Urgent considerations

See Differentials for more details

Anemia 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 stabilization 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 workup 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 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.[39] 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 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 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.[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 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 coagulation support and monitoring, and the appropriate use of local hemostatic measures, tourniquets, calcium, desmopressin, and consideration for tranexamic acid.[41][42]

Definitive management of acute hemorrhage 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]

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.[44]

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.[45] 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.[46]

Microangiopathic hemolytic anemias

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

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 done 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 headaches (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 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 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.[47]

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, as these patients may be transplant candidates.[19][48]

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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