deamino-arginine-vasopressin and Ehlers-Danlos-Syndrome

The Ehlers-Danlos Syndromes comprise a heterogeneous group of diseases, which are characterized by fragility of the soft connective tissues and widespread manifestations in skin, ligaments and joints, blood vessels and internal organs. The clinical spectrum varies from mild skin and joint hyperlaxity to severe physical disability and life-threatening vascular complications. The current Villefranche classification recognizes six subtypes, most of which are linked to mutations in one of the genes encoding fibrillar collagen proteins or enzymes involved in post-translational modification of these proteins. Establishing the correct EDS subtype has important implications for genetic counselling and management and is supported by specific biochemical and molecular investigations. Over the last years, the characterisation of several new EDS variants has broadened insights into the molecular pathogenesis of EDS by implicating genetic defects in the biosynthesis of other extracellular matrix molecules, such as proteoglycans and tenascin-X, or genetic defects in molecules involved in intracellular trafficking, secretion and assembly of extracellular matrix proteins.

Topics: Ascorbic Acid; Collagen; Deamino Arginine Vasopressin; Ehlers-Danlos Syndrome; Gene Expression Regulation; Genetic Counseling; Hemostatics; Humans; Joints; Mutation; Protein Isoforms; Proteoglycans; Signal Transduction; Skin; Tenascin

Easy bruising and bleeding are prominent features of some heritable disorders of connective tissue (HDCT), resulting from fragility of capillaries and the perivascular connective tissue rather than clotting or platelet dysfunction. The bleeding tendency is most prominent in the Ehlers-Danlos syndrome (EDS), a heterogeneous group of HDCT sharing clinical manifestations of fragility in skin, ligaments, blood vessels and internal organs. Most EDS-subtypes are caused by mutations in genes encoding fibrillar collagens type I, III or V, or genes encoding enzymes involved in the posttranslational modification of collagens. In the vascular subtype of EDS, caused by defects in type III collagen, fragility of vessel walls can lead to life-threatening bleeding and premature death. Bleeding tendency is also a common feature in other EDS-subtypes, leading to bruising either spontaneously or after minimal trauma. This paper reviews the clinical aspects of bleeding and bruising in different HDCT and covers diagnostic and therapeutic aspects relevant to bleeding in these disorders.

Topics: Collagen Type III; Connective Tissue Diseases; Deamino Arginine Vasopressin; Ehlers-Danlos Syndrome; Extracellular Matrix; Hemorrhage; Hemostasis; Hemostatics; Humans

Spontaneous bilateral carotid-cavernous fistulae and cervical artery dissection is reported in a 20-year-old woman with Ehlers-Danlos syndrome Type IV. The clinical features of 16 previously published cases of spontaneous carotid-cavernous fistulae associated with Ehlers-Danlos syndrome Type IV are reviewed, for a total of 17 cases. The mean age of the 14 women and three men was 31.6 years. Only direct fistulae were encountered. Diagnostic neuroangiography carried morbidity and mortality rates of 36% and 12%, respectively; neuroradiological treatment resulted in death in one of six patients. The possible value of desmopressin in the management of these patients is discussed. In view of the risks of arterial puncture and surgery, the authors emphasize the importance of early recognition of Ehlers-Danlos syndrome.

Topics: Adult; Arteriovenous Fistula; Carotid Artery, Internal; Cavernous Sinus; Deamino Arginine Vasopressin; Ehlers-Danlos Syndrome; Embolization, Therapeutic; Female; Humans; Radiography

Parturients with vascular Ehlers-Danlos syndrome are at particular risk of hemorrhage, and there is little evidence to guide prevention or management of hemorrhage in these patients. We present the case of a patient with vascular Ehlers-Danlos syndrome who had a cesarean delivery complicated by an intraoperative hemorrhage. Administration of desmopressin and tranexamic acid appeared to be of marked benefit in achieving hemostasis. To the best of our knowledge, this is the first report of the use of desmopressin during major obstetric hemorrhage in vascular Ehlers-Danlos syndrome.

Topics: Blood Loss, Surgical; Cesarean Section; Deamino Arginine Vasopressin; Ehlers-Danlos Syndrome; Ehlers-Danlos Syndrome, Type IV; Female; Humans; Pregnancy

Ehlers-Danlos Syndrome (EDS) is caused by heritable collagen defects and may be associated with bleeding symptoms. Desmopressin has been described in case reports to decrease bleeding times in these patients. This study sought to assess bleeding time responsiveness to desmopressin therapy in a cohort of children with EDS-associated bleeding manifestations. A retrospective chart review of children with EDS referred for bleeding symptoms was utilized. Twenty-six children were included; 19 (73%) had a desmopressin challenge. The mean bleeding time was 11.26 (+/-4.39) min, decreasing to 5.95 (+/-2.41) min with treatment (P < 0.01). Desmopressin normalizes bleeding times in children with EDS.

Topics: Adolescent; Bleeding Time; Case-Control Studies; Child; Child, Preschool; Deamino Arginine Vasopressin; Ehlers-Danlos Syndrome; Female; Hemorrhage; Hemostatics; Humans; Infant; Male; Retrospective Studies

Topics: Adrenochrome; Adult; Blood Transfusion; Combined Modality Therapy; Deamino Arginine Vasopressin; Drug Therapy, Combination; Ehlers-Danlos Syndrome; Estrogens, Conjugated (USP); Hematoma; Humans; Male; Recurrence; Thigh; Tranexamic Acid

Topics: Adult; Deamino Arginine Vasopressin; Diagnosis, Differential; Ehlers-Danlos Syndrome; Female; Humans; Immunohistochemistry; Microscopy, Electron; Skin

We report on a case of Ehlers-Danlos syndrome, probable type VIII (EDS VIII) in a 6-year-old girl with severe periodontitis, extensive bruising of the shins, abnormal bleeding time, and thin body habitus. The structure and biosynthesis of types I and III colagen were normal. Desmopressin (DDAVP) was found to correct the bleeding time, and the patient underwent an uneventful dental procedure after DDAVP therapy. The finding of childhood or juvenile periodontitis should prompt consideration of a diagnosis of EDS, particularly type VIII, and alert the clinician to the possibility of a treatable bleeding abnormality.

Topics: Blood Coagulation Disorders; Child; Deamino Arginine Vasopressin; Ehlers-Danlos Syndrome; Female; Humans; Periodontitis; Time Factors

Topics: Adult; Deamino Arginine Vasopressin; Ehlers-Danlos Syndrome; Female; Humans; Obstetric Labor Complications; Pregnancy; Pregnancy Complications; Uterine Hemorrhage

Ehlers-Danlos syndrome type IV (EDS IV) is a rare but serious disorder of connective tissue that is characterized by the abnormal production or secretion of type III collagen. Experience with pregnant patients exhibiting this syndrome is limited. This report describes the successful management of a pregnancy in a woman with EDS IV that included activity restriction and complete bed rest after 32 weeks, use of 1-desamino-8-D-arginine vasopressin (DDAVP) before delivery to improve coagulation, and cesarean section before the onset of labor. The possibility of prenatal diagnosis based on genetic linkage studies also is discussed.

Topics: Adult; Bed Rest; Deamino Arginine Vasopressin; Ehlers-Danlos Syndrome; Female; Fetal Diseases; Humans; Phenotype; Pregnancy; Pregnancy Complications; Prenatal Diagnosis