Four Cases of Acquired von Willebrand's Syndrome

Abstract

Four cases are reported in which a bleeding disorder associated with a long bleeding time and a low factor-VIII Icvel, like von Willebrand's disease, appears to have developed in adult life. In each there were abnormalities of plasma proteins, similar to but in some instances more extreme than patterns found in hacmophilia and 'classical' von Willebrand's disease. One patient's bleeding tendency developed in association with a generalized illness, probably systemic lupus erythematosus, and improved rapidly on steroid treatment. The other three patients, with no symptoms of underlying disease, were not treated with steroids. Two patients, infused with plasma, showed rather more than the predicted rise in factor VIII. 'Classical' von Willebrand's discase is a familial, life-long bleeding disorder with a long blecding time and a low level of factor VIII. However, Simone et al(1968) described a similar but acquircd disorder arising in a child with systemic lupus erythematosus (SLE) in whom both conditions improved on steroid therapy; and Veltkamp et al(1g70) observed a like episode lasting 3 wceks in a man who drank a pesticide. This paper describes four unrelated cases in which a bleeding disorder with some laboratory fcatures of von Willebrand's disease developed spontaneously in adult life in patients who are known previously to have responded normally to major haelnostatic challenges. MATERIALS AND METHODS PaticntsThe four patients studied were: H.S., female, 60 yr, Mayo Clinic; E.Ca., male, 76 yr and H.G., male, 5 5 yr, St Thomas's Hospital, London; J.Co., male, 59 yr, Royal South Hams Hospital, Southampton. They were unrclated and none gave a family history of abnormal bleeding. Each proffered clear evidence of normal liaemostasis for at least the first four decades of life. The onset of the bleeding disorder became apparent from a change in the haeniostatic response to trauma, and E.Ca., H.G. and J.Co. also developed spontaneous blceding of the 'capillary' type, characterized by ecchymoses and bleeding from mucous membranes (Table I), for which no local cause was identified in any case.

Acquired Inhibitors in Nonhemophilic Patients

“…Recently, a number of cases of acquired von Willebrand syndrome have been reported [82,104,117,141]. Associated diseases were SLE [82,141] or benign monoclonal gammopathy [104,117].…”

“…Associated diseases were SLE [82,141] or benign monoclonal gammopathy [104,117]. It is tempting to assume that acquired von Willebrand syndrome is caused by antibodies against the von Willebrand factor.…”

Acquired Factor IX Deficiency

“…In his case the factor IX deficiency was due to a circulating anticoagulant. In hereditary hemophilias, circulating anticoagulants occur most often following repeat ed transfusions [30,31], Patients with collagen diseases also may develop circulating anticoagulants against factor VIII [1,[10][11][12]28]. However, we found in the literature only 2 cases of acquired factor IX deficiency due to circulating anticoagulants [14,16].…”

“…Factor IX deficiency was due to a circulating anticoagulant. With corticosteroid treatment, marked clinical im provement occurred in the second patient with some improvement of her coagula tion studies, but it did not seem to effect the circulating anticoagulant level in the first patient.Acquired factor VIII deficiency has been reported in previously nor mal persons [1][2][3][4][5], in patients with collagen diseases, in patients treated with penicillin [1,6,7], following electric shock [8] and in women follow ing parturition [1,9], Von Willebrand's syndrome [10][11][12] and factor IX deficiency [13][14][15][16][17] may also be acquired. We report here transient factor IX deficiency in a 14-year-old boy and in a 31-year-old female.…”

Acquired von Willebrand’s Syndrome Due to an Inhibitor of IgG Specific for von Willebrand’s Factor in Polycythemia rubra vera

“…Acquired disorders which re sembled von Willebrand's disease have been most fre quently reported in association with autoimmune or lymphoproliferative disorders [1][2][3][4][5]. This association suggests that acquired von Willebrand's disease has an immunologic basis.…”