Massive haemorrhage and transfusion: quick reference

Immediate management

In massive haemorrhage it is rapid control of the bleeding that determines the outcome. Transfusion restores circulating volume, oxygen transport and haemostatic capacity, but it cannot compensate for an uncontrolled source of bleeding. Minimise the time to surgery, endoscopy, an obstetric procedure or angiographic intervention. Summon anaesthesia, the operating specialty, the blood bank and, where needed, coagulation expertise at the same time [1].

Activate the local major haemorrhage protocol early. Protocols improve above all the logistics, the communication and the simultaneous delivery of red cells, plasma and platelets. Observational data from trauma suggest a lower overall mortality after such protocols are introduced, although the effect on 24-hour mortality is uncertain and the evidence for non-traumatic bleeding is weaker [2,3,4].

Do the following immediately:

1. Call for help using the words massive haemorrhage, and state the patient's location and identity, the presumed cause of bleeding, and how the products are to be delivered.
2. Designate a team leader and one person responsible for recording the transfusions, the sampling, the incoming products and contact with the blood bank.
3. Secure large-bore access, or rapid central access, but do not delay transfusion or control of the bleeding in order to obtain a central venous catheter.
4. Take samples for blood grouping and cross-matching before transfusion if this can be done without delay.
5. Start active warming and use a blood warmer.
6. Take a blood gas with lactate, pH, base excess, haemoglobin and ionised calcium, together with a full blood count, INR, APTT and fibrinogen.
7. Give tranexamic acid where it is indicated.
8. Proceed in parallel to definitive control of the bleeding.

Activate the protocol in

Activation must be based on an overall assessment, not on a single threshold value. The combination of physiology, rate of bleeding, the pattern of injury or disease, the response to initial treatment and the expected continued bleeding matters more than an exact estimate of blood loss [1].

Strong indications for activation

• Ongoing bleeding with haemodynamic instability, for example a systolic blood pressure below 90 mmHg, a narrow pulse pressure, peripheral vasoconstriction, impaired consciousness, a rising lactate or a worsening acidosis.
• An assessed need for at least 4 units of red cells within 1 hour.
• An actual requirement of more than 3 units of red cells during any continuous hour. This corresponds to the so-called critical administration threshold and identifies rapid bleeding better than the retrospective definition of at least 10 units of red cells in 24 hours [5].
• A continuing transfusion requirement while definitive control of the bleeding has not yet been achieved.
• Penetrating torso injury with shock.
• A positive FAST scan in an unstable trauma patient.
• An unstable pelvic fracture with circulatory compromise.
• A ruptured aortic aneurysm or another major vascular bleed.
• Perioperative bleeding that rapidly fills the suction, the swabs or the operative field and requires repeated units of red cells.
• Gastrointestinal bleeding with shock and ongoing haematemesis or haematochezia, or a continuing rapid transfusion requirement.
• Obstetric haemorrhage of around 1,500 mL or more with continuing bleeding, or a smaller measured blood loss if there is physiological compromise.

Do not wait for hypotension in young, pregnant or previously athletic patients. Beta blockade, a pacemaker and autonomic neuropathy can at the same time mask the expected tachycardia.

Aids to assessment

The shock index is calculated as the heart rate divided by the systolic blood pressure. A value of around 0.9 to 1.0 or higher in an adult trauma patient suggests significant hypovolaemia and an increased transfusion requirement. Pregnancy, medication and arrhythmia affect its interpretation. The shock index must never replace clinical assessment [1].

In trauma, the ABC score can be used as a decision aid. One point is given for each of:

• a penetrating mechanism of injury
• a systolic blood pressure of 90 mmHg or less
• a heart rate of at least 120 per minute
• a positive FAST scan

Two or more points indicate a high risk of massive transfusion, but a low score does not exclude serious bleeding, and the clinician's judgement alone can justify activation [5].

Do not routinely give 1,000 mL of crystalloid as a diagnostic test before the protocol is activated. This can delay blood products, dilute clotting factors and worsen hypothermia.

During ongoing massive haemorrhage

Control of bleeding according to the cause

Trauma

Control external bleeding with direct pressure, a haemostatic dressing and a tourniquet when pressure is not enough. Apply a pelvic binder at the level of the trochanters when an unstable pelvic ring is suspected. An unstable patient with a clear source of bleeding must not be delayed unnecessarily by extensive imaging. A negative FAST scan does not exclude retroperitoneal, pelvic or early intra-abdominal bleeding [1].

Perioperative bleeding

Optimise the surgical exposure, pack, compress and correct surgical bleeding. At the same time consider whether the bleeding is diffuse and suggests coagulopathy. Inform the blood bank if the rate of bleeding changes. Consider cell salvage where it is technically feasible and locally established.

Gastrointestinal bleeding

Call endoscopic expertise early and consider interventional radiology or surgery if instability continues. A massive transfusion protocol must not replace rapid endoscopic or radiological haemostasis. Tranexamic acid is not routinely part of the treatment of acute gastrointestinal bleeding merely because of the site of the bleed.

Obstetric haemorrhage

Treat the cause in parallel, according to the four Ts:

• Tone: uterine atony; treat with uterotonics, uterine massage and, where needed, bimanual compression.
• Trauma: inspect and repair tears, haematomas, uterine rupture or inversion.
• Tissue: suspect retained placental tissue or the placenta accreta spectrum.
• Thrombin: identify coagulopathy, for example in abruption, amniotic fluid embolism, sepsis or pre-eclampsia.

If atonic bleeding persists, balloon tamponade can be used as a uterus-preserving measure. Escalate without delay to embolisation, compression sutures, vascular ligation or hysterectomy when conservative measures do not control the bleeding [10,11].

Component therapy

Balanced initial transfusion

During the early, uncontrolled phase of bleeding, red cells, plasma and platelets are generally given in a balanced ratio according to the local protocol. A common Swedish pack is around 4 units of red cells, 4 units of plasma and 1 adult dose of platelets. The exact composition of the pack and how the platelet dose is counted vary between blood banks.

The PROPPR trial compared plasma, platelets and red cells in a ratio of 1:1:1 with 1:1:2 in 680 severely injured patients. Overall mortality at 24 hours and 30 days did not differ statistically, but 1:1:1 more often achieved haemostasis and led to fewer deaths from exsanguination [5]. A later Cochrane review found no definite difference in mortality between the strategies and judged that the evidence for an exact optimal ratio is still limited [6].

The practical conclusion:

• Start with a balanced ratio when the bleeding is rapid and results are not yet available.
• Avoid giving many units of red cells before the plasma and platelets arrive.
• Move to targeted treatment as soon as possible on the basis of laboratory tests, the clinical picture and, where available, ROTEM or TEG.
• Stop empirical component therapy once the bleeding is controlled.

Whole blood

Low-titre group O whole blood is used in some trauma centres and can simplify early balanced transfusion. A meta-analysis of mainly observational studies found a lower 24-hour mortality with the combination of whole blood and components compared with components alone, and a lower red cell requirement with whole blood. The evidence base is, however, heterogeneous and randomised data remain insufficient [27]. Follow the local protocol and the availability at your blood bank.

Emergency-issue blood

If the blood group is not yet known, emergency-issue blood must be given according to local procedure. Group O red cells are used initially, often RhD-negative for children, women of childbearing potential and other patients in whom RhD immunisation should particularly be avoided. Switch to group-specific products as soon as the blood bank allows.

Send a sample for blood grouping before the first transfusion if this does not delay treatment. Label the sample at the patient's side. Misidentification is an immediately life-threatening transfusion risk.

Tranexamic acid

Tranexamic acid inhibits fibrinolysis. Its effect is strongly time-dependent, and the drug must not delay control of the bleeding.

Trauma with significant bleeding or a high risk of bleeding

Give:

• 1 g intravenously over 10 minutes as soon as possible
• thereafter 1 g intravenously over 8 hours

CRASH-2 included 20,211 trauma patients. Tranexamic acid reduced 28-day mortality from 16.0 to 14.5 per cent and death from bleeding from 5.7 to 4.9 per cent. Treatment within 1 hour had the greatest effect. Treatment between 1 and 3 hours was still beneficial, while treatment later than 3 hours was associated with a higher mortality from bleeding [7]. A Cochrane review supports early treatment and found no definite increase in vaso-occlusive events [8].

Give tranexamic acid therefore without waiting for ROTEM, TEG or laboratory confirmation of hyperfibrinolysis when major traumatic haemorrhage is suspected and less than 3 hours have elapsed since the injury.

Traumatic brain injury

In traumatic brain injury within 3 hours, with a GCS of 12 or less, or with intracranial bleeding on CT, the same dosing may be considered. CRASH-3 showed the greatest probable benefit in mild to moderate brain injury with reactive pupils. No clear benefit was seen in very severe brain injury, where extensive irreversible damage is often already present [9].

Postpartum haemorrhage

Give:

• 1 g intravenously over about 10 minutes as soon as postpartum haemorrhage is diagnosed
• a further 1 g if the bleeding continues after 30 minutes or recurs within 24 hours

The WOMAN trial showed a reduction in death from bleeding, particularly when tranexamic acid was given within 3 hours of delivery [10]. FIGO recommends treatment as soon as postpartum haemorrhage has been diagnosed, and at the latest within 3 hours of birth [11]. An individual patient data meta-analysis from 2024 found a reduced risk of life-threatening postpartum haemorrhage with no demonstrated increase in thromboembolic events [28].

Other surgical bleeding

Tranexamic acid may be indicated in several surgical procedures, but the dosing and the evidence vary between specialties. Use a procedure-specific or local protocol. The trauma dosing must not automatically be transferred to all other bleeding situations.

Fluid and blood pressure

Crystalloids

Large volumes of crystalloid increase the risk of dilutional coagulopathy, tissue oedema, hypothermia and impaired oxygen transport. Give blood products early therefore when haemorrhagic shock is likely. If blood is not yet available, small boluses of balanced crystalloid can be used as a bridge.

Hydroxyethyl starch must not be used in bleeding trauma. Albumin has no established role in the initial resuscitation of haemorrhagic shock.

Permissive hypotension

In a bleeding trauma patient without brain injury, a systolic blood pressure of around 80 to 90 mmHg or a mean arterial pressure of around 50 to 60 mmHg can be accepted until major bleeding has been controlled, provided the patient has a palpable central pulse and adequate alertness or other evidence of cerebral perfusion [1].

A meta-analysis of five randomised trials suggested a lower mortality and less blood loss with hypotensive compared with conventional resuscitation, but the trials were small and partly methodologically weak [12].

Permissive hypotension is unsuitable, or requires particular caution, in:

• traumatic brain injury
• spinal cord injury with perfusion requirements
• pregnancy, where uteroplacental perfusion is still relevant
• marked chronic hypertension
• ischaemic heart disease
• ongoing myocardial ischaemia
• a long transfer or a long delay to haemostasis

In severe traumatic brain injury the systolic blood pressure should generally be kept at least at around 100 to 110 mmHg, adjusted for age, cerebral perfusion and the local neurotrauma protocol [1].

Target values in massive haemorrhage

The target values should be regarded as practical safety limits. The clinical rate of bleeding and the trend matter more than an isolated result.

Haemoglobin

The haemoglobin can be normal early on despite a large acute blood loss, since both red cells and plasma are lost at the same time. A single normal haemoglobin must therefore not delay transfusion in a patient with clinical haemorrhagic shock.

A target of 80 to 100 g/L is often unnecessarily high once the bleeding has been controlled. For haemodynamically stable adults, international guidelines generally recommend a restrictive transfusion strategy, usually considering transfusion below 70 g/L. Higher thresholds may be justified in certain cardiac operations, orthopaedic surgery or pre-existing cardiovascular disease [21].

Fibrinogen

Fibrinogen is often the first clotting factor to reach a critically low level. Give fibrinogen concentrate or cryoprecipitate according to the local algorithm at a fibrinogen below 1.5 to 2.0 g/L, or with corresponding viscoelastic evidence of fibrinogen deficiency [1].

The FEISTY trial showed that fibrinogen concentrate could be given faster than cryoprecipitate in patients with verified hypofibrinogenaemia, but the trial was not powered for mortality and did not show that either preparation improved clinical outcomes [14]. CRYOSTAT-2 showed that empirical high-dose cryoprecipitate for all trauma patients with an activated protocol did not reduce 28-day mortality [15]. A systematic review from 2025 likewise found no definite mortality benefit from general early fibrinogen replacement [16].

The practical conclusion:

• Treat verified or strongly suspected fibrinogen deficiency rapidly.
• Do not give high-dose fibrinogen routinely to all bleeding patients irrespective of the results.
• Plasma requires too great a volume to correct isolated marked fibrinogen deficiency effectively.

Viscoelastic testing

ROTEM and TEG can rapidly identify:

• low fibrin-based clot strength
• the platelet contribution to low clot strength
• prolonged initiation of coagulation
• hyperfibrinolysis
• persistent coagulopathy after component therapy

Use a validated local algorithm. Do not give individual products on the basis of a trace alone without taking into account active bleeding, the products already given and the timing of the sample.

ITACTIC compared viscoelastically guided treatment with treatment guided by conventional coagulation tests, on top of a balanced massive transfusion protocol. Viscoelastic testing led to earlier and more numerous targeted haemostatic interventions but gave no definite improvement in survival or in freedom from massive transfusion [13]. The Cochrane assessment from 2025 likewise found no definite mortality advantage [6].

ROTEM or TEG should therefore be used for rapid individualisation and to reduce blind component therapy, not as a substitute for clinical judgement or control of the bleeding.

Calcium

The citrate in red cells, plasma and platelets binds ionised calcium. During rapid transfusion the citrate load can exceed the metabolic capacity of the liver and other tissues, particularly in shock, hypothermia, acidosis and liver failure. Hypocalcaemia impairs coagulation, platelet function, vascular tone and myocardial contractility [17].

Monitor the ionised calcium on the blood gas:

• at activation
• after every transfusion pack
• after any substantial calcium replacement
• with hypotension, a prolonged QT interval, arrhythmia or unexpectedly poor coagulation

A retrospective study of severely injured patients found that the lowest ionised calcium during the first 24 hours was independently associated with 28-day mortality. A value of around 0.95 mmol/L identified an increased risk, but the study does not show that any particular replacement dose improves survival [18]. Hypocalcaemia is also common with large intraoperative transfusion and occurred in 70 per cent of cases in one surgical cohort [19].

Replace with calcium chloride or calcium gluconate according to the local protocol. The preparations contain different amounts of elemental calcium and are not interchangeable by dose. Calcium chloride is irritant to tissue on extravasation and is best given through secure venous access. Avoid both persistent hypocalcaemia and uncontrolled overcorrection.

Temperature, acidosis and the lethal diamond

The classical lethal triad consists of:

• hypothermia
• acidosis
• coagulopathy

Hypocalcaemia should be regarded as a fourth component, making it a lethal diamond. All four elements reinforce one another [17].

Hypothermia

Hypothermia impairs platelet function and the enzymatic reactions of coagulation. It also reduces citrate metabolism. Prevent it from the outset:

• remove wet clothing
• raise the room temperature
• use a forced-air warming blanket or other active external warming
• warm all blood products and larger volumes of fluid
• expose only the part of the body that must be examined or operated on

Acidosis

Severe acidosis reduces the activity of coagulation enzymes and is chiefly an expression of inadequate tissue perfusion. The most important treatment is control of the bleeding and restoration of the circulation with blood products. Bicarbonate does not correct the underlying oxygen debt and cannot substitute for adequate perfusion.

Coagulopathy

Trauma-induced coagulopathy is not merely dilution. Shock, injury to the endothelium and glycocalyx, fibrinogen breakdown, hyperfibrinolysis and platelet dysfunction may all be present on arrival. Acidosis, hypothermia, crystalloids and anticoagulants then make the condition worse [29].

Massive transfusion can in addition cause hyperkalaemia, hypomagnesaemia, transfusion-related acute lung injury, transfusion-associated circulatory overload, haemolysis, and later thromboembolism or organ failure [20].

Reversal of anticoagulants

Stop the anticoagulant and establish which drug, the dose, the time of the last dose, the renal function and any concurrent antiplatelet therapy. Reversal must be given in parallel with control of the bleeding and with transfusion, not instead of them. Discuss the case with a coagulation specialist where possible, but do not delay an urgent antidote in life-threatening bleeding [22].

ANNEXA-4 was an uncontrolled cohort in which andexanet reduced anti-factor Xa activity by around 92 per cent for apixaban and rivaroxaban. Good or excellent haemostasis was recorded in 82 per cent, but 10 per cent had a thrombotic event within 30 days [23].

In ANNEXA-I, which included factor Xa inhibitor-associated intracerebral haemorrhage, andexanet gave better control of haematoma expansion than usual care, which was generally prothrombin complex concentrate. Thrombotic events increased, however, particularly ischaemic stroke, and no clear difference was seen in 30-day mortality or function [24]. Comparative meta-analyses are contradictory and rest largely on observational data [25]. The choice must therefore follow the site of bleeding, the last dose, the thrombotic risk, availability and the local protocol.

Antiplatelet drugs

Routine platelet transfusion must not be given merely because the patient is taking aspirin or a P2Y12 inhibitor. In the PATCH trial, platelet transfusion worsened the outcome in spontaneous intracerebral haemorrhage in patients on previous antiplatelet therapy [26]. The result cannot be transferred directly to traumatic bleeding or to patients requiring emergency neurosurgery, but it argues strongly against routine transfusion.

In life-threatening surgical bleeding, platelets, desmopressin or other measures can be considered individually according to the drug, the last dose, the platelet count, the renal function and the planned procedure.

Continuing sampling and evaluation

Take and repeat:

• a blood gas with pH, lactate, base excess, haemoglobin, potassium and ionised calcium
• a full blood count
• INR
• APTT
• fibrinogen
• ROTEM or TEG where available
• creatinine and liver function tests when they affect the choice of anticoagulant or citrate metabolism
• the temperature, continuously or frequently
• the urine output when the situation allows

Take samples after every major transfusion pack, or every 30 to 60 minutes during rapid bleeding. Samples taken before the most recent products may be out of date by the time the result arrives.

At the same time assess:

• whether the source of bleeding really is controlled
• whether the transfusion requirement is falling
• whether the vasopressor requirement is falling
• whether the peripheral perfusion and the level of consciousness are improving
• whether the lactate and base excess are moving in the right direction
• whether the patient is developing pulmonary oedema, haemolysis, hyperkalaemia or another transfusion complication

A vasopressor may be needed as a short bridge in life-threatening hypotension, particularly during induction of anaesthesia, but it must not be used to mask inadequate volume replacement or continuing bleeding.

When to stop the protocol

Stop or pause the massive transfusion protocol when:

• surgical, endoscopic, obstetric or radiological haemostasis has been achieved
• the patient no longer has a rapid transfusion requirement
• the circulation is stabilising
• laboratory or viscoelastic results can guide further treatment
• continued transfusion is judged to be futile

Tell the blood bank explicitly that the protocol is being stopped. Return unused products according to local procedure so that plasma and platelets are not discarded unnecessarily. Continue targeted correction of fibrinogen, platelets, calcium and temperature as needed.

After haemostasis the transfusion strategy must become restrictive. Check that unnecessary prescriptions are stopped and make a plan for thromboprophylaxis and for restarting anticoagulation once the bleeding risk allows. The thrombotic risk is often high both after major bleeding and after reversal.

Red flags and pitfalls

• A normal blood pressure does not exclude ongoing bleeding. Young and pregnant patients can compensate for a long time and then deteriorate rapidly.
• A normal initial haemoglobin does not exclude a large blood loss.
• Do not wait for 1,000 mL of crystalloid before activating the protocol.
• Beta blockade or a pacemaker can mask tachycardia.
• A negative FAST scan does not exclude serious bleeding.
• Do not order red cells one unit at a time during rapid bleeding. Telephone the blood bank and activate the protocol.
• Do not give red cells alone for a prolonged period. Start balanced component therapy early.
• Do not forget tranexamic acid. In trauma the treatment is time-critical and should normally be started within 3 hours.
• Do not apply the trauma dose of tranexamic acid as a matter of routine to all other bleeding.
• Do not forget the calcium. The ionised calcium can fall rapidly after plasma and platelets.
• Do not forget the fibrinogen. An acceptable INR does not exclude fibrinogen deficiency.
• Do not give empirical high-dose fibrinogen to everyone. Target the treatment on the fibrinogen level or a viscoelastic test where possible.
• Warm the patient from the start. Hypothermia is easier to prevent than to correct.
• Do not delay surgery or intervention in order to normalise laboratory values.
• Do not use a vasopressor as a substitute for blood and control of the bleeding.
• Platelet transfusion does not reliably reverse antiplatelet drugs and can be harmful in spontaneous intracerebral haemorrhage.
• Obstetric haemorrhage requires treatment of the cause at the same time. Uterotonics, uterine compression, repair of trauma and removal of retained placental tissue must not wait for transfusion.
• Announce when the protocol is stopped. Otherwise the blood bank will continue to thaw and deliver products that are no longer needed.
• Document the products in real time. Retrospective recording under stress increases the risk of error and makes decisions about the next pack more difficult.

References

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