Successful thrombolysis following enoxaparin therapy in two pediatric patients with congenital heart disease presenting with intracardiac and cerebral thrombosis

The first patient (patient 1) was a 12-year-old girl with a complex congenital cardiac malformation (heterotaxy syndrome including atrioventricular septal defect and partial anomalous pulmonary venous return), who underwent biventricular repair at the age of 8 months. At the age of 12 years, the girl presented with left-sided hemiparesis. Magnetic resonance imaging (MRI) revealed a right-sided middle cerebral artery infarction (Figure 1a) with infarct demarcation in the right hemispheric white matter. Conventional thrombolysis with rtPA was contraindicated because she presented more than 6 hours after symptoms commenced, which was beyond the therapeutic window recommended for the adult population according to accepted guidelines [12].

Transoesophageal echocardiography was unremarkable with no intracardiac thrombus formations.

Enoxaparin (2.5 mg/kg/d) was administered by CII (anti-Xa levels 0.6–1.0 IU/ml). Hereby we calculated the dosage of enoxaparin according to the guidelines of the American College of Chest Physicians [6] with age specific dosages of 1–1.5 mg twice daily, respectively 2–3 mg/kg/d. We used enoxaparin sodium as pre-filled syringes, which was diluted in 50 ml saline 0.9% and was changed every 24 hours, since the physical and chemical stability was verified for periods longer than 24 h at a temperature of 21°C [13]. Within a few days the girl experienced complete remission of the clinical symptoms and 10 days later the MRI revealed a patent middle cerebral artery (Figure 1b). After 4 days, enoxaparin was switched from CII to a subcutaneous administration with anti-Xa levels still kept above 0.6 - 1 IU/ml. The switch of the administration route was decided in view of the disappearance of the clinically relevant hemiparesis and a normal transcranial doppler profile. D-dimer levels (normal range: 0–0.23 μg/ml) were not elevated during therapy with a maximum of 0.06 μg/ml measured on the first day.The second patient was a 16-year-old boy (patient 2) who had tetralogy of Fallot corrected in late infancy. The patient reported progressive fatigue for one month and recurrent episodes of stomach ache. Echocardiography revealed severe heart failure with an enlarged and poorly contracting left ventricle, a moderate mitral valve insufficiency and a mural thrombus formation in the left ventricular apex (Figure 2a). Enoxaparin was administered at 2 mg/kg/d as a CII, in addition to inotropic medication with dobutamine and levosimendan, amongst others. Due to a modest elevation of anti-Xa levels, enoxaparin was increased to 4 mg/kg/d for a few hours. The thrombus diminished in size and complete dissolution occurred within one week (Figure 2b). During this therapy there was no evidence for thrombus embolization and a cranial CT scan discovered no evidence of intracranial hemorrhage. A chest CT scan confirmed the diagnosis of cardiomegaly and hypodense structures in the apex of the left ventricle correlated with thrombus formation. After 7 days the CII was switched to a subcutaneous administration with similar anti-Xa levels and after 2 weeks the antithrombotic therapy was switched to acetylsalicylic acid because of expected poor compliance in a difficult family situation. During enoxaparin treatment, d-dimer levels increased to a maximum of 5.1 μg/ml after 2 days of therapy.

Cardiac catheterization including myocardial biopsy was performed and showed that the etiology of the severe heart failure was dilative cardiomyopathy of unknown origin. The CII of enoxaparin was paused 4 hours prior to the invasive procedure.

To obtain a more efficient thrombolysis, anti-Xa levels were raised to the upper limits of the recommended therapeutic levels (between 0.7 and 1.0 IU/ml [7]).

Platelet counts were monitored daily. None of the patients had renal dysfunction or manifested signs of heparin induced thrombycytopenia (HIT).

Routine thrombophilia screening, including APC resistance, factor II mutation, protein C and S, antithrombin, homocysteine, lipoprotein (a), antiphospholipid antibodies and factor VIII, was negative in both patients prior to the enoxaparin therapy.

Written informed consent was obtained from the patients for publication of both case reports and any accompanying images. A copy of written consent is available for review by Editor-in-Chief of this journal.