The purpose of this case study is to demonstrate how medical algorithms can be integrated into the clinical decision making process when a patient presents with hereditary hemolytic anemia. Throughout the discussion, relevant medical algorithms are presented which can aid the physician while evaluating and diagnosing the patient.
Case: Woman with Hereditary Hemolytic Anemia
Betty is an 81-year old retired secretary. Her daughter brought her to the Emergency Department because of weakness, cough, and chest pain. She was found to have moderate anemia with macrocytosis. Chest x-ray and EKG were within normal limits. She stated that everyone in her family had a hemolytic anemia. She had had several episodes herself over the years, sometimes triggered by an infection although she could not remember the details. The emergency department physician was not comfortable sending her home and suspected there may be another underlying problem. Betty was subsequently admitted for observation to the hospitalist service.
Laboratory tests indicated normal vitamin B12 and folate levels. Examination of the peripheral blood smear showed increased stomatocytes and no spherocytes or schistocytes. In light of the family history of hemolytic anemia a diagnosis of hereditary stomatocytosis was made.
Because of the unexplained macrocytosis the hospitalist wondered if the patient might also have myelodysplasia. A complete hematology workup was ordered including flow cytometry on the peripheral blood. This showed a small population of monocloncal CD5-positive lymphocytes consistent with very early chronic lymphocytic leukemia.
Workup of Anemia
There are many possible causes of anemia. Several strategies are used to establish a diagnosis. A common approach is to consider red blood cell indices such as mean cell volume (MCV) and red blood cell distribution width (RDW).
- Classification for Anemia Based on MCV and RDW
Hereditary Stomatocytosis
Hereditary stomatocytosis represents a group of disorders associated with defects in the outer membrane of red blood cells. This defect allows leakage of cations across the membranes and increased fragility, the latter leading to a hemolytic anemia. The fact that everyone in the patient’s family had a hemolytic anemia indicates autosomal dominant inheritance.
In stomatocytosis the number of stomatocytes may vary in number, especially after a hemolytic episode. It is not uncommon for a patient to be misdiagnosed with hereditary spherocytosis or another type of hemolytic anemia.
- Microangiopathic Hemolytic Anemia
The tests required to confirm the diagnosis are not available in many hospitals. These involve measurements of red blood cell fragility and structural proteins. If testing is done it is important NOT to send a blood sample collected after the patient has been transfused since the donor’s blood may end up being tested rather than the patient’s.
There are several reasons why recognition of hereditary stomatocytosis is important. The most important is the risk for thrombosis after surgery, especially splenectomy.
Other problems include:
- Pseudohyperkalemia (with in-vitro leakage of potassium out of red blood cells when the sample is stored)
- Transient neonatal hydrops or ascites
Myelodysplastic Syndrome (MDS) and Chronic Lymphocytic Leukemia (CLL)
In an older adult the possibility of myelodysplasia should be considered when there are unexplained abnormalities in myeloid, erythroid, or platelet elements. One presentation is a macrocytic anemia not explained by vitamin B12 or folate deficiency. In this case the increased mean cell volume (MCV) was due to swelling caused by “overhydration” associated with the membrane defect.
Chronic lymphocytic leukemia (CLL) is another condition that is relatively common in the elderly. It is estimated that there are over 14,000 new cases each year.
It may present in several ways. Sometimes it develops slowly over months or years with a low-grade atypical lymphocytosis that can only be diagnosed by flow cytometry.
- International Prognostic Scoring System (IPSS) to Predict Survival in the Myelodysplastic Syndromes
- Rai Staging System for Chronic Lymphocytic Leukemia (CLL)
- Model for Time to First Treatment in a Patient with Chronic Lymphocytic Leukemia (CLL)
Take Home Points
- Hereditary defects of the red cell membrane are uncommon and can be easily missed. Most clinicians do not have experience diagnosing these rare conditions or with managing these patients.
- Algorithms that can help to recognize uncommon conditions can improve patient care.
- Examination of the peripheral blood smear may not be done routinely in many hospitals or institutions. This is often because of the cost and time to complete such a test. It can be a valuable tool in the evaluation of a patient with unexplained anemia and should be done before more expensive tests are ordered.
- Older adults are at risk for several hematologic disorders. Occasionally a patient can have more than one problem. Using medical algorithms can reduce the risk for premature closure of a clinical case by overlooking other concomitant conditions.
The algorithms in this case and thousands more are available online at www.MedicalAlgorithms.com
About the Authors
Dr. Chad Rudnick, MD, FAAP is a board-certified pediatrician in Boca Raton, FL. He is the Medical Director of The Medical Algorithms Company. A proponent of incorporating medical technology into his practice, Dr. Rudnick uses telemedicine and medical algorithms from The Medical Algorithms Company in his daily practice to better serve his patients and their families. An accomplished medical writer, he maintains a popular pediatric blog, All Things Pediatric, and has written for numerous online and print publications including KevinMD.com.
John Svirbely, MD is a founder and Chief Medical Officer of The Medical Algorithms Company and the primary author of its medical algorithms. John is a co-founder of the Medical Algorithms Project and has developed its medical content for nearly 20 years. He has a BA degree from the Johns Hopkins University and his MD from the University of Maryland. He is a board-certified pathologist with a fellowship in medical microbiology and biomedical computing at Ohio State University. Currently he is in private practice in Cincinnati, Ohio. He has authored multiple books and articles on medical algorithms.