Chronic Antithrombinaemia (Antithrombin V) with Haemorrhagic Diathesis in a Case of Rheumatoid Arthritis with Hypergammaglobulinaemia

Abstract

SummaryA report is represented on a 44-year-old patient suffering, since 1938, from very slowly progressive rheumatoid arthritis. Haemorrhagic manifestations have been seen since 1951 (large cutaneous and muscular haemorrhages, microhaematuria and macrohaematuria, possibly also articular haemorrhages). In addition to an extremely marked increase in γ-globulins to values above 8 g/100 ml (γ-globulins with a normal sedimentation constant S 7) a circulating anticoagulant was demonstrable, which is held responsible for the marked increase in clotting time, “prothrombin” time and thrombin time. The hypothesis is forwarded that this is a physiological anticoagulant showing a marked increase. Since it is different from the four antithrombins described by Seegers it is referred to as antithrombin-V. Antithrombin-V occurs both in the plasma and in the serum and appears to be bound to the (ß)γ-fraction. It is a thrombin inhibitor which, unlike antithrombin-II, has no direct effect on thromboplastin and thrombin formation. Antithrombin-V cannot be neutralized by protamine sulphate; it is heat-stable, not dialysable and not adsorbed onto BaSO4. Thrombelastography made it possible clearly to demonstrate that an increase in antithrombin-V is associated with a marked increase in clotting time but causes no pathological course of clot formation.Therapeutic results obtained with ACTH and cortisone are favourable: the activity of antithrombin-V decreases parallel with a decrease in γ-globulin values, and the clotting time is normalized. The patient has received, during the past 16 months, oral cortisone treatment (25 mg thrice daily), and is at present free of complaints, although clinical and laboratory findings show a gradual increase in symptoms respectively γ-globulin values with a slight increase in clotting time.The possible significance of the antithrombin-V activity in the protection against thrombo-embolism is briefly mentioned.

The Maintenance of a Sustained Thrombolytic State in Man. I. Induction and Effects*

“…Plasma antithrombin activity developing during the thrombolytic state has properties different from the conventionally described entities antithrombins I-IV (35). There is, however, a close resemblance between the antithrombin activity found in our patients and that described recently by Loeliger and Hers (36) as "antithrombin V," which term they applied to the antithrombin activity apparent in the plasma of a patient suffering from rheumatoid arthritis. We have evidence to suggest that the antithrombin activity present in our patients was at least partly due to the presence of fibrinogen breakdown products but characterization is as yet insufficiently advanced to be certain that this factor represents the total antithrombin effect.…”

Spontaneous antithrombin in a patient with benign paraprotein

“…This patient did not meet the criteria for multiple myeloma. In general, patients with paraproteinemia most often show abnormalities in clot retraction [16][17][18][19], a prolonged TCT [3,19,, or a decrease in the thickness of their fibrin fibers [ 131. Although carefully studied, specific antigen antibody reactions between paraprotein and fibrinogen, fibrin intermediates, or fibrin have been reported in two multiply transfused afibrinogenemic patients [24,25] and an antifibrin monomer, IgA kappa paraprotein, was reported in a patient with IgA multiple myeloma [26].…”

Mechanical and Enzymatic Thrombolysis of Acute Pulmonary Embolus: Review of the Literature and Cases from Our Institution

“…First clinical use of bovine thrombin was noted in the 1940s at the University of Iowa, and clinical reports of patients with complications related to thrombin exposure date back to the 1950s. 56 Its use increased in the 1960s, and in the 1970s, the US Food and Drug Administration (FDA) allowed clinical application of bovine thrombin because of its increasing use among surgeons. 62,63 In the 1980s, use of bovine thrombin increased in particular because of the fear of using pooled human plasma products owing to the discovery of human immunodeficiency virus (HIV) at that time.…”

“…Reports of patients with immune reactions related to thrombin exposure date back to the 1950s, including a report by Loeliger and Hers in 1957 of a patient with chronic antithrombinemia with hemorrhagic diathesis. 56 In the 1980s, three cases of antithrombin antibodies were reported. [40][41][42] In 1990, Lawson and colleagues isolated and described an antithrombin antibody found in a postoperative cardiac surgery patient exposed to thrombin.…”