I NOACs nelle trombosi venose rare
Bologna, 5 novembre 2015
Guido Finazzi
USS Malattie Mieloproliferative Croniche, USC Ematologia
Ospedale Papa Giovanni XXIII, Bergamo
Thromb Haemost 2013; 110: 626
Hepatology 2014; 60: 425
Acute portal and mesenteric vein thrombosis in a 50year-old patient with liver cirrhosis (CTP class A) and
several comorbidities.
Treated with UFH with subsequent transition to
rivaroxaban 20 mg per day.
After 6-month, complete resolution of the clot (CT
scan). During the follow-up, the patient did not report
any adverse events including bleeding.
Intagliata et al. Hepatology 2015; 61: 738
The lack of reliable reversal agents for newer
anticoagulants could be disastrous during variceal
bleedings
Monitoring anticoagulation intensity, and its reversal, is
vastly superior with warfarin, compared to NOACs
Several cases of probable rivaroxaban-induced liver
injury have been reported. Theoretically, there is an
increased risk of bleeding in patients with impaired
hepatic synthesis and metabolism
Simonetto et al. Hepatology 2015; 61: 738
Report of 14 cases of rivaroxaban-induced liver injury
Russmann et al. J Hepatol 2014; 61: 293
Report of 14 cases of rivaroxaban-induced liver injury
Russmann et al. J Hepatol 2014; 61: 293
There may be a signal, and there may even be an alert.
But is it really an alarm ?
Moore et al. J Hepatol 2014; 61: 198
DOACs remain contraindicated in patients with acute or chronic
severe liver impairment as a result of their partial metabolism
through the cytochrome P450 3A4 system
Blood 2014; 124: 3685
DOACs remain contraindicated in patients with acute or chronic
severe liver impairment as a result of their partial metabolism
through the cytochrome P450 3A4 system
Blood 2014; 124: 3685
Using thrombomodulin-modified thrombin generation testing, we
showed that the in vitro anticoagulant potency of Apixaban and
Rivaroxaban is substantially reduced in patients with moderate
and advanced cirrhosis. These results suggest that anticoagulant
treatment with these drugs will likely not result in
overanticoagulation, with a potentially increased bleeding risk.
Potze et al. Hepatology 2015; 61: 1435
We report the case of BCS development in young Russian male with
primary
APS.
The
patient
underwent
orthotopic
liver
transplantation on August 26, 2012.
At present time his state is good, the blood flow in the liver
restored and its function is not impaired.
We report about the first time the successful use of dabigatran
etexilate for prolonged anticoagulation therapy in APS patient with
BCS. In addition patient is managed with immunosuppressive drugs.
World J Hepatol 2015 ; 7: 2229
Elevated serum erythropoietin in a patient with
polycythaemia
vera
presenting
with
Budd-Chiari
syndrome.
Jones C, Levy Y, Tong AW
In this case report, the patient had a positive response
to cytoreductive therapy (hydroxyurea 500 mg daily),
phlebotomy (750 mL over three phlebotomies) and
rivaroxaban
Jones et al. BMJ Case Rep 2014 Dec 1; 2014
Clinical data for the use of DOACs in MPN patients
and in oncologic patients in general are very limited
to date. Only 2.5-6% of all patients enrolled in the
VTE therapy trials with DOACs were oncologic
patients not further characterised in the
publications.
For these reasons, DOACs should restrictedly used
in patients with MPN
Kreher et al. Ann Hematol 2014; 93: 1953
Studi in corso
Studio prospettico a singola coorte su
rivaroxaban nei pazienti con trombosi
splancniche (W. Ageno)
Studio retrospettivo sul trattamento
delle trombosi venose nei pazienti con
MPN (T. Barbui)
2014;45:2469-2471
Sixteen patients were included: 7 treated with rivaroxaban
and 9 with VKA (after a median of 5 days on heparin).
Overall outcome was excellent in 93.8%, and all patients
showed at least partial recanalization. No statistical
significant differences were found between the groups.
One patient in the VKA and 2 patients in the factor Xa
inhibitor group had minor bleeding within the median
follow-up of 8 months (5–26).
Eighteen patients were admitted for cerebral vein thrombosis.
Dabigatran was started in 11 patients (after a median of 13 days
on heparin) and warfarin was started in 7.
Four patients on warfarin were switched to dabigatran because
of instable INR in 3 and menorrhagia in 1.
A total of 15 patients were treated with dabigatran with median
follow-up time of 19 months. Gastrointestinal adverse effects
were noted in 3/15 patients and alopecia in 2/15.
Excellent outcome was observed in 87% of patients and
recanalization in 80%.
Int J Stroke 2015; 10: 1115
Novel oral anticoagulants in the treatment
of cerebral venous thrombosis
The aim of our work was to review the available
evidence for NOACs in the treatment of CVT.
Based on our literature search there is
insufficient evidence to support the use of
NOACs in CVT, although case series with
rivaroxaban and dabigatran have showed
promising results.
Feher et al. Int. Angiol. 2015 May 21 [EPUB ahead of print]
Studio in programma
Studio randomizzato internazionale con
endpoint composito: recidive + emorragie
maggiori.
Numerosità stimata: 150-180 pazienti.
Inizio studio: entro giugno 2016.
(JM Ferro, F Dentali)
First
presentation
During
VKA therapy
After 4 weeks
of Rivaroxaban
After 6 weeks
of Rivaroxaban
Thromb Haemost 2013; 109: 583
NOACs nelle TV rare: perchè NO
Non c’è sufficiente evidenza di efficacia
dagli studi pubblicati (case reports,
piccole serie di pazienti)
Ci sono dubbi sulla sicurezza nei pazienti
con epatopatia acuta o cronica severa
NOACs nelle TV rare: perchè SI
Per quanto limitata, la casistica finora
trattata ha dimostrato una buona efficacia e
tollerabilità dei NOACs.
Non ci sono ragioni fisiopatologiche per
pensare ad una diversa attività dei NOACs
nelle TV in sedi frequenti o rare.
E’ improbabile che clinical trials con un
adeguato numero di pazienti possano essere
eseguiti in queste forme rare
NOACs nelle TV rare: perchè SI
Per quanto limitata, la casistica finora
trattata ha dimostrato una buona efficacia e
tollerabilità dei NOACs.
Non ci sono ragioni fisiopatologiche per
pensare ad una diversa attività dei NOACs
nelle TV in sedi frequenti o rare.
E’ improbabile che clinical trials con un
adeguato numero di pazienti possano essere
eseguiti in queste forme rare
INSERIRE I PAZIENTI IN STUDI OSSERVAZIONALI
Un ruolo per la FCSA ?
Indagine conoscitiva dei pazienti con
trombosi in sedi rare trattati con
NOACs nei Centri FCSA
‘Consensus statement’ della FCSA
sull’uso attuale dei NOACs in queste
trombosi.