Early Detection of Lupus Anticoagulant-Hypoprothrombinemia Syndrome By Rotational Thromboelastometry

Lupus anticoagulant-hypoprothrombinemia syndrome (LA-HPS) is a rare disorder characterized by association of acquired factor II deficiency and lupus anticoagulant that may cause predisposition to both thrombosis and bleeding. The hemorrhagic episodes are caused by non-neutralizing antibodies directed against prothrombin, resulting in rapid clearance of the antigen-antibody complexes. It is most commonly seen in pediatric population, with a total of less than 100 reported cases in literature. Early diagnosis of LA-HPS is critical, as it may result in fatal complications if not identified early and treated appropriately. Here we present two cases of LA-HPS where Rotational Thromboelastometry (ROTEM) aided early diagnosis.

Case one:

A 28 year-old woman with history of systemic lupus erythematosis (SLE) , anti phospholipid antibody syndrome, and pulmonary embolism presented from an outside facility with spontaneous subdural hematoma. Warfarin therapy had been discontinued 18 days prior to her presentation secondary to bilateral lower extremity hematomas. The INR was 3.59 at the outside facility, for which she received prothrombin complex concentrates and Vitamin K. Laboratory values at time of admission included prothrombin time (PT) of 16.3 seconds, INR of 1.34 and partial thromboplastin time (PTT) of 53 seconds; the patient received an additional two units of plasma after admission. Despite these interventions, the INR increased to 2.02 on day two of hospitalization. At this time, ROTEM was performed which revealed a markedly prolonged EXTEM clotting time (CT) at 502 seconds (reference range: 43 s-82 s) and INTEM CT at 395 s (reference range: 122 s-208 s). Further investigation revealed decreased factor II activity at 6%, with all other Vitamin K dependent factors within reference range. Lupus-like inhibitor was positive and anti-prothrombin antibodies were elevated at 102.6 units (reference range 0.0-19.9 units), confirming the diagnosis of LA-HPS, after which the patient was treated with high dose corticosteroids and cyclophosphamide. PT and APTT decreased to 1.32 and 36 respectively on day two of immunosuppressive therapy. No neurosurgical intervention was undertaken, given the stability of the subdural hematoma and the patient's clinical improvement.

Case two:

A 42 year-old woman with a history significant for lupus anticoagulant presented with symptomatic anemia and hemoperitoneum. Her initial labs included a PT of 16.8 seconds and INR of 1.40 with a PTT of 55 seconds. Exploratory laparotomy revealed two liters of hemoperitoneum arising from a hemorrhagic ovarian cyst. The patient received 654 ml of plasma intraoperatively. A postoperative ROTEM was notable for markedly prolonged INTEM CT (363 seconds) and EXTEM CT (341 seconds). Postoperative PT and PTT were 15.5 seconds and 55 seconds, respectively. Further investigation revealed decreased Factor II activity at 42%; factor V and factor VII activity were within reference range. Elevated anti-prothrombin IgG antibodies (54.6 units; reference range 0.0-19.9 units) and IgM antibodies (28.2 units; reference range 0.0-19.9units) confirmed the diagnosis of LA-HPS. In this case corticosteroids were not administered to the patient given Factor II activity of more than 40 %. The patient's clinical status improved and she was discharged five days later without further sequelae. Outpatient evaluation performed weeks after discharge showed positive antibodies to Cardiolipin and beta-2-glycoprotein-1.

Conclusion:

In both presented cases, the prolongation of the INTEM and EXTEM CT was greater than what the PT and PTT would predict and appear to be an inhibitory pattern. The effects of lupus anticoagulants and anti-prothrombin antibodies on ROTEM has not yet been described in the literature. These cases illustrate the potential of thromboelastometry in early detection of LA-HPS; further investigation of the impact of lupus anticoagulants on ROTEM analysis is warranted.