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.

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.[39] Transfusion thresholds in ischaemic coronary artery disease and resuscitation of septic shock remain controversial.

Acute haemorrhage

Causes of acute haemorrhage include trauma, acute gastrointestinal bleeding, rupture of a vascular aneurysm (especially abdominal aortic aneurysm), and recent surgery. Patients may report associated symptoms such as haematemesis or haematochezia in acute gastrointestinal bleeding, or back or abdominal pain in the case of a ruptured abdominal aortic aneurysm. Patients may feel lightheaded, clammy and nauseous.

Key signs include hypotension, pallor, cold clammy skin, thready pulse, tachycardia, dyspnoea, and altered mental status. Flat neck veins when supine indicate at least 30% to 40% total blood volume loss. All orifices should be examined for bleeding. The mechanism and site of any trauma should also be determined.

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.[40] Obtain intravenous access with two large-bore peripheral intravenous catheters. Perfusion to critical organs must be maintained through early goal-directed therapy, including volume resuscitation with crystaloid fluid and blood products, blood pressure support, and tissue perfusion.

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.[41][42]

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

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.[43]

In Europe, HES solutions for infusion 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.[44] 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.[45]

The FDA, upon completion of a review of the safety of HES products (including data from randomized clinical trials, meta-analyses, and observational studies) requests that the Boxed Warning highlight the risk of mortality, kidney injury, and excess bleeding, as well as stating that HES products should not be used unless adequate alternative treatment is unavailable.[46]

Microangiopathic haemolytic anaemias

Haemolytic uraemic syndrome, disseminated intravascular coagulation (DIC), and thrombotic thrombocytopenic purpura (TTP) produce life-threatening rapid haemolysis.[27][28][30]

Treatment of DIC is aimed at the underlying cause. Corticosteroids and immunosuppression should be commenced if haemolytic uraemic syndrome or TTP is suspected. Intravenous immunoglobulins 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

Patients with malignant hypertension may have microangiopathic haemolytic anaemia. The most common symptoms include headaches (often occipital), visual disturbances, chest pain, dyspnoea, and neurological deficits. Systolic BP >210 mmHg and diastolic BP >130 mmHg indicate malignant hypertension; associated signs may include new murmurs, third heart sound on auscultation of the heart, jugular venous distension, rales or lower-extremity oedema, oliguria or polyuria, focal neurological signs, and hypertensive retinopathy.

The initial goal of therapy in hypertensive emergencies is to reduce mean arterial blood pressure 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.[47]

Leukaemias or aplastic anaemia

Usually present with a normocytic anaemia and co-existing neutropenia and thrombocytopenia. Signs of leukaemia include generalised painless lymphadenopathy, ecchymoses, petechiae, hepatosplenomegaly and abdominal or testicular masses. 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.[19][48]

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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