Development of the Hematopoietic System & Blood Cell Counts

Development of the Hematopoietic System & Blood Cell Counts
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Development of the Hematopoietic System & Blood Cell Counts Dr.Jie Yu, MD. Professor The department of Pediatric, Hematology/Oncology Hello, Good morning. It’s very nice to have this chance to study with you. I would like to introduce myself first. My name is Yu Jie. I graduated from this school in 1989 with master degree. Later,I got my doctor degree. I am now a pediatrician and an association professor in Hematology/Oncology. My professional interesting is in blood diseases and some malignant diseases. It’s my pleasure to take this course.Today we are going to discuss the development of hematopoietic system and anemia in two sections and nutritional anemia in the rest two sections. These are all the contents about blood diseases you will contact at this semester. It’s important,but just a very small part of all. If some of you are interesting in this field I welcome you to our division to continue the study. Before the following study, I would like to ask your a question. For the same two teachers, one teaches in Chinese and another one teaches in English. Which one you would like to choose? I just want to test your intendance or you value about the English teaching. From my personal experience, I really think it’s important for you future development or your career. You probably feel hard right now ,but if you don’t have this you will feel angry about our poor education many years later. For me it’s much easier to teach in Chinese. Let we both try hard to finish our study well.

Contents Development of hematopoietic system
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Contents Development of hematopoietic system Hematopoietic organs Hematopoietic blood cells Characteristic of cell counts and hemoglobin RBC and Hb level Hemoglobin WBC/Platelet/Blood volume Anemia

Development of Hematopoietic System
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Development of Hematopoietic System Under this title I will introduce you the development of hematopoietic organs and cells in fetal hematopoiesis and bone marrow hematopoiesis. Our today’s study has three parts. First let me introduce you the development of hematopoietic

HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL
To learn the development of hematopoiesis we have to bring us with several questions. Look at this picture. What is this? a red blood cell in 3 dimensions. Isn’t it beautiful? The questions are① where it come from? (2)Where it was made? (3)What’s kind of factors regulate this process? Let us try if we can answer these questions after the following study.

constant changes characterize all phases of hematopoiesis.
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL In the embryo and fetus, constant changes characterize all phases of hematopoiesis. Hematopoietic regulation in the human fetus differs markedly from that in an adult. In an adult, homeostatic maintenance is a prime function of hematopoietic regulation, whereas in the embryo and fetus, constant changes characterize all phases of hematopoiesis. Knowledge of developmental hematopoietic regulation helps clinicians to interpret postnatal hematologic data, granulocytopoietic capacities and limitations of prematurely delivered neonates.

Development of Hematopoietic Organs
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Fetal hematopoiesis Mesoblastic Hematopoiesis Hepatic Hematopoiesis Myeloid Hematopoiesis Hematopoiesis after birth Hematopoietic organs are the factories for producing blood cells in different periods of time. Here let we look the fetal hematopoiesis first, this happens mostly before birth. Developmental hematopoiesis occurs in three anatomic stages - mesoblastic, hepatic, and myeloid. Also, there are some other organs such as spleen and lymph nodes as minor hematopoietic organ in this process.

Fetal Hematopoiesis liver

Table 1. Fetal Hematopoiesis
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Table 1. Fetal Hematopoiesis SITES TIME PRODUC Measoblastic hematopoisis Yolk Sac 10-14th day 3-4wk:primitive blasts 10-12wk:ceased Erythroid Hepatic hematopoiesis Liver Spleen 6-8wk:appear 12-16wk:active 6mo:diminish/ stop at birth Myeloid hematopoiesis Bone marrow 4mo:start 6mo:increase/steady after birth: the only Neutrophils Macrophages Mesoblastic Hematopoiesis occurs in extra embryonic structures, principally in the yolk sac, and begins between the 10th and 14th day of gestation. By 3-4 weeks of gestation, primitive blasts are found in yolk sac. By 10-12wk gestations, extra embryonic hematopoiesis has essentially ceased. In this period, RBC is the only production of mesoblastic hematopoiesis. Hepatic Hematopoiesis The organ for it is liver. By 6-8 wk gestation, the liver replaces the yolk sac as the primary site of blood cell production. Hematopoiesis occurs in the liver throughout the remainder of gestation, although the production begins to diminish during the second trimester as bone marrow hematopoiesis increased. The liver, however, remains the predominant hematopoietic organ through wk of gestation. At wk of gestation, more than 85% of the cells in the fetal liver are erythroid and virtually there are few neutrophils and macphages presented. Myeloid Hematopoiesis Bone marrow hematopoiesis starts from Second trimester and increase rapidly until 6mo of gestation It becomes stable at the end of second trimester and the main hematopoietic organ. By wk 2-5 after birth, bone marrow is normally the only hematopoietic place left. The production by myeloid hematopoisis are ( within the bone marrow) are erythroid, nutrophils , and macrophages.

HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Development of Hematopoietic Organs Fetal hematopoiesis Hematopoiesis after birth Bone marrow hematopoiesis Extrmedullary hematopoiesis After we learnt the fetal hematopoiesis, now let us move on to the hematopoiesis after birth.

HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Development of Hematopoietic Organs Hematopoiesis after birth Bone marrow hematopoiesis All blood cells are produced in the marrow after 2nd trimester Newborn and early infancy: red marrow 5-7yr : yellow marrow Extramedullary hematopoiesis In the 3rd trimester , all most all kinds of blood cells can be produced in the bone marrow. In the newborn and during early infancy, hematopoietic marrow (red marrow) fills the bony cavities of the entire axial skeleton, the long bones, and many membranous bones. Thus, during the first year the tibia is often chosen as a convenient site for bone marrow aspiration. With advancing age (5-7yr), hematopoietic tissue gradually retreats to central bones of the body, and the marrow of the extremities and the skull is replaced with fat (yellow marrow), which is a gradual and partially reversible process. Thus after the infancy year the most commonly used site for BM aspiration is the iliac crest, or posterior superior iliac spine.

HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Development of Hematopoietic Organs Hematopoiesis after birth Bone marrow hematopoiesis Extramedullary hematopoiesis In diseases status: red cell production hematopoietic tissue. blood production expands to replace fatty marrow. blood cells production extends to extramedullary sites ( liver and spleen). What is the extramedullary hematopoiesis. Normally, extramedullary hematopoiesis ceased two (2-5wk) months after birth. In diseases status: such as hemolysis, infection, anemia and bone marrow infiltration, the normal rate of red cell production can increase to eight-fold, causing a concomitant increase in the volume of hematopoietic tissue. As a consequence, blood production (H tissue) first expands from the ends of the long bones toward the middle of the shafts to replace the fatty marrow. Next the production of blood cells extends to extramedullary sites, particularly in the liver and spleen. In infants and children, hemolytic disease results in a relatively greater enlargement of the liver and spleen than in adults because most of the bony sites are already filled with red marrow and the marrow reserve (yellow marrow) are relatively lower.

Development of the Hematopoietic Blood Cells
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Development of the Hematopoietic Blood Cells Pluripotent Stem Cells: which are capable of both self-renewal and of clonal maturation into all blood cell lineages. Progenitor cells differentiate under the influence of hematopoietic growth factors We just learned the development of hemapopoiesis organ. Now I want give you some concepts about the development of hematopoiesis of blood cells. This is the most new and important part in the development of hematopoiesis. However, it only tells few in your text book. In the material I give to you, I put some contents there. I wish you can study it by yourself. I have no more time here to get it into details. at the beginning I raised a question of where the blood cells come from. The most primitive blood cells are PSCs

Table 2.The Development of Blood Cells
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Table 2.The Development of Blood Cells PROGENITOR CYTOKINES PRODUC CFU-GM G-CSF NUTROPHIL CFU-Meg TPO PLT CFU-E BFU-E EPO RBC GRANULOCYTOPOIESIS CFU-GM is the progenitors for N, G-CSF is the main factor/cytokine regulating the process. In the ST/2ND , do you still remember what the main production of the hematopoiesis is? Actually, CUF-GM are abundant in the liver, bone marrow and blood, but no netrophils appeared until 3rd trimester.Studies showed that this is due to the lower production of G-CSF during that period. THROMBOPOIESIS ERYTHROPOIESIS

Fig1.Hematopoisis

Now, can you answer the questions I raised at the begging? Where the blood cells come from? Where they are made? What’s factors regulating the process of hematopoisis.

Blood Cell Counts and Hemoglobin
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Blood Cell Counts and Hemoglobin Now, we move to the second part: Of course this is in the situation after birth.

Fig2. Peripheral Blood Cells
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Fig2. Peripheral Blood Cells This is a normal peripheral blood smear. Can you recognize what these cells are? They are red blood cells and white blood cells. WBC includes nutrophils, lymphocytes and monocytes. Leucocyte differential: myelocytes, band neutrophils, segmented neutrophils, esinophil, basophil.

RBC and Hb Level At Birth: Postnatal fall /physiology anemia
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL RBC and Hb Level At Birth: RBC: 5-7x1012/L Hb:150 to 230g/L. Postnatal fall /physiology anemia Infancy  Preschool age: RBC: 4 x 1012/L Hb: 110 g/L 7-12yr: adult level At birth, the concentration of RBC in the blood is up to 5-7x1012/L and the level of Hb ranges from 150 to 230g/L. The level of Hb in premature infant is relatively lower. Six to twelve hours after birth, the number of RBC in the blood have a slight increase because the loss of liquid. The relative polycythemia of the newborn is attributable to the low arterial Po2 levels in utero that simulate erythropoietin production in the fetus and result in a high rate of erythropoiesis.

RBC and Hb level Physiological Anemia.
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL RBC and Hb level Physiological Anemia. Hemoglobin values in term infants drop to their lowest mean of 100g/L at 2-3 mo Causes Erythropoietin production Red cell life span (90/120) Blood volume Preterm infant In the newborn, the number of RBC and hemoglobin level are very high. However, about one week later, the the number of RBC and hemoglobin level fall gradually. Hb values in term infants drop to the lowest mean of 100g/L at 2-3 mo. this is what we called physiological anemia or postnatal fall. The reasons for this drop has several. After birth, with the expansion of the lungs and establishment of normal neonatal cardiorespiratory function, the oxygen saturation rapidly rises from 65% in utero to nearly 100%. Erythropoietin production ceases and shuts down erythropoiesis. This is the most important causes. Second, during this period the red blood cells are mostly produced in utero and its life span is only 90 days compared with 120d in adults. Third , with the rapid increase of body weight, the blood volume increases greatly during this period. This led a slight dilution of the blood. Thus, As a consequence of decreased production and increased destruction, hemoglobin values in term infants drop to their lowest mean of 100g/L at about 2-3 months of age . Preterm infant , the postnatal fall is more marked. When the RBC and HB drop to the lowest level, the relative low oxygen stimulate the production of EPO which is sufficient to maintain a stable mean hemoglobin concentration of 110 g/L, despite the tripling of blood volume and weight that occurs during the first year of life.

RBC and Hb level Reticulocytes Nucleated Red Blood Cells
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL RBC and Hb level Reticulocytes At Birth: 5% / 10% 1-2mo: fall down to 0.3% Later adult level: % Nucleated Red Blood Cells At birth: 3-10/100 WBC; 10-20/100WBC 1wk: disappear Rc reflects active erythropoiesis. In the term new born infant, it averages about 5% (300x109/L). For premature infant it’s 10% at birth. Subsequently, it drops.1-2mo, it fall down to 0.3% and later on reach adult level %. Persistence of a high reticulocyte count between 1-4wk is abnormal and often suggests a hemolytic process or blood loss. nucleated RBC present in peripheral blood often suggests active hemolytic respond to hemolysis or blood loss.

HEMOGLOBIN. Function Construction transport oxygen.
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL HEMOGLOBIN. Function transport oxygen. Construction iron-containing heme plus globins which is a tetramer made up of two pairs of polypeptide chains, Hb is a complex protein consisting of iron-containing heme groups and the protein moiety globins.A dynamic interaction between heme and globins gives Hb its unique properties in the reversible transport of oxygen. The polypeptide chains of various hemoglobins are of chemically different types. The major hemoglobin of a normal adult (HbA) is made up of one pair of alpha (α)and one pair of beta (β) polypetide chains and represented as α2β2. The major hemoglobin in the fetus (HbF) is represented by α2γ2.

Table3. HEMOGLOBINS Hb Chains 8周 6月出生 6-12月 2岁 Embry Gower1 ζ2ε2 8周前，
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Table3. HEMOGLOBINS Hb Chains 8周 6月出生 6-12月 2岁 Embry Gower1 ζ2ε2 8周前， 3月消失 Gower2 α2ε2 Portlan ζ2γ2 Fetal HbF α2γ2 增加 90% 70% <5% <2% Adult HbA α2β2 5-10% 30% >95% HbA2 α2δ2 <1% 2-3% <3.5% Within the RBCs of an embryo, fetus, child, and adult, six different hemoglobins may normally be detected: the embryonic hemoglobins, Gower-1, Gower-2, and Portland; The fetal hemoglobin, HbF; and the adult hemoglobins HbA and A2. Gower-1, Gower-2, and Portland, which has HbF-like mobility. In embryo the Gower hemoglobins predominates in 4-8wk of gestation , but by the 3rd mo they have disappeared. Fetal Hemgolboin ( HbF) containsγpolypeptide chnains in place of the β chains of HbA. Its resistance to denaturation by strong alkali is the basis for determining the presence of fetal RBCs in the maternal circulation. After the 8th gestational wk, HbF is the predominant hemoglobin; at 24wk (6mo) gestations it constitutes 90% of the total hemoglobin. During the 3rd trimester, a gradual decline occurs, so that at birth HbF averages 70% of the total. Synthesis of HbF decreases rapidly postnatal, and by 6-12 mo of age only a trace is present. Less than 2.0% can be detected by alkali denaturation in children beyond 2 yr and adults. In the disease status, the HbF level can be increased. It is seen mostly in β-thalassemia, also in AA, CML. Some HbA (α2β2) can be detected in even the smallest embryos. Accordingly, it is possible as early as wk gestation to make a prenatal diagnosis of major β chain hemoglobinopathies, such as thalassemia major. Prenatal diagnosis is based on techniques that examine the rates of synthesis of β chains or the structure of newly synthesizedβ chains. By the 24th wk of gestation, approximately 5-10% of HbA is present. A steady increase follows, so that at term, HbA averages 30%. By 6-12 mo of age, the normal HbA pattern appears. The HbA average 95% of the total hemoglobin. The minor HbA component HbA2 contains delta (δ) chains and has the structure α2δ2 . It is seen only when significant amounts of HbA are also present. At birth, less than 1.0% of HbA2 is seen, but by 12 mo of age there is % HbA. Throughout life, the normal ratio of HbA to A2 is about 30:1. >95%

WBC Counts At birth: 20 x 109/L Infant: 12 x 109/L
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL WBC Counts At birth: x 109/L Infant: x 109/L Preschool: x 109/L It declines to 12x109/L and maintains at this level during the period of infancy. At preschool age it decreases to 8x109/L and reaches the adult level later (4-10 x 109/L). In infancy period , the WBC counts will be fluctuated by crying, feeding, muscle extraction, pain, and lacking of oxygen.

Fig4. WBC Ratio 淋巴细胞 4-6天 4-6岁中性粒细胞
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Fig4. WBC Ratio (%)70 淋巴细胞 60 50 40 30 20 10 4-6天 4-6岁中性粒细胞 What kind of cells included in WBC? (Nutrophils, Lymphocytes, monocytes) The ratio of neutrophil and lymphocyte varies greatly. At birth, neutrophil accounts for abut 60-65% and lymphocyte accounts for the rest. This ratio changes and crosses at 4th-6th days after birth. During the period of infancy, lymphocyte accounts for the 60% and neutrophil accounts for abut 30%. In early preschool age, the ratio changes to reach the second cross. After about 6yr, the ratio of neutrophil to lymphocytes reaches the adult value gradually. 日数岁数

PLT & Blood Volume PLT: 150-250 x 109/L Blood Volume:
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL PLT & Blood Volume PLT: x 109/L Blood Volume: Term newborn: 85ml/kg Premature infant: 95ml/kg Adult: 75ml/kg Young children: 75-80ml/kg PLT concentration in PBL dose not change very much with advancing age. The normal range of values in children is similar to that in adult.

The Introduction of ANEMIA
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL The Introduction of ANEMIA We just learnt the development of hematopoiesis. We also reviewed the characteristics of RBC and Hb. In the following period, we are going to study the introduction of anemia, which is a very important part.

Definition of Anemia A reduction of the red blood cell volume or hemoglobin concentration below the range of values occurring in healthy persons

Table 4. The definition of Anemia and Degree
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Table 4. The definition of Anemia and Degree Age Anemia Values Anemia Degree Newborn < 145g/L 1-4 mo < 90g/L Mild: g/L 4-6 mo < 100g/L Moderate: g/L 6 mo-6 yr < 110g/L Severe: g/L 6-14 yr < 120g/L Extremelysevere:<30g/L The presence of anemia usually is determined by comparison of the patient hemoglobin with age- and sex-specific normal values (Table 4). Which is built based on the large scale population statistics. In the newborn anemia is determined when Hb level below 145g/L. Also, the degree of anemia was usually divided into to four classes (Table 4). Although a reduction in the amount of circulating hemoglobin deceases the oxygen-carrying capacity of the blood, few clinical disturbances occur until the hemoglobin level falls below 70-80g/L.

Pathophysiology of Anemia
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Pathophysiology of Anemia Pathophysiology increased cardiac output increased oxygen extraction blood flow toward vital organs and tissues. In addition, the concentration of 2,3-DPG increases within the RBC. I am sure you have learnt this in physiology. Here we just make a short review. Physiologic adjustments to anemia include increased cardiac output, increased oxygen extraction, and a shunting of blood flow toward vital organs and tissues. In addition, the concentration of 2,3-DPG increases within the RBC. The oxygen dissociation curve shift to the right, reducing the affinity of hemoglobin for oxygen, results in more complete transfer of oxygen to the tissues. Self study

Fig5:The oxygen dissociation curve
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Fig5:The oxygen dissociation curve In addition, the concentration of 2,3-DPG increases within the RBC. The oxygen dissociation curve shift to the right, reducing the affinity of hemoglobin for oxygen, results in more complete transfer of oxygen to the tissues. Self study

Manifestation of Anemia
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Manifestation of Anemia Acute onset elevated pulse, hemic flow murmur, poor exercise tolerance, headache, excessive sleeping, poor feeding, and syncope may occur. Slow onset weakness, tachypnea, shortness of breath on exertion, tachycardia, cardiac dilatation, and congestive heart failure Anemia that is acute in onset often is poorly compensated in terms of cardiovascular function. An elevated pulse, hemic flow murmur, poor exercise tolerance, headache, excessive sleeping, poor feeding, and syncope may occur. When moderately severe anemia develops slowly, surprisingly you will find few symptoms or objective findings because the body has more time to make some adjustments, but ultimately weakness, tachypnea, shortness of breath on exertion, tachycardia, cardiac dilatation, and congestive heart failure will result from increasingly severe anemia, regardless of its cause. Self study

Classification-morphology
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Classification-morphology Table 5 MCV（fl） MCH（pg） MCHC（%） Normal ranges 80-94 28-32 32-38 Macrocytic >94 >32 Normocromic /Normocytic Microcytic <80 <28 32-28 Hypochromic /Microcytic < 32 There are many kinds of anemia. For clinical purpose, there are basically two types of classifications. Morphological classification is a useful classification. It divides the anemia into three/four groups by the RBC indices. They are mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) (Table 5 ) If the RBC index are all in normal range, is there still any problem?

Classification- Etiology
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Classification- Etiology Reduced capacity to produce red blood cells Hemolysis Blood Loss Anemia is just a symptom/or sign. Knowing the anemia is not our purpose. The most important thing about the anemia is knowing the cause, etiology. That is what we can use for the treatment. For this purpose, according to the causes of anemia, we classify them into several categories. You can look at the Table 3 in your materials. Reduced capacity to produce RBC. This means that the red blood cells can not be made or produced either because of the bone marrow failure or lacking of materials to make. Hemolysis. RBCs were destructed for some reasons. Blood loss. This is easy to understand. You break your vessels and loss blood including red blood cells. Your body will adjust this loss until the anemia happen. THANK YOU

Classification- etiology
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Classification- etiology Reduced capacity to produce RBC Aplastic anemia Fanconi’s anemia Acquired aplastic anemia Pure red cell aplasia congenital hypoplastic anemia (Diamond-Blackfan) Acquired hypoplastic anemia For pure red cell aplasia, congenital hypoplastic anemia is rare and 90% of the patients had their anemia within 6mo. 25% of patients associates with some congenital malformations. Acquired hypoplastic anemia happened after birth, in which the production of red blood cells were suppressed by some factors or unknow reasons. It could be resolved naturally. AA usually involves erythroid, myeloid and megakaryocytes. The ability of production of red cells , nutrophils and PLT is all suppressed.

Classification- etiology
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Classification- etiology Reduced capacity to produce RBC Marrow Infiltration Leukemia Lymphoma Neuroblastom LCH In malignant diseases like leukemia, malignant cells proliferate and fill the bony cavity. The normal hematopoiesis was suppressed. Ultimately, normal blood cells in the blood and marrow decrease, resulting anemia, bleeding and infection.

Classification-etiology
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Classification-etiology Reduced capacity to produce RBC Deficiency Syndrome Iron Folate Vitamin B12 Vitamin E Vitamin B6 Elements like iron and folate are all important for production of red blood cells. Without these elements, the hematopoiesis process couldn't’t be finished. The anemia is sue to be occurred.

HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Classification-etiology Hemolysis Iintrinsic RBC abnormalities Hemoglobinopathies Enzymopathies Membrane disorders extrinsic RBC abnormalities Immunologic: AIHA According to the cause there are intrinsic RBC abnormalities and extrinsic RBC abnormalities. For a RBC, any problem happened to the membrane, hemoglobin and enzyme can cause the RBC unstable, shouter life span and easy to be destructed

HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Classification-etiology Hemolysis:intrinsic RBC abnormalities Intrinsic membrane defects Hereditary Spherocytosis: Hemoglobinopathy Thalassemia RBC enzyme defects G6PD defect This group of anemia is the the destruction of the red blood cells due to a defect within the red blood cells themselves. Intrinsic hemolytic anemias are often inherited, such as HS and thalassemia. These conditions produce red blood cells that do not live as long as normal red blood cells Hereditary spherocytosis is the most common red cell membrane disorder. The clinical severity varies greatly, ranging from a severe hemolytic anemia with growth failure, splenomegaly and chronic transfusion requirements to mild anemia without apparent anemia. The diagnosis should be suspected in patients with even a few spherocytosis exhibited on the blood smear. Splenectomy corrects the anemia and normalizes the red blood cell survival, but the morphologic abnormalities persist. Hemoglobinopathies is a group of diseases. Beta thalassemia major is an important one. It is caused by mutation that alter beta chanin synthesis . As we just learnt that HbA is consisted of two alpha chains and two beta chains. When beta chain synthesis decreases, excess alpha chains precipitate within the red blood cells, resulting in cell destruction. As an adjustment, HbF increases. Majority of the patients are transfusion dependent from infancy. There are numerous red cell enzyme deficiencies, but only a few are clinically important. G6PD is the most common one ,esp in our area, and present as several types. Favism cause by broad beans is one of the most common types. Children with favism usually have acute hemolytic anemia after eating broad beans. The diagnosis is based on the G6PD level as well as the G6PDgene detect. The treatment is supportive including transfusion and protecting the kidneys. Avoid some drugs and broad beans can prevent hemolysis in patient with G6PD. .

HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Classification-etiology Hemolysis:extrinsic RBC abnormalities Immunologic hemolysis Isoimmune (Rh, ABO in neonate) Autoimmune Hemolytic Anemia (AIHA) extrinsic - A disorder resulting from an abnormality of the immune system that destroys red blood cells prematurely. The cause is unknown Infections ( such as hepatitis, cytomegalovirus (CMV), Epstein-Barr virus (EBV), typhoid fever, E. coli, or streptococcus ), medications ( such as penicillin, antimalaria medications, sulfa medications, or acetaminophen), leukemia or lymphoma , autoimmune disorders (such as systemic lupus erythematous (SLE, or lupus), rheumatoid arthritis, Wiskott-Aldrich syndrome, or ulcerative colitis ), various tumors Idiopathic autoimmune hemolytic anemia is an acquired disease that occurs when antibodies form against the person’s own red blood cells. In the idiopathic form of this disease, the cause is unknown. There are other types of immune hemolytic anemias where the cause may result from an underlying disease or medication. Idiopathic autoimmune hemolytic anemia accounts for one-half of all immune hemolytic anemias. The onset of the disease may be quite rapid and very serious. Risk factors are not known. coomb’s test positive Treatment with prednisone is the first therapy that is tried. If prednisone does not improve the condition, a splenectomy (removal of the spleen) may be considered. Immunosuppressive therapy is given if the person does not respond to prednisone and splenectomy. Imuran and Cytoxan have both been used. Blood transfusions are given with caution, if indicated for severe anemia, because of the potential that blood may not be compatible and precipitate a reaction. Rh-negative mothers who have become sensitised to the D-antigen in an Rh-positive fetus develop anti-D antibodies which can cross the placenta and attack the blood of Rh-positive fetuses in subsequent pregnancies. This leads to the condition usually referred to as Rhesus Isoimmunisation 1 2, but also referred to as Haemolytic Disease of the Newborn and Erythroblastosis fetalis ABO incompatibility is most often seen in the setting of mother being group O and the baby being groups A or B. It is milder than Rhesus disease, and rarely affects the fetus. They typically have jaundice that becomes apparent on day 1 or 2, but which responds well to phototherapy. Exchange transfusion for ABO incompatibility in the otherwise well, term infant is rarely required. Consequences of disease Kernicterus (bilirubin encephalopathy) Early: This clinical syndrome includes hypertonia progressing to opthistotonia, seizures, and often death. At autopsy, such babies display evidence of bilirubin staining of the basal gangia. Late: Survivors may go on to develop sensorineural hearing impairment and cerebral palsy, often with ataxia and chorioathetosis. Anaemia

HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Classification-etiology Blood loss Gastrointestinal bleeding Ankylostomiasis Menstrual Trauma Trauma cause blood loss and anemia. This is easy to understand. Menstrual is also a cause for blood loss. Usually there are 40ml blood loss during each menstrual. If the amount of blood loss is greater and the food is not iron containing. IDA will occur. You will learn that there many reasons for gastrointestinal bleeding. Here I just want you to remember that ankylostomiasis is one of them, causing chronic and small amount of GI bleeding, finally IDA. You have to distinguish this IDA with nutritional IDA very often. Especially when the patients is from remote area or countryside.

Mount Raniner, Seattle

Hematopoiesis Related Terms
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL Hematopoiesis Related Terms CFU-GM colony –forming units granulocyte-macrophages CFU-Meg colony-forming unite-megakaryocyte CFU-E colony-forming units-erythroid BFU-E burst-forming units-erythroid G-CSF colony-stimulating factor TPO thrombopoietin EPO erythropoietin

RBC Index MCV MCH MCHC Mean corpuscular volume
HEMATOLOGY/ONCOLOGY, CHILDREN’S HOSPITAL MCV Mean corpuscular volume MCH Mean corpuscular hemoglobin MCHC Mean corpuscular concertration

This is a normal peripheral blood smear. Here, I just want to show you how the normchromic and normocytic cells look like. If it’s in anemia, the number of RBC will below the normal range, but shape of RBC is still normchromic and normocytic.

This picture shows you microcytic and hypochromic red blood cells.

When we look at this picture. It almost empty, no cells. The open spaces are fat. This one is kind of typical and severe. Otherwise we can also see some cells, fewer.

The marrow is monotonous. Similar and the same face. There are essentially no normal myeloid elements, with replacement by immature lymphoblasts

Not every RBC in HS is spherocytic. The arrows point to the best examples on this smear. Note the lack of central pallor. This smear could also come from a person with a non-hereditary form of spherocytic anemia. You should know what the other possibilities are

Thalassemia major peripheral smears have RBCs that are very bizzare-looking, with very little hemoglobin in them, and a fair amount of target cells. Most of the cells are also hypocromic and microcytic. By now you already know there are two anemia with hypochromic and microcytic red blood cells. Note that this smear has many nucleated RBCs, which is particularly common in these patients after they have had their spleens removed. Thalassemia major peripheral smears have RBCs that are verry bizzare-looking, with very little hemoglobin in them, and a fair amount of target cells. Note that this smear has many nucleated RBCs, which is particularly common in these patients after they have had their spleens removed.

Development of the Hematopoietic System & Blood Cell Counts

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Presentation on theme: "Development of the Hematopoietic System & Blood Cell Counts"— Presentation transcript:

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