| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 2002;74:2179-2181
© 2002 The Society of Thoracic Surgeons
a Pediatric Cardiology. Medical University of South Carolina, Charleston, South Carolina, USA
b Pharmacy Services, Medical University of South Carolina, Charleston, South Carolina, USA
c Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
d Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
Accepted for publication July 1, 2002.
* Address reprint requests to Dr Simsic, Division of Pediatric Cardiology, Medical University of South Carolina, 165 Ashley Ave, P.O. Box 250915, Charleston, SC 29425; USA.
e-mail: simsicjm{at}musc.edu
 |
Abstract |
|---|
 Top Abstract IntroductionCommentReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionCommentReferences |
|---|
A full-term, 2.8-kg Caucasian male infant was diagnosed with transposition of the great arteries, ventricular septal defect, and pulmonary stenosis. Ductal patency was maintained with prostaglandin E1. On day of life 2, he underwent balloon atrial septostomy. Subsequent attempts to discontinue prostaglandin therapy were unsuccessful due to cyanosis (systemic oxygen saturation 60%). On day of life 7, he underwent placement of a 4-mm right modified Gortex Blalock-Taussig shunt and ductal ligation. Successful postoperative anticoagulation with intravenous heparin was achieved (aPTT [activated partial thromboplastin time] 60 to 80 seconds), only after antithrombin III replacement (level = 47%; adult normal mean 100% [range, 65% to 130%]; full-term newborn normal mean 60% [range, 42% to 80%]) [1]. Aspirin (41 mg per day) was started on postoperative day 2 and intravenous heparin was discontinued.
Two hours after extubation on postoperative day 4, the patient suffered acute cardiorespiratory collapse accompanied by severe metabolic acidosis (base deficit, -23; lactate, 27 mmol/L) and laboratory evidence of disseminated intravascular coagulopathy (PT [prothrombin time], 34 seconds; INR [international normalized ratio], 5.4; aPTT, 141; fibrinogen, 68 mg/dL). Echocardiography showed biventricular dysfunction and could not demonstrate flow through the shunt. Arterial pO2 was 33 torr. Due to persistent hemodynamic instability, the patient was placed on veno-arterial extracorporeal membrane oxygenation (ECMO) via the right internal jugular vein and the right carotid artery. While on ECMO, antithrombin III was again administered to achieve heparinization (activated clotting time 180 to 200 seconds).
After 60 hours of ECMO, there was improvement in end-organ function and resolution of disseminated intravascular coagulopathy. Cultures of blood, urine, and sputum were negative. Ultrasound of the head and abdomen were unremarkable. The patient was returned to the operating room for shunt replacement and ECMO decannulation. Both shunt anastomoses sites were found to be widely patent. However, the mid-portion of the shunt was occluded by thrombus. The shunt was removed and replaced with a direct anastomosis of the right subclavian artery to the right pulmonary artery (classic Blalock-Taussig shunt). ECMO cannulas were removed, and the right internal jugular vein and right carotid artery were primarily repaired.
The postoperative course was again notable for difficulty in achieving adequate anticoagulation with intravenous heparin, in the setting of a low antithrombin III level (48%). Aspirin was restarted on postoperative day 2, and intravenous heparin was discontinued. On postoperative day 6, the patient had an acute decrease in systemic oxygen saturation from 80% to 55%. An echocardiogram was able to demonstrate only trivial flow through the classic Blalock-Taussig shunt.
Tissue plasminogen activator was infused intravenously (bolus of 0.1 mg/kg over 10 minutes followed by an infusion of 0.5 mg/kg/h for 2 hours), with a resultant rise in systemic oxygen saturation to 85%. Repeat echocardiogram showed improvement of shunt flow. Intravenous heparin was restarted and aspirin was continued. Goal aPTT of 60 to 80 was only achieved at a heparin dose of 50 U/kg/h and further antithrombin III replacement. Intravenous heparin was transitioned to low–molecular weight heparin (Enoxaparin 1 mg/kg administered subcutaneously every 12 hours).
Results of hematologic studies sent at the time of initial shunt thrombosis revealed the patient to be heterozygous for factor V Leiden mutation, functional protein C level was 36% (normal, 21% to 47%) [1], total protein S antigen was 60% (normal, 22% to 55%) [1], free protein S antigen was 77% (normal, 33% to 67%) [1], total homocysteine was 7.6 µmol/L (normal <10.5 µmol/L) [2], anitphospholipid antibody IgG was 0.2 IU and IgM was 1.5 IU (normal <5 IU) [2], and a prothrombin G20210A mutation was absent on DNA analysis.
At hospital discharge (6 weeks of age) and 3 months later, antithrombin III levels were 100%. The patient continued to receive Enoxaparin until he underwent a successful Rastelli procedure at 6 months of age.
|
Comment |
|---|
|
TopAbstractIntroductionCommentReferences |
|---|
Whereas factor V Leiden mutation is not thought to be a major risk factor for arterial thrombosis in the adult population, it may be in the pediatric population [8]. In a multicenter prevalence study, Aschka and associates [3] found a 12% incidence of factor V Leiden mutation in a normal pediatric control population. In those patients less than 6 months of age, or between 10 and 18 years of age with documented thrombotic events, the factor V Leiden mutation was found in 29% [3]. In a review of 85 children with documented thrombotic events, Hagstrom and associates [4] found that 14% were heterozygous for factor V Leiden mutation; none was homozygous. Factor V Leiden mutation was found in 17% of patients with arterial thrombosis, and 12% of those with venous thrombosis [4]. Among neonates with arterial thrombosis, 27% were found to have factor V Leiden mutation [4]. Others documented a fivefold increase in ischemic stroke in pediatric patients heterozygous for factor V Leiden [8]. It is impossible to say if factor V Leiden mutation resulted in the thrombotic events in our patient. However, we did not find a clear etiology for either event.
Our patient’s course was further notable for low antithrombin III levels and difficulty achieving adequate heparinization. Hereditary antithrombin III–deficient patients have a 50% probability of having a thrombolic event at 27 years of age. This probability increases to 75% by an age of 50 years [9]. Our patient’s low antithrombin III levels were not attributed to hereditary antithrombin III deficiency, but were thought to represent the relatively low antithrombin III level commonly seen in the normal-term newborn [1, 10, 11]. As the anticoagulation activities of heparin are mediated by antithrombin III, it is not surprising that newborns have a relative heparin resistance and require higher dosages of heparin, compared with adults, to achieve similar levels of anticoagulation [11]. Whether our patient’s low antithrombin III levels may have contributed to his shunt thrombosis remains unclear. It may be that low antithrombin III level factors seen in the normal newborn in combination with other hypercoagulable factors place the newborn at increased risk of thrombosis.
Long-term treatment in at-risk patients to prevent recurrence of thromboses involves anticoagulation with low–molecular weight heparin (LMWH) or warfarin [11, 12] Warfarin functions by reducing the vitamin K–dependent proteins. In newborns, the levels of the vitamin K–dependent proteins are 50% of adult values; they do not approach adult levels until 6 months of age [13]. These physiologic decreases in vitamin K–dependent proteins are thought to influence dosing and safety of warfarin therapy in infants [12]. In addition, warfarin requires frequent monitoring secondary to the potential for unpredictable and variable bioavailability as a result of the patient’s age, underlying disease state, and interaction between warfarin and other medications or diet [11, 12]. Frequent monitoring may be challenging secondary to the limited venous access in an infant. For these reasons, LMWH was chosen over warfarin as long-term anticoagulation therapy for our patient.
LMWH offers several advantages over other anticoagulation agents used in children. These advantages include consistent bioavailability, permitting predictable dosing and therefore minimal monitoring [12]. Unlike warfarin, concomitant medications or diet do not alter LMWH’s anticoagulant effect [13]. However, like warfarin, the immature hematologic system of the infant may influence the anticoagulant effects and dosing of LMWH. Infants require a higher dose compared with older children and adults secondary to increased clearance of the drug. With therapeutic ranges of LMWH anticoagulation (anti–factor Xa level, 0.5 to 1.0 U/mL), the aPTT is unaffected [12].
Early Blalock-Taussig shunt failure, due to occlusion, has been reported to occur in 3% to 5% of patients [14, 15]. In light of this infrequent nature of early Blalock-Taussig shunt failure, our patient’s two thrombotic events early after shunt placement led us to be suspicious of inherited abnormalities of coagulation factors. We suggest a complete hematologic evaluation, including proteins C and S, factor V Leiden, and antithrombin III, for any patient with congenital heart disease and a thrombotic event. We also suggest considering anticoagulation therapy with either LMWH or warfarin in those patients found to have documented inherited coagulation disorders who continue to be at risk for thrombosis.
|
References |
|---|
|
TopAbstractIntroductionCommentReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  J. A. Connor Factor V Leiden and Its Effect on Children With Cardiac Pathology Journal of Pediatric Oncology Nursing, May 1, 2005; 22(3): 176 - 181. [Abstract] [PDF]
|
|
|
|
 |
|
 E. Tireli and M. Basaran Early Blalock-Taussig shunt thrombosis in a neonate with protein C deficiency. Ann. Thorac. Surg., June 1, 2004; 77(6): 2260 - 2261. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
