a) Single centre Randomised Control Trial
(b) Methodology:
* Study population : Children aged6months-18 years with Decompensated Cirrhosis with histologic or image proven liver cirrhosis of any etiology with INR \>2.5 and/or PLT count 20,000/mm3- 50,000/mm3 and who are listed for the following invasive procedure
* Low risk of bleeding
1. Central venous cannulation
2. Haemodialysis catheter
3. Ascitic or Pleural tapping
4. EVL
5. EST
High risk of bleeding
6. TIPPS
7. ERCP with sphicterotomy
8. PCD Insertion
9. Biopsies other than liver biopsy
* Study design:Randomised Control Trial
* Study period: 2 year: October 2022 to October 2024
STATISTICAL ANALYSIS: Sample size calculation for the RCT
* Appropriate statistical test for correlation analysis will be applied
* Assuming a 20% difference in the average transfusion requirements of the two groups based on a previous study, assuming a 5% alpha error and power of 90% along with an expected dropout rate of 10%, we got a sample size of 90 (45 patients in each arm) and 1/3rd patients of this would be for Liver Biopsy.
Intervention :
* Children with decompensated cirrhosis listed for invasive procedures and with deranged INR between \>2.5and/or deranged platelet count between 20,000/mm3-50,000/mm3 will be included in the study and will undergo block randomization into two groups. To prevent bleeding during the procedure, one group will receive prophylactic transfusion of either FFP, Platelet or Cryoprecipitate based on the following protocol
1. If INR: \> 2.5 FFP will be transfused at 15 ml/kg
2. If Platelet Count is 20,000/mm3-50,000/mm3 RDPC will be transfused at 10 ml/kg
3. If Fibrinogen \< 80 mg/dl Cryoprecipitate will be transfused at 5 ml/kg The second group will undergo ROTEM based correction. ROTEM bcorrection will be based on the following protocol
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1. EXTEM CT \> 80 sec - FFP will be transfused at 15 ml/kg MCF \< 35 mm- Platelet will be transfused at 10 ml/kg
2. FIBTEM MCF \< 7 mm- Cryoprecipitate will be transfused at 5 ml/kg
Following correction, the procedure will be done in both the groups. Patients randomised in the ROTEM group will undergo repeat ROTEM and INR, Platelet, Fibrinogen testing (depending on the component transfused), post the procedure, to look at the correction achieved. Similarly, patients randomised in the conventional group will undergo repeat INR, Platelet,fibrinogen testing depending on the component transfused.
Patients will be followed for 24 hours indoors for any evidence of bleeding or transfusion reaction. Significant Bleeding have been defined as fall in Hb by 3 g/dl in 24 hours and /or hypotension CBC will be repeated at 24 hours, to look for any fall. Transfusion reactions that will be looked for Early (within 24 hours of transfusion) Severe allergic reaction - Acute hypotension, lower airway obstruction with urticaria, angioedema or generalized pruritis Transfusion related acute lung injury-New acute lung injury within 6 hours of a transfusion; Hypoxemi with PaO2/FiO2 \< 300 mm Hg ( or O2 \< 90%) and bilateral Chest X ray infilterates with lack of other risk factors for pulmonary edema.
Transfusion associated circulatory overload- Acute onset of congestive heart failure as a direct result of blood transfusion with
1. Dyspnea, orthopnea, bilateral rales with hypoxia or
2. Systolic Hypertension, tachycardia, jujgular venous distension, pedal edema with A) X rays with bilateral basilar infiltrates or B) Hypoxemia (\< 90% saturation on room air)
Patient will be followed up in OPD after 5 days to look for any late transfusion reaction Delayed reactions looked forwill be Delayed hemolytic transfusion reaction Hemolysis after 24 hours with anemia, DCT positivity, spherocytes on peripheral smear Monitoring and assessment:The amount of total blood components (FFP, Platelet, Cryoprecipitate) transfused in each group will be assessed, along with the amount of individual components transfused. The bleeding episodes will be assessed by fall in Hb or blood pressure in each group, as will be the transfusion reactions (Acute respiratory distress syndrome, Transfusion related acute lung injury, Heart failure or majortransfusion reactions.
STATISTICAL ANALYSIS: Sample size calculation for the RCT Appropriate statistical test for correlation analysis will be applied
\- Adverse effects: Patientsreceiving transfused blood componets based on ROTEM or conventional methods will be monitored for clinically significant bleeding till 24 hours post procedure. Transfusion reactions in the form of ARDS, TRALI will be looked for.
\- Stopping rule: Interim analysis will be done after 20 patients. If significant increase in the bleeding rate or transfusion reactions in the ROTEM group, trial will be stopped
e) Ethical issues in the study and plans to address these issues: The transfusion requirement in the ROTEM group is expected to reduce as compared to the transfusion requirement in the Conventional group. This is expected to reduce the number of transfusion reactions and the cost of therapy in the ROTEM group. The additional of cost of doing ROTEM tests is expected to be mitigated by the reduction in cost from decreased transfusion requirement and decreased transfusion reaction.
