deamino-arginine-vasopressin and Sickle-Cell-Trait

Gross and microscopic hematuria are well-known complications in patients with sickle cell hemoglobinopathy. Most of these episodes of gross hematuria are self limiting, but rarely may be severe and persistent requiring definitive intervention. Before subjecting these patients to surgical management such as partial or total nephrectomy, several medical therapies of variable benefit have been suggested. We report a patient with sickle cell trait who experienced severe, intractable gross hematuria for 5 months and showed a dramatic response to multiple doses of 1-desamino-8-D-arginine vasopressin (DDAVP) infusion. The remarkable response observed in this patient suggests that treatment with DDAVP infusion may be considered in patients with unremitting gross hematuria associated with sickle cell trait.

Topics: Child; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Hematuria; Humans; Infusions, Intravenous; Male; Renal Agents; Sickle Cell Trait

A defect in urine concentrating ability occurs in individuals with sickle cell trait (HbAS). This may result from intracellular polymerization of sickle hemoglobin (HbS) in erythrocytes, leading to microvascular occlusion, in the vasa recta of the renal medulla. To test the hypothesis that the severity of the concentrating defect is related to the percentage of sickle hemoglobin present in erythrocytes, urinary concentrating ability was examined after overnight water deprivation, and intranasal desmopressin acetate (dDAVP) in 27 individuals with HbAS. The HbAS individuals were separated into those who had a normal alpha-globin genotype (alpha alpha/alpha alpha), and those who were either heterozygous (-alpha/alpha alpha) or homozygous (-alpha/-alpha) for gene-deletion alpha-thalassemia, because alpha-thalassemia modulates the HbS concentration in HbAS. The urinary concentrating ability was less in the alpha alpha/alpha alpha genotype than in the -alpha/alpha alpha or -alpha/-alpha genotypes (P less than 0.05). After dDAVP, the urine osmolality was greater in patients with the -alpha/-alpha genotype than with the -alpha/alpha alpha genotype (882 +/- 37 vs. 672 +/- 38 mOsm/kg H2O) (P less than 0.05); patients with the -alpha/alpha alpha genotype had greater concentrating ability than individuals with a normal alpha-globin gene arrangement. There was an inverse linear correlation between urinary osmolality after dDAVP and the percentage HbS in all patients studied (r = -0.654; P less than 0.05). A linear correlation also existed for urine concentrating ability and the calculated polymerization tendencies for an oxygen saturation of 0.4 and O (r = -0.62 and 0.69, respectively). We conclude that the severity of hyposthenuria in HbAS is heterogeneous. It is determined by the amount of HbS polymer, that in turn is dependent upon the percentage HbS, which is itself related to the alpha-globin genotype.

Topics: Adult; Deamino Arginine Vasopressin; Female; Hemoglobin, Sickle; Humans; Kidney Concentrating Ability; Male; Middle Aged; Polymers; Sickle Cell Trait; Thalassemia

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