Challenges of the anticoagulation treatment

Introduction: Anticoagulant treatment is extremely important and frequently found in the management of cardiovascular disease. Sometimes achieving a thera-peutic efficacy is difficult due to the existence of partial resistance, otherwise impossible-complete resistance. Resistance to antivitamin K drugs is an important is-sue in everyday practice because it occurs in about 1: 1,000 patients; in the existing literature being described below 10 cases of Acenocumarol resistance. Managing such a case is a challenge, so we are proposing one for the analysis.
Case presentation: A 41-year-old patient was admitted to the emergency room for pain and swelling of the left inferior limb, following minor ankle trauma. The initial suspicion raised by the clinical picture and Wells score was confirmed by venous ultrasound: non-obstructi-ve thrombosis in the muscle veins with the proximal end of the thrombus in the popliteal vein. Under these circumstances, as the patient was complaining of left latero-thoracic pain and D-dimer were higher than the normal range, we decided to perform a thoracic CT an-giography that eliminated the possibility of thrombo-embolism. The presence of rectal bleeding brings into discussion a possible neoplastic etiology of the throm-bosis but these were due to internal hemorrhoids and colonic polyps without signs of dysplasia. However, given the patient’s age, we considered the existence of a possible thrombophilia that could not be confirmed during hospitalization (technical reasons)
As we established the diagnosis of deep vein throm-bosis, anticoagulation treatment with Enoxaparin was initiated in therapeutic dose. It was associated with an antivitamin K drug (Acenocumarol) at a loading dose of 4mg on the first and second day, while on the 3rd day it was reduced to 2 mg (1/2tb). On the 5th-day, we have tested the INR (after 14 mg of Acenocumarol) which was 1.14. Following this result we have increased the dose to 6mg (1 + 1/2tb) for the next two days. How-ever, when we have tested the INR on the 7th day, it was 1.13. At this time, we suspected resistance to Acen-cumarol, which has been confirmed by highlighting a polymorphism of the VKORC1 ASP 36 tyr gene. The patient was discharged with the recommendation to continue the anticoagulation treatment with Dabiga-tran for at least 3 months, to dose genetic factors in-volved in thrombophilia and re-evaluation. After 6 months the patient’s general condition was favorable with complete thrombus resorbtion . At this point, the anticoagulant treatment was discontinued. During the re-evaluation at 6 months after discontinuation of the anti-coagulant treatment, the patient did not show any clinical or echographical evidence of deep vein throm-bosis.
The particularity of the case: In the present patient, highlighting the genetic determinism of resistance to Acenocumarol has transformed a classic approach to a deep vein thrombosis case into a real challenge by requiring consideration to be given to the impact of polymorphism on the pharmacokinetics and pharma-codynamics of the future anticoagulant preparation chosen. Dabigatran was chosen, under which the evo-lution of our patient was favorable, with the disappea-rance of the thrombus at 6 months. On the other hand, the duration of anticoagulant treatment and the conti-nuation of anticoagulation after the initial episode are important decisions for which there is no specific al-gorithm and therefore raises many issues of approach. Moreover, although we do not know whether or not there is a thrombophilia in our patient, the contribu-tion of their presence in predicting a new thrombotic event is controversial. A Cochrane review published in 2009 and updated in 2012 did not report any randomi-zed controlled trial to study the importance of throm-bophilia screening in predicting the risk of recurrence. Thus, in the present patient, although the Dash score was 2, which estimated a recurrence risk of 6.3%, it was decided to interrupt the anticoagulant treatment after 6 months.
Conclusions: Anticoagulant therapy is widespread in clinical practice and the problems it generates have an important impact on the patient’s evolution. In conclu-sion, the case draws attention to the challenges posed by daily anticoagulation treatment, the choice of the drug and the individual variability of the response to treatment.

ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
The Romanian Journal of Cardiology is indexed by:
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CODE: 379
CME Credits: 10 (Romanian College of Physicians)