deamino-arginine-vasopressin and Anemia--Sickle-Cell

Nocturnal enuresis is a prevalent and challenging problem in children and young adults with sickle cell disease (SCD). Limited progress has been made in elucidating etiology and pathophysiology of nocturnal enuresis in individuals with SCD. Among adults with SCD ages 18-20 years, approximately 9% report nocturnal enuresis. Nocturnal enuresis contributes to decreased health related quality of life in people with SCD, resulting in low self-esteem and sometimes social isolation. Postulated non-mutually exclusive causes of nocturnal enuresis in individuals with SCD include hyposthenuria leading to nocturnal polyuria, decreased bladder capacity or nocturnal bladder overactivity, increased arousal thresholds, and sleep disordered breathing. No evidence-based therapy for nocturnal enuresis in SCD exists. This review is focused on describing the natural history, postulated causes and a rational approach to the evaluation and management of nocturnal enuresis in children and adults with SCD.

Topics: Anemia, Sickle Cell; Antidiuretic Agents; Brain; Cholinergic Antagonists; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Quality of Life; Sleep Apnea Syndromes; Urinary Bladder

Desmopressin (dDAVP), a synthetic analog of the neurohypophyseal nonapeptide arginine vasopressin, has enhanced antidiuretic potency, markedly diminished pressor activity, and a prolonged half-life and duration of action compared to the natural hormone. Desmopressin is the treatment of choice for central diabetes insipidus and can be administered either intranasally or parenterally. A newly approved indication is treatment of mild classical hemophilia and von Willebrand's disease, in which deficient concentrations of factor VIII and von Willebrand's factor are transiently increased to levels that allow minor surgery.

Topics: Anemia, Sickle Cell; Animals; Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Synergism; Enuresis; Hemophilia A; Humans; Kidney Concentrating Ability; Learning; Memory Disorders; Structure-Activity Relationship; Urinary Incontinence; von Willebrand Diseases

The available literature is reviewed with reference to earlier and present therapies. When possible, methods used in clinical trials with different substances are briefly described, also giving their historical background. The substances studied or methods used are reported in chronological order. A total of 117 references have been made. Of these only 14 reported controlled double blind clinical trials (5 with urea, 3 with alkalines, 2 with phenothiazines, 2 with antisludging agents and one each with the defibrinating agent Arvin and cyanate). The controlled trials could not confirm the benefits claimed for the substances in the prevention or treatment of sickle cell crises. Treatment of the crises is still symptomatic and conventional.

Topics: Anemia, Sickle Cell; Antisickling Agents; Azepines; Clinical Trials as Topic; Cyanates; Deamino Arginine Vasopressin; Drug Therapy, Combination; Erythrocyte Deformability; Erythrocyte Membrane; Hemoglobinometry; History, 20th Century; Humans; Piracetam; Procaine; Urea; Zinc

The prevalence of enuresis and management options for this condition were studied in our population of sickle cell patients. A total of 91 active patients (6 to 21 years old) followed at our regional sickle cell center was surveyed for the symptoms of primary nocturnal enuresis. Of the 91 patients 27 (29.6%) had primary nocturnal enuresis. Of those with enuresis 17 had homozygous sickle cell anemia, 5 had hemoglobin sickle cell disease, 4 had sickle cell beta + thalassemia and 1 had sickle cell beta zero-thalassemia. Of 10 patients who elected to receive intranasal desmopressin acetate 6 (60%) had complete or partial resolution of nocturnal enuresis. Our data confirm the high prevalence of nocturnal enuresis in patients with sickle cell disease and support the role of desmopressin acetate in the treatment of these patients.

Topics: Adolescent; Adult; Anemia, Sickle Cell; Child; Deamino Arginine Vasopressin; Enuresis; Humans; Prevalence

The available literature is reviewed with reference to earlier and present therapies. When possible, methods used in clinical trials with different substances are briefly described, also giving their historical background. The substances studied or methods used are reported in chronological order. A total of 117 references have been made. Of these only 14 reported controlled double blind clinical trials (5 with urea, 3 with alkalines, 2 with phenothiazines, 2 with antisludging agents and one each with the defibrinating agent Arvin and cyanate). The controlled trials could not confirm the benefits claimed for the substances in the prevention or treatment of sickle cell crises. Treatment of the crises is still symptomatic and conventional.

Topics: Anemia, Sickle Cell; Antisickling Agents; Azepines; Clinical Trials as Topic; Cyanates; Deamino Arginine Vasopressin; Drug Therapy, Combination; Erythrocyte Deformability; Erythrocyte Membrane; Hemoglobinometry; History, 20th Century; Humans; Piracetam; Procaine; Urea; Zinc

Eight patients with sickle cell anemia were treated for acute painful crises with DDAVP and intravenous fluids; five were treated with placebo and the same regimen of fluid administration. Although hyponatremia was produced in both treatment groups, duration of hospitalization did not differ between them, nor did it differ from concurrent hospitalization of other patients who received conventional treatment. Safe induction of hyponatremia required intensive laboratory surveillance, and serum sodium could be lowered without use of DDAVP. These data suggest that a controlled trial hyponatremia for acute sickle cell crises should not be performed.

Topics: Acute Disease; Adult; Anemia, Sickle Cell; Arginine Vasopressin; Deamino Arginine Vasopressin; Female; Fluid Therapy; Humans; Male; Sodium

Because the formation of sickle cells is dependent on the intracellular concentration of deoxyhemoglobin S, we investigated the possibility of altering or preventing sickle-cell crises by reducing serum sodium so as to cause red cells to swell. In three patients with sickle-cell anemia who had been disabled by recurrent painful crises, sustained dilutional hyponatremia was induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in combination with a high fluid intake. Mean corpuscular hemoglobin concentration fell, and the degree of sickling at low partial oxygen pressure was reduced, as determined by morphologic criteria and by increased oxygen affinity of blood. Chronic hyponatremia (serum sodium, 120 to 125 mmol per liter) reduced the frequency of painful crises, whereas acutely induced hyponatremia abbreviated the duration of crises. These results, although preliminary, are encouraging enough to warrant further study of the safety and effectiveness of induced hyponatremia in the prevention and treatment of sickle-cell crises.

Topics: Adult; Anemia, Sickle Cell; Arginine Vasopressin; Clinical Trials as Topic; Deamino Arginine Vasopressin; Female; Fluid Therapy; Hemoglobin, Sickle; Humans; Hyponatremia; Male; Oxygen; Sodium

To determine the role of von Willebrand factor (vWF) in adhesion of sickle (SS) erythrocytes in microvascular flow conditions, we have perfused the ex vivo mesocecum vasculature of the rat with desmopressin, an analogue of vasopressin that causes the release of endothelial vWF. Analysis of vWF in the venous effluent of the isolated vasculature showed mainly the presence of extra-large molecular weight forms characteristic of endothelial vWF, which in the presence of desmopressin showed an average increase of 54%. Also, desmopressin induced a significant increase in adhesion of washed oxygenated (oxy) unseparated SS erythrocytes, accompanied by a persistent microvascular obstruction and a pronounced increase in the peripheral resistance (PRU). In contrast, infusion of SS deformable discocytes (SS2) in desmopressin-perfused vasculature resulted in a significant adhesion but not in persistent vasoocclusion, showing that SS2 discocytes alone are not sufficient for microvascular obstruction. Furthermore, SS4 erythrocytes (dense discocytes and irreversibly sickled erythrocytes) caused a persistent microvascular blockage and a significantly higher PRU than SS2 discocytes. However, the increase in PRU for SS4 erythrocytes following desmopressin treatment was 50% less compared with a corresponding increase for SS2 discocytes over the control values, which showed a smaller effect of desmopressin on the hemodynamic behavior of SS4 dense erythrocytes. Incubation of desmopressin-treated vasculature with anti-vWF antibodies resulted in a pronounced decrease in adhesion and significantly improved hemodynamic behavior of SS cells. Also, in untreated vasculature, similarly incubated with anti-vWF antibodies, there was almost complete inhibition of adhesion. Under the described perfusion conditions, antibodies to fibronectin and thrombospondin, as well as incubation of SS erythrocytes with anti-vWF antibodies did not affect adhesion. These results are compatible with a model for SS vasoocclusion in which extra-large vWF-mediated adhesion of deformable SS erythrocytes is the first step followed by an accelerated entrapment of dense SS erythrocytes.

Topics: Adult; Anemia, Sickle Cell; Animals; Cecum; Cell Adhesion; Deamino Arginine Vasopressin; Endothelium, Vascular; Erythrocytes; Humans; Microcirculation; Muscle, Smooth, Vascular; Rats; Reference Values; Regression Analysis; Vascular Diseases; Venules; von Willebrand Factor

Different morphologic and density classes of sickle cells (SS) may play distinct roles in the generation of vasoocclusion, explaining the complexity of this phenomena. The densest SS red blood cells (RBCs) (SS4) can induce vasoocculsion in ex vivo microcirculatory preparations as well as in an intact animal model. Previous studies of the interaction of SS deformable discocytes with endothelial monolayers or the rat ex vivo mesocecum preparation have shown adhesion that is desmopressin (dDAVP)-stimulated, von Willebrand factor (vWF)-mediated, and limited to the small venules. However, in vivo adhesion of SS RBCs to the endothelium has neither been demonstrated nor characterized; and, in particular, the relation of adhesion to vasoocclusion is unknown. Using an intact animal model that involves injecting saline-washed, density-defined SS RBCs into the femoral artery of a rat, we find that: (1) Quantitative studies of RBCs retained in the rat thigh using 99mTc-labeled RBCs and gamma camera imaging showed that dDAVP induces a threefold increase in retention of normal (AA) cells and deformable SS discocytes (SS2). (2) electron microscopy and Microfil injection show that the retention of SS2 cells is due to adhesion to the vascular endothelium with no evidence of obstruction. (3) H-1 magnetic resonance imaging showed that retention of SS4 cells induced a dose-dependent increase in tissue edema (presumable secondary to tissue hypoxia), while retention of AA or SS2 cells produced no change. We conclude that endothelial adhesion of deformable SS discocytes can be demonstrated in an in vivo animal model, that this adhesion is enhanced by dDAVP (presumably related to, but not necessarily limited to the release of vWF), and that this phenomenon per se does not lead to vasoocclusion. Nevertheless, adhesion of deformable SS discocytes may have consequences. We hypothesize that adhesion of SS discocytes could narrow the lumen of postcapillary venules and facilitate secondary trapping of SS4 cells and lead to subsequent vasoocclusion.

Topics: Anemia, Sickle Cell; Animals; Cell Adhesion; Deamino Arginine Vasopressin; Edema; Endothelium, Vascular; Erythrocytes; Female; Humans; Microcirculation; Microscopy, Electron, Scanning; Rats; Rats, Inbred Strains; Vascular Diseases

Topics: Adult; Anemia, Sickle Cell; Deamino Arginine Vasopressin; Hemophilia A; Hemorrhage; Humans; Male

Persistent gross hematuria associated with sickle hemoglobinopathy that fails to respond to conventional supportive therapy represents a difficult management dilemma. Two such patients with protracted, often painful, sickle trait macrohematuria are described. Both patients had normal renal anatomy and vasculature and had failed to respond to bed rest, intravenous hydration, and a trial of oral epsilon-aminocaproic acid. Patient 1 had normal coagulation function. Patient 2 had von Willebrand disease (decreased factor VIII antigen and quantitative ristocetin cofactor activity). Patient 1 responded to intravenous desmopressin acetate at a dose of 0.3 microgram/kg with a 155% increase in factor VIII clotting activity and a 135% increase in ristocetin cofactor and cessation of her macrohematuria within 18 hours after completion of the desmopressin infusion. She remained free of gross hematuria for 5 months with the exception of short-lived trauma-induced hematuria (in three voids) 6 weeks after desmopressin therapy. Patient 2 did not respond to intravenous desmopressin infusion despite a 234% and a 360% increase in factor VIII clotting activity and ristocetin cofactor, respectively. Intravenous desmopressin acetate may be helpful in halting protracted significant macrohematuria associated with sickle trait hemoglobinopathy in some patients when conventional management fails.

Topics: Adolescent; Anemia, Sickle Cell; Blood Coagulation Factors; Deamino Arginine Vasopressin; Female; Hematuria; Humans; Infusions, Intravenous; Male; Sickle Cell Trait; von Willebrand Diseases

Since the rate of polymerization of sickle hemoglobin is exquisitely dependent on its concentration, a small reduction in intracellular hemoglobin concentration should cause a significant inhibition of sickling. In three patients with homozygous sickle cell anemia, sustained hyponatremia was induced by a program consisting of a high fluid intake, a low salt diet and a vasopressin analog, DDAVP. During periods of hyponatremia, mean corpuscular hemoglobin concentration (MCHC) fell 13% and in vitro sickling was reduced as assessed by morphology and oxygen affinity. The frequency and duration of sickle cell crises appeared to be decreased during periods when patients were hyponatremic. These preliminary results indicate that reduction in intracellular hemoglobin concentration is an effective approach to the treatment of sickle cell anemia.

Topics: Anemia, Sickle Cell; Deamino Arginine Vasopressin; Diet, Sodium-Restricted; Erythrocyte Indices; Erythrocytes, Abnormal; Hemoglobin, Sickle; Humans; Hyponatremia; Oxygen; Sodium; Water-Electrolyte Balance

Topics: Anemia, Sickle Cell; Arginine Vasopressin; Deamino Arginine Vasopressin; Humans; Sodium

An analogue of arginine vasopressin (desmopressin, DDAVP) was evaluated for production chronic hyponatremia and prevention of sickle cell crisis. With sodium restriction (100 meq Na + / day) and water loading ( greater than 3 liters/day), persistent hyponatremia could not be achieved, nor could crises be prevented or aborted. Patients would not comply with a regimen of lower salt and higher fluid intake. More rigorous treatment might be practical during acute sickle cell crises, and a regimen similar to that used here might be more effective in children, whose renal concentrating mechanisms are still intact.

Topics: Adult; Anemia, Sickle Cell; Arginine Vasopressin; Deamino Arginine Vasopressin; Erythrocyte Aging; Female; Humans; Hyponatremia; Male; Osmolar Concentration; Pain; Sodium; Urine

Topics: Adult; Anemia, Sickle Cell; Arginine Vasopressin; Deamino Arginine Vasopressin; Erythrocyte Indices; Erythrocytes, Abnormal; Female; Hemoglobin, Sickle; Humans; Male; Oxygen; Recurrence; Sodium