anna.krysicka@umed.lodz.pl
Dariusz Moczulski1dariusz.moczulski@umed.lodz.pl
1Department of Internal Medicine and Nephrodiabetology, Lodz, Poland
CORRESPONDENCE
Marlena Frydrysiak, Department of Internal Medicine and Nephrodiabetology
ul. Żeromskiego 113 90-549 Lodz, Poland
Tel.: +48 42 639 35 71
Email: marlenaf@poczta.fm
FUNDING INFORMATION
No sources of funding were declared for this study.
A KEY CLINICAL MESSAGE
Lupus anticoagulant caused aPTT prolongation in rare case can cause bleeding tendency especially when combined with other hemostasis abnormalities. In such cases aPTT value can be corrected by immunosuppressants within several days of treatment. When anticoagulation therapy is needed vitamin K antagonist are a good option for treatment.
ABSTRACT
Lupus anticoagulant antibodies despite causing aPTT prolongation are commonly associated with increased risk of thrombosis. We present a rare case of patient when these autoantibodies resulted in dramatic aPTT prolongation and combined with associated thrombocytopenia resulted in minor bleeding events. In presented case treatment with oral steroids resulted in aPTT values correction followed by resolution of bleeding tendency within several days. Later the patient developed chronic atrial fibrillation and was started on anticoagulation treatment with vitamin K antagonist without bleeding complications during follow-up period. Corresponding changes in patient’s aPTT time in a course of whole treatment is presented.
KEY WORDS
lupus anticoagulant, bleeding, aPTT prolongation, case report
INTRODUCTION
Coagulation screening prior to surgery or any other invasive procedure is performed routinely to identify patients with increased bleeding risk. Isolated prolongation of activated partial thromboplastin time (APTT) is not common finding in general population and it is most often attributable to anticoagulant therapy(1) or antiphospholipid antibodies. Less common reasons include deficiencies of a factor of the contact pathway, deficiencies of factors of the intrinsic and common pathways, von Willebrand disease, liver disease/vitamin K deficiency, hypofibrinogenemia, disseminated intravascular coagulation and supercoumarin intoxication(2).
Lupus anticoagulant is a class of antiphospholipid antibody causing a phospholipid-dependent prolongation of the clotting time but is not usually associated with bleeding tendency but rather with increased risk of thrombosis and pregnancy morbidity. Lupus anticoagulant is regarded as rare case of bleeding(3,4) with few examples that can be found in literature (2,5). In special cases lupus anticoagulant caused aPTT prolongation can be also associated with acquired factor II deficiency causing lupus anticoagulant-hypoprothrombinemia syndrome which is a rare disease predisposing to severe bleeding(6,7).
CASE PRESENTATION
A 64-year-old woman was referred to our hospital by nephrologist due to observed nephrotic proteinuria. The patient had a history of systemic lupus erythematosus diagnosed 30 years ago with cutaneous lesions and arthritis treated with glucocorticosteroids and chloroquine without any documented further relapses. Her past medical history included chronic kidney disease stage G3/G4, gout, hypertension, complex heart defect correction - implantation of pericardial mitral bioprosthesis and tricuspid valve repair (2010), traffic accident (2014) followed up by skin grafts (2015, 2016), abdominal hernia repair (2016) and cholecystectomy.
6 months before the patient had proteinuria of 2.5 g/day which increased to 6.75 g/day with stable serum creatinine level and periodically observed lower extremity oedema. Additionally the patient complained of several episodes of epistaxis. With the suspicion of lupus nephropathy the patient was admitted for kidney biopsy. She had slight lower extremity oedema and elevated blood pressure 195/96 mmHg. Her laboratory tests revealed an isolated prolongation of aPTT to maximum value of 172.6 sec (normal range 22.6 – 34 sec), slight normochromic anemia (hemoglobin 11 g/dL), thrombocytopenia (115 10^3/µL), elevated serum creatinine (170 µmol/L), ESR 75 mm/1h (normal <20), parathormone (147 ng/L) and TSH levels (7.670 mIU/L). Due to observed abnormalities in coagulation tests and tendency to extended bleeding, bruising and epistaxis patient was disqualified from kidney biopsy because of the high risk of bleeding. Further coagulation tests were performed. 1:1 mixing study showed no aPTT correction (107.9 sec) what suggested a presence of anticoagulant or inhibitor of factor VIII. Serum levels of factor VIII, IX, XI and XII were normal. Lupus anticoagulant test was positive at high titers along with positive anti-dsDNA antibodies and ANA level of 1:1280. Anticardiolipin and anti-beta 2-glycoprotein I antibodies were found negative. Systemic lupus erythematosus relapse was diagnosed. After exclusion of infections sites the therapy with prednisone was started (60 mg of prednisolone per day). After five days of treatment the aPTT decreased to 100.8 sec. The previously observed tendency to bleeding was resolved. After 30 days of treatment aPTT decreased to 40.5 sec. Because diabetes was diagnosed after two months of prednisolone treatment, the dose was reduced and the therapy with mycophenolate mofetil was started.
Four months later the patient had to be admitted to the hospital because of symptoms of chronic heart failure i.e. general malaise, increasing lower extremity oedema, heart palpitations and chest pain. Atrial fibrillation was diagnosed with rapid ventricular response 130-140/min. Increased natriuretic peptides were found and serum creatinine increased to 232 µmol/L. Echocardiography showed enlarged left atrium. Despite of implemented treatment atrial fibrillation did not convert to sinus rhythm. Due to implemented treatment with good control of heart rate the patient’s condition improved significantly. Four months after the start of treatment aPTT was 50 sec and proteinuria was 3.59 g/day. Because of the high risk of ischemic stroke associated with atrial fibrillation an anticoagulation treatment was started. Low molecular weight heparin was contraindicated because of persistent thrombocytopenia and high risk of heparin-induced thrombocytopenia (HIT). Treatment with NOAC (non-vitamin K antagonist oral anticoagulants) was also contraindicated because of its impact on aPTT, which was used to control the treatment of SLE. Therefore, the treatment with acenocumarol, a vitamin K antagonist (VKA), was started.
During the period of follow-up no bleeding were observed. Table 1 presents aPTT before treatment, during immunosuppressive therapy and during the therapy with acenocumarol.
Table 1 . Changes of patient’s aPTT during treatment