A 43 year old woman is retrieved to your hospital by helicopter following a motor vehicle crash. She was initially awake and complaining of severe abdominal and pelvic pain at the scene but deteriorated with shock and abdominal distention, and was intubated.
She received 3 litres of crystalloid and 8 units of O negative packed red blood cells from the rural hospital and the retrieval physician prior to admission.
On admission BP is 85/30 mmHg, HR is 140/min, and central capillary refill time is 8 seconds.
What are the problems of giving O negative un-crossmatched blood to this patient?
Problems with crossmatching:
- Attempts at ABO blood grouping following a transfusion of uncrossmatched blood causes "Mixed-field RBC agglutination", which is a case of "false chimerism".
- This is a situation where there are two very different blood cell populations, confusing the automated testing apparatus.
- It may take longer for the technicians to identify some safely transfuseable crossmatched blood after receiving a specimen like that.
Problems with future transfusion
- Sensitization can occur, leading to haemolytic reactions. The chances of this happening are around 0.4%.
What are the adverse events associated with blood transfusion?
- ABO-incompatible blood transfusion (due to administrative error)
- Bacterial contamination of platelet components (1:2,000)
- Sepsis from bacterial contamination of red cell components(1:500,000)
- HIV infection ( 1:2,135,000)
- Hep C infection (1:1,935,000)
- Hep B infection (1:205,000)
- Human T-lymphocytic viruses (1:2,993,000)
- Transfusion-related acute lung injury (TRALI)
- Fluid overload and heart failure
- Dilutional coagulopathy
Which blood products need to be crossmatched?
Need for Crossmatch
Packed red blood cells
Fresh Frozen Plasma
What is a "crossmatch"? What is blood grouping?
Crossmatching is compatibility testing which is used to determine whether a donor's blood is compatible with the blood of the recipient.
Crossmatch usually involves grouping, or ABO and RhD typing of recipient's red cells
In short, the grouping refers to which antigens your RBCs possess.
- You can have only A, only B, both A and B, or no antigens whatsoever.
- You will have antibodies (usually IgM) which are to the antigents which you dont have, i.e. if you are blood group A then you will have B antibodies.
This patient's group was apparently AB negative. Which blood groups can she receive?
People with A and B antigens can receive any blood, as they have no antibodies.
- Everyone can receive O blood (the cells have no agglutinins on them).
- O people can have O blood only (they have antibodies to both A and B agglutinins)
- A people can get A or O blood only (they have anti-B agglutinins)
- B people can get B or O nlood only (they have anti-A agglutinins)
- AB people can receive any blood: they have no anti-aggutinin antibodies, but their AB cells are covered in agglutinins.
- Nobody other than other AB people can receive AB blood (as it is covered in A and B agglutinins)
The patient goes to theatre for urgent laparotomy. A massive transfusion protocol activation is requested.
What is a "massive" transfusion?
No standard definition exists
- A "massive transfusion" is defined by the volume of blood lost.
- It is the replacement of one's entire blood volume
- That would be about 7% of a person's body weight, or about 10 units of PRBCs
- Others use time-defined criteria (the replacement of half of one's blood volume over 4 hours) or bleeding-defined criteria (rate of blood loss in excess of 150ml/min).
A single "massive transfusion resuscitation volume" would include:
- 4units of PRBCs
- 2 units of FFP (15ml/kg)
- 1 adult dose of platelets
- 3-4g of fibrinogen (in cryoprecipitate).
What are the possible complications of massive transfusion?
- Acute hemolytic transfusion reactions
- Febrile nonhemolytic transfusion reactions
- Allergic reaction to blood products
- Tranfusion-associated lung injury
- Transfusion-associated circulatory overload
- Bacterial sepsis
- Hypocalcemia due to citrate
- Hyperkalemia due to high PRBC K+content
- Dilutional coagulopathy
- Dilutional thrombocytopenia
- Delayed hemolytic transfusion reactions
- Transfusion-related immune modulation
- Transfusion-transmitted diseases
- Posttransfusion graft-vs-host disease
- Posttransfusion purpura
The trauma team mentions that they intend to perform "haemostatic resuscitation". What do you understand by this term?
- Rapid correction of haemostasis-impairing factors, such as hypothermia hypocalcemia and acidosis
- Resuscitation with a balanced combination of blood products, which in combination resemble the composition of whole blood, aiming to avoid dilutional coagulopathy.
- Reverse hypothermia
- Reverse acidosis
- Limit crystalloid load
- Use blood components in a proportion which resembles whole blood
- Reverse fibrinolysis associated with massive blood loss
- Achieve this whole-blood-like ratio within the first 6 hours of resuscitation
What is the rationale for the choice of resuscitation fluid (crystalloid or blood products) in trauma?
Rationale for avoiding large volumes of crystalloid
- Aggressive resuscitation with crystalloid leads to haemodilution.
- Haemodilution decreases the concentration of clotting factors and leads to coagulopathy.
- 75% of the crystalloid volume load distributes into the extravascular space; organ and tissue oedema ensues, putting the patient at risk of pulmonary oedema and abdominal compartment syndrome (among other problems).
- Crystalloids do not contribute to the transport of oxygen; by diluting the blood they actually decrease its oxygen-carrying capacity.
- In the case of saline, crystalloid resuscitation may exacerbate the acidosis.
Rationale for using a balanced blood product ratio
- Transfusion of packed red cells does not restore clotting factors.
- Coagulopathy will develop if packed red cells are the sole resuscitation fluid.
- Transfused PRBCs suffer from storage lesions. Their oxygen-carrying capacity isn't very good anyway.
- The citrate in the PRBCs tends to chelate the patient's calcium; this can't be good for their clotting function.
- It stands to reason that whole blood is the best resuscitation fluid to replace whole blood which is lost by haemorrhage.
- A "balanced" ratio of blood products resembles whole blood.
- The precise ratio of platelets plasma and PRBCs is still being debated.
What are the possible problems with this strategy?
- The ideal resuscitation fluid would of course be whole blood.
- Whole blood is usually not available.
- One may try to recombine stored blood products to achieve an end result which resembles whole blood, but it is never quite the same due to lesions of processing and storage.
- All blood products suffering storage lesions are cold (contributing to hypothermia) and acidic (because of cellular metabolism in storage, as well as due to citrate-based storage media)
- The infusion of massive amounts of blood products exposes the patient to risks of massive transfusion which are not trivial, and it is debatable whether these risks outweigh the risks of massive crystalloid load
What is the evidence regarding the optimum ratio of blood products?
In summary, the evidence suggests that:
- Best ratio is probably under 2:1:1 (blood:FFP:platelets)
- Best outcomes are when platelets and FFP are given early
There are many trials:
- PROMMTT study (2013): multicentre prospective cohort study; 905 patients enrolled. This was a time-varying study: the authors did not direct therapy, but merely observed what happened. What happened was the early death of patients who received more red cells than platelets and plasma within the first 6 hours. For these people, mortality was increased 3-4 times. On the other hand, those who received 1:1 transfusion of plasma or platelets and red cells tended to survive more. Furthermore, the survival benefit was concentrated in the first six hours: of the patients who survived the first 24 hours, there was no difference in mortality at 30 days, regardless of what transfusion ratio was used.
- Khan et al (2014): a prospective cohort study of ROTEM and lactate measurements. 106 patients were enrolled; samples were taken after every 4 units of PRBCs. The authors found the ROTEM data and lactate kept getting worse in spite of "haemostatic resuscitation", and were forced to conclude that it was neither haemostatic nor resuscitative. However critics responded (Stensballe and Holcomb, 2015) with the criticim that Khan et al did not use enough platelets (1 unit to every 8 bags of PRBCs) nor enough FFP (0.5 units per every bag PRBCs), and thus were not practicing "proper" haemostatic resuscitation.
- PROPPR trial (2015): multicentre RCT, 680 patients randomised to receive plasma, platelets and red cells in a 1:1:1 or 1:1:2 ratio. There was no difference in mortality. Or rather, the difference was small (4% improvement in absolute mortality, favouring the 1:1:1 group) but the study was not powered to detect this. The major difference between groups was death by exsanguination within the first 24 hours (much better in the 1:1:1 group, 9.2% vs 14.6%).
- CRYOSTAT trial (2015): feasibility study; no 28-day mortality difference, whether or not you receive 2 units of cryoprecipitate early.