CADs Having Trouble with RBC/CBC Blood Testing
As a person living with Cold Agglutinin Disease (CAD), you may eventually encounter a disconnect between standard blood testing procedures used by professional laboratories and the specific specimen-handling requirements needed for accurate testing in some CAD patients.
This disconnect can lead to disagreement or confusion—even with your own physician—particularly if they are unfamiliar with CAD or have never encountered a patient whose blood agglutinates (red blood cells clump together) enough to interfere with standard CBC/RBC testing protocols.
In general, the more cold-sensitive or cold-reactive a CAD patient becomes, the more frequently these testing conflicts arise.
Many physicians and blood testing facilities have never encountered a CAD patient who has progressed through different levels of cold sensitivity. As a result, they may not realize that specimen-handling requirements can change over time. Or even be necessary
Link to Printable Phlebotomist – Lab advisory.
Why increasing cold sensitivity affects blood testing
Cold sensitivity in CAD is not always static. Over time, some patients become reactive at temperatures that previously caused no issues. “Reactive” may include visible symptoms, but it also includes non-visible activity in the blood such as agglutination and hemolysis (destruction of red blood cells).
Hemolysis can occur without the patient feeling cold, experiencing pain, or noticing any outward symptoms. In CAD, these reactions often occur silently at the cellular level.
A CAD patient’s primary defense against hemolysis is maintaining warmth consistently—before symptoms appear.
Waiting until you “feel cold” or see physical signs may already be too late.
We describe below what many CAD patients refer to informally as “stages.”
Some CAD patients remain mildly cold-sensitive and may experience few or no noticeable symptoms.
In these cases, CAD may first be suspected only after abnormal blood test findings.
This scenario is reported less often in support communities, likely because those with more severe symptoms are more actively seeking information.
This page focuses on CBC/RBC testing failures
This article specifically addresses situations in which CBC/RBC blood tests fail to result correctly
or begin producing inconsistent or unreliable values in CAD patients.
One early warning sign is when laboratories report the need to reheat a specimen in order to run the CBC/RBC, yet results remain inconsistent or “hit and miss.”
Most other routine blood tests are not affected.
Some tests that may fail when “Keep it Warm” techniques are not followed include the following.
This varies by individual CAD patient.
A complete list of Tests that may be impacted – With additional information
This article is not about CAD treatment or overall disease severity. It is about the practical challenge of obtaining accurate CBC/RBC results when cold agglutination interferes with testing.
If you are newly diagnosed, you may also want to visit:
I was just informed I have CAD. Now what?
About the use of the term “stages” some CADs may refer to.
The word “stage” only a practical label to describe differences in CBC/RBC testing requirements. It is not an official medical term and does not describe disease progression.
To our knowledge, there is no official medical term that defines this testing scenario or categorization.
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[Originally posted 2019 — no documented contradiction has been provided to date.]
We use the dictionary definition of “stage”:
A single step or degree in a process; a particular phase or position in a sequence.
STAGE = our label to explain changes in CBC/RBC testing requirements
STAGE 1 (Level 1 Testing – Standard Protocol
Standard protocol works and is accurate consistently
In Stage 1, standard blood draw and lab processing methods produce reliable CBC/RBC results.
Specimens may be drawn at satellite facilities, shipped, and processed later without special handling.
Lab notes may mention agglutination, but results are still accurate.
STAGE 2 – Level 2 Testing Method
Standard Protocol does not result accurately/consistently
“Keep it Warm” techniques required but work/are accurate consistently
In Stage 2, standard protocols begin failing frequently.
Specimens must be pre-warmed, kept warm continuously, and processed STAT (immediately)—ideally near body temperature (98.6°F / 37°C).
Written instructions from a hematologist are strongly recommended.
Satellite collection and delayed processing often fail at this stage.
STAGE 3 – Level 3 Testing Method
Plasma / Saline Replacement required
Stage 3 is rare. In these patients, even “Keep it Warm” techniques fail, and a non-standard laboratory process is required.
PLASMA REPLACEMENT TECHNIQUE
To print only the protocol below:
PRINTABLE FORM ONLY
Date 11/19/16
Subject: Strong Cold Agglutinin for (omitted patient name)
The CBC for (omitted patient name)
will require special handling. Tube must be prewarmed using infant heel warmers and tube needs to be kept warm after
collection and delivery straight to the lab.
Heme tech: Put CBC tube in 37 degree heat block. Have blood Bank put saline in 37 degree water bath for 1 hour.
Perform plasma replacement technique on separate CBC tube with prewarmed saline.
Return to CBC tube to 37 degree heat block for 1 hour.
Run well mixed tube on hematology analyzer in manual mode, do not allow results to autoverify.
Report results with documentation of steps taken.
Report whether hemolysis is observed in the supernatant while processing.
A copy of these written instructions must accompany tube to lab department.
Thank you
(Omitted Lab Manager Name & Facility)
