Effect of Desmopressin (DDAVP) on Protein C and Protein C Inhibitors in Uremia

Tekin, Mustafa; Özdemir, Oktay; Arık, Nurol; Demırkan, Fatih; Sungur, Cem; Özcebe, Osman; Dündar, Semra; Yasavul, Ünal; Turgan, Çetin; Kirazlı, Şerafettin

doi:10.1159/000187319

Cited by 4 publications

(4 citation statements)

References 7 publications

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“…Since the levels of well-known inhibitors of PC. PAI-3 and ai-antitrypsin, did not change after DDAVP infusion, it has been suggested that the decrease in PC was not linked to the inhibitors per se [4], There was no change in these inhibitors in our study as well.…”

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confidence: 41%

“…Mannucci et al [1] have suggested that the appearance of larger forms of the FVIILvWF complex, induced by DDAVP, or the release of vWF from stor age sites, may be effective in promoting platelet adhesion to endothelium. DDAVP is expected to reduce PC activity which is a potent anticoagulant and this might contrib ute to the normalization of bleeding tenden cy in uremic patients and even in healthy subjects [4,5]. Since the levels of well-known inhibitors of PC.…”

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confidence: 99%

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Low-Dose Intranasal Desmopressin (DDAVP) for Uremic Bleeding

Özen

Saatçi

Bakkaloğlu

et al. 1997

Nephron

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In children with advanced chronic renal failure, bleeding is a frequent complication which contributes to morbidity and even mortality. In the last decade, desmopres sin (l-deamino-8-D-argininc vasopressin; DDAVP). a synthetic analogue of antidiuret ic hormone, has been used to treat uremic bleeding. The exact mechanism by which DDAVP corrects uremic bleeding is still not clear; DDAVP-induccd release of large von Willebrand factor (vWF) multiniers or re lease of serotonin from uremic platelets has been among the suggested mechanisms [1. 2]. Although DDAVP has usually been ad ministered parenterallv in uremic patients, this route of application requires a physician and is not very feasible for children. Intra nasal DDAVP at high doses has also been put into use in uremic patients [3],In the presented study, we have exam ined the effect of low-dose (10 and 20 pig) intranasal DDAVP (Minirin) on bleeding time, factor VIII procoagulant activity (FVIIEC). vWF. protein C (PC) activity, plasminogen activator inhibitor-3 (PAI-3). di-antitrypsin and thrombomodulin in our uremic children on maintenance hemodialy sis. We have thus attempted to investigate the mode of action of low-dose intranasal DDAVP and clarify its action in potentiat ing hemostasis. The patient group consisted of 11 children hemodialyzed thrice weekly with cuprophane membranes. The age range was 12-21 years (median 16). Six of them had clinical signs of bleeding diathesis in the form of dysmenorrhea, or oral or nasal/nasopharyngcal bleeding and/or gastrointestinal bleeding, or in the form of spontaneous ecchymotic skin lesions. DDAVP was admin istered intranasally at a dose of 10 pg at the first phase of the study (44 h after the termi nation of the previous dialysis session). At the second phase of the study. 2 days later. 20 ug DDAVP was given by the same route. In only 1 patient (No. 2), who developed heparin-induced thrombocytopenia, a third dose of DDAVP was administered intrave nously (0.3 pg-kg-1).Ivy bleeding times were measured before and 2 h after DDAVP administration by a medical person who was blinded to the aim of the procedure and the medications given to the study subjects. Statistical analysis was performed by repeated measures two-way analysis of variance. In this analysis, time (be fore vs. after) and dose (10 vs. 20 pg) effects as within-subjects factors and also time-dose in teraction were included in the model. A statis tical package for social sciences (SPSS) for Windows v5.1 software was used.In the 6 patients with bleeding diathesis, a clinical response was achieved: the abnor mal bleeding subsided within 1-3 days in all and did not recur during the 2 weeks of treat ment with DDAVP 20 pg daily. Mean bleed ing time shortened from 8.2 ± 4.8 to 7.1 ± 4.8 min at the first stage (10 pg DDAVP) and from 8.3 ± 4.6 to 6.9 ± 4.7 min at the second stage (20 pg DDAVP: dose effect, p = 0.49; lime effect, p = 0.0002: time-dose in teraction. p = 0.33; table 1). The number of KARGER 0 1996 S. Karger AG. Basel

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confidence: 41%

mentioning

confidence: 99%

Low-Dose Intranasal Desmopressin (DDAVP) for Uremic Bleeding

Özen

Saatçi

Bakkaloğlu

et al. 1997

Nephron

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“…Desmopressin is the treatment of choice for uremic bleeding when only a short-term effect is required; it is indicated to prevent hemorrhage after biopsies or minor surgical procedures or to treat acute bleeding. A significant reduction in protein C activity after desmopressin infusion in uremic patients has been described [60,61]. A few elderly uremics with atheroscle rosis have been reported to develop stroke or myocardial infarction after desmopressin administration.…”

Section: Management O F Bleedingmentioning

confidence: 98%

Bleeding and Thrombosis in Chronic Uremia

Sagripanti¹,

Barsotti²

1997

Nephron

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“…A low activity of protein C (PC) has been described in uremia [2][3][4] and PC activity is further reduced after infusion of DDAVP in uremic patients [2,4], This further decrease in PC activity might contribute to the explanation of the normalization of the bleeding tendency after DDAVP infusion. Protein S (PS) and anti thrombin III (AT-III) may have some role in the inactivation of PC activity [5], The aim of this study was to clarify the effect of DDAVP on AT-III and PS in uremia.…”

mentioning

confidence: 99%