Interpretation of Reticulocyte lab values

Reticulocytes and their significance

This is a really confusing topic because of misnomers.  Wikipedia and link above (which wikipedia cited) helped a lot in breaking this down.


Reticulocyte Count is not really a "count".  It might be called a "count" but it's usually a percentage.  If the retic count is 5, that means that 5% of the RBCs are reticulocytes.
This becomes an issue in anemia, where the total number of RBCs decrease, and therefore the "retic count" will be spuriously high.  Example - if x = number of reticulocytes and T = total number of RBCs, then the ratio of X/T ("the retic count") will increase as T decreases.

The next part is intuitive.  The "retic count" is corrected for the degree of anemia by multiplying by the ratio of the patient's Hct/normal Hct.  The normal Hct in calculations is generally 45.
So if the patient's "retic count" is 5% or 5, and the patient's Hct is 25.  Then the "corrected retic count" is 5 x (25/45) = 25/9 .  In calculations, 5 (and not 0.05) is used for 5%.

To make things more confusing, sometimes the "corrected retic count" is also known as "reticulocyte index."  (This is confusing because another term we'll address known as the "reticulocyte production index" is also sometimes called the "reticulocyte index."  WTF)



Okay, so we've somewhat corrected the "retic count" for the degree of anemia.  The next part is to take into account that reticulocytes take about 4 days to mature --- In normal conditions this means 3 days in the bone marrow and 1 day in the peripheral blood.  In anemia, however, the bone marrow will "prematurely release" reticulocytes.  So this means that you'll have more circulating reticulocytes, but this doesn't necessarily mean that the BM has amped up its erythropoiesis in response to the anemia.  It could just mean that the BM just prematurely released the reticulocytes.

My interpretation of this calculation is that you're not supposed to consider "premature reticulocytes" as reticulocytes in your final reticulocyte value.
So to correct for the premature release of reticulocytes, we use something called the "maturation factor."  It makes sense intuitively ---- If we're going to divide by this "maturation factor,"as the degree of anemia worsens (Hct decreases), the maturation factor increases.  (interestingly the maturation factor = number of days in the peripheral blood spent by the reticulocyte to mature)

Maturation factor for degree of anemia:
                   
                     Maturation Factor
Hct 36 - 45         1
Hct 26 - 35         1.5
Hct 16 - 25         2
Hct < 15             2.5


Reticulocyte Production Index =  (Corrected Reticulocyte Count) / Maturation Factor

Once again:
-Reticulocyte Count is usually reported as a percentage
- In calculations using the "retic count", if it's 5%, use "5" and not "0.05"
-Corrected Reticulocyte Count can also be known as the Reticulocyte Index
-Reticulocyte Production Index can also be known as Reticulocyte Index

From Wiki:

• The reticulocyte index (RI) should be between 1.0% and 2.0% for a healthy individual.
• RI < 2% with anemia indicates loss of red blood cells, but decreased production of reticulocytes (ie, and inadequate response to correct the anemia) and therefore red blood cells.^[2]
• RI > 3% with anemia indicates loss of red blood cells (from causes such as destruction, bleeding, etc.), with an increased compensatory production of reticulocytes to replace the lost red blood cells.^[2]

Improving Outcomes in Acute Stroke

Two articles on management strategies in Acute Stroke and their affect on outcomes:

Processes in Acute Stroke, JAMA, 2010
Mannitol in Acute Stroke, Cochrane, 2009

After reading, should be able to answer the following questions:

What processes of care improve outcomes in acute stroke? (3)
Is mannitol indicated in the treatment of brain edema in the setting of acute stroke?


Bonus:

Read this:

Preventing VTE in Stroke, 2005

What may be the number one cause of mortality in the acute period post-stroke?


Answers

Rheumatoid Arthritis - Essentials

What are the diagnostic criteria for RA?
What's the most specific lab test for RA?
What is the treatment for RA? (3 parts)
What are the 4 DMARDs (1 is a group)?

Answers

Appropriate Hypercoagulable Testing

EFFECTS OF ANTICOAGULANT THERAPY ON HYPERCOAGULABLE TESTING
AND OTHER ISSUES AFFECTING RESULTS from Institute of Transfusion Medicine, by Irina Chibisov, MD. 2012.

SUMMARY
Many factors interfere with results and interpretation of hypercoagulable studies. When possible, hypercoagulable testing should be done outside of an acute event, including thrombosis, infection, inflammation, and most definitely prior to the initiation of anticoagulation therapy.

Factor V and prothrombin DNA testing is fairly definitive.  Test results for protein S, C, and antithrombin III deficiencies are more difficult to interpret as environmental factors can influence the results. Clinical and family history should always be used to aid in testing interpretation. It is important to rule out acquired protein S, C, and antithrombin III deficiency prior to establishing a diagnosis.

Treatment with Coumadin can interfere with protein C and S testing. Ideally, Coumadin use should be held for two weeks prior to undergoing these tests. Alternatively, heparin use can replace the Coumadin during that time frame. Acquired protein S deficiency is quite common, frequently caused by factors such as pregnancy, liver disease, inflammatory conditions, and thromboembolism.

Acquired antithrombin deficiency can result from mild liver disease, acute thrombosis, nephrotic syndrome, and heparin anticoagulant therapy. Protein S assays are not reliable during pregnancy and heparin therapy can result in a false positive antithrombin III test result; but, antithithrombin III can be checked on Coumadin.

It is always important to remember that protein C, S, and antithrombin III congenital deficiencies are rare and should be suspected in strongly thrombophilic patients: i.e., those with a venous thromboembolism prior to age 50, recurrent venous thromboembolism, or with an extensive family history of thrombosis. When results are borderline, repeat testing and comparative studies of other family members can be appropriate.

Finally, direct thrombin inhibitors cause significant interference with all functional coagulation assays and hypercoagulable testing should not be ordered inpatients on these agents.

INCOMPLETE - needs to be edited to be more blog-friendly & clinically applicable. Case?

Tuberculosis

Comprehensive review article on tuberculosis from NEJM by Zumla et al, 2013.

Related: An article from Journal of ID, Metcalfe, et al. 2011, re: the use of inteferon-gamma release assays in diagnosis of active pulmonary TB.

CME Questions for this article from the NEJM website:

1. Risk of developing active TB among pt's with latent infection?
2. Which is true re: diagnosis of latent or active TB?
1. TB skin test is as specific as interferon-gamma release assay but less sensitive in diagnosing latent TB. 
2. solid culture medium is the standard for diagnosis of active TB. 
3. interferon gamma release assays are useful in the diagnosis of active TB. 
4. the Xpert MTB/RIF assay test is more sensitive than smear microscopy. 
3. Which is true re: HIV & TB coinfection?
1. Early ART therapy has no effect on mortality. 
2. Early ART therapy improves outcomes in pts with TB meningitis. 
3. IRIS occurs in at least 10% of HIV-infected patients who start ART during TB treatment. 
4. The most common manifestation of IRIS is a maculopapular rash.