Vol.:(0123456789) 1 3
Internal and Emergency Medicine
https://doi.org/10.1007/s11739-019-02186-1
CE - RESEARCH LETTER TO THE EDITOR
Direct oral anticoagulants in factor VII defciency patient
Fulvio Pomero
1
· Laura Spadafora
2
· Salvatore D’Agnano
3
· Francesco Dentali
4
· Luigi Maria Fenoglio
5
Received: 27 June 2019 / Accepted: 26 August 2019
© Società Italiana di Medicina Interna (SIMI) 2019
Dear Sir,
Factor VII (FVII) is a vitamin K-dependent coagulation
factor synthesized in the liver which plays a major role in
the coagulation extrinsic pathway which is initiated at tis-
sue damage sites, following the formation of a complex
between activated FVII (FVIIa) and tissue factor. Plasma
levels range around 0.35–0.60 mg/L (for a normal coagulant
activity comprised between 70 and 140%), which is 10 times
less than other vitamin K-dependent factors. Its half-life is
extremely short (4–6 h) [1]. Inherited FVII defciency, with
an estimated prevalence of 1:300,000 population in Euro-
pean countries, is the most common among the rare congeni-
tal coagulation disorders, characterized by autosomal reces-
sive inheritance. As with other forms of hemophilia, FVII
defciency can also be caused by medications such as vita-
min K antagonists (VKA), medical conditions or malabsorp-
tion [2, 3]. Suspicion of FVII defciency arises in presence
of a reduced FVII coagulant activity (FVII:C), a prolonged
prothrombin time and an elevated international normalized
ratio (INR) in the setting of normal liver function and a nor-
mal activated partial thromboplastin time [1]. Clinical phe-
notypes correlate poorly with FVII activity levels although
hemorrhage rarely appears when FVII:C is above 30% and
complete absence of FVII in plasma is usually incompat-
ible with life and individuals die shortly after birth due to
severe hemorrhage [4]. Nevertheless, venous and arterial
thrombotic events have been reported in 3–4% of patients
with FVII defciency. Thus, in some cases, “antithrombotic
efect” of FVII defciency seems to be overwhelmed by the
presence of thrombotic risk factors underlying the need of
an antithrombotic prophylaxis even in these patients [5].
However, it is not well established how to manage the anti-
coagulation therapy and the available evidences are based
only on few case reports. Here, we describe a case of FVII
defciency patient afected by atrial fbrillation (AF) treated
with a direct oral anticoagulant (DOAC). In October 2017,
an 89-year-old woman presented to the emergency depart-
ment complaining of acute post-prandial pain in peri-umbil-
ical region. On past medical history, she reported factor VII
defciency, diagnosed at the age of 62 at the time visiting an
anesthesiologist for a planned intervention of cholecystec-
tomy. On this occasion, INR was 2 and the assays of VK-
dependent factors showed a reduced FVII:C of 15%; at the
time the patient was not taking any therapy. In 2011, she was
hospitalized for acute heart failure caused by hypertension
and AF: the physicians did not prescribe anticoagulants for
hemorrhagic risk due to FVII defciency. In 2015, she was
admitted to Neurology for a cerebellar ischemic stroke and
was in treatment with clopidogrel at discharge. The patient
had no other comorbidities including diabetes or dyslipi-
demia; she regularly took furosemide, bisoprolol and clopi-
dogrel. She weighed 58 kg, and was 161 cm high (body
mass index 22.4). Upon physical examination, the patient
was awake, alert and oriented to time, person, place and
situation. Her blood pressure was 120/90 mmHg, heart rate
of 90 beats/min with irregular rhythm. The abdomen was
soft, slightly tender in the lower quadrants. Laboratory test
showed increased white blood cells (12,170/uL), elevated
INR (2.4), while C-reactive protein, amylase and troponin
were within normal range. Creatinine was 0.89 mg/dl, ala-
nine and aspartate transaminase were 27 IU/L and 33 IU/L,
respectively. Fibrinogen was 2.4 g/L, D-dimer was 0.8 ug/
ml, aPTT was 30 s, and FVII:C was reduced to 10%. Her
ECG showed atrial fbrillation. A contrast-enhanced CT
scan was then performed, confrming the clinical suspicion
of acute mesenteric ischemia: CT showed an occlusion of
* Fulvio Pomero
fulviopomero@yahoo.it
1
U.O. Medicina Interna, Ospedale S. Lazzaro, Via P. Belli 26,
12051 Alba, Italy
2
Emergency Department, S. Paolo Hospital, Savona, Italy
3
Specialty Training in Internal Medicine, University of Turin,
Turin, Italy
4
Department of Clinical Medicine, University of Insubria,
Varese, Italy
5
Department of Internal Medicine, ASO S. Croce E Carle,
Cuneo, Italy