Overview of Anemia MSN

Putting These Tests Together

Identifying anemia is present Helps to point to a cause based on - Size (MCV) - hemoglobin concentration (MCHC) - proliferative capacity (retic)

Peripheral Smear

tells us the Size, Color, and Shape of red blood cells Many abnormal shapes can identify causes Abnormal white blood cells and platelets (like leukemic cells)

Signs and Symptoms

Can be VERY non-specific Related to the degree of anemia, how long it takes for the patient to become anemic, and how well the patient can compensate Fatigued Light-headed or dizzy Headaches (migraines) Palpitations Chest Pain Dyspnea on Exertion Shortness of Breath Decreased exercise tolerance Pallor Tachycardia "i don't feel quite right" type symptoms

Other Causes of Decreased Production

- Alcohol- through B12/folate AND through direct toxicity...ETOH can actually poison the bone marrow - Liver Disease (Also decreased production of some blood making components) - Drugs - Hypothyroidism

Sideroblastic Anemia Lab results: MCV Relic Iron levels

- CBC: Microcytosis - Low reticulocytes (because the body just gives up trying to replace them) - High iron levels (b/c there is a ton of iron with nowhere to go)

Diagnosis

- Complete Blood Count (this is your MAIN tool) this is probably what will tell you your patient is anemic in the first place Hemoglobin, Hematocrit, RBC, MCV - Reticulocyte Count - Peripheral Blood Smear YOUR THREE CORE TESTS ARE: CBC, Retic, and Smear!!!!! Other Tests as Indicated: - Iron, iron saturation, total iron binding content, ferritin, transferrin - B12, folate (methylmalonic acid) - LDH, haptoglobin, bilirubin - Hemoglobin electrophoresis, hemoglobin A2 and hemoglobin F - Serum protein electrophoresis - Renal function - Bone Marrow Biopsy

Measuring Iron Levels

- Ferritin*** Ferritin reflects total iron binding stores - Iron Saturation - Total Iron Binding Content - Transferrin Ferritin in women ranges btwn 12 - 150.... if your ferritin level is less than 10 YOU ARE IRON DEFICIENT regardless of what else is going on. FERRITIN - Reflects total body iron stores (how much iron you have floating around). The ferritin blood test measures the level of ferritin in the blood. - Ferritin is a protein inside your cells that stores iron. It allows your body to use the iron when it needs it. A ferritin test indirectly measures the amount of iron in your blood. Ferritin isn't the same thing as iron in your body. Instead, ferritin is a protein that stores iron, releasing it when your body needs it. Ferritin usually lives in your body's cells, with very little actually circulating in your blood. - Women: 12 to 150 - Men: 10 to 345 - Incredible sensitive test, may go down before anemia is even present - May go up in iron overload - Also an acute phase reactant (so if you are inflamed for whatever reason, it will quickly pop up!) SERUM IRON indicates decreased in iron deficiency, but of little use alone as a lab because most iron is bound to proteins. this just tells us how much iron is hanging around solo in the serum. Does not take into account how much iron is bound to proteins. TIBC (TIBC = total iron binding content) when it is HIGH there is more room to bind iron...potential space waiting for some iron to come and bind to it. this is carrying capacity. TRANSFERRIN ...transferrin is a transport protein, synthesized in the liver, regulates iron absorption through a highly regulated process TRANSFERRIN SATURATION =serum iron/ TIBC x 100 Normal values are 15-50% high= lots of iron low= low iron state You need ferritin, serum iron and TIBC together to determine if pt truly has iron deficinecy anemia Iron needs to be absorbed in an acidic environment....they can take it with OJ...vitamin C. You measure response by measuring ferritin levels

Information on a CBC

- Hemoglobin - Hematocrit - MCV (mean corpuscular volume) tells you how big the cells are - MCHC (mean corpuscular hemoglobin content) how much hemoglobin did the body actually manage to pack into the cells? Size: MCV Microcytic: <80 = tiny cell Normocytic: 80 - 100 Macrocytic: >100 = great big funky cells Hemoglobin Content (Color): MCHC Hypochromic: MCHC <31.5 (= not enough color) Normochromic: MCHC 31.5 - 36 Hyperchromic: MCHC >36 = too much color) Other cell lines: - white blood cells with their differential - platelets

Anemia of Inflammation

- Iron in present, but locked in storage due to acute or chronic immune system activation - Anemia of Chronic Disease - Anemia of Critical Illness; can also have a decreased response to erythropoietin - CBC: normocytic, normochromic - Reticulocytes are low - High ferritin, Low TIBC (basically the labs will look pretty normal. Iron is there and good, the body just isn't able to access it! on is there but its stuck in macrophages or in parasites or bacteria....

Iron Deficiency Anemia

- Most common cause of anemia worldwide - mostly its dietary - Poor absorption - Menstruation (ie metromenoragia) - Slow chronic losses - GI bleeding If you have an iron deficiency anmeia you must ask WHY ...Human bodies are good usually at absorbing iron. Colon cancer, gi bleed, etc.... In the US there is no reason for someone to have any kind of low iron, so if they are anemic, there is likely a pathology. ALWAYS ASK WHY Patients may experience Pica Spooning of nails - CBC: microcytic anemia (no iron means not enough building blocks which means tiny cells) - Low reticulocyte count (because without the building block that is iron, why bother?) - Smear: small, pale cells, some abnormal shapes - Diagnosed using iron studies

Prevalence

- Prevalence is 24.8% worldwide - 1.3% of people in the US - 9.6% of patients older than 65 - Almost 50% of nursing home residents ...In the elderly, anemia is an strong predictor of decline in physical and cognitive function, frailty, disability and mortality

Foreman: Erythropoietin

- Produced in kidneys in response to low oxygen - Anemia of renal disease: Red blood cells in patients with renal failure also have shorter life spans due to metabolites which have accumulated in the blood...kidneys arent filtering blood and not healthy enough to create eryhtropoitin

Case 8 You see a 22 year old man for worsening anemia. He has a history of sickle cell anemia with multiple annual painful crises and acute chest syndrome 2 years ago. His medications include hydroxyurea, folate, and oxycodone, but he has trouble remembering to take them. On physical examination he has conjunctival pallor, tachycardia to 114, a well-healed cholecystectomy scar on his abdomen, and intact vibratory and position sense. You review his recent lab studies including: WBC 8.2 - NORMAL Hemoglobin 4.1 - LOW Platelets 197,000 - MCV 108 Retic 0.7% - LOW What is the most likely diagnosis? Hemolysis from sickle cell Vitamin B12 deficiency Folate Deficiency Anemia of Chronic Disease

A Goes to hospital to be transfused Low retic means that his hemoglobin tomorrow will be even lower

Sickle Cell Anemia

A QUALITY PROBLEM - Creates an a red blood cell that turns into a sickle shape when in low oxygen state = sticky = clumped chain = sickle shaped rbcs - Can no longer warp and change shape and squeeze to move through small blood vessels. they are also more fragile, so they have increased hemolysis - INCREASED HEMOLYSIS - Painful crises b/c these warped sticky cells get caught in small vessels LAB WORK will show: - CBC: will show Normocytic Anemia - Increased Reticulocyte Count (Increased reticulocyte count because the blood cells have to regenerate...replace the lost cells. Retic count does not ALWAYS correlate with a crisis, though) ...we don't know what will cause a crisis, BTW DIAGNOSED with hemoglobin electrophoresis: Separates the different hemoglobin chains according to size and charge - Presence of hemoglobin S - Treatment is supportive care. try to help with painful crisis. try to treat whatever caused crisis - Referral to hematology for other tx she recommends making a pain contract with patients that states what they need for pain all the time and then for breakthrough pain, and then that states what they require for pain med in crisis. they can then take that with them if the need to go to the ED

Blueprint Problems - Thalassemia

A QUANTITY PROBLEM - A blood disorder involving less than normal amounts of an oxygen-carrying protein. - its just a numbers game. its just a ration issue - Also a genetic change problem, like sickle cell Thalassemias- α or β Mutation in hemoglobin genes - α: Africa, American Indian, Asian; Chr. 16 - β: Greek, Italian, and Middle Eastern; Chr. 11 - QUANTITATIVE defect in hemoglobin chain production (can vary from none to some) - Symptoms depend on how many copies of the gene are affected = much hemoglobin you can make ....you either make more alpha chains or more beta chains..not an equal number like you should have. (its a ratio issue) without enough pairs of the alpha and beta chains, you can't complete a whole hemoglobin. CBC: microcytic anemia* (not enough hemoglobin to pack into the cells, so they end up tiny!) the cells are the same, just miniature versions - Normal reticulocyte count - Because it is a quantitative and not qualitative problem, you cannot use hemoglobin electrophoresis to diagnose - Diagnose with Sequencing, Hemoglobin A2 levels Treatment: Counseling, Transfusions

Also known as: LDH Formal name: Lactate Dehydrogenase

A lactate dehydrogenase (LD or LDH) test is a non-specific test that may be used in the evaluation of a number of diseases and conditions. LD is an enzyme that is found in almost all of the body's cells (as well as in bacteria) and is released from cells into the fluid portion of blood (serum or plasma) when cells are damaged or destroyed. Thus, the blood level of LD is a general indicator of tissue and cellular damage. The level of LD may also rise in other types of body fluids (e.g., cerebrospinal fluid, pleural fluid, etc.) in the presence of certain diseases. To detect and monitor progressive conditions such as anemia, including hemolytic anemia and megaoloblastic anemia, or severe infections

Reticulocyte Index

A way to determine if the increased production is enough Correcting the reticulocyte count for the amount of anemia RI = RC x (Patient Hct / Normal Hct) <2% inadequate IF YOUR RETICULOCYTE INDEX IS LESS THAN 2% YOU ARE NOT MAKING ENOUGH RETICS TO REPLACE DYING RBCS *There are further formulas to correct for the increased longevity of reticulocytes but this is the idea.

Blood Loss

Acute Remember patients can hide the lost blood: abdomen and GI tract Chronic Slow losses may not be appreciated

Putting These Tests Together

Based on MCV and MCHC Anemia can be classified as Normocytic, Normochromic Normocytic, Hypochromic Microcytic, Hypo- or Hyper- chromic Macrocytic, Hypo- or Hyper- chromic

Production of RBCs

Blueprints = DNA Building Blocks = Iron, B12, folate Factory/Workers = Bone marrow Foreman = Erythropoietin

The Factory

Bone Marrow - Contains all the cells for each lineage - Looks like a coral reef with multiple different cell types present - The amount of cells varies with age - Looks like a flower field with lots of different flowers, species etc. (it should be a variety, should not be homogenous)

Reticulocyte Count

Immature Red Blood Cells Expressed as the % of red blood cells released into the circulation from the bone marrow on a daily basis Normal Value: 0.5 - 2.5% red blood cells have a shelf life so you should always have some reticulocytes out there... Reticulocytes are produced every day to replace aging red blood cells - RBC life span 90-120 days ...so, in theory, if you are anemic, you should always have a high reticulocyte count ...the amount that you are making should compensate for the amount that you are down If blood cells are being lost more quickly (acute anemia) then erythropoietin causes the bone marrow to increase red blood cell production = more reticulocytes

What are some reasons sideroblastic anemia might be required?

Can also be acquired; excessive EtOH, Pb (lead poisoning)

Your patient is in sickle cell crisis. What will their CBC and Retic be?

CBC: will show Normocytic Anemia Increased Reticulocyte Count (Increased reticulocyte count because the blood cells have to regenerate...replace the lost cells. Retic count does not ALWAYS correlate with a crisis, though)

Case 9 A 33 year old woman presents to you with a history of increasing fatigue for the last 3 months. She has usually been very active but now can only run 1 mile instead of her normal 5. She has headaches several times per week and craves ice. She remembers being told she was iron deficient before but has not been on supplements for many years. You agree to order some lab work and see her in follow up when it is complete. Decreased exercise tolerance can be an indicator WBC 4.2 Hemoglobin 8.1 -LOW Platelets 130,000 MCV 70 Retic 0.3% Iron 15% - IRON DEFICIENCT TIBC 500 Ferritin 2 - low Smear: hypochromic, microcytic cells with multiple pencil-shapes You arrange to treat the patient with IV iron for her severe iron deficiency. Is this case over? ALWAYS FIND THE SOURCE OF THE IRON DEFICIENCY 3 possible endings for this case

Case 9- Version 1 On specific questioning the patient explains to you that she has a history of very heavy periods ever since menarche at age 12. She soaks a pad in 3 hours for 7 days every 28 days. She also tells you that her mother and sister have similarly heavy periods and that her sister had bleeding issues when a wisdom tooth was removed last year. On further testing it was revealed that this patient had von Willebrand's disorder and she was treated successfully with DDAVP for her menorrhagia. Case 9- Version 2 On further questioning the patient explains that she has been under a lot of stress for the last 6 months. She has been drinking 4 cups of coffee during the day to work and then 2 glasses of wine at night to fall asleep. When she started having headaches she treated them with aspirin which she took on an empty stomach. She has noticed a few episodes of dark stools and did have one episode of coffee ground emesis a week ago. A fecal occult blood test was positive. An EDG revealed gastritis with no culprit bleeding lesions (it was just angry everywhere) She was placed on a PPI (proton pump inhibitor) and given counseling regarding stress management, alcohol intake, and avoidance of gastric stimulants and high acid content foods. Case 9- Version 3 On questioning the patient explains that she had made the decision to become a vegan about 6 months ago. She has not been taking supplements but has tried to vary her diet to meet her daily requirements but was unsure how to do so. You review food choices with her to help her increase her iron intake

Causes of Anemia

Impaired Production Never made the rbc in the first place Increased Destruction Made 'em and killed them Loss- Acute or Chronic Made 'em and put them somewhere else

Increased Destruction

Improperly Made Cells Membrane abnormalities Hereditary spherocytosis, eliptocytosis (these patients might benefit from splenectomy) If the issue is improperly mades cells these patinets rae candidates for splenectomy....the spleen sees the cells and says i dont think so and destroyes them Enzyme abnormalities G6PD: Gucose-6-Phosphate Dehydrogenase Deficiency: hemolysis in times of stress or when exposed to certain drugs Destructive Processes Mechanical: Valves, Marathon Runners, drummers Autoimmune Hemolytic Anemia - Frequently found with other autoimmune disorders. If there is something marking the RBC that the immune system IDs as 'bad' it will launch attack! - Warm or Cold

Case 2 A 27 year old African American male comes to you with signs of a bacterial sinusitis. You prescribe him trimethoprim-sulfamethoxazole (Bactrim). 3 days later he returns to you with dark urine, yellow eyes, and mild shortness of breath. He appears uncomfortable and on physical exam with a temp of 100.2, heart rate of 112, respiratory rate of 20. He is icteric on exam. What other questions do you have for him? What tests would you like to order? What do you think is going on? He has not been taking any other medications besides the Bactrim. He has never had something like this happen to him before but does remember something similar occurring with his older brother. You order a CBC, Reticulocytes, Peripheral Smear (BECAUSE YOU ALWAYS ORDER THESE THREE), LFTs, LDH, haptoglobin, Coombs, and urinalysis WBC 13 - high but he has an infection Hemoglobin 10.2 - prob low for him Platelets 249,000 - MCV 102 - HIGH Retic 11% - HIGH Total Bilirubin 5.2 - HIGH LDH 1145 - WAY HIGH Coombs negative - because not autoimmune Urinalysis 3+ bilirubin (bili in the urine) Smear: Bite Cells

Does he have sickle cell trait Does he take other medications ? Have you ever taken bactrim before? When did the symptoms start? (a day after bactrim started) Dark urine and icteric eyes = liver issue = billi high = hemolytic anemia (G6PD deficiency is more common in african american men) You tell the patient that this is likely G6PD Deficiency and he asks you what can be done. What do you tell the patient both about his care right now and in the future? Should you test his G6PD level now to confirm? Bactrim is the trigger here. Bactrim must be discontinued immediately. The hemolytic crisis should resolve with supportive care within 7 days. The patient should be counseled to avoid trigger medications and told that this can be passed on to the next generation. G6PD levels should NOT be checked during an acute crisis as they can be falsely high. Check later though. If you took the level at this time the G6PD would look normal. This should be listed LIKE a drug allergy so future providers know FYI: sometimes patients with hemolytic anemia can have abdominal pain because when the RBCs break down they release nitric oxide which leads to and pain.

Case 7 A 93 year old man was brought to the hospital after being "found down" in the house where he lives alone. He is thin and dehydrated. His creatinine is initally 3. After being given fluids his renal function returns to normal. His mental status is poor. Deep tendon reflexes are 1+ at best. Labs include the following: WBC 5.4 - LOW hemoglobin 6.3 - LOW platelets 149,000 - just a little low MCV 105 - big globby cells Retic 0.3% - low...in the crapper...nothing is being made LDH 850 - HIGH because the body is destroying those big, globby, worthless cells. What other studies do you want to order? You ask for a B12 AND folate levels AND iron studies!!!! B12 190 (200-800) - LOW Folate 6.5 (2.5-20) - NORMAL Iron 20 (60-160) - LOW TIBC 450 (250-460) - NORMAL Ferritin 10 (15-200) - LOW How would you supplement him?

Give him... - Folate 1 mg PO daily - B12 = Cyanocobalamin 1000 mcg IM QD x 2 weeks, then Qweek until the hemoglobin is normal - IV iron If his B12 level was 250 (200-800), what would you have done? Check MMA levels (methylmalonic acid) His kidneys were fine, he was just dehydrated Erythropoietin needs to be gone for a long time before a patient is anemic Key: altered mental status....think b12 get this lab How is he eating, his diet? Get iron studies too

Haptoglobin

Haptoglobin testing is used primarily to help detect and evaluate hemolytic anemia and to distinguish it from anemia due to other causes. Testing is used to help determine whether red blood cells (RBCs) are breaking apart or being destroyed prematurely. Haptoglobin is an acute-phase reactant whose principal clinical utility is in defining conditions of hemolysis. levels can also become elevated in infection and inflammation. The reference range of haptoglobin in adults is 30-200 mg/dL.

Increased Destruction

Hemolytic Anemias - Either from incorrectly produced cells (cells that are fragile or frail) or from - Actively destructive processes in the body

Case 4 (2:48min) A 64 yo woman presents for a routine examination. Her only complaint is osteoarthritis for which she takes ibuprofen twice daily. She has no other complains. Physical examination is remarkable only for crepitus in the right knee. As a part of your routine testing you order a CBC and see the following: WBC 5.8 - NORM hemoglobin 9.7 - LOW, but she is not symptomatic platelets 265,000 - NORM MVC 82 - NORM What do you do next? You ask for additional laboratory studies to help you determine the cause of this anemia including: get the labs for iron stores... Retic 0.5% - low Iron 40 (60-160) - low TIBC 200 (250-460) - low Ferritin 210 (15-200) - slightly HIGHER than normal range How do you interpret these findings? What treatment do you recommend? she has low iron and a low TIBC...she doesnt have a lot of space to store more iron because it is all bound up already. So she does have the iron

Hemoglobin is low, the only low lab ....do the retic and smear = NORMOCYTIC, NORMOCHROMIC ANEMIA ....it is an anemia of inflammation You counsel the patient that her iron studies show anemia of inflammation- anemia of chronic disease. No specific therapy is needed as she is not symptomatic from this anemia and there are no other concerning findings on her CBC. you say enjoy gardening, but get a stool to reduce inflammation

Blueprint Problems - Sideroblastic

Inherited ALA synthase deficiency (X chromosome)...You start out to make hemoglobin but the job does not get completed right. the hemoglobin just gets shoved into the cells (the iron is trapped in the micoplasm?) and you end up with globby looking cells. You start out to make the hemoglobin but just don't take it to completion. - Can also be acquired; excessive EtOH, Pb (lead poisoning) - CBC: Microcytosis - Low reticulocytes (because the body just gives up trying to replace them) - High iron levels (b/c there is a ton of iron with nowhere to go) - Bone Marrow: Ringed Sideroblasts (if you do an bone marrow biopsy you will see iron halos around these early cells) - Treat with transplant (if the pt actually lacks the enzyme needed here) .....or you can try to give pyridoxine supplements (vitamin B6)...this might push the reaction forward EXTRA: Sideroblastic anemia is suspected in patients with microcytic anemia or a high RDW anemia, particularly with increased serum iron, serum ferritin, and transferrin saturation (see Iron Deficiency Anemia).

Case 6 A 58 year old man comes to you on routine follow up. He has a long history of iron deficiency and hypertension that you manage with atenolol and ferrous sulfate. He also underwent a proximal bowel resection 7 years ago due to a gunshot wound. Today he appears pale and unwell. He tells you he has been more fatigued recently and has been chewing ice. He has not been sleeping well and feels like he cannot get his legs comfortable when he goes to sleep at night. Physical examination reveals pale conjuntiva but is otherwise unremarkable. You are an expert at anemia at this point and order the following labs: Hemoglobin 7.3 - LOW Retic 0.3% -LOW Iron 13 - LOW TIBC 427 - HIGH (its waiting for iron) Ferritin 1 - VERY LOW TIBC = room to bind more iron...the available rooms to fill iron Bowel resection = inablel to absorb the iron What is your plan to replete his iron? - Add ascorbic acid to improve absorption - Increase daily dose from 325 to 650 mg ferrous sulfate - Change his formulation from ferrous sulfate to desferoxamine - Switch to IV iron

Iron deficiency b/c ferritin is less than 10 GIVE IV IRON because ferritin is low and he is symptomatic

Case 5 A 72 year old woman presents with 3 months of increasing fatigue. She has no known past medical history and takes no medications. She felt well prior to these 3 months. She now feels like she can walk only 2 blocks without becoming short of breath. She denies any other symptoms. Physical exam shows pallor but is otherwise unremarkable. You order a CBC and see the following: WBC 2.8 - LOW hemoglobin 7.8 - LOW platelets 560,000 - HIGH What would you do next? You refer the patient to hematology because of the presence of leukopenia, anemia, and thrombocytosis. Your hematology consultant performs a bone marrow biopsy and informs you that the patient has hypercellular marrow with dysplasia of both the erythroid and myeloid lineages: consistent with a diagnosis of myelodysplastic syndrome.

Low WBC low Hemogloin platelets are high Something is going on in the bone marrow Myelodysplatstic syndorme ...something abnormal withing the marrow that is causeing and imbalance in what cells are produced.

B12 and Folate Deficiency

Megaloblastic Anemia Required for DNA synthesis (building blocks!) - Dietary- alcoholism - Absorption- autoimmune diseases like pernicious anemia, short gut, celiac disease, IBD (inflammatory bowel disease), pancreatic insufficiency, tapeworm - Increased Needs- high cell turnover, hemolysis, pregnancy (these patients are given supplements)...basically if there is a lot of cell turnover, the body doesnt have enough of the building blocks it needs to make more cells. Runs out of B12. - Drugs- sulfasalazine, methotrexate (these meds can block b12 usage) Alcoholism and absorbtion disease can cause malabsorbtion of these nutrients = magloblastic anemia There are meds that block B12 absorbtion (ie methotrexate) so these pts need to take extra B12 Can experience NEUROLOGIC SYMPTOMS: loss of balance- poor vibratory sense (use the tuning fork and put it next to the toe...they may not notice it) and position sense in the legs, sensation, confusion, memory loss CBC: macrocytic red blood cells are big and bulky - Reticulocytes decreased - Smear: hypersegmented neutrophils - Bilirubin: may be increased (because your body is making defective cells that are just discarded because they are worthless = more turnover)

Anemia Levels by Gender:

Men: < Hct. 42 or ≤ Hgb 14 (WHO says 13) (Normal: 42- 52 %) Women: < Hct. 37 or ≤ Hgb. 12 (Normal: 37- 47 %) less for women because women menstruate

Building Blocks- Nutrition

Multiple nutrients are required for synthesis of red blood cells - Iron: hemoglobin - B12, folate: DNA

Definition

Not a disease itself, but a sign of an underlying disorder Decreased # of Red Blood Cells Decreased hematocrit Decreased concentration of hemoglobin

Pernicious Anemia

Parietal cells in the stomach secrete intrinsic factor (IF) that is required to absorb B12 in the terminal ileum Lack of IF (intrinsic factor) is pernicious anemia Either from removal of the stomach or by antibodies produced that destroy IF An autoimmune version of B12 deficiency. An autoimmune disease deestroyes Diagnose by low B12 levels PLUS antibodies to intrinsic factor Associated with thyroid dysfunction, so remember to check TFTs too TREATMENT of B12/folate deficiency - Oral: 1000 mg daily Ineffective in Pernicious Anemia Can be used to maintain stores - Intranasal: 500 mcg IN once a week - IM 1000 mcg IM QD x 2 weeks, then Qweek until the hemoglobin is normal, or 1000 mcg IM every 2 - 3 months Follow until hemoglobin is normal, which may take months Folate 1 mg daily Monitor hemoglobin levels, no need to recheck folate and B12

Hemolytic Anemia

Patients may be jaundiced, have large spleens (b/c the spleens are working overtime) CBC: macrocytic (b/c as you start to have high turnover of RBCs you have more reticulocytes and reticulocytes are larger in size than RBCs. This inaccurately bumps up your MCV and RDW. - Reticulocytes are HIGH - Smear: can show abnormal membranes, broken cells, high number of reticulocytes - Elevated bilirubin from breakdown - Elevated LDH, decreased haptoglobin (because all the contents of the cells are spilling out) - Coombs test: specifically looking for the presence of antibodies in the patient's serum that can destroy red blood cells. Coombs test tells us if it is an autoimmune cause TREATMENT: based on cause - if due to G6PD: avoid certain medications! http://www.g6pd.org/G6PDDeficiency/SafeUnsafe.aspx - if Mechanical: avoid or remove source - if Autoimmune: immunosuppression - Folic Acid- for high cell turnover. These patients need folic acid because they need it to repalce the cells. These patients need folic acid because they need it to repalce the cells

Signs and Symptoms

Some signs/symptoms are specific to certain types of anemia - Pica (dirt, ice): occurs with IRON DEFICIENCY - Peripheral Neuropathy, Dementia, even obtunded: B12 DEFICIENCY....because b12 is used for nerve pathways - Macroglossia (fat tongue): B12 DEFICIENCY - Jaundice: HEMOLYTIC ANEMIA (look for icterus or look sublingually) also chewing ice cubes chalky things...

Six Sites Where RBCs Made:

Sternum Ribs Vertebrae Pelvis Proximal end, femur Proximal end, humerus it is at these sites that we draw bone marrow samples

Blueprint Problems - Sickle Cell Anemia

The body makes the cells wrong Humans make multiple different types of hemoglobin chains, and these types change over time (fetal -> adult life) 2 α and 2 β chains = 1 hemoglobin (in other words, hemoglobin consists of 2 alpha chains and 2 beta chains) Mutation on the hemoglobin β chain (valine replaces glutamic acid) that makes a qualitative change 2 mutated chains= SS (sickle cell anemia) 1 mutated chain= SC (one little amino acid mutation causes sickle cell trait)

Case 3 A 58 year old man presents with 2 months of increased fatigue and has recently noted easy bruising an petechia (little red dots that appear from broken blood vessels when there aren't enough platelets) on his ankles. He denies any recent fevers, chills, or sweats. His wife believes that he looks pale. He has previously been healthy with a history of hypertension well-controlled on lisinopril. On physical exam you confirm the presence of ecchymoses and petechia. He has conjunctival pallor but no icterus. The remainder of the exam is unremarkable. What tests would you order? CBC, Retic and Smear (always the 3 you order!!) WBC 1.5 - LOW Hemoglobin 6.8 - LOW Platelets 3,000 - LOW What do you do next?

This patient requires immediate hospitalization and consultation with a hematologist for a bone marrow biopsy. all three values are low. IF ALL THREE LINES ARE DOWN SOMETHING IS REALLY WRONG. Aplastic anemia = his diagnosis Pale, peticahia and The differential diagnosis for pancytopenia includes multiple life-threatening disorders. This patient was diagnosed with aplastic anemia and was given ATG and cyclosporine (immune suppression).

Case 1 (@2:30) A 72 yo man with a history of rheumatoid arthritis presents with shortness of breath, tachycardia, chest pain on exertion. His wife thinks that he looks pale and that his eyes are yellow. What other questions would you ask? Any physical exam findings you would look for? What tests would you order? What medicaitons do you take (is it medication induced?) He was feeling well until 2 days ago. He did not note any recent illnesses or infections and has not taken any new medications. This has never happened to him before. On exam he is pale, tachycardic but comfortable when resting. Vitals signs are within normal limits with the exception of a heart rate of 110. He has no JVD, no new murmurs, no lymphadenopathy or hepatosplenomegaly. There is mild scleral icterus. You ask for a CBC, Reticulocyte count, Peripheral Smear, and Liver function tests You may choose to order LDH, haptoglobin, and a Coombs test now or after you have those results. WBC 9 - NORM Hemoglobin 6 - LOW Platelets 189,000 - NORM MCV 99 - BIG Retic 8% - HIGH Total Bilirubin 3.1 - HIGH LDH 500 - HIGH Haptoglobin <10 - LOW Coombs positive - POSITIVE Smear: shows microspherocytes What kind of anemia is this? Does he require hospitalization? Does he require a hematology consult?

You diagnose him with IMMUNE-MEDIATED HEMOLYTIC ANEMIA because of his severe anemia and symptom of chest pain you admit him to the hospital He is transfused and started on corticosteroids Hematology consultation may be helpful to guide titration of immunosuppression and further identify this as a warm or cold AIHA = Autoimmune hemolytic anemia This pt should get hospitalized And hematology referral THOUGHT PROCESS: First, he is anemic because he is symptomatic.. what kind of anemia? well, he is yellow so that is an indicator of destruction. You will draw a bilirubin. This doesn't mean you are off the hook about asking about dietary iron intake and potential sources for loss. It could be more than one kind of anemia. ALWAYS DRAW a - CBC - Reticulocyte count - Peripheral smear then because yellow, - bilirubin and Because you are considering autoimmune disorder, get - LDL and - haptoglobin - COOMBS test

Measuring B12 and Folate

how do you figure it out? look for B12 and folate acid serum levels in the blood. So if you think an anemia is due to a B12 deficiency, but their B12 looks normal, still draw the methylmalonic acid lab METHYLMALONIC ACID: can be used to determine if there is B12 deficiency with low or borderline levels methylmalonic acid is a byproduct of the Kreb cycle that accumulates when there is not enough B12 to act as a cofactor to move the cycle forward...so it builds up. Its almost a test of how much B12 you have hanging around doing stuff. --> indicates b12 deficiency HOMOCYSTEINE: can be used to determine deficiencies in both B12 and folate B12 and folate are both needed to metabolize homocysteine into methionine If they are absent, there is increased homocysteine --> You end up with a lot of homocysteine if folate deficiency

Bone Marrow

if empty = aplastic anemia - Life-threatening - Autoimmune, Post-infection: hepatitis Replaced - metastatic cancer, infection, sarcoidosis, fibrosis Abnormal - myelodysplasia (just abnormal), hematologic malignancies (abnormal and malignant)