af is associated with 5-fold increased stroke and 2-fold increased mortality risk.1 ) thromboprophylaxis is the cornerstone of treatment in these patients .
dabigatran etexilate is one of the new oral anticoagulants shown to reduce the risk for stroke in patients with af .
it is an oral direct thrombin ( factor iia ) inhibitor approved by united states food and drug administration ( fda ) in 2010.2 ) dabigatran etexilate is a prodrug that is excreted mainly by the kidneys.2 ) it is superior to warfarin for prevention of stroke or systemic emboli without increasing bleeding in patients with non - valvular af.3 ) various bleeding complications associated with dabigatran were previously reported.4)5 ) however , there are very few cases of hemopericardium associated with dabigatran use.6)7 ) in this case , we described a patient with af who suffered from hemopericardium under dabigatran treatment .
a 66 year - old female patient was admitted to the emergency room for progressive shortness of breath and poor health condition for 1 week .
her blood pressure was 80/50 mmhg and arterial blood gas analysis was ph ; 6.98 , pco2 ; 99 mmhg , po2 ; 66 mmhg .
echocardiography revealed massive pericardial effusion with cardiac tamponade ( posteriorly 3 cm , anteriorly 2.5 cm , laterally 2 cm and 2.7 cm in adjacency with the right ventricle ) .
the patient had non valvular af and been receiving dabigatran etexilate 150 mg twice daily for one year .
in addition to dabigatran , the other medications included verapamil , budesonide , valsartan , and hydrochlorotiazide .
she had a history of chronic obstructive pulmonary disease , hyperthyroidism , hypertension and gastroesophageal reflux disease .
her blood tests performed 1 year ago showed serum creatinine 0.5 mg / dl ( normal range 0.5 - 0.9 mg / dl ) and estimated creatinine clearance 136 ml / minute ( using the cock - croft - gault equation ) . on admission
her blood tests showed blood urea nitrogen 163.9 mg / dl ( normal range 16.6 - 48.5 mg / dl ) , creatinine 3.99 mg / dl ( normal range 0.5 - 0.9 mg / dl ) , estimated creatinine clearance 16 ml / minute ( using the cock - croft - gault equation ) , fasting glucose 83.9 mg / dl ( normal range 74 - 109 mg / dl ) , sodium 130 mmol / l ( normal range 136 - 145 mmol / l ) , potassium 5.3 mmol / l ( normal range 3.5 - 5.1
mmol / l ) , prothrombin time ( pt ) 44.5 s ( normal range 11.5 - 15 s ) , activated partial thromboplastin time ( aptt ) 123.7 s ( normal range 26 - 32 s ) , international normalized ratio ( inr ) 4.79 , white blood cell count 10.59 10/ul ( normal range 4.4 - 11.3 10/ul ) , hemoglobin 7.7 g / dl ( normal range 11.7 - 16.1 g / dl ) , hematocrit 25.7% ( normal range 35 - 47% ) , and platelet count 183 10/ul ( normal range 152 - 396 10/ul ) .
urgent pericardiocentesis was performed with echocardiographic guidance and 1500 ml of hemorrhagic fluid was removed .
pericardial fluid analysis showed hemoglobin 7 g / dl and plasma hemoglobin level of the patient was 7.7 g / dl .
biochemical tests showed total protein 5.4 mg / dl , lactate dehydrogenase 707 mg / dl and albumin 2.98 mg / dl .
six hours after pericardiocentesis , the patients ' blood pressure was over 100 mmhg systolic and she began to urinate .
red blood cell and fresh frozen plasma transfusions were made and post - transfusion hemoglobin level was 12 g / dl , pt 36.4 s ( normal range 11.5 - 15 s ) , aptt 100.5 s ( normal range 26 - 32 s ) , and inr 4.1 . on the second day after pericardiocentesis ,
hemorrhagic fluid flow via drainage catheter persisted and additional fresh frozen plasma transfusion was administered .
pericardial drainage was terminated after achievement of no flow through catheter and no pericardial effusion on control echocardiography .
laboratory tests repeated on the fourth day of admission were as follows : blood urea nitrogen 109 mg / dl , creatinine 1.4 mg / dl , inr 1.4 and hemoglobin 12 g / dl .
it has constant bioabsorption and limited individual variability , hence , it does not require monitoring.8)9 ) since it is not metabolized by cytochrome p450 enzyme , drug interactions are scarce.9 ) bleeding rate associated with dabigatran was not higher than vkas in relevant trials.8 ) however , bleeding with dabigatran is a considerable problem because there is no direct antidote or blood product to reverse the anticoagulant effect entirely .
the thrombin clotting time is not useful for coagulaopathy with dabigatran since it is highly sensitive .
ecarin clotting time is a sensitive test providing dose - dependent response ; however , it is not yet approved for routine coagulation test and not approved by the fda for monitoring of dabigatran etexilate.10 ) there are a small number of case reports about hemopericardium associated with dabigatran use.6)7 ) our patient had been using dabigatran etexilate for 1 year before she suffered hemopericardium and cardiac tamponade .
acute renal failure was attributed to hypotension due to dehydration and hemodynamic compromise secondary to af with rapid ventricular rate .
impaired hemodynamics triggered by hemopericardium and impaired renal perfusion might have caused acute renal failure ; however , dabigatran overdose due to acute renal failure might have induced hemopericardium as well .
patients receiving dabigatran treatment are exposed to increased bleeding risks secondary to dabigatran overdose in cases of renal failure since more than 80% of dabigatran etexilate is excreted via the renal pathway.8 ) detection of aptt>90 s and inr>2 was shown to be associated with dabigatran overdose in several trials.11)12 ) dabigatran inhibits thrombin that helps conversion of fibrinogen to fibrin therefore it effects all routine coagulation tests to a certain extent . since inr measures prothrombin time of the extrinsic coagulation cascade , therapeutic concentrations of dabigatran cause only mild elevation of inr levels .
however , increased plasma levels of dabigatran exhibit a linear relationship with inr.12 ) epistaxis and elevated inr levels ( 8.8 ) were reported in a patient with chronic renal failure , receiving both hemodialysis and dabigatran treatment.13 ) similarly , our patient had elevated inr levels ( 4.8 ) on admission . meanwhile ,
many other studies demonstrated insensitivity of aptt and inr at therapeutic doses of dabigatran and found no linear relationship between.14 ) further studies are needed to investigate the relationship between inr and bleeding risk of dabigatran etexilate .
further evidence is required to evaluate the relationship between inr and bleeding risk of dabigatran etexilate .
 dabigatran etexilate is one of the new oral anticoagulants approved to reduce the risk of stroke in patients with atrial fibrillation ( af ) . a variety of bleeding complications with dabigatran 
 have been reported , but reports of hemopericardium are rare . 
 we described a case of a 66 year - old female patient with non - valvular af receiving dabigatran etexilate 150 mg twice daily for one year who suffered from hemopericardium . 
 her laboratory tests performed 1 year prior were normal and her admission tests revealed acute renal failure and elevated international normalized ratio ( inr ) level ( 4.79 ) . 
 urgent pericardiocentesis was followed by improved renal functions and normalized inr . 
 dabigatran etexilate is a new oral anticoagulant that is increasingly used in daily practice . 
 however , life - threatening complications warrant caution . elevated inr may be related with overdose but the association of bleeding risk of dabigatran and inr requires further confirmation . 