Catheter-directed thrombolysis for in situ pulmonary artery thrombosis in children.

In situ pulmonary artery thrombosis (ISPAT) is a unique form of pulmonary embolism characterized by local formation of thrombus in the pulmonary arteries. We present here a baby with hypoplastic left heart syndrome who developed ISPAT after Glenn surgery. The patient underwent catheter-directed thrombolysis, followed by systemic anticoagulation with excellent results. Copyright:

INTRODUCTION

Even though considered rare in children, pulmonary embolus (PE) is increasingly recognized as a unique illness in terms of pathophysiology, presenting symptoms and treatment strategies.[12] There are two different patterns of PE in children: classic thromboembolic PE (TE-PE) and in situ pulmonary artery thrombosis (ISPAT). While TE-PE has similar characteristics as adults, ISPAT has distinctive features including younger age at presentation and a local formation of thrombus in pulmonary arteries. ISPAT is not necessarily related to deep vein thrombosis (DVT) but rather a consequence of heart surgery, pulmonary artery anomalies, or lung transplantation.[3] Catheter-directed thrombolysis (CDT) includes a placement of a catheter under radiologic imaging directly into the thrombus and delivering a thrombolytic agent. We describe the use of CDT for thrombus removal in a child with hypoplastic left heart syndrome (HLHS) who developed ISPAT after Glenn surgery.

CASE REPORT

An 8-month-old full-term baby boy with HLHS was electively admitted for bidirectional Glenn procedure. His past medical history included Sano-modified Stage I Norwood palliation in the neonatal period. He underwent the bidirectional Glenn procedure with pulmonary artery plasty, due to severe right pulmonary artery stenosis diagnosed on the pre-Glenn catheterization. Surgery was uneventful, and he was successfully extubated. On day 9 after surgery, nasal swab was positive for an RSV infection, and he was reintubated and started on inotropic support and nitric oxide for severe hypoxemia. Echocardiogram showed no flow in the left pulmonary artery (LPA). Catheterization demonstrated a complete occlusion of the LPA by a long segment thrombus [Figure 1]. Thrombectomy and LPA plasty using Gore-Tex membrane (0.6 mm) were performed followed by a computed tomographic angiography (CTA) that showed patent pulmonary arteries. Following the procedure, heparin therapy was resumed, yet a follow-up CTA 6 days later demonstrated re-occlusion of the LPA. Following multidisciplinary consultation, an urgent catheterization was performed during which the LPA was re-canalized using a glide catheter and 0.35” Terumo© glide wire with repeat manual suction of the thrombus. Surgical opinion was to avoid stenting the artery, so the catheter was left in situ in the thrombus for local administration of tissue plasminogen activator (TPA) to be given for 24 hours at a dose of 0.2 mg/kg/hr. The sheath inserted in the right internal jugular vein and the catheter left in place [Figure 2] were sewn securely in the neck for the duration of treatment and removed as soon as this was discontinued, with easy manual hemostasis achieved. Throughout treatment, the patient's laboratory parameters including fibrinogen, plasminogen, platelet counts, and D-dimer levels were monitored. CDT was disconnected after 18 h due to mild bleeding at the sheath site and stabilization of D-dimer levels. No complications were noted. Following the procedure, bivalirudin infusion was started, as we suspected some heparin resistance and opted to apply a short-acting and potent anticoagulant. Repeat CT showed patency of the occluded vessel, and the patient was successfully extubated. Three weeks later, he underwent repeat catheterization for balloon dilation of the distal LPA [Figure 3] and has since undergone further dilation. Continued dilation is planned for rehabilitation of the pulmonary tree. In the meantime, the child has been discharged with long-term anticoagulation therapy with low-molecular weight heparin and is doing well with a room air oxygen saturation of 80%.

Figure 1

Angiogram in the superior vena cava demonstrating complete re-occlusion of the left pulmonary artery on repeat catheterization

Figure 2

Angiogram in the left pulmonary artery after recanalization showing thrombus in situ. The catheter was left in this position for catheter-directed thrombolysis, as described in the text

Figure 3

Angiogram after balloon dilation the left pulmonary artery and upper lobe branch three weeks after catheter directed thrombolysis. Note a widely patent central pulmonary artery with limited distal pulmonary tree

DISCUSSION

We present a young infant with a rare complication of local thrombus formation in a pulmonary artery following Glenn palliation for HLHS who underwent successful CDT.

Whereas the mainstay of treatment of acute pediatric thrombosis is systemic anticoagulation, the management of ISPAT is usually more aggressive.[4] A rapid restoration of occluded vessels is necessary and therefore most patients undergo intervention.[56] A systematic review found either surgical thrombectomy or stent placement, to be the preferred initial intervention in children who developed ISPAT.[3] However, more recent studies have showed the efficacy and safety of CDT in children with PE in general and ISPAT in particular [Table 1].

Table 1

Summary of data on catheter directed thrombolysis in patients with pulmonary emboli

Author, year	Number of patients, age	ISPAT rate	Location	Thrombolysis (tPA) dose and duration	Outcome
Dabin Ji, 2020	9, 6-19 year	None	5 B/L PA	0.5 mg/h18-37 h	44% complete resolution56% partial resolution
			4 unilateral	1 mg/h 16-73 h	No complications
Marvin K, 2019	1, 12 year	None	RPA	2.5 mg bolus followed by 1 mg/h32 h (8 h and then 24 h)	Marked clinical and radiological improvementNo complications
Belsky J, 2019	5, 3-21 year	None	4 B/L1 RPA	0.03-2 mg/h11.5-72.5 h	4 complete resolution1 partial resolutionNo complications
Khan A, 2018	2 (children with PE out of 10 reported cases)	None	LPA	0.25-1 mg/h16-25 h	Complete resolutionNo complications
Akam-Venkata J, 2018	9, 12-20 year	N/A	5 B/L3 RPA1 LPA	2 mg bolus followed by 1 mg/h8-24 h	4 clinical improvement7 survived2 minor GI bleeding
Bavare AC, 2014	5, 11-17 year	None	3 B/L PA2 RPA	0.75-2 mg/h24 h	3 complete resolution2 partial resolutionNo mortalityNo complications
Cannizzaro V, 2005	2, 10-13 year	None	1 B/L PA	Bolus 0.02-0.03 mg/kgFollowed by 0.025 mg/kg/h28-32 h	Hematoma at the access siteMild epistaxis
Ruud E, 2003	1 (out of 2 reported cases)12 year	1	LPA	0.008-0.016 mg/kg/h	Complete resolution
Beitzke A, 1996	1, 3 year	1	N/A	N/A	N/A

PE: Pulmonary emboli, ISPAT: In situ pulmonary artery thrombus, tPA: Tissue plasminogen activator, RPA: Right pulmonary artery, LPA: Left pulmonary artery, B/L: Bilateral, PA: Pulmonary arteries, GI: Gastrointestinal, N/A: Not available

The first successful CDT for acute pulmonary artery embolism was reported in 1996 by Beitzke et al.[7] in a 3-year-old girl who presented with near lethal PE 3 weeks after Fontan operation. Nomura et al. described, in 2014, a case of 20-year-old woman with thromboembolism of the subsegmental branches of the right pulmonary artery after a Glenn procedure with a successful CDT.[8] Over the years, rare cases of pulmonary artery occlusion treated with CDT have been published. Most of the patients had a background of hypercoagulable states, and their clinical presentation was similar to that of adults with PE. Only two patients described had associated structural cardiac disease.

PE in adults is usually triggered by DVT, underlying thrombophilic risk factors or acquired conditions promoting hypercoagulability (e.g.,: cancer, immobility, hormonal therapy, and presence of antiphospholipid antibodies). The prevalence of postcardiac surgery PE in children is considered extremely rare even with concomitant respiratory infection, as in our case. In these cases, PE may be localized to MPA. Treatment duration of isolated pediatric PE (unlike adult PE) may be relatively short, especially when prothrombotic systemic risk factors cannot be established.

The distinction in choice preference between surgery and direct thrombectomy is still unclear. Given the long segment thrombus and surgical preference, we first performed surgical thrombectomy. However, due to re-occlusion propagated by high pulmonary resistance, pulmonary artery stenosis, and a concomitant viral infection, we decided to resolve the occlusion by direct thrombolysis. Factors which led our team to favor thrombolysis over stenting were mainly surgical preference due to a small distal pulmonary artery and young patient age. Indeed, the child may undergo future stenting of the pulmonary artery; however, this management allowed gradual rehabilitation of the pulmonary tree and the ability to place a larger stent later which will be effective until adulthood. Endovascular catheter-directed therapy has the advantage of installation of lower doses of thrombolysis into or close to the thrombus, therefore reducing risk of bleeding. Strict monitoring during thrombolysis with tPA is critical. D-Dimer levels can particularly help to keep track of direct tPA therapy, as an elevated level reflects active fibrinolysis and stable or decreased levels indicate the absence of further thrombolysis and suggest thrombolysis may be discontinued.[9] Bleeding remains a major concern, specifically in postsurgical cardiac patients, and is usually a primary end point for treatment.[10]

Notably, bivalirudin therapy has been successful in young infants.[11] The drug, usually indicated for the treatment of heparin-induced thrombocytopenia, is highly potent as it binds to the thrombin-bound clot and promotes thrombus recanalization. It may be easily monitored and has a very short half-life, the latter being extremely beneficial in postsurgical situations with increased bleeding risk. After treatment, the patient's condition markedly improved, and his recovery was fast and uneventful.

CONCLUSION

To the best of our knowledge, this is the youngest reported case of patient with ISPAT undergoing CDT. The infant presented with severe hypoxemia after bidirectional Glenn procedure due to complete occlusion of the LPA. A direct catheter approach and local administration of thrombolysis allowed for successful re-canalization of his pulmonary artery and important clinical improvement.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.