An Unusual Form of Immune Thrombocytopenic Purpura Characertized by a Platelet Activating IgG Antibody.

Autoimmune thrombocytopenia (ITP) is classically a disorder of accelerated platelet clearance and ineffective platelet production due to antibodies directed against common platelet membrane glycoproteins. The most common clinical manifestation of severe thrombocytopenia is bleeding. We report an unusual case of ITP in a 49 y.o. female with a 4 year history of thrombocytopenia, venous and arterial thrombosis secondary to a platelet activating IgG antibody.

The patient was referred to one of the authors (HAL) for a second opinion with a diagnosis of ITP and a history of venous and arterial thrombosis. On presentation the patient was noted to have a platelet count of 34 × 10⁹/L, a decreased fibrinogen of 128 mg/dL and D-dimers of greater than 4000 ng/ml. A diagnosis of chronic DIC was made and the patient was treated with therapeutic doses of LMW heparin resulting in an increase in her fibrinogen to 260 mg/dL, reduction in her D-dimers to <500 ng/ml and an increase in her platelet count to 118 × 10⁹/L. An extensive clinical and laboratory evaluation, included screening for occult malignancy, cavernous hemangioma, antiphospholipid antibodies, dysfibrinogenemia, inhibitory antibodies against protein C and S, failed to disclose an etiology for her chronic consumptive coagulopathy. After 2 months of LMWH therapy the patient had a progressive drop in her platelet count to <30 × 10⁹/L without evidence of recurrent coagulopathy. The patient’s thrombocytopenia was refractory to corticosteroids, Rituxan, azathioprine, cyclosporine, but responsive to IVIG. When the patients LMW heparin was stopped, the patient had evidence of a recurrence of her DIC as defined by an increase in her D-dimer and decreased fibrinogen. The patient underwent an open splenectomy which was complicated by portal vein and superior mesenteric vein thrombosis requiring catheter directed fibrinolysis and reinstitution of LMW heparin therapy. Repeated ELISA and functional assays for heparin induced thrombocytopenia were negative. However, the patient’s heat inactivated plasma and serum were shown to induce spontaneous aggregation. Patient IgG was subsequently isolated by staph A chromatography and found to be a potent inducer of platelet aggregation. Platelet specific IgG was further isolated from the patient’s IgG by affinity chromatography on a column of solubilized platelet membrane proteins. The affinity isolated antibody was then analyzed by the Western blotting using solubilized platelet membranes. Patient antibody was found to react with a 50 kD platelet membrane protein which has yet to be fully characterized.

At the present time the patient remains on LMW heparin, but requires frequent infusions of IVIG to maintain platelet counts above 30 × 10⁹/L. We are aware of only one other reported case of a spontaneous platelet activating antibody and no other case characterized by chronic DIC.