Episode 093: Heme Consult Series: Warm Autoimmune Hemolytic Anemia
Next in our heme consult series is all about the workup and management of warm autoimmune hemolytic anemia (wAIHA), a very scary situation! These patients can often be very sick and there can be a lot of underlying issues that may be causing this to occur. Rest assured- after this episode, you’ll be a pro at identifying this disorder and know how to manage it should you ever come across this.
If you have not done so already, we recommend you check out our initial episode about hemolytic anemias (Episode 091)
If you are concerned about a patient having warm autoimmune hemolytic anemia, what should the initial work up include?
CBC
CMP
Reticulocyte count: High retic count indicates high cell turnover
Pro tip: It is always rule out acute blood loss!
Important questions to ask for a new episode of acute anemia.
Blood thinner prescriptions
NSAID prescription and OTC use / overuse
Recent trauma
Black/tarry stools - folks may not know this is blood
Unusual bruising along the flanks, abdomen, and thighs
New aches/pains (bleeding into a small area?)
Thorough physical exam to reveal any bruising.
If bleeding is ruled out, suspect hemolysis.
What to look for in peripheral smear?
Spherocytes and possibly even some RBC doublets (IgG mediated process).
Schistocytes would be unusual (more associated with mechanical hemolysis as opposed to direct autoimmune attack on the RBCs).
What other tests do you order if you suspect hemolytic anemia?
LDH (high)
Haptoglobin (low as it binds free Hb)
Coomb’s test: IgG + (most active at 37C) - We discuss this in a lot of detail in Episode 091!
There is a risk of thrombosis in wAIHA!
Brisk hemolysis is a high-risk pro-thrombotic state. Phosphatidylserine exposure in the inner layer of RBC membrane causes a high thrombotic state.
Examine extremities for unilateral swelling.
If a physical exam is compelling, consider four extremity doppler ultrasounds to look for DVT.
Is it safe to transfuse blood to patients with active wAIHA?
Transfuse in symptomatic patients: reduces the risk of MI, CVA in these states of severe anemia.
Patients with wAIHA are incompatible with their own blood.
Determining blood type is also challenging: panagglutinin or an antibody that binds to some common red cell antigen, causing agglutination of cells regardless of the ABO type.
However, transfusions is a life saving intervention and in case of need, start trauma blood, O+ve or +-ve units.
Connect with the blood bank sooner than later, for an effective strategy.
What is the underlying driver that can cause wAIHA?
Dysregulation of B cell function and production of anti-RBC autoantibodies.
Examples: CLL, Hodgkin disease, other autoimmune disorders like ALPS or SLE.
Infections: HIV
Medications: penicillins, cephalosporins
Idiopathic
Outline of treatment for wAIHA
Acute situations: supportive care and intense immune suppression.
Rituximab + High dose Steroids are key!
Rituximab (CD20 directed antibody that kills B cells)
375 mg/m2 weekly x 4 doses
Screen for hepatitis panel
High dose steroids.
Prednisone at 1 mg/kg/day.
PJP prophylaxis
Supplemental B12 and folate (as there is a rapid cell turnover)
If there is a hematologic malignancy driving this, often you want to consider treating the underlying disorder, except in the case of CLL, where you can use rituximab and steroids
Long term: treatment of underlying causes provides long term remission from wAIHA.
For example: for wAIHA in association with CLL, adding rituximab to suppress the clone.
How do we monitor the patient for response in the acute setting (TFOC approach!)?
CBC Q12h followed by daily, along with daily reticulocyte count, LDH, and bilirubin.
Haptoglobin - great screening test, and is very sensitive for hemolysis, but it’s non-specific. Other parameters improve before haptoglobin, so not a great marker to keep trending.
Monitor for hemoglobin stabilization.
The immune system has constant antigenic stimulation - RBCs floating around stimulating these abnormally sensitized B cells to proliferate and make antibodies - so it can take a while for treatments to have their effect. It is not unusual for patients to have an ongoing transfusion requirement for weeks after starting therapy.
What if the patient is not responding or requires transfusions for an extended period of time? Is there a role for IVIg?
If a patient is still requiring really frequent transfusions going into their 3rd week of therapy, consider IVIg.
Remember, IVIg can increase risk of VTE at high doses in this already high prothrombotic state. So definitely want to weigh the pros and cons of therapy here
Use smaller doses: 400-500 mg/kg/day over 4 or 5 days.
Remember, IVIG is used as a rescue measure for patients with ITP.
Is there any role for plasma exchange?
A few meta-analyses looking at small trials of PLEX for patients with wAIHA.
Consider if PLEX is done via peripheral access.
Data about this is limited and it remains a questionable option, but something to consider if all else fails.
TFOC tips to long term management of wAIHA:
Slow steroid taper to reduce the risk of glucocorticoid withdrawal (this is not a perfect science).
Initially: 1 mg/kg/day dose until they are no longer transfusion dependent.
At the time of taper: reduce the dose by 10 mg each week. Make sure to check in on hemoglobin level and LDH to make sure there is no recurrence.
If transfusion independent but hemoglobin level lingering in the 8s or 9s, taper even more slowly, by 5 mg a week.
After a week at 20 mg, can slow taper: tapering by 5 mg every two weeks, and after 2 weeks on 5 mg/day, to 2.5 mg/day for 2 weeks, then 1 mg/day for 2 weeks before stopping altogether.
PJP prophylaxis (consider using inhaled pentamidine)
PPI/H2 blocker prophylaxis to decrease reflux.
Calcium and Vitamin D to prevent bone loss.
Sustained remission from disease after a single round of treatment, many patients see episodes of recurrence that may necessitate a return to steroids or alternative treatments in the future.
Dan Hausrath’s expert tip for long term monitoring.
Every 3months x 1 year followed by every 6 months x 1 year followed by yearly!
Patients can relapse so need to monitor
How do you approach relapse/refractory cases?
If relapses 6 months or more after they finish their initial taper, repeat their initial treatment regimen.
If it relapses < 6 months, this is a more refractory form of the disease and may have to reach for alternate regimens.
Options for refractory wAIHA:
Cyclophosphamide
T-cell targets like mycophenolate mofetil or cyclosporine A
Bortezomib
Fostamatinib
Persistently refractory to multiple lines of medical therapy:
consider splenectomy after careful consideration
invasive procedure
life-long immunocompromised state
may not even have a durable effect if there are splenules present that hypertrophy or once the reticuloendothelial system elsewhere hypertrophies to compensate.
Summary
Diagnostics: rule out acute blood loss and confirm AIHA on labs
Initial management: alert the blood bank early, determine pace of hemoglobin fall, and support with transfusions
Definitive management: Treat any underlying condition and give steroid/rituximab for idiopathic disease
Outpatient management: When hemoglobin is stable, taper steroids and monitor for recurrence.
The crew behind the magic:
Show outline: Dan Hausrath
Production and hosts: Ronak Mistry, Vivek Patel, Dan Hausrath
Editing: Resonate Recordings
Shownotes: Srijan Valasapalli
Social media management: Ronak Mistry
We are proud to partner with HemOnc.org!
Want to learn more about the trials that lead to the regimens discussed today? What about dosing schedules? See links in the show notes for a link to HemOnc.org
