deamino-arginine-vasopressin and Disseminated-Intravascular-Coagulation

Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Cardiopulmonary Bypass; Combined Modality Therapy; Deamino Arginine Vasopressin; Disseminated Intravascular Coagulation; Extracorporeal Circulation; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Thrombocytopenia; Thrombosis

Infusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established. A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor alpha 2-antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated alpha 2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system. Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex. We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

Topics: Adult; alpha-Macroglobulins; Antibodies, Monoclonal; Deamino Arginine Vasopressin; Disseminated Intravascular Coagulation; Fibrinolysin; Fibrinolysis; Humans; In Vitro Techniques; Infusions, Intravenous; Plasminogen; Radioimmunoassay; Thrombosis

Here we report of a patient who developed a Moschcowitz-like syndrome following a desmopressin treatment of severe postpartum hemorrhage. The patient got an anaphylactic reaction after cervical ripening with dinoproston, leading to an emergency cesarean. A postpartum uterine atony with a blood loss more than 1500 ml resulted in a disseminated intravascular coagulation that was treated with mass transfusion of blood products, including platelets and factor VII. Desmopressin is used as rescue medication in situations of severe bleeding. It was given in this life-threatening situation and presumably triggered a Moschcowitz-like syndrome. Desmopressin exerts its haemostatic effect by releasing von Willebrand factor, which is elevated in pregnancy per se. This results in an increased risk of developing microthrombi, leading to a Moschcowitz-like syndrome. In conclusion, desmopressin should not be administered in pregnant patients owing to its potential risk of triggering the development of thrombotic-thrombocytopenic purpura.

Topics: Adult; Blood Transfusion; Cesarean Section; Deamino Arginine Vasopressin; Dinoprostone; Disseminated Intravascular Coagulation; Female; Hemostatics; Humans; Oxytocics; Postpartum Hemorrhage; Pregnancy; Purpura, Thrombotic Thrombocytopenic; Uterine Inertia; von Willebrand Factor

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Disseminated Intravascular Coagulation; Female; Humans; Hypogonadism; Pituitary Diseases; Pituitary Gland; Pregnancy

Topics: Adult; Aminocaproic Acid; Antiphospholipid Syndrome; Aprotinin; Blood Coagulation Tests; Blood Loss, Surgical; Combined Modality Therapy; Contraindications; Crystalloid Solutions; Deamino Arginine Vasopressin; Disseminated Intravascular Coagulation; Erythrocyte Transfusion; Factor VII; Factor VIIa; Female; Fluid Therapy; Hemorrhage; Hemostatics; Humans; Isotonic Solutions; Lupus Coagulation Inhibitor; Plasma; Platelet Transfusion; Pressure; Recombinant Proteins; Retroperitoneal Neoplasms; Shock; Thrombophlebitis; Tranexamic Acid

Elevated plasma concentrations of von Willebrand factor (vWf) are increasingly recognized as a cardiovascular risk factor, and are used as a marker of endothelial activation. However, the factors which determine the rate of vWf release from the endothelium in vivo have not been defined clearly. In addition, vWf plasma levels may also be influenced by adhesion of vWf to the vascular wall or to platelets, and by its rate of degradation. The propeptide of vWf (also called vWf:AgII) is stored and released in equimolar amounts with vWf. In the present study we attempted to determine whether this propeptide could be a more reliable marker of endothelial secretion than vWf itself. To accomplish this we developed an ELISA based on monoclonal antibodies. The propeptide levels in normal plasma were found to be 0.7 microgram/ml, more than 10 times lower than vWf itself. Administration of desmopressin (DDAVP) induced a rapid relative increase in propeptide (from 106 to 879%) and in vWf (from 112 to 272%). However, the increases in vWf and propeptide were equivalent when expressed in molar units. A time course study indicated a half-life of the propeptide of 3 h or less. In a baboon model of disseminated intravascular coagulation (DIC) induced by FXa, vWf increased by less than 100%, whereas the propeptide concentrations increased by up to 450%. In view of the massive thrombin generation (as assessed by fibrinogen depletion), the increases in vWf are small, compared to the strong secretory response to thrombin and fibrin previously observed in vitro. Our results suggest that due to its rapid turnover, the propeptide could provide a sensitive plasma marker of acute endothelial secretion.

Topics: Adult; Animals; Antibodies, Monoclonal; Antigens; Biomarkers; Deamino Arginine Vasopressin; Disseminated Intravascular Coagulation; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Exocytosis; Factor Xa; Female; Fibrin; Fibrinogen; Half-Life; Humans; Male; Papio; Phospholipids; Protein Processing, Post-Translational; Thrombin; von Willebrand Factor

It has been shown that the most important inhibitor of plasmin is alpha 2-antiplasmin, however, other protease inhibitors are able to inhibit this proteolytic enzyme as well. The contribution of the various protease inhibitors to the inhibition of plasmin in vivo has never been quantitatively assessed. To assess the relative contribution of the different protease inhibitors on the inhibition of plasmin we developed a series of sensitive immunoassays for the detection of complexes between plasmin and the protease inhibitors alpha 2-antiplasmin, alpha 2-macroglobulin, antithrombin III, alpha 1-antitrypsin and C1-inhibitor, utilizing monoclonal antibodies that are specifically directed against complexed protease inhibitors and a monoclonal antibody against plasmin. It was confirmed that alpha 2-antiplasmin is the most important inhibitor of plasmin in vivo, however, complexes of plasmin with alpha 2-macroglobulin, antithrombin III, alpha 1-antitrypsin- and C1-inhibitor were also detected. Particularly during activation of fibrinolysis complexes between plasmin and inhibitors other than alpha 2-antiplasmin were detected. It was observed that during different situations the inhibition profile of plasmin was not constant e.g. in patients with diffuse intravascular coagulation plasma levels of plasmin-alpha 1-antitrypsin and plasmin-C1-inhibitor were increased whereas in plasma from patients who were treated with thrombolytic agents complexes of plasmin with alpha 2-macroglobulin and with antithrombin III were significantly elevated. In conclusion, we confirmed the important role of alpha 2-antiplasmin in the inhibition of plasmin, however, in situations in which fibrinolysis is activated other protease inhibitors also account for the inhibition of plasmin in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: alpha-Macroglobulins; Antithrombin III; Complement C1 Inactivator Proteins; Deamino Arginine Vasopressin; Disseminated Intravascular Coagulation; Fibrinolysin; Fibrinolysis; Humans; Protease Inhibitors; Radioimmunoassay; Sensitivity and Specificity

We have evaluated the effect of 1-Deamino-8D-arginine vasopressin (DDAVP) on an experimental model of intravascular coagulation (DIC) induced in rabbits by injection of 20 micrograms kg-1 h-1 during 6 h of E. coli lipopolysaccharide. DDAVP significantly ameliorated the platelet drop and fibrinogen decrease (p less than 0.01) induced by endotoxin in control animals. A significant reduction in factor XII consumption (p less than 0.01) and a decrease in the generation of endotoxin induced PAI-1 activity in rabbits circulation was also observed (p less than 0.005). Moreover, fibrin deposition in kidneys of rabbits receiving DDAVP was significantly reduced as compared to control animals. Finally, the mortality rate in the control group was significantly higher than in DDAVP-treated rabbits (p less than 0.01). The hemostatic changes induced by DDAVP correlated with lower fibrin deposition and reduction in mortality rates.

Topics: Animals; Blood Coagulation; Deamino Arginine Vasopressin; Disseminated Intravascular Coagulation; Drug Administration Schedule; Fibrin; Fibrinolysis; Kidney; Lipopolysaccharides; Male; Plasminogen Activator Inhibitor 1; Rabbits