Fredrick L. Kiechle, MD, PhD
Q. In the “Q&A” column published in December 2006, Steven H. Kroft, MD, discussed the diurnal biological coefficient of variation in the MCV in healthy individuals. I would like to know what the diurnal biological coefficients are of the MCH and MCHC. We are evaluating our delta checks because we have far too many. We would like to have delta checks only on the MCV, MCH, and MCHC, based on the diurnal biological coefficients.
A. As Dr. Kroft noted in his excellent discussion, it is best to use delta checks with analytes that exhibit little diurnal variation when looking for specimen compromise. The MCV is the analyte best suited to this purpose in the complete blood count, as it shows little change over 24 hours. As Dr. Kroft noted, the diurnal biological coefficient of variation in the MCV in healthy individuals is only 0.5 percent, as reported in one article.1 Since this is typically a measured analyte with a low coefficient of variation, there is little analytic variability to account for changes in this measurement on a day-to-day basis. It has been postulated that small changes in the MCV may reflect changes in plasma osmolarity, in the absence of transfusion or hemolysis.1
Other erythrocyte attributes that are typically measured directly include RBC and hemoglobin. The diurnal coefficient of variation in these analytes is higher (3.5 percent and three percent, respectively), being influenced by additional biologic variables such as bleeding, transfusion, hematopoietic activity, hemolysis, and hydration status.1 The MCHC and MCH are both calculated from a combination of these measured analytes. The MCHC = (hemoglobin/HCT) x 10, in which the hematocrit = MCV x RBC; and the MCH = (hemoglobin/RBC) x 10. In general, however, the measured analytes used in these equations tend to influence these measurements in the same direction and with a similar approximate magnitude. Thus, the diurnal changes in the MCH and MCHC appear to be small, similar to the MCV,1 possibly because these variables tend to negate each other in the calculation. Unfortunately, the article Dr. Kroft cited does not give the diurnal variation of these analytes,1 but these variations could be calculated in your own laboratory using methods similar to those described in the paper, if you have the interest and available volunteers.
In a different approach to the subject of actionable criteria for review of automated CBCs, the International Consensus Group for Hematology Review published a statement in which it briefly discusses delta checks.2 Although it does not recommend specific delta checks for hematology parameters, suggesting that individual laboratories determine these values for themselves, the group proposes using delta check failures only as a secondary criterion for review of automated CBCs and WBC differentials, and for three parameters only: WBC, platelets, and MCV.
1. Jones AR, Twedt D, Swaim W, et al. Diurnal change of blood count analytes in normal subjects. Am J Clin Pathol. 1996;106:723–727.
2. Barnes RW, McFadden SL, Machin SJ, et al. The International Consensus Group for Hematology Review: Suggested criteria for action following automated CBC and WBC differential analysis. Lab Hematol. 2005;11:83–90.
Katherine A. Galagan, MD
Director of Clinical Laboratories
Virginia Mason Medical Center
Q. How does Schistosoma haematobium cause proteinuria? What is the etiology and clinical manifestation of S. haematobium disease? How does the United States hope to help developing countries cope with this disease?
A. Proteinuria is a general condition indicating the excess of protein in the urine. This can be seen in infectious as well as noninfectious (for example, diabetes) causes. For S. haematobium, it has been suggested that the worm and egg burden within the human host, along with the migration of the eggs through the bladder wall to be excreted in the urine, causes renal damage. A consequence of this can be bleeding and the release of proteins in the urine. This has been shown in the hamster animal model.1 Various articles have been published describing the sensitivity of and predictive values for the presence of proteinuria as a predictor of S. haematobium disease.2, 3
The etiology of schistosomiasis, or bilharziasis, is namely five species (S. haematobium, S. mansoni, S. japonicum, S. mekongi, and S. intercalatum). S. haematobium causes urinary schistosomiasis. Free-swimming cercariae are released from their intermediate host (snail) and penetrate human skin. Infections are usually acquired in contaminated water. The penetrating cercariae then enter the circulation, mature to adulthood in the blood, and reside in the blood vessels around the urinary bladder. After male and female worms mate, eggs are produced and work their way through the bladder wall to eventually be excreted in the urine. These eggs are fully embryonated when they leave the human host. The miracidia mature when released from the egg in water. A suitable snail host is found, and the cycle starts again.
The accumulation of eggs in the bladder wall can lead to significant pathology. Symptoms can include hematuria, proteinuria, and difficulty with micturition. Infections with S. haematobium are thought to be a predisposing factor for the development of squamous cell carcinoma of the bladder.
Laboratory diagnosis involves the examination of urine for S. haematobium eggs. However, the eggs can also be found in stool. The sensitivity of egg examination can be maximized during the time of day when egg excretion occurs (usually between 10 AM and 2 PM). Sedimentation and filtration of the urine may also improve the diagnostic yield.
Schistosomiasis in general is second only to malaria in public health importance.4 About 200 million people worldwide are infected, and 20,000 deaths are associated with the severe consequences of infection. The presence of control programs and socioeconomic development has eliminated schistosomiasis in some parts of the world. However, other parts of the world have not seen this type of successful eradication.
Vaccine experimentation has been performed in animal models, but the results have been mixed depending on the schistosomal antigen used. Phase I and II clinical trials with a S. haematobium vaccine developed by Institut Pasteur de Lille (France) was shown to be safe and have good immunogenicity in human volunteers. The Schistosomiasis Vaccine Development Programme, supported by USAID (U.S. Agency for International Development), has looked at antigens from S. mansoni. Scientists are looking at perhaps a cocktail of antigens to be used in a potential vaccine in the hopes that this will increase the effectiveness of the vaccine.
1. Brouwer KC, Munatsi A, Ndhlovu PD, et al. Urinary schistosomiasis in Zimbabwean school children: predictors of morbidity. Afr Health Sci. 2004;4(2):115–118.
2. Murare HM, Taylor P. Haematuria and proteinuria during Schistosoma haematobium infection: relationship to intensity of infection and the value of chemical reagent strips for pre- and post-treatment diagnosis. Trans R Soc Trop Med Hyg. 1987;81(3):426–430.
3. Hammad TA, Gabar NS, Talaat MM, et al. Hematuria and proteinuria as predictors of Schistosoma haematobium infection. Am J Trop Med Hyg. 1997;57(3):363–367.
Rodney C. Arcenas, PhD, D(ABMM) Clinical Scientist –
Pathology Consultants of South Broward
Memorial Healthcare System
Q. My questions are about the critical absolute neutrophil count, which is <0.5 x 109/L in our facility. Is the value the same for pediatric and adult? Since band is neutrophil, is it counted as part of the total absolute neutrophil count?
A. The definition of neutropenia is age- and race-related. The reference range for an absolute neutrophil count in infants greater than one year of age through adulthood is 1,500 to 7,000 µL. For neonates and infants, the lower limit is 2,500 µL. Studies have demonstrated that black children and some healthy adults have a lower limit of the absolute neutrophil count in the 1,000 to 1,500/µL range.
For all ages except infants, absolute neutropenia is classified as mild: 1,000 to 1,500/µL, moderate: 500 to 1,000/µL, and severe: <500/µL. If your facility’s medical staff have decided on the absolute neutrophil count critical value of <500/µL, this can be used for all patients greater than one year of age.
When a manual differential is performed, the total of segmented and band neutrophils is combined to give the absolute neutrophil count.
Nathan DG, Orkin SH, Ginsburg A, Look T. Hematology of Infancy and Childhood. 6th ed. Philadelphia, Pa.: WB Saunders; 2003.
Deb Perry, MD
Department of Pathology
Children’s Hospital and
Member, CAP Point of Care
Dr. Kiechle is medical director of clinical pathology, Memorial Healthcare, Hollywood, Fla.