Severe autoimmune Heparin Induced Thrombocytopenia with persistence over years: a case report

Introduction: Autoimmune Heparin Induced Thrombocytopenia (aHIT) is a rare condition with autoantibodies that do not need heparin to bind platelet factor 4 (PF4) and activate platelets. We report on a markedly severe aHIT, both in terms of duration and thrombotic events.

Method: A woman born in 1981 with history of astrocytoma and scoliosis surgeries during childhood with subsequent paraplegia and low BMI (16kg/m²), suffered in her 20’s from recurrent deep venous thromboses, treated with LMWH and prolonged VKA (2008). Platelet counts (PC) were normal till July 2011, when a decrease to 148x10⁹/L was noticed. PC were around 75x10⁹/L in 2013 when cerebral venous thrombosis occurred during an UFH bridge for thyroidectomy. The diagnosis of HIT, “classical”, was made on the basis of antibodies to PF4-heparin and positive platelet activation test. Anticoagulant treatment was therefore Danaparoid then VKA. PC continued to fall, at 37x10⁹/L in May 2014, as immunothrombocytopenia was suspected. A course of steroids had a modest effect (increase to 100x10⁹/L) while rituximab and various other immuno-modulatory or -suppressive therapies had no effect.

Results: Over more than 10 years 8 VTE and 6 arterial thrombotic events (strokes, coronary and peripheral arteries) occurred while on antithrombotic therapy (last event DVT in 2023); with no documented underdosing. Infectious episodes worsened thrombocytopenia and often lead to thrombosis.

The first IV polyvalent Ig infusion was in Dec 2015, after the first arterial event, and PC rose from 40 to 80x10⁹/L. When diagnosis of aHIT was reached[TL1] [NM2] in May 2021, iterative IVIg were initiated (1 g/kg monthly) and PC were maintained>100x10⁹/L. As of 2024, the antithrombotic drugs were Dabigatran (110mg bid) and Aspirin (75mg daily), without bleeding.

Inherited thrombophilia screening was negative. Antiphospholipid antibodies were never detected.

ELISA Ig GAM (Asserachrom HPIA, Stago) has been repeatedly positive since Feb 2013, up to 2.56 OD. Platelet activation (LTA) of test-platelets in presence of patient’s plasma has been present over years, often in absence of added heparin, always abrogated in presence of 100IU/mL.Homemade solid-phase (immobilized PF4 and PF4-heparin) immunoassays were performed (Scientific-Haemostasis-Consulting) with blood samples drawn at different times of the follow-up, and showed high persistent titres in both assays, IgG class.

Conclusion: (1) Whether this is persistent HIT (triggered by exposure to UFH) or genuine aHIT cannot be settled. Key to the diagnosis is activation of test-platelets in presence of patient’s plasma even without heparin. (2) IVIg seems effective, presumably by interfering with platelet CD32. Parallelism with the results of platelet activation testing was only partial, thus clinical relevance could be not evident. CD16 and CD64 on leukocytes could be the actual target. Whether Dabigatran is the anticoagulant of choice is debatable; it did not prevent thrombotic events before the inception of IVIg.

Publication History

Article published online:
13 February 2025