BMH Medical Journal

BMH Med. J. 2020; 7 (Suppl): Early Online. Geriatrics & Gerontology Initiative: International Workshop on Care of the Elderly

Blood contains several cell types, each having a specific biological function of its own. Hematopoiesis is the production of these various cell types from a single multipotent progenitor cell, the hematopoietic stem cells (HSC) [1].

Hematopoiesis initially starts in the yolk sac in small blood islands followed by the aorta-gonad-mesonephros and splanchnopleura. With the onset of circulation, at around 1 month, hematopoiesis occurs in the placenta and liver. By 3 months, hematopoiesis simultaneously starts in the bone marrow. The bone marrow becomes the sole site of hematopoiesis at birth.

Hematopoietic stem cells can also migrate under stress conditions to colonize organs like the liver, spleen and begin extramedullary hematopoiesis.

The red blood cells die after 100 to 120 days. The proposed explanations for this normal red cell death are energy depletion with age of the circulating RBC, changes in the red cell enzymes, oxidative injury, alterations in calcium balance, alteration in membrane surface charge, development of autologous antibodies to the membrane antigens and changes in the symmetry of membrane phospholipids. Red cell destruction occurs intravascularly within macrophages of the spleen and a smaller proportion, in the liver and bone marrow. Only 10 to 20% of normal destruction occurs intravascularly. Transfused RBCs have a half-life of around 31 days [2].

All the leukocytes other than the T lymphocytes differentiate, proliferate and mature in the bone marrow. The mature leukocytes are released into the circulation briefly until they move into the tissues. The neutrophils circulate for around 7.5 hours before they migrate to the tissues. Neutrophils that are not activated die within 1-2 days and those that are activated live for 3 to 5 days [2]. Transfused granulocytes have a half life of 3.8 to 6.7 hours. Activated monocytes after transfusion have a life span of up to 5 days. Transfused lymphocyte survival is difficult to study as they are extremely radiosensitive [2].

Megakaryocytes within the bone marrow give rise to circulating platelets. Each megakaryocyte produces 1000 to 5000 platelets from its cytoplasm and the remaining nuclear material is removed by marrow macrophages. The platelets have a circulatory half-life of 10 days. Platelet survival after transfusion depends on the platelet activation which occurs with an increase in platelet storage over 5 days and these platelets are selectively cleared soon after transfusion [3].

Changes in the hematopoietic stem cells during aging

Changes occurring in the hematopoietic stem cells can be divided into intrinsic and extrinsic parameters [5]. The intrinsic parameters include stem cell exhaustion, which is an important hallmark in aging hematopoietic stem cells. This refers to the decrease in the function of adult tissue-specific stem cells to maintain homeostasis. During cell division, there is a shortening of telomeres in human HSC and eventually, there is an accumulation of cell cycle arrested senescent cells during normal aging. Mutations also occur in the DNA repair thus leading to accumulation of DNA damage and thus, stem cell dysfunction. After each cell division, there is an asymmetric distribution of specific proteins causing increased polarity.

Another factor is the impaired autophagy due to the accumulation of mitochondria leading to higher levels of reactive oxygen species, which in turn, induces metabolic stress.

The extrinsic parameters include a lack of humoral stimulation and also a reduced response to humoral stimulation. Diminishing body mass and or physical activity causes a decrease in the oxygen need, which also contributes to the decrease in hemoglobin.

Erythropoietin levels seem to be decreased in the elderly and may be implicated in the unexplained anemia of aging. There is also a concomitant decrease in renal excretory function that accompanies aging also.

Changes in the bone marrow

It is well known that with an increase in age, there is a concomitant increase in adipose tissue and a decrease in the hematopoietic cells [6].

Changes in the blood cell parameters

Hemoglobin concentration, red blood cell count and hematocrit decrease in men in their sixth decade and in women in their seventh decade of life.

A study showed that the Mean corpuscular volume (MCV) tends to increase with age and the changes in mean corpuscular hemoglobin (MCH) were not much with increasing age.

This study also considered distinguishing a fit patient from a frail person while using the WHO definition of anemia and proposed age-adjusted diagnostic criteria for anemia.

With advancing age, the white blood count and platelet had a tendency to decrease and with an increase of WBC band forms, and neutrophilia.

Studies show that there is an association between a lower value of hemoglobin and morbidity and mortality. Even higher levels or upper normal hemoglobin levels are associated with increased morbidity/mortality as the increased viscosity increases the risk of thromboembolic events.

The platelet count shows an inverse relation with the age of the individual after the covariates have been adjusted like nutritional deficiencies, medications, inflammatory conditions, autoimmune or viral illnesses.

Platelet hyperactivity is noted with a decrease in the bleeding time. The older individuals show increased sensitivity to aggregation and a higher level of proteins beta-thromboglobulin and platelet factor 4, which are secreted from the platelet alpha granules [7].

Conclusion

With an increase in age, all the blood cell counts and parameters have a tendency to decrease, other than the MCV which increases. Platelet function is increased although the counts decrease. These reflect the changes in the bone marrow due to ageing.

References

1. Wintrobe's Clinical Hematology, John P. Greer, Daniel A. Arber, Bertil Glader, Alan F. List, Robert T. Means Jr., Frixos Paraskevas, George M. Rodgers; editor emeritus, John Foerster. Clinical hematology 13th edition(2013).

2. Progressive platelet activation with storage: evidence for shortened survival of activated platelets after transfusion H. M. Rinder MD M. Murphy J. G. Mitchell J. Stocks K. A. Ault R. S. Hillman https://doi.org/10.1046/j.1537-2995.1991.31591263195.

3. Rossi's Principles of Transfusion Medicine, Toby L. Simon MD, Jeffrey McCullough MD,Edward L. Snyder MD,Bjarte G. Solheim MD, PhD, Ronald G.S trauss MD2016 by John Wiley & Sons, Ltd.

4. Clinical laboratory hematology.McKenzie, Shirlyn B., Joanne Lynne Williams, and Kristin Landis-Piwowar. 2015.

5. Hematologic disease at older age. Aging of hematopoietic stem cells Gerald de Haan and Seka Simone Lazare European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

6. Aging and erythropoiesis: current state of knowledge Blood Cells Mol Dis. 2008 Sep-Oct;41(2):158-65.

7. Platelet Function in Aging, Jessica Le Blanc and Marie Lordkipanidzé. https://www.frontiersin.org/people/u/173567

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