A four-days-old full term female infant, born vaginally through meconium stained amniotic fluid, presented to us with respiratory distress, lethargy and poor feeding. Infant had cried immediately after birth. There was no history of umbilical arterial catheterization. The mother had pregnancy induced hypertension and two spontaneous second trimester abortions in the past. There was no family history of thrombotic events. Examination revealed mild respiratory distress with Downe’s score of 3 and normal heart rate, with absent femoral pulsations. Blood pressure was normal in upper limbs and was not recordable in lower limbs. Pulse oximetry revealed saturation of 95-96% in upper limbs and 91-92% in lower limbs. Systemic examination was normal. A provisional diagnosis of hypoplastic left heart syndrome was made.

Investigations showed normal renal functions, serum electrolytes and serum calcium, and negative sepsis screen. Chest radiograph was suggestive of meconium aspiration syndrome. Echocardiography depicted structurally normal heart. Doppler ultrasonography of abdomen revealed echogenic aortic thrombus (2.7x1.3cm) distal to origin of inferior mesenteric artery upto bifurcation of the abdominal aorta.

The baby was started on low molecular weight heparin (1.5 mg/kg/dose 12 hourly) via subcutaneous route. In view of abdominal aortic thrombosis with no classic predisposing factors, tests for prothrombotic disorders were sent. Lupus anticoagulant, anticardiolipin antibody, antithrombin III levels, protein C, protein S levels were within normal limits and Factor V Leiden mutation was negative. Serum homocystine levels were 25.51 micromole/L (normal range 0-10 micromole/L) by CMIA technology and qualitative test of urine homocystine was positive. After two weeks of therapy, lower limb pulses were palpable. Repeat doppler study revealed complete resolution of thrombus. The aorta was recanalized with restoration of blood flow distal to the obstruction after four weeks of therapy. In view of diagnosis of congenital homocystinuria, infant was started on pyridoxine, folic acid and betaine, and methionine-restricted diet. Additional work-up of homocystinuria revealed normal ophthalmological examination and normal peripheral smear. Serum methionine levels were high 18 mg/dl (normal range <1 mg/dl) and test for MTHR gene mutation was negative. The baby’s parents, screened subsequently had normal values of serum homocystine and methionine. This confirmed the diagnosis of classic homocystinuria due to cystathionine beta synthase deficiency. The patient responded to above stated treatment with normalization of serum homocystine values after three months of therapy.

Thrombotic diseases are rare in neonates. A German study reported a prevalence of 5.1 per 100,000 live births [5], and a multicenter study reported a prevalence of 2.4 per 1000 NICU admissions [6]. In both studies, the thrombotic manifestations mainly involved large venous vessels as central line complications. To the best of our knowledge, there is no documented case in medical literature citing congenital classic homocystinuria causing aortic thrombosis in neonatal period.

The optimal treatment depends on the availability of surgical expertise, the associated risk factors for bleeding and degree of organ ischemia. Recent recommendations from the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy [7] suggests "the urgent, aggressive use of thrombolytic or surgical therapy supported by anticoagulation with heparin or low molecular weight heparin for children experiencing spontaneous aortic thrombosis with evidence of renal ischemia. It is unclear which thrombolytic agent is most effective; however, tissue plasminogen activator has become the agent of choice for several reasons, including experimental evidence of improved clot lysis in vitro compared with that using urokinase and streptokinase, fibrin specificity and low immunogenicity [7].

The support of thrombolysis with concomitant heparin may be synergistic; however, whether LMWH or unfractionated heparin (UFH) is better is still unclear. A case series by Klinger, et al. [8] suggests successful treatment of severe aortic thrombosis in two neonates with LMWH alone. Our patient was successfully treated with LMWH and showed complete improvement after completion of therapy.

This case report underlines the importance of inherited thrombophilia as the cause for isolated aortic thrombosis in neonates. Once the diagnosis of homocystinuria is established it is imperative to sub-classify it according to the enzyme defect as the treatment modality and future health implications differ amongst the three common subtypes.

Acknowledgements: Dr. Sandhya Kamat, Dean, Seth G.S.Medical College and KEM Hospital for granting the permission to publish this manuscript.

Contributors: All the authors have contributed, designed and approved the manuscript. BJ: will act as guarantor.

Funding: None; Competing interests: None stated.

1. Suro M, Ramji S, Thirupuram S, Sharma BK. Spontaneous aortic thrombosis in a neonate. Indian Pediatr. 1994:31:846-9.

2. Boo N-Y, Wong N-C, Syed Zulfikli SZ, Lye M-S. Risk factors associated with umbilical vascular catheter associated thrombosis in newborn infants. J Pediatr Child Health. 1999:35:460-5.

3. Sanchez J, Velasco F, Alvarez R, Roman J, Torres A. Aortic thrombosis in a neonate with hereditary antithrombin lll deficiency: successful outcome with thrombolytic and replacement treatment. Acta Paediatr. 1996:85:245-7.

4. Hagstrom JN, Walter J, Bluebond-Langner R, Amatniek JC, Manno CS, High KA. Prevalence of the factor V Leiden mutation in children and neonates with thromboembolic disease. J Paediatr.1998:133:777-81.

5. Hughes GRV. The antiphoslipid syndrome: ten years on. Lancet. 1993:342:341-4.

6. Schmidt B, Ansdrew M. Neonatal thrombosis: report of a prospective Canadian and International registry. Pediatrics. 1995;96:939-43.

7. Williams MD, Chalmers EA, Gibson BE. Haemostasis and Throbosis Task Force, British Committee for Standards in Haematology. The investigation and management of neonatal haemostasis and thrombosis. Br J Haematol. 2002;119:295-309.