deamino-arginine-vasopressin and Myocardial-Infarction

Desmopressin is a synthetic vasopressin analog that increases the plasma levels of coagulation factor VIII, von Willebrand factor, and tissue plasminogen activator. This hemostatic agent, which can be administered either parenterally or intranasally, has been approved for use in the prevention and treatment of hemorrhagic events during surgery in patients with hemophilia A, in cases of prolonged idiopathic bleeding, and for complications associated with platelet antiaggregant therapy. This case report describes cardiac toxicity associated with desmopressin administered according to the recommended indications: a 55-year-old woman diagnosed with Wegener's granulomatosis (WG) was treated with desmopressin to improve hemostasis and shorten bleeding time before a planned renal biopsy. She developed cardiac arrest within 60 minutes of the desmopressin injection. Cardiopulmonary resuscitation began immediately and was successful, although the patient subsequently died of WG-associated complications. Desmopressin administration thus appears, in some cases, to be associated with a high risk of thrombotic events, possibly by stimulating the rapid release of endothelial factors such as an abnormal multimeric form of von Willebrand factor, which might cause platelet aggregation. Clinicians should be aware of the possible occurrence of this little-known but potentially serious cardiac event associated with desmopressin administration and be prepared to initiate cardiopulmonary resuscitation immediately if needed.

Topics: Biopolymers; Biopsy; Bleeding Time; Deamino Arginine Vasopressin; Disease Progression; Endothelium, Vascular; Fatal Outcome; Female; Granulomatosis with Polyangiitis; Heart Arrest; Hemorrhage; Hemostatics; Humans; Immunosuppressive Agents; Kidney; Middle Aged; Myocardial Infarction; Thromboembolism; Thrombolytic Therapy; von Willebrand Factor

Von Willebrand disease (vWD) is a frequent inherited disorder of hemostasis that affects both sexes. Two abnormalities are characteristic of the disease, which is caused by a deficiency or a defect in the multimeric glycoprotein called von Willebrand factor: low platelet adhesion to injured blood vessels and defective intrinsic coagulation owing to low plasma levels of factor VIII. There are 2 main options available for the treatment of spontaneous bleeding episodes and for bleeding prophylaxis: desmopressin and transfusional therapy with plasma products. Desmopressin is the treatment of choice for most patients with type 1 vWD, who account for approximately 70% to 80% of cases. This nontransfusional hemostatic agent raises endogenous factor VIII and von Willebrand factor 3 to 5 times and thereby corrects both the intrinsic coagulation and the primary hemostasis defects. In patients with the more severe type 3 and in most patients with type 2 disease, desmopressin is ineffective or is contraindicated and it is usually necessary to resort to plasma concentrates containing both factor VIII and von Willebrand factor. Concentrates treated with virucidal methods should be preferred to cryoprecipitate because they are equally effective and are perceived as safer. (Blood. 2001;97:1915-1919)

Topics: Blood Loss, Surgical; Combined Modality Therapy; Contraindications; Deamino Arginine Vasopressin; Endothelium, Vascular; Factor VIII; Female; Hemorrhage; Humans; Isoantibodies; Male; Myocardial Infarction; Postoperative Hemorrhage; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; Receptors, Vasopressin; Safety; Stroke; Thrombocytopenia; Transfusion Reaction; Virus Diseases; von Willebrand Diseases; von Willebrand Factor

Excessive bleeding may complicate cardiac surgery, and is associated with increased morbidity and mortality. Pharmacological strategies to decrease perioperative bleeding have been investigated in a large number of controlled trials, most of which have shown a decrease in blood loss. However, most studies lacked sufficient power to detect a beneficial effect on clinically more relevant outcomes. We did a meta-analysis of all randomised, controlled trials of the three most frequently used pharmacological strategies to decrease perioperative blood loss (aprotinin, lysine analogues [aminocaproic acid and tranexamic acid], and desmopressin).. Studies were included if they reported at least one clinically relevant outcome (mortality, rethoracotomy, proportion of patients receiving a transfusion, or perioperative myocardial infarction) in addition to perioperative blood loss. In addition, a separate meta-analysis was done for studies concerning complicated cardiac surgery.. We identified 72 trials (8409 patients) that met the inclusion criteria. Treatment with aprotinin decreased mortality almost two-fold (odds ratio 0.55 [95% CI 0.34-0.90]) compared with placebo. Treatment with aprotinin and with lysine analogues decreased the frequency of surgical re-exploration (0.37 [0.25-0.55], and 0.44 [0.22-0.90], respectively). These two treatments also significantly decreased the proportion of patients receiving any allogeneic blood transfusion. By contrast, the use of desmopressin resulted in a small decrease in perioperative blood loss, but was not associated with a beneficial effect on other clinical outcomes. Aprotinin and lysine analogues did not increase the risk of perioperative myocardial infarction; however, desmopressin was associated with a 2.4-fold increase in the risk of this complication. Studies in patients undergoing complicated cardiac surgery showed similar results.. Pharmacological strategies that decrease perioperative blood loss in cardiac surgery, in particular aprotinin and lysine analogues, also decrease mortality, the need for rethoracotomy, and the proportion of patients receiving a blood transfusion.

Topics: Aminocaproates; Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Blood Transfusion; Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Hemostatics; Humans; Myocardial Infarction; Placebos; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Reoperation; Thoracotomy; Tranexamic Acid; Treatment Outcome

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Drug Evaluation; Hemorrhage; Humans; Middle Aged; Myocardial Infarction; Postoperative Complications; Prevalence; Risk; Thromboembolism

The aim of the present study was to find out whether plasminogen activator inhibitor type-1 (PAI-1) controls the formation of plasmin in patients with ischaemic heart disease. We examined PAI activity, PAI-1 antigen, tissue type plasminogen activator (t-PA) activity, t-PA antigen, plasmin-alpha2-antiplasmin complex (PAP-complex) and fibrin degradation products D-dimer in 62 patients before (unstimulated) and after infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; stimulated). DDAVP was used in a standardized dose to trigger the release of t-PA from the vascular endothelium. We observed that under basal conditions (unstimulated) median plasma t-PA activity for the whole group of patients was 86.5 mIU/ml (0-900), and after stimulation 2550 mIU/ml (0-6800), P < 0.0001; median plasma concentration of t-PA antigen was 14.7 ng/ml (7.0-115.5) under basal conditions, and after stimulation 34.1 ng/ml (15.8-58.6), P < 0.0001; median plasma PAI activity was 16.9 IU/ml (1.5-144.8) under basal conditions, and after stimulation 3.1 IU/ml (0-118.5), P < 0.0001; median plasma concentration of PAI-1 antigen was 21.5 ng/ml (8.1-132.2) under basal conditions, and after stimulation 14.9 ng/ml (4.8-149.0), P < 0.0001; the median plasma concentration of PAP-complex was 469.5 ng/ml (185.0-1802.0) under basal conditions, and after stimulation 695.5 (243.0-2292.0), P < 0.0001; median plasma concentration of D-dimer was 298.0 ng/ml (103.0-948.0) under basal conditions, and after stimulation 296.5 ng/ml (97.0-917.0), P < 0.0008.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Amino Acid Sequence; Angina Pectoris; Biomarkers; Deamino Arginine Vasopressin; Endothelium, Vascular; Enzyme Activation; Female; Fibrinolysin; Fibrinolysis; Humans; Male; Middle Aged; Molecular Sequence Data; Myocardial Infarction; Plasminogen; Plasminogen Activator Inhibitor 1; Prospective Studies; Tissue Plasminogen Activator

The effects of single or repeated doses of desmopressin on blood loss were examined in uncomplicated cardiac surgery, while assessing the potential for thrombogenic side effects. Seventy patients undergoing elective coronary artery bypass grafting (CABG) were studied. Patients were randomized into three blinded groups: Group I received DDAVP (0.3 micrograms/kg), IV, after cardiopulmonary bypass (CPB) and 12 hours later in the Intensive Care Unit (ICU); Group II, DDAVP (0.3 micrograms/kg), IV, after termination of CPB and saline (placebo) 12 hours later in the ICU; Group III, saline (placebo) IV after CPB and 12 hours later in the ICU. Blood loss and bleeding time decreased for Group I at 24 hours (P < 0.04) when compared to Group III; however, blood product replacement, as well as intraoperative and total blood loss at 36 hours, were not different among treatment and control groups. There were four myocardial infarctions recorded in Group I, two in Group II, and one in Group III. These differences were not found to be statistically significant. It is concluded that in routine CABG the prophylactic use of single or repeat dose DDAVP does not effectively decrease blood loss or blood product replacement.

Topics: Bleeding Time; Blood Coagulation; Blood Loss, Surgical; Coronary Artery Bypass; Deamino Arginine Vasopressin; Drug Administration Schedule; Humans; Middle Aged; Monitoring, Intraoperative; Myocardial Infarction; Placebos; Postoperative Care; Prospective Studies; Single-Blind Method; Thrombosis

Impairment of platelet function commonly occurs after cardiopulmonary bypass, and may result in substantial bleeding. Because desmopressin acetate (a synthetic analogue of vasopressin) shortens bleeding time in a variety of platelet disorders, a controlled clinical trial of intravenous desmopressin was performed in 39 patients with excessive mediastinal bleeding (greater than 100 ml/h) and a prolonged template bleeding time (greater than 10 minutes) more than 2 hours after termination of cardiopulmonary bypass. Twenty-three desmopressin recipients and 16 control patients (no desmopressin) were similar in surgical procedure, pump time, platelet count, template bleeding time and amount of bleeding before therapy (p = NS). Compared with the control group, the patients receiving desmopressin (20 micrograms; mean 0.3 micrograms/kg) utilized fewer blood products (29 +/- 19 versus 15 +/- 13 units/patient; p less than 0.05), especially platelets (12 +/- 9 versus 4 +/- 7 units/patient; p = 0.004), while achieving a similarly effective reduction in mediastinal bleeding (4.8- and 4.3-fold, p = 0.001 for both). Severe platelet dysfunction was partially corrected within 1 hour after desmopressin infusion, during which interval no blood products were administered: the template bleeding time shortened (from 17 to 12.5 minutes, p less than 0.05), whereas the platelet count remained unchanged (at 96 +/- 35 and 105 +/- 31 X 10(3)/mm3, p = NS). The plasma levels of two factor VIII components increased: procoagulant activity (VIII:C) from 0.97 +/- 0.43 to 1.52 +/- 0.74 units/ml (p less than 0.05) and von Willebrand factor (VIII:vWF) from 1.28 to 1.78 units/ml (p less than 0.05); these increases correlated with the shortening of the bleeding time (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Platelet Disorders; Blood Transfusion; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Hematologic Tests; Hemorrhage; Humans; Myocardial Infarction; Postoperative Period; Reoperation

We describe a case of a 67-year-old man who required emergency surgery for acute intracranial bleeding after having received a loading dose of aspirin and ticagrelor for an acute ST-elevation myocardial infarction. Before and during the craniocervical decompression, the assessment of platelet function was performed using the Multiplate® analyzer. Biological evaluation of platelet function was consistent with the clinical impression, suggesting that platelet transfusion and desmopressin administration in the presence of ticagrelor had very little, if any, hemostatic effect.

Topics: Adenosine; Aged; Aspirin; Combined Modality Therapy; Deamino Arginine Vasopressin; Fatal Outcome; Hemostatics; Humans; Intracranial Hemorrhages; Male; Myocardial Infarction; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Platelet Transfusion; Purinergic P2Y Receptor Antagonists; Ticagrelor

Topics: Angioplasty, Balloon, Coronary; Deamino Arginine Vasopressin; Electrocardiography; Hemophilia A; Hemostatics; Humans; Male; Middle Aged; Myocardial Infarction; Perioperative Care; Premedication; Stents

Topics: Anemia, Hemolytic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Deamino Arginine Vasopressin; Female; Hemolytic-Uremic Syndrome; Hemostatics; Humans; Middle Aged; Myocardial Infarction; Thrombosis

Impaired endogenous tissue-type plasminogen activator (t-PA)-mediated fibrinolysis may be involved in the evolution of myocardial infarction. t-PA-mediated fibrinolysis is believed to depend on the amount of active t-PA present in the circulation. Accordingly, we investigated the possible mechanisms responsible for impaired t-PA-mediated fibrinolysis in patients with ischaemic heart disease.. Forty-five survivors of acute myocardial infarction were examined 8 weeks after discharge from hospital. Intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; 0.4 micrograms/kg bodyweight) was used to stimulate the endogenous fibrinolytic system, and blood samples were collected before and after infusion. We compared the response of the t-PA-plasminogen activator inhibitor type-1 (PAI-1) fibrinolytic system in patients with preinfusion levels of active t-PA below or at the detection limit of the assay with that in patients with higher preinfusion levels of active t-PA.. All patients responded to DDAVP infusion with an increase in plasma concentration of t-PA antigen. This response did not differ between the two groups. In contrast, the preinfusion levels of PAI activity were significantly higher in patients with undetectable plasma levels of active t-PA compared with patients with higher levels of active t-PA (22.3 versus 12.8 IU/ml; P < 0.01). Subgroup analyses demonstrated that patients treated with diuretics had significantly higher plasma concentrations of PAI-1 antigen (28.5 versus 17.9 ng/ml; P < 0.03) and a trend towards higher PAI activity (24.0 versus 14.6 IU/ml; P = 0.07) compared with patients not receiving diuretics.. Our study strongly suggests that a high plasma level of PAI-1, the main inhibitor of t-PA, is responsible for impaired t-PA-mediated fibrinolysis in patients with ischaemic heart disease, and that treatment with diuretics may be associated with an unfavourable effect on the fibrinolytic system.

Topics: Aged; Deamino Arginine Vasopressin; Diuretics; Enzyme-Linked Immunosorbent Assay; Female; Fibrinolysis; Humans; Lipoproteins; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Plasminogen Activator Inhibitor 1; Tissue Plasminogen Activator

An inadequate efficiency of the fibrinolytic system was revealed in 50-60% of subjects suffering young age from venous thrombosis or myocardial infarction. In a group of 27 patients with the history of deep venous thrombosis of the idiopathic type the authors revealed a significant relationship between the elevated body weight and inadequate fibrinolysis manifested by a reduced fibrinolytic capacity and excess inhibitor of plasminogen activator and its inadequate decline after desmopressin infusion (DDAVP). In a group of 29 patients, who had suffered a myocardial infarction when young, the authors revealed a significant association between reduced fibrinolytic capacity and elevated body weight, hypertriglyceridaemia and increased immunoreactive insulin secretion after a glucose load. In half the investigated subjects it proved possible to improve the reduced fibrinolytic capacity by a low energy diet.

Topics: Adult; Deamino Arginine Vasopressin; Energy Intake; Female; Fibrinolysis; Humans; Male; Middle Aged; Myocardial Infarction; Risk Factors; Thrombophlebitis

Topics: Blood Donors; Deamino Arginine Vasopressin; Factor VIII; Humans; Male; Middle Aged; Myocardial Infarction

Topics: Aged; Bundle-Branch Block; Deamino Arginine Vasopressin; Gastrointestinal Hemorrhage; Humans; Male; Myocardial Infarction

Topics: Coronary Disease; Coronary Thrombosis; Deamino Arginine Vasopressin; Humans; Myocardial Infarction

Topics: Aged; Deamino Arginine Vasopressin; Hemophilia A; Humans; Male; Myocardial Infarction

Topics: Adult; Arginine Vasopressin; Deamino Arginine Vasopressin; Female; Fibrinolysis; Humans; Male; Middle Aged; Myocardial Infarction; Thrombophlebitis

The fibrinolytic capacity was assessed in 18 healthy subjects and in 8 patients each with non-idiopathic venous thrombosis, idiopathic venous thrombosis and myocardial infarction after intravenous administration of 1-deamino-8-D-arginine vasopressin (DDAVP) (0.4 microgram/kg) in comparison to venous occlusion. In healthy subjects the results obtained by either stimulus were approximately in agreement. Compared to the control group, in patients with non-idiopathic venous thrombosis the fibrinolytic capacity was not changed either after venous occlusion or after administration of DDAVP. In 5 out of 8 patients with idiopathic venous thrombosis the capacity was significantly reduced both after venous occlusion and after administration of DDAVP. In 4 out of 8 patients with myocardial infarction the capacity was significantly below the limit after administration of DDAVP while it was not after venous occlusion. In determining the fibrinolytic capacity DDAVP proved to be superior to venous occlusion.

Topics: Adult; Blood Coagulation Tests; Deamino Arginine Vasopressin; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Middle Aged; Myocardial Infarction; Prognosis; Thrombophlebitis; Thrombosis