Management of Acute Liver Failure: A Pediatric Perspective

Bhatt, Heli; Rao, Girish S.

doi:10.1007/s40124-018-0174-7

Cited by 35 publications

(47 citation statements)

References 81 publications

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“…Clinically significant gastrointestinal bleeding is rare in PALF, however the American Association of Study of Liver Disease (AASLD) guidelines recommend histamine (H2) blockers or proton pump inhibitors for prophylaxis of gastric bleeding in ICU setting ( 8 , 34 , 48 ).…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

“…There are no guidelines for the resuscitation of acute bleeding in acute liver failure and transfusion of blood products have been associated with increased morbidity ( 48 ). Restrictive transfusion strategy with a threshold hemoglobin of >7 g/dL with a post-transfusion target of 7–9 g/dL are frequently utilized in a hemodynamically stable patient ( 15 , 25 , 42 ).…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

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Hemostatic Balance in Pediatric Acute Liver Failure: Epidemiology of Bleeding and Thrombosis, Physiology, and Current Strategies

2020

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Pediatric Acute Liver Failure (PALF) is a rapidly progressive clinical syndrome encountered in the pediatric ICU which may rapidly progress to multi-organ dysfunction, and on occasion to life threatening cerebral edema and hemorrhage. Pediatric Acute Liver Failure is defined as severe acute hepatic dysfunction accompanied by encephalopathy and liver-based coagulopathy defined as prolongation of International Normalized Ratio (INR) >1.5. However, coagulopathy in PALF is complex and warrants a deeper understanding of the hemostatic balance in acute liver failure. Although an INR value of >1.5 is accepted as the evidence of coagulopathy and has historically been viewed as a prognostic factor of PALF, it may not accurately reflect the bleeding risk in PALF since it only measures procoagulant factors. Paradoxically, despite the prolongation of INR, bleeding risk is lower than expected (around 5%). This is due to “rebalanced hemostasis” due to concurrent changes in procoagulant, anticoagulant and fibrinolytic systems. Since the liver is involved in both procoagulant (Factors II, V, IX, XI, and fibrinogen) and anticoagulant (Protein C, Protein S, and antithrombin) protein synthesis, PALF results in “rebalanced hemostasis” or even may shift toward a hypercoagulable state. In addition to rebalanced coagulation there is altered platelet production due to decreased thrombopoietin production by liver, increased von Willebrand factor from low grade endothelial cell activation, and hyperfibrinolysis and dysfibrinogenemia from altered synthetic liver dysfunction. All these alterations contribute to the multifactorial nature of coagulopathy in PALF. Over exuberant use of prophylactic blood products in patients with PALF may contribute to morbidities such as fluid overload, transfusion-associated lung injury, and increased thrombosis risk. It is essential to use caution when using INR values for plasma and factor administration. In this review we will summarize the complexity of coagulation in PALF, explore “rebalanced hemostasis,” and discuss the limitations of current coagulation tests. We will also review strategies to accurately diagnose the coagulopathy of PALF and targeted therapies.

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Section: Therapeutic Implicationsmentioning

confidence: 99%

Section: Therapeutic Implicationsmentioning

confidence: 99%

Hemostatic Balance in Pediatric Acute Liver Failure: Epidemiology of Bleeding and Thrombosis, Physiology, and Current Strategies

2020

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“…At the time of admission, evidence of acute liver injury was assessed through analysis of international normalised ratio (INR), elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin [ 10 , 11 ]. Patient clinical outcomes were classified as uncomplicated, complicated, or deceased within further analysis.…”

Section: Methodsmentioning

confidence: 99%

A retrospective study assessing the clinical outcomes and costs of acute hepatitis A in Cape Town, South Africa

et al. 2022

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Background While some evidence has been demonstrated the cost-effectiveness of routine hepatitis A vaccination in middle-income countries, the evidence is still limited in other settings including in South Africa. Given this, the evidence base around the cost of care for hepatitis A needs to be developed towards considerations of introducing hepatitis A vaccines in the national immunisation schedule and guidelines. Objectives To describe the severity, clinical outcomes, and cost of hepatitis A cases presenting to two tertiary healthcare centers in Cape Town, South Africa. Methods We conducted a retrospective folder review of patients presenting with hepatitis A at two tertiary level hospitals providing care for urban communities of metropolitan Cape Town, South Africa. Patients included in this folder review tested positive for hepatitis A immunoglobulin M between 1 January 2008 and 1 March 2018. Results In total, 239 folders of hepatitis A paediatric patients < 15 years old and 212 folders of hepatitis A adult patients $$\ge$$ ≥ 15 years old were included in the study. Before presenting for tertiary level care, more than half of patients presented for an initial consultation at either a community clinic or general physician. The mean length of hospital stay was 7.45 days for adult patients and 3.11 days for paediatric patients. Three adult patients in the study population died as a result of hepatitis A infection and 29 developed complicated hepatitis A. One paediatric patient in the study population died as a result of hepatitis A infection and 27 developed complicated hepatitis A, including 4 paediatric patients diagnosed with acute liver failure. The total cost per hepatitis A hospitalisation was $1935.41 for adult patients and $563.06 for paediatric patients, with overhead costs dictated by the length of stay being the largest cost driver. Conclusion More than 1 in every 10 hepatitis A cases (13.3%) included in this study developed complicated hepatitis A or resulted in death. Given the severity of clinical outcomes and high costs associated with hepatitis A hospitalisation, it is important to consider the introduction of hepatitis A immunisation in the public sector in South Africa to potentially avert future morbidity, mortality, and healthcare spending.

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“…Pediatric patients with liver dysfunction may have significant hemostatic abnormalities from impaired synthetic function including coagulation factor defects, thrombocytopenia and platelet dysfunction, alterations in the fibrinolytic system, and alterations in endogenous inhibitors of coagulation. While clotting times may be significantly elevated in these patients, these abnormal results often do not correlate with bleeding risk ( 124 , 125 ). Indeed, assessment of hemostatic balance in patients with liver disease generally demonstrates a neutral or mildly pro-thrombotic hemostatic system ( 126 , 127 ).…”

Section: Special Considerationsmentioning

confidence: 99%

Hemostatic Testing in Critically Ill Infants and Children

Nair

Parker

2021

Front. Pediatr.

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Children with critical illness frequently manifest imbalances in hemostasis with risk of consequent bleeding or pathologic thrombosis. Traditionally, plasma-based tests measuring clot formation by time to fibrin clot generation have been the “gold standard” in hemostasis testing. However, these tests are not sensitive to abnormalities in fibrinolysis or in conditions of enhanced clot formation that may lead to thrombosis. Additionally, they do not measure the critical roles played by platelets and endothelial cells. An added factor in the evaluation of these plasma-based tests is that in infants and young children plasma levels of many procoagulant and anticoagulant proteins are lower than in older children and adults resulting in prolonged clot generation times in spite of maintaining a normal hemostatic “balance.” Consequently, newer assays directly measuring thrombin generation in plasma and others assessing the stages hemostasis including clot initiation, propagation, and fibrinolysis in whole blood by viscoelastic methods are now available and may allow for a global measurement of the hemostatic system. In this manuscript, we will review the processes by which clots are formed and by which hemostasis is regulated, and the rationale and limitations for the more commonly utilized tests. We will also discuss selected newer tests available for the assessment of hemostasis, their “pros” and “cons,” and how they compare to the traditional tests of coagulation in the assessment and management of critically ill children.

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Management of Acute Liver Failure: A Pediatric Perspective

Cited by 35 publications

References 81 publications

Hemostatic Balance in Pediatric Acute Liver Failure: Epidemiology of Bleeding and Thrombosis, Physiology, and Current Strategies

Hemostatic Balance in Pediatric Acute Liver Failure: Epidemiology of Bleeding and Thrombosis, Physiology, and Current Strategies

A retrospective study assessing the clinical outcomes and costs of acute hepatitis A in Cape Town, South Africa

Hemostatic Testing in Critically Ill Infants and Children

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