PATHO - Term Test I (Hematologic System) Flashcards

Question

True or False: Granulocytes contain enzymes for killing microorganisms and catabolizing debris ingested via phagocytosis, and are capable of amoeboid movement.

Answer 1

* neutrophil (65-75% of total WBC count) * chief phagocytes of early inflammation but quickly dies in 1-2 days due to how sensitive it is to the environment of damaged tissue * neutrophils breakdown and release digestive enzymes that dissolve cell debris and prepare site for healing

Answer 2

* have large, coarse granules and account for 2-5% of WBC count * uses pattern recognition receptors (PRRs) to allow for diapedesis and phagocytosis * induced by IgE-mediated hypersensitivity reactions to attack parasites * control inflammation processes (release proinflammatory molecules) * high levels in Type I hypersensitivity allergic reactions and asthma

Answer 3

* \<1% of WBCs, structurally similar to mast cells * contain histamine, chemotactic factors, preoteolytic enzymes, and heparin * when stimulated, induces synthesis of leukotrienes and cytokines that affect Th1 and Th2 cell differentiation * rich in IL-4 that guides B cell differentiation into plasma cells to secrete IgE

Answer 4

consists of monocytes that differentiate without dividing and reside in tissues and ingests/destroys unwanted materials

Answer 5

lymphocytes

Answer 6

megakaryocytes spleen macrophages primarily in the spleen

Answer 7

**Primary lymphoid organs:** * thymus * bone marrow **Secondary lymphoid organs:** * spleen * lymph nodes * tonsils * Peyer patchs in ileum of small intestine

Answer 8

* Spleen **Functions:** * site of fetal hematopoiesis * filters blood-borne antigens and cleanses blood through MPS * initimates immune response to blood-borne microorganisms * destroys old RBCs * blood reservoir

Answer 9

trabeculae; splenic pulp

Answer 10

**Splenic pulp:** masses of lymphoid tissue containing macrophages, lymphocytes, and lymphoid follicles; divided into white and red pulp * **White pulp:** contains lymphocytes and macrophages; where immune function occurs because this is where antigens encounter lymphocytes causing B cells to proliferate and differentiate (humoral immune response) * **Red pulp:** contains RBCs and venous sinuses; also has some macrophages for splenic filtration (this is the principal site)

Answer 11

c) it can store more than 300mL of blood BUT up to 200mL can be expeled into venous circulation when BP drops; increases Hct up to 4% Other notes: * it has slow circulation to allow for macrophages to easily eat up old, damaged, dead blood cells, debris, microorganisms etc. * iron from catabolized RBCs are released back into the blood which the blood then goes to the liver

Answer 12

* leukocytosis * decreased circulating iron levels * severely diminished immune response to encapsulated bacteria (decreased IgM levels) = increased risk of infections * increase in structurally defective RBCs in circulation

Answer 13

Lymph enters through small afferent lymphatic vessels ⇒ subcapsular sinus ⇒ drains into cortical sinuses ⇒ medullary sinuses ⇒ lymph collected and leaves via efferent lymphatic vessel

Answer 14

Blood flows in via lymphatic artery ⇒ post-capillary venules in outer cortex ⇒ drained through lymphatic vein

Answer 15

* lymphocytes enter the lymph node via post-capillary venules and diapedesis * macrophages already reside inside the lymph node to phagocytize things * once an antigen is present, B cells are sitmulated to proliferate and differentiate into memory cells and plasma cells ⇒ causes lymph node enlargement

Answer 16

**Red marrow:** aka myeloid tissue; active marrow where hematopoietic stem cells (HSCs) are created and reside **Yellow marrow:** inactive marrow

Answer 17

* flat bones of pelvis (34%) * vertebrate (28%) * cranium and mandible (13%) * sternum and ribs (10%) * humerus and femur (4-8%)

Answer 18

**1) hematopoietic stem cells (HSCs)** - progenitors of all hematologic cells **2) mesenchymal stem cells (MSCs)** - stomal cells (connective tissue cells) that differentiate into osteoblasts, adipocytes, chondrocytes, sinusoidal endothelial cells, fibroblasts

Answer 19

**Osteoblasts:** derived from fibroblasts, responsible for bone construction **Osteoblasts:** multinucleate cells from monocytes that remodel bone by resorption

Answer 20

**1) Lymphoid lineage:** T and B lymphocytes, NK cells **2) Myeloid lineage:** monocytes, macrophages, neutrophils, basophils, eosinophils, platelets, RBCs

Answer 21

False. Conversion of yellow marrow ⇒ red marrow can be accomplished via erythropoietin (EPO - produced in kidney to stimulate RBC production) which will increase circulating levels of hematologic cells

Answer 22

* production of blood cells * constantly ongoing, occurs in liver and spleen (in fetus) and ONLY in bone marrow (after birth) * continues throughout life and increases in response to need for replenishment or response to infection

Answer 23

* Blood cell production in tissues other than bone marrow (eg. liver, spleen) * usually a sign of disease (can occur in blood disorders/leukemias)

Answer 24

within bone marrow: **progenitor cells** ⇒ **proerythroblasts** ⇒ **normoblast** (while progressively eliminating intracellular structures, synthesizing Hb, and becoming more compact to assume RBC shape/traits) ⇒ **reticulocyte** (last immature form, enters blood stream, where nucleus is lost) ⇒ **erythrocyte** **\***quantity of Hb increases in each step while nucleus decreases in size until it is lost

Answer 25

FALSE. Remains constant

Answer 26

EPO gets secreted by peritubular cells in kidney ⇒ increased EPO levels circulating and carried to bone marrow ⇒ stimulates RBC production

Answer 27

* made in bone marrow by RBCs * the oxygen-carrying protein of RBCs, ~90% of the cell's dry weight * composed of 2 pairs of polypeptide chains (**globins**) and 4 iron + protoporphyrin complexes (**hemes**)

Answer 28

Hb A - two alpha chains, two beta polypeptide chains Hb F - two alpha chains, two gamma chains (binds oxygen with a much greater affinity than adult Hb)

Answer 29

* Heme (can carry one molecule of oxygen so 4 hemes = 4 oxygens in one Hb) * Hb is "saturated" if all 4 oxygen-binding sites are occupied by oxygen

Answer 30

**Oxyhemoglobin:** normal oxygen-carrying form of Hb where O₂is bound to ferrous iron (Fe²⁺) temporarily oxidizing it from Fe²⁺to Fe³⁺ **Deoxyhemoglobin:** when O₂ is released and body reduces the iron to Fe²⁺ which reactivates Hb ("reduced Hb") **Methemoglobin:** non-reduced ferrous iron (Fe³⁺) form of Hb so cannot bind to O₂ (this happens with certain drugs/chemicals that reduce oxygen-carrying capacity)

Answer 31

* Hb undergoes conformational change where when one iron molecule binds O₂, the porphyrin ring changes shape to increase exposure of the three remaining iron atoms to O₂ (this greatly increases affinity for oxygen-carrying capacity of Hb) * once O₂ is unloaded, oxygen-carrying capacity is low to faciliate transport of CO₂ back to lungs

Answer 32

* **Role:** structural component of plasma membrane * **Deficiency results in:** decreased strength, elasticity, and flexibility of membrane leading to hemolytic anemia (RBCs destroyed faster than they are produced)

Answer 33

* **Role:** DNA synthesis, RBC maturation, facilitator of folate metabolism * **Deficiency results in:** Macrocytic (megaloblastic) anemia (abnormally large RBCs that do not function properly)

Answer 34

* **Role:** DNA and RNA synthesis, maturation of RBCs * **Deficiency:** Macrocytic (megaloblastic) anemia

Answer 35

* **Role:** heme synthesis * **Deficiency results in:** microcytic-hypochromic anemia

Answer 36

* **Role:** oxidative reactions * **Deficiency results in:** normocytic-normochromic anemia

Answer 37

* **Role:** iron metabolism, acts as reducing agent to maintain iron in ferrous (Fe2+) form * **Deficiency results in:** normocytic-normochromic anemia

Answer 38

* **Role:**?heme synthesis, protection against oxidative damage in mature RBCs * **Deficiency results in:** hemolytic anemia with increased cell membrane fragility

Answer 39

IRON: * **Role:** Hb synthesis * **Deficiency:** iron deficiency anemia COPPER: * **Role:** optimal mobilization of iron from tissues to plasma * **Deficiency:** microcytic-hypochromic anemia

Answer 40

* metabolic processes in RBC diminished resulting in less ATP available to maintain membrane ⇒ more fragile and less able to reversibly deform ⇒ increased chance of rupturing in microcirculation * plasma membrane also rearranges to signal macrophages to sequester them * During Hb digestion, conjugated bilirubin is the end product which is excreted from liver into intestine or bile ⇒ transformed into urobilinogen that is MOSTLY excreted via feces, some reabsorbed and excreted by kidneys

Answer 41

* ~67% of total body iron bound to heme in RBCs * 5-10% bound to heme-containing myoglobin in muscle cells * ~30% stored in macrophages (mononuclear phagocytes) or as ferritin (in liver) or hemosiderin (in liver) * 3% lost daily in urine, sweat, bile, sloughing of epithelial cells

Answer 42

* 1-2 mg iron from dietary intake * remaining is obtained from continual recycling of iron from RBCs through the **iron cycle**

Answer 43

**Ferritin:** intracellular protein that stores iron **Apoferritin:** ferritin without attached iron **Hemosiderin:** large intracellular iron store complexes resulting from excess accumulation of iron **Apotransferrin:** the thing that iron is bound to when being transported in the blood **Transferrin:** the protein form when apotransferrin is bound with an iron

Answer 44

* protein synthesized in the liver and controls body's iron homeostasis * production of hepcidin regulated by iron levels in the body, rate of erythropoiesis, and % O₂ sat * Hepcidin induces internalization and degradation of ferroportin (membrane protein that trnasports iron in and out of cells) ⇒ leads to increased intracellular iron stores, decreased dietary iron absorption, and decreased levels of circulating iron * Decreased hepcidin production ⇒ leads to release of stored iron and increased dietary absorption

Answer 45

**Myelopoiesis:** development of granulocytes and monocytes from differentiation of myeloid progenitor cells in bone marrow **Lymphopoiesis:** development of lymphocytes from lymphoid progenitor cells to undergo further maturation in primary and secondary lymphoid organs **Thrombopoiesis:** development of platelets

Answer 46

**Progenitor cells** ⇒ **megakaryocytes** (nucleus enlarges and number of chromosomes increase but no cell division occurs which is why it expands; cell develops cell surface elongations and branches that progressively fragment) ⇒ **platelets** (no nucleus, but have granules that promote stickiness)

Answer 47

2/3 splenic pool thrombopoietin (TPO)

Answer 48

* TPO primarily produced in the liver and indues platelet production in bone marrow * Platelets have TPO receptors and when circulating platelet levels are normal, TPO is absorbed onto platelet surface and prevented from accessing bone marrow to initiate further platelet production * When platelet levels are low, amount of TPO exceeds number of available platlet TPO receptors which allows for free TPO to enter the bone marrow and stimulate platelet production

Answer 49

* arrest of bleeding by blood clot formationi at sites of vascular injury * helps damaged bloow vessels maintain a relatively steady state of blood volume, pressure, and flow * Three equal components of hemostasis: * **Vasculature** (endothelial cells and subendothelial matrix) * **Platelets** * **Clotting factors**

Answer 50

1. vascular injury leads to transient arteriolar vasoconstriction to limit blood flow to the affected site 2. damage to endothelial lining exposes subendothelial matrix which results in platelet adherence and activation and formation of **hemostastic plug** (this is **primary hemostasis)** 3. TF produced by endothelium work with platelet factors/platelets to activate clotting system to form fibrin clots and further prevent bleeding (**secondary hemostasis)** 4. fibrin clot contracts to form a more permanent plug & regulatory pathways are activated (fibrinolysis) to limite plug size and begin healing process

Answer 51

False. Pinpoint petechial hemorrhage (involving capillaries, venules, etc.) generally are small and only requiring direct sealing or fused platelets. Bigger sources of bleeding (in arteries) require greater vascular contraction, more fused platelets, and greater hemostatic factor activation

Answer 52

* Endothelial cells produce nitric oxide and prostacycclin which are both vasodilators that modulate blood flow and pressure and maintain platelets in inactive state * Endothelium also produces adenosine diphosphatase that degrades ADP (a platelet activator) * Surface of endothelium contains anti-thrombotic molecules (i.e. heparin sulfate) that limites platelet activation and fibrin deposition.

Answer 53

* Endothelial cells contain **von Willebrand factor (vWF, clotting factor VIII)** which is released during vascular injury which activates platelets

Answer 54

1. **Vasospasm** - induces vasoconstriction during vascular injury to regulate blood flow into damaged site 2. **Prevent further bleeding** - intiates platelet-platelet interactions which result in formatio of platelet plug 3. **Clotting cascade activation** - to stabilize platelet plug 4. **Initiating repair process** - clot retraction and fibrinolysis (clot dissolution), release of growth factors

Answer 55

a) 150 000 - 400 000/mm³ of blood

Answer 56

abnormally low numbers of platelets (\<100 000/mm³ blood) and likely having longer than normal clotting times

Answer 57

1. **adhesion:** increased platelet adhesion to damaged vascular wall (mediated by platelet receptor glycoprotein Ib binding to vWF) 2. **activation:** occurs when there is an interaction with endothelium/subendothelial matrix + inflammatory mediators; platelet degranulates which stimulates changes in platelet shape (turns into spiny projections to increase SA) and biochemistry 3. **aggregation:** stimulated by TXA₂ and ADP; occurs as platelet-vascular wall and platelet-platelet adherence increases 4. **activation of clotting system:** and development of fibrin-platelet meshwork

Answer 58

1. **Dense bodies:** * **ADP:** recruits an activates other platelets * **Serotonin:** increases vasodilation and vascular permeability * **Calcium:** needed for adhesive interactions and intracellular signaling mechanisms to control platelet activation 2. **Alpha granules:** mix of clotting factors, growth and angiogenic factors, and angiogenesis inhibitors * **fibrinogen** * **platelet derived growth factor (PDGF):** stimulates smooth muscle cells and promotes tissue repair * **Platelet factor 4:** enhances clot formation at injury site 3. **lysosomes**

Answer 59

**Description:** inherited autosomal dominant pro-coagulant conditions that causes thrombi in blood vessels **Etiology:** pro-coagulation caused by increased platelet stickiness (aggregation) when stressful events cause release of epi or ADP **S/S:** frequent but silent until significant stressful event; arterial thrombosis, pregnancy complications (fetal growth retardation and fetal loss), potential venous thromboembolism **Dx:** lab evaluation of platetlet aggregation **Tx:** low dose aspirin (ASA), clopidogrel if aspirin-resistant

Answer 60

**Intrinsic pathway:** activated by Hageman factor (factor XII) in plasma when it contacts negatively charged subendothelial substances exposed due to vascular injury **Extrinsic pathway:** activated by thromboplastin TF (released by damaged endothelial cells) interacting with clotting factors (particularly factor VII) * both pathwas converge to **common pathway** and activation of factor C which leads to clot formation * several complexes subsequently activate the next one resulting in activation of prothrombin into thrombin * thrombin converts fibrinogen ⇒ fibrin forming a fibrin clot

Answer 61

a) hypercoagulation (increased clotting) these are all factors and mechanisms that typically prevent spontaneous activation of hemostasis so if they are deficient, hypercoagulation can occur

Answer 62

a) **anti-thrombin III (AT-III):** binds to heparin sulfate OR with administered heparin to prevent thrombosis b) **TFPI:** joins prothrombinase complex and inhibits clotting factors in clotting pathway c) **Thrombomodulin:** binds to thrombin on surface of endothelial cells; mediates Protein C activation and inhibits thrombin activity d) **Protein C:** binds to thrombomodulin which activates it and works in association with cofactor **protein S** to degrade clotting factors

Answer 63

* fibrin strands shorten (become denser and stronger) whih approximates edges of the injured vessel wall and seals injury site * platelets trapped into the fibrin meshwork also contract and "pull" fibrin threads closer together while releasing a factor that stabilizes the fibrin * Contraction expels serum from fibrin meshwork * begins within few minutes after clot formation

Answer 64

* Fibrinolysis * plasminogen (produced by the liver) is converted to plasmin by **tissue plasminogen ativator (t-PA)** or by **urokinase-like plasminogen activator (u-PA)** * t-PA laragely involved in intravascular fibrinolysis while u-PA is extravascular fibrinolysis * t-PA is expressed by endothelial cells and is max activated after binding to fibrin * u-PA binds to specific u-PA receptor on cell that causes activation of plasminogen

Answer 65

* plasmin * major FDP: D-dimer (would be elevated in medical conditions where clots form like DVT and PE)

Answer 66

* rise; decrease * rise in values is due to accelerated hematopoiesis during fetal life and increased number of cells that result from trauma of birth and cutting of umbililcal cord (body thinks it is losing blood so it makes more)

Answer 67

* Hypoxic in nature so it stimulates EPO production in fetus which accelerates fetal erythropoiesis ⇒ causes polycythemia in newborns * after birth, oxygen from lungs saturate arterial blood which allows more oxygen to be delivered to the tissues (changing from placental to pulmonary oxygen supply) which leads to body detecting that EPO and rate of erythropoiesis can slow down

Answer 68

* WBCs develop and mature during fetal life but have weak function at birth due to them being immature cells * high lymphocyte and neutrophil count at birth and continues to rise for 1st year of life (lymphocyte) or first few days (neutrophils) then falls to adult levels * eosinophil and monocyte counts are also high in the first year of life * children tend to have more atypial lymphocytes as a reuslt of frequent viral infections * newborns at risk for impaired phagocytosis, bacterial infections, and delayed wound healing

Answer 69

a) little changes to blood composition but some components can be altered with iron deficiency b) normal RBC life span but slow replenishing of RBCs and fragile plasma membranes (may be due to iron depletion, decreased iron binding capacity, or iron absorption in intestine) c) low Hb levels d) decreased lymphocyte function e) decreased platelet numberes but platelet adhesiveness increases f) increased fibrinogen and clotting factor levels

Answer 70

* Anemia * results from inadequate erythropoiesis (most commonly caused by iron deficiency) or early destruction of RBCs * iron deficiency can result from insufficient dietary intake or chronic iron loss from bleeding

Answer 71

hemolytic disease of the fetus and newborn (HDFN) aka **eyrthroblastosis fetalis**

Answer 72

glucose-6-phoosphate dehydrogenase (G6PD)

Answer 73

**Description:** acquired; the most common nutritional disorder worldwide; anemia caused by iron deficiency **Etiology:** dietary lack of iron (most common during first few years of life), problems with iron absoprtion, blood loss (most common during childhood and adolescence), increased requirement of iron, impaired absorption, chronic diarrhea * other causes: medications causing GI bleeds (ASA, NSAIDs); surgeries that decrease stomach acidity; eating disorders; excessive menstrual bleeding; GI cancers/lesions **Prevalence/Inidence:** highest incidence between 6 mos-2yo and prevalence is greatest among toddlers, adolescent girls, and women of childbearing age * risk factors: living in poverty, elderly with restrictive diets, teenagers with poor diets * also high risk for infants due to low bioiavailability of iron in cow's milk + milk has protein that causes microhemorrhaging) * chronic parasitic infections are a risk factor in children in developing countries (*H. pylori*, helminths) * increased prevalence in overweight children, adolescents, women, and those undergoing bariatric surgery **Pathophysiology:** hypochromic-microcytic anemia; body may try to compensate by increasing RBC activity in bone marrow but eventually deplete stores and anemia occurs (no dysfunction in iron metabolism though); 3 stages: 1. **Stage 1:** decreased bone marrow iron stores; Hb and serum iron remain normal (compensation) 2. **Stage 2:** iron transportation to bone marrow diminished reuslting in iron-deficient erythropoiesis 3. **Stage 3:** starts when small Hb-deficient cells enter circulation to replace normal aged RBCs (this is where S/Sx appear) **S/Sx:** * **IN CHILDREN** listlessness and fatigue (mild); general irritability, decreased activity tolerance, weakness, lack of interest in play; * anorexia, pallor, tachycardia, systolic murmurs * chronic IDA: splenomegaly, widened skull sutures, decreased physical growth, developmental delays, pica, altered neuro and intellectural functions * **IN ADULTS**: fatigue, weakness, SOB, pale earlobes/palms/conjunctivae; koilonychia (spoon shaped fingernails); cheilosis, stomatitis, glossitis, dysphagia, neuromuscular changes, headache, irritability, tingling/numbness **Dx:** lab tests (Hb, Hct, serum iron, ferritin levels, total iron-binding capacity), Hx taking, diet, physical exam **Tx:** * **IN CHILDREN:** PO simple ferrous salt; iron supplements with vit C to increase absorption, diet modifications, cow milk intake restriction * **IN ADULTS:** eliminate source of blood loss if possible; iron replacement therapy (Hct levels should improve in 1-2 mos); PO iron supplement for menstruating females

Answer 74

**Description:** acquired alloimmune disease where antigens of fetal RBCs differ from antigens on maternal erythrocytes **Etiology:** most cases caused by ABO incompatibility (diff blood types between fetus and mother - 20 to 25% of cases); 1/3 cases caused by Rh incompatibility * *Pathophysiology:** 3 conditions to be met for HDFN to occur 1) mother has preformed antibodies against fetal erythrocytes or produces them when exposed to fetal erythrocytes 2) sufficient amounts of antibody (IgG) cross placenta and enter fetal blood 3) IgG binds with sufficient numbers of fetal RBCs to cause widespread antibody-mediated hemolysis or splenic removal * Wtih Rh incompatibility - First Rh incompatibility pregnancy presents with no difficulties because only large numbers of fetal RBCs enter maternal bloodstream once placenta is detached at birth, so baby already delivered * Next pregnancy: anti-Rh antibodies were already in the maternal bloodstream and enter fetal circulation leading to fetal RBCs to be coated with antibodies and destroyed = anemia develops + immature cells released into bloodstream * degree of anemia depends on: length of time antibody has been in fetal circulation, antibody concentration, ability for fetus to compensate for increased hemolysis **S/Sx:** mild ⇒ slightly pale, slight enlargement of liver/spleen * Severe ⇒ pronounced pallor, splenomegaly, hepatomegaly * hyperbilirubinemia ⇒ may lead to neonatal jaundice or kernicterus (biliribun buildup in brain due to bilirubin levels exceeding liver's ability to rid, leads to cerebral damage including intellectual disabilities, high freq. deafness, CP, potential death) * hydrops fetalis: severe edema in body (usually dead in utero) **Dx:** if ABO incompatibility - no additional monitoring or tx required * Coombs test: measure antibodies in mother's circulation OR antibodies already bound to fetal RBCs * Hx taking - presence of fetal hemolytic disease **Tx:** prevention is KEY - RhoGAM injection (anti-D antibodies) to prevent Rh-ve woman producing antibodies (given within 72 h of exposure to Rh+ve)

Answer 75

**Description:** group of autosomal recessive disorders (inherited) characterized by production of Hb S within RBCs (specific sickle cell conditions in another flashcard) **Etiology:** genetic mutation (valine AA replaces glutamic acid) **Prevalence/Incidence:** most common among desendants of sub-Saharan Africa; 7-13% of African Americans of sickle cell trait (provides protection against lethal forms of malaria so may be genetic advantage) **Pathophysiology:** usually causes no problems if properly oxygenated * hypoxemia, decreased pH, dehydration, acute illness, low temp, living at altitude causes Hb S to stretch and elongate into a sickle shape * sickled cell tend to plug blood vessels ⇒ increase blood viscosity ⇒ slow circulation and cause vascular occlusion, pain, organ infarction, further sickling * leads to anemia * sickling is reversible unless plasma membrane of RBC is damaged **S/Sx:** general - pallor, fatigue, jaundice, irritability * extensive sickling can precipitate 4 types of acute crises: vasoocclusive crisis, sequestration crisis, aplastic crisis, hyperhemolytic crisis * Sx usually do not show up until infant is at least 6 months old * infection (most common cause of death related to sickle cell disease) * sepsis, meningitis **Dx:** hematologic tests - sickle solubility test (presence of Hb S) & Hb electrophoresis (amount of Hb S in RBCs); amniocentesis **Tx:** support to prevent consequences of anemia and avoiding crises * adequate hydration, infection prevention, pain management, genetic counseling/psych support * common tx: hydroxyurea * transfusion therapy (may lead to iron overload and need for chelation therapy) * HSC transplant but with potential risks

Answer 76

* homozygous form (most severe and only has sickle cell Hb)

Answer 77

* heterozygous inheritance of Hb S and alpha- or beta- thalassemia) * Hb S x defective/insufficient a- or b- chains of Hb A * mildest clinical manifestations * microcytic-hypochromic erythrocytes make then less likely to occlude microcirculation even in sickle state

Answer 78

* heterozygous inheritance of Hb S x Hb C or D (both abnormal Hb) * milder clinical manifestations than sickle cell anemia * main clinical problems relaed to vasoocclusive crises * in older children, potential: retinopathy, renal necrosis, aseptic necrosis of femoral heads along with obstructive crisis

Answer 79

* carrier state (heterozygous inheritance of Hb S and normal Hb, Hb A) * typically does not affect life expectancy or interfere with daily activities * RARE but may lead to vasoocclusive crisis from severe hypoxia (shock), vigorous exercise at high altitudes, flying at high altitudes in unpressurized aircraft, undergoing anesthesia

Answer 80

**Vasoocclusive crisis (thrombotic crisis):** sickling occurs in microcirculation and obstructs blood flow leading to vasospasm and logjam ⇒ lead to thrombosis and infarction if not reversed, extremely painful, can lead to conditions such as stroke **Sequestration crisis:** seen only in \<5 y.o. where large amounts of blood become acutely pooled in liver and spleen ⇒ high mortality if not recognized; may be recurrent **Aplastic crisis:** profound anemia caused by lowered erythropoiesis despite increased need for new erythrocytes (and bone marrow unable to compensate to replace lost cells); lasts 7-10 days **Hyperhemolytic crisis:** unusual; may occur in association with certain drugs or infections or acute/chronic reaction following a blood transfusion

Answer 81

**Description:** inherited autosomal recessive disorders that result in impaired/decreased synthesis of alpha chain of adult Hb (Hb A) **Incidence/Prevalence:** * Alpha-thalassemia: more common among Chinese, Loatian, Viet, Cambodian * also common among black people **Pathophysiology:** microcytic-hypochromic anemia * further classified into major or minor (based on number of genes controlling a- or b- chain synthesis and combination of mutations (homozygous - major; heterozygous - minor) * 4 forms * **Alpha trait:** heterozygous carrier state - single alpha chain-forming gene is defective * **Alpha-thalassemia minor** - two genes defective * **Hb H disease** - three genes defective * **Alpha thalassemia major** - all 4 genes defective (often fatal in utero) **Sign/Symptoms:** * **Alpha trait:** mildest form - usually Sx free or mild microcytosis * **Alpha-thalassemia minor:** identifcal to beta-thalassemia minor (mild microcytic-hypochromic reticulocytosis, bone marrow hyperplasia, increased serum [iron], moderate splenomegaly * **Alpha-thalassemia major:** hydrops fetalis (severe tissue anoxia leading to severe intrauterine CHF) - fetal distress evidenct in 3rd trimester **Dx:** familial disease hx, clinical manifestations, blood tests ⇒ peripheral blood smears show microcytosis; Hb electrophoresis showing diminished a-chains **Tx:** supportive; regular transfusions and chelation therapy (for iron overload); allogeneic HSC transplant for thalassemia major types

Answer 82

**Description:** inherited autosomal recessive disorders that result in impaired/decreased synthesis of beta-chains of adult Hb (Hb A) **Incidence/Prevalence:** * Beta-thalassemia: more common than alpha type; prevalent among Greek, Italian, Arab, Jewis * Common among black people **Pathophysiology:** microcytic-hypochromic anemia * further classified into major or minor (based on number of genes controlling a- or b- chain synthesis and combination of mutations (homozygous - major; heterozygous - minor) * **Beta-thalassemia minor** - b-globin chain production is depressed moderately * **Beta-thalassemia major** - b-globin chain production depressed severely (Cooley anemia) * Free alpha chains accumulate but are unstable so precipitate in RBCs which are destroyed by MPS in marrow ⇒ anemia **S/Sx:** * **Minor:** mild-mod microcytic-hypochromic anemia ⇒ skeletal changes, slight elevation in serum iron and bilirubin levels, mild splenomegaly, bronze colouring of skin, bone marrow hyperplasia * **Major:** impaired physical growth and development; significant CV burden with CHF (due to anemia); liver and spleen enlargement; skeletal changes (length discrepancies); chipmunk-like face (facial bone deformities from bone marrow hyperplasia) **Dx:** familial disease hx, clinical manifestations, blood tests ⇒ peripheral blood smears show microcytosis; Hb electrophoresis showing diminished a-chains **Tx:** supportive; regular transfusions and chelation therapy (for iron overload); allogeneic HSC transplant for thalassemia major types

Answer 83

Group of inherited bleeding disorders resulting from mutations in coagulation factors

Answer 84

**Description:** X-linked recessive condition caused by mutation in *F8* gene which codes factor 8 (cofactor in clotting cascade) **Prevalence/Incidence:** the most common hereditary disease associated with life-threatening bleeding; more common than Hemophilia B and all racial groups equally affected **Pathophysiology:** inherited from mother who is heterozygous for mutation in *F8* gene (and then occasionally new mutation) * affected individuals within the same family will have same mutation but may be different across families * Sx are evident in males because they have only one X chromosome * Females (heterozygous carriers) usually do not experience excessive bleeding because other X chromosome sufficiently provides normal functioning clotting factor **S/Sx:** depends on level of F8 activity * joint bleeding (knees, ankles, elbows), muscle bleeding, oral bleeding spontaneous painless hematuria * potential fatal bleeds (intracranial bleeding, internal bleeding, neck/chest/abdo bleeding) * first signs by age 3-4 with episodes of persistent bleeding from minor injuries **Dx:** +ve family hx, prenatal genetic testing, personal bleed hx, lab testing (prolonged PTT; measuring factor 8 levels), physical ax **Tx:** Recombinant factor 8 via IV

Answer 85

**Description:** X-linked recessive condition caused by mutation in *F9* gene which codes factor 9 (cofactor in clotting cascade) - aka Christmas disease **Prevalence/Incidence:** 5x less common than hemophilia A **Pathophysiology:** inherited from mother who is heterozygous for mutation in *F9* gene (and then occasionally new mutation) * affected individuals within the same family will have same mutation but may be different across families * Sx are evident in males because they have only one X chromosome * Females (heterozygous carriers) usually do not experience excessive bleeding because other X chromosome sufficiently provides normal functioning clotting factor **S/Sx:** depends on level of F9 activity * joint bleeding (knees, ankles, elbows), muscle bleeding, oral bleeding spontaneous painless hematuria * potential fatal bleeds (intracranial bleeding, internal bleeding, neck/chest/abdo bleeding) * first signs by age 3-4 with episodes of persistent bleeding from minor injuries **Dx:** +ve family hx, prenatal genetic testing, personal bleed hx, lab testing (prolonged PTT; measuring factor 9 levels), physical ax **Tx:** Recombinant factor 9 via IV

Answer 86

autosomal recessive condition that results from deficiency in factor XI (11)

Answer 87

Conditions caused by immune response where antibody-mediated destruction or inflammatory reactions to allergens occur, resulting in blood vessel damage and seepage into tissues All appear during infancy/childhood

Answer 88

**Description:** most common disorder of platelet consumption **Pathophysiology:** caused by autoantibodies (often IgG class) binding to platelet plasma membranes (against glycoproteins) leading them to be sequestered and destroyed by MPS in spleen and other lymphoid tissues; 70% of cases are preceded by viral illness (CMV, EBC, parvovirus, resp tract infection) **Signs and Symptoms:** * bruising and generalized petechiae rash 1-3 weeks after viral illness ⇒ may develop into ecchymoses * asymmetrical bruising often in legs/trunk * hemorrhagic bullae (blood blisters) in gums, lips, mucous membranes * uncontrollable/severe epistaxis * acute phase lasts 1-2 weeks but thrombocytopenia persists * most serious complication: intracranial hemorrhage **Dx:** lab exam - low isolated platelet count; blood smear showing few but large platelets; prolonged bleeding time **Tx:** observation (primary tx) regardless of platelet count ⇒ if bleeding present, then IVIG or short course of corticosteroids **Prognosis:** most recover within 3 months, S/Sx likely subside after acute phase but if ITP persists \>12 months then they are considered chronic and immunosupressive therapies needed

Answer 89

a) Acute lymphoblastic leukemia (ALL) b) acute myeloid leukemia (AML) c) chronic lymphocytic leukemia (CLL) d) chronic myeloid leukemia (CML)

Answer 90

ALL (75% of leukemias); remaining cases are AML chronic leukemias are rare (\<5% cases)

Answer 91

**Description:** the most common type of leukemia in children/teens **Prevalence/Incidence:** most common in early childhood (peak b/w 2-4 y.o.) and more common in boys, Hispanics, and white children; increased incidence in high SES **Pathophysiology:** ALL composed of immature B or T cells (lymphoblasts) that fill bone marrow and replace normal marrow causing a disruption in normal function * **in children:** chromosomal abnormalities (aneuploidy) causing dsyregulation of expression/function of transcription factors needed for normal B-/T-cell development * **in adults:** mix of cancers of precursor B- and T-cell origin **Signs and Symptoms:** abrupt and insidious onset (may occur 1 week prior to dx) * pallor, fatigue, petechiae, purpura, ++bleeding * fever may occur (due to infection and decreased neutrophils, hypermetabolism from rapid growth/destruction of leukemic cells, or excess WBC causing leukostasis which is intravascular clumping of cells leading to infarction and hemorrhage usually in brain/lung) * hyperuricemia leading to renal failure * weight loss and anorexia (in adults) * liver, spleen, lymph node enlargement * abdo pain and tenderness * extramedullary invasion: * CNS: increased ICP (early AM headaches, N/V, irritability, lethargy) * bones and joints: pain in these areas (bone pain with no inflammation, migratory and vague pain) **Dx:** blood tests and smears; bone marrow aspiration ⇒ reduced RBC, granulocytes, platelet counts; hallmark of acute leukemia is blast cell (80-100% in bone marrow vs. \<5% in healthy children) **Tx: chemotherapy,** radiation therapy * in adults - supportive tx (blood transfusions, antibiotics, antifungals, antivirals) * two phases of treatement: remission induction and postremission **Prognosis:** ~85% of children with ALL will survive to 5 years at least

Answer 92

**Description:** leukemia caused by acquired oncogenic mutations that impair differentiation reuslting in accumulation of immature myeloid blasts in marrow/other organs **Prevalence/Incidence:** for children - more common in first 2 years of life and during teen years; equal occurrence in boys/girls and all races; * most common in adults (dx ~70 y.o.) * increased incidence seen with large ionizing radiation doses, smoking, infections with HIV and hep C virus **Pathophysiology:** AML can result from acquired oncogenic mutations (epigenetic alterations) leading to bone marrow being so crowded by blast cells that bone marrow fialure and complications (anemia, thrombocytopenia, neutropenia) occurs **Signs and Symptoms:** abrupt and insidious onset (may occur 1 week prior to dx) * pallor, fatigue, petechiae, purpura, bleeding * fever may occur (due to infection and decreased neutrophils, hypermetabolism from rapid growth/destruction of leukemic cells, or excess WBC causing leukostasis which is intravascular clumping of cells leading to infarction and hemorrhage usually in brain/lung) * extramedullary invasion: * CNS: increased ICP (early AM headaches, N/V, irritability, lethargy) * bones and joints: pain in these areas (bone pain with no inflammation, migratory and vague pain) **Dx:** blood tests and smears; bone marrow aspiration ⇒ reduced RBC, granulocytes, platelet counts; elevated blast cell levels in bone marrow **Tx: combination chemotherapy** (harder to treat than ALL); potential HSC transplant; tyrosine kinase inhibitors (targeted therapy that inhibits overactive/high levels of enzymes in cancer cells)

Answer 93

* cancer of the lymphatic system: HL and NHL * develop from proliferation of malignany lymphocytes in lymphoid system * HL and NHL is rare \< 5y.o and incidence increases throughout childhood (boys more often) * increased risk for those with inherited or acquired immunodeficiency syndromes

Answer 94

**Description:** cancer of immune cells (lymphocytes) with diverse group of lymphoma * 4 major types: B-cell NHL (Burkitt/Burkitt-like lymphoma); Diffuse large B-cell lymphoma; Lymphoblastic lymphoma; Anaplastic large cell lymphoma **Prevalence/Incidence:** * most common types in children ⇒ BL (40%), lymphoblastic lymphoma (25-30%); large cell lymphoma (10%) * **in adults:** median age dx 67, higher occurrence in men; risk factors: old white male with autoimmune disorders, chemical exposures, infections, immune supression, risk of gastric infection with *H. pylori*, ?also high in meats and fats **Pathophysiology:** All forms of BL associated with translocations of *MYC* gene on chromosome 8 leading to increased MYC protein levels; most BLs are also latently affected with EBV * progressive clonal expansion of B, T, or NK cells **S/Sx:** NHL may arise from any lymphoid tissue so S/Sx are specific for involved site * associated signs: swelling of lymph nodes in neck, underarm, stomach, groin; trouble swallowing/breathing; painless lump/swelling in testicle; weight loss of unknown cause; night sweats * In African BL: involvement of facial bones (jaw) **Dx:** physical exam, health hx, needle biopsy of disease sites * findings will show non-contiguous lymph node invovlvement **Tx: intensive chemotherapy** (curative); radiation, potential stem cell transplant, monoclonal antibody tx

Answer 95

**Description:** type of lymphoma characterized by Reed-Sternberg (RS) cells which are derived from germinal centers of B cells * 5 types: nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depletion, lymphocyte predominance * first 4 types are "classic types" that has similar RS cell expression; last one is where RS cells are different and presents with earlier stage disease, longer survival BUT may turn into large B-cell lymphoma in 10 years in 10% of patients **Prevalence/Incidence:** * **in children:** more common among adolescents **(**rare in childhood/YA) * **in adults:** males, ~64 y.o., whites \> blacks **Pathophysiology:** genetic re-arrangements or EBV infection lead to abnormalities in gene expression of RS cells (they fail to express most of the normal B- and T-cell markers) * arises in a single chain of lymph nodes and spreads initially in a contiguous way to lymphoid tissue **S/Sx:** painful lymphadenopathy in lower cerival chain (sides and back of the neck) with/out fever (most common sx) and potentially axillary, groin, retroperitoneal (like lower abdo) * potential mediastinal involvement causing pressure on trachea/bronchi ⇒ airway obstruction * Initial sx: anorexia, malaise, fatigue * potential weight loss * **in adults:** 1/3 ppl have common systemic sx such as infeciton, night sweats, itchy skin, pruritus, fatigue **Dx:** well-defined staging system that considers extent and location of tissue +/- presence of fever, weight loss, night sweats; physical exam, CBC, blood tests, lymph node biopsy **Tx: chemotherapy and radiation therapy**; targeted therapies (monoclonal antibodies, immune checkpoint inhibitors), surgery (for adults) **Prognosis:** survivors have greater risk of developing secondary cancer

Answer 96

**Description:** reduction in the total number of erythrocytes in circulating blood or decrease in quality/quantity of Hb **Etiology:** impaired erythrocyte production; acute or chronic blood loss; increased erythrocyte destruction (or a combination of all three) **Pathophysiology:** reduced oxygen-carrying capacity of blood which leads to tissue hypoxia * initial compensation for cellular loss by movement of intersitial fluid into the blood causing increase in plasma volume but viscosity decreases ⇒ thinner blood flows fast and more turbulent causing a hyperdynamic circulatory state leading to increased SV and HR **Signs and Symptoms:** hypoxemia causes dilation of blood vessels to increase flow through them and increased SV and HR to meet oxygen demands but then it may lead to heart failure * classic S/S: SOB (dyspnea), rapid and pounding heartbeat, dizziness, fatigue, weakness * in mild cases, Sx may only be present during physical exertion/increase O₂ demand * pale skin, mucous membranes, lips, nail beds, conjunctivae (from reduced Hb) OR jaundiced (because of bilirubin build up) * other neuro system sx, GI issues, low-grade fever **Treatment:** if slowly developing conditions, then treat the underlying condition and decreasing the associated symptoms * transfusions, dietary correction, supplemental vitamins/iron

Answer 97

- cytic: cell size (macrocytic, microcytic, normocytic) - chromic: Hb content (normochromic, hypochromic, hyperchromic)

Answer 98

**Anisocytosis:** RBCs assuming various sizes **Poikilocytosis:** RBC's assuming various shapes

Answer 99

large (abnormally shaped); normal [Hb] Examples: **pernicious anemia, folate deficiency anemia**

Answer 100

small (abnormally shaped); reduced [Hb] Examples: * **Iron deficiency anemia** * **Sideroblastic anemia** * **Thalassemia**

Answer 101

normal size RBCs, normal [Hb] Examples: * **aplastic anemia** * **post-hemorrhage anemia** * **hemolytic anemia (acquired or hereditary)** * **sickle cell anemia** * **anemia of chronic inflammation**

Answer 102

**Description:** normocytic-normochromic anemia caused by acute blood loss **Etiology:** most trauma-related blood loss **Pathophysiology:** within 24h of blood loss, water and electrolyes from tissues and interstitial spaces get pulled into vasculature to replace lost plasma but this causes Hct to decrease (aka hemodilution); EPO also stimulated to increase RBC production in bone marrow **Treatment:** restoring blood volume through fluids (saline, dextran, albumin, plasma) and blood transfusions for larger blood losses

Answer 103

Iron deficiency anemia (because iron stores become depleted after body tries to intially compensate)

Answer 104

* characterized by unusually large stem cells (megaloblasts) in the marrow that mature into RBCs that are unusually large in size, thickeness, and volume * result of ineffective erythrocyte DNA synthesis common from nutritional deficiencies (vitamin B12 and folate) * RBCs in these anemias die prematurely (known as **eryptosis**) which decreases their numbers in the circulation causing anemia

Answer 105

**Description:** macrocytic-normochromic anemia that is caused by vitamin B12 deficiency **Prevalence/Incidence:** most common in those \>30 y.o. who are Northern European descent **Etiology:** congenital IF deficiency, surgical removal of stomach or parts of intestine, tapeworms * Association conditions that increase B12 demand: pregnancy, hyperthyroidism, chronic infection, disseminated cancer, hx of infection with *H. pylori*, things that contribute to chronic gastritis (excess alcohol/hot tea intake, smoking) **Pathophysiology:** main disorder is absence of IF (intrinsic factor is needed to form a complex with vitamin B12 in order for it to be absorbed) therefore pernicious anemia commonly associated with autoimmune gastritis (condition that impedes IF production) **Clinical Manifestations:** develops slowly over 20-30 years with nonspecific and vague early sx (infections, mood swings, GI/cardiac/kidney issues) * Classic symptoms: weakness, fatigue, paresthesia of feet and fingers, difficulty walking, loss of appetite, abdopain, weight loss, and sore tongue that is smooth aand beefy red * sallow skin (lemon yellow) - combination of pallor and jaundice * enlarged liver or spleen * neurological: loss of position and vibration sense, ataxia, spasticity * depression **Diagnosis:** S/sx and tests (blood tests, bone marrow aspiration, serologic studies for antibodies, gastric biopsy with indications of no HCl (achlorhydria) **Treatment:** **B12 replacement** (Weekly IM injections until corrected + monthly injections for rest of life) - or higher B12 doses if taken PO ⇒ should see rise in reticulocyte count, and normal blood count after 5-6 weeks * untreated is fatal usually due to heart failure; relapse can occur which is due to noncompliance with tx

Answer 106

**Description:** macrocytic-normochromic anemia caused by deficiency in folic acid **Prevalence/Incidence:** more common than vitamin B12 deficiency; more common in alcoholics and those with chronic malnourishment **Pathophysiology:** folic acid is essential for RNA and DNA synthesis within the maturing RBC and humans are totally dependent on dietary intake (50-200mg/day) with increased needs in lactating/pregnant females * folate gets absorbed from upper small intestine and then stored in the liver so if you are deficient, you have abnormal and less RBCs **Clinical Manifestations (S/Sx):** similar to malnourished appearance as those with pernicious anemia but specifically show these Sx: * cheilosis (scales/fissures in mouth) * stomatitis (inflammation of the mouth) * painful ulcerations of buccal mucosa and tongue characteristic of burning mouth syndrome * may also have dysphagia, flatulence, watery diarrhea * potential absorption issues in the GI tract (bowel diseases, sprue) * typically no neurological manifestations **Diagnosis:** blood tests, measurement of serum folate levels, clinical manifestations **Treatment:** PO folate daily until adequate blood levels are obtained and S/Sx reduced (typicall in 1-2 weeks); dietary modifications

Answer 107

iron deficiency anemia (IDA)

Answer 108

**Description:** normocytic-normochromic anemia resulting from decreased erythropoiesis and impaired iron utilization in those with chronic inflammation diseases (infections, cancer, autoimmune, etc.) **Etiology:** common in hospitalized individuals (go figure), elderly predisposed due to age-associated hematopoietic changes and increased inflammatory cytokines **Pathophysiology:** Combination of 1) decreased RBC life span 2) suppressed EPO production 3) ineffective bone marrow response to EPO and 4) altered iron metabolism and iron dynamics in macrophages * chronic inflammation and infection activates macrophages that release cytokines and decrease RBC production and increased RBC destruction (eryptosis) * lactoferrin is also released from neutrophils to bind iron and reudce its availability to bacteria causing all of this to be removed by MPS and converted into iron storage form (apoferritin also works similarly and is involved in decreasing iron availability) * starts off normocytic-normochromic but eventually becomes hypochromic and microcytic **Clinical manifestations:** usually mild/moderate and if Hb levels drop significantly, then S/Sx look like IDA **Dx: high total body iron storage but inadequate iron released from bone marrow** (most significant finding); failure to respond to conventional iron replacement therapy; lab tests (low EPO, low/normal total iron-binding capacity, normal or high serum ferritin levels, low transferrin) **Treatment: easement of underlying disorder** (PRINCIPAL TREATMENT) * use of EPO to increase iron stores * blood transfusions (but may worsen outcome and increase mortality/morbidity)

Answer 109

**Description:** Microcytic-hypochromic anemia characterized by presence of ringed sideroblasts in bone marrow (basically erythroblasts that have circles of mitochondria filled with iron around the nucleus because the iron has not been synthesized into Hb) **Pathophysiology:** * **Acquired Sideroblastic anemias (ASAs):** most common, unknown cause (idiopathic) OR associated with other myeloproliferative disordesr (excess proliferation of bone marrow elements) * **Reversible Sideroblastic anemias:** secondary to alcoholism (folate defiency), drug reactions (that interfere with B12 metabolism), copper deficiency (interferes with conversion of ferric iron to ferrous iron), and hypothermia (causes decreased heme sythesis + incorporation into Hb) * **Hereditary (congenital) sideroblastic anemia:** rare, almost only in males (so potential recessive X-linked transmission * SA is present in infancy/childhood but undetected until mid-life * Leading cause: **myelodysplastic syndrome (MDS)** - abnormal growth of RBC, granulocytes, megkaryocytes **Clinical Manifestations:** common anemia S/Sx, hemachromatosis (iron overload), liver and spleen enlargement, bronze-tinted skin, arrhythmias if iron builds up in cardiac tissue, impaired growth and development in severely affected kids **Diagnosis:** bone marrow biopsy to determine presence of sideroblasts **Treatment:** identify causative agent and remove it (so drugs, toxins, etc.) * **Transfusions** - primary tx * oral **pyridoxine** (vitamin B6) * phlebotomies and chelating agents * EPO administration and stem cell transplant

Answer 110

**Description:** normocytic normochromic anemia caused by hematopoietic failure or bone marrow aplasia with reduced effective RBC production **Pathophysiology:** rare; may result from infiltrative disorders of bone marrow, autoimmune diseases, renal failure, spleen dysfunction, vitamin B12/folate deficiency, infections, exposure to radiation/drugs/toxins; may be congenital **Clinical Manifestations:** pancytopenia (reduction of all three blood cell types) * Classic CV and resp manifestations with thrombocytopenia, hemorrhage into tissues, leukopenia * infection **Diagnosis:** bone marrow biopsy (determines whether anemia is caused by pure red cell aplasia or hypoplasia) **Treatment:** treat underlying disorder or prevent further exposure to causative agents * blood transfusions * marrow transplant * stimulation of bone marrow function with drugs

Answer 111

Reduction/absence of all three blood cell types (anemia, neutropenia, and thrombocytopenia)

Answer 112

**Description:** anemia caused by premature accelerated destruction of RBCs **Pathophysiology:** * can be acquired (infections, disease, drugs/toxins, abnormal immune responses) * hereditary (abnormalities in RBC membrane/cytoplasm) * can be from RBCs themselves (when they become rigid and slow, they increase their vulnerability to phagocytosis) **Clinical Manifestations:** enlarged spleen, jaundice; bones can become more deformed and fragile leading to pathologic fractures (with severe disease); CV and resp manifestations correspond to anemia severity **Dx:** blood tests, bone marrow biopsy **Treatment:** blood transfusions

Answer 113

excess RBC production

Answer 114

**Relative polycythemia:** blood gets concentrated (hemoconcentration) due to dehydration (decreased water intake, diarrhea, vomiting, increased diuretics use) ⇒ usually minor and resolves with fluids **Absolute polycythemia:** when more RBCs are produced than normal and their count is truly elevated; two forms: * **Primary polycythemia:** polycythemia vera (PV) * **Secondary polycythemia:** more common of the two and occurs as a physiologic response resulting from EPO secretion caused by hypoxia (so high altitudes, smokes, COPD/HF patients, abnormal types of Hb)

Answer 115

**Description:** slowly growing blood cancer (non-malignant) characterized by too many RBCs made by bone marrow (uncontrolled and abnormal proliferation or RBC precursors) **Etiology:** Janus Kinase 2 gene (JAK2 gene) mutation resulting in overproduction of blood cells **Prevalence/Incidence:** rare; peak incidence between 60-80 y.o.; males are 2x more likely to develop PV; more common in white ppl of Easern European Jewish ancestry * also rarely seen in children or in multiple members of a single family **Pathophysiology:** overproduction of RBC frequently with increased WBC and platelet counts toos * gene mutation causes proliferation of RBC progenitor cells without EPO stimulation but also the mutation increases EPO receptor activity so that it's constantly active regardless of EPO level **Clinical Manifestations:** uncommon and subtle (insidious) * because of increased RBC mass and Hct, leads to increased blood viscosity (hypercoagulative state) leading to occlusion of blood vessels = ischemia and infarction (and potential death) * ruddy, red color of face, hands, feets, ears, mucous membranes * engorgement of retinal and cerebral veins * Other Sx: headache, drowsiness, delirium, mania, psychotic depression, chorea (involuntary irreg. movement), visual disturbances * Enlarged spleen with abdo pain and discomfort * increased BP (due to increased blood volume) - may lead to Raynaud's and thromboangiitis obliterans (inflammation in hands and feet) * unique feature: **development of intense, painful itching that appears intensified with heat/exposure to water** - related to mast cells in skin **Diagnosis:** thrombotic event, splenomegaly, aquagenic pruritus * blood and lab findings (increase in RBCs and blood volume) * presence of JAK2 mutation **Treatment:** * phlebotomy (to reduce blood volume) and ASA * hydroxyurea: cancer durg that slows growth of new cells to slow RBC and platelets * radioactive phosphorus - supresses erythropoiesis **Prognosis:** common to survive 10-15 years (but if not proper tx, ppl die within 18 months of Sx onset due to thrombosis/hemorrhage) * may also turn into acute myeloid leukemia

Answer 116

**Description:** autosomal recessive disorder of iron metabolism, characterized by increased GI iron absoprtion with subsequent tissue iron deposition, 4 types: 1. Type 1: most common 2. Type 2: juvenile onset (iron build up begins early in life) 3. Type 3: usually intermediate between 1 and 2, sx onset before 30 y.o. 4. Type 4: begins as adults, aka "ferroportin disease" **Prevalence:** affects men more readily because women get rid of more typically **Pathophysiology:** gene mutations leading to abnormal iron regulation ⇒ excess iron becomes deposited in liver/pancreas (first) and then heart, joints and endocrine glands which can be very pain * excess can cause tissue damage that can lead to diseases * hepcidin (governs iron regulation) also not regulated due to gene mutation **Clinical Manifestations:** abdo pain, weakness and weight loss (all early Sx) * risk of cirrhosis * progressive increase in skin pigmentation, CM, CHF, dysrhythmias, arthritis, hypogonadism **Diagnosis:** specialied MRI technique to estimate hepatic iron concentration **Treatment:** phlebotomy to remove excess iron (initially weekly and then maybe every 2-3 months for maintenance)

Answer 117

**Quantitative leukocyte disorders:** result from decreased WBC production in bone marrow or accelerated destruction of cells in circulation **Qualitative leukocyte disorders:** disruptions in leukocyte function (such as phagocytes losing their ability to act effectively or lymphocytes losing their ability to respond to antigens)

Answer 118

**Leukocytosis:** elevated WBC count (higher than normal) * can occur as a normal protective response to stressors (exercise, infection, hormones, emotions, etc.) but can also be pathologic in nature (tumors, disorders) **Leukopenia:** lower than normal WBC count (\<4000 cells/ul) * THIS IS NEVER NORMAL (always pathologic in nature) * decrease leads to increased risk of infection * potential causes: certain drugs/toxins, radiation, autoimmune diseases, immune deficiencies, anaphylactic shock

Answer 119

* increase in granulocytes (neutrophils, eosinophils, basophils) and begins when blood cells are released * can also be described as **neutrophilia** since neutrophils is the most numerous (occurs in early stages of infection/inflammation)

Answer 120

Physiologic

Answer 121

**Shift-to-the-left:** aka **leukemoid reaction;** occurs when there is a premature release of immature leukocytes into the blood which typically indicates infection **Shift-to-the-right:** WBC levels returning back to normal; happens when infection/inflammation diminishes and granulopoiesis replenishes circulating granulocytes

Answer 122

**a) acute infection** neutropenia - reduction in circulating neutrophils * occurs during prolonged infection when granulocyte produciton cannot keep up with demand * all the other ones indicate there would be a reduction in neutrophils

Answer 123

**Granulocytopenia:** severe lower than normal levels of granulocytes **Agranulocytopenia:** complete absence of granulocytes in blood

Answer 124

severe infection especially in respiratory system leading to septicemia, general malaise, fever, tachycardia, mouth and colon ulcers if not treated, sepsis develops and death occurs in 3-6 days

Answer 125

**definition:** aboslute increase in total number of circulating eosinophils (\>450/ul) * usually found in areas with abundant mas cells (so resp and GI tract) **Causes:** * type I allergic disordesr associated with hay fever, asthma, parasitic infections, and drug reactions * hypersensitivity reactions (trigger release of chemotactic factors and histamine that attract eosinophils to area) * dermatologic disordesr * parasitic invasion

Answer 126

**Definition:** decrease in number of circulating eosinophils **Causes:** * generally migration of eosinophils into inflammatory sites * Cushing syndrome * result of stress caused by surgery, shock, trauma, burns, mental distress

Answer 127

**Basophilia:** increase in numbe rof circulating basophils * rare, generally a response to inflammation and immediate hypersensitivity reactions (because it contains histamine) * also seen in myeloproliferative disorders **Basopenia:** decrease in circulating numbers of basophils * seen in hyperthyroidism, acute infectioni, ovulation, pregnancy, long-term steroid therapy

Answer 128

**Monocytosis:** increase in numbers of circulating monocytes * usually associated with late stage/recovery stage when many are needed to phagocytize surviving microorganisms and debris * may also indicate marrow recovery from agranulocytosis * often seen in chronic infections **Monocytopenia:** decrease in number of circulating monocytes * rare but identified in hairy cell leukemia (bone marrow makes too many B cells in blood) and prenisone therapy

Answer 129

**Lymphocytosis:** increase in number/proportion of lymphocytes in blood * occurs in acute bacterial (rare) and viral (common) infections (such as EBV) **Lymphocytopenia:** decrease in number of circulating lymphocytes in blood * may be attributed to abnormalities in lymphocyte production; destruction by drugs, viruses, radiation; also could be unknown cause

Answer 130

**Description:** benign, acute, self-limiting viral infection of B cells transmitted through saliva (personal contact) **Etiology:** most commonly - Epstein Barr Virus (EBV) - herpesvirus **Prevalence/Incidence:** YA, between 15-35 y.o (peak between 15-24 y.o., uncommon to occur over 40 and if it does occur, usually caused by CMV); more susceptible in children with low SES **Pathophysiology:** typically (in healthy people) our B and T cells work find to fight against EBV-infected cells but in mono, B cells are affected and cannot fight against the virus appropriately causing the virus to be able to infect systemically **S/Sx:** incubation period ~30-50 days * First 3-5 days: early flu-like sx (headache, malaise, joint pain, fatigue) * Classic sx: pharyngitis, lymphadenopathy, fever * spleen enlarged (ALWAYS enlarged and can be seen radiographically 100% of the time) and liver enlargement ⇒ spleen could potentially rupture due to mild trauma or increased pressure from coughing (primarily in young males) which is the most common cause of death related to IM * eye sx: inflammations and dry eyes * Reye syndrome (swelling of brain and liver) in childre with EBV infection **Diagnosis:** blood tests - increased lymphocyte numbers; positive heterophile antibody reaction (IgM antibodies presence); rising titer of specific antibodies for EBV antigens **Treatment:** self-limiting, medical attention rarely required (rest, alleviation of Sx with analgesics and anti-pyretics) * other tx that are case specific, antibiotics, spleen removal if ruptured, steroids for severe complications **Treatment:**

Answer 131

**Leukemia:** clonal maligant disorder of bone marrow and usually related to blood * where leukemic blasts (immature WBCs) crowd out the bone marrow leading to pancytopenia * eventually get ejected into the blood where they accumluate in various organs **Lymphoma:** neoplasms that develop from proliferation of malignany lymphocytes in lymphoid system

Answer 132

1) Precursor B-cell neoplasm (immature B cells) 2) Peripheral B-cell neoplasms (mature B cells) 3) Precursor T-cell neoplasm (immature T cells) 4) Precursor T-cell and NK-cell neoplasms (mature T and NK cells) 5) Hodgkin lymphoma (RS cells and wariants)

Answer 133

**Acute leukemia:** characterized by undifferentiated or immature cells (usually **blast cells**) * has rapid and abrupt onset (without treatment, short survival time) **Chronic leukemia:** predominant cells are more differentiated but doe snot function normally, relatively slow progression

Answer 134

acute myelogenous leukemia (AML) followed by CLL

Answer 135

**Description:** slow progressing cancer where too many blood cells (not lymphocytes) made in bone marrow **Etiology:** exposure to ionizing radiation **Prevalence:** mostly adults (peak incidence 50-60 y.o) **Pathophysiology:** chronic leukemia cells are well differentiaed and readily identified * though to arise from HSC * Philadelphia chromosome (gene mutation) **Clinical Manifestations:** slow and subtle * most common finding: **lymhadenopathy** * neutropenia * infection, fever, weight loss * may progress through 3 phases: **chronic phase** (2-5 years, no sx) ⇒ **accelerated phase** (6-18 mos, primary sx develop and excessive proliferation of malignant cells occur) ⇒ **terminal blast phase** (survival of 3-6 mos) **Diagnosis:** lab analysis, blood/bone marrow **Treatment:** combined chemotherapy, biologic response modifies, allogenic stem cell transplantation

Answer 136

**Description:** slow progressing cancer where too many immature lymphocytes are found (mostly in blood and bone marrow) **Etiology:** unknown **Prevalence:** most common in western societies **Pathophysiology:** malignant transformation and progressive accumulation of B lymphocytes (and B cells fail to mature into plasma cells that make Ig) **Clinical Manifestations:** most significant for CLL -**suppression of humoral immunity, increased infection with encapsulated bacteria** * initially asymptomatic * lymphadenopathy * hyperuricemia (may produce gouty arthritis) **Diagnosis:** detecting monoclonal B-cell lymphocytosis in blood **Treatment:** periodic observation * conditions that progress, tx with chemotherapy

Answer 137

* enlarged lymph nodes (due to increase in size and number of germinal centers caused by proliferation of lymphocytes and monocytes OR by invasion of malignant cells * can be localized or generalized * generally results from 4 types of conditions: * neoplastic disease * immunologic or inflamamtory conditions * endocrine disorders * lipid storage diseases * Dx requires location and size of lymph nodes + age, sex, and geographic location

Answer 138

**Description:** A B-cell NHL that is highly aggressive anf fastest growing tumor; three main types: * **Endemic BL:** commonly occurs in Africa, linked to RBC and involves rapidly growing tumor of jaw and facial bones * **Sporadic BL:** occurs worldwide * **Immunodeficiency-related BL:** most often seen in those with AIDS **Prevalence/Incidence:** most often in children/YA; rare in US **Pathophysiology:** EBV infection with potential suppression of immune system by other illnesses * B cells undergo chromosomal trasnlocations leading to MYC protein being made which increases expression of pro-grwoth genes) - chromosomes 8 and 14 most common **Clinical Manifestations:** * in non-african BL: abdo swelling most common * tumors at extranodal sites * common sx: N/V, loss of appetite or change in bowel habits, GI bleed, Sx of acute abdo condition, intestinal performation, renail failure **Diagnosis:** presence of tumors in facial bones and jaw; enlarged lymph nodes; bone marrow containing malignant B cells * Lab studies: CBC, electrolytes, liver and renal function tests, hep B, HIV, uric acid, lactate dehydrogenase (from tissue damage) **Treatment:** combination chemotherapy (NO radiation therapy)

Answer 139

**Description:** rare variant of NHL with predominant T-cell origin (similar to ALL) **Prevalence:** male predominance, more common in children and adolescents **Pathophysiology:** arises from clone of relatively immature T cells that become malignant in thymus * associated with translocations (chromosomes 7 and 14 often as they encode the T-cell receptors) * result in increased expression of a variety of transcription factors and loss of growth control **Clinical Manifestations:** * first sign: **painless lymphadenopathy in neck** * peripheral lymph nodes in chest become involved (most node involved are located above diaphragm) * presents stage IV in most ppl (very aggressive) * **unique mediastinal mass** (due to origina of tumor in thymus) - reuslts in dyspnea, chest pain, potential bronchi or superior vena cava compression) * may suppress hematopoiesis **Treatment:** combined chemotherapy (intensive therapy) - high response rate and increased survival rate in early disease stages but also high relapse rate

Answer 140

**Thrombus:** stationary clot attached to vessel wall – made of fibrin and RBC and can develop in either arterial or venous system * **Arterial thrombi**: form under conditions of high blood flow and are composed mostly of platelet aggregates held together by fibrin strands * **Venous thrombi**: form under conditions of low blood flow, composed mostly of RBCs with larger amounts of fibrin and fewer platelets

Answer 141

blood clot circulating in bloodstream – may become lodged in smaller blood vessels blocking blood flow into the local tissue or organ and leading to ischemia

Answer 142

removing/dissolution of clot and supportive measures * anticoagulant therapy (for **venous thrombi**) * parenteral heparin for thromboembolism * oral coumarin drugs * fibrinolytic or thrombolytic therapy

Answer 143

1) injury to the blood vessel endothelium 2) abnormalities of blood flow 3) hypercoagulability of the blood

Answer 144

* Sites of turbulent flow in arteries and stasis of blood flor in veins will increase the risk of thrombus formation * in turbulent areas: platelets and endothelial cells may be activated leading to thrombosis * in sites of stasis, platelets remain in contact with endothelium for prolonged periods of time and clotting factors are not dilated so they become activated

Answer 145

* Blood disorder that makes the blood in your veins and arteries more likely to clot * due to mutations in platelet receptors, coagulation proteins, fibrinolytic proteins, other factors (there are many) * Tests to determine condition: prothrombin tibe, partial thromboplastin time, levels of protein C, S, and AT-III

Answer 146

e) all are associated with acquired protein deficiencies

Answer 147

**Description:** an autoimmune syndrome characterized by autoantibodies against plasma membrane phospholipids and phospholipid-binding proteins **Prevalence/Incidence:** predominantly females of reproductive age **Pathophysiology:** related to autoantibodies reacting with platelets or endothelial cells causing increased risk for thrombosis; or on placental surface (causing damage to the placenta); considered as an acquired hypercoagulable state **S/S:** thrombosis risks; obstetric complications for pregnant women; potential death from recurrent major thrombus formation **Dx:** measuring coagulation time of blood; specific tests for antibodies against phospholipids/proteins that bind to phospholipids **Tx:** low molecular weight heparin with low dose ASA to prevent obstetric complications

Answer 148

**Description:** plasma cell malignancy (plasma cell cancer) characterized by slow proliferation of tumor cell masses in bone marrow which these masses associated with lytic bone lesions (round, punch out regions in the bone) * variants: **solitary myeloma** (single mass in bone/soft tissue); **smoldering myeloma** (lack of sx and high plasma abnormal antibody protein M) **Prevalence/Incidence:** occurs in all races but incidence is 2x in blacks \> whites; usually 40+ and peak incidence is 65-70; slightly more commen in men * risk factors: exposure to radiation/chemicals; hx of plasma cell disorder with M protein in blood (monoclonal gammopathy) or plasmocytoma **Pathophysiology:** multiple mutations (anueploidy, translocations) leading to malignant plasma cells that come from B cells that produce ++amounts of one class of antibody that is frequently defective (M protein most prominent) * cytokine IL-6 also as to stimulate osteoblasts causing those bone lesions and hypercalcemia * normal plasma cells are supressed by myeloma (cells that reside in bone marrow) resulting in diminished/absent normal antibodies * myeloma also produces free Ig light chain (**Bence Jones protein**) that is present in blood/urine and causes renal tubular cell damage **Clinical Manifestations:** hypercalcemia, bone lesions, anemia, renal failure * pain and pathologic fractures from bone destruction (often the verebrae most involved) * amyloidosis: antibody proteins sticking together in nerves/organs (fatigue, purple spots on skin, enlarged tongue, diarrhea, edema, numbness in legs/feet) * proteinuria * potential hyperviscosity syndrome due to high amounts of paraprotein (M protein) * infections (leading cause of death from MM) * neuro sx: confusion, headaches, blurred vision 2' to hypercalcemia **Dx:** Sx, radiographic and lab studies, bone marrow biopsy, measurement of Ig and levels of M protein, Bence Jones protein **Treatment:** combination chemotherapy (others: drug therapy, targeted therapy, chemo with stem cell transplant, radiation, sometimes surgery) **Prognosis:** ~3 years

Answer 149

* MGUS often precedes MM and is dx by presence of M protein in blood/urine without additional evidence of MM (nonpathologic and requires no treatment) * MM is a progressive disorder so MGUS can progress to asymptomatic MM and finally to symptomatic MM

Answer 150

a) phagocytosis of blood cells and particle matter (bacteria) b) antibody production c) hematopoiesis d) sequestration of formed blood elements

Answer 151

True. It can be present in ppl without evidence of disease

Answer 152

a) cytopenias (anemia, leukopenia, thrombocytopenia or a combination) b) cellular bone marrow c) splenomegaly d) improvement after splenectomy

Answer 153

**Primary:** unknown cause **Secondary:** occurs in the presence of another condition

Answer 154

**Description:** spleen enlargement **Etiology:** Acute or chronic infections, congestive (cirrhosis, heart failure, splenic vein obstructions), infiltrative (diabetic lipemia, amyloidosis), tumors/cysts **Pathophysiology:** * infection causes splenomegaly due to icnreased demand for defense activities (may cause them to be so enlarged hat it loses its rubbery resilience and ruptures) * **Congestive splenomegaly:** most often caused by liver cirrhosis leading to splenic veins being obstruced * **Infiltrative splenomegaly:** caused by engorgment by macrophages with indigestible material (often associated with storage diseases) * tumors/cysts themselves can cause spleen growth **Clinical Manifestations:** overactivity of spleen causes alterations in all blood components * up to 50% RBC sequestration, granulocytes, platelets * **spleen size** is the determining factor (and degree of blood flow into it) for rate of splenic pooling * anemia (due to RBCs being exposed to splenic conditions and being destroyed) * may lead to dilutional effect (increased blood volume but decreased [RBC]) **Treatment:** attempt at repair and preservation but if can't, then splenectomy (potential complication post-op is **overwhelming post-splenectomy infection (OPSI)** which may progress to septic shock and DIC

Answer 155

platelets coagulation factors

Answer 156

red or purple discoloured spots on skin that occur when there is a deficiency of normal platelets necessary to plug damaged vessels to prevent leakage from tiny tears that occur daily with capillaries

Answer 157

**Thromboembolic disease:** genetic or acquired disorders that result in clotting (whether activated or spontaneous) **Hypercoagulability:** any blood disorder that predisposes to blood clotting

Answer 158

**Description:** platelet count \< 150 000 platelets/ul of blood; * pseudothrombocytopenia: phenomenon that results from platelet counting errors in a blood sample when analyzed by an automated cell counter (to be ruled out prior to dx of thrombocytopenia) * thrombocytopenia may be falsely dx due to dilutional effect after massive transfusion to treat bleeding * can be induced by spleni sequestering (hypersplenism) * can also be induced by hypothermia (but reversible) **Pathophysiology:** results from decreased platelet production or increased consumption of both; acquired is more common and may occur due to viral infections (EBV, rubella, CMV, HIV), drugs, chronic renal failiure, bone marrow hypoplasia, rad therapy, cancer * most common forms of thrombocytopenia are result of increased platelet consumption

Answer 159

**Description:** drug-induced thrombocytopenia (by heparin which is the most common cause of this type) **Pathophysiology:** caused by immune-mediated adverse drug reaction caused by IgG antibodies against heparin platelet factor 4 complex leading to platelet activation (results in increased platetlet consumption and decreased platelet counts 5-10 days after heparin administration) **Clinical Manifestations:** HALLMARK - thrombocytopenia (~50% platelet count decreases in most ppl) * potential risk for venous/arterial thrombosis due to prothrombic state caused by antibody binding to platelets * venous thrombosis more common (DVT, PE) * arterial thromvosis affects LE causing limb ischemia, may lead to CVAs and MIs * bleeding is uncommon **Dx:** clinical observations (platelet counts, test to measure anti-heparin platelet factor 4 antibodies) **Tx:** withdraw from heparin use, use other anticoagulants

Answer 160

**Description:** most common cause of thrombocytopenia 2' to increased platelet destruction; may be acute or chronic * **Acute:** usually 2' to infections (especially viral) or drug allergies, conditions that lead to large amounts of antigen in blood; immune complexes are formed and bind to Fc receptors on platelets leading to destruction in spleen * **Chronic:** caused by autoantibodies (generally IgG) against platelet-specific antigens ⇒ recognized and removed from circulation by macrophages in spleen **Prevalence/Incidence:** acute ⇒ frequently observed in children, lasts 1-2 months with complete remission; chronic ⇒ more common in adults (women 20-40 esp.); incidence increases with age **Clinical Manifestations:** * initially, can range from minor bleeding to major hemorrhage from mucosal sites * rare to have intracranial bleeding/internal bleeding in other areas **Dx:** hx of bleeding and associated sx (weight loss, fever, headache); physical exam to note the bleeding; Ax for evidence of infections, medications, family hx, evidence of thrombosis * CBC, blood smears * NO evidence of splenectomy **Treatment:** acute form usually resolves without major clinical consequences; chronic form may have multiple remissions/exacerbations * glucocorticoids (prednisone) to supress immune response and further platelet sequestration * IVIG to prevent major bleeding * splenectomy if other therapies are ineffective (to remove site of destruction) * immunosuppressants if splenectomy doesn't work

Answer 161

**Description:** aka **Moschcowitz disease;** a multisystem disorder characterized by small/microvessle disease where platelets aggregate and cause occlusion of arterioles/capillaries within microcirculation**; two types:** * **Familial type (chronic relapsing TTP):** rare; usually seen in children; chronic relapses ~3 week intervals * **Acquired TTP:** more common; acute/severe, occurs mostly in females in their 30s and rare in infants/older adults * note that these thrombi are not the same as fibrin clots; minimal fibrin and red cells in these platelet aggregates **Etiology:** most cases related to dysfunction/mutation of plasma enzyme ADAMTS13 which is repsonsible for digesting larger precursor molecules of vWF into smaller molecules **Pathophysiology:** because ADAMTS13 is defected, large vWF on endothelial cells are not broken down into smaller ones and leads to formation of large aggregates of platelets which break off and form occlusions in smaller vessels ⇒ aggregates lead to increased platelet consumption (thus thrombocytopenia) **Clinical Manifestations:** * chronic relapsing TTP: usually recognized and sucessfully treated * Acquired form: pathognomonic pentad (group of five) in 20-30% of cases * extreme thrombocytopenia * intravascular hemolytic anemia * ischemic S/Sx most often involving CNS * kidney failure * fever **Diagnosis:** blood smear showing fragmented RBCs (schizocytes) produced by shear forces when they come in contact with clot; also high LDH levels and potentially LDL too **Treatment: plasma exchange with fresh frozen plasma to replenish functional ADAMTS13;** steroids (glucocorticoids); splenectomy for those not responding to conventional tx; immunosupressants **Prognosis:** may lead to complete recovery with no LT complications

Answer 162

**Description:** platelet count \> 450 000/ul (but usually asymptomatic until it reaches 1 mil/ul of blood) **Pathophysiology:** two types * **Essential (primary) thrombocythemia (ET):** excessive platelet production resulting from defect in bone marrow megakaryocyte progenitor cells ⇒ abnormal blood clotting occurs * most common mutated genes: JAK2, CALR * **Secondary thrombocythemia:** may occur 2' to splenectomy because platelets that would normally be stored in spleen remain in circulating blood; may also occur during some inflammatory conditions as cytokines increase TPO production leading to increased megakaryocyte production **Clinical Manifestations:** * risk of arterial/venous thrombosis (DVT, PE) * **microvascular thrombosis** (ischemia in fingers, toes, cerebrovascular regions) - sx of this is erythromelalgia (burning sensation and redness, congested, in hands and feet), headache, paresthesias * hemorrhaging and clotting simultaneously **Diagnosis:** CBC; you need to have sustained high platelet count, bone marrow biopsy showing proliferation of megakaryocytes and no increases in the other cells, failure to meet criteria of other conditions, presence of JAK2 or other clonal marker **Treatment:** prevention of thrombosis/bleeding * hydroxyurea - suppresses platelet production * IFN - inhibits growth of megakaryocyte precursors * low dose ASA to relieve erythromelalgia

Answer 163

1) drugs (aspirin, NSAIDs) 2) systemic inflammatory conditions (chronic renal or liver disease, autoimmune disorders, etc.) 3) hematologic alterations (MM, leukemias, etc.)

Answer 164

increased; normal

Answer 165

one or more clotting factors common causes: liver disease, vitamin K deficiency

Answer 166

* vit K is needed for synthesis and regulation of prothrombin, some procoagulant factors, and anticoagulant factors within liver (so if you don't have it, then hemostasis will be impaired) * primary source of vit K: green leafy vegetables * most common cause of vit K deficiency: IV feeding with antibiotics that destroy gut bacteria * treatment: IV vitamin K

Answer 167

* liver disease causes defects in clotting/fibrinolytic systems and platelet function because liver cells produce most of the factors involved in hemostasis (and major site for production of plasminogen, TPO, ADAMTS13 * thrombocytopenia often seen * Treatment: **fresh frozen plasma;** alternatives: exchange transfusions

Answer 168

* Group of conditions with range of symptoms and generally considered ot be disease processes that complicate primary disease states * unclear definition, dx, treatment and management BUT most common is DIC

Answer 169

**Description:** acquired condition characterized by widespread activation of coagulation leading to formation of fibrin clots in medium and smal vessels or microvasculature throughout the body ⇒ leads to blackage of blood flow to organs ⇒ multiple organ failure * may be acute/severe; localized (one organ) or generalized (multiple organs) **Etiology:** wide variety of conditions specifically those capable of activating clotting cascade (most commonly associated with SEPSIS); can also be from microorganisms, trauma, liver disease, heat stroke, tumors, preg complications, vascular abnormalities, toxic/immune reactions (like snake bites, rec drug use, etc.) **Pathophysiology:** primary initiator of DIC is endothelial damage/tissue factor * TF binds clotting factor VI which leads to conversion of prothrombin to thrombin leading to clot formation AND anticoagulant systems can't keep up ⇒ clots deposited throughout vascular system **S/Sx:** bleeding from lines/puncture sites; purpura, petechiae, hematomas (usually bleeding at three or more unrelated sites); potential shock that is disproportionate to blood loss; cyanosis in fingers and toes; jaundice **Diagnosis:** evidence of clotting activation, fibrinolytic activation, consumption of clotting inhibitors, end-organ damage/failure **Treatment:** eliminate condition (remove trigger), control thrombosis (heparin), maintain organ function (fluids)