deamino-arginine-vasopressin and Thrombosis

Von Willebrand disease (VWD) is the most common genetic bleeding disorder. VWD is caused by a deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates the initial adhesion of platelets at sites of vascular injury and binds and stabilises coagulation factor VIII (FVIII) in the blood. Prophylaxis of surgical bleeding in patients with VWD requires consideration of the individual situation, including the type of procedure and the bleeding rate, before decisions about treatment type, dose, duration and adjunctive therapy with antifibrinolytics or antithrombotic prophylaxis can be made. Although desmopressin (DDAVP)-stimulated release of endogenous VWD is an effective treatment strategy in many patients, plasma concentrates containing VWF are the preferred option for most patients undergoing surgical procedures. Recommendations for the management of surgery in patients with VWD are summarised, including the severity of VWD and the type of the surgical procedure.

Topics: Clinical Decision-Making; Deamino Arginine Vasopressin; Disease Management; Factor VIII; Hemorrhage; Humans; Premedication; Surgical Procedures, Operative; Thrombosis; Treatment Outcome; von Willebrand Diseases; von Willebrand Factor

Essentials The optimal management of patients with platelet dysfunction undergoing surgery is unclear. This meta-analysis compared perioperative administration of desmopressin to placebo. Desmopressin reduced red cell transfusions, blood loss and risk of re-operation due to bleeding. There were too few events to determine if there was a change in the risk of thrombotic events.. Background Platelet dysfunction, including that caused by antiplatelet agents, increases the risk of perioperative bleeding. The optimal management of patients with platelet dysfunction undergoing surgery is unclear. Objectives To assess whether desmopressin reduces perioperative allogeneic red cell transfusion and bleeding in patients with platelet dysfunction. Patients/Methods We searched for randomized controlled trials in The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, the Transfusion Evidence Library and the ISI Web of Science to 7th July 2016. Data were pooled using mean difference (MD), relative risks or Peto odds ratios (pOR) using a random-effects model. Results Ten trials with 596 participants were identified, all in the setting of cardiac surgery. Platelet dysfunction was due to antiplatelet agents in six trials and cardiopulmonary bypass in four trials. Patients treated with desmopressin were transfused with fewer red cells (MD, -0.65 units; 95% Confidence Interval [CI], -1.16 to -0.13 units), lost less blood (MD, -253.93 mL; 95% CI, -408.01 to -99.85 mL) and had a lower risk of re-operation due to bleeding (pOR, 0.39; 95% CI, 0.18-0.84). The GRADE quality of evidence was very low to moderate, suggesting considerable uncertainty over the results Conclusions Desmopressin may be a useful agent to reduce bleeding and transfusion requirements for people with platelet dysfunction or with a history of recent antiplatelet drug administration undergoing cardiac surgery.

Topics: Blood Loss, Surgical; Blood Platelet Disorders; Blood Platelets; Blood Transfusion; Deamino Arginine Vasopressin; Erythrocyte Transfusion; Hemorrhage; Hemostatics; Humans; Platelet Aggregation Inhibitors; Platelet Transfusion; Randomized Controlled Trials as Topic; Thrombosis; Treatment Outcome

Therapy for von Willebrand disease (VWD) aims to restore the hemostatic function conferred by von Willebrand factor (VWF), which facilitates platelet adhesion and aggregation, and serves to increase potentially low coagulation factor VIII (FVIII) in plasma. In patients unresponsive to desmopressin (DDAVP), the preferred treatment is with plasma-derived VWF-containing FVIII concentrates. Only a few of the available VWF/FVIII concentrates have been licensed for use in VWD based on prospective studies. The efficacy of VWF/FVIII concentrates depends on the content and quality of VWF and FVIII. Several studies have demonstrated the variability of the VWF contents, as well as the differences in the VWF multimer patterns (including the high molecular weight VWF multimers that are most effective in restoring hemostasis), among these concentrates. Treating physicians should be aware of these disparities and the potential clinical implications for patients with different VWD subtypes. Dosing has traditionally been calculated based on the FVIII content of the products, although dosing based on VWF functional activity [e.g., VWF ristocetin cofactor activity (VWF:RCo)] addresses the primary protein deficiency in VWD patients. Several clinical studies have demonstrated the efficacy of concentrates dosed according to VWF:RCo. Dosing is generally consistent across VWD subtypes, although patients with severe phenotypes or undergoing major procedures may require more infusions or longer treatment duration. Other considerations for the use of VWF-containing concentrates include laboratory monitoring of efficacy and safety issues such as thrombosis risk and thromboprophylaxis.

Topics: Clinical Trials as Topic; Deamino Arginine Vasopressin; Drug Combinations; Factor VIII; Hemostasis; Hemostatics; Humans; Platelet Adhesiveness; Platelet Aggregation; Thrombosis; Time Factors; von Willebrand Diseases; von Willebrand Factor

Patients with essential thrombocythemia (ET) and polycythemia vera (PV), complicated by microvascular ischemic or thrombotic events, have shortened platelet survival, increased beta-thromboglobulin, platelet factor 4, and thrombomodulin levels, and increased urinary thromboxane B2 excretion. These are all reversible by inhibition of platelet cyclooxygenase 1 with aspirin, and are therefore indicative of platelet activation and platelet-mediated thrombotic processes. The thrombotic tendency persists as long as platelet counts are above the upper limit of normal (400 x 10 (9)/L). Despite strong evidence of in vivo platelet activation, the ex vivo platelet function tests are impaired. Platelet dysfunction in ET and PV typically is characterized by a missing second-wave adrenaline aggregation, an increased adenosine diphosphate aggregation threshold, and reduced secretion products, but a normal arachidonic acid or collagen-induced aggregation. The proposed concept is that platelets in thrombocythemia (ET and PV) are hypersensitive. Due to the existing high shear stress in the microvasculature (end-arterial circulation), platelets spontaneously activate, secrete their products, form aggregates mediated by von Willebrand factor (vWF) that transiently plug the microcirculation, deaggregate, and then recirculate as exhausted defective platelets with secondary storage pool disease on ex vivo analysis. At increasing platelet counts from below to above 1000 x 10 (9)/L, the thrombotic condition changes into an overt spontaneous bleeding tendency as a result of a functional vWF deficiency that is caused by proteolysis of large vWF multimers. This is consistent with acquired type 2 von Willebrand syndrome (AvWS). AvWS is reversible by reduction of the platelet count to normal. The acquired JAK2 V617F gain of function mutation is the cause of trilinear myeloproliferative disease with the sequential occurrence of ET and PV. Heterozygous JAK2 V617F mutation with slightly increased kinase activity is enough for the induction of spontaneous megakaryopoiesis and erythropoiesis, and an increase of hypersensitive platelets is the cause of aspirin-sensitive, platelet-mediated microvascular ischemic and thrombotic complications in ET and early PV mimicking ET. Homozygous JAK2 mutation with pronounced increase of kinase activity is associated with pronounced trilinear megakaryocyte, erythroid, and granulocytic myeloproliferation, with the most frequent clinical picture of classic

Topics: Aspirin; Bleeding Time; Blood Platelets; Deamino Arginine Vasopressin; Hemorrhage; Humans; Microcirculation; Mutation; Platelet Activation; Platelet Function Tests; Polycythemia Vera; Thrombocythemia, Essential; Thrombosis; von Willebrand Factor

Disorders of thrombosis and hemostasis represent both diagnostic and therapeutic challenges for the clinician, in part because of sex-based differences in incidence and presentation. The hemophilias are characterized by specific sex-linked patterns of inheritance, and there are sex differences in the presentation of the autosomally inherited disorders, particularly von Willebrand's disease. The diagnosis of these disorders can be affected by variations in either endogenous or exogenous estrogens, and the hemostatic stresses presented by menstruation and childbirth render any coagulopathy more severe in females than in males. Women are also at increased risk for developing thrombotic and embolic problems while on exogenous estrogens and during pregnancy. This article presents recommendations about the most appropriate and cost-effective ways to screen for the inherited disorders of both thrombosis and hemostasis in men and women. Recommendations are also developed for the treatment of women with these disorders, particularly in the context of pregnancy, contraception, uterine bleeding, and postmenopausal management.

Topics: Contraceptives, Oral, Hormonal; Deamino Arginine Vasopressin; Estrogen Replacement Therapy; Female; Hemophilia A; Hemostasis; Humans; Infusions, Parenteral; Male; Risk Factors; Sex Factors; Thrombosis; Venous Thrombosis; von Willebrand Diseases; X Chromosome

This paper discusses clinical experience of the use of desmopressin in patients with either congenital or acquired bleeding disorders. The bleeding disorders reviewed herein are haemophilia A, von Willebrand's disease and platelet function disorders (congenital bleeding disorders); uraemia, liver cirrhosis and drug-induced bleeding (acquired bleeding disorders).

Topics: Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Thrombosis; von Willebrand Diseases

Any therapy must have a benefit and a risk. The benefit of aprotinin therapy in reducing bleeding is well known. Data presented over the past 12 months have confirmed this efficacy and the superiority and consistency of aprotinin therapy in direct comparison with other pharmacologic (desmopressin, tranexamic acid) and physical (administration of fresh platelet concentrate) interventions. The debate has now changed to focus on issues of the safety of this agent. In particular, concerns have been expressed as to the effect of this agent on renal function, thrombotic potential (and thus graft patency), and adverse reactions on a second exposure. Most recent reports show plasma creatinine concentrations are higher in treated than in nontreated patients on the 3rd or 4th postoperative day. The concentrations reached were not outside the clinical range, and there were no clinical sequelae of this biochemical abnormality. Focused studies have shown no effect of the use of aprotinin therapy on early graft patency or the incidence of thromboembolic complications. The reporting of hypersensitivity reactions following aprotinin administration suggests that the incidence is not different to other agents used in open heart surgery. Three reports of fatal or near-fatal cardiovascular collapse associated with the use of aprotinin followed the apparently inappropriate administration of the agent.

Topics: Aprotinin; Coronary Artery Bypass; Creatinine; Deamino Arginine Vasopressin; Drug Hypersensitivity; Hemostasis, Surgical; Hemostatics; Humans; Kidney; Platelet Transfusion; Safety; Thrombosis; Tranexamic Acid; Vascular Patency

Topics: Aged; Blood Coagulation Disorders; Blood Coagulation Factors; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Hemorrhagic Disorders; Hemostasis; Humans; Male; Platelet Adhesiveness; Postoperative Complications; Signal Transduction; Thrombosis

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

Topics: Antigens; Deamino Arginine Vasopressin; Endothelium, Vascular; Factor VIII; Hemophilia A; Hemorrhagic Disorders; Hemostasis; Hemostasis, Surgical; Hemostatics; Humans; Receptors, Angiotensin; Receptors, Vasopressin; Thrombosis; von Willebrand Factor

Treatment of hemophilia and von Willebrand's disease has become easier in recent years because of the development of more effective factor replacement products. The median age and the life expectancy of patients with hemophilia have risen markedly, as has the median age at death.

Topics: Acquired Immunodeficiency Syndrome; Antigens; Blood Coagulation Factors; Cerebral Hemorrhage; Danazol; Deamino Arginine Vasopressin; Factor VIII; Female; Gastrointestinal Hemorrhage; Hemophilia A; Hemorrhage; Hepatitis B; Hepatitis C; Humans; Pregnancy; Surgical Procedures, Operative; Thrombosis; Tooth Extraction; von Willebrand Diseases

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

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

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Blood Coagulation Factors; Cerebral Hemorrhage, Traumatic; Cerebral Intraventricular Hemorrhage; Clopidogrel; Deamino Arginine Vasopressin; Female; Fractures, Bone; Hematoma; Hematoma, Subdural, Intracranial; Hemostatics; Humans; International Normalized Ratio; Intracranial Hemorrhage, Traumatic; Male; Middle Aged; Pelvic Bones; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Subarachnoid Hemorrhage, Traumatic; Thrombosis; Warfarin

We report an unusual case of severe abdominal arterial thrombosis in a young woman using oral desmopressin. Only a few cases with cerebrovascular accidents and coronary syndromes have been described so far, which could be attributed to intravenous administration of desmopressin. Because extensive diagnostic and laboratory investigations for (un)common coagulation disorders could not identify an alternative explanation associated with arterial thrombosis, we hypothesise that desmopressin in an oral dose of at least 200 ug once daily must have been sufficient to cause this dramatic vascular complication. Supportive of our hypothesis, we found remarkably high levels of factor VIII activity, Von Willebrand factor (vWF) antigen and vWF ristocetin cofactor activity (268%, 740%, 590% respectively). To the best of the authors' knowledge, this is the first report suggesting a relationship between oral desmopressin use and life-threatening abdominal arterial thrombosis.

Topics: Abdominal Pain; Adult; Blood Coagulation Disorders; Cerebrovascular Disorders; Deamino Arginine Vasopressin; Echocardiography; Factor VIII; Female; Hemostatics; Humans; Ristocetin; Thrombosis; Tomography, X-Ray Computed; von Willebrand Factor

To elucidate how unusually large von Willebrand factor (UL-VWF) multimers facilitate thrombus formation, their behavior was analyzed together with that of platelets in living mice deficient in the gene encoding the protease that cleaves UL-VWF, a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13-/-). By crossing ADAMTS13-/- mice with green fluorescent protein-expressing transgenic mice (GFP mice), GFP-ADAMTS13-/- mice were obtained. The dynamics of GFP-expressing platelets were monitored employing intravital confocal fluorescent microscopy. Administration of a vasopressin derivative, DDAVP, a secretagogue of VWF increased the number of platelets adhered to vascular endothelial cells (VECs) on mesentery at sites recognized by an anti-VWF antibody. Some of these platelets were interconnected and aligned as beads on a string. They reached their maximum length at 5 min and were longer in GFP-ADAMTS13-/- mice than in GFP mice (5.3 ± 4.3, N = 6 vs 2.9 ± 2.1 μm, N = 4) (mean±SE). Focal injury of VECs by topical application of FeCl(3) developed longer (25, 3-50 vs 10, 2-25 μm, P < 0.01) (mean, 10th-90th percentile) and more stable (1.3, 0.3-6.3 vs 0.3, 0.2-1.3 s, P < 0.01) connected platelets in GFP-ADAMTS13-/- mice than in GFP mice. This study revealed that ADAMTS13 cleaves platelet-bound UL-VWF multimers, both during their secretion from VECs and after their adherence to injured vascular walls in veins. UL-VWF multimers either being secreted from VECs or circulating in plasma of ADAMTS13-/- mice appeared to facilitate the accumulation of longer and more stable VWF strings with more associated platelets on injured vascular walls.

Topics: ADAMTS13 Protein; Animals; Blood Platelets; Deamino Arginine Vasopressin; Endothelium, Vascular; Lasers; Metalloendopeptidases; Mice; Mice, Transgenic; Microscopy, Confocal; Platelet Adhesiveness; Protein Multimerization; Thrombosis; von Willebrand Factor

Prothrombin complex concentrates are frequently used to rapidly reverse anticoagulation with vitamin K antagonists associated with life-threatening bleeding. We report a patient receiving warfarin who presented to the emergency department with an international normalization ratio greater than 12.8 in cardiac tamponade and received prothrombin complex concentrate for rapid reversal of anticoagulation. On correction of the tamponade, the patient developed a massive and fatal right-sided ventricular thrombus. Thrombogenic complications of treatment with prothrombin complex concentrate have been reported before. Caution should be used when using prothrombin complex concentrates for reversal of anticoagulation.

Topics: Aged; Blood Coagulation Factors; Cardiac Tamponade; Coagulants; Deamino Arginine Vasopressin; Drug Synergism; Fatal Outcome; Heart Diseases; Heart Ventricles; Hemostatics; Humans; International Normalized Ratio; Male; Pericardial Effusion; Prothrombin Time; Thrombosis

Topics: Blood Coagulation; Blood Coagulation Factors; Chemistry, Pharmaceutical; Coagulants; Deamino Arginine Vasopressin; Drug Interactions; Evidence-Based Medicine; Humans; Thrombosis

Topics: Deamino Arginine Vasopressin; Factor VIII; Humans; Thrombosis; von Willebrand Diseases; von Willebrand Factor

Topics: ADAM Proteins; ADAMTS13 Protein; Administration, Intranasal; Child; Deamino Arginine Vasopressin; Enuresis; Female; Hemostatics; Humans; Purpura, Thrombotic Thrombocytopenic; Recurrence; Syndrome; Thrombosis

Desmopressin (DDAVP) is commonly used in cadaveric organ donors to treat diabetes insipidus. The thrombogenic potential of DDAVP is well known. Recent animal data have demonstrated that DDAVP impairs pancreas graft (PG) microcirculation and perfusion. The aim of this study was too evaluate the effect of DDAVP on the incidence of PG thrombosis in clinical pancreas transplantation. A retrospective review of simultaneous kidney-pancreas transplant (SKPT) entered in the Scientific Registry of Transplant Recipients (SRTR) between 10/5/87 and 9/27/02 was performed. Patients were included for analysis if there was definitive documentation as to whether DDAVP was (DDAVP-Y) or was not (DDAVP-N) administered to the donor. Both dose and duration of DDAVP treatment were not recorded by SRTR. A total of 2804 SKPTs were available for analysis. Mean follow-up was 1.75 years (range, 1 month to 8.4 years). A total of 1287 SKPT patients (46%) received a PG from a DDAVP-Y donor. Graft ischemia times, donor and recipient ages, recipient gender distribution, surgical techniques, and immunosuppressive regimens were similar in both groups. The overall incidence of PG thrombosis was 4.3%. The incidence of PG thrombosis in recipients of grafts from DDAVP-Y donors was 5.1% compared to 3.5% in recipients of grafts from DDAVP-N donors (P =.04). Fifty-eight percent of thrombosed PG came from DDAVP-Y donors compared to 42% from DDAVP-N donors (P =.04). We conclude that there appears to be a relationship between donor treatment with DDAVP and PG thrombosis. A prospective study is needed to verify these findings and to determine their clinical significance.

Topics: Cadaver; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Humans; Male; Pancreas; Pancreas Transplantation; Postoperative Complications; Retrospective Studies; Thrombosis; Time Factors; Tissue Donors

Aspirin causes a coagulation disorder. Desmopressin has haemostatic effects by increasing the plasma levels of coagulation factor VIII and von Willebrand factor. The precise effects of desmopressin on thrombogenesis are not known. In an in vivo model, we investigated the effect of the drug on thrombus formation and platelet function after aspirin use. Male Lewis rats weighing 250-300 g were used. Four groups with 10 animals each were formed: control, aspirin, desmopressin and aspirin + desmopressin. In each animal, the femoral artery was dissected. A thrombogenic vessel injury was created by inverting a full thickness portion of the proximal edge of the incised artery into the lumen. The following parameters were measured: maximum thrombus size, time period until maximum thrombus size was reached and overall platelet function. In addition, the thrombi generated were investigated histologically. Thrombus formation time was significantly shorter with desmopressin compared with the animals treated with aspirin (P < 0.0001) and controls (P = 0.008). Maximum thrombus size was larger in the desmopressin and desmopressin + aspirin groups when compared with the group treated with aspirin only. Overall platelet function was significantly enhanced with desmopressin compared with controls (P = 0.025) and with aspirin (P < 0.0001). The differences were confirmed histologically. In conclusion, desmopressin significantly accelerates thrombus formation in aspirin-treated animals. It can also re-establish thrombus size after the use of aspirin. Overall platelet function is significantly increased by desmopressin.

Topics: Animals; Aspirin; Blood Platelets; Deamino Arginine Vasopressin; Hemostatics; Male; Platelet Aggregation Inhibitors; Platelet Function Tests; Rats; Rats, Inbred Lew; Thrombosis

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

Topics: Animals; Deamino Arginine Vasopressin; Hemostatics; Humans; Microcirculation; Pancreas; Pancreas Transplantation; Postoperative Complications; Thrombosis; Tissue Donors; Treatment Failure

The objective of this study was to investigate the effects of isovolemic hemodilution with dextran-70 on thrombus formation and blood flow in synthetic venous vessel grafts. Polytetrafluoroethylene grafts (length, 11 mm; inner diameter, 3 mm) were inserted into the vena cava of rabbits. Six groups were studied: (1) the control group; (2) animals that underwent isovolemic hemodilution with dextran-70 to a hematocrit of about 30%; (3) animals that underwent isovolemic dextran hemodilution combined with a bolus injection of heparin; (4) animals that underwent heparin treatment only; (5) animals that underwent isovolemic dextran hemodilution combined with infusion of desmopressin; and (6) animals that underwent an identical treatment to group 3 but with a 2-week, instead of a 2-day, follow-up. Vena cava blood flow was measured before and after hemodilution and graft insertion and at the termination of the experiments at 2 days (groups 1 to 5) and 2 weeks (group 6) after surgery. Graft patency and thrombus mass weight were evaluated. In the control group, most of the vessels occluded within 2 days. Hemodilution with dextran improved blood flow and reduced thrombus mass weight significantly. Desmopressin, which increases factor VIII, did not influence the effects of hemodilution with dextran, which suggests that the effects of dextran are not mediated by a reduction in the level of this coagulation factor. A single bolus dose of heparin did not reduce thrombus formation in the grafts but did potentiate the effects of isovolemic hemodilution on thrombus mass and graft blood flow. We conclude that isovolemic dextran hemodilution combined with a single bolus of heparin had beneficial long-lasting effects. The grafts in groups 3 and 6 were all patent.

Topics: Animals; Anticoagulants; Blood Vessel Prosthesis Implantation; Deamino Arginine Vasopressin; Dextrans; Female; Hemodilution; Heparin; Male; Polytetrafluoroethylene; Rabbits; Thrombosis; Vascular Patency; Vena Cava, Inferior

The effects on hemostatic and thromboprophylactic mechanisms of intravenous desmopressin (DDAVP, 0.3 micrograms/kg) and dextran 40 and 70 given both separately and in various combinations were evaluated in five male volunteers. Dextran did not inhibit the DDAVP-induced hemostatic changes. The dextran-induced decrease in platelet adhesiveness and the prolonged bleeding time were totally reversed by DDAVP. Hematocrit decrease was seen after both drugs, lasting longer when they were combined. We conclude that DDAVP and dextran may be used concomitantly, each with maintained beneficial properties. DDAVP will still act hemostatically by increasing platelet adhesiveness, factor VIII and von Willebrand factor and by shortening the dextran-induced prolongation of bleeding time. Dextran and DDAVP may even have additive antithrombotic effects due to the DDAVP-induced stimulation of the fibrinolytic activity, which is not inhibited by dextran, and to rheologic changes such as hematocrit decrease induced by both drugs.

Topics: Adult; Blood Coagulation Factors; Deamino Arginine Vasopressin; Dextrans; Fibrinolysis; Hematocrit; Hemostasis; Humans; Male; Platelet Adhesiveness; Reference Values; Thrombosis

Topics: Aged; Deamino Arginine Vasopressin; Humans; Middle Aged; Thrombosis

Topics: Adult; Aged; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Factor XII; Female; Humans; Male; Middle Aged; Thrombosis

Topics: Blood Coagulation; Deamino Arginine Vasopressin; Fibrinolysis; Humans; Thrombosis

The multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the "in vivo" proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities. The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring "in vivo" rather than "in vitro", and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.

Topics: Deamino Arginine Vasopressin; Hemorrhage; Humans; Myeloproliferative Disorders; Protein Conformation; Syndrome; Thrombosis; von Willebrand Factor

Topics: Adult; Deamino Arginine Vasopressin; Female; Humans; Kidney Failure, Chronic; Renal Dialysis; Risk Factors; Thrombosis

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

Immunoradiometric determination of the blood/tissue plasminogen activator was in plasma from patients before and after response to venous occlusion, infusion of DDAVP or exercise. The raise in the level of plasminogen activator was most pronounced after venous occlusion. In patients who earlier had had verified thrombosis the levels of plasminogen activator compared to normals did not show any significant difference.. Although etiology of thrombosis is multifactoral, the single common defect in the majority of case is the deficiency of plasminogen activators in the fibrinolytic defense system. Development of a new immunoradiometric method for determining blood/tissue activators prompted an examination of plasminogen activator blood levels in patients with previously verifed thrombosis. After immunoradiometric testing of plasma of 26 confirmed thrombosis patients, according to the detailed procedure described, and comparing the results with plasma levels of a control group before and after response to venous occlusion, infusion of DDAVP, or exercise, no significant differences were seen between levels in thrombosis patients and controls; increase of plasminogen activator activity was most pronounced in the controls after venous occlusion. The method has shown that 3 stimuli cause an increase in plasminogen activator levels. This is in agreement with previous observations, i.e., that these stimuli increase fibrinolytic activity in the blood. These results do not indicate, however, which of the tests is most suitable for detecting predissposition to thrombosis in certain patients. In order to clarify this point, tests of patients with recurring thromboses must be conducted. Furthermore, this method would not appear to be suitable as a screening process for women taking oral contraceptives to determine possible thrombosis tendency due to the excessive expense involved.

Topics: Contraceptives, Oral; Deamino Arginine Vasopressin; Female; Fibrinolysis; Humans; Male; Plasminogen Activators; Risk; Thrombosis

In 20 patients the fibrinolytic capacity was assessed by the venous occlusion test and by stimulation with DDAVP injection (0.4 microgram/kg). Irrespective of the test used, all cases were classified into the same group of responsiveness (responder, low responder, non-responder) with the exception of one patient. DDAVP injection caused subjective discomfort only in some cases, while the venous occlusion test was invariably accompanied by pain.

Topics: Arginine Vasopressin; Arm; Blood Coagulation Tests; Blood Flow Velocity; Deamino Arginine Vasopressin; Fibrin; Fibrinolysis; Humans; Thrombosis; Veins