deamino-arginine-vasopressin and Lymphoproliferative-Disorders

Acquired von Willebrand disease (aVWD) occurs in association with a variety of underlying disorders, most frequently in lymphoproliferative and myeloproliferative disorders, other malignancies, and cardiovascular disease. aVWD is a complex and heterogeneous defect with a multifactorial etiology and the pathophysiologic mechanisms remain unclear in many cases. Assays for anti-factor VIII (FVIII)/von Willebrand factor (VWF) activities often yield negative results although antibodies may be present in autoimmune disease and some lymphoproliferative disorders. Functional assays of VWF in patients' plasma and particularly in heart valve disease, VWF multimer analysis are important for aVWD diagnosis. In patients with normal partial thromboplastin times and normal VWF activity, the diagnosis of aVWD is based on clinical suspicion and a careful bleeding history, which should prompt the clinician to initiate further laboratory investigations. Management of bleeding in aVWD relies mainly on desmopressin, FVIII/VWF concentrates and high-dose intravenous immunoglobulin. The half-life of VWF may be very short, and in bleeding episodes high doses of FVIII/VWF concentrates at short intervals may be necessary even when high-dose intravenous immunoglobulin was applied before. Since the optimal treatment strategy has not yet been defined for aVWD of different etiology, controlled multicenter trials aiming at the development of standardized treatment protocols are urgently needed.

Topics: Antibody Specificity; Autoantibodies; Autoantigens; Autoimmune Diseases; Deamino Arginine Vasopressin; Heart Diseases; Hemorrhage; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lymphoproliferative Disorders; Neoplasms; von Willebrand Diseases; von Willebrand Factor

Topics: Antigens; Autoimmune Diseases; Cardiovascular Diseases; Deamino Arginine Vasopressin; Disease Management; Hemorrhage; Humans; Immunosuppressive Agents; Incidence; Lupus Erythematosus, Systemic; Lymphoproliferative Disorders; Myeloproliferative Disorders; Neoplasms; Prospective Studies; Registries; von Willebrand Diseases; von Willebrand Factor

Acquired von Willebrand disease (AvWD) is a relatively rare acquired bleeding disorder that usually occurs in elderly patients, in whom its recognition may be delayed. Patients usually present predominantly with mucocutaneous bleeding, with no previous history of bleeding abnormalities and no clinically meaningful family history. Various underlying diseases have been associated with AvWD, most commonly hematoproliferative disorders, including monoclonal gammopathies, lymphoproliferative disorders, and myeloproliferative disorders. The pathogenesis of AvWD remains incompletely understood but includes autoantibodies directed against the von Willebrand factor (vWF), leading to a more rapid clearance from the circulation or interference with its function, adsorption of vWF by tumor cells, and nonimmunologic mechanisms of destruction. Laboratory evaluation usually reveals a pattern of prolonged bleeding time and decreased levels of vWF antigen, ristocetin cofactor activity, and factor VIII coagulant activity consistent with a diagnosis of vWD. Acquired vWD is distinguished from the congenital form by age at presentation, absence of a personal and family history of bleeding disorders, and, often, presence of a hematoproliferative or autoimmune disorder. The severity of the bleeding varies considerably among patients. Therapeutic options include desmopressin and certain factor VIII concentrates that also contain vWF. Successful treatment of the associated illness can reverse the clinical and laboratory manifestations. Intravenous immunoglobulins have also shown some efficacy in the management of AvWD, especially cases associated with monoclonal gammopathies. Awareness of AvWD is essential for diagnosis and appropriate management.

Topics: Age Distribution; Age of Onset; Aged; Autoimmune Diseases; Comorbidity; Deamino Arginine Vasopressin; Diagnosis, Differential; Factor VIII; Hemorrhage; Hemostatics; Humans; Lymphoproliferative Disorders; Myeloproliferative Disorders; Paraproteinemias; Prevalence; Risk Factors; Severity of Illness Index; Treatment Outcome; von Willebrand Diseases

Topics: Autoantibodies; Cardiovascular Diseases; Deamino Arginine Vasopressin; Diagnosis, Differential; Drug Combinations; Factor VIII; Humans; Lymphoproliferative Disorders; Myeloproliferative Disorders; Platelet Membrane Glycoproteins; Receptors, Cell Surface; von Willebrand Diseases; von Willebrand Factor

In seven patients with acquired von Willebrand's disease (AvWD) associated with lymphoproliferative disorders or benign monoclonal gammopathies, the platelet contents of von Willebrand factor antigen and ristocetin cofactor (vWF:Ag and vWF:RiCof, respectively) were normal. All the multimers of vWF:Ag could be seen in the 1.6% SDS-agarose gel electrophoresis patterns of plasma and platelet lysates. Infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) augmented plasma levels of vWF:Ag and vWF:RiCof of all patients and corrected prolonged bleeding times (BT). However, compared with patients with congenital vWD type I and comparable degrees of baseline abnormalities treated in the same way, vWF:Ag and vWF:RiCof were increased less and cleared more rapidly from plasma and the BT remained normal for a shorter period of time. These studies provide evidence that these AvWD patients have qualitatively normal vWF in plasma, but at lower concentrations, that vWF in platelets is normal both qualitatively and quantitatively, and that cellular vWF can be rapidly released into plasma by DDAVP to correct the hemostatic abnormalities. However, vWF is removed rapidly from plasma, making the correction more transient than in congenital vWD type I.

Topics: Adult; Aged; Antibodies; Blood Platelets; Deamino Arginine Vasopressin; Factor VIII; Female; Humans; Hypergammaglobulinemia; Lymphoproliferative Disorders; Macromolecular Substances; Male; Middle Aged; von Willebrand Diseases; von Willebrand Factor