deamino-arginine-vasopressin and Autoimmune-Diseases

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 syndrome (aVWS) is a rare bleeding disorder with laboratory findings similar to those for congenital von Willebrand disease (VWD). However, unlike congenital VWD, it arises in individuals with no personal or family history of bleeding. aVWS occurs in association with a variety of underlying disorders, most frequently in lymphoproliferative disorders, myeloproliferative disorders, and cardiovascular diseases. Through an analysis of the more recent literature data, the pathophysiology and the clinical, laboratory, and therapeutic aspects of this syndrome are concisely reported in this review.

Topics: ADAM Proteins; ADAMTS13 Protein; Adsorption; Autoantibodies; Autoimmune Diseases; Blood Coagulation Tests; Cardiovascular Diseases; Deamino Arginine Vasopressin; Endocrine System Diseases; Factor VIII; Hematologic Diseases; Humans; Immunoglobulins, Intravenous; von Willebrand Diseases; von Willebrand Factor

Acquired von Willebrand's disease or syndrome (AVWS) is a rare bleeding disorder distinguished from congenital von Willebrand's disease by age at presentation and absence of personal and family history of bleeding disorders. We report on 22 patients with AVWS seen over 25 years. Mean age at diagnosis was 61.3 years (range 38-86 years); most patients had a spontaneous or a post-operative hemorrhage at presentation. Gastrointestinal bleeding and epistaxis were the most common spontaneous symptoms. Bleeding time was prolonged in most patients, associated with marked reductions in plasma von Willebrand factor antigen and ristocetin cofactor activity. Plasma VWF multimer distribution was normal (type 1 pattern) in 5 patients, indeterminate (no multimers detectable) in 6 patients (type 3 pattern), and abnormal (decreased higher-molecular-weight multimers, type 2 pattern) in 11 patients. None of 17 patients tested had an inhibitor of ristocetin cofactor activity. An underlying malignant or benign hematologic disease was found in 18 patients, and 1 patient had Crohn's disease. Desmopressin was effective in only half the patients so treated, but all patients responded to treatment with VWF-containing concentrates. Resolution of AVWS occurred with therapy of lymphoma (1 patient) and chronic lymphocytic leukemia (1 patient). Sixteen patients were alive at last follow-up; no deaths were related to bleeding. AVWS may be more prevalent than has been appreciated; we estimate up to 0.04%. Awareness of the existence of AVWS is essential for diagnosis and appropriate management. Therapy of associated diseases may improve the bleeding disorder.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibody Specificity; Autoantibodies; Autoimmune Diseases; Bleeding Time; Crohn Disease; Deamino Arginine Vasopressin; Female; Hematologic Diseases; Hematologic Neoplasms; Humans; Male; Middle Aged; Minnesota; Paraproteins; Postoperative Hemorrhage; Retrospective Studies; von Willebrand Diseases; von Willebrand Factor

This paper discusses selected reports on the management of acquired haemophilia A, a rare bleeding disorder characterized by the development of an autoantibody directed against plasma coagulation factor VIII (FVIII) (Morrison et al., Blood 81:1513-1520, 1993). The current literature consists of reports of cohorts of patients from referral centres and retrospective surveys of referral centres (Green and Lechner, Thromb Haemost 45:200-203, 1981). This suggests that the current literature may be biased both by referral practice to tertiary centres and reporting bias of these centres and may not be representative of the full spectrum of the disease. The published studies describe various immunosuppressive regimens to eradicate factor VIII inhibitors but usually lack control patients. Only one report describes a randomized, controlled study. Studies that address treatment of bleeding episodes give data on safety and efficacy for individual products but no comparative studies are available.

Topics: Adrenal Cortex Hormones; Adult; Animals; Autoantibodies; Autoimmune Diseases; Bias; Blood Coagulation Factors; Deamino Arginine Vasopressin; Factor VIII; Female; Hemophilia A; Humans; Immunoglobulins, Intravenous; Immunosorbent Techniques; Immunosuppressive Agents; Postpartum Hemorrhage; Pregnancy; Retrospective Studies; Swine

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

The development of auto-antibodies against clotting factor VIII is a rare disease that occurs predominantly in adults: in pregnant women or people with various immunologic disorders or with no apparent underlying disease. As a consequence of an immune system dysregulation, the evolution of this condition is unpredictable. The aim of treatment is to restore normal factor VIII levels in circulation using desmopressin (DDAVP), massive doses of factor VIII (human or porcine), plasmapheresis and factor VIII infusions. In patients with high-titer inhibitors, products with 'bypasing' activity can be used. The most difficult task is to treat the immune disorder. High-dose infusions of immunoglobulins might be useful, due to the presence of anti-idiotypes to factor VIII inhibitors in the commercial preparations. Corticosteroids and cyclophosphamide are currently the most widely used treatments for the immune disease.

Topics: Adult; Autoantibodies; Autoimmune Diseases; Deamino Arginine Vasopressin; Factor VIII; Female; Hemophilia A; Humans; Immunoglobulins, Intravenous; Pregnancy

Factor VIII auto-antibody inhibitors, though rare, may present significant and often life-threatening haemorrhage. These auto-antibodies, arising predominantly in older individuals, occur in association with autoimmune disorders, lymphoproliferative disorders, solid tumours, medications and the postpartum state. Almost half of the patients develop auto-antibodies spontaneously without an underlying medical condition. Factor VIII auto-antibody inhibitors are characterized as polyclonal IgG immunoglobulins directed against the FVIII procoagulant activity. Laboratory diagnosis is made by performing the aPTT clotting time in conjunction with a mixing study, and subsequently with specific factor assays. Auto-antibodies are quantified most commonly utilizing the Bethesda assay. Acquired inhibitors to other coagulation factors, including factors IX, XI, XIII, vWF protein, and the vitamin K-dependent proteins are extremely rare. The principles of therapy are similar to those which apply to the management of factor VIII auto-antibodies. Treatment of patients with acquired factor VIII auto-antibody inhibitors varies depending upon the underlying medical condition, the titre of the inhibitor, and the clinical presentation. Acutely bleeding patients with high-titre auto-antibodies generally respond well with infusions of porcine factor VIII concentrate, PCCs or rFVIIa. Extracorporeal plasmapheresis with exchange will acutely reduce circulating antibodies and can be used in conjunction with factor infusions and/or IgIV. Haemorrhage in a patient with a low titre auto-antibody will usually respond to high doses of human factor VIII concentrate. DDAVP may also increase factor VIII levels in patients with low-titre inhibitors. Long-term reduction of auto-antibodies can be achieved by immuno-suppressive regimens using steroids and/or cytotoxic agents, IgIV and interferon-alpha. The selection of the appropriate treatment depends upon the associated medical condition, likelihood of spontaneous remission, risk of toxicities of therapy and cost. Determining the efficacy and safety of new treatment modalities for factor VIII auto-antibodies and other coagulation factor inhibitors will require multicentre randomized clinical trials.

Topics: Adult; Aging; Animals; Antibodies, Anti-Idiotypic; Autoantibodies; Autoimmune Diseases; Blood Coagulation Disorders; Blood Coagulation Factors; Deamino Arginine Vasopressin; Factor VIIa; Factor VIII; Female; Hemophilia A; Hemorrhage; Humans; Immunization; Immunoglobulin G; Immunoglobulins, Intravenous; Immunosuppressive Agents; Incidence; Interferon-alpha; Isoantibodies; Male; Plasma Exchange; Plasmapheresis; Pregnancy; Prothrombin; Puerperal Disorders; Recombinant Proteins; Swine

There have only been thirty cases of total post-partum hypopituitarism published in the literature and these have nearly all been secondary to Sheehan's syndrome. The authors report a case of partial anterior hypopituitarism associated with diabetes insipidus which arose after an uneventful Caesarean operation and the origin of which seems to lie in auto-immune hypophysitis. The authors first describe the morphological and endocrine changes that the hypophysis undergoes during pregnancy and then point out that auto-immune hypophysitis seems to have been only recently recognised. This can be used to explain some cases of post-partum hypophyseal insufficiency occurring almost silently without any history of third haemorrhage. Research has been made systematically for anti-hypophyseal antibodies and for specific antibodies of the organ, but has not always been positive. So the diagnosis of auto-immune hypophysitis is often made only after eliminating other reasons for it. A brief review of the physiopathological mechanisms of diabetes insipidus makes it possible to suggest that vasopressinase coming from the placenta together with prostaglandins could play a role.

Topics: Adult; Autoimmune Diseases; Cesarean Section; Cystinyl Aminopeptidase; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Female; Humans; Hypopituitarism; Magnetic Resonance Imaging; Pituitary Gland, Anterior; Pregnancy; Prostaglandins; Puerperal Disorders

Topics: Animals; Antigens; Autoantibodies; Autoimmune Diseases; Deamino Arginine Vasopressin; Factor IX; Factor VIII; Female; Hemophilia A; Hemorrhagic Disorders; Humans; Immunoglobulin G; Immunosuppressive Agents; Isoantibodies; Plasmapheresis; Postpartum Period; Pregnancy; Swine

Patients with monoclonal gammopathies of uncertain significance (MGUS) may develop an acquired bleeding disorder similar to congenital von Willebrand disease, called acquired von Willebrand syndrome (AvWS). In these patients, measures to improve hemostasis are required to prevent or treat bleeding episodes. We diagnosed 10 patients with MGUS and AvWS: 8 had IgGkappa (3) or lambda (5) MGUS and 2 IgM-kappa MGUS. Three therapeutic approaches were compared in them: (1) desmopressin (DDAVP), (2) factor VIII/von Willebrand factor (FVIII/vWF) concentrate, and (3) high-dose (1 g/kg/d for 2 days) intravenous Ig (IVIg). In patients with IgG-MGUS, DDAVP and FVIII/vWF concentrate increased factor VIII and von Willebrand factor in plasma, but only transiently. IVIg determined a more sustained improvement of the laboratory abnormalities and prevented bleeding during surgery (short-term therapy). In addition to the standard 2-day infusion protocol, a long-term IVIg therapy was performed in 2 patients with IgG-MGUS: repeated (every 21 days) single infusions of IVIg did improve laboratory abnormalities and stopped chronic gastrointestinal bleeding. On the other hand, IVIg failed to correct laboratories abnormalities in patients with IgM-MGUS. These comparative data obtained in a relative large and homogeneous group of patients with AvWS and MGUS confirm that DDAVP and FVIII/vWF concentrates improve the bleeding time (BT) and FVIII/vWF measurements only transiently, whereas IVIg provides a sustained treatment of AvWS associated with IgG-MGUS, but not with IgM-MGUS.

Topics: Adult; Aged; Autoimmune Diseases; Bleeding Time; Cross-Over Studies; Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Paraproteinemias; Paraproteins; Treatment Outcome; von Willebrand Diseases; von Willebrand Factor

Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI.

Topics: Adult; Arginine Vasopressin; Autoantibodies; Autoimmune Diseases; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Female; Humans; Pregnancy

Lymphocytic hypophysitis is an unusual inflammatory lesion that is caused by autoimmune destruction of the pituitary gland. We report a case of 42-year-old man who presented with a 6-month history of severe headache, blurred vision in the right eye, hearing loss, polyuria, polydipsia, and impotence. Medical history showed that he and his mother had osteopetrosis. The results of the physical examination and laboratory tests showed that secondary hypothyroidism, hypogonadism, and hypocortisolism had developed. Central diabetes insipidus was diagnosed by water deprivation test. MRI of the sella showed pituitary enlargement with symmetrical suprasellar expansion, compression of the chiasma, thickened infundibulum, and involvement of both bilateral cavernous sinuses and clivus. Hormonal substitution with hydrocortisone, levothyroxine, and DDAVP resulted in rapid improvement of all symptoms and signs. Transsphenoidal biopsy was diagnostic of lymphocytic hypophysitis. In spite of extensive literature reviewing, we have not been aware of any case of lymphocytic hypophysitis with clivus involvement. The present case represents a variant of lymphocytic hypophysitis which has progressed to involve bilateral cavernous sinuses and the clivus.

Topics: Adult; Autoimmune Diseases; Cavernous Sinus; Cranial Fossa, Posterior; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Hormone Replacement Therapy; Humans; Hydrocortisone; Hypopituitarism; Lymphocytosis; Male; Thyroxine

Two young female patients presented with polyuria and polydipsia. In one patient we additionally found idiopathic vitiligo, there were no relevant previous diseases. The gynaecological history was unremarkable.. In both cases a water deprivation test confirmed the diagnosis of central diabetes insipidus, the MRI investigation of the pituitary region showed a prominent and thickened pituitary stalk.. After exclusion of a systemic granulomatous inflammation we diagnosed an autoimmune hypophysitis based on the typical morphological lesions of the pituitary gland and stalk. TREATMENT AND FOLLOW-UP: High-dose glucocorticoid therapy was without any beneficial effect on the central diabetes insipidus. Desmopressin treatment was initiated and led to a normalization of the pre-existing polyuria and polydipsia.. Autoimmune hypophysitis is a very rare disease and the diagnosis is mostly achieved by excluding other causes. Systematic evaluations on large patient cohorts are lacking in the literature with respect to diagnostic procedures, therapy and outcome, the existing knowledge and experience is largely based on case reports. For this reason it appears desirable to create a central register to collect and to evaluate the course of disease in patients with autoimmune hypophysitis.

Topics: Adult; Antidiuretic Agents; Autoimmune Diseases; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Female; Humans; Inflammation; Magnetic Resonance Imaging; Pituitary Diseases; Pituitary Gland; Polyuria; Thirst

Topics: Aged; Aged, 80 and over; Aminocaproic Acid; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Autoantibodies; Autoimmune Diseases; B-Lymphocyte Subsets; Blue Toe Syndrome; Bradycardia; Combined Modality Therapy; Compartment Syndromes; Deamino Arginine Vasopressin; Factor VII; Factor VIIa; Factor VIII; Female; Hematoma; Hemorrhage; Humans; Immunoglobulins, Intravenous; Pacemaker, Artificial; Plasmapheresis; Platelet Transfusion; Postoperative Hemorrhage; Recombinant Proteins; Rituximab

Cytoplasmic autoantibodies to vasopressin-cells (AVPcAb) have been detected not only in patients with overt central diabetes insipidus (CDI), but also in patients with endocrine autoimmune diseases without CDI. This suggests that complete CDI can be preceded by a preclinical stage. Among 878 patients with endocrine autoimmune diseases without CDI, 9 patients found to be AVPcAb positive and 139 AVPcAb-negative controls were enrolled in this open prospective study. They were evaluated for AVPcAb and posterior pituitary function at least yearly for about 4 yr (range, 37-48 months); during this span, magnetic resonance imaging (MRI) of posterior pituitary and stalk was performed only in the AVPcAb-positive patients. Five of the 9 AVPcAb-positive patients had normal posterior pituitary function at study entry. They were AVPcAb positive throughout the follow-up period. At later stages of the study, 3 of them developed partial CDI, and 1 developed complete CDI. The remaining 4 patients showed impaired response to the water deprivation test at study entry and were diagnosed as having partial CDI. Two of them agreed to receive desmopressin replacement for 1 yr. After this treatment, the patients became negative for AVPcAb and displayed normal posterior pituitary function until the end of the follow-up. Conversely, the 2 untreated patients with partial CDI remained AVPcAb positive. One of them developed overt CDI. None of the controls became AVPcAb positive or developed CDI. The normal hyperintense MRI signal of the posterior pituitary, present at study entry, persisted subsequently in all 9 AVPcAb-positive patients, including those developing overt CDI, only disappearing in the late phase of complete CDI. In asymptomatic subjects, the monitoring of AVPcAb, but not MRI, seems to be useful to predict a progression toward partial/overt CDI. Early desmopressin therapy in patients with partial CDI could interrupt or delay the autoimmune damage and the progression toward clinically overt CDI.

Topics: Adolescent; Adult; Autoantibodies; Autoimmune Diseases; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Pituitary Gland, Posterior; Prospective Studies; Vasopressins; Water Deprivation

Of 260 patients enrolled, 25 patients (9.6%) were associated with acquired von Willebrand syndrome (AvWS). We studied 25 patients with AvWS, retrospectively. AvWS was diagnosed by reduced levels of von Willebrand factor (vWF) (decrease of von Willebrand factor antigen [vWF:Ag] and von Willebrand ristocetin cofactor [vWF:RCoF]), a decrease of ristocetin-induced platelet agglutination (RIPA), sometimes decreased high-molecular-weight multimers, and prolonged bleeding time with neither prior nor family histories of bleeding problems and the evidence of normal vWF:RCoF in their families. The inhibitor of vWF was determined by mixing patient plasma with pooled normal plasma. Eight patients in this study had the inhibitors to vWF that were of the IgG class; the subclasses were IgG1 (7 cases) and IgG2 (1 case). Multimeric analysis of vWF showed selective loss of large multimers in most patients with AvWS similar to that of congenital type-2 von Willebrand disease (vWD). All inhibitors blocked ristocetin-mediated vWF binding to platelets. Five out of 6 IgGs evaluated here recognized the 39/34-kD fragment (residues 480/481-718) and Fragment III (residues 1-1365) that implied binding domain of glycoprotein Ib (GPIb), whereas 1 recognized Fragment I (residues 911-1365). A close relationship was found between the presence of the inhibitor and bleeding tendency. Of the 7 patients with inhibitors, 6 patients (86%) had a bleeding tendency, as well as 1 of the 15 patients without inhibitors (6%). The efficacy of treatment of underlying diseases and/or therapy with deamino D-arginine vasopressin (DDAVP) for the treatment of AvWS also depends on the presence of an inhibitor. Four of 8 patients with inhibitors (50%) had poor response to treatment of the underlying disease and/or therapy with DDAVP, as well as 1 of the 16 patients without inhibitors (6%). These results indicate that patients with AvWS developing inhibitors to vWF are likely to have bleeding problems and might be resistant to treatment of underlying diseases and/or therapy with DDAVP for bleeding to AvWS. We also showed evidence that intravenous immunoglobulin therapy (0.3 g/kg, 3 days) was effective to correct a hemostatic defect and manage severe bleeding in a patient with AvWS developing inhibitors. We might consider an additional treatment including expensive high-dose immunoglobulin therapy when uncontrollable bleeding is continued after the treatment of the underlying diseases and/or therapy with DDAVP.

Topics: Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Deamino Arginine Vasopressin; Epitopes; Female; Hematologic Diseases; Hemorrhage; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Male; Middle Aged; Molecular Weight; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIb-IX Complex; Retrospective Studies; von Willebrand Diseases; von Willebrand Factor

An 82-year-old patient with acquired von Willebrand's disease in association with a non-Hodgkin's lymphoma and a benign IgG-lambda monoclonal paraproteinemia is described with severe recurring nasopharyngeal bleedings, who responded poorly to desmopressin (DDAVP) and factor VIII/von Willebrand factor concentrates but was successfully treated with high-dose e intravenous gamma-globulin therapy.

Topics: Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases; Deamino Arginine Vasopressin; Factor VIII; Hemorrhage; Humans; Immunoglobulin lambda-Chains; Immunoglobulin M; Immunoglobulins, Intravenous; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Monoclonal Gammopathy of Undetermined Significance; von Willebrand Diseases; von Willebrand Factor

A rare case of a postmenopausal (60-year-old) female with lymphocytic adenohypophysitis manifesting as a sudden onset of diabetes insipidus is reported. Magnetic resonance imaging with gadolinium-diethylene-triaminepentaacetic acid enhancement showed a spherical lesion, approximately 1 cm in diameter, in the sella turcica and a thickened, deviated pituitary stalk. The abnormal tissue was totally removed. Histological examination showed marked infiltration of lymphocytes and plasma cells. Postoperatively, the pituitary stalk became normal. Preoperative differentiation of lymphocytic adenohypophysitis from pituitary adenoma is extremely difficult, and biopsy is essential.

Topics: Adenoma; Autoimmune Diseases; Biopsy; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Female; Humans; Lymphocytes; Magnetic Resonance Imaging; Menopause; Middle Aged; Pituitary Diseases; Pituitary Gland, Anterior; Pituitary Neoplasms; Plasma Cells

A patient with acquired von Willebrand's syndrome associated with polycythemia rubra vera is described. Ristocetin cofactor activity was decreased, while the levels of vWF:Ag and VIII:C were normal. Crossed immunoelectrophoretic analysis showed that vWF:Ag was composed of much more anodic component. The mixture study using pooled normal plasma and the patient IgG fractions showed the inhibition of ristocetin cofactor and the decrease of less anodic parts of vWF:Ag in normal plasma. After 1-deamino-8-arginine vasopressin (DDAVP) infusion the marked increases of vWF:Ag, VIII:C and ristocetin cofactor and a rapid return of ristocetin cofactor to the baseline were observed. Transient increase of vWF:Ag after DDAVP infusion showed less anodic forms and in the relative proportion as normal plasma. The present study showed that the patient IgG fractions had the specific inhibitory activity against the antigenic sites on the active subfractions of von Willebrand's factor.

Topics: Aged; Antigens; Autoantibodies; Autoimmune Diseases; Bleeding Time; Deamino Arginine Vasopressin; Factor VIII; Female; Humans; Immunoglobulin G; Platelet Aggregation; Polycythemia Vera; von Willebrand Diseases; von Willebrand Factor