Neonatal and geriatric assessment of hematological parameters

ABSTRACT

OBJECTIVE: This work aims at highlighting the hematological variables of these groups (neonates and elderly) and call for the hematological values at all the different stages of these groups.

METHOD: Consultation of different scientific presentation were made and relevant information were retrieved.

CONCLUSION: Hematological changes are obvious in both the neonates and the elderly persons and at such, different hematological variables must be implemented in various developing stages of the neonates as well as the different classes of aged elderly individuals. Also among the elderly, certain hematological disorders are more dominants and clinicians should be attentive to this.

KEYWORDS: Hematology, Parameters, Neonates, Elderly

Corresponding Author: Peter Ubah Okeke

Student, School of Science & Engineering,

Atlantic International University, Honolulu- Hawaii

www.aiu.edu

Term paper

INTRODUCTION TO NEONATAL HEMATOPOIESIS

The newborn infant, older child and adults all exhibit profound hematologic differences. Because children mature at different rates, it is inappropriate to use adult reference ranges for the assessment of pediatric blood values. Pediatric hematology has emerged as a specialized science with age- specific reference ranges that correlate the hematopoietic, immunologic and chemical changes of a developing child.

Hematopoiesis, the formation and development of blood cells from stem cells begins in the first weeks of embryonic development and proceeds systematically through three phases of development; Mesoblastic (yolk sac), Hepatic ( liver), and myeloid (bone marrow). The cells produced in the developing embryo are primitive erythroblasts formed in the yolk sac. These cells are particularly interesting because they do not develop into mature erythrocytes. They are erythropoietin insensitive and have the ability to differentiate into other cell lines on exposure to appropriate growth factors Christensen R D (1989).

By the second month of gestation, hematopoiesis ceases in the yolk sac and the liver becomes the centre for hematopoiesis, reaching its peak activity during the third and fourth gestational months. Leukocytes of each cell type systematically make their appearance. In week 9 of gestation, lymphocytes can be detected in the region of the thymus. They are subsequently found in the spleen and lymph nodes. During the fourth and fifth gestational months, the bone marrow emerges as major site of blood cell production and it becomes the major site by birth Forestier F et al (1995).

Hematopoietically active bone marrow is referred to as red marrow, as opposed to inactive yellow (fatty) marrow. At the time of birth, the bone marrow is fully active and extremely cellular with all hematopoietic cell lineages undergoing cellular differentiation and amplification. In addition to the mature cells in fetal blood, there are significant numbers of circulating progenitor cells in cord blood Linch et al (1982)

In a full term infant, hepatic hematopoiesis has ceased except in widely scattered small foci that become inactive soon after birth Hann et al (1983). Postembryonic extramedullary hematopoiesis is abnormal in a full term infant. In a premature infant, foci of hematopoiesis are frequently seen in the liver and occasionally observed in the spleen, lymph nodes or thymus Yoder et al (2002)

Different neonatal developmental stages

Pediatric hematologic values change markedly in the first weeks and months of life. As a result, many variables influence the interpretation of what might be considered normal values at the time of birth. It is important to provide age appropriate pediatric hematologic values that span from neonatal life through adolescence. The pediatric population can be divided into three different developmental groups;

• 1. The neonatal period, which represents the first four weeks of life.

• 2. Infancy, which incorporates the first year of life.

• 3. Childhood, which spans form age 1 to puberty (8 to 12 years).

The RBC count increases during the first 24 hours of life, remains at this plateau for about 2 weeks and then slowly declines. This elevation may be explained by the partial in utero anoxia that becomes more progressive as the fetus grows. Anoxia, the trigger for increased secretion of erythropoietin, stimulates erythropoiesis Zaizov & Matoth (1976). At birth, the physiologic environment changes and the fetus makes the transition from its placenta- dependent oxygenation to the increased tissue oxygenation of the lungs. After this brisk elevation, there is a continuous decline in the number of RBCs. The mechanism may be a decrease in the secretion of erythropoietin Pahal et al (2000). Studies show erythropoietin levels before birth equal to or greater than adult levels with gradual drops to near zero a few weeks after birth Christensen et al (2000). This corresponds with the physiologic anemia seen at 5 to 8 weeks of life. The span of erythrocytes in full term infants is shorter than that of adult erythrocytes; the life span of RBCs in premature infants is considerably shorter. The more immature the infant is, the greater the degree of reduction.

Erythrocyte morphology at birth

Segal & Palis (2006) reported that early normoblasts are megaloblastic, hypochromic and irregulary shaped. During hepatic hematopoiesis, normoblasts are smaller than the megaloblasts of the yolk sac but are still macrocytic. Erythrocyte morphology remains macrocytic from the first 11 weeks of gestation until day five of post natal life, Soldin et al (2005).The macrocytic RBC morphology gradually changes to the characteristic normocytic normochromic morphology. Orthochromic normoblasts frequently are observed in the full term infant on the first day of life but disappear within post natal days three to five. Nucleated RBC may persist longer than a week in immature infants. The presence of nucleated RBCs for more than five days suggests hemolysis, hypoxic stress or acute infections Luchtman- Jones et al (2006).

Reticulocytes

An apparent reticulocytosis exists during gestation decreasing from 90% reticulocytes at 12 weeks gestation. Reticulocytosis persists for about 3 days after birth then declines abruptly to 0.8% on postnatal days 4 to 7. At 2 months, the number of reticulocytes increases slightly followed by a slight decline from 3 months to 2 years, when adult levels are attained Thomas et al (1983).

Anemia of the neonates

The hemoglobin(Hb) concentration of term infants decreases during the first 5 to 8 weeks of life a condition called physiologic anemia of infancy. Infants born prematurely also experience a decrease in Hb concentration which is termed physiologic anemia of prematurity Cavaliere T A (2004). Additionally, the fetal RBC has a shorter life span than normal erythrocytes. Studies conducted with chromium labeled newborn RBCs, corrected for the elution rate of chromium from newborn cells estimated a survival time of 60 to 80 days Segal & Palis(2006). This physiologic anemia is not known to be associated with any abnormalities in the infant. The reasons for the shortened life span are unclear. Along with Hb, there is a reduction in the number of RBCs, a decrease in the reticulocytes percentages and undetectable levels of erythropoietin. When the lungs replace the placenta as the source of oxygen, the increased oxygen saturation of the blood may generate a negative feed back response, slowing erythropoietin production Geaghan S M (1999) and erythropoiesis Halvorsen & Finne(1968).

White blood cell and Platelet values of the newborn

Fluctuations in the number of WBCs are common at all ages but are greatest in infants. Leukocytosis is typically at birth for full term and preterm infants alike at the first 12 hours of life Dallman P R (1977). There is an excess of polymorphonuclear Neutrophils, bands and occasional metamyelocytes with no evidence of disease. During the subsequent days the leukocyte count continue to decrease, the trend continues until fourth year. Neutrophilic leukocytes of Term and preterm infants show a greater absolute neutrophil count than of older children, who normally maintain higher lymphocytes.

The platelet count usually ranges from 100 to 400 X 109/L for full term and preterm infants respectively. Low normal platelet counts have been associated with birth trauma. Platelets of newborn show great variation in size and shape. Adult reference ranges are achieved by 6 months of age. Thrombocytopenia in premature infants should be considered abnormal not physiologic Christensen R D (2000).

INTRODUCTION TO THE ELDERLY HEMATOPOIESIS

The life expectancy and quality of life of the elderly have improved dramatically in recent years. Global aging is occurring at a record breaking rate. Although age 65 is considered the mean geriatric age, this number is constantly rising with 122 as the upper limit. The World Health Organization reports that by 2050, one fifth of the global population will be adults 65 years and older (Federal interagency form on aging related statistics-2006).

The elderly can be roughly divided into three age categories according to Zauber & Zauber (1987);

• 1. The young- old age 65 to 74

• 2. The old- old age 74 to 84

• 3. The very old age 85 and older.

The care of the elderly has become a growing trend as the life expectancy of the population continues to increase. Disease and disabilities are not a function of age, although age may be a risk factor for many diseases. With the increase in the aging population, the incidence of age related health conditions also is likely to increase.

Geriatric medicine is a rapidly growing branch of medicine. Inappropriate reference values may lead to unnecessary testing and investigations or more importantly, they may fail to detect a critical underlying disease. A growing concern about the interpretation of hematologic data in context with age is due partly to the tremendous heterogeneity of the aging process and partly to the difficulty in separating the effects of age per se from the effects of occult diseases that accompany aging Chatta & Dale (1996).

Aging process and Hematopoiesis

The aging process is associated with the functional decline of several organ systems, such as cardiovascular, renal, musculo-skeletal, pulmonary and bone marrow reserve. Certain cells lose their ability to divide (example nervous tissue, and muscles) whereas bone marrow and the gastrointestinal mucosa, remain mitotic. Marrow cellularity begins at 80% to 100% in infancy and decreases to about 50% after 30 years, followed by a decline to 30% after age 65 years Lansdorp P M (1997).

Assessment of Hematologic parameters in healthy elderly adults

Erythrocytes

Anemia is frequently found in the elderly. Males characteristically have higher Hb levels than females, owing to the stimulating effects of androgens on erythropoiesis, however the difference narrows with decreasing androgen levels in elderly males Allan & Alexander (1965).

Leukocytes

In the healthy elderly with no underlying pathologic condition, there are no statistically significant differences in the total leukocyte count or WBC differential between old-old compared with middle- aged adults Salive et al (1992).

Lymphocytes

Immune senescence, age –related defects in lymphopoiesis, affects humoral and cellular immunity. The thymus disappears by early middle age and adults depend on T lymphocyte response in the secondary tissue Globerson A (1995). The number of naïve T cells decreases in the elderly, increasing the dependency on memory T cells. T cells of the elderly have impaired responsiveness to mitogens and antigens as a result of a decreased expression of co-stimulator CD28. B lymphocyte function depends on T cell interaction. When T cell inadequacies occur, there may be a decreased ability to generate an antibody response Song et al (1993).

Platelets

The platelet count is not significantly changed with age. There have been reports of increased levels of ß- Thromboglobulin and platelet factor 4 in the a granules and decreased platelet membrane protein kinase C activity Grubeck-Lobenstein B (1997).

Anemia and the elderly

The World Health Organization defines anemia as hemoglobin less than 13 g/dl in males and less than 12g/dl in females. Based on this definition, the prevalence of anemia in males older than 85 years is approximately 44% Smith D (2002). It is unclear however, if the low Hb levels observed in the elderly are due to disease or normal changes related to aging. Most elderly persons maintain a normal blood count and elderly individuals with low Hb levels have an underlying health problem. The variables contributing to anemia are a decrease in bone marrow function, a decline in physical activity, cardiovascular disease and chronic inflammatory disorders. Iron deficiency anemia and anemia of chronic inflammation are the most common causes of anemia in the elderly.

To lesser degree, the elderly are prone to anemias such as sideroblastic, aplastic, hemolytic, myelophthisic or anemia due to protein calorie malnutrition. Hypoproliferation or decreased production of RBCs is a common form of anemia in the elderly. Initially, this form of anemia was called unexplained anemia, senile anemia and anemia of senescence. Hypoproliferative anemia often occurs secondary to iron deficiency, vitamin B12 or folate deficiency, renal failure, hypothyroidism, chronic inflammation or endocrine disease Howe R B (1983). Often the etiology of anemia in the elderly cannot be determined.

Hematologic neoplasia in older individuals

Although hematologic malignancies may occur at any age, certain disorders are common in those older than 50 years.

Myelodysplastic syndrome

Myelodysplastic syndromes a heterogenous group characterized by a defect in the hematopoietic stem cell that may affect multiple cell lineages are diagnosed more frequently in the elderly and in some patients myelodysplastic syndrome terminates in acute leukemia.

Myeloproliferative disorders

Myeloproliferative disorders are monoclonal proliferations of hemapoietic stem cells with overaccumulation of RBCs, WBCs or platelets in various combinations. The average age of patients with polycythemia vera is 60 years. The incidence of chronic myelogenous leukemia increases after age 50. Chronic idiopathic myelofibrosis occurs in age between 50 to 70 years.

Chronic Lymphocytic Leukemia (CLL)

CLL is the most common cause of lymphocytosis in the elderly and constitute 30% of all leukemias seen in western countries. The onset is usually asymptomatic at a median age of 60 to 65 years and it occurs twice as often in males as compared with females Rozman & Montserrat (1995).

Multiple Myeloma

Multiple myeloma is a plasma cell cancer characterized by monoclonal gammopathy and multifocal destructive bone lesions throughout the skeleton. The neoplastic plasma cells secret complete or incomplete immunoglobulins. The age of peak incidence for multiple myeloma is 67 years, with 80% of cases occurring after 60 (American cancer society 2006). It occurs at an equal frequency in males and female.

Conclusion: The hematological changes are obvious in both the neonates and the elderly persons and at such, different hematological variables must be implemented in various developing stages of the neonates as well as the different classes of aged elderly individuals. Also among the elderly, certain hematological disorders are more dorminant and clinicians should be attentive to this.

References

Allan R N & Alexander M K (1965); A sex difference in the leukocyte count. J Clin Pathol. 21:691

American cancer society (2006); at www.cancer.org/docroot/home/index/asp

Cavaliere T A (2004); Red blood cell indices: implications for practice . NB1N (4):231

Chatta G S & Dale D C (1996), Aging and hematopoiesis: Implications for treatment with hemopoietic growth factors. Drugs aging 9:37.

Christensen R D (1989); Hematopoiesis in the fetus and neonates. Pediatr Res. 26:531.

Christensen R D (2000); Expected hematologic values for term and preterm neonates. Hematologic problems of the neonates. Philadelphia:117

Dallman P R (1977); Reference ranges for leukocyte counts in children. In Rudoiph A M (ed): Pediatrics, 16th ed. New York: Appleton – century:1178

Federal interagency forum on aging related statistics( 2006); Older Americans: Key indicators of well being.at:www.agingstats.gov

Forestier F et al (1991); Developmental hematopoiesis in normal human fetal blood. Blood 77:2360

Geaghan S M (1999), Hematologic values and appearances in the healthy fetus, neonate and child. Clin Lab Med 19:1-37

Globerson A (1995); T lymphocytes and aging. Int. Arch Allergy Immunol 107:491

Grubeck- Lobenstein B (1997); Changes in the aging immune system. Biologicals 25:205

Halvorsen S & Finne P H (1968); Erythropoietin reduction in the human fetus and newborn. Ann NY Acad. Sci 149:576

Hann I M et al (1983); Development of pluripotent hematopoietic progenitor cells in the human fetus. Blood 62:118

Howe R B (1983), Anemia in the elderly. Postgrad. Med 73:153

Landsdorp P M (1997); Self renewal of stem cells. Biol blood marrow transplant 3:171

Linch D C et al (1982); Studies of circulating hematopoietic progenitor cells in human fetal blood. Blood 59: 976

Luchtman- Jones et al (2006); Hematologic problems in the fetus & neonates. In Martin R J et al (eds): Neonatal – perinatal medicine 8th ed st. Louis:1287.

Newborn services clinical guidelines(2006); Normal hematological values at:www.adhb.gov.nz/newborn/guidelines/blood/hematological values.htm

Pahal G S et al (2000); Normal development of human fetal hematopoiesis between eight and seventeen weeks gestation. Am J Obstet Gynecol 183:1029

Rozman C & Montserrat (1995); Chronic lymphocytic leukemia. New Engl. J Med 333:1052

Salive M E et al (1992); Anemia and hemoglobin level in older persons: relationship wth age gender and healthy status. J AM Geriatr Soc 40:489

Segal G B & Palis J (2006); Hematology of the newborn. In Lichtman et al (eds): Williams hematology 7th edn. New York. Mcgraw Hill 81-98.

Smith D (2002); Management and treatment of anemia in the elderly. Clin Geriatr 10:8

Soldin S et al (2005); Pediatric reference intervals 5th ed. Washington DC :AACC press

Song L et al (1993); Age related effects in T cell activation and proliferation. Exp Gerontol 28:313

The leukemia lymphoma society (2006): Disease information at www.leukemia-lymphoma.org

Thomas R M et al (1983); Erythropoietin and cord blood hemoglobin in the regulation of human feta erythropoiesis. Br J Obstet Gynecol. 90:795

World health Organization / UNICEF/UN university (1997) : indicators and strategies for iron deficiency and anemia programs. Report of a consultation, WHO, Geneva.

Yoder M C (2002); Embryonic hematopoiesis. In Christensen R D (ed): Hematologic problems of the neonate. Philadelphia saunders:3-20

Zaizov & Matoth Y (1976); Red cell values on the first post natal day during the last 16 weeks of gestation. Am J Hematol 1:275

Zauber N P & Zauber A G (1987); Hematologic data of healthy old people. JAMA 257:2181

Autor:

Peter Ubah Okeke

2011