Journal of Clinical Gastroenterology. 2020. 54 (3): 255-262.
Rout G, Gunjan D, Mahapatra SJ, Kedia S, Garg PK, Nayak B.
There is a rebalanced status of coagulation forces in cirrhotic patients, hence in this population, conventional assays such as INR and APTT are not suitable for defining coagulation abnormalities and predict bleeding tendency.
Thromboelastography which provides a global assessment of various factors promoting coagulation and anticoagulation should in theory be more accurate than the conventional assays used.
AIM OF STUDY
To assess the use of thromboelastography- directed blood product transfusion in cirrhotic patients with acute variceal bleeding compared with convectional transfusion with correction of coagulopathy.
DESIGN AND LOCATION
- Open label randomised controlled trial.
- Variceal patients presenting to the department of gastroenterology, All India Institutes of Medical Sciences March 2017 to December 2017
- Inclusion criteria:
- cirrhosis of the liver with acute variceal bleeding, as defined by Baveno VI consensus.
- age between 18 – 65 years
- presence of significant coagulopathy defined as platelet count <50,000/mm3 and/or INR >1.8; and
- willingness to participate in the study.
- Exclusion criteria:
- presence of malignancy/disseminated intravascular coagulation/known coagulation disorder apart from cirrhosis
- intake of platelet inhibitors (eg, aspirin, clopidogrel) and/or drugs affecting coagulation cascade (eg, vitamin K antagonists) within the past 7 days
- blood product transfusion (FFP and/or platelets before TEG)
- presence of shock (systolic BP <90mmHg)
- presence of sepsis
- acute on chronic liver failure (ACLF)
- acute kidney injury or chronic renal failure
- presence of hepatic encephalopathy
- contraindication to endoscopy
- Cirrhotic patients with severe coagulopathy and acute variceal bleeding (as per inclusion and exclusion criteria mentioned above) were randomised to either a TEG-guided blood product transfusion or conventional transfusion.
- TEG was performed, within 6 hours of hospital admission, by using an automated thromboelastometer (MonoTEM-A) (FramarHemologix, Rome, Italy), according to the manufacturer’s instructions.
- TEG group Patients received FFP at a dose of 5 mL/ kg of ideal body weight when R time was >15 minutes. Patients were transfused platelets when the MA was <30mm (3 units of platelets over 30 to 60min).
- Conventional group patients received FFP 5mL/kg of ideal body weight when the INR was >8 and received 3 units of platelet transfusion when the platelet count was <50,000/mm3.
- Patients from both groups received standard management protocol as per the following:
- PRBC transfusion to achieve a target Hb level of 7g/dL to 8g/dL
- Endoscopy within 12 hours of hospital presentation with endoscopic variceal ligation for haemostasis
- Prophylactic parenteral antibiotics (cefotaxime 2g bd for 7 days)
- Carvedilol 3.125mg bd post endoscopy.
- Difference in the amount of FFP (volume in mL) and/or platelets transfused before endoscopy between the 2 groups to correct coagulopathy
- Rebleeding at day 5 and 42
- Mortality at 6 weeks
- All analyses were performed according to the intention to treat principle.
- Student t test or Mann- Whitney U test was used for continuous variables; the χ² or the Fisher test for discrete variables.
- To estimate the cumulative probability of survival, Kaplan-Meier analysis with the log-rank test was used.
- A 2-sided P value of <0.05 was taken as significant.
- 60 patients were randomised into the study with 30 patients in each group.
Blood products transfusion requirements: Significantly less in TEG group
|Blood Products transfusion||TEG GROUP (N=30)||Conventional transfusion group (N=30)||P value|
|FFP or platelet||4 (13.3%)||30(100%)||<0.001|
|Platelets||3 (10.0%)||21 (70.0%)||<0.001|
Mortality at 6 weeks: No significant difference between the 2 groups
- TEG group vs conventional group- 13.3% vs 26.7%, log-rank test, p= 0.176 (hazard ratio, 0.446; 95% CI, 0.134-1.484)
Rebleeding at day 5: No significant difference between the 2 groups
- TEG group vs conventional group- 3.3% vs 13.3%, P= 0.167
Rebleeding at day 42: Significantly less in TEG group
- TEG group vs conventional group- 10.0% vs 36.7%, log-rank test, P=0.012 (hazard ratio, 0.224; 95% CI 0.062-0.805)
- TEG-guided strategy is superior to conventional in determining the amount of blood product transfusion in cirrhotic patients with coagulopathy presenting with acute variceal bleeding.
- There was no difference in the control of variceal bleeding at admission, day 5 rebleeding, mortality and adverse events between the TEG and conventional transfusion groups.
- There was a higher risk of rebleeding at day 42 among patients who received blood products for correction of coagulopathy in the conventional transfusion group.
STATED LIMITATIONS FROM STUDY
- Patients with acute on chronic liver disease were excluded. Hence, results cannot be extrapolated to cover these patients.
- Patients with sepsis were excluded.
- Study was not blinded which may have resulted in bias. However, the study outcomes were objectively defined, and randomisation and concealed allocation were carried out to minimise bias.
- Fibrinogen level was not measured and none of the patients were transfused with cryoprecipitate.
- The TEG parameters after blood transfusion were not reassessed, which could have provided ideal cutoff targets for correction of these TEG parameters.
- The lack of a control arm that did not receive any prophylactic products.
Other trials with similar findings:
- Kumar et al 2020- TEG guided blood component use in patients with cirrhosis with non- variceal bleeding: A RCT
Conclusion of study:
The use of viscoelastic tests to determine transfusion requirements in patients with cirrhosis with non-variceal upper gastrointestinal bleeding does not result in superior control of bleeding compared to the use of routine diagnostic tests to guide transfusion, although blood product transfusion was much lower in the viscoelastic test group.
- De Pietri et al 2016- TEG guided blood product use before invasive procedures in cirrhosis patients with severe coagulopathy: A RCT
Conclusion of study:
TEG-guided transfusion resulted in a significantly lower requirement of blood products in patients with cirrhosis and significant coagulopathy undergoing various invasive procedures.
Current guidelines regarding this matter:
- European Association for the study of liver disease (EASL):
In patients with cirrhosis who are actively bleeding, there is initial evidence that the use of viscoelastic tests is associated with decreased blood product use in patients with cirrhosis and active upper gastrointestinal bleeds, without differences in bleeding control and mortality.
Given the benefits of reducing blood transfusion, viscoelastic tests can be used when available (LoE 1, strong recommendation).
- American association for study of liver disease (AASLD):
The AASLD do not recommend use of FFP as part of the management of portal hypertensive bleed; the rationale being that INR is not a reliable indicator of coagulation status in cirrhosis.
No recommendations can be given regarding platelet transfusion in patients with variceal haemorrhage.
- British Society of Gastroenterology (BSG):
The BSG recommends transfusion of FFP in patients with acute variceal bleeding having significant coagulopathy and transfusion of platelets if platelet count less than 50,000.
Discussion from journal club
- No clear consensus from different guidelines whether to use TEG or not in cirrhosis patients with variceal bleeding. EASL does encourage its use though.
- Paper provides good support for use of TEG to minimise unnecessary blood products use in cirrhosis patients with variceal bleed. However, larger trials need to be done and to include patients on the sicker end of the spectrum, i.e sepsis, AKI, ACLF
Image from MedPage Today.
Summary by Dr M Bankur. Journal Club Meeting 9 March 2023.