DL-HA represents 30-40% of autoimmune hemolytic anemia in children, that is generally self-limiting.
1 Autoantibody responsible for DL-HA is a cold-reacting immunoglobulin known as, DL autoantibody, capable of causing severe hemolysis even when the titre detected is low.
2 The DL autoantibody hold on tightly to red blood cell (RBC) surfaces during the peripheral circulation, where temperatures are cooler than 30°C in comparison to core body temperature.
3 After attachment to RBC surface, the DL autoantibody activates the complement cascade, leading to RBC membrane perforation and intravascular hemolysis, hence the dark coloured urine.
3 Complement activation and consequential hemolysis would become reality if binding RBCs travel to the core part of the body at a warmer temperature. Results of the direct antiglobulin test (DAT) with anti-C3 are likely to be positive, while negative for anti-IgG or anti-IgM.
3 In contrast, in cold agglutinin disease (CAD) IgM is positive.
3 The most prominent difference between DL-HA and CAD is this causative agent. Hence, a distinction must be established for proper diagnosis and treatment. Given that hemoglobinuria and personal history of travel to cold areas is not always present, diagnosis relies on lab testing.
2 A peripheral smear is always essential for diagnosis of hemolytic anaemia and may reveal spherocytes, or rouleaux formation suggestive of warm autoimmune haemolysis.
4 The best initial therapy for this patient is to keep him warm with gloves and warming blanket.
4 Warm intravenous fluids and red blood cell transfusion are vital for treatment.
4 If an underlying etiology is determined, it should be treated. The most likely etiology for this patient’s DL-HA is the history of a previous viral illness and initiation of amoxicillin-clavulanate (drug-induced immune hemolytic anaemia). Though corticosteroids represent the first-line treatment for patients with autoimmune hemolytic anaemia, about 30% of patients require second-line treatment.
5 Plasmapheresis should only be used in severe cases, that are refractory to initial therapy.
4| References : |
- Eder AF. Review: acute Donath-Landsteiner hemolytic anemia. Immunohematology. 2005;21:56-62. Erratum in: Immunohematol. 2005;21:132.
- Emedicine. Donath-Landsteiner Hemolytic Anemia. Available at URL: https://emedicine.medscape.com/article/955176-overview. Accessed on 28th Feb 2021.
- Ogose T, Wakata Y, Kaneko M, Shinahara K, Takechi T, Kotani H. A case of recurrent paroxysmal cold hemoglobinuria with the different temperature thresholds of Donath-Landsteiner antibodies. J Pediatr Hematol Oncol. 2007;29):716-719.
- American Society of Hematology. Case Study: Four-Year-Old Male with Red Urine and Fever. Available from URL: https://www.hematology.org/education/trainees/fellows/case-studies/child-red-urine-fever. Accessed on 5th March 2021.
- Lechner K, Jäger U. How I treat autoimmune hemolytic anemias in adults. Blood. 2010;116:1831-1838.
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