Etiology and Risk Factors of Deep Vein Thrombosis

What are the causes of deep vein thrombosis?

Blood is meant to flow; if it becomes stagnant there is a potential for it to clot. The blood in veins is constantly forming microscopic clots that are routinely broken down by the body. If the balance of clot formation and resolution is altered, significant clotting can occur. A thrombus can form if one, or a combination of the following situations is present.

Immobility - causes blood flow in the veins to be slow. Slow-flowing blood is more likely to clot than normal-flowing blood.

• Prolonged travel and sitting, such as long airplane flights ("economy class syndrome"), car, or train travel
• Hospitalization

• Surgery
• A surgical operation that lasts more than 30 minutes is the most common cause of a DVT. The legs become still when you are under anaesthetic. Blood flow in the leg veins can become very slow.

• Trauma to the lower leg with or without surgery or casting
• Pregnancy, including 6-8 weeks post partum
• About 1 in 1,000 pregnant women have a DVT while they are pregnant, or within about six months after they give birth.
• Obesity

Hypercoagulability (coagulation of blood faster than usual)

• Medications (for example, birth control pills, estrogen)
• The contraceptive pill and hormone replacement therapy (HRT) that contain oestrogen can cause the blood to clot slightly more easily.
• Smoking
• Genetic predisposition
• Polycythemia (increased number of red blood cells)
• Cancer
• Conditions that cause the blood to clot more easily than normal (thrombophilia)
• Some conditions can cause the blood to clot more easily than usual. For example, nephrotic syndrome and antiphospholipid syndrome. Some rare inherited conditions can also cause the blood to clot more easily than normal. For example, factor V Leiden

Trauma to the vein - Damage to the inside lining of the vein increases the risk of a blood clot forming. For example, a DVT may damage the lining of the vein. So, if you have a DVT, then you have an increased risk of having another one in the future. Some conditions such as vasculitis (inflammation of the vein wall) and some drugs (for example, some chemotherapy drugs) can damage the vein and increase the risk of having a DVT.

• Fracture to the leg
• Bruised leg
• Complication of an invasive procedure of the vein

Complication of Deep Vein Thrombosis (DVT)

Complication of Deep Vein Thrombosis (DVT)

Primary Complication

1.Pulmonary embolism

-Artery in the lungs is blocked by thrombus (usually from the legs)

-At least 10% of patients with DVT hv PE

-Can be fatal

-Sign and symptoms of pulmonary embolism include: unexplained dyspnea, angina (get worse when patient take a deep breath or cough), lightheaded/dizzy, and cough out blood

-Complication of PE includes: palpitation, heart failure, and pulmonary hypertension

2.Post-phlebitic syndrome

-Aka post-thrombotic condition

-2/3 patients will have this.

-A collection of signs and symptoms, including: edema, leg pain, hyperpigmentation, skin ulcer, varicose vein, PE

-Caused by damage to the veins, or a valve in the vein from the blood clot

-It reduces blood flow in the affected area

Other DVT Complications:

-less common

-renal vein thrombosis

-blood clot in the heart, leading to myocardial infarction

-stroke

References:

http://www.webmd.com/dvt/deep-vein-thrombosis-complications

Veganism

What is a vegan?
Veganism is a philosophy and lifestyle whose adherents seek to exclude the use of animals for food, clothing, or any other purpose.
Vegans endeavor not to use or consume animal products of any kind
A vegan does not eat any fish, meat, poultry, eggs, dairy products or foods that contain any of these products.
They also do not use any non-food items that contain products from animals, including wool from sheep, leather and silk.
Vegans often do not eat honey, because bees may be killed while harvesting it.
According to many vegans, it is pronounced VEE-gun. A vegan diet consists of vegetables, grains, beans, nuts, fruits and seeds. This diet tends to be high in fiber and moderate in protein and fat.
A vegan will not use margarine that has casein, a milk product, in it.
They also do not use products that are tested on animals, as are many cosmetics.
 Properly planned vegan diets are healthful and have been found to satisfy nutritional needs, and may offer protection against heart disease, cancer, and other diseases. Poorly planned vegan diets can be low in levels of calcium, iodine, vitamin B12, iron and vitamin D.
 Various polls have reported vegans to be between 0.2%[4] and 1.3%[9] of the U.S. population,
 People who avoid meat are reported to have lower body mass index than those following the average Canadian diet; from this follows lower death rates from ischemic heart disease; lower blood cholesterol levels; lower blood pressure; and lower rates of hypertension, type 2 diabetes, and prostate and colon cancer.[6]


• Lacking those essential nutrients can cause several different complications
 Anaemia
 Rickets
 Cretinism
 Osteomalacia
 hypothyroidism





DEFICIENCY IN B12
 It is a bacterial product that cannot be easily found in plant food.
 Lacking this can cause anemia and neurodegenerative disease
 The Vegan Society and Vegan Outreach, among others, recommend that vegans either consistently eat foods fortified with B12 or take a B12 supplement to prevent deficiency.
IRON DEFICIENCY
 Lead to iron deficiency anaemia
 Those are especially in risk are
 Menstruating
 Breastfeeding
 Pregnant woman
 Iron is less absorbed in a vegetarian diet
 Only 10 % compared to omnivorous diet of 18 %.
 Vegans take Molasses as iron supplement

CALCIUM AND VITAMIN D
 It is recommended that vegans eat three servings per day of a high calcium food, such as fortified soy milk, almonds, hazelnuts, and take a calcium supplement as necessary
 The EPIC-Oxford study showed that vegans have an increased risk of bone fractures over both meat eaters and vegetarians, likely due to lower dietary calcium intake, but that vegans consuming more than the UK's estimated average requirements for calcium of 525 mg/day had risk of bone fractures similar to other groups.

The American Dietetic Association considers well-planned vegan diets "appropriate for all stages of the life cycle, including pregnancy and lactation,"[6] but recommends that vegan mothers supplement for iron, vitamin D, and vitamin B12.

Complete Blood Count

COMPLETE BLOOD COUNT (FBC)

PURPOSE

• Performed under many different conditions and to assess many different symptoms or diseases
• The test can reveal problems with RBC production and destruction, or help diagnose infection, allergies, and problems with blood clotting.
• MCV, MCH, and MCHC values reflect the size and hemoglobin concentration of individual cells, and are useful in diagnosing different types of anemia.

HOW IS IT PERFORMED?

·         Blood drawn from a vein (on inside of the elbow or the back of the hand) and site is cleaned with antiseptic.

·         Elastic band wrapped around the upper arm to apply pressure to the area and make the vein swell with blood.

·         Needle inserted into vein and blood is collected into airtight vial or tube.

COMPONENTS

·         White blood cell count (WBC or leukocyte count)

o    Number of white blood cells in a volume of blood

·         White blood cell (WBC) differential count

o    Granulocytes, lymphocytes, monocytes, eosinophils, and basophils.

o    Differentiated by shape and size

o    Automated or manual WBC differential

·         Red cell count (RBC or Erythrocyte Count)

o    Number of red blood cells in a volume of blood

·         Hemoglobin (Hb)

o    Amount of hemoglobin in a volume of blood.

·         Hematocrit (Hct). 

o    Ratio of the volume of red cells to the volume of whole blood.

o    Measured by centrifugation

·         Mean corpuscular volume (MCV) 

o    Average volume of a red blood cell.

·         Mean Corpuscular Hemoglobin (MCH) 

o    Average amount of hemoglobin in the average red cell.

o    Calculated value derived from the measurement of Hb and RBC count.

·         Mean Corpuscular Hemoglobin Concentration (MCHC)

o    Average concentration of hemoglobin in a given volume of red cells.

·         Red Cell Distribution Width (RDW) 

o    Measurement of the variability of red cell size and shape.

o    Higher numbers indicate greater variation in size.

o    Normal range is 11 to 15.

·         Platelet count.

o     The number of platelets in a specified volume of blood.

o    Normal range: 150,000 to 400,000/ cmm (150 to 400 x 109/liter).

·         Mean Platelet Volume (MPV).

o     The average size of platelets in a volume of blood

o   7.5-11.5

NORMAL VALUES

• RBC count (varies with altitude):
• Male: 4.7 to 6.1 million cells/mcL
• Female: 4.2 to 5.4 million cells/mcL
• WBC count: 4,500 to 10,000 cells/mcL
• Hematocrit (varies with altitude):
• Male: 40.7 to 50.3 %
• Female: 36.1 to 44.3 %
• Hemoglobin (varies with altitude):
• Male: 13.8 to 17.2 gm/dL
• Female: 12.1 to 15.1 gm/dL
• MCV: 80 to 95 femtoliter
• MCH: 27 to 31 pg/cell
• MCHC: 32 to 36 gm/dL

(cells/mcL = cells per microliter; gm/dL = grams per deciliter; pg/cell = picograms per cell)

REFERENCES
http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm
http://www.medicinenet.com/complete_blood_count/page2.htm

Differential Diagnosis of Anaemia

Iron deficiency anaemia : heavy menstrual , gastrointestinal cancer• The haemoglobin level. Haemoglobin is the iron-rich protein in red blood cells that carries oxygen through the body. The normal range of haemoglobin levels for the general population is 11.1-15.0 g/dL. A low haemoglobin level means a person has anaemia.
• The haematocrit (hee-MAT-oh-crit) level. The normal range for haematocrit levels for the general Red blood cell size. The mean cell volume measures the average size (volume) of red blood cells. In iron-deficiency anaemia, the red blood cells are often smaller than normal.
• A low haematocrit level is another sign of anaemia.
• Serum iron. This test measures the amount of iron in the blood. The level of iron in the blood can be normal even when the total amount of iron in the body is low. For this reason, other iron tests are done.
• Serum ferritin. Ferritin is a protein that helps store iron in the body. Results of this test give doctors a good idea of how much of the body's stored iron has been used up.
• Transferrin level or total iron-binding capacity. Transferrin is a protein that carries iron in the blood. Total iron-binding capacity measures how much of the transferrin in the blood is not carrying iron. People with iron-deficiency anaemia have a high level of transferrin that has no iron.
Gastrointestinal cancer :
One of the first tests ordered is the faecal occult blood test. This test checks the stool for signs of blood. It can detect even small amounts of bleeding anywhere in the intestines. If blood is found in the stool, further tests may be used to find the source of the bleeding, including:
• Colonoscopy. In this test, a thin, flexible tube attached to a video camera is used to examine the rectum and colon for sources of bleeding.
• Upper GI endoscopy. In this test, a thin, flexible tube attached to a video camera is used to examine the stomach and upper intestines. The doctor looks for signs of bleeding.
• Pelvic ultrasound. This test uses sound waves to look at the uterus and other pelvic organs. It checks for causes of heavy vaginal bleeding, such as fibroids.

Vitamin B12 deficiency (pernicious anaemia):• the red blood cells will be the usual colour but larger than normal.
• If the blood test shows a low vitamin B12 count, it must be established whether it is pernicious anaemia or if there is some other cause.
• The Schilling test measures the body's ability to absorb vitamin B12 from the bowel. This will show whether the anaemia is caused by a lack of intrinsic factor.
• Blood tests will also confirm if you have any antibodies to intrinsic factor.


Sickle cell: (haemolytic anaemia)
• Sickle cell anemia is suggested when the abnormal sickle-shaped cells in the blood are identified under a microscope. Testing is typically performed on a smear of blood using a special low-oxygen preparation. This is referred to as a sickle prep.
• Other prep tests can also be used to detect the abnormal hemoglobin S, including solubility tests performed on tubes of blood solutions.
• The disease can be confirmed by specifically quantifying the types of hemoglobin present using a hemoglobin electrophoresis test.The hemoglobin electrophoresis test precisely identifies the hemoglobins in the blood by separating them. The separation of the different hemoglobins is possible because of the unique electrical charges they each have on their protein surfaces, causing them each to move characteristically in an electrical field as tested in the laboratory.

Thalassemia:
• A CBC: People who have thalassemias have fewer healthy red blood cells and less hemoglobin in their blood than normal. People who have alpha or beta thalassemia trait may have smaller than normal red blood cells.
• Hemoglobin tests: People who have thalassemias have problems with the alpha or beta globin protein chains of hemoglobin.
• This involves taking a family medical history and doing blood tests on family members to show whether any have missing or altered hemoglobin genes.

Leukemia:• Blood tests: The lab does a complete blood count to check the number of white blood cells, red blood cells, and platelets. Leukemia causes a very high level of white blood cells. It may also cause low levels of platelets and hemoglobin, which is found inside red blood cells.
• Biopsy: Your doctor removes tissue to look for cancer cells. A biopsy is the only sure way to know whether leukemia cells are in your bone marrow.
• Bone marrow biopsy: The doctor uses a very thick, hollow needle to remove a small piece of bone and bone marrow.The bone marrow is examined under a microscope, where the presence of leukemic cells confirms the suspected diagnosis.
• Genetic studies: The chromosomes of the abnormal cells are examined to look for irregularities. This helps in classifying the various types of leukemia.

Aplastix Anaemia : (eg. Chronic kidney disease)
Doctors diagnose aplastic anemia using blood tests and bone marrow biopsy.
• Blood tests. Normally, red blood cell, white blood cell and platelet levels stay within a certain range. Your doctor may suspect aplastic anemia when all three of these blood cell levels are very low. Many conditions can cause low blood cell counts, but usually of just one type of blood cell. For example, other types of anemia cause a decrease in red blood cells. If you have an infection, your white blood cell count alone may be low.
• Bone marrow biopsy. To confirm a diagnosis, you'll need to undergo a bone marrow biopsy. In this procedure, a doctor uses a needle to remove a small sample of bone marrow from a large bone in your body, such as your hipbone. The bone marrow sample is examined under a microscope to rule out other blood-related diseases. In aplastic anemia, bone marrow contains fewer blood cells than normal. The few cells that are present, however, are normal. In certain diseases such as leukemia and myelodysplastic syndrome, the bone marrow is full of abnormal blood cells.

Chronic kidney disease:• If a person has lost at least half of normal kidney function and has a low hematocrit, the most likely cause of anemia is decreased EPO production.
• The estimate of kidney function, also called the glomerular filtration rate, is based on a blood test that measures creatinine.

Aluminium poisoning

Hypothyroidism : (macrocytic anaemia)
Anemia is often present, usually normocytic-normochromic and of unknown etiology, but it may be hypochromic because of menorrhagia and sometimes macrocytic because of associated pernicious anemia or decreased absorption of folate. Anemia is rarely severe (Hb > 9 g/dL). As the hypometabolic state is corrected, anemia subsides, sometimes requiring 6 to 9 mo.

B12 , Folic Acid and Iron

Vitamin B12
• Most chemically complex of all vitamins.
• Foods that come from animals, including fish and shellfish, meat (especially liver), poultry, eggs, milk, and milk products
• Fx- DNA synthesis and regulation / Fatty acid synthesis and energy production / Folate.
• Cyanocobalamin – synthetic form, supplements and food addictive. Body converted to methylcobalamin and adenosylcobalmin leaving cyanide behind. Hydroxycobalamin is the another form from bacteria and it’s more epx than cyanocobalamin cause it’s easier converted to active forms.
• Starts absorption in the mouth where unbound B12 and acid in stomach where protein bounded B12 is digested and freed by binding to intrinsic factor. IF/B12 complex is recognized by ileal receptors and transported to portal circulation and stored in liver.
• Two enzymatic reaction dependent of B12[co-factor]

• Methionine is required for lipid synthesis for myelin synthesis.
• Pernicious anemia – lack of intrinsic factor that would cause incapable of B12 absorption.
• Usually B12 deficiency is due to genetic factors which limit the absorption.
Folic Acid [B9]
• Both animal and plants –green leafy vegetables, legumes, yeast, fish
• Active forms – tetrahydrofolate and dihydrofolic acid.
• Fx – DNA synthesis and repair / cofactor involving folate reaction.
• Folate deficiency causes neural tube defects in 1st trimester [spina bifida, anencephaly] / cancer development
Both B9 and B12
• Deficiency causes elevated Homocysteine
o Homocysteine is an amino acid in the blood. Too much of it is related to a higher risk of coronary heart disease, stroke and peripheral vascular disease
Mineral: Iron
• Heme and non heme iron. Heme from animals such as red meat, fish and poultry. Non heme from plants such as lentils and beans. Heme iron is absorbed better.
• Fx
o Both an electron donor and acceptor.

o Used to produce Heme. Heme+globulin become hemoglobin order to transport oxygen from the lungs to the tissues and to export carbon dioxide back to the lungs. Iron is also an essential component of myoglobin to store and diffuse oxygen in muscle cells.
o Bacterial protection by limiting the storage of irons in the body. Iron is important for the survival of the bacteria. Hemochromatosis individuals are more susceptible to infections.
• Body stores 3-4g iron in bod. Men got more stores of iron than women due to the heavy usage of women during menstruation, pregnancy and lactation.
• Lose 1-1.5mg perday by sweating and shedding cells from skin and mucosal lining of GIT.
• Iron absorption

o Ferric Fe3+ to Ferrous Fe2+ before can be absorbed. [ferric reductase enzyme] at brush border of enterocyte.
o Body stores iron in the form of Ferritin. Ferritin is then bounded to transferin through a pore called ferroportin to be carried to parts of the body. Mostly to the liver hepatocytes for storage, bone marrow and spleen.

How to differentiate different types of anaemia based on FBC and other investigation?

How to differentiate different types of anaemia based on FBC and other investigation?


1. Iron Deficiency Anaemia
a. Plasma ferritin

i. A very specific test
ii. Subnormal level is due to iron deficiency, hypothryroidism or Vitamin C deficiency
iii. Can be raised by liver disease andnin an acute phase response (can be up to 100millig/l and still associated with absent bone marrow iron stores
b. Plasma iron and total iron binding capacity (TIBC)

i. Affected by many factors
ii. Low during an acute phase response and raised in liver disease and haemolysis.
c. Transferrin saturation

i. Lowered by malnutrition, liver disease, acute phase response and nephritic syndrome
ii. Raised by pregnancy or OCP
iii. Transferrin saturation of less than 16% is consistent with iron deficiency but is less specific than a ferritin measurement.
d. Transferrin receptors

i. All proliferating cells express membrane tranferrin receptors to acquire iron
ii. Small amount of transferring receptor is shed into blood and found in a free soluble form
iii. At time of poor iron stores, cells up-regulate transferring receptor expression so levels of soluble plasma transferring receptors increase.
iv. Measure by immunoassay


2. Megaloblastic Anaemia

a. Haemoglobin: often reduced, may be very low
b. MCV: usually raised, commonly > 120 fl
c. Erythrocyte count: low for degree of anaemia
d. Blood film: ocal macrocytosis, poikilocytosis, red cell fragmentation, neutrophil hypersegmentation
e. Reticulocyte: low for degree of anaemia
f. Leucocyte: Low or normal
g. Platelet count: low or normal
h. Bone marrow: increased cellularity, megaloblastic changes in erythroid series, giant metamyelocytes, dysplastic megakaryocytes, increased iron in stores, pathological non-ring sideroblasts

3. Anaemia of Chronic Disease

a. Difficult to distinguish anaemia of chronic disease associated with a low MCV from iron deficiency anaemia.
b. Anaemia of chronic disease: increased/normal Ferrition, decreased iron, TIBC, transferring saturation, decreased/ normal soluble transferring receptor
c. Iron Deficiency anaemia: decreased ferritin, iron, transferring saturation, increased TIBC and soluble transferring receptor.

Complications of Blood Transfusions

Complications for Transfusion (I will briefly also talk about what transfusion means, not mentioned here)

Acute hemolytic transfusion reaction (AHTR): AHTR usually results from recipient plasma antibodies to donor RBC antigens. ABO incompatibility is the most common cause of AHTR. Antibodies against blood group antigens other than ABO can also cause AHTR. Mislabeling the recipient's pretransfusion sample at collection or failing to match the intended recipient with the blood product immediately before transfusion is the usual cause, not laboratory error.
Hemolysis is intravascular, causing hemoglobinuria with varying degrees of acute renal failure and possibly disseminated intravascular coagulation (DIC). The severity of AHTR depends on the degree of incompatibility, the amount of blood given, the rate of administration, and the integrity of the kidneys, liver, and heart. Dyspnea, fever, chills, facial flushing, and severe pain may occur, especially in the lumbar area. Shock may develop, causing a rapid, feeble pulse; cold, clammy skin; low BP; and nausea and vomiting. Jaundice may follow acute hemolysis.

Delayed hemolytic transfusion reaction: Occasionally, a patient who has been sensitized to an RBC antigen has very low antibody levels and negative pretransfusion tests. After transfusion with RBCs bearing this antigen, a primary or anamnestic response may result (usually in 1 to 4 wk) and cause a delayed hemolytic transfusion reaction. Delayed hemolytic transfusion reaction usually does not manifest as dramatically as AHTR. Patients may be asymptomatic or have a slight fever. Rarely, severe symptoms occur. Usually, only destruction of the transfused RBCs (with the antigen) occurs, resulting in a falling Hct and a slight rise in LDH and bilirubin.

Febrile nonhemolytic transfusion reaction: Febrile reaction may occur without hemolysis. Antibodies directed against WBC HLA from otherwise compatible donor blood are one possible cause. This cause is most common in multitransfused or multiparous patients. Cytokines released from WBCs during storage, particularly in platelet concentrates, is another possible cause.

Allergic reactions: Allergic reactions to an unknown component in donor blood are common, usually due to allergens in donor plasma or, less often, to antibodies from an allergic donor. These reactions are usually mild, with urticaria, edema, occasional dizziness, and headache during or immediately after the transfusion. Simultaneous fever is common. Less frequently, dyspnea, wheezing, and incontinence may occur, indicating a generalized spasm of smooth muscle. Rarely, anaphylaxis occurs, particularly in IgA-deficient recipients.

Volume overload: The high osmotic load of blood products draws volume into the intravascular space over the course of hours, which can cause volume overload in susceptible patients (eg, those with cardiac or renal insufficiency). RBCs should be infused slowly. The patient should be observed and, if signs of heart failure (eg, dyspnea, rales) occur, the transfusion should be stopped and treatment for heart failure begun.

Acute lung injury: Transfusion-related acute lung injury is an infrequent complication caused by anti-HLA and/or anti-granulocyte antibodies in donor plasma that agglutinate and degranulate recipient granulocytes within the lung. Acute respiratory symptoms develop, and chest x-ray has a characteristic pattern of noncardiogenic pulmonary edema.

Altered oxygen affinity: Blood stored for > 7 days has decreased RBC 2,3-diphosphoglycerate (DPG), and the 2,3-DPG is absent after > 10 days. This absence results in an increased affinity for O2 and slower O2 release to the tissues. There is little evidence that 2,3-DPG deficiency is clinically significant except in exchange transfusions in infants, in sickle cell patients with acute chest syndrome and stroke, and in some patients with severe heart failure. After transfusion of RBCs, 2,3-DPG regenerates within 12 to 24 h.

Graft-vs-host disease (GVHD): Transfusion-associated GVHD is usually caused by transfusion of products containing immunocompetent lymphocytes to an immunocompromised host. The donor lymphocytes attack host tissues. GVHD can occur occasionally in immunocompetent patients if they receive blood from a donor who is homozygous for an HLA haplotype (usually a close relative) for which the patient is heterozygous. Symptoms and signs include fever, skin rash (centrifugally spreading rash becoming erythroderma with bullae), vomiting, watery and bloody diarrhea, lymphadenopathy, and pancytopenia due to bone marrow aplasia. Jaundice and elevated liver enzymes are also common. GVHD occurs 4 to 30 days after transfusion and is diagnosed based on clinical suspicion and skin and bone marrow biopsies.

Complications of massive transfusion: Massive transfusion is transfusion of a volume of blood greater than or equal to one blood volume in 24 h (eg, 10 units in a 70-kg adult). When a patient receives stored blood in such large volume, the patient's own blood may be, in effect, “washed out.” . Microvascular bleeding (abnormal oozing and continued bleeding from raw and cut surfaces) may result.
Hypothermia due to rapid transfusion of large amounts of cold blood can cause arrhythmias or cardiac arrest. Hypothermia is avoided by using an IV set with a heat-exchange device that gently warms blood.

Infectious complications: Bacterial contamination of packed RBCs occurs rarely, possibly due to inadequate aseptic technique during collection or to transient asymptomatic donor bacteremia. Refrigeration of RBCs usually limits bacterial growth except for cryophilic organisms such as Yersinia sp, which may produce dangerous levels of endotoxin. All RBC units are inspected before issue for bacterial growth, which is indicated by a color change. Because platelet concentrates are stored at room temperature, they have greater potential for bacterial growth and endotoxin production if contaminated. To minimize growth, storage is limited to 5 days. The risk of bacterial contamination of platelets is 1:2500. Therefore, platelets are routinely tested for bacteria.

Neck I: Posterior Region of Neck

Task I: Nabila & Nicholas
Task II: Timothy
Task III: Fahad
Task IV:Yi Zhen
Task V: Wen Jye
Task VI:Chesvin
task VII:Da Wei & Xin Yi
Task VIII:Phey Chien & Rebekah
Task IX:Nabila

Types of Anemias

Anemias can be classified using two basic approaches:

• etiology (pathophysiology): the causes of erythrocyte and hemoglobin depletion
• morphology: the characteristic changes in the erythrocytes red blood cells (RBCs), size, shape, and color

An etiologic classification is based on the various conditions that can result from any of the physiologic changes and helps determine direction for planning care. A morphologic classification provides an orderly method for ruling out certain diagnoses when establishing a cause for a particular anemia.

Such morphologic changes in the red blood cell are described in this manner:

• Cell size: (Terms that refer to cellular size end with "cytic".)

normocytes (normal)

microcytes (smaller than normal)

macrocytes (larger than normal)

anisocytes (various sizes)

• Cell shape:

poikilocytes (irregularly-shaped cells)

spherocytes (globular cells)

drepanocytes (sickle cells)

• Cell color: (generally refers to the staining characteristics which reflects the hemoglobin concentration. Terms that describe hemoglobin content end with "chromic".)

normochromic (sufficient or normal amounts of hemoglobin)

hyperchromic (containing an unusually high concentration of hemoglobin in its cytoplasm)

hypochromic (containing an abnormally low concentration of hemoglobin)

These changes produce the following categories of anemias:

• Macrocytic-normochromic anemias (pernicious and folate-deficiency)
• Microcytic-hypochromic anemias (iron-deficiency, sideroblastic, thalassemia)
• Normocytic-normochromic anemias (aplastic, posthemorrhagic, hemolytic, chronic disease, sickle cell)

Macrocytic-normochromic anemia, also known as megaloblastic anemia, produces large, abnormally shaped erythrocytes but normal hemoglobin concentrations. The unusually large stem cells (megaloblasts) in the bone marrow mature into abnormally large erythrocytes (macrocytes) in the circulation. Megaloblastic stem cells are larger at all maturational stages than normal stem cells (normoblasts). In addition, the nucleus of the megaloblast is unusually small in relation to the size of the cell. As the cell matures and begins to synthesize hemoglobin, chromatin in the nucleus fails to clump normally, although the hemoglobin content remains normal. Defective DNA synthesis, caused by deficiencies of vitamin B12 or folate, produces a pattern of ineffective erythropoiesis (cell formation), causing premature cell death with reduced numbers of mature erythrocytes. It is unknown why such a deficiency would cause this outcome, but suggested mechanisms include a delay in nuclear maturation and an imbalance in the normal distribution of RNA and DNA. Nuclear functions or DNA replication and cell division are blocked or delayed. However, RNA and protein synthesis, both cytoplasmic functions proceed normally. The imbalance in the RNA/DNA ratio causes derangement of cell growth.

Microcytic-hypochromic anemia produces small, abnormally small erythrocytes and reduced hemoglobin concentrations. However, hypochromia can occur even in cells of normal size. This type of anemia results from a variety of conditions that are caused by disorders of iron metabolism, porphyrin and heme synthesis, or globin synthesis.

Normocytic-normochromic anemia produces a destruction or depletion of normal or mature erythrocytes. Although the erythrocytes are relatively normal in size and in hemoglobin content, they are insufficient in number. This type does not share any common cause, pathologic mechanism, or morphologic characteristics and is less common than the others. The five distinct anemic conditions exemplify the diversity of this classification.

• Aplastic anemia (caused from depressed stem cell proliferation resulting in bone marrow aplasia)
• Posthemorrhagic anemia (caused from an abnormal amount of blood loss)
• Hemolytic anemia (premature destruction [lysis] of mature erythrocytes in the circulation)
• Anemia of chronic disease (chronic infection or inflammation or malignancy causes an abnormally increased demand for new erythrocytes)
• Sickle cell anemia (congenital dysfunction of hemoglobin synthesis causing abnormal cell shapes)

Data used to identify anemia types include the erythrocyte indicators:

• mean corpuscular volume (MCV), measures the average erythrocyte volume
• mean corpuscular hemoglobin (MCH), measures the average amount of hemoglobin per erythrocyte
• mean corpuscular hemoglobin concentration (MCHC), measures the average concentration of hemoglobin in erythrocytes.

Some types of anemia include the following:

• Achrestic anemia is a megaloblastic type, morphologically resembling pernicious anemia but with multiple other causes.
• Aplastic anemia is a form generally unresponsive to specific anti-anemia therapy and is often accompanied by granulocytopenia (a sudden drop in the production of leukocytes) and thrombocytopenia (a decrease in the number of platelets in circulating blood), in which the bone marrow may not necessarily be lacking cells or a normal cellular structure (acellular) but still fails to produce adequate numbers of blood elements. The term actually is all-inclusive, generally encompassing several clinical syndromes.
• Autoimmune hemolytic anemia (AIHA) is a general term used to cover a large group of anemias involving auto-antibodies against red cell antigens.
• Cooley's anemia is the homozygous form of beta-thalassemia.
• Deficiency anemia refers to a nutritional deficiency that causes anemia.
• Drug-induced immune hemolytic anemia is, as the name suggests, an immune hemolytic anemia caused by drugs, classified by such mechanisms as:

the penicillin type, in which the drug, acting as a hapten is bound to the red cell membrane which induces the formation of specific antibodies

the methyldopa type, in which the drug, possibly by inhibition of suppressor T cells, indicates the formation of anti-Rh antibodies, and

the stibophen or "innocent bystander" type, in which the circulating drug-antibody immune complexes binds nonspecifically to red cells.

• Erythroblastic anemia (see Cooley’s anemia).
• Hemolytic anemia is caused by a shortened survival of mature erythrocytes and the ability of bone marrow to compensate for their decreased life span. It may be hereditary or acquired and usually results from an infection or chemotherapy, or occurs as part of an autoimmune process. Hypochromic anemia occurs when there is a decrease in hemoglobin that is proportionately much greater than the decrease in the number of erythrocytes.
• Hypoplastic anemia is the result of the incapacity of blood-forming organs. Such anemias as Diamond-Blackfan, Pearson’s, transient,erythroblastopenia of childhood (TEC), and Fanconi’s are classified under hypoplastic anemia.
• Hypoplastic congenital anemia, also called erythrogenesis imperfecta and Fanconi's syndrome, is an idiopathic progressive form occurring in the first year of life and without leukopenia and thrombocytopenia. It is unresponsive to hematinics (an agent that improves the quality of the blood) and requires multiple blood transfusions to sustain life.
• Iron-deficiency anemia is characterized by low or absent iron stores, low serum iron concentration, low transferrin saturation, elevated transferrin (total iron-binding capacity), low hemoglobin concentration or hematocrit, and hypochromic and microcytic red blood cells. Its frequent occurrence in children is usually the result of prolonged milk feeding without the provision of a variety of foods or supplemental iron.
• Lederer's anemia is an acute hemolytic form of short duration and unknown etiology.
• Macrocytic anemia results when the erythrocytes become much larger than normal.
• Mediterranean anemia (see Cooley’s anemia)
• Megaloblastic anemia is characterized by the presence of megaloblasts in the bone marrow. Megaloblasts are large, nucleated, immature progenitors of an abnormal erythrocytes and form in certain types of anemia. These cells are irregular in shape and size but contain normal concentrations of hemoglobin and the numbers are below normal. This reaction involves the abnormal production of red cells, white cells, and platelets. There are two types of megoblastic anemias and both are the result of a deficiency (folic acid or B12).
• Microcytic anemia is characterized by a decrease in size of erythrocytes.
• Myelopathic, or myelophthisic, anemia is caused by the destruction or crowding out of hematopoietic tissues by space-occupying lesions. (Hematopoietic pertains to or affecting the formation of blood cells.)
• Normochromic anemia occurs despite the hemoglobin content of the red blood cells, as measured by the MCHC (mean corpuscular hemoglobin concentration), is still within the normal range.
• Normocytic anemia is characterized by proportionate decreases in hemoglobin, packed red cell volume, and the number of erythrocytes per cubic millimeter of blood.
• Nutritional anemia, also known as "deficiency anemia", is caused by a deficiency of an essential substance in the diet, and may be caused by poor dietary intake or by malabsorption.
• Pernicious anemia is a serious form that results from a lack of vitamin B12, generally because of a decreased secretion by the gastric mucosa of IF (intrinsic factor) essential to the formation of erythrocytes and the absorption of vitamin B12. This condition may be secondary to an illness or idiopathic (formed from unknown causes). Treatment consists of regular, lifetime administrations of the vitamin.
• Sickle cell anemia, sometimes called sickle cell disease, is a genetically determined defect of hemoglobin synthesis associated with poor physical development and skeletal anomalies.
• Spur-cell anemia occurs when the red cells have a bizarre spiculated shape and are destroyed prematurely, primarily in the spleen. It is an acquired form occuring in severe liver disease and represents an abnormality in the cholesterol content of the red cell membrane.
• Von Jaksch’s anemia, also known as pseudoleukemica infantum, is an anemic leukemia of infants and probably not a distinct disease. It is a syndrome caused by many factors: malnutrition, chronic infection, malabsorption, or other conditions. There seems to be some developmental basis for the inability of these babies to react to infectious processes in a normal manner. This disease follows, or is associated with, some severe nutritional or infectious disease and is characterized by anemia of increasing severity, splenomegaly and myeloid leucocytosis, together with the symptoms of the underlying disease. It is possible that symptoms of severe malnutrition ordinarily supposed to be the cause of the anemia, may really be the earlier symptoms of the disease itself, as an entity caused by developmental defect in the spleen and red bone marrow. It was once considered to be a specific entity in children under the age of three.