Non-specific non-antiphospholipid inhibitor in a 26-years-old woman: a case report with few answers and many questions

A 26-years old woman was admitted to the ambulatory of internal medicine the “Miulli” Hospital of the city of Acquaviva delle Fonti (Bari) for hypochromic microcytic anemia, with hemoglobin levels of 7 g/L and severe iron deficiency. The patient was in good health except for slight asthenia in the last months and the prior diagnosis of euthyroid autoimmune thyroiditis. She had neither personal nor familiar history of bleeding, whereas she referred heavy menstrual bleeding lasting 7 days from the age of menarche (15 years). The patient’s anemia was promptly solved after intravenous iron infusions. However, on the occasion of the diagnosis, routine coagulation tests were started, with the demonstration of a prolonged PT ratio (1.29) and aPTT ratio (2.0), confirmed at the following controls. The patient was sent to a laboratory specialized in coagulation disorders which, following the laboratory tests results (aPTT ratio 2.20 with uncorrected mixing, SCT screening 2.82, SCT mixing 1.99, SCT confirm 2.10, dRVVT screening 1.47, dRVVT mixing 1.43, dRVVT confirm 1.28). Coagulation factors activity tests were run, with the following results: fVIII 7.6%, fXI 8.0%, fIX 4.0%, fX 64%, fII 48%, fVII 53%, fV 52%. In addition, thrombin time (TT) was 1.34, fibrinogen (Clauss method) 198 mg/dL, von Willebrand antigen 92% and RCoF 72%, and anti-cardiolipin and anti-beta 2 glycoprotein 1 antibodies were negative. Furthermore, anti-thyroid peroxidase antibodies were tested at high titer (2837 IU/mL). The laboratory concluded for non-specific non-antiphospholipid inhibitor. In order to confirm such diagnosis, we consulted a second coagulation laboratory. The second laboratory tests were the latter: aPTT ratio 1.92 with uncorrected mixing, SCT screening 3.74, SCT mixing 2.48, SCT confirm 1.15, dRVVT screening 1.85, dRVVT mixing 1.53, dRVVT confirm 1.43. Unlike the first one, the second laboratory come to the diagnosis of lupus anticoagulant. After 18 months from the first diagnosis of anemia, the patient was hospitalized for hemoperitoneum due to corpus luteal cyst rupture. For the above reason, after receiving two red blood cells units and one plasma unit transfusions, she underwent an ovarian surgical excision without bleeding complications. Thus, the patient received indication of estrogen-progestin hormone therapy, in order to prevent a second corpus luteal cyst rupture that could compromise the remaining ovary.

This case highlights the difficulty in reaching a clear diagnosis in patients with acquired inhibitors of coagulation factors. Despite the similar results in coagulation tests, different laboratories came to divergent conclusions. The case is still open because we have not isolated yet the inhibitor responsible for the patient’s impaired laboratory results. Also, a possible role of the anti-thyroid peroxidase antibodies (tested at a high titer) has been hypothesized but remains unproven. However, the patient’s autoimmune diathesis seems to play a pivotal role in the pathogenesis or her hemostasis disorder. Moreover, the real patient’s bleeding risk remains unknown.