1. 72° CONGRESSO NAZIONALE http://www2.sicardiologia.it/wsc2011/eabstract/html/542.htm
72° CONGRESSO NAZIONALE
della Società Italiana di Cardiologia
Roma, 10 – 12 dicembre 2011
Triple antithrombotic treatment with aspirin, clopidogrel and dabigatran etexilate in a young
patient with anterior myocardial infarction and combined deficiency of protein C and protein S.
Armando D'Angelo (a), Jacopo Pizzicannella (b), Patrizia Della Valle (a), Carlo Meloni (b), Francesca
Sampietro (a), Domenico Cianflone (b), Norma Maugeri (a), Paolo Camici (b)
(a) Coagulation Service and Thrombosis Research Unit , (b) Department of Cardiothoracic and Vascular
Diseases, Scientific Institute San Raffaele, Milano, Italy
Background. In general, congenital deficiencies of the natural anticoagulant systems (tissue factor pathway inhibitor,
antithrombin, protein C) are not hold responsible for arterial thrombotic events. However, in a large retrospective family
cohort study, subjects with protein S or protein C deficiency showed a 5-fold increased risk for arterial thromboembolic
events before 55 years of age compared with non-deficient family members, independent of prior venous thromboembolism.
Case Report. A 29-year old man of African origin with acute anterior STEMI was submitted to coronary angiography within 2
hours from the occurrence of symptoms. No atherosclerotic lesions were observed. The thrombus in the proximal LAD
coronary artery was aspirated, followed by instillation of Integrilin® and PTCA with positioning of two medicated stents, but
no reflow was observed (TIMI 1).
The patient was a moderate smoker (< 10 cigarettes/day) without additional risk factors. He reported of the death of a sister
affected by MI at the age of 30. At screening for thrombophilia, a combined heterozygous deficiency of protein C and protein S
(type III) was observed on repeated occasions (Table). A patent foramen ovale was ruled out.
PT ratio 1.06 FIX:C (%) 88-104
aPTT ratio 0.96 FVIII:C (%) 130-175
Fibrinogen (mg/dL) 337 Antithrombin 90
Lipoprotein(a) 0.11 Factor V Leiden Homozygous wild-type
t-Homocysteine (mmol) 10.3 Prothrombin mutation Homozygous wild-type
Lupus anticoagulant absent Protein C:Ac (%) 34-44
Anti-phospholipid Abs absent Protein S:Ac (%) 43-56
FVII:C (%) 70-71 Free protein S (%) 57-61
FX:C (%) 86-90 Total protein S (%) 85-111
In a thrombin generation test (TGT), the acceleration parameter was greatly increased compared to normal plasma – consistent
with the reduced activated protein C-independent anticoagulant activity of protein S -, and there was no response upon
addition of exogenous thrombomodulin to the patient plasma. As expected, the amount of activated protein C generated by the
patient plasma in the TGT at different thrombomodulin concentrations (5 and 10 nmol) was approximately half of that
generated in normal pooled plasma. Given the combined treatment with aspirin and clopidogrel, three weeks after PTCA the
patient was put on intermediate-dose low molecular weight heparin (6000 anti-Xa IU/day). Protein C deficient patients are at
risk of coumarin-induced skin necrosis when treated with anti-vitamin K drugs, a risk presumably even greater for patients with
combined deficiency of protein C and protein S. After obtainment of approval by the IRB of our Institution and of informed
consent from the patient, after 2 months of heparin treatment he was shifted to oral anticoagulation with dabigatran etexilate
(Pradaxa®), initially at a dose of 150 mg o.d. The dose was increased to 185 mg o.d. after 15 days and to 220 mg o.d. after two
months. The table shows selected clotting parameters measured at nadir dabigatran plasma concentration levels (diluted
thrombin time with dabigatran calibration).
On LMWH On dabigatran etexilate
6000 a-Xa IU 150 mg o.d. 185 mg o.d. 185 mg o.d. 185 mg o.d. 220 mg o.d.
Diluted TT (ng/ml) - 20 19 30 15 16
PT ratio 1.00 0.99 1.07 1.09 1.11 1.08
aPTT ratio 1.01 0.97 1.04 1.14 1.11 1.20
Throbin time ratio - 2.30 2.37 6.50 5.00 7.25
EXTEM (CT ratio) 3.14 1.12 0.96 1.79 1.60 0.99
INTEM (CT ratio) 1.30 1.27 1.28 1.39 1.50 1.41
Conclusion.To our knowledge, this is the first description of myocardial infarction in a young patient with combined
deficiency of protein C and protein S treated with the combination of aspirin, clopidogrel and dabigatran etexilate for
compassionate use.
Chiudi Stampa
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