2025 – PAGE 281 – HEMATOLOGY & ONCOLOGY

HEMOLYTIC ANEMIAS

Hemolytic anemias are normocytic anemias because normal-sized red cells are being lysed, and the normal-sized red cells that are not hemolyzed have a normal MCV. Look for JAUNDICE (as mentioned in the neonatology section). Other findings may include an elevated reticulocyte count (> 1%), elevated indirect/unconjugated bilirubin, hemosiderin/bilirubin in the urine, a low serum haptoglobin, or a positive Coombs test if it is an autoimmune hemolytic anemia.

COOMBS TEST PEARLS

The Coombs test helps to identify AUTOIMMUNE hemolytic anemias. Whether the test is DIRECT or INDIRECT can be confusing and is probably LOW-YIELD. If it causes you anxiety, here’s the simplified version.

* DIRECT COOMBS TEST: The patient’s RBCs are placed DIRECTLY into a solution containing “anti-antibody antibodies.” If the RBCs taken from the patient are being destroyed by an autoimmune process, then the cells will be coated with antibodies, and the “anti-antibody antibodies” will latch onto them.

• MNEMONIC: DIRECT the patient to the lab and then DIRECT the patient’s RBCs DIRECTLY into the solution.

* INDIRECT COOMBS TEST: The patient’s serum is used to indirectly figure out if the patient possibly has autoimmune hemolytic anemia. Someone else’s RBCs that are similar to the patient’s own RBCs (Rh compatible and ABO compatible) are placed in the patient’s serum. If the serum causes hemolysis of the alien RBCs, it’s assumed that the same thing is happening in the patient.

(DOUBLE TAKE) RHESUS DISEASE (AKA RH DISEASE)

When checking for Rhesus Disease (AKA RH Disease), look for an Rh- mom in her SECOND pregnancy: Maternal IgM antibodies are made during the FIRST pregnancy after exposure to the Rh antigen and are too large to cross over into the fetal circulation. During the SECOND pregnancy, IgG antibodies are present that are small enough to cross. (This can cause ERYTHROBLASTOSIS FETALIS if they cross early in pregnancy.) Rh- moms are supposed to get RHOGAM at 28 weeks gestation, and then again after delivery if the baby is found to be Rh+.

* KLEIHAUER BETKE TEST: Check MATERNAL blood to see if there are FETAL red cells present.

PEARL: RH disease is never present in a “first” pregnancy. ABO incompatibility can occur in ANY pregnancy.

(DOUBLE TAKE) ABO INCOMPATIBILITY

ABO incompatibility usually occurs in mothers with an “O” blood type. Naturally occurring “anti-A” or “anti-B” IgG antibodies may be present. This can result in hemolytic disease of the newborn in a FIRST pregnancy. So for hemolysis in a G1P1 baby, consider ABO incompatibility as the etiology.

TRANSFUSION REACTIONS

Transfusion reactions occur during or shortly after blood transfusion. Symptoms may include fever, chills, rash, dyspnea, back pain, hypotension, and hemoglobinuria. Stop transfusion immediately if any reaction occurs, maintain IV access, notify the blood bank, and send the transfusion product for workup. Pediatric management follows general principles but includes weight-based dosing and recognition that non-verbal children may present with nonspecific symptoms like irritability or lethargy. Specific types of transfusion reactions are discussed below:

• Febrile Non-Hemolytic Reaction: Most common transfusion reaction, caused by cytokines released by donor white blood cells during storage or by recipient antibodies against donor white blood cells. Symptoms include fever, chills, and headache. Treat with antipyretics. Premedication with acetaminophen and/or antihistamines may be considered for future transfusions, although leukoreduced blood products reduce this risk significantly.
• Febrile Non-Hemolytic Reaction: Most common transfusion reaction, caused by cytokines released by donor white blood cells during storage or by recipient antibodies against donor white blood cells. Symptoms include fever, chills, and headache. Treat with antipyretics. Premedication with acetaminophen and/or antihistamines may be considered for future transfusions, although leukoreduced blood products reduce this risk significantly.
• Acute Hemolytic Reaction: Life-threatening reaction due to ABO incompatibility. Symptoms include fever, chills, hypotension, hemoglobinuria, renal failure, back pain (from kidney injury), and in severe cases, DIC. Labs may show a positive direct antiglobulin test (DAT), indicating antibodies or complement on red blood cells, as well as other findings of hemolysis (e.g., low haptoglobin, elevated LDH, and indirect hyperbilirubinemia). Treat with IV fluids and diuresis to prevent renal failure. Severe hemolysis and anemia may require carefully cross-matched transfusions.
• Allergic Reaction: Caused by an allergic reaction to donor plasma proteins. Symptoms include rash, itching, or urticaria (without fever). Wheezing, stridor, nausea, vomiting, or diarrhea may also occur. Labs are generally unremarkable. Treat with antihistamines (e.g., diphenhydramine). Consider future premedication with antihistamines.
• Anaphylactic Reaction: Typically occurs in IgA-deficient patients with anti-IgA antibodies or due to severe hypersensitivity to donor plasma proteins. Symptoms may include hypotension, dyspnea, wheezing, stridor, nausea, vomiting, diarrhea, and shock. Send labs to check for IgA deficiency. Treat with epinephrine, IV fluids, steroids, and antihistamines. Use washed blood products or IgA-deficient donor blood products for future transfusions.
• Transfusion-Related Acute Lung Injury (TRALI): Significant cause of transfusion-related mortality in children, particularly in critically ill patients. Caused by donor antibodies reacting with recipient leukocytes. Symptoms typically present within 2 hours of transfusion but can occur up to 6 hours later and include acute respiratory distress, hypoxemia, tachypnea, fever, and hypotension. Chest X-ray may show bilateral pulmonary infiltrates without evidence of cardiac failure. Labs may show leukopenia or neutropenia. Diagnosis is clinical, and other causes of lung injury (e.g., sepsis, ARDS) must be excluded. Treat with supportive care, including oxygen or mechanical ventilation as needed. Future transfusions may require washed blood products or plasma from male-only donors to reduce risk.