What We Know We Don’t Know

Case Study on XLA Jennifer L. Appelbaum, MT(ASCP)

Barnes-Jewish Hospital

St. Louis, MO

What we know in the blood bank today

• All patients make immunoglobulins

• Once a patient is CMV positive, they will always be positive.

• Patients who have low IgA levels have IgA deficiency

Commonly accepted conclusions we, as

Blood Bankers, make every day

• 31 year old male

• Fatigue, low grade fever and loss of appetite

• Low hemoglobin

• Ordered 2 units of pRBCs

• Type and screen showed

• No history of bone marrow transplant or other quickly explainable cause of discrepancy.

• Patient had no history at Barnes

ABO A B D Anti-A Anti-B

IS 0 0 4+ 0 0

Case of Patient X

• Later discovered patient had been in National Institutes of Health (NIH) in Bethesda, MD from Oct 2011-Feb 2012

• Patient diagnosed with X-linked agammaglobulinemia (XLA)

• Patient was given 4 pRBCs and 2 platelets

• Patient tested CMV positive

More history

• X-linked Agammaglobulinemia

• Humoral Immunodeficiency

• Presents at 3-18 months of age

• Characterized by a near absence of CD19+ B cells because of a defect in Bruton Tyrosine Kinase (BTK)

• Rare-occuring in 1/379,000 live births

• Family history in 40% of cases

• Maternal origin

• Suseptible to encapsulated bacteria and blood borne viruses

What is XLA?

• Patients with family history are diagnosed sooner

– 3 years of age vs. about 5.4 years of age

• Lab tests

– Immunoglobulin levels

– Flow cytometry

• <2% B cells (CD19+)

• Criteria

– <2% B Cells with a family history

– <2% B Cells with a mutation of BTK gene

• Patient X had nearly no B cells and a family history

Diagnosis

• NIH

• IVIg

• Bone marrow transplant

– Few animal models

– Successful transplants in China

• Chemotherapy

– Infection of adenovirus-lost 100 lbs

– Blind for a few days

– Transplant aborted

• Returned to St. Louis, MO

Patient X and treatments

• CMV negative requested

– Barnes tested CMV negative

• How could this be?

• Patient received IVIg from pooled population containing CMV antibodies

• Patient received pRBCs and platelets

• 5 days later, patient had pleural effusions on two different occasions

• Barnes called NIH

Barnes visit

• CMV negative pRBCs

• Delayed reactions to transfusions-5 days later

– Hemoptysis (pulmonary vasculitis

– Pleural effusions (cellular)

• Not reported to the blood bank

Products received at NIH

• Ordered 2x washed pRBCs and platelets

• Requested IgA deficient platelets

• ARDP

• Individuals who fail to produce this protein at a level ≥ 0.05mg/dL are classified as IgA-deficient according to the criteria of the American Rare Donor Program. http://www.redcrossblood.org/sites/arc/files/IRL%20Guide_Final.pdf

• Once an individual produces anti-IgA, he/she should receive IgA-depleted cellular products or IgAdeficient plasma and derivatives when transfusion is indicated. http://www.redcrossblood.org/sites/arc/files/IRL%20Guide_Final.pdf

• Patient X did not meet the criteria for IgA deficient to get IgA depleted products.

Strange request by Barnes clinician

• Washing units for can reduce IgA in products

IgA Concentration in Washed Red Blood Cells

• Popovsky, M., Transfusion Reactions, Bethesda, Maryland, AABB Press, 2007.

Research by Barnes clinician

Number of Wash Cycles

Total Volume of Normal Saline Used (liters)

Observed IgA Content (mg/dL)

Results of Passive Hemagglutination Inhibition Assay

3 1.0 0.11-0.27 Positive

4 1.3 0.01-0.04 Weakly positive

6 2.0 0.00 negative

• Patient sample run on Provue

• Sample forwarded to our reference bench

• Serum was then incubated at 4 degrees C for 15 minutes with no change. Tech then incubated at 4 degrees C for 30 minutes and we were able to get a w+ reaction in the Anti-A and Anti-B tubes.

• Patient wasn’t making immunoglobulins almost at all.

A B D D control Anti-A Anti-B

0 0 3+ 0 0 0

A B D D control Anti-A Anti-B

0 0 3+ 0 0 0

ABO/Rh typing

• Decided to give patient O Positive and AB platelets

• 1x washed unit with 1 liter of normal saline/CMV neg

• Patient coughs up blood

• 2x washed unit with 2 liters of normal saline/CMV neg

• Patient has no reaction

• Begin giving patient 2x washed RBC and platelets/CMV neg

• Patient received this therapy for a number of days.

Barnes visit-Trial and error

• Challenged some of our beliefs

• Don’t know why the washing worked for this patient exactly

• Not all patients make immunoglobulins

• Just because someone has tested CMV positive in the past doesn’t make that tried and true.

• Not all patients with low or absent IgA have IgA deficiency

Conclusion