Is it just me...or is it warm in here?

In morning report today we discussed the case of a patient who was transferred to TGH from a peripheral hospital presenting with fatigue, dyspnea, jaundice, and anemia.

Ultimately DAT was positive and diagnosed as having Warm Autoimmune Hemolytic Anemia.

Clinically the patient looked well initially, but within a 12 hour timeframe condition deteriorated with a starting hemoglobin of 97 that dropped to 33. Unfortunately despite treatment with steroids, IVIG, and RBC transfusion given severity, the patient passed away. This case will leave us with unanswered questions, but does remind us of how quickly things can deteriorate especially when the underlying cause of the AIHA is unknown. 

We will discuss anemia, and more specifically the diagnostic approach to hemolytic anemias with management considerations.

The approach to anemia is a 'bread and butter' medicine topic and so very quickly (non-exhaustive):

Think micro, normo, macrocytic.

Microcytic anemia "TAILS"

• Thalassemia: alpha, beta. Clue is markedly low MCV
• Anemia of chronic disease: Due in part to hepcidin release that imparis iron utilization
• Iron deficiency*: always find out why they are iron deficieny (intake, absorption, loss)
• Lead poisoning
• Sideroblastic anemia
• ...and porphyria should be in DDx

Macrocytic anemia

• Active blood loss, and hemolysis initially can have macrocytosis
• Megaloblastic (ie DNA synthesis problem)
• B12, folate, drugs (eg methotrexate, AZT, HU)
• Non megaloblastic
• Etoh, liver disease, hypothyroidism, MDS

Normocytic anemia
Decreased retics (marrow problem)

• combined iron and b12/folate deficiency
• anemia of chronic disease
• marrow replacement (fibrosis, malignancy)
• aplastic anemia
• pure red cell aplasia

Increased retics (meaning marrow is working overtime)

• Active blood loss
• Hemolysis

Approach to hemolytic anemia

Intrinsic RBC

• RBC membrane (e.g. spherocytosis), Hemoglobin disorder (e.g. SCD, thal), Enzyme deficiency (e.g. G6PD, PK deficiency) 

Extrinsic RBC
Non-immune 

• MAHA: TTP, HUS, DIC, Malignant HTN, HELLP, Scleroderma crisis
• Macroangiopathy: Mechanical heart valves

Immune

• Warm (IgG +/- C3d)
• primary or secondary (malignancies ie CLL, CTD, meds including fludarabine, interferon)
• Cold (IgM)
• primary or secondary (lymphoproliferative disorders, CTD, EBV, Mycoplasma)
• Paroxysmal cold hemoglobinuria (IgG and C3d)

Management considerations for Warm AIHA

Get help: hematology, transfusion medicine
Identify, if possible, the cause of the AIHA and treat appropriately
Transfuse only if life threatening anemia. Alert blood blank if transfusion required
Limited evidence exists for treatment and is largely expert opinion
Steroids are first line
Second line include splenectomy, rituximab
Some evidence exists for the use of different cytotoxic agents
Unclear evidence for IVIG, plasma exchange

See this review on the treatment of warm AIHA specifically

Also, this article on general treatment approaches to AIHA is very helpful.