Use of viscoelastic monitoring and prothrombin complex concentrate in a paediatric patient with polytrauma and severe traumatic brain injury

Abstract

Viscoelastic monitoring (VEM) tools, such as rotational thrombelastometry, have been used extensively to measure coagulopathy in adults but have received less attention in paediatric care. The presented case involves a 5-year-old boy who was brought to the emergency department after a motor vehicle collision with a Glasgow Coma Scale score of 6T and extensive injuries, including a subdural hematoma. VEM was used to monitor the patient’s coagulopathy and to inform treatment measures by allowing real-time visualisation of the patient’s coagulation status. VEM was additionally used to direct blood product replacement in preparation for neurosurgical intervention, and 4-factor prothrombin complex concentrate (PCC) was used to help reverse the coagulopathy. The patient underwent successful hemicraniectomy after improvement of his coagulopathy. In paediatrics, VEM and PCC are increasingly being used for post-trauma coagulopathy, and this case highlights their potential promise and the need for further research.

Background

A significant number of trauma patients, especially those with severe traumatic brain injury (TBI), demonstrate post-injury coagulopathy.^1–5 Post-TBI coagulopathy is associated with increased morbidity, mortality and unfavourable outcomes, in both children and adults.^{1 2 6} As such, it is imperative to improve our ability to assess and manage post-traumatic coagulopathy to improve outcomes for patients with TBI.

Commonly used coagulation measurements such as international normalised ratio (INR), prothrombin time (PT) and partial thromboplastin time (PTT) have several inadequacies in the trauma setting.⁷ These standard measures do not capture the haemostatic process in real time, and they do not assess the quality or strength of a resultant clot.^8–10 As such, they may be more suitable for monitoring anticoagulation therapy than for measuring acute post-traumatic coagulopathy. Additionally, the turnaround time for these traditional measures may be more than 1 hour (median time 78–88 min).^{11 12} This lengthy turnaround time could potentially lead to inadequate treatment of the coagulopathy or an overuse of corrective blood products, which carry their own risks.^{13 14} Viscoelastic monitoring (VEM) tools, including rotational thrombelastometry (ROTEM) and thromboelastography (TEG), provide a measure of whole blood clotting in as few as 5 min.^{11 12} Both ROTEM and TEG are performed by exerting a constant rotational force on a sample of blood and then monitoring viscoelastic properties to determine clot formation, clot strength and clot degradation over time.⁷ Of note, we used ROTEM intrinsic pathway (INTEM) and ROTEM extrinsic pathway (EXTEM) assays specifically, which measure clot formation, fibrin polymerisation and fibrinolysis via the intrinsic and extrinsic pathways, respectively.

Additionally, another risk in caring for patients with TBI with coagulopathy is delay in surgical intervention secondary to efforts to reverse an elevated INR using fresh frozen plasma (FFP). The authors wanted to highlight this case to communicate the potential that these therapies may have in the care for paediatric trauma patients. While more research is clearly needed, the ability to more rapidly diagnose and correct coagulopathy following TBI may shorten the time to surgical intervention and make such interventions safer.

Case presentation

A previously healthy 5-year-old boy was involved in a motor vehicle collision in which the horse-drawn carriage he was riding in was stuck by a recreational vehicle travelling approximately 55 miles per hour. At the scene, the child was noted to have a Glasgow Coma Scale (GCS) score of 3, a palpable pulse and no apparent respiratory effort. His trachea was intubated prior to transport by the aeromedical helicopter team, and he was brought directly to our Level 1 Paediatric Trauma Centre. On initial evaluation, he was noted to have a GCS score of 6T. Head CT without contrast showed a 4 mm right-sided, isodense subdural hematoma; a corresponding 4 mm right-to-left midline shift and diffuse cerebral oedema (figure 1). Cervical spine CT showed malalignment of the craniocervical junction, suggesting ligamentous injury, and CT angiogram of the head/neck was negative for pathology but highlighted the isodense subdural hematoma. Additionally, CT of the abdomen and pelvis showed a grade 3 splenic laceration and a small grade 1 pancreatic duct laceration, and chest radiograph demonstrated a small right pneumothorax. The patient also had several orthopaedic injuries, including a right clavicular fracture, left humeral shaft fracture and bilateral lower extremity fractures. His Injury Severity Score was 41 (head 4, abdomen 4 and extremity 3).¹⁵

Figure 1.

Non-contrast head CT done prior to surgical intervention, showing cerebral oedema and midline shift. Hounsfield units for the subdural hematoma and the underlying brain were 32.2 and 39.5, respectively.

Treatment

Given his clinical presentation and radiographic findings, the surgical plan was to perform a right-sided frontotemporoparietal craniectomy with placement of an intracranial pressure monitor. While in the emergency department, the patient received two units of packed red blood cells (pRBC), 1 g/kg mannitol and prophylactic levetiracetam. Following initial resuscitation, he was transferred to the operating room for surgical management.

Initial blood panels showed the patient was coagulopathic: PT was 25.3 s (reference 12.4–14.7), PTT was 70 s (reference 24–36) and INR was 2.23. His haemoglobin was 73 g/L (reference 115–135 g/L). Based on the initial coagulation studies and haemodynamic fluctuations, the patient was given two additional units of pRBCs, two units of FFP, 10 mg of vitamin K, 1000 units (50 units/kg) of 4-factor prothrombin complex concentrate (PCC), and one unit of platelets. Additionally, a ROTEM study was sent to direct treatment of the coagulopathy. This initial test (figure 2A) showed an extrinsic pathway clotting time (EXTEM CT) of 94 s (reference 43–82 s), extrinsic pathway clot formation time (EXTEM CFT) of 396 s (reference 48–127 s) and extrinsic pathway maximum clot firmness (EXTEM MCF) of 40 mm (reference 52–72 mm). It also showed an intrinsic pathway clotting time (INTEM CT) of 240 s (reference 122–208 s), intrinsic pathway clot formation time (INTEM CFT) of 293 s (reference 45–110 s) and intrinsic pathway clotting time (INTEM MCF) of 42 mm (reference 51–74 mm).

Figure 2.

Rotational thromboelastometry studies examining the extrinsic coagulation pathway done prior to correction (A) and after correction (B). Labels include clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF).

Based on these results, another two units of FFP, two units of platelets and one unit of cryoprecipitate were administered. Additionally, based on the hematocrit and blood pressure, three additional units of pRBCs were given. While coagulopathy correction was being carried out, splints were applied to the patient’s bilateral lower extremities and left upper extremity. Also, while awaiting correction, the patient became haemodynamically unstable, demonstrated abdominal distention and his haemoglobin acutely decreased. Given his clinical picture, the general surgery service performed an emergent laparotomy, and the bleeding source was determined to be the spleen, which was removed.

Repeat coagulation studies revealed a persistent, but improving, coagulopathy: PT of 17.7 s, PTT of 46 s and INR of 1.42. Fibrinogen was normal at 185. Repeat ROTEM showed an EXTEM CT of 70 s, EXTEM CFT of 134 s, EXTEM MCF of 55 mm, INTEM CT of 227 s, INTEM CFT of 141 s and INTEM MCF of 53 mm. This second ROTEM revealed significant improvements from prior and only mildly abnormal metrics. Due to the patient’s acuity and improving coagulopathy, we proceeded with a right-sided frontotemporoparietal hemicraniectomy, followed by placement of a left frontal intracranial pressure monitor. The obtained bone flap was handled in a sterile fashion and stored at −80°C. Immediately prior to the procedure, the patient was given another unit of pRBCs and a unit of FFP. During the procedure, a unit of platelet was administered. Estimated blood loss for the neurosurgical procedures was 250 mL. A final ROTEM was drawn during the craniectomy and showed normalised haemostatic parameters for both the extrinsic (figure 2B) and intrinsic pathways with an EXTEM CT of 60 s, EXTEM CFT of 91 s, EXTEM MCF of 63 mm, INTEM CT of 200 s, INTEM CFT of 81 s and INTEM MCF of 61 mm. Postoperative head CT showed resolution of the midline shift, improvement in the cerebral oedema and no evidence of new haemorrhage (figure 3).

Figure 3.

Non-contrast head CT done immediately following the hemicraniectomy, showing postoperative changes, resolution of the midline shift and improvement in the cerebral oedema.

Outcome and follow-up

Seven days following placement, the intracranial pressure monitor was removed, and his trachea was successfully extubated 9 days after presentation. Neurosurgical intervention was complicated by a cerebrospinal fluid (CSF) leak from the surgical incision which required a return to the operating room for wound revision 22 days after the patient’s original presentation. Three days after this, the patient had a subsequent CSF leak and then had an external ventricular drain (EVD) placed for presumed post-traumatic hydrocephalus. Nine days after EVD placement, the EVD was removed, a ventriculoatrial shunt was inserted and an autologous cranioplasty was performed. He was able to be discharged home slightly less than a month and a half after the original trauma. At the time of discharge, he did have residual left-sided weakness, but he was antigravity on that side, able to stand for seconds at a time, and able to transfer efficiently. While inpatient rehabilitation was recommended, the family decided for discharge to home. By 3 months following discharge, the patient was ambulatory, and by his 1-year follow-up, he had fully reintegrated back into his normal work and school routines.

Discussion

Severely injured trauma patients are at risk for coagulopathy and downstream complications such as multi-organ failure, and risk factors for subsequent multi-organ failure include early hypocoagulopathy, haemorrhagic shock and evidence of fibrinolysis, all of which were present on the admission labs in this case.¹⁶ Particularly in children, TBI is a common factor in post-injury coagulopathy, perhaps due to release of tissue factor with subsequent protein C pathway C activation.¹⁷ For injuries that require neurosurgical intervention, invasive procedures may be significantly delayed by coagulopathy, so methods to quickly identify and treat coagulopathy may expedite treatment and potentially improve outcome.¹⁸

In neurosurgery, VEM has been used to monitor patients both prior to procedures and after trauma to measure coagulopathy, and studies have consistently associated abnormalities on VEM with poor outcomes and increased need for intervention.4 9 19–27 In TBI, coagulopathy measured by VEM has specifically been associated with increased mortality, higher incidence of neurosurgical intervention and increased intensive care unit and hospital days.^{4 23 26} One of the benefits of VEM, when compared with traditional coagulopathy measures, is its potential use for improved goal-directed therapy in real time. It has been used in cardiothoracic surgery, liver transplantation surgery and trauma to direct the replacement of blood products with decreased allogenic blood product use.^28–31 Of note, one study in trauma patients that found survival benefit specifically excluded patients with TBI.³²

While VEM has been used extensively to measure coagulopathy in adults, it has seen less use in the care of critically ill and traumatised children, but its utility is becoming better recognised by paediatric trauma centres.³³ Specific to paediatric neurosurgery, VEM has been used to measure coagulopathy prior to craniotomy for tumour resection.³⁴ Some studies have used VEM to document coagulopathy in paediatric trauma patients, associating acute traumatic coagulopathy with higher mortality, especially in patients with TBI.^{3 6} It has been suggested that VEM-directed use of antifibrinolytics is effective for treating post-TBI coagulopathy in children.³

The currently presented case describes how we used ROTEM to quickly identify coagulation disturbances in a paediatric patient with TBI in real time, and the case also shows how this technology can be used for goal-directed reversal of coagulopathy. Traditional coagulation tests may not be timely or accurate enough in trauma situations to allow for goal-directed correction of coagulopathy in an efficient manner. Additionally, giving empiric blood products to treat a presumed coagulopathy is imprecise and may lead to the administration of excessive or inaccurate use of blood products. We believe that, in this case, we may have avoided the risks of using excessive blood products by monitoring the patient’s coagulation status with ROTEM to measure his haemostatic properties in real time.

For paediatric trauma practice, VEM offers several other potential advantages: availability as a point-of-care test, rapid response time (initial results within 15 min) and low volume of blood required per test sample.^35–37 Potential disadvantages to the use of VEM in paediatric trauma practice include the cost of laboratory setup and sample processing, and the establishment of reference ranges for children has not been as robust as in adults.^{36 38 39}

Moreover, we used 4-factor PCC to help correct this patient’s coagulopathy following TBI. It should be noted that PCC is approved by the United States Food and Drug Administration for the ‘urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (eg, warfarin) therapy in adult patients with acute major bleeding’.⁴⁰ So, our use of this medication was an ‘off-label use’; however, use of PCC for trauma-related coagulopathy correction is becoming more common, and several studies have shown promise for its effectiveness and benefits in decreasing exposure to blood products.29 32 41–43 Other advantages of PCC over FFP include that it (1) can be stored at room temperature, (2) has reduced immunogenic properties and (3) requires a smaller volume to be infused.⁴⁴ There is some literature on the use of PCC in paediatric patients, but it has mostly been related to cardiac surgery,⁴⁴ and only a limited number of case studies have been published regarding the use of PCC for correction of coagulopathy in paediatric emergencies.^{45 46}

Learning points.

• Viscoelastic monitoring can be used to diagnose coagulopathy and monitor its reversal in paediatric patients with traumatic brain injury (TBI).

• For coagulopathy due to TBI, some paediatric patients may benefit from treatment with pooled plasma products, such as prothrombin complex concentrate, for rapid correction.

• While early observations for these novel diagnostic tests and treatments are encouraging, further research is needed to determine the safety and efficacy of their use in paediatric trauma and TBI.