Major haemorrhage

Major haemorrhage is bleeding that threatens life through loss of circulating volume, oxygen carrying capacity and clotting function. It is defined by any of the following.

• Loss of one blood volume in 24 hours (about 70 mL/kg in adults, 80 mL/kg in children, 90 to 100 mL/kg in neonates).
• Loss of 50% of blood volume in 3 hours.
• Ongoing loss over 150 mL/min.
• Bleeding with systolic pressure under 90 mmHg or shock index (heart rate divided by systolic pressure) over 1.0.

Haemorrhage classes.

Mechanisms of coagulopathy. Tissue injury and shock cause endothelial activation, fibrinogen consumption and hyperfibrinolysis. Dilution by crystalloid and red cells, hypothermia, acidosis (pH under 7.2) and hypocalcaemia then impair thrombin generation and platelet function. Anticoagulants and antiplatelet drugs add to the defect.

Sites. Traumatic, gastrointestinal, obstetric, perioperative, vascular (ruptured aneurysm) and spontaneous or coagulopathic.

Key distinctions. Blood pressure and haemoglobin are normal in early bleeding and underestimate loss. Concealed sites are chest, abdomen, pelvis, retroperitoneum and thigh (1 to 2 L in a closed femoral fracture). Beta blockers, pacemakers and older age mask tachycardia, and children and pregnant women maintain pressure until late collapse.

History (from patient, relatives or ambulance crew). Mechanism and time of injury, visible blood loss, haematemesis, melaena or vaginal bleeding, pregnancy or recent delivery, recent surgery or procedure.

Also record anticoagulant or antiplatelet name and time of last dose, liver or kidney disease, bleeding disorder, alcohol, and the patient's wishes about blood transfusion (including any valid refusal).

Examination.

• Pulse, blood pressure, capillary refill, mottling, respiratory rate, urine output, Glasgow Coma Scale, temperature.
• Obvious external bleeding (scalp, limb wounds), expanding haematoma, pulsatile abdominal mass, distended or rigid abdomen, unstable pelvis, long bone deformity, flank or groin bruising.
• Gum bleeding, petechiae, purpura or oozing from line sites suggest a coagulopathy.
• Rectal and vaginal examination when indicated.

Red flags.

• Systolic pressure under 90 mmHg, shock index over 1.0, lactate over 4 mmol/L, base deficit worse than minus 6 mmol/L.
• Ongoing bleeding after 4 units of red cells, anticoagulant use, temperature under 35 °C.
• Pregnancy over 20 weeks, a pulsatile abdominal mass, or tearing back pain.

Special groups.

• Children: use age based weight estimates, intraosseous access early, and weight based product doses.
• Pregnancy and postpartum: blood volume is expanded by 40 to 50%, so hypotension is a late sign. Use left lateral tilt after 20 weeks and aim for fibrinogen over 2 g/L.
• Older adults and anticoagulated patients: low energy injury causes major bleeding, and reversal is needed early.
• Patients who decline blood: involve senior clinicians and use cell salvage, tranexamic acid, iron, erythropoietin and early haemostatic surgery within the person's accepted limits.

Traumatic. Haemothorax, splenic rupture, liver laceration, renal injury, mesenteric injury, retroperitoneal haematoma, unstable pelvic fracture, femoral fracture, major arterial injury, traumatic amputation, scalp laceration.

Gastrointestinal. Peptic ulcer disease, oesophageal varices, gastric varices, Mallory-Weiss tear, Dieulafoy lesion, aortoenteric fistula, diverticular bleeding, angiodysplasia, colorectal cancer, ischaemic colitis.

Vascular. Ruptured abdominal aortic aneurysm, aortic dissection with rupture, ruptured visceral artery aneurysm, aortobronchial fistula, ruptured hepatocellular carcinoma, pseudoaneurysm.

Obstetric and gynaecological. Ruptured ectopic pregnancy, placental abruption, placenta praevia, placenta accreta spectrum, uterine atony, retained placenta, genital tract trauma, uterine rupture, uterine inversion, ruptured ovarian cyst.

Perioperative and procedural. Surgical bleeding, anastomotic leak with bleeding, post tonsillectomy bleeding, vascular access injury, post biopsy bleeding, post thyroidectomy neck haematoma.

Coagulopathic. Anticoagulant related bleeding, antiplatelet related bleeding, disseminated intravascular coagulation, thrombocytopenia, liver failure, haemophilia, acquired haemophilia, von Willebrand disease, uraemic platelet dysfunction, thrombolytic related bleeding.

Mimics. Non-haemorrhagic shock (sepsis, tamponade, tension pneumothorax, anaphylaxis, adrenal crisis) and anaemia with no active bleeding.

Resuscitation and diagnosis run together.

Immediate tests. Blood gas with lactate, haemoglobin, potassium and ionised calcium (ionised calcium under 1.1 mmol/L is abnormal), full blood count, coagulation with Clauss fibrinogen, urea, creatinine, electrolytes, liver tests.

Also group and crossmatch (send the sample before any transfusion where possible), pregnancy test, troponin and ECG in older patients, and creatine kinase after crush injury.

Viscoelastic testing where available. FIBTEM amplitude at 5 minutes under 10 mm suggests low fibrinogen, EXTEM clotting time over 80 seconds suggests a need for plasma or prothrombin complex concentrate, and evidence of hyperfibrinolysis supports tranexamic acid. Use laboratory tests if viscoelastic testing is not available, and do not wait for results to start transfusion.

Targets to correct.

• Temperature over 36 °C, pH over 7.2, ionised calcium over 1.1 mmol/L
• Platelets over 50 x 10^9/L (over 100 x 10^9/L in central nervous system injury or ongoing bleeding)
• Fibrinogen over 1.5 g/L (over 2 g/L in obstetric bleeding)
• Prothrombin time and aPTT ratio under 1.5, and a falling lactate

Imaging.

• Bedside ultrasound for pericardial fluid, haemothorax, intraperitoneal free fluid and aortic aneurysm.
• Chest and pelvis radiographs in trauma if they do not delay care.
• CT with arterial and portal phases for patients who are stable or responding, and CT angiography for suspected vascular sources. Unstable patients with a positive ultrasound go to theatre or interventional radiology.
• Urgent endoscopy for gastrointestinal bleeding after resuscitation.

Limitations. Haemoglobin is a late and unreliable marker in acute bleeding. Ultrasound misses retroperitoneal and hollow viscus injury. Usual clotting tests are slow and do not show hyperfibrinolysis. Contrast should not be withheld from an unstable patient because of kidney function.

Activate the massive transfusion plan at once when bleeding is ongoing with shock or a shock index over 1.0, and call senior surgical, anaesthetic and haematology help.

Stop the bleeding.

• External: direct pressure, tourniquet 5 to 7.5 cm over a limb wound (record the time), haemostatic dressing, wound packing and a pelvic binder at the greater trochanters.
• Internal: surgery, endoscopy or interventional radiology as early as possible. Do not delay haemostatic surgery for imaging in an unstable patient. Damage control surgery (control bleeding and contamination, pack, correct physiology, return later) is used for the most unstable.

Blood products.

• Give uncrossmatched group O blood in extreme emergency (group O RhD negative for females under 50 years and for unknown sex, O RhD positive acceptable for males), changing to group specific blood as soon as available.
• First pack: 4 units red cells, 4 units plasma (15 mL/kg) and 1 adult dose of platelets, then continue red cells, plasma and platelets in near equal proportions (about 1:1:1) in further packs, all through a warmer. Limit crystalloid to under 1 L in total. Give further products directed by the results of viscoelastic and laboratory tests.
• Fibrinogen: if under 1.5 g/L (or FIBTEM low), give fibrinogen concentrate 2 to 4 g IV or cryoprecipitate 2 pools (about 10 units); repeat directed by the level. Do not use plasma as a fibrinogen source alone.
• Platelets to over 50 x 10^9/L, over 100 x 10^9/L in central nervous system injury.
• Red cell targets: haemoglobin 70 to 90 g/L once bleeding is controlled (80 to 100 g/L with cardiovascular disease). During active bleeding, give by clinical state and not by haemoglobin.
• Rapid transfusion can cause hyperkalaemia, hypothermia and citrate related hypocalcaemia, and rarely transfusion related lung injury or circulatory overload.

Drugs.

• Tranexamic acid 1 g IV over 10 minutes, as early as possible and within 3 hours of injury or birth, then 1 g IV over 8 hours; monitor for thrombosis and seizures; reduce the maintenance dose in kidney impairment.
• Tranexamic acid in children: 15 mg/kg IV (maximum 1 g), then 2 mg/kg/hour. Obstetric bleeding: a second 1 g dose may be given after 30 minutes if bleeding continues.
• Calcium chloride 10% 10 mL IV over 5 to 10 minutes after every 4 units of red cells and for ionised calcium under 1.1 mmol/L; extravasation damages tissue, so use a large vein or central line; monitor ionised calcium and ECG.
• Warfarin: 4 factor prothrombin complex concentrate 25 to 50 units/kg IV (dose adjusted to INR and product label) with vitamin K 5 to 10 mg IV over 10 minutes; monitor INR at 30 minutes and thrombosis.
• Dabigatran: idarucizumab 5 g IV (two 2.5 g doses). Factor Xa inhibitors: prothrombin complex concentrate 50 units/kg IV, or the specific antidote dosed from the product label.
• Heparin: protamine 1 mg for each 100 units given in the previous 2 to 3 hours, by slow IV injection over 10 minutes; maximum 50 mg in one dose; monitor for hypotension, bradycardia and anaphylaxis.
• Desmopressin 0.3 micrograms/kg IV over 20 minutes as a single dose for uraemic bleeding, von Willebrand disease or antiplatelet effect (evidence is limited); monitor sodium and avoid repeated doses over 24 to 48 hours because of hyponatraemia; avoid in coronary disease and with fluid overload.
• Recombinant factor VIIa is not used routinely and is reserved for refractory bleeding under haematology direction.

Blood pressure. Permissive hypotension (systolic 80 to 90 mmHg) until bleeding is controlled in penetrating torso injury and ruptured aneurysm. Avoid it with head or spinal injury, where systolic pressure over 110 mmHg is wanted, and in pregnancy.

Obstetric haemorrhage (in addition). Rub up the uterus and empty the bladder. Oxytocin 5 units IV slowly over 1 to 2 minutes, then an infusion of 40 units in 500 mL isotonic saline at 125 mL/hour (10 units/hour) for 4 hours; monitor for hypotension with rapid injection and for hyponatraemia. Carboprost 250 micrograms IM every 15 minutes, maximum 8 doses (2 mg); avoid in asthma. Misoprostol 800 micrograms sublingually, single dose.

Ergometrine 500 micrograms IM, avoided in hypertension, pre-eclampsia and cardiac disease. Intrauterine balloon tamponade, compression sutures, uterine artery embolisation and hysterectomy follow if bleeding persists.

Cell salvage for surgical and obstetric bleeding where available. Reverse hypothermia with warmed fluids and warming devices.

After control. Venous thromboembolism prophylaxis with enoxaparin 40 mg subcutaneously once daily started when bleeding is controlled (usually 24 to 72 hours). Use 20 mg daily if CrCl 15 to 30 mL/min, and unfractionated heparin 5000 units subcutaneously every 8 to 12 hours if CrCl under 15 mL/min. Mechanical prophylaxis until then.

Stop the transfusion plan when bleeding is controlled and review the need for ongoing products with laboratory results.

Monitoring. Continuous ECG, arterial line, saturation, core temperature, hourly urine output, blood gas with lactate and ionised calcium every 30 to 60 minutes, laboratory or viscoelastic coagulation every 30 to 60 minutes, and a record of all products and times.

Referral and escalation. Surgery or interventional radiology for source control, anaesthesia and critical care, haematology and the blood bank, and obstetrics for pregnancy. Transfer unstable patients to a centre with surgical and transfusion capacity only after bleeding is controlled as far as possible.

Admission criteria. All patients with major haemorrhage go to theatre, interventional radiology or critical care.

Discharge and safety netting. Discharge after bleeding has stopped, haemoglobin is stable and iron replacement is planned. Patients are told to return for dizziness, breathlessness, black stool, further bleeding, abdominal swelling or pain, or limb swelling. Offer debriefing and psychological support, and inform patients about any transfusion given.