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