Transfusion Practices in Critically Ill Children with Malignancy and their outcomes

Introduction

Transfusion practices in critically ill children are standardised mainly with respect to packed red blood cell products.7 Use of platelet, plasma, cryoprecipitate and other products are still a focus of research. There is an increased risk of bleeding in critically ill children with cancer due to primary disease, organ dysfunction, including bone marrow suppression, hepatic insufficiency, consumptive or dilutional coagulopathy, concomitant medications like anticoagulants, invasive procedures, etc.1

They receive plasma and platelet transfusions to control and prevent bleeding. There is a considerable proportion of prophylactic transfusion in non-bleeding children. These transfusions are associated with increased length of stay, nosocomial infections and multiple organ failure, and mortality2. For children with leukemia, the number of transfusions received is an independent risk factor for poor survival.3

Children may have an increased rate of bleeding compared with adults. Many guidelines suggest thresholds for transfusion, but children with cancer are a unique cohort with challenges of concomitant coagulopathy and impaired platelet function. The thresholds change, rather become liberal in conditions of sepsis, hemodynamic instability, minor bleeding, fever; as clinicians tend to err on the side of caution.4.5 The decreasing or increasing trends also guide our decision. The risks of pre-surgical transfusions need to be weighed against the child’s underlying comorbidities, severity of illness, etiology of the coagulopathy, type of surgical procedure, risk of bleeding, and additional hemostatic measures.

Furthermore, blood products such as granulocyte, cryoprecipitate and modification techniques such as leucodepletion and gamma irradiation are also used in children in our centre. This is mainly owing to the unique population of oncological patients who suffer from bone marrow dysfunction and immunosuppressed states. Guidelines regarding the use of these blood products are sparse and lacking.8,9

The practice of using thresholds as indications or end points for transfusion is suboptimal as laboratory coagulation values and platelet counts are ex vivo measures applied to in vitro expectations of hemostatic balance. Hence, we propose this study to understand our transfusion practices and their outcomes better.

Our current practice is to transfuse packed red blood cell if the hemoglobin level is below 7 g/dL and platelet transfusion in non-bleeding children if the count is below 10,000/uml.6 Platelets are also transfused before invasive procedures to meet the pre-procedural criteria of 50,000. The plasma is transfused for invasive procedures when INR is above 1.5 in non-bleeding patients. Cryoprecipitate is provided to children with fibrinogen levels below 100 mg/dL. Granulocyte transfusion is reserved for critically ill children with profound neutropenia (absolute neutrophil count < 100 cells/mm3). The end points of therapeutic transfusion in bleeding patients varies from case to case basis.

The demographic data of patients will be recorded such as age, sex, weight, primary diagnosis, ICU diagnosis.

We aim to record

1.The percentage of patients receiving transfusion and number of occasions of transfusion.

2.Their indications- a) prophylactic when below the threshold or undergoing invasive procedure or b) therapeutic for active bleeding

3.Dose of transfusion i.e. volume ml/kg of PRBC/RDP/SDP/FFP/Cryo/Granulocyte including any modified product usage.

4.Pre and post transfusion investigations suggesting the threshold/trigger and efficacy

5.Associated organ dysfunction (suggested by organ support such as ventilation, vasopressors, renal replacement therapy)

6.Associated all cause mortality

7.Transfusion related reactions and adverse effects.

Sample Size:

Critically ill children admitted in the intensive care unit from the IEC approval and CTRI registration will be screened to enroll 200 participants

Statistical analysis:

Continuous variables will be presented as mean with standard vision or medians with interquartile range, and will be compared by Student’s t-test or Mann-Whitney U test. Univariate analysis using Chi-square test and unpaired t-test for categorical and continuous variables, respectively, will be done.

Step wise logistical regression analyses will be applied to assess the risk factors for the development of complications related to the transfusion and associated all cause mortality. Those considerable covariates (p < 0.10 or have important clinical significance) will be included in multivariate analysis. Interactions among the covariates in multivariate analyses will be tested by collinearity diagnosis. A P value < 0.05 (two-tailed) will be considered to be statistically significant.