deamino-arginine-vasopressin and Liver-Cirrhosis

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

Cirrhosis frequently affects multiple components of hemostasis. Reversal of the coagulopathy of these patients is frequently required in case of bleeding episodes, or as prophylaxis before invasive procedures. Although 1-deamino-8-D-arginine vasopressin (DDAVP) is widely used as a pro-hemostatic agent in patients with cirrhosis, it is unclear whether DDAVP truly enhances hemostasis in these patients. Here we investigated the hemostatic effects of a single bolus of DDAVP in patients with cirrhosis.. Ten patients with cirrhosis (child B or C) and ten patients with mild haemophilia A received an intravenous single bolus of 0.3 microgram/kg DDAVP. Plasma was collected prior to and at 1, 3, 6, and 24 h after DDAVP administration. Levels of Von Willebrand factor (VWF), VWF propeptide, factor VIII (FVIII), and ADAMTS13 were measured in all plasma samples, whereas VWF multimers and functional VWF-dependent platelet adhesion were determined in the samples pre- and 1 h after DDAVP administration.. Following DDAVP administration, VWF, FVIII, and VWF propeptide levels increased in patients with haemophilia, while patients with cirrhosis only showed an increase in VWF propeptide and FVIII levels. High molecular weight VWF multimers and VWF-dependent platelet adhesion increased in patients with haemophilia one hour after DDAVP administration, but did not change in the patients with cirrhosis. Levels of ADAMTS13 were unaffected in both patient groups after DDAVP.. The lack of relevant effects of DDAVP on laboratory indices of primary hemostasis in patients with cirrhosis is in line with previous clinical study results in these patients.

Topics: ADAM Proteins; ADAMTS13 Protein; Adult; Biomarkers; Deamino Arginine Vasopressin; Factor VIII; Female; Hemophilia A; Hemostasis; Hemostatics; Humans; Infusions, Intravenous; Liver Cirrhosis; Male; Middle Aged; Netherlands; Time Factors; Treatment Outcome; von Willebrand Factor

Cirrhotic patients waiting for liver transplantation who need dental extractions are given fresh frozen plasma and/or platelets to correct coagulopathy. This is costly and may be associated with transfusion reactions and fluid overload. We evaluated the efficacy of intranasal desmopressin as an alternative to transfusion to correct the coagulopathy of cirrhotic patients undergoing dental extraction.. Cirrhotic patients with platelet counts of 30,000 to 50,000/microL and/or international normalized ratio (INR) 2.0 to 3.0 were enrolled in a prospective, controlled, randomized clinical trial. Blood transfusion (fresh frozen plasma 10 mL/kg and/or 1 unit of single donor platelets, respectively) or intranasal desmopressin (300 microg) were given before dental extraction. A standard oral and maxillofacial surgical treatment protocol was performed by the same surgeon. Patients were followed for postextraction bleeding and side-effects over the next 24 to 48 hours.. No significant differences were noted between the 2 groups in gender, age, INR, platelet count, creatinine, total bilirubin, ALT, albumin, MELD score, or number of teeth removed (median 3 vs 4). The number of teeth removed ranged between 1 and 31 in the desmopressin group and 1 and 22 in the transfusion group. No patients in desmopressin group required rescue blood transfusion after extraction. One patient in the transfusion group had bleeding after the procedure and required an additional transfusion. Another patient experienced an allergic reaction at the end of transfusion, which was effectively treated with diphenhydramine. Treatment associated average costs were lower for desmopressin ($700/patient) compared with transfusion ($1,173/patient).. Intranasal desmopressin was as effective as blood transfusion in achieving hemostasis in cirrhotic patients with moderate coagulopathy undergoing dental extraction. Intranasal desmopressin was much more convenient, less expensive, and well tolerated.

Topics: Administration, Intranasal; Adult; Blood Coagulation Disorders; Blood Loss, Surgical; Blood Transfusion; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; International Normalized Ratio; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Plasma; Platelet Count; Platelet Transfusion; Premedication; Tooth Extraction

To determine the effects of desmopressin on coagulation and blood loss in patients undergoing elective partial hepatectomy.. A randomized, controlled and double-blind study on 59 patients who received either 0.3 micro g x kg(-1) of desmopressin or an equal volume of normal saline (control) infused intravenously over 20 min after induction of general anesthesia.. There was an increase in plasma levels of factors VIII and von Willebrand after the infusion of study drug in both groups (P < 0.001). The activated partial thromboplastin time was shortened in Group D whereas prothrombin time was prolonged in Group C; (P = 0.02). A large range of intraoperative blood loss (400-7128 mL) was observed, with no significant differences between groups. There were no changes in plasma electrolyte levels or osmolality. Transfusion requirements were similar in both groups.. Desmopressin did not reduce intraoperative blood loss or transfusion requirements during hepatectomy despite raising clotting factor levels and improving tests of hemostasis.

Topics: Blood Coagulation Tests; Blood Loss, Surgical; Blood Transfusion; Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemoglobins; Hemostatics; Hepatectomy; Humans; Liver Cirrhosis; Male; Middle Aged; Osmolar Concentration; Platelet Count; Potassium; Prospective Studies; Sodium

Desmopressin (DDAVP), a synthetic analogue of vasopressin, has been shown to improve the bleeding time in patients with cirrhosis. The duration of this effect and the hemodynamic changes associated with DDAVP have not been studied so far. To evaluate these issues, 14 cirrhotics with portal hypertension were studied in basal conditions and after DDAVP (0.3 uk/kg). In 8 patients, hemostatic tests were done at basal conditions and 1, 3, 6 and 24 hs after drug administration. In the remaining 6 patients, mean arterial pressure, cardiac output, portal and femoral blood flows were evaluated. Hemodynamic parameters were measured by Doppler ultrasound. DDVP caused a marked decrease in bleeding time at 1, 3, 6 and 24 hs (14 +/- 9 vs 8 +/- 3, 7 +/- 4, 6 +/- 4 and 8 +/- 4 min, respectively); the decrease was maximal and statistically significant at 6 hs (55 +/- 15%, p < 0.02) after DDAVP infusion. Bleeding time reduction was observed in every patient studied. In the hemodynamic study, DDAVP caused a mild but significant decrease in mean arterial pressure (12 +/- 8%, p < 0.05); no significant changes were observed in the rest of hemodynamic parameters studied. These findings show that DDAVP can be used to shorten the bleeding time for a period of at least 24 hs in patients with cirrhosis, without deleterious hemodynamic effects. This beneficial effect may be of potential relevance in the medical management of patients with chronic liver diseases.

Topics: Bleeding Time; Deamino Arginine Vasopressin; Female; Hemodynamics; Hemostasis; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Renal Agents; Time Factors

1-Deamino-8-D-arginine vasopressin (DDAVP, desmopressin), a synthetic analog of the antidiuretic hormone L-arginine vasopressin, improves hemostasis parameters in cirrhotic patients. Hence its use in combination with a vasoactive drug such as terlipressin might improve the performance of this drug in controlling variceal bleeding. The aim of this trial was to compare the efficacy of desmopressin plus terlipressin with that of terlipressin alone in controlling acute variceal hemorrhage. Cirrhotic patients with active variceal hemorrhage diagnosed endoscopically were randomized within 2 hr of admission to receive desmopressin plus terlipressin or placebo plus terlipressin. Terlipressin (2 mg, intravenous bolus) was given at time 0 and every 4 hr thereafter for 24 hr. Desmopressin (0.3 microgram/kg, intravenously) or placebo was given in saline solution over 30 min at time 0 and at 26 hr. Patients were monitored for 24 hr after cessation of treatment. Treatment failure was defined as recurrence of active bleeding during treatment or within the 24 hr after treatment. After enrolling 51 of the planned 84 patients, we carried out an interim analysis. Treatment failure occurred in 13 of 24 patients randomized to receive desmopressin plus terlipressin (54.2%) and in 6 of 22 patients randomized to receive terlipressin (27.3%) (p = 0.06, Fisher's exact test). The trial was interrupted at this stage because patients treated with the "new" therapy fared worse than those treated with the standard therapy, and the possibility of reversing this trend by completing the trial was deemed remote. The addition of desmopressin does not improve and may worsen the efficacy of terlipressin in controlling acute variceal bleeding in cirrhotic patients.

Topics: Acute Disease; Deamino Arginine Vasopressin; Double-Blind Method; Drug Therapy, Combination; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Lypressin; Male; Middle Aged; Terlipressin; Treatment Failure

The intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) shortens the prolonged bleeding time in patients with congenital or acquired bleeding disorders, including patients with uremia or liver cirrhosis. We carried out a double-blind, placebo-controlled crossover study in ten patients with liver cirrhosis to evaluate whether or not their prolonged bleeding times could be shortened by subcutaneous injections of DDAVP (0.3 microgram/kg), a more practical route of administration than intravenous infusions. One hour after DDAVP injection the bleeding time was significantly shortened (p less than 0.05). After 4 h, however, the bleeding time shortening was no longer statistically significant. There was no bleeding time change after placebo. Plasma levels of von Willebrand factor antigen (vWF:Ag) did not significantly increase after DDAVP or placebo. The study shows that subcutaneous DDAVP is an alternative method for short-term shortening of the bleeding time in liver cirrhosis.

Topics: Adolescent; Adult; Aged; Antigens; Bleeding Time; Child; Deamino Arginine Vasopressin; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Liver Cirrhosis; Male; Middle Aged; von Willebrand Factor

The synthetic vasopressin derivative desmopressin (DDAVP) shortens a prolonged bleeding time (BT) in patients with uremia, congenital platelet dysfunction, and von Willebrand disease. To establish the limits of the clinical usefulness of DDAVP, a controlled randomized study was carried out in 53 patients and ten volunteers with different conditions that have in common a prolonged BT. DDAVP significantly shortened the BT in 21 cirrhotics (P less than .01), in eight patients with unclassified prolonged BT (P less than .05) and in ten volunteers taking the antiplatelet drugs aspirin (P less than .05) and ticlopidine. The BT changes were not statistically significant in 15 patients with severe thrombocytopenia nor in nine with congenital platelet dysfunction, even though a few patients with storage pool deficiency responded with a marked BT shortening. Our findings indicate that DDAVP might be given when biopsies or other surgical procedures must be carried out in patients with prolonged BT. However, the compound is often ineffective in patients with thrombocytopenia or congenital platelet dysfunction.

Topics: Adolescent; Adult; Aged; Aspirin; Bleeding Time; Clinical Trials as Topic; Deamino Arginine Vasopressin; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Platelet Count; Platelet Function Tests; Random Allocation; Thiophenes; Thrombocytopenia; Ticlopidine; von Willebrand Factor

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.

Topics: Bleeding Time; Chronic Disease; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Humans; Liver Cirrhosis; Random Allocation; von Willebrand Factor

Recent data demonstrated that amongst patients undergoing elective surgery the prevalence of cirrhosis is 0.8% equating to approximately 25 million cirrhotic patients undergoing surgery each year worldwide. Overall, the presence of cirrhosis is independently associated with 47% increased risk of postoperative complications and over two and a half-increased risk of in-hospital mortality in patients undergoing elective surgery. In particular, perioperative patients with chronic liver disease have long been assumed to have a major bleeding risk on the basis of abnormal results for standard tests of hemostasis. However, recent evidence outlined significant changes to traditional knowledge and beliefs and, nowadays, with more sophisticated laboratory tests, it has been shown that patients with chronic liver disease may be in hemostatic balance as a result of concomitant changes in both pro- and antihemostatic pathways. The aim of this paper endorsed by the Liver Intensive Care Group of Europe was to provide an up-to-date overview of coagulation management in perioperative patients with chronic liver disease focusing on patient blood management, monitoring of hemostasis, and current role of hemostatic agents.

Topics: Anemia; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Loss, Surgical; Deamino Arginine Vasopressin; Elective Surgical Procedures; Europe; Factor VIIa; Fibrinogen; Fibrinolysis; Fibrinolytic Agents; Hemostasis; Hemostatic Techniques; Hemostatics; Humans; Liver Cirrhosis; Perioperative Care; Plasma; Platelet Function Tests; Platelet Transfusion; Postoperative Hemorrhage; Recombinant Proteins

Decompensated hepatitis C virus (HCV)-related cirrhosis is the main indication for liver transplantation. We report the first successful living-related liver transplantation in a 49-year-old hemophilia A patient with end-stage HCV-related cirrhosis using a graft obtained from his 20-year-old daughter, an obligate carrier.. The donor's autologous fresh-frozen plasma rich in factor VIII (FVIII) by treatment with 1-deamino-8-D-arginine vasopressin was prepared before the operation. At induction, 1-deamino-8-D-arginine vasopressin was given to the donor to increase plasma FVIII level. In addition, autologous fresh-frozen plasma containing high FVIII concentrate was infused intraoperatively. The right lobe was harvested from the donor and transplanted orthotopically. The recipient was treated postoperatively with recombinant FVIII and immunosuppressive agents.. The donor did not receive recombinant FVIII or allogenic blood during perioperative periods. No bleeding was encountered in the donor perioperatively. The recipient showed a steady increase in FVIII activity postoperatively and was discharged 40 days after transplantation. Ribavirin and interferon-alpha were provided for 3 months postoperatively to prevent potential recurrence of HCV infection. Serum HCV-RNA by RT-PCR became negative after such treatment.. End-stage liver disease in patients with hemophilia A can be an indication for living-related liver transplantation. Furthermore, a graft from a living-related donor with hemophilia A carrier seems to be suitable provided such individuals receive adequate support for coagulopathies.

Topics: Deamino Arginine Vasopressin; Factor VIII; Hemophilia A; Hepatitis C; Humans; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Tissue Donors

Qualitative abnormalities in von Willebrand Factor (vWF) in patients with cirrhosis have been little studied with contrasting results. We used crossed immunoelectrophoresis (2-DIE) and multimeric analysis of vWF in eight patients with stable hepatic cirrhosis to evaluate abnormalities in vWF before and 1 h following intravenous administration of three doses of desmopressin acetate (0.3 micrograms/kg) given at baseline, 4 and 24 h. We thought that qualitative abnormalities might be more easily detected following desmopressin as this is known to release vWF from storage sites. There was an increased electrophoretic mobility on 2-DIE in all patients with no change following desmopressin. The multimeric analysis did not show an increase in lower molecular weight multimers, but showed a statistically significant increase in higher molecular weight multimers following desmopressin (P less than 0.02). These results suggest that the vWF of cirrhotics has an abnormal charge (not altered by release following desmopressin) which would explain the increased electrophoretic mobility on 2-DIE with a normal pattern of lower molecular weight multimers using multimeric analysis.

Topics: Deamino Arginine Vasopressin; Factor VIII; Humans; Immunoelectrophoresis, Two-Dimensional; Liver Cirrhosis; Macromolecular Substances; von Willebrand Factor

Authors describe the simultaneous occurrence of ascites due to liver cirrhosis and diabetes insipidus in a patient with consistently normal urine volume. The diagnosis of diabetes insipidus has been proved by the water deprivation test combined with the administration of dDAVP as well as by serial determinations of plasma arginine vasopressin levels before and during infusion of hypertonic sodium chloride solution. Authors discuss the differential-diagnostic difficulties of the case and consider the mechanisms playing a role in the abolishment of diabetic polyuria by hepatic disease.

Topics: Aged; Arginine Vasopressin; Ascites; Body Water; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuretics; Humans; Injections, Intravenous; Kidney; Liver Cirrhosis; Male; Sodium Chloride

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

Topics: Bleeding Time; Deamino Arginine Vasopressin; Humans; Liver Cirrhosis

Topics: Adult; Aged; Arginine Vasopressin; Blood Coagulation; Blood Coagulation Disorders; Chronic Disease; Deamino Arginine Vasopressin; Female; Humans; Liver Cirrhosis; Male; Middle Aged