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Year : 2015  |  Volume : 4  |  Issue : 3  |  Page : 199-202

Umbilical venous catheter-related ischemia of fingers, right atrial thrombus treated with recombinant tissue plasminogen activator and lethal pulmonary hypertension in a preterm infant

Department of Pediatrics, King Abdulaziz Hospital, Ministry of National Guard, Al-Ahsa, Saudi Arabia

Date of Web Publication2-Jul-2015

Correspondence Address:
Sameer Y Al-Abdi
Department of Pediatrics, King Abdulaziz Hospital, Ministry of National Guard, P.O. Box 2477, Al-Ahsa 31982
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2249-4847.159911

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We report the second case in English literature of limb ischemia related to umbilical venous catheter (UVC) use. This case was an extremely low birth weight preterm infant who otherwise remained stable during the first 8 days of life. On day 9, she developed intermittent ischemia of the distal phalanges of four fingers on the right hand. On day 11, the ischemia worsened during obtaining a blood for culture from the UVC. Blood cultures yielded cloxacillin-sensitive Staphylococcus aureus. On day 15, a large right atrial thrombus (RAT) was found after an echocardiogram (ECHO). Through consecutive ECHOs, we determined that the RAT was increasing in size. After administering a single dose of recombinant tissue plasminogen activator, size of the RAT decreased significantly, and no anticoagulants, it was deemed unnecessary. On day 147, the patient developed pulmonary hypertension (PH), which was attributed to severe bronchopulmonary dysplasia, and the patient died on day 168. After thorough analysis of the case, it is possible that PH might have been caused by a pulmonary embolism (PE). If a long-term anticoagulant was administered, or PE was considered and treated, the final patient outcome might have been different. In summary, a diagnosis of UVC-related ischemia requires a high index of suspicion. It may be of value to administer a long-term anticoagulant after successful treatment of RAT, and it would be prudent to consider a PE in a preterm infant who then develops PH.

Keywords: Extremely premature infant, ischemia, pulmonary hypertension, thrombosis, umbilical venous catheter

How to cite this article:
Al-Abdi SY, Dabelah K, Mousa T, Al-Algirim H. Umbilical venous catheter-related ischemia of fingers, right atrial thrombus treated with recombinant tissue plasminogen activator and lethal pulmonary hypertension in a preterm infant. J Clin Neonatol 2015;4:199-202

How to cite this URL:
Al-Abdi SY, Dabelah K, Mousa T, Al-Algirim H. Umbilical venous catheter-related ischemia of fingers, right atrial thrombus treated with recombinant tissue plasminogen activator and lethal pulmonary hypertension in a preterm infant. J Clin Neonatol [serial online] 2015 [cited 2020 Jul 13];4:199-202. Available from: http://www.jcnonweb.com/text.asp?2015/4/3/199/159911

  Introduction Top

While sepsis and development of a right atrial thrombus (RAT) are well-known complications of umbilical venous catheter (UVC) use, ischemia of fingers, and toes related to an UVC has only been reported in one female extremely low birth weight (ELBW) neonate prior to this case. [1],[2] This is a report of a second case of ischemia of fingers related to UVC use in an ELBW neonate. This patient also developed RAT that was treated by a single dose of recombinant tissue plasminogen activator (r-tPA) and subsequently developed lethal pulmonary hypertension (PH).

  Case Report Top

This female preterm neonate was born at a gestational age of 28 weeks and weighed 590 g. She was delivered by emergency cesarean section because of intrauterine growth restriction and maternal preeclampsia. Her parents are the Saudi double-first cousin. The infant's mother was a 26-year-old, gravida 2, with a history of one spontaneous abortion, sickle cell anemia, and ulcerative colitis. After birth, the neonate received one dose of surfactant and 1-day of mechanical ventilation. A 4 French double UVC was inserted and secured at 7 cm. Its pathway was confirmed by X-ray, and the tip was in a satisfactory position [Figure 1]. Patency of the line was maintained by a continuous infusion of 0.5 units/kg/h of heparin. [3] Insertion of an umbilical arterial catheter (UAC) was attempted but proved unsuccessful.
Figure 1: An X-ray image shows the umbilical venous catheter in a satisfactory position

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The patient remained stable day 9 of life when she developed intermittent ischemia of the distal phalanges of four right fingers. None of her peripheral arteries were manipulated. On day 11, she developed tachycardia, increased oxygen requirement, and feeding intolerance. A full septic workup was performed at this time, including a chest X-ray and lumbar puncture. Ischemia of fingers worsened during obtaining a blood culture from the UVC, and this finding prompted us to remove the UVC. The ischemia resolved without complication after applying a 5 mg nitroglycerin transdermal patch over the wrist daily for 3 days.

Blood cultures collected from a peripheral vein and the UVC yielded cloxacillin-sensitive Staphylococcus aureus. Platelet count on the day of deterioration was 195 × 10 9 /L but dropped to 34 × 10 9 /L by the following day. The baby continued to have thrombocytopenia despite two platelets transfusions and negative follow-up blood cultures 4 days after starting cloxacillin. For this reason, an initial echocardiogram (ECHO) was performed on day 15. It revealed a nonobstructing RAT that measured 6 mm × 8 mm and was attached to the interatrial septum and inferior vena cava. Because blood cultures grew S. aureus, and family history was negative for inherited prothrombotic tendencies, a diagnosis of infective endocarditis was made. Thus, investigations for a thrombotic disorder were not done. As the patient would require 6 weeks of parenteral antibiotics, and vascular access of the patient was difficult to obtain, a peripheral inserted central catheter (PICC) was inserted on day 22. The PICC was inserted at the right cubital fossa, and its tip was at the right mid-clavicle. Its patency was maintained by continuously infusing 0.5 units/kg/h of heparin. [3]

An ECHO done on day 23 indicated that the RAT had increased in size to 17 mm × 6 mm, protruded forward and backward throughout tricuspid valve, and covered most of the right atrium [Figure 2]. After analyzing these findings, the cardiologist contacted local cardiac referral centers to discuss the possibility of surgical intervention. On day 25, 2 mg daily of aspirin was started while waiting for feedback from referral centers. [3] The third ECHO was performed on day 28 and revealed the same findings as the second one. On day 36, we made the decision to utilize r-tPA as the treatment option for this very large RAT as surgical intervention would be risky in such ELBW neonate.
Figure 2: Transthoracic echocardiogram (subcostal view) shows the right atrial thrombus

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All relevant blood work was obtained prior to starting r-tPA. [3],[4] This included prothrombin, partial thromboplastin time, and fibrinogen all values were within the normal range. Thrombocytopenia resolved by day 29 after a total of three platelet transfusions and platelets count remained within normal range throughout patient's life. Aspirin was discontinued, and a dose of solvent-detergent plasma (10 ml/kg) was infused. Then, r-tPA (1.2 mg/kg) was administered over 6 h via the PICC after obtaining informed consent from the father. [3],[4],[5] A follow-up ECHO on the next day showed that the RAT had become spherical, and it had attached to the interatrial septum. It had decreased in size to 2 mm × 2 mm after the single dose of r-tPA. The RAT remained the same size on eight subsequent ECHOs. After having four previous normal head ultrasound (HUS) examinations, a repeat HUS on day 29 revealed a grade 1 intraventricular hemorrhage on the right side. A follow-up HUS on the next day of r-tPA use showed no change from the previous HUS done on day 29. The RAT remained attached to the interatrial septum and measured 2 mm × 2 mm during the five follow-up ECHOs that were performed between days 38 and 88.

This patient required 35-45% of oxygen on day 52 (36 weeks postmenstrual age), and she required a nasal cannula after extubation until day 98. Thus, she was labeled as a case of severe bronchopulmonary dysplasia (BPD). On day 98, she was weaned to room air and remained stable, with only intermittent self-resolved episodes of desaturations and tachypnea. On day 143, a nasal cannula was again required for prolonged desaturations down to 80% and increased work of breathing. On day 147, an ECHO revealed that the RAT was still attached to the interatrial septum and was still measuring 2 mm × 2 mm since the last ECHO on day 88. However, it also revealed a new finding of severe PH. Serial chest X-rays showed a presentation of bilateral pneumonia with atelectatic changes. [Figure 2] depicts the chest X-ray a few hours before death. We performed an upper gastrointestinal series to rule out aspiration caused by gastroesophageal reflux, and it was negative. Her health status continued to deteriorate. On day 155, she was connected to continuous positive airway pressure and on day 161 to mechanical ventilation. Cultures of blood, cerebrospinal fluid, tracheal aspirate, and urine were negative. Respiratory syncytial virus, influenza A and B, and parainfluenza 1-3 viruses were not detected by a rapid direct immunofluorescence assay. The PH did not respond to high-frequency oscillation ventilation, inhaled nitric oxide, sildenafil, bosentan, and adjuvant therapy including antibiotics, inotropes, fentanyl, and pancuronium. This persistent deterioration was attributed to severe BPD, pneumonia, and clinically suspected sepsis [Figure 3]. A chest computed tomography was planned, but the patient was too unstable to be moved to the radiology suite, and the patient expired on day 168.
Figure 3: The X-ray image that was performed a few hours before death

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  Discussion Top

This case is the second reported neonatal case of ischemia related to a UVC in English literature. [1] In the previous case, the authors determined the umbilical catheter to be a UVC based on clinical assessment. [1] Because of the lack of radiological confirmation, it is possible that the catheter may have been a UAC. In our case, however, catheter location was confirmed with X-ray as a UVC. If the catheter in the previous case was, in fact, a UAC, it could explain why the two cases differ with onset, extension, severity, and resolution of the ischemia. In our case, the ischemia developed 9 days after UVC insertion, affected the distal phalanges of four right fingers, and resolved without permanent damage. The ischemia in the previous case developed immediately after umbilical catheter insertion, affected two right fingers and all of the toes, and it ended with self-amputations of two distal phalanges as well as the nail beds of the toes on the right foot. [1]

Worsening of the ischemia by blood sampling from UVC inspired the idea that the ischemia was related to UVC. Nevertheless, we have no clear explanation as to cause of the ischemia. A study on 20 early-preterm neonates found that drawing 3.3 ml of blood from UVCs over 40 s had no effect on pulse oximetry, but it did reduce brain blood volume and oxygenation. [6] These adverse effects intensify when duration, volume, and frequency of sampling increases. [6] An alternative hypothesis is that ischemia might be due to a vascular dysregulation as both cases involve females, and vascular dysregulation occurs more frequently in females than males. [7] However, this hypothesis would need further study.

This patient developed a RAT that was treated by a single dose of r-tPA. The significant thrombolysis after the single dose of r-tPA may be due to the close proximity of the PICC line to the RAT. There are no standard criteria for when neonatal RAT should be treated, however, some experts recommend aggressive treatment of a RAT when any of the following criteria present: (1) Clot size > 4-5 mm in any dimension, (2) pedunculation, (3) mobility, (4) snake-shaped and mobile, or (5) symptomatic. [2],[8] The type of treatment to use for a RAT remains controversial, and options include thrombolytics, anticoagulants, thrombolytics followed by long-term anticoagulants or surgery. [3],[5],[9],[10] The r-tPA is preferred to other thrombolytics or anticoagulants because of its clot selectivity, short half-life (4 min), and low affinity toward plasminogen. [4]

Some experts advocate administering a long-term low-molecular-weight heparin even after successful treatment of an intracardiac thrombus to prevent recurrence of RAT. [4] Use of a long-term anticoagulant in this case was considered but deemed unnecessary because of the significant thrombolysis after the single dose of r-tPA and the high risk of serious bleeding in ELBW neonates. 4 months after the diagnosis and treatment of the RAT, the patient was found to have PH. Her PH was attributed to her severe BPD, pneumonia, and clinically suspected sepsis. However, a study done in 2014 found that ELBW infants are at an increased risk to develop pulmonary embolism (PE) during infancy compared to full-term infants (adjusted hazard ratio 28.38, 95% confidence interval: 2.88-279.33). [11] Therefore, in retrospect, this PH could have been due to a PE. Four reasons contributed to, not considering the possibility of a PE at that time. First, a long time (4 months) elapsed between the diagnosis and treatment of RAT and the diagnosis of PH. Second, PH in infants with BPD is very common (18-25%) whereas thromboembolic PH is rarely reported in preterm infants. [12],[13],[14] Third, RAT remained static in location and size after treatment, thus, low risk for developing a PE. Fourth, serial chest X-rays and ECHOs were not suggestive of PE. Undoubtedly, definitive exclusion or inclusion of a PE is impossible without appropriate diagnostic investigation of PE or performing an autopsy. [14] Retrospectively, if a long-term anticoagulant had been administered or PE was considered and treated, the outcome might have been different. Nevertheless, PH in both BPD and PE is associated with significant mortality. [12],[14]

In summary, we present a preterm infant with ischemia of fingers related to use of a UVC, RAT treated by single dose of r-tPA, and lethal PH. Diagnosis of UVC-related ischemia requires a high index of suspicion. This case is an additional support to use r-tPA in ELBW infants, and it may support the notion of utilizing a long-term anticoagulant after successful treatment of a RAT. However, an individualized treatment approach for RAT is the rule of thumb in ELBW infants until its appropriate treatment is established in a multicenter clinical trial. It may be prudent to also consider a PE in ELBW infants with PH.

  Acknowledgments Top

The authors are grateful to Ms. Jessica Marie Housman, assistant manager of intermediate care nursery for her English editing of the manuscript.

  References Top

Ancora G, Soffritti S, Faldella G. Diffuse and severe ischemic injury of the extremities: A complication of umbilical vein catheterization. Am J Perinatol 2006;23:341-4.  Back to cited text no. 1
Yang JY, Williams S, Brandão LR, Chan AK. Neonatal and childhood right atrial thrombosis: Recognition and a risk-stratified treatment approach. Blood Coagul Fibrinolysis 2010;21:301-7.  Back to cited text no. 2
Monagle P, Chan AK, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-Göttl U, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9 th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e737S-801.  Back to cited text no. 3
Rimensberger PC, Humbert JR, Beghetti M. Management of preterm infants with intracardiac thrombi: Use of thrombolytic agents. Paediatr Drugs 2001;3:883-98.  Back to cited text no. 4
Saxonhouse MA. Management of neonatal thrombosis. Clin Perinatol 2012;39:191-208.  Back to cited text no. 5
Hüning BM, Horsch S, Roll C. Blood sampling via umbilical vein catheters decreases cerebral oxygenation and blood volume in preterm infants. Acta Paediatr 2007;96:1617-21.  Back to cited text no. 6
Flammer J, Konieczka K, Bruno RM, Virdis A, Flammer AJ, Taddei S. The eye and the heart. Eur Heart J 2013;34:1270-8.  Back to cited text no. 7
Yang JY, Williams S, Brandão LR, Chan AK, Mondal T. Neonatal and childhood right atrial thrombosis: Critical clot size. Blood Coagul Fibrinolysis 2013;24:458.  Back to cited text no. 8
van Elteren HA, Veldt HS, Te Pas AB, Roest AA, Smiers FJ, Kollen WJ, et al. Management and outcome in 32 neonates with thrombotic events. Int J Pediatr 2011;2011:217564.  Back to cited text no. 9
Bose J, Clarke P. Use of tissue plasminogen activator to treat intracardiac thrombosis in extremely low-birth-weight infants. Pediatr Crit Care Med 2011;12:e407-9.  Back to cited text no. 10
Zöller B, Li X, Sundquist J, Sundquist K, Crump C. Gestational age and risk of venous thromboembolism from birth through young adulthood. Pediatrics 2014;134:e473-80.  Back to cited text no. 11
Baker CD, Abman SH, Mourani PM. Pulmonary Hypertension in Preterm Infants with Bronchopulmonary Dysplasia. Pediatr Allergy Immunol Pulmonol 2014;27:8-16.  Back to cited text no. 12
DeMeo SD, Sherwood A, Hornik CD, Goldberg RN, Cotten CM, Bidegain M. Pulmonary artery thrombus in a premature neonate treated with recombinant tissue plasminogen activator. J Perinatol 2014;34:569-71.  Back to cited text no. 13
Paes BA, Nagel K, Sunak I, Rashish G, Chan AK, Thrombosis and Hemostasis in Newborns (THiN) Group. Neonatal and infant pulmonary thromboembolism: A literature review. Blood Coagul Fibrinolysis 2012;23:653-62.  Back to cited text no. 14


  [Figure 1], [Figure 2], [Figure 3]


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