All Bleeding Stops Eventually
Treating hypovolemic shock secondary to haemorrhage seems very simple. Replace blood for blood. As I grew in my career, I realised that this is far more complex than I thought.
James Blundell was the first to notice the importance of blood transfusion, as he observed many females were dying in postpartum period due to PPH. In 1829, he invented first blood transfusion set and saved lives of many. Thereafter, transfusion medicine has evolved rapidly.
The most dangerous complication of massive transfusion is DEATH. This is attributed to well-known TRIAD of Death, which comprised of Hypothermia, Acidosis & Coagulopathy.
Reason for this is very simple. Instead of giving warm fresh blood, we prefer to give component therapy ( PRBC+FFP+Cryo+Platelets). Due to the addition of the preservative, the total volume of component therapy is 650 ml vs 500 ml of warm whole blood. This leads to inevitable dilution and thus DILUTIONAL Coagulopathy. Though warm whole fresh blood sounds logical and physiologically apt choice, we don’t practice it anymore due to the risk of transmission of blood borne diseases.
One of the interesting finding demonstrated by Miller in 1971, is still valid. As transfusion dose increases, the patient develops thrombocytopenia.
Massive Transfusion Increases Morbidity & Mortality
Various studies have shown the association between dose of transfusion and mortality & morbidity.
But What is Massive Transfusion?
Massive transfusion is defined in various different ways and unfortunately, there is NO consensus as to what constitutes massive transfusion.
The definitions in literature are –
- Transfusion of ≥10 red blood cell (RBC) units, which approximates the total blood volume (TBV) of an average adult patient, within 24 h
- Transfusion of 4 RBC units in 1 h with anticipation of continued need for blood product support
- Replacement of 50% of the TBV by blood products within 3 hours.
These definitions are arbitrary and not very helpful to bedside clinicians to activate Massive transfusion protocol (MTP). The definitions used in trials are not the same either. So makes it harder to define the effect of the intervention.
There is, even more, confusion about what constitutes MTP. Below the table is just an example.
Does 1:1:1 ratio makes any difference?
In order to achieve physiological composition, it has been advised that we should transfuse RBC: FFP: Platelet in 1:1:1 ratio. However, whether this intervention affects mortality is controversial. Most of the data come from retrospective observational trials. The only prospective observational trial “PROMMT” demonstrated significant mortality ( at 6hr) difference in favour of 1:1 ratio. However, the only RCT on this topic ” PROPPR” trial failed to replicate this result. In both trials, there was no difference in 24 hour mortality.
One of the barriers to achieving 1:1 ration in the early period is getting FFPs from the blood bank. It takes atleast30-45 min to thaw FFP and most of the centres do not store thawed plasma in ED/OR/ICU. This also adds a Survivor bias as only those who survive an initial hour of resuscitation will receive plasma.
So this leaves us with the question whether 1:1 ratio really matters? I don’t know the answer. We will definitely need a large RCT to answer this much-awaited question.
Is Tranexamic acid a life saver?
2 trials CRASH 2 & WOMEN have demonstrated that tranexamic acid reduces mortality significantly in Trauma patients and Obstetric patients with PPH respectively. These are 2 very well conducted large multicentre RCTs and will hopefully help to change the practice especially in resource poor countries where there is no easy access to blood and blood products. However, generalising this recommendation to all subsets of bleeding patients will be a bit too much.
The key take home messages for me so far –
- Initiating MTP in first 6 hours of major bleeding is crucial.
- Thrombocytopenia is the major component of dilutional coagulopathy. So transfusing Platelets early along with FFP is necessary.
- Give tranexamic acid (1gm) in < 3hours to bleeding trauma patients and obstetric patients with PPH.