 1 h after the subcutaneous injection and DDAVP was eliminated with a mean half-life of 3.1 h. DDAVP produced a 2.5-fold (3.0-fold) increase of factor VIII:C (factor VIII:Ag) and a 1.9-fold (2.2-fold) increase of von Willebrand factor:Ag (ristocetin cofactor) over baseline levels. Additionally, a 2.1-fold increase of tissue-type plasminogen activator antigen was observed. Factor VIII and von Willebrand factor were rapidly eliminated with a half-life ranging from 1.3 to 5.7 h and from 1.1 to 11.4 h, respectively. In haemophilia A patients, DDAVP produced a 2.3-fold increase of factor VIII:C 1 h after the injection. DDAVP was given on 8 occasions for management of bleeding, and only in 1 patient did a wound haematoma (after herniotomia) occur. In 7 of the 8 patients with uraemia the bleeding time shortened, and in all patients an increase of platelet retention and a decrease of platelet count was observed (p less than 0.05). No serious local or systemic untoward side effects were observed.

Topics: Adult; Antigens; Bleeding Time; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Drug Evaluation; Factor VIII; Female; Hemophilia A; Heterozygote; Humans; Injections, Subcutaneous; Male; Middle Aged; Uremia; von Willebrand Factor

The effect of 1-deamino-8-D-arginine vasopressin (DDAVP) on protein C was investigated in 10 uremics and 10 normal subjects. The protein C antigen was higher in the uremic patients than in the normal subjects. DDAVP had no influence on the level of protein C antigen. However, functional protein C in uremics was lower than in normals even before administration of DDAVP. Furthermore, there was a decrease in functional protein C in the uremics after administration of DDAVP. Further studies are needed to clarify the low functional protein C in uremics both before and during administration of DDAVP.

Topics: Adult; Antigens; Bleeding Time; Deamino Arginine Vasopressin; Factor VIII; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Protein C; Time Factors; Uremia; von Willebrand Factor

Effects of 1-deamino-8-D-arginine vasopressin (DDAVP; 0.4 microgram/kg iv) were studied in 11 patients with uremia. Bleeding time, platelet retention on glass beads, factor VIII activities, plasma catecholamine levels, and studies on platelet interaction with the subendothelium were performed before, 1 hour after, and 6 hours after DDAVP infusion. Perfusates consisting of normal washed platelets, uremic platelet-poor plasma (u-PPP) and washed red blood cells were perfused through the Baumgartner perfusion system at a shear rate of 800 sec-1. One hour after DDAVP infusion, a shortening in the bleeding time and an increase in platelet retention on glass beads were noticed in these patients (p less than 0.01). Simultaneously, plasma levels of noradrenaline, factor VIII coagulant (FVIII:C), and von Willebrand factor (vWF) activities were statistically increased. Platelet deposition and platelet aggregate formation on subendothelium were consistently increased (p less than 0.05) in perfusions carried out with blood reconstituted with u-PPP obtained 1 hour after DDAVP. The "in vitro" addition of 1 U/ml vWF or 1 U/ml vWF plus 1 U/ml factor VIII to the pretreatment u-PPP had no significant influence on the parameters that quantify platelet-subendothelium interaction. However, after the addition of 10 ng/ml noradrenaline to a similar system containing basal u-PPP, a clear improvement (p less than 0.05) in platelet deposition was noticed. Our results confirm the hemostatic effectiveness of DDAVP in patients with uremia and reveal an increased platelet interaction with subendothelium mediated by a factor present in uremic plasma after DDAVP administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Bleeding Time; Blood Coagulation Factors; Blood Platelets; Deamino Arginine Vasopressin; Endothelium, Vascular; Female; Humans; In Vitro Techniques; Infusions, Intravenous; Male; Middle Aged; Reference Values; Renal Dialysis; Uremia

Topics: Blood Platelets; Deamino Arginine Vasopressin; Humans; Serotonin; Uremia

Topics: Adult; Deamino Arginine Vasopressin; Erythropoietin; Female; Hemorrhage; Humans; Uremia

An elderly patient with evidence of atherosclerosis and uremic bleeding diathesis developed two foci of cerebral thrombosis immediately after an infusion of desmopressin (DDAVP). Because large molecular weight multimers of von Willebrand factor (vWF) have been demonstrated to cause platelet aggregation under conditions of elevated fluid shear stress as occurs in atherosclerotic vessels, we investigated his plasma vWF at the time of the event and compared it to baseline values obtained 2 weeks later. Unusually large vWF multimers induced by the DDAVP infusion were present and likely contributed to the thrombotic process. Consequently, we believe DDAVP should be given with greater caution to patients with atherosclerosis.

Topics: Aged; Deamino Arginine Vasopressin; Hemorrhage; Humans; Intracranial Embolism and Thrombosis; Male; Uremia; von Willebrand Factor

Bleeding in uraemia is frequently manifest as diffuse gastric mucosal haemorrhage. In a patient with acute renal failure, prolonged bleeding time and life-threatening bleeding of this type, effective haemostasis was established with platelet-rich blood products and 1-deamino-8-D-arginine vasopressin (DDAVP).

Topics: Adult; Deamino Arginine Vasopressin; Female; Gastrointestinal Hemorrhage; Humans; Uremia

1-deamino-8-D-arginine vasopressin (DDAVP) was administered intranasally in a dose of 2 micrograms/kg BW to 17 uremic patients (16 maintained on chronic hemodialysis and 1 treated conservatively). The bleeding time was significantly shortened 120 minutes after DDAVP administration (from 18.1 +/- 7.5 minutes to 12.3 +/- 6.4 minutes p less than 0.001). Factor VIII related antigen (VIII: Ag) did not change. Factor VIII ristocetin cofactor activity (VIII: RCof) significantly increased (from 251.2 +/- 162.0 to 336.5 +/- 167.2 p less than 0.025). Platelet count decreased significantly after DDAVP (from 174.9 +/- 43.8 X 10(9)/l to 155.6 +/- 45.9 X 10(9)/l 30 minutes p less than 0.01 and 129.8 +/- 45.2 X 10(9)/l p less than 0.005 120 minutes after DDAVP). Antithrombin III concentration, and hematocrit did not change. Our data indicate that further clinical studies of intranasal DDAVP in uremic patients during episodes of bleeding are warranted.

Topics: Administration, Intranasal; Adult; Bleeding Time; Chronic Disease; Deamino Arginine Vasopressin; Factor VIII; Female; Humans; Male; Middle Aged; Platelet Count; Platelet Function Tests; Uremia

The roles of hemodialysis and 1-deamino-8-D-arginine vasopressin (DDAVP) in the control of hemorrhage following oral surgery in a severely uremic patient are described.

Topics: Adult; Deamino Arginine Vasopressin; Dental Care for Disabled; Hemostasis, Surgical; Humans; Kidney Failure, Chronic; Male; Oral Hemorrhage; Renal Dialysis; Tooth Extraction; Uremia

Topics: Adult; Bleeding Time; Deamino Arginine Vasopressin; Factor VIII; Female; Fibrinogen; Humans; Uremia; von Willebrand Factor

Topics: Deamino Arginine Vasopressin; Humans; Thrombocytopenia; Uremia

Hemophilia A, von Willebrand's disease and uremia prolong the bleeding time in affected children. Management of hemorrhage is difficult in these patients, and often requires multiple therapeutic modalities. Desmopressin, a synthetic analog of arginine vasopressin (DDAVP), decreases the bleeding time in patients with these disorders. We describe a case of a child with uremia and spontaneous epistaxis originating from the adenoid. Bleeding was controlled with administration of DDAVP and other measures. DDAVP is effective for the rapid, temporary correction of prolonged bleeding time associated with hemophilia A, von Willebrand's disease or uremia. The use of DDAVP avoids the risks associated with blood component transfusion. DDAVP may be used as a single hemostatic agent in minor surgical procedures, or in combination with other therapeutic modalities in major surgical procedures.

Topics: Adenoids; Blood Coagulation; Child; Deamino Arginine Vasopressin; Drug Evaluation; Epistaxis; Female; Humans; Uremia

Topics: Adolescent; Adult; Arginine Vasopressin; Bleeding Time; Deamino Arginine Vasopressin; Female; Humans; Male; Middle Aged; Platelet Function Tests; Renal Dialysis; Uremia

Topics: Adult; Aged; Bleeding Time; Blood Pressure; Deamino Arginine Vasopressin; Factor VIII; Female; Humans; Male; Middle Aged; Platelet Function Tests; Uremia

Clinical bleeding in uremia is a frequent problem and seems to correlate with a prolonged bleeding time. The vasopressin analog deamino-8-D-arginine vasopressin has been shown to shorten the bleeding time and to decrease clinical bleeding when administered intravenously to uremic patients. In the present study we administered the readily available intranasal deamino-8-D-arginine vasopressin to 2 uremic patients and demonstrated a decreased bleeding time and improvement in clinical bleeding.

Topics: Administration, Intranasal; Aged; Arginine Vasopressin; Bleeding Time; Deamino Arginine Vasopressin; Female; Gastrointestinal Hemorrhage; Humans; Middle Aged; Time Factors; Uremia

Topics: Adolescent; Adult; Arginine Vasopressin; Deamino Arginine Vasopressin; Factor VIII; Female; Humans; Male; Middle Aged; Uremia; von Willebrand Factor

Topics: Deamino Arginine Vasopressin; Factor VIII; Hemorrhage; Humans; Platelet Adhesiveness; Uremia; von Willebrand Factor