Urgent considerations

See Differentials for more details

Anaemia is life threatening if there is more than 40% loss of total body volume. These patients should receive packed red blood cell (RBC) transfusions for stabilisation as soon as possible, especially if there are underlying cardiac or pulmonary comorbidities. A reticulocyte count, ferritin, and peripheral smear should be obtained before transfusion, if possible, as this makes subsequent work-up more accurate. Dilutional, or consumptive, coagulopathy from tissue injury may result from the decrease of platelets and coagulation factors (factor V, factor VIII, and fibrinogen) in massive transfusions and must be corrected by the addition of these factors.

Generally, healthy individuals tolerate extreme anaemia well, with cardiovascular status being the major limiting factor. The landmark TRICC study showed that, in haemodynamically stable patients without active bleeding, Hb levels between 70 g/L (7 g/dL) and 90 g/L (9 g/dL) were well tolerated with equivalent or lower mortality/morbidity outcomes compared with a liberal transfusion trigger of <100 g/L (<10 g/dL).[44] It is generally recommended that determination of transfusion requirements are based upon severity of illness parameters rather than arbitrary Hb levels. Clinical guidelines from the AABB (formerly known as the American Association of Blood Banks) suggest a restrictive transfusion threshold of 70 g/L (7 g/dL) in hospitalised haemodynamically stable patients, and 80 g/L (8 g/dL) in those undergoing orthopaedic or cardiac surgeries, or with pre-existing cardiovascular disease, unless there is an underlying acute coronary syndrome, severe thrombocytopenia, or chronic transfusion dependence.[45] Transfusion thresholds in ischaemic coronary artery disease and resuscitation of septic shock remain controversial.

Acute haemorrhage

Causes of acute haemorrhage include trauma (such as gunshot wounds, major fractures, and crush injuries), acute gastrointestinal (GI) bleeding, rupture of a vascular aneurysm (especially abdominal aortic aneurysm), and recent surgery. Rapid evaluation, identification, and control of bleeding are essential before any further work-up. Dilution does not occur acutely, so haemoglobin (Hb) and haematocrit levels do not provide an accurate reflection of the degree of blood loss and anaemia. Perfusion to critical organs must be maintained through early goal-directed therapy, including crystalloid volume resuscitation (using 2-4 times the estimated volume of blood loss), blood pressure support, and tissue perfusion.

A meta-analysis concluded that the use of hydroxyethyl starch (HES) solutions to decrease volume overload in large volume resuscitations was associated with increased risk of acute kidney injury and death.[46] HES solutions for infusion have been significantly restricted across the European Union and are contraindicated in critically ill patients and those with sepsis or renal impairment. These measures were introduced to protect patients from the increased risk of kidney injury and death associated with HES.[47] The restrictions followed a January 2018 review by the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee, which recommended that HES should be suspended from the market because, despite initial warnings, it was still being used in these at-risk patient populations.[48]

Cross-matched blood (or O negative, if cross-match is unavailable) should be given as soon as possible.

In addition, bleeding following major trauma requires coagulation support and monitoring, and the appropriate use of local haemostatic measures, tourniquets, calcium, desmopressin, and consideration for tranexamic acid.[49][50]

Tranexamic acid has been shown to reduce mortality in trauma patients with haemorrhage when given within 3 hours of injury, and should be administered as soon as possible in people with acute severe haemorrhage due to trauma.[49][51] A meta-analysis of data from over 40,000 patients with traumatic bleeding or post-partum haemorrhage found that delays in administration of tranexamic acid were associated with reduced survival (survival benefit decreasing by about 10% for every 15 minutes of treatment delay until 3 hours, after which there was no benefit).[52]

Definitive management of acute haemorrhage depends on the underlying cause, but usually requires surgery.

Microangiopathic haemolytic anaemias

Haemolytic uraemic syndrome, disseminated intravascular coagulation (DIC), and thrombotic thrombocytopenic purpura (TTP) produce life-threatening rapid haemolysis.[34] The underlying cause must be quickly assessed and treatment tailored accordingly to minimise end-organ damage and the likelihood of death. Treatment of DIC is aimed at the underlying cause. Corticosteroids and immunosuppression should be commenced if haemolytic uraemic syndrome or TTP are suspected. Intravenous immunoglobulins (IVIG) or urgent plasmapheresis may be necessary for rapid clearance of autoantibodies. Antibody screening should be done prior to blood transfusion. Antibody-free blood products should be used to prevent additional alloimmune haemolysis.

Malignant hypertension

This condition is characterised by very high blood pressure in association with bilateral retinal changes, including exudates and haemorrhages, with or without papilloedema. The most common symptoms include headaches (often occipital), visual disturbances, chest pain, dyspnoea, and neurological deficits. Results include cerebral infarction or haemorrhage, transient blindness or paralyses, seizures, stupor, or coma. The initial goal of therapy in hypertensive emergencies is to reduce mean arterial BP by no more than 25% (within minutes to 1 hour), then, if stable, to 160/100 to 110 mmHg within the next 2 to 6 hours. Labetalol is the agent of choice.

Sickle cell vaso-occlusive crisis

This is a common complication of sickle cell anaemia, which presents with severe pain precipitated by cold, dehydration, infection, or ischaemia (often due to strenuous exercise). The crisis may give rise to skeletal pain due to bone infarction or avascular necrosis, especially of the hip or shoulder. Other presentations include acute abdominal pain and acute chest syndrome, which is clinically indistinguishable from pneumonia. Treatment involves adequate analgesia, hydration with oral or intravenous fluids, oxygen, and treatment of the underlying cause.

Combined vitamin B12 and folate deficiency

If a patient has folate deficiency, it is essential to check for and correct any co-existing vitamin B12 deficiency before giving folate. Folate is believed to exacerbate inhibition of vitamin B12-containing enzymes, thereby worsening vitamin B12-associated neuropathy and subacute combined degeneration of the spinal cord.[53] If vitamin B12 levels are normal, methylmalonic acid levels should be checked to definitively exclude vitamin B12 deficiency, as this is a more sensitive test. An elevated serum methylmalonic acid indicates vitamin B12 deficiency, unless there is a history of renal insufficiency, where levels may be artificially elevated due to inadequate renal clearance.

Leukaemias or aplastic anaemia

Usually present with a normocytic anaemia and co-existing neutropenia and thrombocytopenia. Circulating blasts may be reported on peripheral smear. If these conditions are suspected, an immediate haematology consultation is required for bone marrow biopsy and flow cytometry studies. If the anaemia requires transfusion, only leuko-reduced, irradiated blood products should be used, as these patients may be transplant candidates.[20][54]

Decreased physiological reserve

It is important to identify patients with decreased physiological reserve, such as those with co-existing cardiovascular or pulmonary disease, as these patients are less able to tolerate anaemia and have more severe symptoms.

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