I have stopped using rFVIIa in major non-haemophilic bleeding as my experience indicates that microvascular bleeding can be brought under control with quick, efficient use of blood components.  This comment is made against a background of standard laboratory testing blood screen (platelets and Hb/HCT), fibrinogen, PT and APTT.  I do not currently have access to a TEG /Rotem although I suspect that will could provide faster access to information and give additional information on the kinetics of coagulation and platelet function (although not a reliable indication of FXIII activity.

An outline of my standard practice with major bleeding is:

1. Know the pre-op test results, the nature of any co-morbidities (especially liver impairment/injury and renal impairment with a creatinine 1.5x upper limit of normal).  Anticipate when haemodilution will lead to significant reduction in platelet count and fibrinogen - they are equally critical in ensuring effective haemostasis.  Platelets are critical for stopping bleeding in the microvasculature and the fibrinogen level is critical for ensuring that clot strength is adequate to withstand movement of tissues and handling by the surgeon.

2. Consider using tranexamic acid 15mg/kg at an early stage of major bleeding.  A single dose is often sufficient but a second dose after 6 hours if post-operative haemostasis is still not adequate is appropriate.

3. Ensure Hb/Hct is not allowed to fall too low as platelet function is impaired and bleeding time increases significantly when Hb falls to 80 g/L or lower.  I aim for an Hb of 80-90 usually but if renal failure is present would aim higher depending on the circumstances.  This means that blood screen and coagulation screen must be repeated regularly during the surgery to ensure you, the anaesthetist and the operating team are not 'flying blind'.  When the Hb reaches the threshold level switch to transfusion of 1:1 red cells and fresh frozen plasma and STOP crystalloids (and any colloids - if used).  Crystalloids and colloids (inlcuding albumin) are unhelpful as they will only continue to haemodilute the haemostatic state of the patient.  This step is especially important if the APTT and or PT are starting to increase and must be done before they reach a 1.5x prolongation (above mean normal values; the INR reaching 1.5 in the case of the PT).  The lag time between seeing an increasing APTT and PT test result and making the change in fluid replacement is often of the order of 30-60 minutes and the change in these test parameters will be greater at that time.  The Blood Bank should be part of the process and understand that they must thaw the required plasma in advance of being requested - 'keep 2 units ahead' with thawed plasma. [Get to lnow your local Blood Bank staff personally - they are not on a remote planet!.  You would not operate with a team whom you did not know and did not know you and how you work.]

4. Ensure that the platelet count is not allowed to fall below about 70-80 x10^9/L (in major bleeding cases).  Once a need exists to supply platelets more are likely to be needed as the increment with each adult dose is not great in an average-sized adult (about 20-40 x10^9/L usually).

5. If the fibrinogen falls below about 1.5 g/L in major bleeding, infuse a dose caculated to increase the level to above 2 g/L is usually appropriate - the strength of the clot is crtical.  I use cryoprecipitate but some prefer fibrinogen concentrate.  Cryoprecipitate in New Zealand has the benefit it is provided in larger dose sizes than in other countries ~1g/bag.  Cryo. also provides FXIII nlike fibrinogen concentrates.

6. In major cardiac surgery where signficant haemdilution occurs in the bypass circuit it can be helpful to add a modest dose of a Prothrombin Complex concentrate (PCC) at the end of the bypass and reversal of heparin, eg 20 u/kg (lean body weight - reduce the weight estimate if BMI >~25).  Caution is needed with giving larger doses as an increasing imbalance between the procoagulant factors in the concentrate and antithrombin circulating in the patient will arise and create a prothrombotic state.  It should not be used in the absence of a significanlty prolonged APTT and PT in other patients and only after fibrinogen and platelet issues have been dealth with.  It can be of assistance in acute trauma bleeding after adeqaute use of blood components as described.

In cancer patients I would not normally consider a PCC due to the underlying prothrombotic state in almost all patients in this group.

7. If the major bleeding is originating from large tumour circulation vessels or large vessels that were feeding a large cancer and surgical difficulty exists in controlling bleeding from those vessels after removal of the tumour, conservative damage control surgery - 'pack and get out' should be considered, with or without interventional radiology to embolise the vessels.  Haemostatic mechanisms (inlcuding FVIIa) cannot stop bleeding from large vessels - only a surgeon or radiologically introduced emboli can achieve that goal.  The role of the support team in that setting is to ensure that the patient's overall haemostatic state is not allowed to deteriorate to a point of microvascular failure through any of - low platelet count, reduced fibrinogen and prolonged PT / APTT or lack of sufficiently frequent testing.

Knowing when to stop the use of crystalloids (and colloids if used) before switching to a 1:1 red cell to plasma protocol is important.

A haematologist who is experience in working with surgical bleeding qand will 'stay with the case' and continue to monitor lab test results and advise can be just as important in contributing to the team as each of the other specialists.

I hope this brief account helps.