3/12/2018 Causes of Anemia/Autoimmune Hemolytic Anemia

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I. Review Broad Classification Schemes for Anemia
Two ways to think about anemia, Destruction/Blood Loss vs Underproduction
Master List
A. Destruction/Blood Loss
1. Blood Loss - bleeding (GIB, menstruation, trauma, etc).
Cardiology 2. Hemolysis
a) Intrinsic Causes – something structurally wrong with the RBC or hemoglobin, that predisposes to hemolysis

Endocrinology Glucose-6-phosphate dehydrogenase

Sickle Cell Anemia
Thalassemias
Gastroenterology Hereditary Spherocytosis
Paroxysmal Nocturnal Hemogloburia

General Inpatient b) Extrinsic Causes

Medicine
Autoimmune Hemolytic Anemia
Infections – Malaria, Babesiosis
Hematology Microangiopathic Hemolytic Anemias – DIC, TTP-HUS
Hypersplenism
Traumatic (e.g. shearing from mechanical valve)
Infectious Disease

Nephrology B. Underproduction
Here, the morphological approach based on MCV is helpful, although many of these overlap with things in the
increased destruction category
Neurology 1. Microcytic (MCV < 80) = TICS (Thalassemias, Iron Deficiency, Chronic Disease, Sideroblastic Anemia)
2. Macrocytic (MCV >100) - I love my mnemonic HALF MD (which I made up when was I was half of an MD in 3rd
Oncology year of medical school).
Hypothyroidism
Outpatient & Alcoholism
Preventative Medicine Liver disease
Folate/B12 deficiency – Megaloblastic anemia
Myelodysplastic Syndrome
Palliative Care Drugs – e.g. AZT and other drugs that interfere with folate metabolism (5-FU, Methotrexate)
Unfortunately, this mnemonic does not include Reticulocytosis which is a very common cause of
macrocytosis (since reticulocytes are bigger than mature RBCs).
Psychiatry
3. Normocytic (MCV 80-100) – Anemia of Chronic Disease and basically everything else
Pulmonary/Critical
Care

II. Overview of Autoimmune Hemolytic Anemia

Rheumatology AIHA refers to acquired, antbody-mediated RBC destruction.
A. Warm Antibody AIHA:
Mechanism - Abs opsonize RBCs at body temperature, and RBCs are removed by the reticuloendothelial
system (mainly the spleen).
Often idiopathic, but can be due to: viral infections, autoimmune diseases (SLE), malignancies of immune
system (CLL etc), prior HSCT, and drugs (cephalosporins, PCN, NSAIDs, quinine derivatives)
See spherocytes on smear (due to RBC membrane deformity)
Potive direct coombs for IgG +/- C3
Can be associated with venous thromboembolism
Treatment: Initial treatment with corticosteroids, if poorly responsive or resistant disease, consider
elective splenectomy. For patients unwilling or unable to undergo splenectomy, or for those who have
failed or relapsed following splenectomy, consider other immunosuppressive or cytotoxic agents (ie.
rituximab, azathioprine, cyclophosphamide, cyclosporine). There is insufficienct information from RCTs to
choose one of these agents over another.

B. Cold Antibody AIHA:

Mechanism: IgM's that agglutinate at cold temperatures (<37 degrees), which leads to complement
fixation and intravascular hemolysis (as opposed to warm Ab AIHA where RBCs are removed by the
spleen).
See anti C3-d on direct coombs
Often associated with malignancy (CLL, lymphoma, etc) or infection (mycoplasma, mononucleosis)
Treatment is usually directed at the underlying cause (ie. infection) and avoidance of cold triggers. In
contrast to warm ab AIHA, steroids are generally ineffective, and more commonly hematologists
will jump to other immunosuppressants like Rituximab.

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3/12/2018 Causes of Anemia/Autoimmune Hemolytic Anemia

Overview of Evans syndrome (Coombs’-positive autoimmune hemolytic anemia and thrombocytopenia)

AIHA: Results when IgG present which reacts with RBC antigens at room temperature
Causes: viral infections, autoimmune disease (e.g. SLE), immune deficiency, liquid tumors, post-
hematopoietic stem cell transplant
Pathophysiology: IgG (and subsequently fixed complement) adhere to phagocytes, resulting in
partial ingestion and creation of spherocytes, which are cleared by spleen
Direct complement lysis is rare, as this requires two IgG molecules to be bound to RBC (as opposed
to one in IgM-mediated hemolysis)

In Evans syndrome, antibody is directed against the Rh locus

Treatment:
Steroids: induce remission in 2/3 of patients
If disease refractory to steroid taper, can initiate steroid-sparing immunosuppression
Splenectomy: equivalent efficacy to steroids
IVIG: only occasionally effective (unlike in ITP)

Prognosis:
Often refractory so standard AIHA/ITP therapy, with more chronic, relapsing course
Following steroids and splenectomy, optimal therapy unclear
Responses in hemoglobin and platelets is often discordant - immune hemolysis may protect platelets,
as spleen is saturated
Death often results from infection, cardiovascular complications, or underlying malignancy

(Christopher Woo MD, 6/9/11)

(Chanu Rhee MD, 5/16/11)

© 2011 Stanford School of Medicine

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