Thrombus calcification after removing peripherally inserted central catheters in extremely preterm infants
- 1 Neonatology, Fukuoka Children's Hospital, Fukuoka, Fukuoka, Japan
- 2 PGDip in Neonatal Medicine, Cardiff University, Cardiff, UK
- Correspondence to Dr Takashi Shima; ShimaT@cardiff.ac.uk
Abstract
Pericatheter thrombus calcification is a complication that arises due to central venous catheter insertion and is particularly rare in peripherally inserted central catheters (PICCs). In this case report, we reviewed the clinical course of two neonates experiencing thrombus calcification. The first case involved a male neonate weighing 445 g. His PICC dwelt in the superior vena cava for over 49 days. Although a radiograph after removal did not show any silhouette, subsequent radiographs and CT depicted a catheter-like outline. Percutaneous intravascular retrieval was performed to salvage the object. Pathological examination revealed it to be a calcified cast. The calcified thrombosis was successfully dissolved with 6 months of warfarin therapy. The second case involved a male neonate weighing 534 g. After PICC removal, a catheter-like structure was shown on ultrasonograms. It was determined that invasive procedures were unnecessary for diagnosing the calcified thrombosis based on experience with the first case.
Background
Peripherally inserted central catheters (PICCs) are widely used in unwell neonates requiring long-term medical interventions. Reliable vascular access is an integral part of neonatal intensive care. However, PICCs are associated with several complications, including catheter-related bloodstream infections (CRBSI) and venous thrombosis.1 Thrombus calcification (calcified ‘casts’) is a known complication related to central venous catheter (CVC) insertion.2–7 However, only a few reports have described calcified cast formation after PICC placement.8 9 We report two such cases of calcified cast formation after PICC placement. The first case is a full case report, so its clinical course, examinations and interventions are thoroughly described. The second case was a patient whose calcified cast was successfully recognised without invasive procedures. Informed consent was obtained from the parents of both patients for the publication of this manuscript.
Case 1: case presentation
A male baby weighing 445 g was born at 22 weeks of gestation via vaginal delivery, following preterm, prelabour rupture of membranes. The patient was immediately intubated in the delivery suite, and surfactant was administered. Subsequently, the patient was placed under mechanical ventilation in the neonatal intensive care unit (NICU). A PICC (Argyle PI catheter II, COVIDIEN, Tokyo, Japan) was inserted via the right saphenous vein for total parenteral nutrition administration, sedation (fentanyl) and antibiotic (ampicillin and gentamicin) administration. Due to the high risk of persistent pulmonary hypertension in neonates, inhaled nitric oxide was delivered for the first 3 days. Chest radiograph on the sixth day showed increased lung opacity, suggesting the onset of pulmonary injury due to mechanical ventilation. Furosemide was administered to reduce pulmonary oedema. On day 10, the patient presented with symptoms of postnatal sepsis that led to neonatal acute respiratory distress syndrome.10 Hydrocortisone was started to reduce pulmonary inflammation via a new PICC. Long-term administration of steroids was required to mitigate lung impairment. Extubation followed by immediate non-invasive ventilation was performed on day 44. Intravenous caffeine and doxapram hydrochloride hydrate were administered via a PICC in the superior vena cava (SVC) to address the patient’s refractory apnoeic spells (figure 1A). His status gradually improved, and the catheter was easily removed 96 days after birth, bringing the total catheter dwell time in the SVC to 49 days. Although there were no silhouettes of catheter remnants on chest radiograph 4 days after removal (figure 1B), a distinct catheter-like outline gradually became visible on subsequent radiographs (figure 1C).
Cropped radiographs of the right chest. (A) The plain radiograph shows the presence of a peripherally inserted central catheter (PICC) (black arrows) in the right subclavian vein (SCV) and superior vena cava (SVC). (B) The radiograph 4 days after uneventful PICC removal does not show a linear opacity in the right SCV and SVC. (C) The radiograph 36 days after PICC removal describes a catheter-like structure (black arrows) in the right SCV and SVC, but its silhouette is slightly coarser than the catheter seen on figure 1A.
Investigations
On day 132, non-contrast chest CT clarified a linear catheter-like object in the SVC (figure 2). Ultrasonography showed a hyperechoic line at the same position (figure 3). However, neither CT nor ultrasonography showed a distinction between retained endovascular devices and calcifications due to their similarity in appearance and density.2 3
Plain CT of the thorax 36 days after peripherally inserted central catheter removal. Selected soft tissue window coronal slice demonstrates a linear radiopaque density (black arrows) located in the right subclavian vein and superior vena cava, which corresponds to the finding on figure 1C.
Transthoracic ultrasonogram with a linear 12 MHz transducer. The ultrasonogram on the right subclavian area reveals a hyperechoic, slightly crooked linear structure in the longitudinal view of superior vena cava (white arrows).
Differential diagnosis
Linear opacity was presumed to be a retained catheter fragment because of its shape and location in the imaging studies. However, the delayed clarity of the silhouette suggested that it was unlikely to be a catheter remnant. Therefore, we considered calcified thrombosis, as had been mentioned in an infantile case report on a calcified cast.8
Treatment
Following an in-depth deliberation, endovascular retrieval was attempted in order to salvage the catheter-like object. The procedure was unsuccessful because of bilateral femoral vein occlusion that may have been caused due to antecedently placed peripherally inserted (PI) catheters in the femoral veins. However, a fragment was successfully collected. Pathological examination (figure 4A,B) confirmed that the object was composed of fibrinous materials and calcified red blood cells. Since the patient was clinically stable, the thrombus calcification was left in situ, and warfarin therapy was initiated.
Pathological examination of the linear object obtained by endovascular retrieval. (A) Low-power field HE stain. B High-power field HE stain. The obtained specimen shows a lump of red blood cells (RBCs) covered with a layer composed of calcification (Cal) and fibrinous materials (Fib). The retained structure was diagnosed as thrombus calcification based on the pathological findings.
Outcome and follow-up
On day 170, the patient was discharged from the hospital and followed up in the outpatient department. He was monitored via serial radiology and serology (international normalised ratio monitoring). At 10 months of age, radiograph showed no linear opacification, suggesting thrombus dissolution. As a result, warfarin treatment for the calcified thrombi was discontinued. During the follow-up period of 3.5 years in our outpatient department, the patient was doing well with subnormal development. Developmental outcomes were examined at 3 years of corrected age using the Kyoto Scale of Psychological Development, a standard developmental test for children in Japan.11 The results were as follows: overall developmental quotient (DQ) of 76, postural-motor DQ of 88, cognitive-adaptive DQ of 79, and language-social DQ of 76. Anthropometric measurements at 3 years of age revealed body weight of 11 kg (−1.8 SD), height of 85 cm (−2.7 SD) and head circumference of 46 cm (−2.1 SD).
Case 2: case presentation
At 19 weeks of gestation, a mother with monochorionic diamniotic twins was diagnosed with twin-to-twin transfusion syndrome (TTTS). Selective foetoscopic laser photocoagulation was conducted at 23 weeks and 1 day of gestation. The twins were delivered via an emergency caesarean section at 24 weeks and 1 day of gestation due to umbilical cord prolapse following the prelabour rupture of membranes. One twin with TTTS (recipient) was a male weighing 534 g. Immediate intubation and surfactant administration was performed at the delivery suite, and standard neonatal intensive care (including PICC placement and mechanical ventilation) was provided in our NICU. The clinical course of the patient presented several difficulties (eg, colostomy due to necrotising enterocolitis, prolonged chylous ascites that developed after colostomy, and cerebral shunt placement for hydrocephalus due to severe intraventricular haemorrhage). On day 74, the patient suddenly went into shock, possibly due to CRBSI from a prolonged indwelling time (41 days). The PICC was removed from the innominate vein uneventfully (figure 5A), and a new PICC was inserted into the right subclavian vein (figure 5B). The actual cause of shock turned out to be a late-onset circulatory collapse of prematurity. The appearance and length of the catheter were carefully checked after removal, and the condition of the innominate vein was examined using ultrasound study based on our experience with the first case. The possibility of catheter breakage was excluded because the retrieved PICC was undamaged. However, ultrasonography revealed a cylindrical hyperechoic object with a slightly rough surface in the innominate vein (figure 6A), separate from the new PI catheter in the right subclavian vein (figure 6B). There was no need for invasive examinations as the removed catheter was intact and identified as a calcified cast.
Cropped radiographs of the chest. (A) The radiograph shows a peripherally inserted central catheter (PICC) placed in the innominate vein and the left subclavian vein (SCV) (black arrows). (B) The radiograph after PICC replacement demonstrates a new PICC inserted in the right SCV and superior vena cava (SVC) (white arrows). Meanwhile, radiographic opacification cannot be seen in the place where the used PICC was placed (innominate vein and left SCV).
Transthoracic ultrasonogram with a linear 18 MHz transducer. (A) The ultrasonogram on the left peri-clavicle area delinates a linear hyperechoic density with slightly coarse surface (black arrow) in the longitudinal view of innominate vein, suggesting a calcified cast. (B) The ultrasonogram on the right subclavian area shows a linear hyperechoic density with smooth surface (white arrow) in the longitudinal view of the right subclavian vein, describing an indwelling peripherally inserted central catheter.
Outcome and follow-up
The patient eventually died from the refractory chylous abdomen.
Discussion
The two cases demonstrate a unique sequence of PI catheter-related complications. A calcified cast is a complication of CVCs, as described in several studies (table 1). However, this phenomenon is mostly associated with long-term (ie, over a year) implanted central venous access devices, with leukaemia as the most common underlying disease.2–5 7 Based on our research, few studies have reported calcified casts after PICC placement in neonates.8 9 Our reported cases are noteworthy for neonatologists since thrombus calcification on imaging studies masquerades as a fragment of broken PICC.
A review of literature on catheter casts
| Authors | Year | Age | Primary disease | Position | Devices | Indwelling time | Diagnostic approach | Interventions | Outcomes |
| Hughes et al 2 | 2006 | 4 | ALL | Lt IJV | 5Fr Infusaport | 2.5 years | US, CT | Unsuccessful surgical extraction | Left in situ, Survived |
| Sabbaghian et al 3 | 2007 | 15 | ALL | INNV | 9.6Fr implantable port | 3.5 years | CT, venogram | Watchful waiting | Died due to primary disease |
| Muszynska-Roslan et al 4 | 2011 | 12 | ALL | Lt SCV | 5Fr CVC | 3 years | US, CT | Watchful waiting | Left in situ, survived |
| Van Bastelaar et al 5 | 2012 | 19 | ALL | Lt SCV | Venous access port | 2 years | CT | LMWH, antibiotic administration | Unmentioned, survived |
| Capitanini et al 6 | 2013 | 45 | ESRF | Lt IJV | Tunnelled HD catheter | 5 years | CT | Watchful waiting | Left in situ, survived |
| Keehn et al 7 | 2015 | 4 | ALL | Rt IJV | 5Fr Infusaport | 1.5 year | CT | Partially successful surgical extraction | Left in situ, survived |
| Anderson et al 8 | 1998 | 0 | MAS | Rt FV | 1.9Fr Per Q Cath | 49 days | US, CT | Successful surgical extraction | Removed, survived |
| Katayama et al 9 | 2020 | 0 | ELBWI | Rt GSV | 27G Argyle PI catheter II | 31 days | CT | Watchful waiting | Left in situ, survived |
| Current case 1 | 2022 | 0 | ELBWI | Rt SVC | 27G Argyle PI catheter II | 49 days | CT, pathology | Unsuccessful catheter retrieval, warfarin | Resolved, survived |
| Current case 2 | 2022 | 0 | ELBWI | INNV | 27G Argyle PI catheter II | 41 days | US | Watchful waiting | Died due to primary disease |
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Manufacturers of devices: Per Q cath, Bard Access System, Salt Lake City, Utah, USA; Infusaport, Kendall Healthcare, Mansfield, Massachusetts, USA; Argyle PI catheter II, COVIDIEN, Tokyo, Japan.
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ALL, acute lymphoblastic leukaemia; CVC, central venous catheter; ELBWI, extremely low birth weight infant; ESRF, end-stage renal failure; FV, femoral vein; GSV, greater saphenous vein; HD, haemodialysis; IJV, internal jugular vein; INNV, innominate vein; LMWH, low molecular weight heparin; MAS, meconium aspiration syndrome; SCV, subclavian vein; SVC, superior vena cava; US, ultrasonography.
Several factors are related to the mechanism of catheter-related thromboses, such as vascular damage due to catheter insertion, stagnant blood flow from an indwelling catheter and prolonged catheter usage.8 Gradual radiographic changes after catheter withdrawal may reflect calcium phosphate deposition on the thrombosis.7 In the second case, for example, although the ultrasound study could describe the calcified thrombosis in the innominate vein (figure 6B), the radiograph of figure 5B did not visualise the high-density line. This episode exemplifies the depositional process of thrombus calcification.
Retrospectively, the unique clinical course in the first case (ie, the emergence of catheter-like structure on radiographs after catheter removal) indicated the development of a possible calcified cast. Nonetheless, we had no prior knowledge of the optimal approach to this pathology. Such knowledge would have enabled bypassing of the invasive procedure and introduction of warfarin therapy.
In contrast, some intravascular catheter fragments have been detected after CVC removal.12 13 Therefore, careful examination of the length and shape of the removed PICC is necessary to exclude possible residual CVCs, as mentioned in the second case.
Unfortunately, there is no robust evidence regarding the numerical threshold for the duration of catheterisation. Therefore, NICUs have differing criteria for PICC replacement. Considering our experience and published cases,8 9 PICCs are tentatively valid for 1 month with regard to neonates. Additionally, thrombotic vascular occlusion followed by calcification should be checked by imaging studies, such as radiography or ultrasonography.
The role of warfarin therapy in calcified thrombosis is controversial. Warfarin is one of the major anticoagulant therapies for thromboembolism in paediatric patients.14 However, there are negative opinions on the use of warfarin in neonates because of the unacceptable risk of haemorrhage.15 Warfarin therapy was selected for the first case in our report because we were most familiar with its anticoagulant regimen. However, limited evidence suggests that low molecular weight heparin may have been the better choice for CVC-related thrombosis, including calcified cast, in neonates from the viewpoint of bioavailability and safety.5 16 If the calcified thrombosis seems to be asymptomatic, watchful waiting can be a reasonable option as most asymptomatic calcified thrombosis are innocent.2 4 6 7 9
In conclusion, there are few published reports on calcified thrombosis in neonates; therefore, our report might help health professionals in neonatal units acquaint themselves with this phenomenon. The faultlessness of the removed PI catheter must be checked carefully to rule out the possibility of a retained PI catheter, since it is arduous to diagnose the retained object in the vessel as calcified cast without prior information. Management plans for calcified cast ought to be considered based on a balance of the risks and benefits of anticoagulants and surgical retrieval.
Learning points
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This report describes calcified ‘casts’, which are rare complications related to peripherally inserted (PI) catheter placement.
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Awareness of this phenomenon will help avoid invasive exploration such as surgery and catheter interventions in similar clinical cases.
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PI catheters should be closely examined after removal to detect possible fractures.
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The indications of pharmacological and surgical interventions for calcified casts should be cautiously discussed based on their advantages and disadvantages.
Ethics statements
Patient consent for publication
Ethics approval
The ethical committee of Fukuoka Children’s Hospital approved this case report (permission number: 2021-1657).
Acknowledgments
We are grateful to Dr Kenichi Kohashi of Kyushu University for the pathological diagnosis. We thank Editage (www.editage.com) for English language editing.
Footnotes
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Contributors TS, primary physician, was in charge of the patients and wrote the manuscript. T Kusuda, senior neonatologist, worked as a team in diagnosing these cases and critically appraised the literature. NK, senior cardiologist, was involved in managing the case and approved the final manuscript. T Kinjo, senior neonatologist, supervised TS and guided the writing and editing of the manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
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