A Special Lab Week

We are currently in the middle of Lab Week 2020.  Medical Laboratory Professionals Week is an annual week-long celebration of the professionals who work in our nation’s laboratories.  In normal years, we come together for social events, meals, games and contests, etc.  This is not a normal year.

While our celebration this week is mostly virtual, our gratitude is not.  We are so blessed to work with some of the finest professionals a hospital, city, state, and country could hope for.  When the news reports the daily tally of new COVID cases, please take a moment to remember that behind each of those tests is a huge team dedicated to ensuring the quality and accuracy of that result.  And not just COVID results – our laboratories do millions of other tests every year.

Our colleagues work behind the scenes, but as we like to say about the medical profession:  “Without the laboratory, you’re only guessing.”

Tissue Adequacy

The issue of “how much tissue is enough” for various ancillary testing often comes up, especially in the realm of cancer diagnostics.  The amount of tissue a pathologist needs to make a diagnosis varies, but quite a bit more tissue is necessary for molecular testing.  As we continue to move into the era of targeted therapeutics (that is, medicines that are active against tumors which express certain genes or proteins, but not active against tumors which don’t express those genes or proteins), pathologists find ourselves asking our clinical colleagues for more and more tissue.

In general, core needle biopsies are superior to fine needle aspirations for the purpose of obtaining sufficient tissue for molecular studies (Am J Clin Pathol. 2015 Feb;143(2):193-200), and larger bore FNA needles are also superior to smaller FNA needles (J Bronchology Interv Pulmonol. 2018 Dec 14.), although much depends on the skill of the proceduralist.  Adequacy assessment at the time of biopsy by a trained cytotechnologist or pathologist improves yield (Archives of Pathology & Laboratory Medicine 2016 140:11,1191-1199) by giving the proceduralist the opportunity to collect more tumor immediately.

However, even when enough tissue has been obtained initially, sometimes making the diagnosis of cancer requires the use of some of that tissue.  If the diagnostic workup is extensive, little tissue may be left over for molecular studies.

How much tissue is “enough”?  Well, for IHC or FISH studies (like PDL-1 or ALK, respectively), as little as a square millimeter of tissue is usually necessary.  However, for PCR-based molecular tests, tumor must be dissected out of paraffin blocks, requiring much more tissue –  technically, at least 5 ng of tumor DNA or 1000 cells (Arch Pathol Lab Med. 2016;140(11):1191–1199).  However, the tumor needs to be as free of normal tissue as possible to ensure that only the cancer is tested (testing normal tissue will potentially result in false-negatives).  In addition, various other factors can interfere with the analysis (like necrosis).  Combined with the necessity of having enough tissue for diagnostic purposes, these factors have led some to recommend up to four separate cores and 2 cm of tissue.

Please contact us if you have any questions about tissue adequacy before or after procedures.

Patient Blood Management at PHC

Dr. Dean Joelson has been named Medical Director of the Piedmont Healthcare Patient Blood Management Program.  He has been and will be working closely with PHC’s new Transfusion Safety Officer and medical staff at all Piedmont Hospitals to ensure our patients have the highest quality of care in the arena of Transfusion Medicine.

So what is patient blood management?  The idea behind it is simple: it’s a patient-centered approach designed to maximize the amount of a patient’s own blood flowing within him/her and minimize the amount of other people’s blood flowing within him/her.

Blood transfusions have been linked with worse patient outcomes, including increased hospital-acquired infections, increased length of stay within the hospital, and increased mortality.  The reason behind these poorer outcomes is that a blood transfusion is, quite simply, a liquid organ transplant.  Sometimes, of course, we are willing to accept these risks in order to save an anemic or bleeding patient’s life.

But as we gain more knowledge about human physiology, we have begun to learn that most patients can tolerate quite a bit of anemia, and that it’s often safer to allow them to recover on their own than to transfuse them someone else’s blood.  So we strive to ensure that every transfusion is absolutely necessary.

Because patient blood management is about the patient.

Thromboelastograph Hemostasis Testing at PAH now 24/7

The hematology laboratory at Piedmont Atlanta Hospital is excited to now be offering Thromboelastograph (TEG) Hemostasis testing 24 hours a day/7 days a week.  TEG is a diagnostic testing modality that provides comprehensive whole blood hemostasis testing to facilitate the assessment of bleeding and thrombotic risk, as well as to monitor antithrombolitic therapy. By providing a more complete picture of your patients’ hemostasis, TEG can help you understand their hemorrhagic or thrombotic risk to deliver more targeted therapy. By expanding testing hours we hope to provide a more accurate “real-time” assessment of your patients’ hemostatic state to properly target therapies and decrease unnecessary blood product usage.

For any questions regarding TEG or other testing provided by the hematology department, please contact Dr. Katherine Chandler, consulting pathologist for PAH hematology laboratory at (404)605-3247.  The main laboratory at PAH can be reached at 404-605-3300.

– Katherine L. Chandler, M.D., Hematology Consulting Pathologist PAH

A patient’s own blood is best

Blood can save lives, but blood transfusions are also inherently dangerous. Remember: a blood transfusion is an organ transplant. A recent JAMA study showed that each unit of transfused blood increased patient mortality by 1.2%.1 The effect was dose dependent. Other studies have shown worse early, mid-term, and long-term outcomes related to transfusion. The most effective and safest blood management strategy is preserving the patient’s own blood. View blood transfusion as the option of last resort.

1. JAMA. 2010;304(14):1559-1567.

– Dean W. Joelson, M.D., Chemistry Consulting Pathologist at PAH

Frozen sections – A Primer

Frozen section is the main form of intraoperative consultation in which the surgeon sends tissue to the pathologist during the operation for rapid diagnosis in order to make immediate management decisions and to triage tissue for different studies. Other forms of intraoperative consultation include gross examination and smear preparations.  Most commonly, frozen section is used during oncological surgery or when tumor is suspected.

Due to the rapidity and nature of the freezing process, there are numerous artifacts that limit interpretation of the tissue, including lack of cellular or nuclear detail, tears or missing tissue, or ice crystals in certain tissues.  Therefore, frozen section is not a substitute for definitive diagnosis, and the expectations are lesser. The information provided to the surgeon may consist of:

  • just the adequacy of the specimen
  • whether the lesion is benign or malignant
  • the status of a margin
  • or the general category of tumor such as whether a neoplasm is carcinoma, whereby a surgeon may proceed with definitive surgery, or lymphoma in which additional surgery is suspended and the final classification rests upon further studies.

Nevertheless, frozen section diagnosis accuracy rates can be expected to be above 90%, except in certain cases, such as mucinous neoplasms of the ovary, in which reported rates are in the range of 60% due to inherent sampling issues. Frozen sections are distinguished from permanent sections, the latter of which are produced after extensive tissue processing (usually overnight) and are considered the gold standard of microscopy-based tissue evaluation.

The process begins with alerting the Pathology Gross Room of an impending frozen section and immediate delivery of the specimen by either OR personnel or the pneumatic tube system. The College of American Pathologists (CAP) turn-around-time guideline is 20 minutes from the time the specimen is received in the laboratory to the time the diagnosis is reported to the surgeon. The turn-around time for single, small biopsies is often faster than 20 minutes. However, in complex cases, when inking or dissection of the specimen is needed, when multiple sections are required, or when concurrent frozen sections are requested, the turn-around time can be longer than 20 minutes. The frozen section diagnosis is incorporated into the final surgical pathology report with resolution of any discrepancies.

Tips for successful Frozen Section consultation:

1)  Effective communication:  Clinicians should convey pertinent clinical history, especially prior cancer history, preoperative diagnoses, radiological findings, and precise anatomic location; they should also clarify the management algorithm when appropriate; finally, they should ask questions when the diagnosis is not clear or does not correlate with clinical impressions.

2) Sampling:  Unfixed (i.e. “fresh” and not in formalin) tissue should be sent. Bone or tissue with extensive calcifications cannot be frozen and cut, and fat is very difficult to cut. The pathologist may need additional tissue if the original sample is inadequate.

3) Unnecessary frozen sections, in which the diagnosis does not modify immediate intraoperative management, should NOT be requested, as it may compromise the pathologist’s ability to make a diagnosis on permanent sections.

4) Some frozen section diagnoses may need to be deferred.

5) Among pathologists, consultation with colleagues is encouraged.

6) Some requests for frozen section may not be honored, as in the case of melanoma, since the integrity of the tissue sample for final diagnosis is the paramount responsibility of the pathologist.

– Jeanette D. Cheng, M.D., Consulting Pathologist for the Anatomic Pathology Laboratory at PAH

Massive transfusion protocol (MTP) vs Emergency release of Blood

Both massive transfusion protocol (MTP) and Emergency Release are orders for the blood bank to release blood immediately.

  • A type/screen or type/cross is not needed to release blood products.
  • A type/cross specimen should be sent ASAP so that type specific products can be dispensed.
Massive transfusion protocol (MTP)  

Emergency Release

 

Call the blood bank to let them know MTP has been activated. Call the blood bank to let them know you need emergency released uncrossmatched blood products.
Products to be released areFIXED. You will get two O neg units of RBCs immediately.
You CANNOT customize order or change it. Products can be CUSTOMIZED, so you need to specify which products you want and how much.
Red cells, FFP, platelets or cryo are typically released in a 1:1:1 ratio, every 30 minutes.  
Call the blood bank to de-activate MTP so that products are not wasted.

– Tamela M. Snyder, M.D., Blood Bank Consulting Pathologist at PAH

Cold Agglutinin Recognition – Avoid Hypothermia

Cold agglutinins are autoantibodies that cause agglutination of red blood cells at colder temperatures.  Therefore, cold agglutinins are important to recognize in patients who receive intentional hypothermia.  Typical therapeutic uses of hypothermia include cold cardioplegia during cardiovascular surgery and in cases following cardiac arrest for neurologic stabilization. Hypothermia in patients with cold agglutinins may cause severe, life threatening complications due to hemolysis and microvascular occlusion. Some of the most commonly reported complications include acrocyanosis, stroke, and death.

The patient’s history may reveal cold intolerance and acrocyanosis. A focused review of systems could ask screening questions such as “How does cold weather affect your fingers?” Clues to recognition on physical exam are non-specific and include pallor, jaundice, lymphadenopathy, and hepatosplenomegaly.

Classic laboratory findings typically reveal an abnormal CBC with MCHC > 36, often with a comment attached to the report describing the presence of a probable cold agglutinin. Hemoglobinuria may be present. Routine Blood Bank Type and Screen testing may also alert to the presence of a cold autoantibody.

The clinical significance of these antibodies depends on their etiology and strength, although most cold agglutinins detected in the laboratory have little to no clinical significance. Healthy adults may have naturally occurring cold agglutinins in low concentrations. Pathologic cold agglutinins may be idiopathic, acutely present in the recovery phase of infections (Mycoplasma, mononucleosis, CMV), or occur in the setting of a B-cell lymphoproliferative disease. Strength and reactivity are dependent on antibody concentration (titer) as well as the temperature in which agglutination occurs, known as the thermal amplitude.

Whenever a cold agglutinin is suspected, a confirmatory cold agglutinin test can be ordered. Patients should be referred to a Hematologist, when indicated, and educated on the importance of cold avoidance.  Pathologists are also available to answer specific questions about cold agglutinins detected within the laboratory.

– Dr. Bruce Walker, Medical Director at PAH