Autoimmune hemolytic anemia risk factors

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Shyam Patel [2], Irfan Dotani

The risk factors for autoimmune hemolytic anemia include systemic lupus erythematosus and immunotherapeutic medications. Systemic lupus erythematosus is thought to be a strong risk factor for autoimmune hemolytic anemia. However, immunotherapeutic medications may become a more prevalent risk factor in the coming years as these agents are becoming used increasingly for a variety of cancers. These medications include anti-PD-1 antibodies and anti-CTLA-4 antibodies.

In the majority of cases of autoimmune hemolytic anemia, the etiology is not found, and patients have no predisposing risk factors. However, there are certain conditions that can predispose a person to develop autoimmune hemolytic anemia. These conditions have an immunologic or autoimmune basis, with aberrant immune activation that results in the generation of autoantibodies against oneself.

• Systemic lupus erythematosus:
  • The best autoimmune-related known risk factor is systemic lupus erythematosus.^[1]
  • SLE is a multisystem rheumatologic disease that is characterized by production of anti-double stranded DNA and anti-nuclear antibodies, with resultant autoimmune-mediated damage to a variety of organs including the kidneys, brain, skin, and peripheral blood.^[1]

• Immunotherapy:
  • Another risk factor for autoimmune hemolytic anemia is the use of immunotherapeutic agents to treat underlying cancer.
  • Treatment of immunotherapy-related autoimmune hemolytic anemia involves corticosteroids and rituximab.^[2]
    • Pembrolizumab^[3]: This is a humanized monoclonal antibody against PD-1. It is FDA-approved for metastatic or unresectable melanoma. It is approved for metastatic non-small cell lung cancer. It is approved for metastatic head and neck squamous cell carcinoma. It is approved for Hodgkin lymphoma in patients who experienced progression after 3 or more lines of therapy. It is indicated for metastatic urothelial cancer who are ineligible for platinum-based therapy. It is indicated for patients with metastatic gastric or gastroesophageal cancer expressing PD-L1. It is indicated for microsatellite instability-high (MSI-H) tumors after progression on chemotherapy.
    • Nivolumab^[4]: This is a monoclonal antibody against PD-1. This medication is FDA-approved for metastatic melanoma or for adjuvant treatment of melanoma involving regional lymph nodes. It is also approved for metastatic non-small cell lung cancer after progression on platinum-based chemotherapy. It is approved for renal cell carcinoma in patients who have received prior anti-angiogenic therapy. It is approved for patients with Hodgkin disease who have relapsed after autologous stem cell transplant and post-transplant brentuximab. It is approved for recurrent or metastatic head and neck squamous cell carcinoma after relapse with platinum-based chemotherapy. It is approved for metastatic urothelial cancer after progression on platinum-based chemotherapy. It is indicated for microsatellite instability-high (MSI-H) metastatic colon cancer after progression on standard chemotherapy. It is approved for hepatocellular carcinoma after treatment on sorafenib.
    • Ipilimumab^[5]: This is a humanized monoclonal IgG1 antibody against CTLA-4, which is an inhibitory receptor on T lymphocytes. It is FDA-approved for metastatic or unresectable malignant melanoma or for adjuvant treatment for non-metastatic melanoma that involves regional lymph nodes greater than 1mm.
    • Atezolizumab: This is a humanized monoclonal antibody against PD-L1 on tumor cells. This medication is FDA-approved for patients with advanced or metastatic urothelial cancer who are ineligible for cisplatin-based therapy or have disease progression within 12 months of neoadjuvant or adjuvant chemotherapy. It is also approved for patients with metastatic non-small cell lung cancer who have had disease progression on platinum-based chemotherapy.
    • Avelumab: This is a humanized monoclonal IgG1 antibody against PD-L1 on tumor cells. This medication is FDA-approved for patients above the age of 12 with metastatic Merkel cell carcinoma.

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