Prothrombin complex concentrate in the treatment of multitransfusion dilutional coagulopathy in a paediatric patient

Design

Case presentation

A 5-month-old (8 kg) infant was admitted to the pediatric intensive care unit (PICU) with hypovolemic shock secondary to liver failure caused by abuse. On admission, the patient exhibited severe mixed acidosis (pH 6.67) and profound anemia (hemoglobin 4 mg/dL) alongside markedly elevated liver enzymes. Initial hemodynamic stabilization was achieved with volume expanders, blood transfusions, dopamine, and sodium bicarbonate. Imaging revealed free intraperitoneal fluid, and an emergency laparotomy identified hepatic bleeding from torn segments, which was surgically addressed without liver resection. Postoperatively, persistent hypotension and coagulopathy ensued with continuous hemorrhagic drainage despite administration of fresh frozen plasma (FFP), platelets, and packed red blood cells (PRBCs). A second laparotomy revealed ongoing bleeding requiring partial liver resection.

Given refractory bleeding and laboratory evidence of dilutional coagulopathy (prothrombin activity 34%, activated partial thromboplastin time [aPTT] 51 seconds), prothrombin complex concentrate (PCC) was administered at 30 IU/kg in conjunction with vitamin K, resulting in rapid cessation of bleeding and hemodynamic stabilization. Coagulation parameters improved significantly post-PCC, increasing prothrombin activity from 19% (INR 2.9) to 54% (INR 1.5).

The patient’s clinical course thereafter was favorable, allowing discharge from the PICU after 12 days without thrombotic complications attributable to PCC. 

Study Author Conclusions

PCC was effective in controlling severe bleeding and regaining hemodynamic stability in a pediatric patient with multitransfusion dilutional coagulopathy. 

At the time of publication, there were no clinical trials of PCC as a treatment for severe bleeding caused by dilutional coagulopathy in children. Although not focused on the neonatal patient population and specific to hepatic coagulopathy (vs emergent reversal prior to surgery or major non-coagulopathic bleeding), this case suggests prospective studies to evaluate its effectiveness, dosage, and safety in children are indicated.

Use of Confidex to Control Perioperative Bleeding in Pediatric Heart Surgery: Prospective Cohort Study

Prospective, single-center, observational cohort study in Italy

N= 25

To evaluate the effect of a commercially available prothrombin complex (Confidex, a four-factor prothrombin complex concentrate [4F-PCC])) administered in cardiac surgery after weaning from cardiopulmonary bypass (CPB) of infants with nonsurgical bleeding

Confidex group (n= 14)

Control group (n= 11)

Infants younger than 1 year who underwent cardiac surgery with a cross-clamping time longer than 60 min or a total CPB time longer than 120 min and had nonsurgical bleeding

Infants received a Confidex bolus of 0.1 mg/kg (1 mL/kg of reconstituted solution) 30 min after weaning from CPB. Per institutional protocol, first-line use of 10 mL/kg platelet transfusions (regardless of platelet count) was employed in all bleeding infants immediately post-CPB wean. Postoperative packed red blood cell (PRBC) transfusion was administered to target a hematocrit of 38%; fresh frozen plasma (FFP) transfusion was used if prothrombin time (PT) <50%, and platelet transfusions were used if platelet counts <50,000 cells/mm³.

Coagulation was monitored before surgery, 30 min after bypass, at arrival in the pediatric intensive care unit (PICU), and 24 h after admission. Individual point-of-care hemostasis was assessed using thromboelastography (TEG, with TEG 5000). Daily echocardiogram monitoring was performed to exclude intracardiac thrombus formation.

November 2010 to February 2012

Primary: Safety with respect to intracardiac thrombotic events and side effects

Secondary: Reduction in postoperative bleeding, volume of blood products transfused

Confidex (n= 14)

ACT = activated clotting time; aPTT = activated partial thromboplastin time; AT = antithrombin; CPB = cardiopulmonary bypass; INR = International Normalized Ratio; PT = prothrombin time; RACHS = Risk- Adjusted Classification for Congenital Heart Surgery.

Confidex (n= 14)

No side effects such as anaphylaxis or intracardiac thrombotic events were observed.

The use of Confidex for infants undergoing cardiac surgery was safe and effective. It reduced postoperative bleeding and allowed fewer units of packed red blood cells to be infused in the postoperative phase without major side effects.

The study was not randomized, which may introduce selection bias. The decision to use Confidex was based on the attending anesthesiologist's preference, potentially enrolling more severely bleeding patients in the Confidex group. Echocardiographic evaluation may have missed smaller clots, and more invasive evaluations were not feasible. This study did include a predominantly neonatal population (~80% per group), and use of Confidex may not be directly generalizable to other 4F-PCC commercial formulations (e.g., Kcentra). CPB-related bleeding is also very complex and involves transfusion of multiple blood products, introducing potential confounders to efficacy and safety of treatment effects.

Prothrombin Complex Concentrate for Intracerebral Hemorrhage Secondary to Vitamin K Deficiency Bleeding in a 6-Week-Old Child

Design

Case presentation

A previously healthy, full-term, exclusively breastfed 6-week-old female infant who had not received vitamin K prophylaxis at birth presented with altered mental status and multiple intracranial hemorrhages (ICHs) confirmed by computed tomography (CT) and magnetic resonance imaging (MRI). The patient was found to be profoundly coagulopathic with an International Normalized Ratio (INR) >10 and markedly prolonged prothrombin time (PT). Initial management included empiric antibiotics for suspected meningitis, packed red blood cell (PRBC) transfusions for anemia, and neuroprotective strategies such as hypertonic saline and mannitol for cerebral edema. The working diagnosis was ICH secondary to late-onset vitamin K deficiency bleeding (VKDB).

To rapidly reverse coagulopathy amid life-threatening bleeding, four-factor prothrombin complex concentrate (4F-PCC) was administered at 50 units/kg alongside intravenous vitamin K and fresh frozen plasma (FFP). Post-4F-PCC administration but prior to vitamin K infusion, the INR normalized to 1.3, and subsequent imaging demonstrated stable hematomas without progression of hemorrhage.

Despite an identified right leg deep venous thrombosis (DVT), this thrombotic complication was considered more likely catheter-related rather than a direct effect of 4F-PCC administration. The infant’s clinical course included seizure management and neurodevelopmental follow-up, with eventual resolution of seizures and appropriate developmental milestones. 

Study Author Conclusions

This report underscored that 4F-PCC, containing vitamin K-dependent coagulation factors II, VII, IX, and X, achieved prompt INR correction more rapidly than FFP alone and was a critical adjunct in emergent hemostasis.

Given the scarcity of pediatric data on 4F-PCC use for VKDB, this case illustrated the potential benefit of 4F-PCC for acute reversal in life-threatening vitamin K deficiency bleeding when rapid factor replacement is necessary and highlighted the importance of early recognition and intervention to mitigate morbidity and mortality.

Effectiveness and Safety of 4-factor Prothrombin Complex Concentrate (4PCC) in Neonates With Intractable Bleeding or Severe Coagulation Disturbances: A Retrospective Study of 37 Cases

Retrospective, single-center study

N= 37

To describe the experience regarding the effectiveness and safety of prothrombin complex concentrate (PCC) administration in newborns with severe bleeding or coagulopathy resistant to conventional therapy

All neonates (N= 37)

Neonates diagnosed with persistent bleeding and/or severe coagulation disturbances, resistant to conventional hemostatic therapy (per department protocol), who received PCC treatment

All patients received intravenous bolus administration of 20 units/kg or 30 units/kg PCC per dose. Prothrombin time (PT), International Normalized Ratio (INR), and activated partial thromboplastin time (aPTT) coagulation parameter values were measured before and after PCC administration. A 20 units/kg dose was used if INR <2, and a 30 units/kg dose was used if INR >2. A single additional PCC dose could be administered if needed, reaching a maximum of 50 units/kg within 4 hours.

January 2011 to June 2017

Primary: Efficacy of PCC in treatment of refractory hemorrhage or severe coagulopathy

Secondary: Safety and tolerability of PCC, occurrence and severity of adverse events

All patients (N= 37)

Before PCC

No acute adverse events or thromboembolic complications were observed in all neonates.

PCC seemed to be a safe and effective intervention for hemostasis in neonates with intractable bleeding or severe coagulation disturbances. Early intervention was more effective as a rescue therapy, without any adverse event. Further prospective controlled trials are required to determine optimal dose and timing of PCC administration in neonates.

The study provides valuable insights into the use of PCC in neonates, showing significant improvements in coagulation parameters. However, the retrospective design, small sample size, and lack of a control group limit the generalizability of the findings; differentiation of use of 3- vs 4-factor PCC (3F-PCC vs 4F-PCC, respectively) was not mentioned, which limits application of these findings strictly to one type of PCC over the other. Larger randomized controlled trials are needed to confirm these results and establish guidelines for PCC use in neonates. 

Hemorrhagic Disease of the Newborn as a Consequence of Vitamin K Refusal Due to Language Barrier

Design

Case presentation

A 5-week-old, full-term infant presented with symptoms including non-bloody vomiting, diarrhea, tactile fever, and irritability. The infant had not received prophylactic vitamin K at birth due to parental refusal influenced by a language barrier involving a rare Spanish dialect that impeded clear comprehension despite the use of a standard Spanish medical interpreter.

Initial evaluation revealed normocytic normochromic anemia, thrombocytosis, hyponatremia, mild transaminitis, hyperbilirubinemia, and metabolic acidosis. The infant’s condition rapidly deteriorated with altered mental status, unilateral fixed pupil dilation, and bleeding from invasive sites. Neuroimaging identified a large mixed-attenuation left-sided subdural hemorrhage (SDH) with significant midline shift, mandating urgent intubation, transfusion with packed red blood cells (PRBCs) and fresh frozen plasma (FFP), and emergent neurosurgical decompression with hematoma evacuation. Coagulation studies performed prior to treatment demonstrated profound coagulopathy (prothrombin time [PT] >300 seconds, International Normalized Ratio [INR] >4, PTT >300 seconds) consistent with vitamin K deficiency bleeding (VKDB).

Immediate administration of intravenous vitamin K and prothrombin complex concentrate (PCC) rapidly normalized coagulation parameters within two hours. Subsequent clinical management included seizure prophylaxis and supportive care with complete recovery and successful discharge on hospital day seven. Follow-up brain magnetic resonance imaging (MRI) at four weeks showed resolution of the hemorrhage with no residual mass effect or edema but revealed focal cerebral volume loss indicative of prior infarction. 

Study Author Conclusions

This case underscores the critical importance of timely vitamin K prophylaxis for newborns and highlights the complexities introduced by linguistic and cultural barriers that can lead to preventable, life-threatening hemorrhagic complications in infants. 

However, detailed administration data on PCC were not provided, including dosing (fixed vs weight-based) and formulation (3-factor vs 4-factor PCC), limiting the broader applicability of this case's results.