Pancytopenia, Overview of SPEP/UPEP, Refractory Platelet Transfusions

I. Differential Diagnosis of Pancytopenia
Helpful to think in terms of mechanisms of whether the problem is in the bone marrow and what is going on there, vs outside the bone marrow.

1.   Hypocellular Bone Marrow – most common manifestation of this is Aplastic Anemia.

• Idiopathic
• Radiation
• Chemotherapy
• Chemicals (e.g. Benzene)
• Idiosyncratic medication reactions
• Viruses – HIV, Parvovirus B19, HHV-6, EBV, Hepatitis viruses (most commonly Hepatitis B)
• Graft vs Host Disease
• Autoimmune – SLE, etc
• Paroxysmal Nocturnal Hemoglobinuria

2.  Cellular Bone Marrow with Ineffective Hematopoiesis  - Myelodysplastic Syndromes

3.  Marrow Replacement or Infiltration

• Myelofibrosis
• Leukemia/Lymphoma
• Metastatic tumors to the bone

4.   Problem outside the Bone Marrow:   Hypersplenism,  Sepsis – multifactorial reasons, but mostly from consumption and DIC

 

 

II.  Overview of SPEP/UPEP and Immunofixation for Monoclonal Proteins

1) SPEP – screening test to look for M-protein, but sometimes get false positives where M-protein is actually a polyclonal increase in Ig.  Benefit is cheap, easy, and also gives a quantitative estimate of the concentration of the M-protein.
2) Serum Immunofixation – always done with SPEP, uses monospecific Abs for heavy and light chains – increases sensitivity to pick up M-protein and determines clonality (monoclonal vs polyclonal). Unlike SPEP, does not give quantitative estimate.
3) UPEP and Urine Immunofixation – 24 hour urine collecton – similar concepts as above.   Main reason to do this is that it picks up many patients who have light chain secretion only, as those are rapidly excreted in the urine and thus are often not picked up on SPEP.
4) Serum Free Light Chains Assay – even more sensitive for detection of low levels of monoclonal free light chains in the serum than is the UPEP, and is also important in following response to therapy.

Basically, SPEP has a sensitivity of ~80% for multiple myeloma, and sensitivity is increase to >95% with addition of Serum immunofixation and UPEP/Urine Immunofixation, as ~20% of multiple myeloma patients secrete ONLY light chains which are better picked up by the UPEP.

 

 

III. Platelet Transfusion Refractoriness

• Usually defined as a response of < 10k in platelets after a transfusion of an apheresis unit in an average sized adult.  A normal increase in platelet count is generally about 30 k.

Etiologies (this is not an exhaustive list):
A.   Non-Immune Causes – account for approximately 2/3rd of cases.

• Sepsis – multiple mechanisms including platelet consumption and sequestration, decreased production by bone marrow, and sometimes concomitant DIC.
• Splenomegaly – transfused platelets get sequestered in the spleen.
• Bleeding – although this is confusing since bleeding is commonly a result of platelet transfusion refractoriness. 
• DIC – due to platelet destruction

B.  Immune Causes – mainly Alloimmunization.

• Diagnosis – a platelet count check 10 minutes to 1 hour after transfusion, along with one ~24 hours after transfusion, is extremely help.
• A normal rise in platelets after 1 hour, but a return to baseline count within 24 hours, is typical of most  non-immune causes of platelet transfusion refractoriness (i.e. sepsis, splenomegaly).  If this is the case, then the appropriate move is to treat the underlying cause.
• If the 1 hour platelet count shows little to no increase, this is more typical of alloimmunization.  Once this is recognized, the primary team should work with the blood bank to HLA-matched platelets to maximize the yield of transfusions.

 

(Chanu Rhee MD, 5/10/11)