Urgent considerations
See Differentials for more details
Anemia is life threatening if there is >40% loss of total body volume. These patients should receive packed red blood cell (RBC) transfusions for stabilization as soon as possible, especially if there are underlying cardiac or pulmonary comorbidities. A reticulocyte count, ferritin level, and peripheral smear should be obtained before transfusion, if possible, as this makes subsequent workup more accurate.
Massive transfusion subsequent to tissue injury should follow balanced protocols (that include the addition of platelets and coagulation factors [factor V, factor VIII, and fibrinogen]) to avoid dilutional, or consumptive, coagulopathy.
Clinical guidelines from the AABB (formerly known as the American Association of Blood Banks) suggest a restrictive transfusion threshold of 7 g/dL in hospitalized hemodynamically stable patients, and 8 g/dL in those undergoing orthopedic or cardiac surgeries, or with pre-existing cardiovascular disease, unless there is an underlying acute coronary syndrome, severe thrombocytopenia, or chronic transfusion dependence.[65] This restrictive blood transfusion threshold of 7-8 g/dL can reduce the amount of blood transfused and reduce the risk of unnecessary transfusions.[66]
Transfusion thresholds in ischemic coronary artery disease and resuscitation of septic shock remain controversial.
Acute hemorrhage
Causes of acute hemorrhage include trauma, acute gastrointestinal bleeding, rupture of a vascular aneurysm (especially abdominal aortic aneurysm), and recent surgery. Patients may report associated symptoms such as hematemesis or hematochezia 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, dyspnea, and altered mental status. Flat neck veins when supine are suggestive of volume loss. All orifices should be examined for bleeding. The mechanism and site of any trauma should be determined.
Rapid evaluation, identification, and control of bleeding is essential before any further workup. Dilution does not occur acutely, so hemoglobin (Hb) and hematocrit levels do not provide an accurate reflection of the degree of blood loss and anemia.[67] 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 crystalloid fluid and blood products, blood pressure support, and tissue perfusion.
Crossmatched blood (or O negative, if crossmatch is unavailable) should be given as soon as possible.
In addition, bleeding following major trauma requires tourniquets, coagulation support and monitoring, monitoring of hemostasis, maintenance of calcium (within the normal range following major trauma), and consideration for tranexamic acid.[68][69]
Definitive management of acute hemorrhage depends on the underlying cause, but usually requires surgery.
Solutions containing hydroxyethyl starch (HES), which decrease volume overload in large volume resuscitations, are associated with adverse outcomes including kidney injury and death, particularly in critically ill patients and those with sepsis.[70][71] In July 2021, the US Food and Drug Administration (FDA) issued safety labeling changes for solutions containing HES, stating that HES products should not be used unless adequate alternative treatment is unavailable.[72] The Pharmacovigilance Risk Assessment Committee of the European Medicines Agency, in February 2022, recommended suspending HES solutions for infusion in Europe.[73]
Microangiopathic hemolytic anemias
Hemolytic uremic syndrome, disseminated intravascular coagulation (DIC), and thrombotic thrombocytopenic purpura (TTP) produce life-threatening rapid hemolysis.[52][54][56]
Treatment of DIC is aimed at the underlying cause. Corticosteroids and immunosuppression should be commenced if hemolytic uremic syndrome or TTP is suspected. Intravenous immunoglobulins or urgent plasmapheresis may be necessary for rapid clearance of autoantibodies. Antibody screening should be performed prior to blood transfusion. Antibody-free blood products should be used to prevent additional alloimmune hemolysis.
Malignant hypertension
Patients with malignant hypertension may have microangiopathic hemolytic anemia. The most common symptoms include headache (often occipital), visual disturbances, chest pain, dyspnea, and neurologic 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 edema, oliguria or polyuria, focal neurologic 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 anemia, which presents with severe pain precipitated by cold, dehydration, infection, or ischemia (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 chest syndrome, which can be clinically indistinguishable from pneumonia, and acute abdominal pain.
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 coexisting 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.[74]
Leukemias or aplastic anemia
Usually present with a normocytic anemia and coexisting neutropenia and thrombocytopenia. Signs of leukemia include generalized 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 hematology consultation is required for bone marrow biopsy and flow cytometry studies. If the anemia requires transfusion, only leukoreduced, irradiated blood products should be used.[39][75][76][77]
Decreased physiologic reserve
It is important to identify patients with decreased physiologic reserve, such as those with coexisting cardiovascular or pulmonary disease, as these patients are less able to tolerate anemia and have more severe symptoms.
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