RBC disorders

MCV: Mean cell volume

The average volume per red cell, expressed in femtoliters, Hematocrit/number of erythrocytes

MCH: Mean cell hemoglobin

The average mass of hemoglobin per red cell, expressed in picograms, Hemoglobin/number of erythrocytes

MCHC: Mean cell hemoglobin concentration

The average concentration of hemoglobin in a given volume of packed red cells, expressed in grams per deciliter, Hemoglobin concentration/Hematocrit

RDW: Red cell distribution width

the coefficent of variation of red cell volume

Three causes of anemias

Blood loss (hemorrhage), Increased red cell destruction (hemolysis), decreased red cell production

Small red blood cells are called and caused by

Microcytic (caused by iron deficiency, thalassemia)

Large red blood cells are called and caused by

Macrocytic (caused by folate or B12 deficiency)

Hereditary spherocytosis manifests as:

spherocytic shaped cells with anemia, splenomegaly, and jaundice. There is both a dominant and recessive form (dominant mutation usually due to ankkyrin) recessive is usually worse

Folate deficiency and B12 deficiency both interfere with what cellular process?

DNA synthesis

What is the most common type of anemia in hospitalized patients?

Anemia of chronic disease (induced by chronic inflammation)

What diseases are associated with anemia of chronic disease?

Microbial infections (ex. Osteomyelitis, endocarditis), Chronic immune disorders (ex. Rheumatiod arthritis), Neoplasms (ex. Hodgkin lymphoma)

How does folate deficiency differ from B12 deficency?

Neurologic abnormalities do not occur with folate deficency

Unless otherwise suggested a defciency of B12 in the western world is caused by:

pernicious anemia (i.e. inadequate absorption of b12, b12 need intrsinic factor for absorption)

Aplastic anemia is:

a disorder in which multipotent myeloid stem cells are suppressed leading to marrow failure and pancytopenia. Can be caused by radiation, toxins, drugs, viruses, inherited reactions and idiosyncratic reations

Myelophthisic anemia is:

a form of anemia caused by extensive replacement of the marrow by tumors (usually from breast, lung or prostate) or other lesions, this leads to the release of early erythroid and granulocytic precursors (leukoerythroblastosis) and the appearance of tear-drop red cells in the peripheral blood

Megaloblastic anemia:

Caused by folate or b12 deficiency, results in enlarged abnormal hematopoietic precursors (megaloblasts) in the bone marrow and often pancytopenia, and hypersegmented neutrophils

Hematopoeisis starts where? Where does it end in adulthood?

It starts in the yolk sac in the 4th month it migrates to the bone marrow, by adulthoold on the vertebrae, ribs, sternum, skull, pelvis, and proximal regions of humerus and femur retain red marrow

If hematopoeisis is needed what happens?

Old areas like distal bones and liver can compensate upregulating hematopoesis

The two elements of blood:

Plasma (liquid component) and formed elements (RBC, WBC, platelets)

During red blood cell development what happens morphologically?

The nucleus becomes smaller (eventually eliminated), the cytoplasm becomes bigger, final stage RBC is reticulocyte (still has some RNA in the cell, bluer color)

Average life span of a RBC:

120 days, (200 billion new RBCs are made everyday)

Heme is broken down into:

iron and biliverdin (which is further reduced into bilirubin), Globin is reduced to amino acids and recycled

how does bilirubin get from the spleen to the liver?

Bilirubin binds to albumin since the bilirubin is normally insoluble

The two organs associated with RBC removal:

The liver and the spleen (the spleen is the primary source of RBC removal)

What is bilirubin used for?

It is helpful in the absorption of fats and certain vitamins

Haptoglobin is used in what?

Intravascular hemolysis (it binds to heme and transports it to the liver), it is important because if haptoglobin is low then there is possibly increased intravascular hemolysis. Also hemopexin is another heme binding protein but can't be used to test for intravasuclar hemolysis

If you have a big increase extravascular hemolysis what will you see happen to bilirubin?

There will be an increase in unconjugated bilirubin since the liver won't be able to conjugate the bilirubin fast enough

What is the only aquired hemolytic anemia?

Paroxysmal nocturnal hemoglobinuria

In normal individuals what portion of transferrin is saturated with iron?

About one third (i.e. if there is 120 ug/dl of iron in the serum the total iron binding capacity is 360ug/dl)

How is iron removed from the body in normal individuals?

1-2mg is lost a day through shedding of mucosal skin and epithelial cells. The body doesn't have a way to excrete excess iron. Bleeding can cause excess lost of iron

where does most iron absorption occur?

Proximal duodenum

What is hepcidin how does it work?

it is a protein used in regulating iron absorption. If iron levels are too high it will block ferroportin 1 in the intestinal lumen. (ferroportin is also in macrophages) In chronic disease hepcidin is upregulated preventing release of iron from macrophages

Iron deficency in western adults is usually due to?

Blood loss until proven otherwise

Iron deficency manifests as:

hypochromic microcytic anemia (low MCHC and low MCV), and increased platelet count

Iron deficency only manifests when:

iron stores are completely depleted and is accomplanied by low serum iron, increase ferritin and total iron binding capacity

what role does Il-6 play in anemia

It increases the level of hepcidin which prevents iron utilization causing anemic of chronic disease

best way to test for B12 deficiency

test for elevated levels of homocysteine and methyl malonic acid in the serum if only homocysteine levels are elevated then it is a folate deficiency

Falconi anemia

a rare autosomal recessive inheirited aplastic anemia caused by deficit in DNA repair protein

Most common cause of pure red cell aplasia

Parvo virus B19

Anisocytosis:

Variation is size (measured with RDW)

Poikilocytosis:

Variation in shape

Anisocytosis can be caused by:

Iron deficiency, transfusion, reticulocytosis, MDS (myelodysplastic syndrome), B12/folate def

Howell-jolley bodies:

associated with megaloblastic anemia, remanats of DNA, associated with increase erythropoiesis, also ass with splenectomy

myleoplastic syndromes:

Cytopenias, oval macrocytes, Dimorphic RBC populations, hypogranular neutrophils, abnormal platelet granules

Depanocyte

sickle cell, elongated cells with a point on each end

Echinocyte

Burr or crenated cells, evenly spaced projections, associated with artifact (most common), uremia, pyruvated kinase deficiency

acanthocyte

spur cell, irregularly spaced projections, associated with end stage liver disease, Mcleod phenotype, abetalipoproteinemia, splenectomy, hypothroidism

helmet cells (keratocyte)

bite cells, ass w/ thrombotic thrombocytopenic purpura, DIC, hemolytic uremic syndrome

Codocytes

target cells, associated with hemoglobinopathies, thalassemias, iron def

darocyte:

tear drop cells, associated with myelofibrosism pyelophthisic anemia, extramedullary hematopoiesis, thalassemia, pernicious anemia

elliptocytosis/ovalocyte:

Associated with hereditary elliptocytosis, thalassemia major, iron-deficiency anemia (pencil cells)

Schistocyte/schizocyte

Indicate red cell fragmentation, associated with Burns, DIC, TTP, mechanical valves

stomatocyte:

RBC with a slit-like area of central palor, associated with hereditary stomatocytosis, alcoholism, liver disease, artifacte

Pappenheimer bodies:

siderotic granules, light blue composed of non-heme iron, smaller than howell-jolley bodies, associated with splenectomy, hemolytic anemia, megaloblastic anemia

Polychromasia/reticuloctye

Immature erythrocytes, Precipitated RNA (stain with methylene blue), associated with acute and chronic hemorrhagem hemolysis

Heinze bodies

Aggregates of Hb, can only be seen with supra vital stains

Basophilic stippling

Composed of RNA, even distribution, associated with lead posioning

Rouleaux

RBCs arranged in a stack, associated with monoclonal gammopathies, hyperfibrinogenemia, increased polyclonal gammaglobulins

Cold agglutination:

Associated with increased IgM, only seen at low temperature , associated with mycolasma pneummoniae infection , infectious mononucleosis, hematologic neoplasms

Name the two sub-classes of lymphoma

Hodgkins and non-hodgkins lymphoma

Leukemia is defined as:

a cancer of the blood or bone marrow

Lymphoma is defined as:

a cancer of lymphatic cells

Chronic myeloid leukemia (CML) is associated with what genetic abnormality?

90% + of patients have philadelphia chromosome (balanced translocation) between chromosome 9 and 22, found in all hematopeotic cells except t lymphocytes, causes BCR ABL gene fusion

Acute myeloid leukemia (AML)

85% have chromosomal abnormalities in varying areas (ex. AML1/ETO t(8;21) APL t(15;17) must know)

Acute promyeloid leukemia (APL)

associated with t(15;17) PML/RAR fusion gene, only seen in APL

Rare inheirited form of leukemia

Familial platelet disorder (FPD)

FLT3 and c-kit are:

important secondary genes associated with leukemia development

Acute Lymphoblastic Leukemia (ALL)

characterized by clonal expansion of leukemic cells in the bone marrow, lymph nodes, thymus or spleen. High hyperdiploidy (51-65 chromosomes: good prognosis) Near haploidy (23-29 chromosome: poor outcome), t(12;21) good, t(9;22) bad

Children with down syndrome have an increased risk of:

20 fold increased risk of developing acute leukemia

Burkitt lymphoma is associated with

activation of MYC gene, t(8;14) (always invloves translocation of chromosome 8)

Minimal residual disease (MRD)

Treatments can reduced levels of leukemic cells below detection levels (1-5%) this is know minimal residual disease, Only PCR can detect if all leukemic cells are truly gone, patients MRD should be monitored for potential relapses

What is 2,3-BPG

2,3-Bisphosphoglycerate it reduces the affinity of hemoglobin for oxygen thus allowing greater release of O2 in the tissues

What are the principle features of extravascular hemolysis?

anemia, jaundice, pigment gallstones, iron overload (hemosiderosis, and secondary hemochromatosis

what are the principle features of intravascular hemolysis?

hemoglobinemia (hemoglobin in the blood), hemoglobinuria (hemoglobin in the urine), jaundice, hemosiderinuria (brown urine caused by shedding of iron bound to hemosiderin into the urine)

What is osmotic fragility test used for?

It is used to CONFIRM hereditary speherocytosis

Name four types of hereditary membrane abnormalities in RBCs:`

1) spherocytosis, 2) Elliptocytosis 3) Pyropoikilocytosis (rare and severe) 4) stomatocytosis (usually an artifact but it can be due to Na/K pump failure, Rh null disease)

What things should never be given to G6PD patients

Anything that will increase oxidative stress, like mararia durgs primaquine or chloroquine. Also NO fava beans

What features are seen in G6PD deficient patients?

Heinz bodies, leading to "bite" cells or helmet cells

What are the key features in pyruvate kinase deficiency?

Decreased ATP, ADP, AMP. Increased 2,3-DPG. Leads to rigid RBCs that cannot cross vasculature effectively and are hemolyized, causing hemolytic anemia. More common in northern europeans. Echinocytes or burr cells seen

What does thalassemia mean? What does hemoglobinopathy mean?

Thalassemia means decreased synthesis of globin. Heompglobinopathy means structurally abnormal hemoglobin

What are thalassemia major characterisitcs?

ansiocytosis, microcytosis, poikilocytosis, hypochromia, target cells, basophilic stipiling, elevated reticulocyte count. Major marrow expansion and possible spenomegaly

What are thalassemia minor characterisitcs?

mild hypochromic, microcytic anemia. Increased hemoglobin A2 levels

Name two tests frequently used to test for sickle cell disease:

Hemoglobin solubility test (patient has sickle cell if hemoglobin is soluble), Hemoglobin electrophoresis

If you see RBC cells described are washington monument cells what should you think of?

Hemoglobin C (mild form of sickle cell disease seen in africans)

Paroxysmal noctural hemoglobinuria (PNH) cause by

mutation in the phosphatidylinositol glycan complement group A gene (PIGA), X-linked, causes deficency in GPI-linked proteins. Most important protein that is effected CD 59 (CD55, and CD8 also effected). When CD59 is effected increased complement lysis of RBCs occur

Characteristics of Warm immune hemolytic anemia

IgG mediated, Occurs at body temp, complement fixation not usually found. Usually extravascular hemolysis