Unit 6 Exam Review (Heme) PDF

Exam 2 review: Hematological system: key component in immune system, includes humeral and cellular components of blood. As well as blood forming structures, gas transports, electrolyte balance. -formed and unformed elements in blood -anemia, hemostasis -blood cell formation -use epo stimulation...

Exam 2 review: Hematological system: key component in immune system, includes humeral and cellular components of blood. As well as blood forming structures, gas transports, electrolyte balance. -formed and unformed elements in blood -anemia, hemostasis -blood cell formation -use epo stimulation -mechanism of hemostatic -patho and tc venous thrombi embolism and anemia -direct uses of oral anticoagulants. (doac) vs coumadin -hematopoiesis which occurs in bone marrow Composition of blood: 50%cells Erythrocytes, leukocytes, platelets , 50%plasma: plasma proteins, albumins, globulins, clotting factors. Review of blood: Needed for gas exchange, transport of nutrients, thermoregulation, homeostasis, immunity. +-----------------------------------+-----------------------------------+ | Plasma | Blood components | +===================================+===================================+ | Primarily water, gases (co2 does | Granular -Neutrophils | | not dissolve well in water, | (phagocytic), basophils (allergic | | protein fractions (albums (most | responses), eosinophils9ALLERGIC | | abundant, acting as osmotic, | RESPONSISE Agranular: | | transport hormones and drugs) | lymphocytes, monocytes | | globulins, fibrinogen, other | | | immune mediates, clotting | Buffy coat 1% contains platelets | | factors) | and wbc's | +-----------------------------------+-----------------------------------+ **REDBLOOD CELLS**: Transport of 02 co2 and PH (4 heme groups and 4 polypeptide chains, -RBC production and EPO: Low oxygen tension stimulates kidney to produce erythropoietin which increased rbc RBC concentration  **Platelets** -originate from Multinucleated megakaryocyte bits of cell membranes and cytoplasm gets pinched off and become small platelets. -Platelets are key components of the clotting cascade -shrink damaged blood vessel -form hemostatic plugs \- clotting via clotting receptors eg plasma phospholipids (Factor xiii have receptors for clotting factors. **Hemopoiesis:** Myeloid and lymphoid are the 2 stem cell lines, all blood cells arise from common stem cell. (the precursor cell in the colony forming unit. The factor that affects of blood cells is nutrition requires a lot of energy. Cytokines have hemopoietic growth stimulating factors(colony stimulating factors or csf are needed to sustain these cells. Differentiation occurs via multiple pathways that result in development of blood cells. Blood cell production if one of the most metabolically active process in the body **Cytokines and hemopoiesis:** various cytokines are responsive for in volved for stimulating and differentiation blood cell lines -key regulators of erythropoiesis -G-csf- stimulate neutrophils, eosinophils, basophils -Gm-csf- stimulates neutrophils, macrophages, eosinophils, -Erythropoietin-erythrocyte \*\* all are produced as recombinants to stimulate hematopoiesis **Erythropoesis:** -erythrocytes, as well as other blood cells develop from stem cells, under the influence of EPO the stem cells start down a developmental pathway to become erythrocytes. -What is the clinical relevancy of the reticulocyte count? checks to see if your bone marrow is making the right amount of red blood cells when old ones die off. If you have too few, your tissues may not get enough oxygen. If you have too many, you could be at risk for blood clots or other health concerns -What stimulates erythropoiesis: decreased in RBC mass = decrease 02 delivery -stimulates erythropoietin -How is EPO used clinically? To stimulate rbc production, treats various anemia such as CKD, bleeding, HIV, Cancers, 5. Myelodysplastic Syndromes (MDS), Prematurity in Newborns -What nutrient are required to maintain RBC production? Iron, B9(Folic acid), B12, copper, vitamin a, vitc, vit e, Explain the mechanism by which blood cell concentrations change from the neonatal period through childhood period? Neonates have high RBC count and produce feal hemoglobin that has higher affinity for 02 binding to perfuse better in UTERO, wbc are higher since the immune system is still developing as transition to childhood occur RBC start to stabilize which reflects improved nutritional status, wbc is stabilized, platelets remain the same **Hemostasis and clot dissolution** -arrest of bleeding -involves interactions between 3 systems : plasma factor (circulate in inactive form in plasma and require other enzymes to activate them , platelets(modulates plasma factors, activated by exposure by plasma factor such as thrombi and collagen in blood vessels, + feedback cycle occurs, fibrin clots which contain intrinsic and extrinsic pathway which are tissue factors that promote clotting which involve Intrinsic pathway involves factors that are found in plasma which promote clothing. Both are inactive until they make contact with other factors that, vasculature( serotonin make contractions) C**oagulation** Factor 8: Clotting cascade: the blood itself is essentially a meshwork of filaments (fibrin)protein that stabilizes the platelet plug., Thrombin one of the coagulation factors converts fibrinogen to fibrin Procoagulant (once activates the anticoagulant system is activated) Clot dissolution or anticoagulation is Thrombolytic system-largely dissolves formed clots -A group of inhibitors (antithrombin3, proteins, protein c) -thrombolytic pathway : x12 is activates by x12awhich activates plasminogen to plasmin which dissolves fibrin polymers aka clots **VIDEO2** \*\*\*the following blood call abnormalities are not diseases per se: rather, they are manifestations of other dysfunctions. +-----------------------------------------------------------------------+ | RBC | +=======================================================================+ | anemia | +-----------------------------------------------------------------------+ | Decrease in RBC \# | +-----------------------------------------------------------------------+ | Loss due to hemorrhage | | | | 2 means by which RBC many decrease: decreased defective erythrocyte | | productions (anemia, carcinoma, lymphoma, leukemia | | | | Increased erythrocyte destruction: | | | | -infection, uremic syndromes, hemorrhage, chronic blood loss, | | hemolysis | | | | How is anemia classified: | | | | 2 characteristics: | | | | Size (cell size) | | | | Hemoglobin content (chromic -color) | | | | MCV: Mean corpuscular volume, can ID 3 types of blood disorders. | | | |  | | | | **Based on MCV and MCHC we can cluster anemia into 3 groups** | | | | -macrocytic/normochromic = folate deficiency, pernicious anemia | | | | -microcytic/hypochromic = iron deficiency anemia, sideroblastic, | | thalassemia | | | | -Normocytic/normochromic = aplastic anemia, sickle cell, anemia from | | chronic illness, hemolytic anemia, post hemorrhagic anemia | | | | Anemia tx depends on type. | | | | Iron deficiency: pregnancy and chronic blood loss (gi bleed, | | | | At risk: female, women childbearing age, poverty, kids | | | | Developing world: dietary insufficiency | | | | How is iron handled in body : | | | | Iron comes from RBC lysis (heme portion) and diet | | | | To transport iron we need to transport iron proteins is transferrin( | | cycle iron to spleen and live rand marrow) and ferratin transport | | iron within plasma into cells. | | | | Both iron binding proteins will transport FE3(ferric) and keep it | | from oxidizing to FE2(ferrous = free radicals) | | | | TIBC: total iron binding capacity: measurement of serum transferrin | | | | Percent transferrin saturation: iron to TIBC ratio | | | | Ferratin: iron stores (not incorporated in hemoglobin) can increase | | with virus | | | | Serum ferratin: level directly linked to the amount of stored iron | | | | -Ferratin is the most sensitive test for iron deficiency | | | | S&S: Stat when iron 70-80g/l (weakness, fatigue, sob, skin pallor, | | brittle, ridged nails, spoon shaped nails (koilonychia), glossitis | | (thick shinny tong) | | | | IDA diagnosis: | | | | Low serum iron | | | | Low ferratin\*\* the best | | | | TIBC high MORE CARRIES since less iron | | | | Microcytic | | | | Thrombocytosis | | | | Elevated RDW | | | | \*\*problem: In early stages HGB, HCT, TDB, INDICES ARE Unchanged, | | | | In later stages: transferrin saturation (serum iron TIBC) IS ALSO | | DIAGNOSTIC | | | | Treatment: | | | | Fix cause eg gi bleed, inflammatory condition such as colitis. | | | | -Iron supplementation (increase in HGB 10-20 = confirmed iron | | deficiency) if no response to treatment may be compliance | | | | -Diet: meat, fish, poultry, orange juice (vit c cofactor for | | absorption of iron in gut), | | | | -Tea and diary may impede uptake | | | | Commonly used iron sulfate (cost) because does not bind as well ( | | better forms for bioavailability: iron succinate, gluconate, fumarate | | | | -Iron dextrans may be given if cannot digest have gastic intestinal | | issue | | | | \-- | | | | **Macrocytic anemia:** | | | | -b12, folate deficiency, etoh, meds, liver disease, Crohn's, celiac, | | hypothyroidism | | | | Pernicious anemia: Vit b12 deficiency, rare in ppl under 30, symptoms | | start slowly. | | | | Vague symptoms at 1^st^ mood swings, weakness, fatigue, paresthesia, | | | | Neuronal manifestations: due to result of nerve demyelination, | | glottis, liver enlargement, pallor | | | | DX: based on a few measures | | | | Elevated MCV- b12 needed for dna synthesis, rate of rna and cytoplasm | | synthesis excess dna production | | | | Low b12: usually die to lack of intrinsic factor which is a enzyme | | required for b12 absorption across the guy | | | | -Autoantibidies to gastric cell | | | | TX: food vit b 13, liver, fish dairy, cereal | | | | Oral 1-2mg daily x2 weeks then 1x per week | | | | Injections 1mcg x1 week qd | | | | **Polycythemia (excess RBC)** | | | | Over production RBC, increase EPO or increased division of | | hematopoietic stem cells | | | | 1ary: mutation in Jak2 gene -\> unregulated cell division | | | | 2^nd^: result of underlying condition. -\> tissue hypoxia, kidney | | disease, hormone medication | | | | Signs and symptoms: fatigue, headache, dizziness, blurred vision, | | parathesis, bruising ,enlarged spleen. | | | | Treatment: phlebotomy, increase hydration, myelosuppressive agents | +-----------------------------------------------------------------------+ **[White blood cell disorders]** are common, abnormalities in function are area. -Abnormalities in number are common, Abnormalities in function are rare -Most frequent are changes in neutrophils -Increased Leukocytosis -- may be a result of a normal adaptation to a physiologic stressor eg: infection -Lymphocytosis can be caused by viral infection -lymphoma: steroid therapy, HIV, Cushing syndrome -Decreased neutropenia is never a normal response **Platelet disorders** -Qualitative: intrinsic cell abnormalities e.g. prevent platelet adherence (drugs), plasma component destruction. -Quantitative: thrombocytopenia -- decreased production of b12, folate and radiation, decreased survival which can be immune mediated (sle) DIC TPP -Thrombocytopenia: myeloproliferative disorders, malignancies, post splenectomy  \- **Pancytopenia: simultaneous reduction of all 3 types of blood cells** **Caused by:** -Bone marrow depression can affect, platelet, rbc and white blood cell level -Nutritional deficiencies -Autoimmune diseases -Infection -chemo/radio -decreased RBC: -Anemia -decreased platelets: thrombocytopenia -Decreased granulocytes-granulocytopenia **Symptoms:** - Anemia Symptoms: Fatigue, pale skin, shortness of breath, dizziness, and irregular heartbeat. - Leukopenia Symptoms: Increased frequency or severity of infections; symptoms may include fever and chills. - Thrombocytopenia Symptoms: Easy bruising or bleeding; prolonged bleeding from cuts; nosebleeds; heavy menstrual flow; petechiae (tiny purple spots on the skin**)** **DIC (disseminated intravascular coagulation)**: -serious blood clotting disorder due to formation of small blood clots through the body's blood vessel. This disrupts the normal clotting process, leading to excessive clotting followed by severe bleeding. Normally caused by a secondary cause such as infection (sepsis) trauma, cancer or complications during pregnancy. There is also chronic DIC which includes DVT, swelling and pain in legs and organ disfunction due to impaired blood flow from clots. how is managed: 1 treat underlying issue (sepsis, surgery from trauma) supportive treatment like anticoagulants such as heparin, transfusions and clotting factor replacement. **WHEN IS TPA indicated** -for emergency treatment of HA (12hr after symptom max) and ischemic stroke(4.5hrmax). Must do head ct to rule out bleed, check for recent head injury and bleeding disorders, recent surgery and HTN. Works by activating plasminogen, TPA binds to fibrin in the clot and activates plasminogen to plasmin plasmin digests fibrin strands in the clot which dissolute and restores blood flow. **VIT k why is it given**: \- prevention of bleeding in newborns, management in hypothrombinemia, reversal of warfarin effect, tx of rare bleeding disorder, osteoporosis management A close-up of a medical information Description automatically generated A close-up of a list of blood indexes Description automatically generated A close-up of a list of blood Description automatically generated **DX tests for hemoglobin metabolism.** -Serum ferratin, total iron binding -Porphyrin analysis -Antibody screen -Direct antiglobulin test -CBC is best most common test and is normally done with a differential A diagram of a blood type Description automatically generated A close-up of a test Description automatically generated A close-up of a test Description automatically generated A close-up of a test Description automatically generated  Anti-clotting drugs: A diagram of a cycloxygenase Description automatically generated  A diagram of a cell Description automatically generated  **Hematopoiesis and composition of blood** -Hematopoiesis Is blood cell formation which occurs in the bone marrow originating from the stem cells ( colony forming unit : granulocyte, monocyte/macrophage, megakaryocyte, lymphoid, (b&t) linage) afterward go through burst forming unit (erythroid line) which gives rise to erythrocytes. colony forming unit (megakaryocytes) give rise to platelets. which follow differential pathway which are affected by cytokines(erythropoietin and thrombopoietin) and growth factors. **Differentiation into white blood cell linages:** -Lymphoid linage: gives rise to lymphocytes (t and b cells) t-cells mature in the thymus gland B-cells mature in the bone marrow -Myeloid linage**:** WBC linage which gives rise to neutrophils, eosinophils, basophils, and monocytes (the myeloid gives rise to platelets and rbc)**\ ** **Cytokines**: act as signaling molecules that bind to specific receptors on hematopoietic stem cells (HSCs) and progenitor cells, influencing their fate decisions such as self-renewal, differentiation, apoptosis, and mobilization from their niche. Examples of cytokines are erythropoietin and thrombopoietin **Erythropoietin** (EPO): produced by peritubular calls in the kidney in response to low partial pressure of oxygen which stimulates erythrocyte production. **Thrombopoietin**(TPO): Produced in liver and kidneys and directly regulated by the rise and fall of megakaryocytes **Differentials:** +-----------+-----------+-----------+-----------+-----------+-----------+ | Neutrophi | Basophil | Eosinophi | Monocyte | Bands | Lymphocyt | | ls | | l | | | es | | | (myeloid | | (myeloid | (myeloid | (lymphoid | | (myeloid | system) | (myeloid | system) | system) | system) | | system) | | system) | | | | | | Polymorph | | (phagocyt | (Left | | | Polymorph | onuclear | Polymorph | e) | shift) | | | onuclear | leukocyte | onuclear | | | | | leukocyte | s | leukocyte | | | | | s | | s | | | | | (phagocyt | (Phagocyt | | | | | | e) | e) | | | | | +===========+===========+===========+===========+===========+===========+ | -Phagocyt | -Refered | -present | -response | -Immature | B and t | | es | to as | in blood | to injury | neutrophi | cells | | that | mast | and | and | ls | | | inject | cells | chemotact | infection | that do | -produce | | and kill | found in | ically | | not have | antibodie | | bacteria | tissue, | attracted | -arrive | a | s | | by means | | to skin | at site 5 | segmented | or | | of free | -have | and | or more | nuclei.(n | immunoglo | | radials | ability | airways | hrs | eutrophil | bins | | or lytic | to | by the | | s | | | compounds | squeeze | neutrophi | -act as | released | -confers | | contained | through | l | phagocyte | premature | humoral | | within | endotheli | chemotact | s | ly | (acquired | | granular | al | ic | that | from bone | immunity) | | inclusion | cells | factor | ingest | marrow) | | | s. | that line | (release | injured | | \- T | | | capillari | signaling | or dead | -Presence | cells are | | -1^st^ | es | factors | cell and | of | key | | cells to | | to attact | microorga | increased | mediators | | be | -found in | other | nism, | numbers | of both | | recruited | gastro | immune | | usually | the | | during an | and resp | cells | -recruite | due to a | cellular | | inflammat | track | known as | d | chronic | and | | ory | | chemotaxi | during | inflammat | humoral | | response. | -contain | s | viral and | ory | immune | | | histamine | where | bacterial | response. | responses | | -numbers | , | cells | infection | | | | can | heparin, | move |. |  left | Lymphocyt | | increase | kinines | toward | | shift can | osis | | after | | higher | | refer to | refers to | | injury, | -involved | concentra | | the early | an | | burn, | in | tions | | release | increase | | infection | allergic | of these | | of | in the | | and heart | and | signaling | | younger | number of | | attack. | stress | molecures | | white | circulati | | | response | ) | | cells, | ng | | -lifespan | | | | such as | lymphocyt | | is | -prevent | \- Eosino | | bands and | es. | | 10hours | thrombi | phil | | metamyelo | Lymphocyt | | afterward | in | numbers | | cytes, | openia | | new | microcirc | increase | | from bone | refers to | | neutrophi | ulation. | during | | marrow | a | | ls | | allergic | | reserve | decrease | | will be | -Known as | and | | into | in the | | released | granulocy | inflammat | | blood | number of | | from bone | tes | ory | | stream; | circulati | | marrow. | due to | reactions | | in other | ng | | | present | and | | words, | lymphocyt | | -Neutroph | of | parasite | | this | es. | | ilia: | granules | infection | | entails a | | | increase | in their | s. | | shift | | | in | cytoplasm | Normal | | from the | | | circulati | which | blood | | right, | | | ng | contain | levels | | (mature | | | neutrophi | enzyme to | range | | cells) | | | ls | fight | from 0-7 | | toward | | | | infection | percent. | | the left | | | -Neutrope | | | | (less | | | nia: | | -Known as | | mature | | | decrease | | granulocy | | cells). | | | in | | tes | | Left | | | circulati | | due to | | shift | | | ng | | present | | normally | | | neutrophi | | of | | means a a | | | ls. | | granules | | bacterial | | | | | in their | | infection | | | -Normal | | cytoplasm | | | | | range | | which | | | | | 45-47% | | contain | | | | | | | enzyme to | | | | | -Known as | | fight | | | | | granulocy | | infection | | | | | tes | | | | | | | due to | | | | | | | present | | | | | | | of | | | | | | | granules | | | | | | | in their | | | | | | | cytoplasm | | | | | | | which | | | | | | | contain | | | | | | | enzyme to | | | | | | | fight | | | | | | | infection | | | | | | +-----------+-----------+-----------+-----------+-----------+-----------+ **Clotting disorders** -activation of platelets and coagulation factors in blood; concomitantly, clot dissolution or fibrinolysis is also typically activated, constituting a negative feedback loop that prevents excessive clotting. Clotting disorders are the result of derangements in one of the coagulation system. the platelets, or the blood vessels; and these disorders can be either acquired or hereditary. The major causes of acquired coagulation disorders are vitamin K deficiency, liver disease, disseminated intravascular coagulation, and development of circulating anticoagulants. Virtually all coagulation factors are made in the liver, and markers such as partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT or APTT) and prothrombin time (PT) are typically elevated in liver disease. Apart from detecting abnormalities in blood clotting, these indicators are also used to monitor the treatment effects with heparin. In particular, PT results are typically reported as an INR (international normalized ratio), which is also used to monitor the efficacy of anticoagulation for patients using coumadin. Decompensated liver disease also causes excessive fibrinolysis and increased bleeding due to decreased hepatic synthesis of α 2-antiplasmin. Deep vein thrombosis (DVT) results from a convergence of the following factors that, collectively, have been called *Virschow\'s Triad*: venous stasis, endothelial damage, and hypercoagulability. Patients at risk of DVT are typically treated by anticoagulation of heparin in the 1930s (see Antithrombotic Therapies below) **Anti-Clotting Agents:** -Four main classes: 1: warfarin, 2. Heparin, 3. Synthetic pentasacchride inhibitors and 4. Direct oral anticoagulants -Warfarin: lonest used, inhibits vitk epoxide reductase which is a enzyme for activating vit K. reduces synthesis of active clotting factors. -Synthetic pentasaccharide inhibitors that have been developed to-date target bind to antithrombin. These include drugs such as Fondiparinux, Idraparinux and Indrabiotaparinux. -DOAC's:  rivaroxaban, apixaban and edoxaban. Unlike heparin and the synthetic peptide inhibitors, these directly inhibit factor Xa. Compared to warfarin, DOACs have a more rapid onset of action and shorter half-life. Moreover, there is less need for dosing adjustments and routine monitoring, and they have few drug interactions and no known dietary interactions. Unlike, warfarin, they cannot be reversed by vitamin K infusion, although there currently exists a reversal agent for dabigatran (idarucizumab). While DOACs are significantly more expensive that warfarin, patients on DOACs do not require routine INR monitoring. **Anemias:** -Anemia refers to an RBC mass, amount of hemoglobin, and/or volume of packed RBCs that is less than normal, as evidenced by low hematocrit or hemoglobin concentration. From a physiological perspective, an anemia exists when insufficient RBCs and/or hemoglobin is available for optimal oxygen transport to tissues and cells. Anemia is a decrease in RBC mass or haemoglobin content of blood below normal levels. Causes include blood loss, bone marrow infiltration, chronic illness, inflammation, or decreased response to erythropoietin. Treatment can include nutritional supplements (iron, vitamin B-12 or folic acid), treatment of infections and inflammations, and blood transfusions. Symptoms: fatigue, weakness, pale skin shortness of breath dizziness lightheaded headache brittle nails chest pain. Treatment: Diet change such as meat fish and chicken, certain foods, IRON supplements, IV therapy, tx underlying cause such as gi bleed, absorption issues  **iron deficiency anemia (IDA)** **-**Lack of sufficient iron in body to produce hemoglobin. Heme groups carry iron. Leading to poor circulation of oxygen. DX: CBC, ferritin, serum iron and total iron binding capacity, peripheral blood smear(size and shape). (**microcytic, hypochromic)** **B12 Anemia**: Occurs when body does not have enough b12 to produce RBC since B12 is needed for DNA synthesis and formation RBC. Can produce large abnormal RBC and are less efficient and transporting oxygen, dx by serum b12, cbc, methymalonic acid test, homocysteine level. Schilling test and intrinsic factors can be done as well. Symptoms: weakness, fatigue, psllor, glossitis and mouth ulcers, sob. TX: Diet (fish,eggs ceareal), oral supplements 1000-2000mcg bid, IM injection QW until levels normalize (MACROCYTIC AND HYPERCHROMICN) **folate-deficiency anemia**:  type of megaloblastic anemia that occurs when there is insufficient folate (vitamin B9) in the body. Folate is essential for DNA synthesis, repair, and methylation, as well as for the production of red blood cells. A deficiency can lead to the production of abnormally large red blood cells ineffective in transporting oxygen. DX: exam of medical history dietary habits complete blood count, serum folate level testing, red blood cell folate testing and other tests to rule out other types of anemia symptoms; Fatigue weakness pale skin shortness of breath dizziness headache, glossitis (MACROCYTIC AND HYPERCHROMIC) **pernicious anemia:**  Pernicious anemia is a type of megaloblastic anemia characterized by the inability of the body to absorb vitamin B12 due to a deficiency of intrinsic factor, a protein produced by the stomach lining. Intrinsic factor is essential for the absorption of vitamin B12 in the intestines. Without adequate levels of this vitamin, red blood cells cannot mature properly, leading to their abnormal enlargement (megaloblasts) and reduced oxygen-carrying capacity. Symptoms; fatigue and weakness, pale skin or jaundice, shortness of breath, nerve damage due to nerves losing myelination, brain fog, gloss itis, vision changes. DX: medical history and exam, complete blood count, peripheral blood smear, B12, intrinsic factor antibody test, methyl malonic acid. Treatment; vitamin B12 injection, oral vitamin B12 supplements, and dietary changes. (Macrocytic normochromic) **thalassemia:** hereditary blood disorder characterized by the reduced production of hemoglobin, the protein in red blood cells responsible for transporting oxygen throughout the body. Symptoms: fatigue, weakness, pale, jaundice, enlarged spleen, bone deformities, delayed growth in children. DX: CBC, MCV, and MCHC, hemoglobin electrophoresis, and genetic testing to confirm thalassemia. THX; in mild cases does not need treatment, for moderate cases needs blood transfusion, iron chelation therapy due to possible overload from too many transfusions in the past, folic acid supplements to produce new red blood cells, bone marrow or stem cell transplant for a potential to cure patients but reserved for severe cases due to risks (microcytic, can be normal chromic and hypochromic) **sickle cell anemia:** Sickle cell anemia is a hereditary blood disorder characterized by the production of abnormal hemoglobin known as hemoglobin S (HbS). This condition is a form of sickle cell disease (SCD), which encompasses several genetic disorders that affect hemoglobin. The mutation in the HBB gene on chromosome 11 leads to the substitution of valine for glutamic acid at the sixth position of the beta-globin chain. Under low oxygen conditions, hemoglobin S polymerizes, causing red blood cells to deform into a rigid, sickle shape. These sickled cells are less flexible and can obstruct blood flow in small vessels, leading to various complications. Symptoms: anemia, pain crisis due to vaso occlusive issues in joints bones and organs, swelling due to block circulation, frequent infections due to compromised spleen function and susceptibility, delayed growth due to chronic anemia, vision problem due to blocked vessels in eyes. Dx: newborn screening in high risk countries, hemoglobin electrophoresis to determine if hemoglobin is S, CBC hemoglobin and hematocrit, genetic testing. TX: pain management, hydroxyurea therapy, blood transfusion, bone marrow or stem cell transplant.(Macrocytic, hypochromic) **aplastic anemia:** Aplastic anemia is a rare but serious blood disorder characterized by the failure of the bone marrow to produce sufficient amounts of blood cells, including red blood cells, white blood cells, and platelets. This condition can lead to a variety of health complications due to the resulting deficiencies in these critical components of the blood. Symptoms: fatigue, weakness, frequent infections due to leukopenia, bruising and easy bleeding due to thrombocytopenia, pale skin, shortness of breath due to inadequate oxygen transportation. DX: medical history and physical exam, CBC to measure levels of red blood cells white blood cells and platelet when all three are low it may indicate potential aplastic anemia, bone marrow biopsy this is done to rule out reduction in hematopoietic stem cells. TX immunosuppressive therapy such as anti thymocyte globulin combined with cyclosporine to reduce the immune systems and tack on the bone marrow, bone marrow transplant normally given for severe cases or young patients with a suitable donor. Supportive care such as blood transfusions platelet transfusions antibiotics in case of infection, medications such as erythropoietin or granulocyte colony stimulating factor to increase red blood cells and white blood cells. (Normocytic or microcytic depending on underlying cause eg nutrition, normal chromic may change). **sideroblastic anemia. ** \- Sideroblastic anemia is a type of anemia characterized by the presence of ringed sideroblasts in the bone marrow. These are erythroblasts (immature red blood cells) that contain iron granules arranged in a ring around the nucleus, which indicates an abnormality in iron metabolism and utilization. This condition leads to ineffective erythropoiesis, resulting in reduced hemoglobin production and subsequent anemia. Causes: 1. **Hereditary Sideroblastic Anemia**: This form is often linked to genetic mutations affecting heme synthesis. The most common genetic cause is X-linked sideroblastic anemia, which results from mutations in the ALAS2 gene, crucial for heme production. 2. **Acquired Sideroblastic Anemia**: This type can arise from various factors, including: alcohol consumption which could interfere with B6 metabolism, lead poisoning, certain medication, nutritional deficits such as B6 or copper, bone marrow disorders such as millado plastic syndromes or leukemia. Symptoms: fatigue and weakness, pale skin, shortness of breath, dizziness, palpitations or heart failure. DX: complete blood count, bone marrow biopsy to determine presence of ringed sideroblast, iron studies, genetic testing, vitamin deficiencies. TX: vitamin supplementation such as B6, avoiding alcohol and lead exposures, blood transfusion, erythropoiesis stimulating agents, bone marrow transplant, iron Chilton therapy in case there are too many blood transfusion and there is too many iron must be removed (Microcytic, normochromic or hypochromic) **Lymphocytes normally represent 20-40% of circulating WBC\'s. What are the common causes of Lymphocytopenia? or Lymphocytosis?** Lymphocytopenia is explained as a lower-than-normal number of lymphocytes. There are several contributing factors to this dysregulation including destruction of lymphocytes by medications (steroids and chemotherapy), viruses (HIV), radiation treatment, and decreased lymphocyte production related to neoplasias and immune function deficiencies (agammaglobulinemia). also occur in heart failure and can be caused by increases in cortisol caused by acute illnesses, including renal failure, aplastic anemia and tuberculosis. Lymphocytosis: increase in lymphocyte counts in the blood. The most common causes of Viral infections (Epstein Barr Cirus, infectious mononucleosis, cytomegalovirus, pertussis, hepatitis, mycoplasma pneumonia and typhoid). It can also be caused by Thyrotoxicosis (excessive thyroid hormones) and adrenal insufficiency, malignancy including chronic lymphocytic leukemia, chronic myelogenous leukemia and acute lymphocytic leukemia.While lymphocytosis is a common finding, special attention should be focused on history and physical exam to direct clinicians to the possible underlying cause. **What are the mechanisms of action of the different classes of NOAC** Direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban). Direct thrombin inhibitors work by directly binding to both soluble and fibrin-bound thrombin without need for antithrombin. Oral factor Xa inhibitors work by binding directly to the clotting factor Xa, which inactivates both free factor Xa and factor Xa in the prothrombinase complex. These anticoagulants improve upon warfarin in many ways. Onset is quicker, routine monitoring is unnecessary, there are few other drug interactions, and patient diet is less restrictive. Reconsider use of NOACs in patients with severe kidney or liver dysfunction, mechanical heart valves, gastrointestinal absorption issues, weight under 50kg or over 140kg, a history of poor medication adherence, and those who may have difficulty affording this medication **How would you counsel a patient being treated for atrial fibrillation who asks about some of the novel anticoagulants that do not require INT testing.** to ensure correct comprehension explain Atrial fibrillation (AFib) increases stroke risk, necessitating anticoagulation therapy. Novel anticoagulants (NOACs): offer an alternative to warfarin, eliminating the need for regular international normalized ratio (INR) testing. Some examples of NOAC's: \- Dabigatran (Pradaxa): Direct thrombin inhibitor \- Rivaroxaban (Xarelto): Factor Xa inhibitor \- Apixaban (Eliquis): Factor Xa inhibitor \- Edoxaban (Savaysa): Factor Xa inhibit The patient would need to know the benefits of NOAC's which includes of course, the lack of INR monitoring. Fixed dosing of medications, Rapid onset/offset of action, and Reduced risk of intracranial hemorrhage (compared to warfarin). Explain risks such as the increased risk of gastrointestinal bleeding, Limited reversibility options factor Xa inhibitors, which can lead to prolonged bleeding and delayed hemostasis.  Lastly I would discuss the cost with the patient as warfarin is cheaper. The patient and their history also needs to be taken into account. There must be no history of significant bleeding, and they need to have stable renal function (CrCl ≥30 mL/min As well as no valve prosthetics or severe valve disease. The patient would be further educated on the importance of , Adherence to medication regimen recognition of bleeding signs, and interactions with other medications (e.g., antiplatelets). Also that they would still need to routinely monitor renal function and blood pressure checks (January et al., 2019) **Which populations are at risk for vitamin b12 deficiency?** B12 vitamin deficiency is mainly due to inadequate dietary intake in vegans, and B12 malabsorption is related to digestive disease Older Adults Another important factor to consider that may affect  vitamin b12 deficiency is at risk groups such as older adults. Who may not have the means of transportation to access or have  assistance preparing food that contain high levels of B12 such as meat, fish, cheese and eggs. Older adults also experience gastric atrophy and low gastric PH (Lindsay, 2009). Poverty:                 People that live in impoverished countries can be vitamin B12 deficiency due to lack of food that contains B12 and poor access to vitamin B12 fortified food. Inherited disease: "Congenital causes are rare and are the result of genetic mutations in genes encoding proteins involved in B12 absorption, transport, and intracellular processing. These include 1) congenital pernicious anaemia, where there is a genetic defect in IF synthesis, leading to B12 malabsorption, 2) Imerslund-Gräsbeck Syndrome (IGS) caused by mutations in genes encoding *cubulin* and *amnionless*, 3) inherited HC or TCII deficiencies, and 4) intracellular cobalamin defects (CblA-CblG defects)" (Elangovan & Baruteau 2022). Pernicious anemia "Intrinsic factor is a glycoprotein produced by parietal cells in the stomach and necessary for the absorption of vitamin B12 in the terminal ileum" (Ankar, Kumar, 2024). When the stomach does not make enough intrinsic factor, the intestine cannot properly absorb vitamin B12 which is usually do to  pernicious anemia. Digestive surgery, inflammatory illness, and infection: obesity, bariatric surgery and gastrectomy causes include pancreatic insufficiency, obstructive Jaundice, tropical sprue and celiac disease, bacterial overgrowth, parasitic infestations, Zollinger-Ellison syndrome, and inflammatory bowel diseases".(Guéant, et al,. 2022).     Common medication such as: (Uptodate) -Metformin -Proton pump inhibitors -colchicine -Proton pump inhibitors \- Aminosalicylic **acid** **Therapy Goals for Treatment of Vitamin B12 and Folate Deficiency** understand the reasoning and importance of treatment. These goals can enhance therapy compliance and prevent deterioration of the condition being treated. Provided below are the goals of therapy for vitamin B12 and folate deficiency. Vitamin B12 Deficiency: Vitamin B12 is essential for proper functioning of the nervous system and for development of blood cells. Vitamin B12 deficiency and its symptoms can arise with inadequate dietary intake or malabsorption of vitamin B12. For individuals with a low dietary intake, the goal of therapy is to increase vitamin B12 levels and prevent onset of deficiency and symptoms. For symptomatic individuals, goals of therapy aim at reversing metabolic abnormalities and alleviating other symptoms. Depending on severity of symptoms and cause for deficiency, these goals are achieved with high doses of oral or parenteral vitamin B12. IM injections can be considered Folate Deficiency: Folate is naturally found in dark leafy greens and legumes Folate deficiency is rare, however, individuals who are pregnant or have digestive disorders are at higher risk for developing this deficiency. For folate deficiency related to digestive disorders, treatment goals aim to relieve symptoms and prevent megaloblastic anemia, a serious progression of the deficiency. In women of childbearing age or during pregnancy, treating and preventing folate deficiency is vitally important. The goal of treatment is to elevate folate levels and prevent neural tube defects. ** What are the roles of Th1, Th2, and TReg lymphocytes?** T helper:   primary cells of the immune response To induce an immune response, antigen-presenting cells (APC) present antigens to Th cells. Depending on the antigen type and APC signals, the Th cell differentiates into subtypes: Th1 and Th2. Some Th cells become Treg cells TH1: support cell-mediated immunity by promoting phagocytosis and cytotoxic killing of infected, cancerous, or damaged cells. A type IV hypersensitivity reaction like skin contact with poison ivy is an example where Th1 cells are produced. TH2: Th2 cells promote humoral immunity by supporting B cell proliferation and differentiation. Th2 cells release cytokines signals that react with the B cell. The B cell then differentiates into a plasma cell that secretes antibodies specific to the antigen. Type I hypersensitivity reaction is an example where Th2 cells are activated. In this type, one is sensitized to an antigen (allergen), resulting in a primary immune response and activated Th2 cells. Disease symptoms then occur after the second exposure. T regulator: Treg cells suppress and control the immune system and promote tolerance against self-antigens by secreting high levels of immunosuppressive cytokines. A lack of tolerance can result in a wide range of autoimmune or hypersensitivity disorders. Treg lymphocytes are known to be unstable and have been shown to have the ability to transform into Th1 and Th2 cells in autoimmune disorders, so instead of suppressing the immune system, they promote It. **Cipro and warfarin** \- In the situation that a patient develops an infection, they may be prescribed Ciprofloxacin, practitioner would have to monitor INR. Warfarin is metabolized by the cytochrome P450 enzymes, whereas Ciprofloxacin is an inhibitor of the cytochrome P450 enzymes. Since Ciprofloxacin inhibits the cytochrome P450 enzymes, warfarin is displaced from the binding sites leading to increased INR levels and a risk for prolonged bleeding **Common cause IDA in north America:** - Increased Iron Requirements: Pregnancy, parturition, lactating phase and growth spurts in infants, children and adolescents.   - Increased Loss: Menstruating girls and women, GI bleeds (cancers, hemorrhoids, peptic ulcer disease, Crohn's or ulcerative colitis, cow milk protein colitis, short gut syndrome, angiodysplasia, esophagitis), regular blood donation, post op patients with significant blood loss, hematuria, intravascular hemolysis, endurance athletes, frequent epistaxis, medications such as NSAIDs and hookworm infection.  - Decreased Dietary Intake of Iron: Poverty, veganism, vegetarian diet, poor dietary intake, eating disorders, low body weight, alcohol use disorder, newcomers from SE Asia and Africa, and age over 65  - Decreased absorption of Iron: Diseases of the upper GI tract (chronic gastritis, Crohn's disease, Celiac disease, gastric lymphoma), medications that bind to iron and decrease gastric acidity (PPIs/antacids), gastrectomy and duodenal bypass, bariatric surgery, H. pylori, atrophic gastritis, chronic renal disease and chronic heart failure. **Oral therapies for IDA (microcytic anemia but may present as normocytic at the begining) -\> ferratin testing is primary** \- Oral iron supplements are considered first-line therapy for IDA due to their relatively low cost and ability to replenish depleted iron stores. Various oral iron supplements are available for use. However, no one preparation is recommended over another; instead, patient tolerance guides treatment choice. Common iron supplements include ferrous sulfate, ferrous gluconate, ferrous fumarate, polysaccharide iron, and heme iron polypeptide. These products vary in therapeutic dose, formulation, cost, and side effects, though commonly include gastrointestinal (GI) symptoms including nausea, vomiting, diarrhea, constipation, and dark stools. While these side effects are usually temporary and self-limiting, they can impact treatment duration and adherence. While intravenous (IV) iron is recommended in many guidelines, its use is often limited to patients who are intolerant to or non-compliant with oral iron therapy **Does an elevated WBC count necessarily indicate an infection for the patient:** No: Leukocytosis can occur as a normal protective response to physiologic stressors such as "strenuous exercise, microorganisms, emotional changes, temperature changes, anesthesia, surgery, pregnancy, and some drugs, hormones, and toxins.  Furthermore, leukocytosis can occur with acute inflammatory conditions such as autoimmune disorders or tissue damage. While there are many factors that can be benign, leukocytosis can also be indicative of malignancy and hematologic disorders