Exam 2 Flashcards

Question

Volume of plasma infusion

Answer 1

• 200 -250 mL • 400 mg fibrinogen • factor 7: half life of four hours, lose quickly once you start thawing • dosage: 10-20 mg/kg, two units should increase factor levels by 20- 30% • AB Plasma is used in emergencies (no antibodies towards A or B)

Answer 2

• INR > 1.8 (plasma is generally ineffective for INR less than 1.8) • PTT > 45” • indicated: emergency reversal of warfarin, if vitamin K or prothrombin complex concentrates do not work

Answer 3

• Six whole blood derived units • 300 mL • 150 mg fibrinogen • bump: 1 SDP should increase platelet count to around 25-40,000

Answer 4

• stored for up to 5 to 7 days at room temperature • highest risk of bacterial contamination and septic transfusion reaction

Answer 5

• 5000/ul has been shown to be the minimum required for maintenance of endothelial integrity Transfuse if : • < 10,000 for normal patient • < 20,000 for mucosal bleed • < 50,000 for active bleeding, surgery, invasive procedure • < 50,000 for infant less than one month old • < 100,000 for neuro or ophthalmologic surgery • if playlist dysfunction due to drugs, or bypass pump

Answer 6

• cold-insoluble portion of a frozen plasma unit that precipitates when the frozen plasma is thawed between 1–6 C • 15mL • 250 mg fibrinogen • factor 8 • vonWillebrand’s factor • factor 13 • fibronectin indication: mainly fibrinogen deficiency, <150mg/dL for active bleeding and <100mg/dL normally

Answer 7

• increases hemoglobin by 1 g/dL and hematocrit by 3% • triggers for transfusion: 7 g/dL, stable, non-bleeding, patients OR 8 g/dL patients with greater oxygen demand

Answer 8

• 10,000 ul for non-bleeding patients • 50,000 ul for procedures/ bleeding patients • 100,000 ul for neurosurgery/ophthalmology

Answer 9

Plasma: transfuse for INR> 1.8 Cryoprecipitate: transfused for 1. Fibrinogen < 150 g/dL in actively bleeding patients 2. Fibrinogen < 100 g/dL in non-bleeding patients

Answer 10

• white blood cells contribute to the overall transfusion reactions, and increase the risk of anti-HLA antibodies which can cause rejection of solid organ, transplants, and platelet refractoriness

Answer 11

• lymphocytes in donor bag may recognize recipient (transfused patient) as foreign and mount an immune attack— irradiation disables lymphocytes • associated lymphocytes can cause transfusion associated graft versus host disease (TA-GVHD) in severely immunocompromise patients— usually fatal

Answer 12

• past current or eminent (two weeks) stem cell transplant • purine analog drugs in the past 12 months (fludarabine, cladribine, and pentostatin) • Campath (alemtuzumab) • congenital, immunodeficiency syndrome (diGeorge, Wiskott-Aldrich, severe combined immunodeficiency, variable, combined immunodeficiency) • pediatric (all newborns up to six months old, intrauterine transfusions, all pediatric cancer patients) • oncology— Hodgkin’s lymphoma only

Answer 13

• if excess potassium is a problem: 1. Compromised cardiac function. 2. Pre-existing hyperkalemia

Answer 14

• plasma proteins cause allergic and anaphylactic a transfusion reactions • washing removes all plasma proteins • indicated when patients have a history of severe allergic reactions or anaphylaxis • severely limits the shelf life: RBC= 24 hours, platelets= 4 hours

Answer 15

• removes excess plasma without washing • useful for patients with volume overload and congestive heart failure (CHF) • can help prevent transfusion associated circulatory overload (TACO) • maybe used with pediatric patients who cannot process volume • also removes plasma, therefore helps patients with a history of allergic reactions

Answer 16

• fever, chills, rigors • pain— infusion site, back pain • respiratory problems • cardiovascular problems • cutaneous: itchiness, hives, erythema, Flushing, jaundice, pallor • GI: nausea, vomiting, diarrhea • urinary: red urine, hemoglobinuria • heme: bleeding, oozing, coagulopathy

Answer 17

1. Stop the transfusion immediately. 2. Keep the IV line open with saline 3. report reaction to the blood bank 4. Return, unused portion of unit was infusion set to the blood bank. 5. Send additional labs— EDTA, red top, urine

Answer 18

• clerical check: confirm intended unit was transfuse to intended patient • repeat ABO blood type and screen for RBC antibodies • direct antiglobulin test (DAT) to test for antibodies on the RBC • check serum color (pink – red for hemolysis) • Gram stain and culture

Answer 19

• 1 to 3% of transfusions • hypersensitivity to plasma proteins • mild reactions cause urticaria • treatment: Benadryl, steroids • ** mild allergy, and patient response to therapy is the only instance where the transfusion may be restarted

Answer 20

• 1 in 20,000-50,000 • platelets> plasma> RBC • more severe reaction: systemic • symptoms: hypertension, bronchospasm, wheezing, local, edema, anxiety, abdominal distress • treatment: Trendelenburg, epinephrine, anti-histamines, steroids, beta 2-agonist

Answer 21

• acute hemolytic reaction occurs within 4 hours of transfusion (usually immediately) • due to the presence of preformed antibody ( RBC transfusion= major incompatibility, platelet/plasma transfusion= minor incompatibility)

Answer 22

Antibody coated RBC activate the complement system —> hemolysis (intravascular) —> cytokine storm —> coagulopathy (DIC)

Answer 23

• fever- most common • red urine (hemoglobinuria) • red plasma (free hemoglobin) • hypotension, shock • severe flank pain • chest tightness, and sense of impending doom • DIC, oozing • vomiting, diarrhea

Answer 24

• positive DAT • elevated LDH • elevated bilirubin • low haptoglobin • low fibrinogen • elevated plasma hemoglobin

Answer 25

• typically occurs 5- 14 days— weeks after an RBC transfusion • formation of a new antibody, especially from the KIDD blood group (kids play hide and seek) • antibody undetectable on screen prior to transfusion • signs: unexplained drop in hemoglobin, unexplained rise in unconjugated bilirubin, and positive DAT (RBCs have antibody on their surface)

Answer 26

• one of the most commonly reported reactions (1%) • fevers, chills, rigors • mechanism: antibodies in recipient plasma to antigens on donor lymphocytes, granulocytes, and platelets. Cytokines present in stored plasma/Supernatant portion of product • treatment: supportive/symptomatic • diagnosis of exclusion

Answer 27

1. Transfusion associated circulatory overload (TACO) 2. Transfusion related acute lung injury (TRALI) 3. Hemolytic transfusion reaction 4. transfusion associated sepsis 5. Anaphylactic/anaphylactoid reactions 6. Coincidental underlying conditions, such as COPD, anxiety, PE, reaction to a medication, or asthma

Answer 28

• acute onset- within six hours of transfusion • acute lung injury: hypoxemia, bilateral infiltrates on chest x-ray, no evidence of left atrial hypertension, no other cause for acute lung injury • previously was the number one cause of transfusion related mortality (is now TACO)

Answer 29

• donor has antibodies to recipient human neutrophil antigens (HNA) or HLA on neutrophils • soluble antibody antigen complex, activate complement —> neutrophil influx —> damage

Answer 30

• pre-existing condition, activates neutrophils • transfused blood has accumulated lipids, that further activate, the already primed neutrophils

Answer 31

• plasma containing products are more frequently implicated in TRALI • multiparous and transfused females are the most likely to have an anti-HNA or anti-HLA • switching to male donor only plasma has significantly reduced rates of TRALI (as well as testing)

Answer 32

• volume overload from transfusion • occurs during or within several hours of transfusion • symptoms: dyspnea, respiratory distress, orthopnea, cyanosis, tachycardia, HTN, rales, jugular venous distention (JVD), S3 on cardiac auscultation, lower extremity edema • treatment: discontinue transfusion and fluids, give diuretics and supportive measures (O2)

Answer 33

1:356 - Increase risk and very young, very old, renal failure, and chronic anemia

Answer 34

• acute severe onset of thrombocytopenia (platelets < 10,000) • 3 to 10 days post transfusion • amnestic response to a platelet antigen, exposure causes removal of both transfused and self platelets— can occur from any type of transfusion (rare)

Answer 35

• engraftment of donor lymphocytes • rash, severe, diarrhea, liver abnormalities, pancytopenia (bone marrow aplasia) • 4-30 days post transfusion • almost always fatal !!

Answer 36

Irradiation (removal/ inhibition of donor lymphocytes)

Answer 37

1. Volunteer donations 2. Selection of healthy donors 3. Universal donor health questionnaire 4. Mini exam (vitals, hemoglobin, check arms for needle tracks) 5. Donor testing

Answer 38

• 1 in 5000 platelets have been confirmed positive culture for bacteria (usually a subclinical amount) • more common with a platelet transfusion: because they are stored at room temperature • symptoms: fever, hypotension, shock, nausea, vomiting, respiratory symptoms, coagulopathy

Answer 39

1. HBV (1 in 205,000-488,000) 2. HCV (1 in 1,935,000) 3. HIV (1 in 2,135,000)

Answer 40

- west Nile virus - CMV

Answer 41

• Chagas disease- Trypanosoma Cruzi • malaria- plasmodium species • Babesia PRION: variant CJD

Answer 42

• hypothermia • citrate toxicity • coagulopathy (dilutional) • electrolyte imbalances (excess potassium) • iron overload • air embolism (very rare)

Answer 43

• RBCs< 80 MCV • low iron: iron deficiency anemia • normal/high iron: ACD/thalassemia

Answer 44

• RBCs 80-100 MCV • reticulocyte count: 1. High: hemolytic anemia or blood loss 2. Low: acute blood loss, aplastic anemia, early IDA, anemia of renal disease, myelopthisic anemia

Answer 45

• RBCs > 100 MCV • normal B12/folate: reticulocyte count for normocytic anemia • low B12/folate: megaloblastic anemia

Answer 46

• most common overall anemia, worldwide • symptoms: pallor, fatigue, dyspnea on exertion, headache, syncope • signs: pallor, spooning of the nails (koilonychia) • when associated with dysphasia/esophageal webs consider: plummer-Vinsen syndrome, Paterson-Kelly syndrome, sideropenic dysphasia

Answer 47

• low, dietary intake: infants, bed exclusively on milk, unbalanced food • increase demands: pregnancy, infancy • malabsorption: celiac, disease, post-gastrectomy, duodenum problems • intravascular hemolysis (think: microangiopathic hemolytic anemia, and proximal nocturnal hemoglobinuria)

Answer 48

1. Serum iron levels (120 µg/dL in men and 100 µg/dL in women) 2. TIBC 300 to 350 µg/dL, indirectly measures transferrin 3. Serum ferritin levels 4. Assessment of BM Fe (reliable, but invasive)

Answer 49

• low hemoglobin • low PCV (packed cell volume) • low red cell count • RDW (anisocytosis) increased • low MCV (<80) • low MCHC and MCH • decreased percent saturation of iron • decrees ferritin • INCREASED TIBC (total iron binding capacity)

Answer 50

an increase in abnormal red blood cells of any shape that makes up 10% or more of the total population. Poikilocytes can be flat, elongated, teardrop-shaped, crescent-shaped, sickle-shaped, or can have pointy or thorn-like projections, or may have other abnormal features.

Answer 51

• cellularity: increased • erythroid hyperplasia • micro-normoblastic maturation • bone marrow iron: (Prussian blue reaction) reduced or absent

Answer 52

• administer iron— oral ferrous sulfate • caution: GI side effects and stool turns black • how do you assess the response to treatment? — reticulocyte response in 7 to 10 days

Answer 53

• chronic infections, inflammation, malignancy, and anemia of renal disease • pathogenesis: IFN, TNF, IL1-beta and IL6 block iron transfer from macrophage store —> RBC (prevent kidney release of erythropoietin) • cells are mildly microcytic and hypochromic • typically resistant iron therapy

Answer 54

Anemia of chronic disease— because of suppression of erythropoiesis by systemic inflammation

Answer 55

• chronic osteomyelitis • bacterial endocarditis • TB/lung abscess • chronic inflammation (rheumatoid arthritis) • neoplasms: Hodgkin’s lymphoma, breast, and lung cancer

Answer 56

• increased hepatic hepcidin synthesis—> increased plasma hepcidin —> blocks transfer of iron to erythropoiesis precursors by down regulating ferroportin in macrophages • ferritin is increased, transferrin is reduced, serum iron is low

Answer 57

• ACD: Decreased TIBC, increased storage iron in bone marrow, serum ferritin • ACD and IDA same: hypochromic and microcytic, low serum iron

Answer 58

• decreased EPO • decreased ACD • normocytic anemia • BURR cells • prolonged bleeding time: defect in platelet aggregation, reversible with dialysis

Answer 59

• Reduce production of erythropoietin • CRF caused by: diabetes, chronic glomerulonephritis, chronic pyelonephritis • lab findings: increased serum, BUN, and creatinine, low reticulocyte count, burr cells • treatment: recombinant erythropoietin

Answer 60

• group of anemias with a defect in heme synthesis in the mitochondria (accumulation) • leads to ring sideroblast

Answer 61

1. Chronic alcoholism. 2. Vitamin B6, pyridoxine deficiency 3. Lead (Pb) poisoning

Answer 62

1. Congenital: X-linked, mitochondrial 2. Acquired: myelodysplastic syndrome, copper or vitamin B6 deficiency, lead poisoning, alcoholism, drugs, porphyria

Answer 63

• moderate to severe anemia • hypochromic, microcytic/normocytic, dimorphic • erythroid hyperplasia in bone marrow, macronormoblastic erythropoiesis • almost complete saturation of TIBC • presence of ringed sideroblasts must be present for diagnosis

Answer 64

• most common in children, ages 1 to 5 • may occur in utero, because it crosses the placenta • causes: pica (eating, lead based paint), pottery painting, factory workers, radiator repair mechanics, air contamination

Answer 65

1. Ferrochelatase: iron, cannot bind with protoporphyrin to form heme 2. ALA dehydratase: causes an increase in Delta-ALA 3. Ribonuclease: ribosomes cannot be degraded and persist in the RBC- results in coarse basophilic stippling

Answer 66

• abdominal colic with constipation • encephalopathy: cerebral edema, papilledema, demyelination • learning disabilities • growth retardation: Pb gets deposited in the epiphysis of growing bone

Answer 67

• peripheral neuropathy: foot drop, claw hand, wrist drop • nephrotoxic damage to proximal renal tubules • lead line in the gums (Burton’s) • reduced RBC survival time

Answer 68

• increased whole blood and urine lead levels • treatment: chelation therapy; succimer, dimercaprol, ethylene diamine tetra acetic acid (EDTA)

Answer 69

• increased serum iron, iron saturation, ferritin • normal to decreased MCV • decreased TIBC • ringed sideroblast in bone marrow aspirate • course basophilic stippling of RBCs due to persistence of ribosomes

Answer 70

• normocytic anemia affecting the hematopoietic stem cells—> malfunction of myeloid stem cells (granulopoiesis, erythropoiesis, thrombopoiesis) • causes anemia, neutropenia, and thrombocytopenia • can be caused by: chloramphenicol, chemotherapeutic agents, benzene, ionizing radiation, biological agents (Parvo B19)

Answer 71

• multipotent myeloid stem cells are suppressed, leading to bone marrow failure and pancytopenia • causes autoreactive, T cells, and defects in telomerase

Answer 72

• normal lymphoid stem cells • decreased cellularity in the bone marrow • increased Adipose tissue in the bone marrow • Pancytopenia on peripheral blood smear

Answer 73

• fever (infection associated with neutropenia) • bleeding (thrombocytopenia) • fatigue (anemia) • does not cause splenomegaly • lymphocytes are present in the bone marrow and peripheral blood

Answer 74

• a rare form of marrow failure, characterized by the absence of red cell precursors in the bone marrow • resulting in decreased RBC production, granulocytic and platelet precursors are normal • causes: Parvo B19, thymoma (myasthenia gravis) • the only manifestation is anemia

Answer 75

• caused by space occupying lesions that distorts the bone marrow • result in decreased productivity • diseases that infiltrate, the bone marrow are known as myelophthisic processes • causes: metastatic cancer, granulomas, tuberculosis, marrow fibrosis • peripheral smear will show: Leukoerythroblastic picture (immature red and white blood cell in the peripheral blood)

Answer 76

• premature destruction— hemolysis • jaundice, gall stones • marked increase in reticulocytes • extravascular: within the macrophages of spleen and liver • intravascular: within the circulation (blood vessels)

Answer 77

• decreased red cell lifespan • compensatory increase in erythropoiesis —> increased reticulocytes and polychromatophilia in peripheral blood • retention of degraded red cell products (including iron— secondary hemosiderosis) • pigmented gallstones

Answer 78

• premature destruction of red cells within phagocytes • reduce deformability of red cells (abnormal shape) • RBCs containing inclusions • big three: anemia, splenomegaly, jaundice

Answer 79

• mechanical damage • enzyme deficiency • complement mediated lysis • hemoglobinemia, hemoglobinuria, hemosiderinuria • plasma haptoglobin is reduced • serum LDH is elevated

Answer 80

Intravascular hemolysis

Answer 81

Acquired/external injury • physical • drugs (alpha-methyldopa, cephalosporins, ibuprofen) • parasite/infections: malaria, septicemia (DIC) Congenital/internal defects • defective membrane: spherocytic anemia • defective Hgb: SCA, thalassemia • deficient enzyme: G6PD deficiency

Answer 82

• intravascular: cola colored • extravascular: dark urine/high colored urine (orange)

Answer 83

Thalassemia

Answer 84

• hereditary Spherocytosis • immune hemolytic anemia • ABO incompatibility

Answer 85

• MAHA • HUS • TTP • DIC • prosthetic heart valve

Answer 86

• thalassemia • alcoholic liver disease • splenectomy

Answer 87

• myelophthisic anemia • myelofibrosis

Answer 88

• sickle cell anemia

Answer 89

• hereditary elliptocytosis

Answer 90

• irregular spicules on surface, seen in abetalipoproteinemia

Answer 91

• uremia, kidney disease

Answer 92

• RBC with bites of cytoplasm being removed by splenic macrophages • seen in G6PD deficiency

Answer 93

• due to compensatory increase in erythropoiesis leading to bone distortions • chipmunk face • frontal bossing (skull malformation) • crewcut Skull x-ray • hyperplasia

Answer 94

non-enzymatic Fenton reaction ( H2O2 + Fe2+ --> OH w/free radical + OH- + Fe3+)

Answer 95

Iron uptake via Hepcidin, there is no regulated iron excretion system

Answer 96

Erythropoiesis

Answer 97

1. hemoglobin iron (F:28 mg/kg, M: 32 mg/kg) 2. Storage iron in the liver (F: 5-6, M: 10-12) 3. Myoglobin iron (F: 4, M: 5)

Answer 98

- By DMT1 in intestinal epithelial cells - exported to the blood at the basolateral side through ferroportin (and oxidation of ferric iron by hephaestin occurs) - Hepcidin produced in the liver regulates the uptake of dietary iron by blocking Ferroportin

Answer 99

- Brush border ferreductase (DcytB) - it can then be brought into the cytoplasm via DMT1

Answer 100

- Hephaestin, a copper dependent enzyme

Answer 101

- Ferritin, a storage of hundreds of atoms of ferric iron. Stored as a mineral crystal - If there is high ferritin in the serum, that indicates iron excess

Answer 102

- Happens at the level of translation 1. high iron --> binds IRP1/2 --> cannot bind mRNA at the 5' end --> transcription (FTH, FTL, ferroportin, HIF2-alpha, and ALAS2 are expressed) 2. High iron --> binds IRP 1/2 --> cannot bind mRNA at the 3' end --> TFR1 and DMT1 mRNA degraded --> uptake from diet is decreased 3. low iron --> cannot bind IRP1/2 --> IRP 1/2 binds mRNA at the 5' end --> NO transcription (FTH, FTL, ferroportin, HIF2-alpha, and ALAS2 are repressed) 4. low iron --> cannot bing IRP 1/2 --> IRP 1/2 binds at mRNA at the 3' end --> TFR1 and DMT1 mRNA stabilized --> increased uptake from the diet

Answer 103

TFS: used to estimate iron status. Normal range: 15-55%, it is DECREASED in iron deficiency, but INCREASED in hemolytic anemia and hemochromatosis EQN: TFS = 100 x Serum iron / total iron binding capacity

Answer 104

iron-bound transferrin (holo-transferrin) --> stimulated endocytosis --> ferric iron becomes ferrous iron via STEAP3 --> transported out of the endosome by DMT1 --> endosome fuses with plasma membrane to release free transferrin (APO-transferrin) -- this is called the Transferrin cycle

Answer 105

- interactions between propionate (polar), arginine, and histidine - methyl and vinyl groups (hydrophobic) on heme interact with hydrophobic amino acids - iron atom is stabilized by 6 interactions: four nitrogens in heme, and two nitrogens from histidines (distal and proximal) in the globin chain

Answer 106

- distal histidine and the iron pulls the proximal histidine towards the heme plane. This changes the shape of the entire molecule

Answer 107

the affinity of other subunits for oxygen. this allosteric effect gives hemoglobin a SIGMOIDAL curve and allows it to accept oxygen in the lungs and donate it in the tissues

Answer 108

- they get taken up by macrophages and destroyed (primarily in the spleen)

Answer 109

Heme oxidase (HO-1)

Answer 110

it binds to haptoglobin. The haptoglobin/hemoglobin complex is taken up by receptor mediated endocytosis

Answer 111

1. Ferritin (liver, spleen, skeletal muscle, marrow) 2. Hemosiderin (macrophages) - excess iron is exported through a similar mechanism as duodenal epithelial cells. The Iron is oxidized by CERULOPLASMIN, a homolog of hephaestin

Answer 112

Transferrin receptor endocytosis. (they can also take up heme bound iron, and free iron via ferreductase and a divalent metal transporter to carry it into the cell)

Answer 113

- LIVER via Hepcidin encoded by the HAMP gene produced in high iron conditions

Answer 114

1. Erythropoiesis (increase in erythropoiesis creates a hepcidin decrease because you need iron to create RBCs) 2. Iron status (Regulated by HFE, TFR1/2, via ERK and SMAD. Increased iron activates and increases hepcidin) 3. Inflammation (IL6 --> JAK/STAT --> increases hepcidin)

Answer 115

- a hormone produced in the kidneys in response to low oxygen (hypoxia) that stimulates the production of reticulocytes, therefore inhibits hepcidin

Answer 116

Prolyl hydroxylase (PHD2). HIF-2 is regulated post-transcriptionally by 5' iron response elements and IRE-BP

Answer 117

1. ribonucleotide reductase in nucleotide synthesis 2. ATPase ABCE1 required for translation 3. primases for DNA replication and transcription (all iron-dependent)

Answer 118

-microcytic, hypochromic - Pagophagia (compulsion to chew on ice) -Koilonychia (spoon nails) - Akathisia (restless leg) - Blue sclera

Answer 119

- blood loss - growth - pregnancy

Answer 120

1. mostly erythroid cells 2. macrophages 3. liver

Answer 121

- macrophages and liver storage decrease first - then the erythrocyte iron (leading to microcytic anemia)

Answer 122

- overproduction of hepcidin - the most common mutation is from the BMPR complex, the Matripase-2 (TMPRSS6) is mutated

Answer 123

a protease in the BMPR complex that propagates the transferrin receptor signal. Mutations in TMPRSS6 cause very high hepcidin expression resulting in iron refractory iron deficiency anemia

Answer 124

- driven by IL6 inflammation (increased hepcidin expression to block pathogen from using iron to reproduce and spread - iron does not get absorbed, and gets sequestered in the liver and macrophages - (IL6 --> IL6R --> JAK1 --> STAT3 --> onto promoter --> increased hepcidin)

Answer 125

- results from disorders in the hepcidin production or ferroportin function - HFE hemochromatosis is most common hereditary form of iron overload, where hepcidin is not produced and iron intake is unregulated

Answer 126

- the loss of function mutations in HFE, a protein required for transferrin receptor signaling - the negative feedback through hepcidin is lost, and iron uptake is uncontrolled

Answer 127

- reduced absolute number of circulating RBCs - reduction in one or more of the major red blood cell measurements (Hgb concentration, Hematocrit, RBC count)

Answer 128

RI <2 is hypoproliferative RI >2 is hyperproliferative

Answer 129

- positive is consistent with warm autoimmune hemolytic anemia - Hemolytic anemia will also have decreased macrocytic erythrocytes with marked anisocytosis, moderate polychromasia, and circulating nucleated RBCs on a peripheral smear

Answer 130

- MCV < 80 - Low MCH - decreased hemoglobin content - hypochromic - Iron deficiency

Answer 131

Ferritin! - Ferritin low = IDA - Ferritin high = ACKD

Answer 132

- Hgb low - Microcytic - RBC count is normal/increased - asymptomatic - iron studies are normal - Hgb analysis is diagnostic

Answer 133

- Life threatening bone marrow failure - Pancytopenia associated with bone marrow hypoplasia/aplasia

Answer 134

- Iron deficiency (IDA) - Thalessemia - Anemia of chronic disease - lead poisoning - zinc deficiency - copper deficiency

Answer 135

- Systemic disorders - anemia of chronic disease/ chronic kidney disease - acute blood loss - early iron deficiency - bone marrow suppression

Answer 136

- Megaloblastic anemia (B12 deficiency or Folate deficiency) - liver disease - alcoholism - hypothyroidism - myelodysplastic syndrome - drugs - multiple myeloma

Answer 137

- fever (101-103), usually low grade - Fatigue - sore throat - swollen lymph nodes (posterior cervical) - swollen tonsils, difficulty swallowing - pharyngitis - presence of atypical lymphocytes on peripheral blood smear

Answer 138

- High WBC - high lymphocytes - low neutrophils - high monocytes - blood serum positive for IgM and IgG against EBV capsid antigen

Answer 139

- Atypical lymphocytes, reactive and large due to antigenic stimulation - associated with viral infection but also *Addison's disease and *Rheumatoid arthritis

Answer 140

- EBV - CMV - T. palladium - Group B strep - HCV - Hantavirus

Answer 141

Heterophile antibodies are antibodies induced by external antigens (heterophile antigens). Some cross-react with self-antigens. For example, in rheumatic fever, antibodies against group A streptococcal cell walls can also react with (and thus damage) human heart tissues. These are considered heterophile antibodies.

Answer 142

- Heterophile antibodies are produced in response to antigens produced during EBV IM (EBV heterophile antigens or Paul–Bunnell antigens) - Serum of patients with infectious mononucleosis contain heterophile anti-Paul- Bunnell (PB) antibodies to erythrocytes of numerous mammalian species

Answer 143

Monospot: Serum from the patient is added to a test card which contains either test red blood cells or latex beads with adsorbed red cell antigen. If heterophile antibodies are present in the patient's serum, there is agglutination which has a speckled appearance on the test card.

Answer 144

- Presence of IgM to viral capsid proteins - appearance of non-specific, heterophile antibodies with the presence of atypical lymphocytes - Screen for HIV because acute HIV and EBV infections can have similar presentations

Answer 145

T-cell mediated. It requires CD8+ T cells

Answer 146

Virus, dsDNA, class 1, linear genome, icosahedral nucleocapsid, enveloped, gamma herpes virus (HHV-4)

Answer 147

- Envelope proteins - Outer tegument - inner tegument - major capsid protein - triplex - portal vertex - nucleocapsid

Answer 148

the oral epithelium - infectious virus in the saliva - lymphocytes in tonsils are directly affected--> massive proliferation - latent infection in memory B cells - linear genome converts to circular episome (B cells immortalized) - CELLULAR IMMUNITY (CD8+ T cells)

Answer 149

CD21 found on B cells

Answer 150

- Potent oncogenes - LMP1 triggers CD40:CD40L -like binding response in the B cell without interaction with any helper T cells to encourage survival and growth - LMP2a mimics intracellular B cell signaling (like Ab:Ag binding and activation of IP3 and DAG) leading to cell survival and proliferation

Answer 151

- Burkitt's lymphoma - nasopharyngeal carcinoma - Lymphoproliferative disease

Answer 152

- Translocation t(8;14) (q24; q32) in 75% of cases: reciprocal translocation involving the c-myc gene (chromosome 8) and heavy-chain Ig locus (chromosome 14) → overactivation of c-myc proto-oncogene → activation of transcription

Answer 153

Burkitt lymphoma is a type of non-Hodgkin lymphoma (NHL). NHL is a cancer of the lymphatic system. It develops when the body makes abnormal B lymphocytes. Commonly develops with co-infection of EBV and malaria

Answer 154

Starry sky pattern: Microscopic finding that resembles a starry sky. Tingible body macrophages (containing many phagocytized tumor cells- white cells) are scattered diffusely within a sheet of uniform neoplastic cells (lymphocytes- dark sky) - Many vacuoles are seen

Answer 155

- EBV infection leads to rapid fulminant hepatitis and hemophagocytic syndrome (fatal or near fatal infections) - Caused by a malfunction in signaling lymphocyte activation molecule-associated protein (SAP) OR by malfunction in X-like inhibitor of apoptosis (XIAP)

Answer 156

a type of cancer that affects the lymphatic system, which is part of the body's germ-fighting immune system. In Hodgkin's lymphoma, white blood cells called lymphocytes grow out of control, causing swollen lymph nodes and growths throughout the body

Answer 157

Reed-Sternberg cells are large, abnormal lymphocytes that may contain more than one nucleus. These cells are found in people with Hodgkin lymphoma.

Answer 158

- EBV - CMV - Hepatitis - Parvo B19 - HIV

Answer 159

- a disease of the mucosa from immunodeficiency leading to unchecked EBV lytic replication, causing white patches on your tongue. It is associated with Epstein-Barr virus (EBV/ HHV4). It occurs most commonly in people infected with HIV.

Answer 160

The association of EBV with epithelial cell tumors, specifically nasopharyngeal carcinoma (NPC) and EBV-positive gastric carcinoma (EBV-GC) is currently thought to be caused by the aberrant establishment of virus latency in epithelial cells that display premalignant genetic changes.

Answer 161

Sickle cell anemia - in malaria endemic parts of Africa - 8% if African Americans are heterozygous for HbS

Answer 162

-autosomal recessive disorder - intrinsic defect with predominantly extravascular hemolysis - homozygotes: all HbA replaced by HbS - heterozygotes: only half HbA replaced with HbS - HbS is a mutation in the beta-globin gene that creates the sickle

Answer 163

a mutation in the beta-globin gene leading to a substitution of valine for glutamic acid at the 6th amino acid residue

Answer 164

red cells containing HbS --> passage through microcirculation of spleen --> low O2 tension--> Sickling occurs --> cell pass through circulation with good O2 tension (other organs) --> desickling --> various cycles of sickling an desickling --> cell membrane affected and change in membrane permeability --> irreversible sickling -->sickled RBCs

Answer 165

(HbSS) in peripheral smears, elongated, spindled, or boat-shaped irreversibly sickled red cells

Answer 166

- severe hemolytic anemia, lifespan of RBC only 20 days - Microvascular obstructions (vaso-occlusive crisis) - increased expression of adhesion molecules on sickled cells - sluggish blood flow, increased transit time for red cells - repeated sickling damages the RBC membrane, making them adhere to the endothelium

Answer 167

1. functional asplenia, nonfunctional spleen 2. Howell Jolly bodies (nucleus remnants) 3. autosplenectomy- small and fibrosed spleen due to repeated episodes of infarction

Answer 168

- retinopathy - blindness - Lung: pneumonia, infarcts, acute chest syndrome - iron overload, heart and liver - pigment: gallstones - stroke - atrophic spleen - Kidney problems - avascular necrosis of femoral head - osteomyelitis - skin ulcers

Answer 169

- HbF high at birth and persists until 5-6 months of age, prevents sickling - has a high affinity for oxygen, therefore preventing sickling - increased by hydroxyurea

Answer 170

- Hydroxyurea

Answer 171

- vascular congestion, thrombosis, and infarction in bones, liver. kidney, retina, brain, and skin - Dactylitis (sausage fingers/toes) from infarction to metacarpal bones, aseptic necrosis - renal papillary necrosis -recurrent leg ulcers - hemosiderosis and pigment gallstones - avascular necrosis of femoral head - proliferative retinopathy--> blindness - end-stage renal failure - Priapism, penile fibrosis and ED

Answer 172

• most common cause of death in young adults with sickle cell disease • vaso-occlusion in pulmonary microcirculation • presents with chest pain, dyspnea, and lung infiltrates • precipitated by pneumonia, bone infarct with fat embolism

Answer 173

• most common cause of death in children with sickle cell disease (2-5 years old) • recurrence rate of 70%

Answer 174

• associated mostly with parvovirus • no reticulocytes in peripheral blood • bone marrow does not produce enough blood cells

Answer 175

• rapid splenic enlargement with entrapment of sickled, RBCs and blood • reticulocytes are present • these individuals are prone to infections such as S. Pneumonia, and salmonella osteomyelitis

Answer 176

Introduced in vitro by exposing cells to market hypoxia (sodium metabisulfite)

Answer 177

• Hb electrophoresis 1. HbSS - disease, HbS 90 to 95%, no HbA 2. HbAS - trait, HbS 40-45% and HbA 55-60%

Answer 178

Analyzing fetal DNA obtained by amniocentesis, or biopsy of chorionic villi to detect the point mutation

Answer 179

• penicillin prophylaxis to prevent pneumococcal infections • pneumococcal vaccine, folic acid supplementation • hydroxyurea to reduce pain crisis, and lessen the anemia by increasing the red cell level of HbF • allogeneic BMT

Answer 180

• intrinsic defect in membrane, RBCs become spheroid and less deformable—> vulnerable to splenic, sequestration and destruction (extravascular hemolysis)

Answer 181

• autosomal dominant inheritance pattern • prevalence is highest in northern Europe, most common intracorpuscular inherited hemolytic anemia in whites

Answer 182

• Autosomal, dominant defect involving spectrin (MC) in the RBC membrane • loss of membrane fragments and decrease in RBC surface membrane—> transformation of spherocytes • other mutations: ankyrin, band 3, or band 4.2

Answer 183

Because spherocytes are created by faulty skeletal problem of the RBC

Answer 184

Mutation of ankyrin gene —> abnormal ankyrin protein —> deficiency of spectrin assembly —> decreased membrane stability

Answer 185

• osmotic, fragility test

Answer 186

1. Chronic hemolytic anemia 2. Plenty of spherocytes (more than in WAHA) 3. Massive splenomegaly 4. cholecystitis, cholelithiasis 5. Aplastic, megaloblastic, hemolytic crisis (coombs)

Answer 187

• autosomal dominant • mutation in spectrin/band 4.1 • intrinsic defect with extravascular hemolysis • mild hemolytic anemia • 25% elliptocytes in peripheral blood

Answer 188

• globin deficiency • defective globin chain synthesis • alpha thal: decrease in alpha-Hb —> beta forms abnormal tetramers —> Heinz bodies, basophilic stippling

Answer 189

• normal/mild, anemia, micro, hypo, target cells

Answer 190

• severe hemolytic anemia (transfusion, dependent)

Answer 191

• African-American, Southeast Asian • deletion of genes for alpha globin chain (4 genes on chromosome 16 • no alpha chain— in utero death • extravascular • P smear: microcytic hypochromic RBCs with many target cells • HbH, Hb Barts

Answer 192

• African-Americans and Mediterranean descent • mutation in beta globin gene • presents after six months, after HbF is gone • extravascular • microcytic hyperchromic, RBCs with many target cells • electrophoresis: reduced HbA, increased HbF & HbA2

Answer 193

• damaged erythroid precursors die by apoptosis • ineffective erythropoiesis, associated with increased absorption of dietary iron leading to iron overload • shortened RBC lifespan, due to extravascular hemolysis • relative folate deficiency

Answer 194

• ineffective erythropoiesis and hemolysis • impaired bone growth, skeletal deformities • expanded marrow fills intramedullary space and invading the bony cortex • hyperplasia of mononuclear cells, splenomegaly, hepatomegaly, lymphadenopathy • growth retardation, and cachexia • severe hemosiderosis

Answer 195

• microcytosis • hypochromia • poikilocytosis • anisocytosis • nucleated red cells (normoblasts)

Answer 196

• most common enzyme deficiency causing homolysis • intrinsic defect with predominantly intravascular, hemolysis and mild extravascular hemolysis • x-linked, prevalent in tropical Africa • G6PD A- : 10% of African-American males in the United States • G6PD Mediterranean : hemolysis is more severe (G6PD half life is markedly reduced, <10%)

Answer 197

• infection • drugs: antimalarial’s (primaquine), sulfonamides, nitrofurantoin, phenacetin, dapsone, aspirin, vitamin K • fava beans

Answer 198

• Heinz bodies (oxidize, hemoglobin, forming intracellular inclusions) • bite cells (splenic phagocytes)

Answer 199

• autosomal recessive • intrinsic defect was extravascular hemolysis • no pyruvate, increased 2,3-DPG • hemolytic, anemia, with jaundice at birth, splenomegaly

Answer 200

• intrinsic defect with **intravascular hemolysis • x-linked, acquired intracorpuscular defect • somatic mutation in PIG-A (impaired synthesis of GPI anchor) on myeloid stem cells • Decay accelerating factor (DAF-CD55) • glycosyl- phosphatidyl inositol required for fixation of CD55, CD59, C8 binding proteins to sell surfaces

Answer 201

• all myeloid lineages are affected (pancytopenia) • leukocytes are also deficient in protective proteins, but less sensitive to complement mediated lysis

Answer 202

• episodic hemolysis (when compliment is activated by mild acidosis— during sleep) • hemoglobinuria noted in first morning void • iron deficiency overtime • play the destruction predisposes to: thrombosis, by releasing TXA2 • increased risk of AML

Answer 203

• flow cytometry— decreased CD55/CD59 expression on RBCs, WBCs, platelets Older tests: • sucrose hemolysis test • ham acidified serum test • urine hemosiderin: positive • peripheral blood: pancytopenia, reticulocytosis

Answer 204

• corticosteroids • targeted therapy with antibody (eculizumab) prevents the conversion of C5 to C5a (increases risk for neisseria infections/meningococcal sepsis) • anticoagulation to prevent thrombosis • bone marrow transportation

Answer 205

• extrinsic defect with intravascular hemolysis • transient hemolytic, anemia in children, with measles, months, influenza, chickenpox (also associated with syphilis) • IgG causes the antibody with bithermal activity (Donath- Landsteiner antibody)

Answer 206

• directed against P blood group antigen on RBCs • add cold temperatures binds to RBCs, and fixes complement— detaches at 37° and activates compliment, causing intravascular hemolysis • hemolysis, when moving from a cold to warm environment, symptoms resolved on moving back

Answer 207

• fevers, rigors, chills • red to brown urine • Reynauds phenomenon • transient hepatosplenomegaly with jaundice • oliguria and renal failure

Answer 208

• primary- idiopathic • secondary- B cell neoplasm, auto immune, drugs (alpha, methyldopa, penicillin, quinidine) • most common immune hemolytic, anemia, caused by IgG at 37 degrees • opsonization of red blood cells by autoantibodies, leading to phagocytosis in the spleen and elsewhere • positive DAT • spherocytes and polychromasia

Answer 209

• post infectious • mycoplasma, EBV, CMV, associated with lymphoproliferative disease • acute: mycoplasma infection, mononucleosis • chronic: idiopathic, B cell lymphoid neoplasms) • low affinity IgM antibodies stop buying to RBC membranes only at temperatures less than 30° • mediated by antibodies to blood group antigen I or i • RBCs, phagocytosis by macrophages and spleen and liver— sludging of blood capillaries do the agglutination often producing Reynaud phenomenon

Answer 210

• viral infection (mycoplasma, EBV) • drugs: quinidine, forms immune complex with IgM to complete compliment, mediated lysis • CLL: IgM Ab against I blood group Ag

Answer 211

• mechanical Hemolysis from aortic stenosis, defective, cardiac valve prosthesis (causing schistocytes)

Answer 212

• DIC • malignant hypertension • SLE • TTP • HUS • disseminated cancer

Answer 213

• schistocytes in peripheral blood • decrease haptoglobin in serum • urine hemosiderin • iron studies: deficiency • MCV: normocytic • reticulocyte count >3%

Answer 214

• plasmodium falciparum • Anopheles mosquitoes • parasites destroy large numbers of infected RBCs, causing intravascular hemolytic anemia • massive splenomegaly and occasional hepatomegaly

Answer 215

• infection of RBCs with P.falciparum induces positively charged surface knobs which bind to adhesion molecules on activated endothelium • traps RBCs in post capillary venules, especially cerebral vessels in children • rapidly, progressive, convulsions, and death usually occur in days to weeks

Answer 216

• massive intravascular hemolysis from malaria • hemoglobinemia • hemoglobinuria • jaundice

Answer 217

Propionyl CoA —> methylmalonyl-CoA — B12 —> succinyl CoA • without B12, you have an accumulation of propionyl CoA which causes demyelination of nerve fibers, and increase urine methylmalonic acid (B12 only, not folate)

Answer 218

• Hyper segmented neutrophils • large, misshapen platelets • morphologic changes in other systems • MCV > 110

Answer 219

• oval, macrocytes, pancytopenia —> cell division • anisopoikilocytosis : hemolysis • hyper segmented neutrophils: large cells/megaloblast in bone marrow

Answer 220

Auto immune attack of intrinsic factor in the duodenum/GI system leads to decreased intake of B12 • atrophic gastritis • associated with: Hashimoto thyroiditis, Addison’s, DM-1

Answer 221

• ryles tube aspirate: achlorhydria • blood: Hypergastrenemia, IF auto antibody • gastric biopsy: chronic atrophic gastritis • increased serum, bilirubin, and LDH (increased RBC breakdown) • Schilling test: absorption corrected by IF

Answer 222

• macrocytes around rather than oval shaped • hyper segmented neutrophils NOT present • leukocytes and platelets are normal • no glossitis and no neuropathy • usually alcohol excess, or hypothyroidism

Answer 223

• non-megaloblastic macrocytosis without anemia • round macrocytes and target cells are seen in chronic alcoholism

Answer 224

Myeloblast —> promyeloblast —> myelocyte —> metamyelocyte —> band form —> mature neutrophil

Answer 225

• Larger than normal neutrophils, bands • blood and bone marrow of patience with vitamin B-12 or folate deficiency • myelodysplasia • patient receiving chemotherapy, such as hydroxyurea

Answer 226

• neutrophils with bilobed nuclei in the pince-nez conformation • nuclear Chromatin denser than normal • presence of hypo segmented neutrophils due to: severe infection, burns, malignancy, chemotherapy, drugs, such as sulfonamides • reverts back to normal, when causative agent is removed

Answer 227

• large • purple or dark blue, azurophilic granules • resembling the primary granules of promyelocytes in the cytoplasm of neutrophils, bands, and metamyelocytes • associated with: severe infection and chemical poisoning

Answer 228

• vacuoles, representing the site of digestion of the phagocytosed material • in the cytoplasm of neutrophils and bands • frequently associated with toxic granulation

Answer 229

• large • purple, or purpleish-black • coarse • azurophilic granules (resembling primary granules of promyelocytes) • seen in cytoplasm of virtually all mature, leukocytes, and occasionally in the precursors • seen mainly in Alder-Reilley anomaly, and autosomal recessive disorder due to a defect in mucopolysaccharides

Answer 230

• seen in May-Hegglin anomaly • associate with purpura and bleeding • giant platelets containing few granules, large basophilic cytoplasmic inclusion bodies in granulocytes resembling Doyle bodies • mutation in MYH9 gene on a chromosome 22 • no bleeding episodes other than in cases of severe thrombocytopenia

Answer 231

• giant abnormal lysosomes, often round • red-blue or greenish-gray granules of variable size seen in cytoplasm of leukocytes, and sometimes in normoblasts in patients with CHS • kill bacteria in neutrophils and monocytes, however process less effective than normal cells, because these neutrophils have impaired locomotion • recurrent infections result

Answer 232

• single or multiple blue, grayish-blue or greenish inclusions of variable size and shape in cytoplasm of neutrophils, bands, and metamyelocytes • remnants of free ribosomes or rough endoplasmic reticulum • scene in association with toxic granules and vacuoles

Answer 233

• pink, or red, round, or rod shaped cytoplasmic inclusions • scene in immature, granulocytes and monocyte precursors in patients with acute non-lymphocytic leukemia’s • represent agglomeration of azurophilic granules • Fagot cell: cell containing multiple Auer rods, clump together in form of a bundle— seen in acute promyelocytic leukemia

Answer 234

Idiopathic neutrophilia, increase neutrophils, asymptomatic

Answer 235

• ethnic, or benign familial neutropenia • cyclical neutropenia: cyclical variation in white blood cell counts • Kostmann’s syndrome: congenital agranulocytosis- lack of G-CSF = severe neutropenia and severe infections • Felty’s syndrome: RA + severe neutropenia • SCID: absent T lymphocytes

Answer 236

Defective microbicidal function, lazy leukocyte syndrome

Answer 237

• defect in neutrophil chemotaxis and deficient random mobility of neutrophils • blood neutrophils cannot migrate to the side of tissue injury • phagocytic, and bacteriocidal activities are normal • abnormalities in migration, or intrinsic to granulocyte • alteration, in structure or function of microfilamentous protein of granulocyte membrane leading to altered deformability— excessive, or under rigidity of neutrophils (cannot leave bone marrow)

Answer 238

• 1 to 2 years of age is one complications occur due to infections • stomatitis • otitis media • bronchitis • recurrent infections in general

Answer 239

• recurrent infection, periodontitis, and stomatitis • TLC low • ANC as low as 100 to 200 • bone marrow contains normal number of mature neutrophils

Answer 240

• autosomal, dominant inheritance • mutation in STAT3 (protein products act as transcription activators) • T17 helper T cells produce aisle, 17 chemotactic agent for monocytes and neutrophils decreases • abnormal chemotaxis of neutrophils and monocytes (cold, soft tissue, abscesses and recurrent pneumonia) • hyper immunoglobulin E syndrome (Hyper IgE) • red hair, leonine face, chronic eczema, eosinophilia, and increased serum IgE

Answer 241

• key finding: toxic changes • left shift: presence of immature, neutrophils in peripheral blood (>10%) • toxic granulation: increases in azurophilic granules • cytoplasmic vacuolation: phagolysosomes indicating presence of phagocytosis • Leukomoid reaction when severe

Answer 242

• exaggerative leukocyte response to serious infections, marked increase in WBC count (>30,000-50,000) • may involve any leukocyte • if neutrophils are involved, peripheral smear, may show marked shift to the left, resembles the finding seen in CML

Answer 243

• perforated acute appendicitis (neutrophils) • whooping cough (lymphocytes) • infectious mononucleosis (lymphocytes) • cutaneous larva migrants (eosinophils)

Answer 244

• LAP: seen in leukomoid reaction, present in specific granules- a marker of mature neutrophil • score is increased in leukomoid reactions • CML has a low score, since the cells are neoplastic (CML also has positive Ph chromo)

Answer 245

• Epstein-Barr virus • B lymphocytes via CD21 receptors • CD8+ T cells respond and form atypical lymphocytes (Downey cells) • classic triad: fever, sore throat, lymphadenopathy, hepatosplenomegaly • complications: hepatic dysfunction, splenic, rupture, rash, if treated with ampicillin • Paul Bunnell reaction: Monospot test • atypical lymphocyte: virocyte

Answer 246

• EBER-1: EBV, viral non-coding RNA • EBNA-1: EBV nuclear antigen • LMP-1: EBV CD40 signaling • LMP-2: EBV BCR signaling (Ab:Ag)