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Clin Med I - Comprehensive > Hematology > Flashcards

Hematology Flashcards

1
Q

What are the factors of the extrinsic pathway?

A

7–>X–>5–>2 (Prothrombin)–>2a (Thrombin) –>1 (Fibrinogen)–>Fibrin–>13 (Tight clot)

NB: X marks the spot for the common pathway

NB2: 13 is not measured in PTT or PT

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2
Q

What are the vitamin K dependent factors?

A

10, 9, 7, 2 (1972 - it was a good year!)NB: Vitamin K is more associated with the extrinsic pathway.

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3
Q

What happens if you are deficient in Protein C or Protein S?

A

You clot out of control (predisposed to major thrombosis)

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4
Q

What are the factors of the intrinsic pathway?

A

TENET - Twelve, Eleven, Nine, Eight, Ten (common)Then remainder of common pathway - 5, 2, 2a, 1, Fibrin, 13

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5
Q

aPTT/PTT measures coagulation in which pathway?

A

Instrinsic (PITT)

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6
Q

PT measures coagulation in which pathway?

A

Extrinsic (PET)

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7
Q

What is PT used for?

A
  • extrinsic and common factors

* used to monitor Coumadin patients

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8
Q

What happens to PT with a Vitamin K deficiency?

A

It is prolonged

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9
Q

When is PTT prolonged?

A
  • von Willebrand disease
  • hemophilia
  • lupus anticoagulant
  • NB: sensitive to Heparin contamination
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10
Q

What does a 1:1 mixing study tell you?

A
  • if it corrects into the normal range, a factor deficiency is the likely culprit
  • if it fails to correct, an inhibitor or anticoagulant is the likely suspect
  • NB: 30% activity is the threshold to correct clotting times
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11
Q

What is the Platelet Function Assay (PFA-100)?

A
  • modern test that replaces old “bleeding time” test
  • push blood through a coated filter and watch the clot formation time on the filter
  • need platelets at least 100 x 109/L
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12
Q

When will the Platelet Function Assay be prolonged?

A
  • von Willebrand disease
  • aspirin
  • platelet function defects
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13
Q

What does a Normal PT/PTT indciate in the presence of a bleeding disorder?

A

Factor XIII deficiencyRemember, it is not measured by PT/PTT

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14
Q

What does both an abornmal PT and PTT suggest?

A
  • fibrinogen deficiency/problem
  • Vitamin K deficiency
  • DIC
  • Liver disease (PT abnormal first)
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15
Q

What does an abnormal PTT with normal mixing result suggest?

A
  • Hemophilia A or B
  • Von Willebrand disease
  • Factor XI deficiency
  • Factor XII deficiency
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16
Q

What might cause a fibrinogen deficiency?

A
  • liver dysfunction

* DIC

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17
Q

Can a reduced level of fibrinogen cause a prolonged PT, PTT or Thrombin Clot Time?

A
  • Generally, no unless fibrinogen is less than 100 mg/dL
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18
Q

What does Thrombin Clot Time (TT) measure?

A

Measures the time for conversion of fibriongoen to fibrinHeparin can contaminate

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19
Q

What is von Willebrand disease?

A
  • Caused by a deficiency or reduced functioning of von Willebrand factor
  • carries and stabilizes factor VIII
  • mediates platelet adhesion and aggregation
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20
Q

What is the most common inherited bleeding disorder?

A

von Willebrand disease

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21
Q

What is the mechanism of inheritance of von Willebrand disease?

A

Usually autosomal dominant

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22
Q

What is the Rx for von Willebrand’s disease?

A
  • DDAVP (Arginine vasopression) - releases stored vWf from endothelial cells
  • reduced efficacy with repeated dosing (tachyphylaxis)
  • Humate-P - factor VIII product that contains vWf
  • Cryoprecipitate - life-threatening bleeds (infectious transmission risks)
  • Aminocaproic acid - Amicar -supportive, effective for mucosal bleeding. acts by stabilizing clot. No for hematuria
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23
Q

What is Hemophilia A?

A

Deficiency or lack of Factor VIII

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24
Q

What is Hemophilia B?

A

Lack or deficiency of Factor IX

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25
Q

How are Hemophilia A and B transmitted?

A

X-linked recessive disorders

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26
Q

What are the three degrees of severity of hemophilia?

A
  • Mild Hemophilia (30-40% of cases)- Factor level 6-50%/uncommon spontaneous bleeding/see sx after major trauma or surgery
  • Moderate hemophilia (10% cases) - factor level 1-5%/see sx after minor trauma/4-6 bleeding episodes per year
  • severe hemophilia (50-70%) - Factor level <1%/spontaneous bleeding occurs/2-4 x month
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27
Q

What type of bleeding episode is most common in hemophila?

A

joint bleeding (60%)most common sites are knee, ankle, elbow

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28
Q

What should you avoid when treating a joint bleed?

A

NSAIDS and Aspirin (you know why)

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29
Q

What are the possiblecomplications of untreated muscle bleeds?

A
  • foot drop
  • flexed hip
  • volkmann’s contracture (hand arm)
  • compartment syndrome
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30
Q

What is the treatment for Hemophilia?

A
  • replacement of missing factor concentrate (on demand/prophylaxis)
  • DDAVP/ Stimate - not for B
  • Antifibrionolytic agents - Amicar
  • Supportive measures - RICE and pain control
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31
Q

What are factor inhibitors and how do you identify when they exist?

A
  • these are antibodies that develop against “foreign” infused factors in hemophilias. They exist in 15-25% of Factor VIII pts and 1.5-3% of Factor IX pts.
  • median of 9-12 exposure days
  • consider when pt. is unresponsive to Rx
  • prolonged PTT after mixing 1:1
  • one BU of activity causes 50% loss of Factor VIII activity
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32
Q

How do you treat inhibitors in hemophilia?

A
  • recombinant FVIIa - push clotting through extrinsic pathway
  • High-dose VIII or IX
  • prothrombin complex concentrates
  • can try to desensitize the immune systemto the factor
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33
Q

What is DIC?

A
  • A disorder of secondary hemostasis caused by consumption of factors in the coagulation system
  • triggered by exposure of blood to tissue factor
  • present with bleeding, petechiae and purpura
  • causes include: infection; major trauma; malignancy
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34
Q

What is the Rx for DIC?

A
  • Most important: TREAT UNDERLYING CAUSE
  • hydration
  • RBC transfusion
  • if bleeding, fresh frozen plasma, cryoprecipitate, orplatelets
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35
Q

What are conditions that can lead to thrombosis?

A 
Virchow's Triad	
* alterations in blood flow (stasis)	
* vascular endothelial injury	
* alterations in constituents of blood
50% of thrombotic events in pts with inherited thrombophilia are affiliated with additional risk factor
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36
Q

What are the causes of inheritied thrombophilia?

A
  • Factor V (Leiden) - most common inherited in causasians 3-8%
  • prothrombin gene mutation (G20210A)
  • Protein S deficiency
  • Protein C deficiency
  • antithrombin deficiency
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37
Q

What is the Rx for venous thromboembolism?

A
  • LMW heparin, vondaparinaux, unfractioned IV heparin
  • overlap with and transition to Vitamin K antagonist
  • Target INR 2.5
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38
Q

Who should be screened for thrombophilia?

A
  • initial thrombus occuring before 40 without provoking factor
  • FH of 1st degree relatives with VTE
  • recurrent VTE
  • thrombosis in unusual vascular beds - liver, cerebral, mesenteric
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39
Q

What are secondary hypercoagulable states?

A
  • pregnancy
  • contraceptive use/HT
  • malignancy
  • systemic inflammation
  • post-operative state
  • immobilization
  • trauma
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40
Q

Elevated Reticulocytes Indicate..

A

Hemoglobinopathies• RBC MembraneDefects• Enzyme deficiencies

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41
Q

Decreased Recitulocytes indicate…

A

Fe deficiency• Lead poisoning• Inflammation• Bone marrow failures syndromes

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42
Q

Hemolytic Anemia Signs/Sx:

A

Pallor, fatigue
Jaundice, dark urine
Splenomegaly, gallstones

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43
Q

Hemolytic Anemia Lab Findings

A

Reticulocytosis, AnemiaElevated bilirubinElevated AST > ALTElevated LDH

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44
Q

Hereditary Spherocytosis (HS) Characteristics

A

Spherocytes: smaller, loss of central pallorCongenital hemolytic anemia• Most common inherited anemia in individuals ofnorthern European descent • Autosomal Dominant Inheritance• ~1/3 are spontaneous mutationsMutations affect RBC membrane• Spectrin, ankyrin• Loss of membrane surface area relative to intracellularvolume

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45
Q

Hereditary Spherocytosis Clinical Signs/Sx

A

Neonatal jaundice• First 24 hours of life• Exaggerated, prolonged physiologic nadirOutside the newborn period:• Incidental Laboratory findings• Acute aplastic event (Parvovirus B19)• Jaundice, Splenomegaly, early gallstones

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46
Q

Parvovirus B19 infection Characteristics

A

• “5th Disease”• Clinical manifestations: URI/pharyngitis, rash (“slapped cheeks”), Very mild anemia• Infects RBC precursors for 7-10 days so rapid decrease in red calls daily• Dx: serology (IgM)

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47
Q

Hereditary Spherocytosis Levels of Infection

A

Depends on Spectrin Content: Mild HS: 20-30% of cases, No anemia, sight Reticulocyte increase, Mild jaundice
Moderate HS: 65-75% of cases, + anemia, +Reticulocytes, + Bilirubin, ± splenomegaly, Occasional transfusions
Severe HS: 5% of cases, ++ anemia, ++Reticulocytes, ++ Bilirubin, Marked splenomegaly, Regular transfusions

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48
Q

Hereditary Spherocytosis Lab Findings

A

AnemiaReticulocytosisMCHC typically > 36%
Wide RDW (small spheres and large reticulocytes)
Often elevated bilirubin, LDH, AST>ALTPresence of spherocytes on peripheral blood smear

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49
Q

Hereditary Spherocytosis Diagnostic Test results

A

Negative Direct Antiglobulin Test (DAT/Coombs)Positive Osmotic Fragility Testing: decreased surface area means no room to swell so burst.

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50
Q

Hereditary Elliptocytosis (HE) Characteristics:

A

• Elliptical, cigar shaped, erythrocytes• Normochromic, normocytic, may or may not be anemic• Defect in spectrin• African and Southeast Asian Variants: 1:100 in parts of Africa• Autosomal Dominant• Many asymptomatic: RBC lifespan decreased by only ~10%

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51
Q

Hereditary Pyropoikilocytosis (HPP) Characteristics:

A

• Newborns with severe hemolytic anemia:– Anemia, jaundice– Poikilocytosis, elliptocytosis, and spherocytosis– Fragments of cells so intra & extravascular lysis• Gradually evolves into mild HE

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52
Q

G6PD Deficiency Characteristics

A

Most common human genetic mutation: X-linked High prevalence re malaria protection> 400 missense Genetic mutations: A- variant most common among African descent Mediterranean variant more severeEffects of G6PD deficiency Incomplete protection against oxidative stressAcute hemolytic anemia after exposure to oxidative stress: Infections Sulfa drugs Naphthalene (moth balls) Fava beans

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53
Q

G6PD Deficiency Signs/Sx:

A

Acute fatigue, jaundice, pallor,dark urine (intravascular hemolysis),+/- history of known trigger

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54
Q

G6PD Deficiency Diagnostic Lab findings:

A

• Normocytic, normochromic anemia• Reticulocytosis
Elevated LDH, Bilirubin**
Hemoglobinuria (+ for blood, no RBCs on microscopic urine)** Blister cells, anisocytosis on blood smear**Assay G6PD activity after resolution of a hemolytic crisis

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55
Q

Autoimmune Hemolytic Anemia (AIHA) characteristics:

A

Incidence: 1 - 3/100,000, children and adultsVariable clinical course: self-limited, short illness, waxing and waning, chronic illnessPrognosis typically good: Morbidity from treatment, Mortality <10%Erythrocyte autoantibodies: IgG, IgM, Complement fixationTypes: Warm vs. ColdLab Test: Direct Antiglobulin Test (Coombs test)

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56
Q

Warm-Reactive AIHA characteristics:

A

IgG autoantibody mediated RBC destruction (G for Georgia = Warm)• Bind RBC surface at warmer temperatures* Extravascular hemolysis—Fc Receptors in the spleen• Occasionally fix complement leading to lysisTypes: -Idiopathic-Immunodeficiency -Secondary: EBV infection

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57
Q

Direct Antiglobulin Test (DAT)AKA “Coombs Test”: How does it work?

A

Sensitized Erythrocytes+Coombs reagent (anti-IgG, anti-C3) =Visual RBC Agglutination (1+ to 4+)

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58
Q

Warm-Reactive AIHA Signs/Sx:

A

• Typically rapid onset anemia• Can be life threatening• Fatigue, dyspnea, heart failure• Scleral Icterus, Jaundice, +/- dark urine (hemoglobinuria)• Splenomegaly

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59
Q

Warm-Reactive AIHA Labs:

A

• Anemia and reticulocytosis• Spherocytes on peripheral blood smear• Positive DAT+ IgG, ± Complement (C3)

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60
Q

Warm-Reactive AIHA

A

Transfusion will not be 100% compatible but may be necessary (Least Incompatible)Glucocorticoids: Once remission has been achieved, wean steroids SLOWLY and mimic physiologic dosing as much as possible (AM dosing)SplenectomyRituximab: Monoclonal antibody directed against CD20 on B-cell surface

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61
Q

Cold Agglutinin Disease(Cold Reactive AIHA) Signs/Sx:

A

Erythrocyte agglutination upon exposure to cold• Mottled or numb fingers and toes• Acrocyanosis (blue extremities)

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62
Q

Cold Agglutinin Disease(Cold Reactive AIHA) Labs:

A

• Mild anemia with reticulocytosis** Red cell agglutination on PBS made at room temperature (but not at 37 C)!** DAT (Coombs) will be positive for complement (C3) only

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63
Q

Cold Agglutinin Disease(Cold Reactive AIHA) Treatment

A

Largely symptomatic–Avoid cold! Rituximab re active or relapsing symptomatic hemolysisSplenectomy and corticosteroids ineffective so avoidIf transfusion is needed—Warm the RBCs!

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64
Q

DDX re Warm-Reactive AIHA vs Cold-Reactive AIHA

A

Warm-Reactive AIHA: IgG, DAT result: +IgG, ± C3 (C3 fixation Variable) Thermal reactivity 37C, RBC destruction: Spleen,
Tx: Steroids, Splenectomy

Cold-Reactive AIHA: IgM Thermal reactivity: 4C +C3 (C3 fixation) RBC destruction: Liver Common therapy: Avoid cold, Rituximab

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65
Q

Hb/Hgb

A

the concentration of hemoglobin: oxygen carryingproteins2 beta and 2 alpha chains. each chain has associated heme group and each heme group has a central iron which binds oxygen.

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66
Q

HCT (%)

A

Hematocrit percent (should be 3x hemoglobin)% of blood volume occupied by RBC

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67
Q

what does MCV mean?

A

mean cell corpuscular volume:tells us the average volume of RBCs collected.relates to RBC size to tell if micro=<80, normo=80-100, or macrocytic>100neonates 110 normal, 70 at 1 year oldif larger, it’s newer cells (macrocytic)

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68
Q

MCH

A

Mean cell hemoglobin: average Hb concentration of the RBCs(when cell size change,

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69
Q

what is MCHC?

A

Mean [Hg] per ONE Red blood cell

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70
Q

What does a Reticulocyte Count mean?How do you evaluate for Anemia?

A

a direct reflection of rate of RBC productionindirect reflection of rate of RBC destruction (elevated in disorders with more destruction)(reported as % and an absolute number “ARC”)Use ARC and%retic x RBC to get the whole pictureif pt has retic of 1% (normal) that’s fine unless their Hg is low, then retic should be high and compensating.

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71
Q

two classifications and 3 sub classifications of anemia

A 
PATHOPHYSIOLOGIC:	
* decreased production	
* blood loss	
* increased destruction
MORPHOLOGIC	
* Macrocytic	
* Normocytic	
* Microcytic
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72
Q

What are disorders with destruction probs

A

HemoglobinopathiesRBC Membrane defectsenzyme deficiencies

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73
Q

What is RBC chromicity

A

clues on [Hg] : color or RBCcentral palor: normalMCH, MCHC can give clues, but Peripheral blood smear is more importanthyperchromic, normochromic, hypochromic, or polychromasia

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74
Q

What diseases are connected with these shapes, and what are these RBC shapes:Target cells,echinocyteAcanthocyteSpherocyte

A

Target cells: looks like a target: liver disease, HbC, HbD, HbE, Thalassemiaechinocyte: spiney like a sea urchin: Uremia, hypokalemia, artifactAcanthocyte: irregularly shaped RBC withthorny projection:liver disease, PK deficiencySpherocyte: sphere shaped, no central palor: HS Immune hemolytic anemia

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75
Q

MicrocyticAnemia causes

A

Fe deficiency anemiathalassemias (alpha &beta)Chronic disease/ inflammationPb toxicicty

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76
Q

Most common anemia

A

Fe deficiency with 3% of young children in US8-10% have Fe deficiency with out anemia(pregnant women, adolescents, elderly)(if Fe deficient and small bodied, a small blood loss could push them over the edge to become anemic)

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77
Q

Etiology of Fe deficiency

A

Increased demand to make blood (infancy, adolescents, pregnant, making more rbcs)
malnutrition (vegetarians, vegans, junk food diets) decreased absorption (gastrectomy, H. pylori, IBD, drugs) GI bleeds benign or malignant, GU bleeding heavy periods, blood donors
drugs: NSAIDS, steroids chronic kidney disease, IBD, heart failure, obesity

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78
Q

Stages of Fe depletion, what labs would you order and why

A

1) Depleted iron stores (marrow iron/serum ferratin) 2-3+2) Iron deficient erythropoiesis: Serum Fe <100ug/dl and %saturation is <303) Iron Deficient Anemia: HCT<40, RBC become microcytic and hypochromic*don’t stop treatment too early, gotta build up stores! Serum Fe increases in one meal, Serum ferratin slower to build

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79
Q

What does low Fe look like with labs?

A

Low: Hg, MCV, MCH, MCHC, RBC countLowuncompensated retic countIncreased TIBC/transferin(nothing to bind them)Low ferritin (deficiency: <10-12ng/L, depletion: 12-20ng/Lnormal is 20-300ng/LInflammation can falsely elevate Ferratineven if you don’t have iron stores

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80
Q

Problems with Fe Tx

A

Ferous sulfate tasteshorrible.Side effects include dyspepsia, constipation, nausea, abd pain,Helps to take with food… decreases absorption, but some is better than not taking it at all.Polysaccharide preparationssweeter

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81
Q

Foods with high Fe

A

Liver, red meatbeans/ greensiron-fortified cereals/ grainsheme: meat, non-heme: vegetarian

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82
Q

therapeutic response to Fe treatment of deficiency

A

Tx works within 3 days. see less hypochromia, increased RDWincreased reticulocytes in 2-3 days,Hg & MCV goes up in a weekSerum iron 1-2 hrsTIBC goes down: 2-3 weeksSerum Ferritin goes up: 1-2 weeks, 3-4 to normal

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83
Q

Why are they having Fe loss in the first place? What would you look for?

A

GI Blood loss: guaiac (occult stool), if positive endoscopyUrea breath testTest Antibodies for H. pylori, anti-transglutaminase (celiac sprue if fails to respond to oral iron)C-reactive protein: inflammation? neoplasm? especially in elderlyMetro/menorrhagia: evaluate for bleeding disorder

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84
Q

Normal Treatment for Fe deficiency

A

Iron Salts 100-200mg elemental Fein 2 dosesFerrous Sulfate, Ferrous GluconateTaken on empty stomach for best absorption,avoid coffee, tea, take with Vit C (acid helps absorption)Kids: 2-6mg/2 doses, NO MILKcontinue Tx 3mths to replenish serum ferritin*

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85
Q

when oral Fe is contraindicated, or another method is indicated

A

IViron therapy : for those who can’t take orally (gastrectomy, duodenal bypass, H. pylori, celiac, IBD, genetic IRIDA, or if needs to be immediate recovery (severe anemia in 2nd-3rd trimester, chronic renal disease, substitution for blood transfusion (religious reasons), chemo anemia (from ESA)contraindicated:1st trimester of pregnancy, iron allergy (hypersensitivity rx)

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86
Q

What is anemia of Chronic Disease

A

Anemia from a chronic state of inflammation(like cancer, chronic infection, lupus, RA, and other autoimmune disease, obesity, aging)that causesimpaired production of RBCs

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87
Q

What’s the pathophysiology Anemia of Chronic Disease that has to do with iron levels?

A

Hepsiden ( regulatory hormone made in liver, excreted to urine) tells Macrophages to keep iron inside cells, and not let it into circulation, andtells duodenal and intestinal cells not to absorb more Fe. This is because it thinks it is being invaded, and Fe makes bacterial infections stronger.We expect higher hepsiden in Fe overload, and infection

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88
Q

lab findings in Anemia of Chronic Disease

A

mild-moderate anemiaMCV: normal to lowRDW: normalRetic Count: lowFerritin: normal tohigh (even if Fe is low)

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89
Q

treatment Anemia of Chronic Disease

A
  • eradicate underlying disease if impossible,
  • transfusions
  • IV iron
  • ErythropoesisStimulating Agents
  • New experimental approaches targeting IL-6 activity
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90
Q

What is macrocytic Anemia? what’s it caused by

A

Larger RBCsCaused by B12 or Folate deficiency (DNA synthesis: mismatch between how much cytoplasm to put in cell and membrane so cells larger)Non-Megaloblastic causes: Phentoin, Bactrim, ART, Chemo, hypothyroid, liver disease, alcoholics, myelodysplasia, bone marrow failure, reticulocytosis

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91
Q

What labs do we order if we suspect Macrocytic Anemia?

A

CBC with peripheral blood smear (hyper-segmented neutrophils/neutropenia)reticulocyte count (to see if MCV 110-140 is bigger because more retics, also to see if production or destruction prob)serum cobalamin, folate, and TSHliver function test (alcoholics)measure folate/cobalamin (needed for DNA synthesis including for RBCs)

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92
Q

Signs and symptoms of macrocytic anemia

A

Both for B12 and Folate deficiency, see glossitis-smooth tongue, and dyspnea with exercise, pallor, etc.For B12, neuropathies, ataxia, seizures, psychiatric probs, decreased sensations

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93
Q

what causes B12 deficiency

A

pernicious anemia: (autoimmune) disease where autoantibodies destroy gastric parietal cells which produce intrinsic factormalabsorption: IBS, chrons disease, celiac, bowel resectionHemolytic anemia, excess blood losspregnancy: when more need is happening

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94
Q

Lab results for Macrocytic Anemia from B12 deficiency

A

moderate -severe anemiaelevated MCV 110-140low reticulocyte (not compensated)hypersegmented neutrophils and macroovalecyteson smearmild thrombocytopenia and/or neutropenialow serum B12, <170 (when normal or 170-210, confirm with elevated methylmalonic acid or homocystine)

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95
Q

Diagnosis for Pernicious Anemia

A

Anti-intrinsic factor antibodies (100%specific, but only 70%sensitive= false neg)Anti-parietal cell antibodies (more sensitive, but less specific=false positive)Shilling test (board answer)

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96
Q

Tx for B12 deficiency

A

IM or subcutaneous injection of 100mcg B12daily x 1 wk, then weekly x 1 month, then monthly for lifeORsublingual 1mg/day for EVER(folic acid also recommended for first few mths of B12 tx)

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97
Q

Response to B12 Tx for Macrocytic Anemia

A

well-being in 1-2 days,brisk retic increase in 3-4 days, and Hg in 10 daysHypokalemia can occur during early response because increased K+ use for RBC production monitorneuropathies improve totally by 6 mths

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98
Q

Labs for Folate Deficiency

A

Mod-severe anemiaelevated MCVlow retichypersegmented neutrophils/macro-ovalcytes on peripheral smearmild thrombocytopenia/neutrophilsRBC folic acid levels (better than serum folate b/c reflects body stores <150 is deficient)also measure B12.

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99
Q

Tx of folate deficiency

A

daily oral folic acid 1 mgResponse is rapid wellbeingretics in 5-7 daystotal correction of hematologic abnormals in 2 mths

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100
Q

Non-megaloblastic anemia causes and Tx

A

anti-retroviral drugs, antiseizure meds, chemo, bactrimhypothyroidismnon-alcoholic liver diseasechronic alcohol use: stop alcohol use, blood returns rapidly

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101
Q

Differential for Normocytic Anemia

A

+++Reticulocyteshemolytic anemiaPost-hemorrhagic anemia—Reticulocytesacute hemorrhageanemia of inflammationrenal/liver diseasemarrow infiltrationmyelodysplastic syndrome

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102
Q

most common causes of inherited hemoglobin disorders

A

DNA deletions or point mutations

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103
Q

what is a quantitative hemoglobin disorder

A

thalassemia

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104
Q

what is a qualitative hemoglobin disorder

A

hemoglobinopathy

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105
Q

normal fetal hemoglobin made of?

A

2 alpha chains and 2 gamma chains

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106
Q

normal adult hemoglobin made of

A

2 alpha chains and 2 beta chains

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107
Q

in thalassemia what is the balance of alpha and beta chains

A

alpha thalassemia- excess betabeta thalassemia- excess alpha

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108
Q

pathophysiology of thalassemia

A

excess globins precipitate and damage the RBC membrane, ineffective erythropoiesis

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109
Q

outcomes of thalassemia

A

anemia, bone marrow expansion, extramedullary hematopoiesis, increased intestinal iron absorption

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110
Q

Sickle cell and thalassemia protects from what disease?

A

malaria

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111
Q

silent carrier in thalassemia

A

one deletion of the functional gene

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112
Q

What is alpha-thalassemia trait

A

two deletions of functional genes ( cis- more common in Asian pops or trans more common in African pop)

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113
Q

HbH disease

A

3 deletions of functional genes

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114
Q

hydrops fetalis

A

4 deletions of functional genes- incompatible with life

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115
Q

alpha thalassemia trait definition

A

reduced alpha globin chain synthesis due to 2-gene deletion- causes an excess amount of gamma globin at birth, or beta globin as an adult

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116
Q

best time to identify alpha thalassemia

A

in newborns- excess gamma globin and fast band production makes it more identifiable with testing. For adults, try to track newborn screen.

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117
Q

Heinz bodies

A

detects protein precipitates, denatured proteins. Test isnot commonly used due to common false negatives

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118
Q

treatment for hydrop fetalis

A

if caught in utero- can do transfusion support.then stem cell transplantation to treat after birth.

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119
Q

beta thalassemia

A

beta-0- producing no beta globinbeta+ produces little beta globin

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120
Q

B-thalassemia major

A

homozygoussevere anemiarequires life-long RBC transfusion

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121
Q

B-thalassemia intermedia

A

mild anemiaoccasional transfusions required

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122
Q

B-thalassemia trait

A

heterozygousasymptomaticconfused with iron deficiency- suspect if patient does not respond to iron therapy

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123
Q

phenotypes for b thalassemiamild moderate severe

A

B+ B+Bo B+Bo Bo

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124
Q

beta thalassemia trait under the microscope

A

unbalanced a:b chainselevated A2elevated Hb Fmicrocyctic anemia

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125
Q

treatment of beta thalassemia intermedia

A

hydroxyurea- increase in fetal hemoglobin production.watch iron absorption- can be increased

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126
Q

outcomes of thalassemia major/erythropoiesis

A

expansion of marrow cavities, extramedullary hematopoiesis, splenic destruction of RBC, hypersplenism, growth failure

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127
Q

treatments for thalassemia major

A

hypertransfusion every 2-4 weekssplenectomy (in non-transfusion dependent)stem cell transplant to curetreat iron overload with chelation

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128
Q

iron overload cause

A

RBC trasfusionsno body mechanism to get rid of excess ironintake of 1 gm/month in chronic transfusion patients

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129
Q

iron overload complications

A

pericarditis, arrhythmias, cardia failurefibrosis, cirrhosis, hepatic failure, cancerdiabeter, growth failure, infertility

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130
Q

how to test for iron overload

A

serum ferritin, liver biopsy, MRI

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131
Q

treatment of iron overload

A

chelation (deferasirox or deferoxamine)- start treatment early to prevent iron overload rather than trying to reduce amount of iron in the body if possible. phlebotomy- regularly remove blood to reduce amount of iron in the blood

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132
Q

sickle cell disease definition

A

group of blood disorders containing HbS

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133
Q

is sickle cell dominant or recessive?

A

autosomal recessive

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134
Q

sickle cell pathophysiology

A

single point mutation on the beta chainAdenine to Thymine at position 6 of the beta globin.changes RBC shape (stiff due to deoxygenation)blood flow obstruction leads to ischemia

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135
Q

epidemiology of sickle cell

A

in US- 8%1/400 births3,000,000 with trait and 100,000 with diseaseglobally more than 400,000 births per year

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136
Q

how does sickle cell trait protect against malaria

A

lower transmissionreduced parasitemiadecreased mortality

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137
Q

how is sickle cell diagnosed in the US?

A

all newborns tested with dried blood spotsmost common disease found by newborn screening

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138
Q

newborn screening resultsFA

A

normal

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139
Q

newborn screening resultsFAS

A

sickle cell trait

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140
Q

newborn screening resultsFS

A

sickle cell anemia

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141
Q

newborn screening resultsFSA

A

sickle B+ thalassemia

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142
Q

newborn screening resultsF

A

thalassemia major

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143
Q

newborn screening resultsFA

A

fast band- alpha thalassemia trait

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144
Q

risks for sickle cell trait

A

hematuriarenal medullary carcinomasudden death during prolonged, strenuous physical activity

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145
Q

hyphema

A

increased occular pressure, loss of visionthose with sickle cell need referral to a specialist to prevent loss of vision

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146
Q

clinical manifestations of sickle cell disease

A

functional asplenia, pneumococcal infectionhemolysis (partially compensated- increased reticulocytes)acute vaso-occlusive events (painful)organ damage

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147
Q

most common cause of death for sickle cell disease patients

A

organ damage- spleen, kidneys, lung, brain, eyes, hips

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148
Q

how to prevent sepsis in newborns with sickle cell disease

A

prophylactic therapy with oral penicillin by 3 months

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149
Q

penicillin regimen for sepsis prophylaxis with sickle cell

A

125mg BID- until age 3250mg BID- until age 5usually has to be refridgerated and picked up every 2 weeks from the pharmacy- difficult to get patients to be compliant

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150
Q

why stop prophylaxis at age 5

A

immunizations with HiB, prevnar, pneumovax, meningovax, no evidence of sepsis prevention beyond age 5

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151
Q

what temperature is considered a medical emergency for patients with sickle cell disease?

A

38.5 or greater

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152
Q

what to order in a SCD patient with fever

A

labs- blood cultures, cbc with retic, UAchest x-raytype and cross-match if increased pallor or splenomegaly or resp/neuro symptoms

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153
Q

treatment of sepsis in SCD patients

A

IV broad spectrum antibiotics

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154
Q

most common manifestation of SCD

A

acute vaso-occlusive pain- occurs as early as 6 months

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155
Q

painful events with SCD

A

sudden onset in extremities, back , and sternum/ribsdactylitis/ hand-foot syndrome

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156
Q

treatment of painful events

A

NSAIDs and opioidsfluids and hydrationearly pain control

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157
Q

warning signs with SCD pain

A

respiratory distress, chest pain- acute chest syndromefever- infectionweakness- strokelethargy- splenic sequestrationabdominal pain/jaundice- cholelithiasis

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158
Q

symptoms of acute splenic sequestation

A

tender splenomegaly, worsened anemia, increased retics, platelets less than 150,000, LUQ pain, SOB, vomiting

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159
Q

typical age of onset of acute splenic sequestation

A

6 months to 3 years

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160
Q

treatment of splenic sequestration

A

RBC transfusionscareful not to overshoot

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161
Q

recurrence rate of splenic sequestration

A

50%

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162
Q

acute chest syndrome signs/symptoms

A

+/-fever, dyspnea, pain, hypoxia, increased WBC, pleural effusion, fat embolism, atelectasis, sickling and intra-pulmonary sequestration

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163
Q

acute chest syndrome treatment

A

admissionantimicrobial treatment- ceftriaxone, azithromycin, levofloxacinO2bronchodilatorsIV fluidstransfusions

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164
Q

avascular necrosis (AVN)

A

osteonecrosis in limited circulation areasfemoral head most common

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165
Q

AVN treatment

A

NSAIDs, PT, hip replacement

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166
Q

SCD and renal manifestations

A

hyposthenuriarenal infarctionprogression to renal failure and proteinuria

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167
Q

priapism

A

prolonged, painful erection40% of men with SCDblood flow is obstructed

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168
Q

priapism treatment

A

analgesics and hydrationaspiration if greater than 4 hoursvasodilators can prevent attacks, but do not treat

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169
Q

sickle retinopathy

A

vitreal hemorrhage and retinal detachmentcauses vision lossseen in HbSC > HbSS

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170
Q

leg ulcers and SCD

A

5-10% of people > age 10 have healing problems

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171
Q

incidence of stroke with SCD

A

11% by age 20 24% by age 45

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172
Q

stroke symptoms

A

hemiparesis (weakness as opposed to pain)visual/language dysfunctionseizuresheadachesaltered sensationaltered mental status

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173
Q

treatment of stroke with SCD

A

transfusion immediatelyCTIV fluidsMRI (can wait a few days)

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174
Q

stroke recurrence with SCD

A

47-93% without treatmenttreat with blood transfusions every 3-4 weeks10-20% still experience recurrence with treatment

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175
Q

stroke prevention in SCD

A

transcranial doppler (TCD) ultrasonography screeningif > 200 cm/sec- abnormal, requires transfusions

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176
Q

indications for simple transfusions

A

splenic sequestrationtransient aplastic crisisanaemiaacute chest syndromepre-ops

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177
Q

indications for chronic transfusions

A

clinical strokeabnormal TCD (>200 cm/sec)multisystem organ failure

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178
Q

What are the signs and symptoms of platelet bleeding (i.e., primary hemostasis)?

A
  • mucouos membrane bleeding
  • epistaxis
  • prolonged oozing from minor wounds
  • brusing
  • menorrhagia
  • abnormal intraoperative bleeding
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179
Q

What is thrombocytopenia?

A

low platelet counts

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180
Q

What is a failure of secondary hemostasis?

A
  • bleeding from large vessels
  • subcutaneous hematomas
  • hemarthroses
  • intramuscular hematomas
    This is a more “coagulation factor deficiency” picture
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181
Q

What are some signs of congenital thrombocytopenia?

A
  • umbilical cord stump bleeding

* bleeding after circumcision that won’t stop

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182
Q

When you see bruising on a person with suspected thrombocytopenia, what distinguishes it from ordinary bruising?

A
  • indurated (hardened)
  • found in locations where simple trauma bruises are unlikely (e.g, abdomen)
  • sometimes accompanied by petechiae
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183
Q

What arethe etiologiesof thrombocytopenia?

A 
Poor platelet production	
* bone marrow failure	
* infections	
* drugs (sulfa)	
* nutritional disorders (B12, folate)	
* inherited
Increased destruction of platelets	
* splenomegaly	
* non-immune mediated (DIC, HUS)	
* immune-mediated platelet destruction
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184
Q

What do normal platelets look like?

A
  • purple color
  • small (much smaller than RBC)
  • little fuzzy granulations
  • count and multiply in a field by 10k to get total
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185
Q

What is immune thrombocytopenia (ITP)?

A

immune system mediated destruction of platelets.

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186
Q

What do the practice guidelines from ASH 2011 say about treatment of ITP?

A
  • mild symptoms (i.e., no “wet” bleeding) can be treated with observation alone
  • First line treatment includes corticosteriods, IVIG or anti-D immunoglobin
  • Adults: consider for platelet less than 30x109/Ltry corticosteriods first, IVIG if rapid or IVIG/Anti-D if you can’t do steroids
  • Kids: probaby will use IVIG/Anti-D FIRST as corticosteroids can MASK underlying Leukemia and hide the diagnsosis from you.
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187
Q

What are the pratical considerations in treating ITP?

A
  • no bright line rules for platelet levels Individualize decisions based upon:
  • patient age (little people are dangerous)
  • clincal symptoms
  • platelets
  • parent/your concern
  • access to medical care (ER)
  • Patients at high risk of significant bleeding should be treated and monitored
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188
Q

What are the symptoms of TTP?

A
  • Note: Rare (congenital < acquired)
  • “Classic” Pentad: thrombocytopenia; microangiopathic hemolytic anema; fluctuating neurological signs; renal impairment; fever.
  • Most patients present WITHOUT the full pentad
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189
Q

How do you diagnose TTP?

A
  • ADAMTS13 below normal range is definitive
  • Normal (<5-10%)
  • Positive ADAMTS13 inhibitor = usually acquired
  • Negative ADAMTS13 inhibitor = indicates congenital TTP (Upshaw-Schulman Syndrome)
190
Q

What does ADAMTS-13 Do?

A
  • It is an enzyme that cleaves von Willebrand multimers
  • It is essential to prevent excessive clot formation low ADAMTS-13 causes multimers to form webs in vessels
  • RBC’s get sheared causing shistocytes
  • platelets get caught in the webs, reducing their numbers
191
Q

What is Hemolytic Uremic Syndrome (HUS)?

A

A disease that causes microangiopathic hemolytic anemia; thrombocytopenia; and renal impairment (predominant)

192
Q
  • What is the most common cuase of HUS?
A
  • shiga-toxin producing E. Coli (STEC)
    absence of this classified as atypical (aHUS)
  • ​leads to uncontrolled activation of the complement system
193
Q

What genetic mutation is commonly seen in patients that acquire aHUS?

A
  • 60% have mutation in genes that protect us from complement activation (Factor H - CFH) and I (CFI)
194
Q

Who is most likely to get HUS?

A
  • Manifests in all ages (note that this is NOT what PPP says)
  • especially in adolescents and adults
195
Q

What is the threatment for HUS?

A
  • Primarily supportive
  • transfusions may be required for anemia
  • platelet transfusion only resereved for severe bleeding
  • dialysis as need for renal
  • watch fluid load
196
Q

What is the prognosis for people with HUS?

A
  • Generally favorable - renal recovery

* hematologic manifestations typically resolve 1-2 weeks

197
Q

What is the treatment for aHUS?

A
  • Plasma exchange Eculizamab - MAb to complement factor C5
  • blocks complement activation
198
Q

What is the prognosis for aHUS?

A

Compared with HUS, prognosis is much poorer. Chronic relapsing course is common and outcome overall is poorer.

199
Q

What is the etiology of immune thrombocytopenia?

A

may present 1-2 weeks after an immune trigger

  • viral illness
  • live virus immunization
  • allergic rxn
  • can be presenting symptom of broader immune disease (HIV, SLE)
  • can be brought on by specific infections - HepC and H. Pylori
  • lymphoid malignancy
200
Q

What is the pathophysiology of congenital TTP?

A

Gene that makes ADAMST13 is mutated, resulting in lowered production of the enzyme

201
Q

What is the pathophysiology of immune-mediated TTP?

A
  • B-cell mediated autoantibody production against von Willebrand cleaving protease (ADAMS13)
202
Q

How do you treat TTP?

A
  • early diagnosis crucial - DO NOT MISS plasmapheresis is the main treatment
  • replaces ADAMST13 and reduces any antibody
  • in acute phase, 1.5 L
  • maintains congenital 3-4 weeks
  • steroids for immune-mediated TTP
  • Platelet transfusions contraindicated unelss bleeding is life-threatening
203
Q

What is the second-line treatment for TTP if plasmaphoresis fails?

A

Immune mediated:

  • splenectomy
  • corticosteriods
  • rituximab (MAb - 95% of case reports)
204
Q

What is secondary hemostasis (coagulative factorbleeding)?

A
  • bleeding from large vessels
  • subcutaneous hematomoas
  • hemarthroses - bleeding into joint spaces
  • intramuscular hematomas
205
Q

What is pseudothrombocytopenia?

A

Where platelet counts are artificially reduced on CBC/peripheral smears because the platelets have all aggregated into clumps (improper handling of sample).

206
Q

What is the epidemiology of ITP?

A
  • all genders, races and ages (used to be thought of as a young woman’s disease - not true)
  • 10-40 per 100k prevalence
207
Q

What are the categories of ITP?

A
  • Acute: within three months of diagnosis
  • persistent: 3-12 months from diagnosis (80% of ITP in childhood will spontaneously resolve in 6-12 months)
  • chronic ITP: lasting more than 12 months (80% of adult cases go on to be chronic)
208
Q

What is the pathophysiology of ITP?

A
  • loss of self-tolerance autoantibodies (IgG) against platelet antigens
  • platelet gycoproteins (IIb/IIIa and Ib/IX)
  • cellular mechanisms
  • platelets get coated with autoantibodies
  • get destroyed (retiuloendothelial system) - bind to Fc receptros on macrophages, then get eaten
  • decreased production
209
Q

What is the key point to know about the pathophysiology of ITP?

A

Polyclonal autoantibodies may inhibit platelet production by inhibiting megakaryocyte maturation

210
Q

What is the clinical presentation of ITP?

A

bleeding mucocutaneous bleeding

  • wet -oral bullae, epistaxis, menorrhagia, gingival and GI bleeding
  • dry - bruising and petechiae
211
Q

What does the CBC/PBS of ITP look like?

A
  • thrombocytopenia <100 x 109/L
  • normal platelet granulation
    occasionallarge platelets
  • normal WBC # and diff
  • normal RBC # and appearance (unless active bleeding)
  • no evidence of hemolysis
212
Q

How do you diagnose ITP?

A
  • Diagnosis of exclusion
  • no splenomegaly, lymphadenopathy
  • other CBC indices normal
213
Q

ITP in adults - what additional tests should be done for new onset?

A

Test for HIV and HCV broader immune dysfunction DAT - prior to anti-D quantiative immunoglobins

214
Q

What are the treatments for ITP?

A
  • IVIg
  • anti-D
  • corticosteroids
215
Q

What is IVIG treatment?

A
  • derived from human plasma
  • blocks Fc receptors on macrophages from binding with autoantibody coated platelets adverse effects include nausea, vomiting, headache (also sx of head bleed),fever
  • aceptic meningitis (rare)
  • alloimmune hemolysis (rare)
  • infection transmission exceedingly rare
  • anaphylaxis in IgA deficient pt.
216
Q

What are the pros and cons of IVIG?

A 
Pros	
* lack of long term side effects	
* efficacious in 1-2 doses (lasts 2-4 wks)
Cons	
* several hour IV infusion	
* very \$\$$	
* difficult side effects	
* derived from pooled human plasma
217
Q

What is Anti-D immunoglobin therapy?

A
  • polyclonal Ab derived from human Ig
  • Rh(D) antigen positive, non-splenectomized pts can receive
  • preferential destruction of antibody-coated RBCs, spares the platelets (sacrifices RBC)
  • adverse events: fever, chills, nausea, vomiting (give premedications)
218
Q

What are the pros and cons of Anti-D therapy?

A

Pros
* short IV infusion
* efficacious
* fewer donors per dose than IVIG
Cons
* side effect of hemolysis
* really small chance <0.05% massive intravascular hemolysis
* no no if baseline hemolysis (DAT/Coombs BEFORE starting therapy)
* have to avoid in anemia, acute illness, abormal renal function, patients > 65

219
Q

What is the biggest risk to avoid in ITP?

A

Intracranial hemorrhage

  • rare <1%, but deadly
  • patients with lowest platelet counts at highest risk <20k
  • life-threatening spontaneous bleeding at very low counts
  • eliminate anti-platelet medications and high risk activity
220
Q

How is corticosteriod therapy used in treating ITP?

A
  • 1st line in adult ITP patients
  • masks leukemia, so you need to avoid as first line in children
  • predinose, methylprednisone, dexamethasone
  • less rapid platelet rise than in other therapies
  • get massive weight gain
221
Q

What are the urgent treatment options for ITP?

A

platelet infusions/drip emergency splenectomy IV methylprednismoe IVIG recombinant FVIIa (extrinsic pathway that will push toward clotting)

222
Q

What is the treatment for chronic ITP?

A

splenectomy

  • effective 75%
  • but many post-splenectomy complications
  • Rituximab (specifically against B cells)
  • thrombopoietin receptor agonists - binds to megakaryocytes and stimulates platelet production
  • Azathioprine - immunosuppressant
223
Q

ITP vs TTP - How do you tell them apart?

A

Patient Population:Young child - suspect ITP over TTP (note congenital TTP)Clinical Symptoms: ITP often has no symptoms other than mucocutaneous bleeding. NO splenomegaly and no hemolytic anemia or neuro symptoms. Diagnosis: ITP is isolated thrombocytopenia, but TTP has hemolytic anemia, increased indirect bilirubin, decreased haptoglobin

224
Q

What is unilineage bone marrow failure

A

one cytopenia:anemia (RBC) ORneutropenia (WBC) ORthrombocytopenia (platelets)

225
Q

What is multilineage bone marrow failure

A

multiple cytopenias:anemia (RBC) ANDneutropenia (WBC) ANDthrombocytopenia (platelets)AKA pancytopenia

226
Q

define pancytopenia

A

all three cell lines (RBCs, WBCs, and platelets) are decreased

227
Q

What are RBCs, WBC, and platelets made from

A

hematopoietic stem cells in the bone marrow

228
Q

Define hematopoiesis

A

process of making blood cells

229
Q

Define erythropoiesis

A

making erythrocytes

230
Q

Define myelopoiesis

A

making neutrophils

231
Q

Define thrombopoiesis

A

making platelets

232
Q

Define bone marrow failure (BMF)

A

refers to peripheral blood cytopenias resulting from decreased or absent blood cell production in the bone marrow

233
Q

Is bone marrow failure (BMF) acquired or inherited (genetics)

A

bothVERY important to distinguish between the two

234
Q

Classifications of bone marrow failure (BMF)

A

severe: bone marrow with less than or equal to 25% cellularity AND meets at lest two criteria of cytopenias (ANC less than 500, platelets less than 20K, or ARC less than 40K)moderatemild

235
Q

ANCARC

A

absolute neutrophil countabsolute retic count

236
Q

Clinical manifestations of bone marrow failure (BMF)

A

as per their cytopeniasie) symptomatic anemia or bleeding or…etc)

237
Q

Diagnosis of bone marrow failure (BMF)

A

examination of bone marrow so do a bone marrow biopsyunexplained inc or dec in blood cell countsunexplained inc or dec in abnormal cells

238
Q

Difference between BMF and Aplastic Anemia (AA)

A

see picture

239
Q

Diff Dx for hematopoietic stem cell (HSC) injury

A

aplastic anemia or bone marrow failure:idiopathicimmune mediateddue to drugs, toxin, virusesinherited BMF syndorme (fanconi anemia or dyskeratosis congenita)

240
Q

Acquired AA/BMF

A

idiopathic (80% of acquired AA/BMF)post-hepatitisdrugstoxinsinfection

241
Q

Congenital AA/BMF

A

Falconi AnemiaDyskeratosis CongenitaDiamond Blackfan Anemia

242
Q

Clinical presentation of AA/BMF

A

sign and symptoms of:anemia (fatigue, pallor)thrombocytopenia (bruising, bleeding)leukopenia/neutropenia (fever, signs/symptoms of severe infection)

243
Q

Diagnostic tests

A

CBC with diffbone marrow aspirate and biopsy

244
Q

Other diagnostic tests for acquired AA/BMF

A

viral studies (parvovirus B19)liver panelvit B12ANA profile (antinuclear antibody: screens for Lupus)PNH (paroxysmal nocturnal hemoglobinuria) by flow cytometry

245
Q

Other diagnostic tests for congenital AA/BMF

A

elevated Hgb Felevated MCVchromosome breakage analysistelomere length testinggenetic panel

246
Q

Treatment for AA/BMF

A

depends on underlying etiology

247
Q

pathophysiology of acquired idiopathic AA

A

not sure, but maybe immune mediated destruction of hematopoietic stem cells (HSC)

248
Q

diagnostic test for acquired idiopathic AA

A

no confirmatory testrule out genetic/congential causes

249
Q

is acquired idiopathic AA life threatening

A

yes, requires urgent evaluations and care as patients are at high risk for serious bacterial infection

250
Q

treatment of acquired idiopathic AA

A

Best/1st choice: hematopoietic stem cell (HSC) transplant2nd choice: immunosuppressive therapy (combo of antithymocyte globulin (ATG) and cyclosporine (CSA): unclear why works but they are lymphocytotoxic so they may decrease immune mediated destruction of HSC) (about 1/3 relapse)also: supportive care with blood transfusions util definitive therapy

251
Q

treatment of acquired post-hepatits AA

A

similar to acquired idiopathic AA

252
Q

treatment of acquired AA due to infection

A

similar to acquired idiopathic AA

253
Q

treatment of acquired AA due to drugs

A

remove offending agent

254
Q

treatment of acquired AA due to toxins

A

remove offending agent

255
Q

another name for congenital/inherited/genetic AA

A

inherited bone marrow failure syndrome (IBMFS)

256
Q

the three IBMFS

A

Falcon AnemiaDyskeratosis CongentiaDiamond Blackfan Anemai

257
Q

why is it important to rule out IBMFS before looking at acquired AA causes for patients with AA prior to initiation of therapy (another way to ask this question: why is it important to distinguish if AA is acquired or congenital

A

IBMFS will not respond to immunosuppressive therapy (have exposed them to drugs that could have nasty side effects and have delayed definitive Dx)other family members may be affected (this is important info if matched related bone marrow transplant is planned)

258
Q

Common phenotypes of IBMFS

A

poor growthendocrinopathiesanatomical abnormalities of the limbs/digits (i.e. thumbs)anatomical abnormalities of genitourinary tractanatomical abnormalities of heart

259
Q

Persons with IBMFS are predisposed to develop what

A

leukemia or other cancers

260
Q

diagnosis of IBMFS

A

genetic testing

261
Q

treatment of IBMFS

A

HSC transplant is curative but not always indicated for IBMFS

262
Q

define falconi anemia (FA)

A

mostly autosomal recessive disorder characterized by PROGRESSIVE BMF leading to pancytopenia (often starts with isolated thrombocytopenia and/or macrocytosis)

263
Q

common congenital abnormalities of falconi anemia (FA)

A

abnormal skin pigment (cafe au lait spot), short stature, skeletal abnormalities (microophthalmia: small eyes), upper limb abnormalities (thumbs), and reproductive organ abnormalities (25% may have no anatomical abnormalities)

264
Q

when are hematologic abnormalities noticed in Falconi Anemia (FA)

A

median age 7

265
Q

diagnostic test for Fanconi Anemia (FA)

A

chromosome breakage: increased chromosome breakage when exposed to DNA cross linking agents

266
Q

treatment of Fanconi Anemia (FA)

A

HSC transplantsupportive blood transfusions until HSCT

267
Q

prognosis of Fanconi Anemia (FA)

A

800-1000x higher risk of developing cancerinc risk of myelodysplastic syndrome (MDS) and progression to acute myeloid leukemia (AML)requires continued monitoring for development of endocrinopathies, cancer surveillance, and anatomic abnormalities

268
Q

characteristics of Dyskeratosis Congenita

A

BMF (may present early on with mild cytopenia, most often thrombocytopenia)high incidence of cancerlung and liver fibrosis

269
Q

what are those with Dyskeratosis Congenita at risk for

A

MDSleukemiahead/neck cancer

270
Q

what percent of those with Dyskeratosis Congentia develop BMF by age 30

A

90%

271
Q

Clinical presentation of Dyskeratosis Congentia

A

leukoplakia (oral)hypo/hyper-pigmentation (reticulate)nail dystrophycan show all together as classic mucocutaneous triad

272
Q

Common family Hx of Dyskeratosis Congentia

A

MDSearly graying of hairnail abnormalitieslung fibrosis

273
Q

Pathogenesis of Dyskeratosis Congenita

A

mutations in genes encoding for factors implicated in telomere function

274
Q

diagnostic test for Dyskeratosis Congenita

A

test for telomere length (will be very short for age)

275
Q

define Diamond Blackfan Anemia (DBA)

A

genetically and clinically heterogeneous due to mutations in the ribosomal subunit, bone marrow will have paucity of erythroid precursors but normal myeloid precursors and megakaryocytic

276
Q

Presentation of Diamond Blackfan Anemia (DBA)

A

isolated macroytic anemia within first year of life, generally rest of CBC looks normal

277
Q

characteristics of Diamond Blackfan Anemia (DBA)

A

skeletal abnormalities (thumb)renal issuescraniofacial or cardiac abnormalitiesshort stature

278
Q

diagnosis of Diamond Blackfan Anemia

A

RBC have inc activity of adenosine deaminase (eADA)

279
Q

what are patients with Diamond Blackfan Anemia at risk for

A

malignancies

280
Q

treatment of Diamond Blackfan Anemia

A

supportive care with RBC transfusionsanemia may respond to steroid therapyHSC transplant if indicated

281
Q

what is the only curative option for congenital/inherited BMF

A

HSC transplant

282
Q

what are your options to treat acquired BMF

A

HSC transplantimmune suppressive therapy

283
Q

HLA matching best source

A

MRD (matched related donor)usually sibling

284
Q

other sources for HLA matching

A

MUD (matched unrelated donor)haploidentical (50% match of related donor so usually parent: not the best outcomes: in emergency situations)

285
Q

complications of HSC transplant

A

graft rejection (original disease returns because recipients immune system attacked and killed donated stem cells)graft vs host disease (when donor stem cells attack the recipients native tissues)above increased with mismatching between donor and recipient

286
Q

complications of HSC transplant if use autologous source (from donor)

A

no complications except that there is a risk of same disease returning

287
Q

define neutropenia

A

absolute dec in number of circulating neutrophils so dec ANC (absolute neutrophil count)

288
Q

what is the lower limit of ANC

A

1500

289
Q

neutropenia classifications

A

mild 1000-1500moderate 500-1000severe less than 500

290
Q

etiology of neutropenia

A

defects in myelopoiesis, drugs, infections, autoantibodies

291
Q

what does a neutrophil do

A

primary cell in immune response to pyogenic (pus) organisms and predominate cell in acute inflammatory infiltrates: so they are the big guns

292
Q

what does neutropenia inc your susceptibility to

A

bacterial and fungal infectionsskin and oral cavity most commonly affectedsepsis is a common complication (morbidity and mortality)signs and symptoms may be altered with neutropenic patient: infection may not look normal because don’t have and WBCs to fight it so no pus forming no inflammation maybe…

293
Q

can you have normal WBC and still have neutropenia

A

yes so look at differential

294
Q

other names for neutrophils

A

granulocytes (GRAN%)segmented neutrophils (SEG%)

295
Q

what are “bands” or banded neutrophils

A

less mature neutrophilsmature neutrophils are segmentedbands can be listed may or may not be listed separately in differentiated CBC

296
Q

gene mutations of severe congenital neutropenia (SCN)

A

autosomal dominant (ELA2 gene) orrecessive disorder (HAX1 gene)

297
Q

characteristics/clinical presentation of severe congenital neutropenia (SCN)

A

ANC < 200 from birthrecurrent fevers and infections from early infancy

298
Q

treatment of severe congenital neutropenia (SCN)

A

as soon as possible: start granulocyte colony stimulating factor (G-CSF): given as a shotfever precautionsappropriate oral/hand hygieneannual surveillance of marrowmanaged by specialist

299
Q

define cyclic neutropenia

A

regular, periodic oscillations in ANCevery 21 days or so (period for your neutrophils!)classically, monocyte count inc with dec ANC

300
Q

gene mutation of cyclic neutropenia

A

autosomal dominant inheritance (ELA2 mutation)

301
Q

diagnosis of cyclic neutropenia

A

identifying cycle or genetic testing

302
Q

can cyclic neutropenia present later in life

A

yes, with Hx of recurrent mouth sores and fever

303
Q

treatment of cyclic neutropenia

A

granulocyte colony stimulating factor (G-CSF)managed by specialist

304
Q

characteristics of autoimmune neutropenia (AIN)

A

isolated neutropenia: no other underlying condition causing neutropenia: immune system attacking neutrophils

305
Q

who normally gets autoimmune neutropenia (AIN)

A

young kids mostly: self resolving condition

306
Q

clue it may be autoimmune neutropenia (AIN)

A

neutropenia is out of proportion to infectious Hx ie) ANC < 200 but otherwise healthy kid

307
Q

diagnosis of autoimmune neutropenia (AIN)

A

anti-neutrophil antibody is helpful but not always diagnosticfollowed by specialist to rule out other causes of neutropenia

308
Q

treatment of autoimmune neutropenia (AIN)

A

can be self resolvingrarely use G-CSFfollows fever precautions

309
Q

what are causes of secondary autoimmune neutropenia (AIN)

A

broader autoimmune disorders (i.e.: Lupus or Sjogren’s)infectionmedications (hydralazine or procainamide)

310
Q

ethnic neutropenia

A

benign mild-moderate neutropeniamostly in Africans, Jewish, and Arab poplnotherwise normal leukocytes/bone marrowNO Hx or RISK of recurrent infectionsdoes NOT require specialist care

311
Q

other causes of neturopenia

A

acquired or inherited BMFinfectiondrugimmune dysfunctionneonatal alloimmune neutropeniametabolic disordersnutritional deficiencies (vit B12 or folate)marrow infiltration (tumors)

312
Q

is severe neutropenia in an ill or febrile patient an emergency

A

yes

313
Q

can neutropenia (even severe) be observed initially in an otherwise healthy person

A

yes

314
Q

diagnostics for neutropenia

A

blood culturesCBC with differentialHx and physical

315
Q

what are the other granulocytes besides neutrophils

A

basophils and eosinophils

316
Q

results of dec absolute eosinophil count so less than 500

A

allergyasthmaparasitic infectionsmalignanciesrheumatologic disordersimmunodeficiencieshypereosinophilic syndrome

317
Q

results of basophilia

A

hypersensitivity reactionsanaphylaxisinfectionschronic myelogenous leukemia (CML)

318
Q

agranulocytes (other leukocytes)

A

lymphocytes and monocytes

319
Q

what are lymphocytes

A

T cellsB cellsNK cellsNKT cellsprimary cell of specific immune recognitionmemory aspectdifferentiate between self and non-self

320
Q

disorders/diseases of lymphocytes

A

lymphocytosis (infection especially viral and leukemias)lymphopenia (rheumatologic diseases)

321
Q

what are monocytes

A

have multiple functions including phagocytosis and antigen presentation

322
Q

disorders/diseases of lymphocytes

A

monocytosis: infections like SBE or TBmalignanciesrheumatologic diseasesSCN

323
Q

A diagnosis of cancer must be based upon….

A

Pathology: usuaully based upon a biopsy obtained EARLY in the evaluation.

324
Q

What are the basics of cytology?

A

Cytology: cellular morphology▪ Aspiration of tumor (fine needle aspiration)▪ Removal and analysis of abnormal fluid (eg: pleuralfluid, ascites)▪ Review and analysis of normal fluid (e.g. CSF)▪ Washings/lavage with saline (e.g., bladder, lung)

325
Q

What are the pros and cons of cytology?

A
  • Advantages: Less invasive; may distinguish malignancy vs. benign disease▪ Disadvantage: CELLULAR samples only (not tissue), so may limit further classification
326
Q

What are the basics of pathologic sampling?

A

Pathology: tissue morphology* core needle biopsy* surgical biopsy* excisional biopsy

327
Q

What are the pros and cons of pathologic sampling?

A

Pros: TISSUE collection allows for further classification may be determined▪ Determination of invasiveness▪ Evaluation of malignant tissue in relationship tonormal tissueCons: more invasive

328
Q

Name the six types of neoplasm

A

CarcinomaMelanomaLymphomaSarcomaGerm CellCNS Tumors

329
Q

Name the 7 types of Carcinoma

A

Adenocarcinoma (most common)Squamous Cell (most common)NeuroendocrineHepatocellularThyroidRenal CellOther

330
Q

What 3 things do you consider when trying to find out if the cancer is primary or metastatic?

A

▪ Clinical presentation▪ Location and number of tumor(s)▪ Pattern of metastatic spread

331
Q

What 3 factors might you consider when deciding what/where to biopsy?

A
  • Most accessible site▪ Site most likely to yield diagnostic results▪ Site most likely to influence treatment
332
Q

What is cancer staging?

A

Determining:HOW MUCH cancer is in the bodyWHERE the cancer is located.Describes SEVERITY of the cancer based on: Characteristics of the primary tumorExtent of the SPREAD around the body.

333
Q

Why do cancer staging?

A

▪ Indication of PROGNOSIS▪ Establish the best TREATMENT PLAN ▪ Evaluate EFFECTIVENESS of treatment▪ COMMUNICATE “the same language” to other clinicians ▪ Provide standardization for valid RESEARCH

334
Q

What are the three parameters of Clinical Staging?

A

T =Tumor: The extent of the primary tumorN =Nodes: The absence or presence and extent of REGIONAL lymph node metastasisM =Mets: The absence or presence of distant METASTASIS

335
Q

Tumor (T) Stage: Which types of cancer are staged by SIZE and which are staged by DEPTH of penetration?

A

Size: Lung, Breast, Ovarian, ProstateDepth: Bowel, Bladder, Melanoma

336
Q

Nodal (N) Stage: What do you consider when assigning the nodal stage?

A

Based on number and location of regional nodes (distant node is metastasis via hematologic spread)Nodes can be assessed byClinical evaluation if PALPABLEImaging for size and appearance (CT,MRI,U/S)Biopsy or aspiration (IF it will affect treatment!)Surgically (at time of primary tumor resection)

337
Q

Metastasis (M) Stage: What do you consider when assigning the metastasis stage?

A
  • History and PE * Patterns of metastasis* Consensus guidelines about radiologic evaluation* Surgical evaluation is rarely used for metastatic staging
338
Q

What do the staging numbers signify for Primary Tumor (T)

A

TX Primary tumor cannot be evaluatedT0 No evidence of a primary tumorTis Carcinoma In SituT1, T2, T3, T4 Increasing size and extent of tumor

339
Q

What do the staging numbers signify for Regional Lymph Nodes? (N)

A

NX Regional lymph nodes cannot be evaluatedN0 No evidence of disease in lymph nodesN1, N2, N3 Increasing disease involvement in regional lymph nodes

340
Q

What do the staging numbers signify for Distant Metastasis (M)?

A

MX Distant metastasis cannot be evaluatedM0 No evidence of metastasisM1 Distant metastasis

341
Q

What is the difference between clinical and pathological staging?

A
  • Clinical Stage: before starting therapy or having surgery▪ Pathological Stage: surgical exploration and tissue histology.▪ Both should be recorded if possible.
342
Q

Based on TNM score, how do you decide whether the cancer is Stage I, II, III or IV?

A

Depends on the cancer

343
Q

If a patient has M1 cancer, what stages are possible?

A

Stage IV only

344
Q

Can a patient have N1 and have Stage I cancer?

A

No. Regardless of cancer, Stage I must have N=0

345
Q

What is the basis of histopathologic grading?

A

Histology and morphology of cancerous cells seen with a microscope

346
Q

Which is more important: grading or staging?

A

Equally important: a small but aggressive cancer can be more dangerous than a large, indolent cancer.

347
Q

What are Grades GX through G4?

A

GX: Grade cannot be evaluatedG1: Well-differentiatedG2: Moderately differentiatedG3: Poorly differentiatedG4: Very poorly differentiated/Anaplastic

348
Q

What is the difference between well-differentiated cells and poorly-differentiated cells?

A

Well-differentiated: closely resemble the normal cells in architecture (and less aggressive)Poorly-differentiated: do not resemble the normal cells (more aggressive)

349
Q

What are other kinds of cancer qualifiers in considering prognosis and therapies besides Stage and Grade?

A

AgeSerum Markers (eg: PSA, CEA-125)Tumor Genetics (eg: EGFA expression in lung cancer)Patient Genetics (eg: BRCA)

350
Q

If the patient has a stage I cancer, what is theeffective treatment most likely to be?

A

Depends on the location: surgical resection (because it is self-contained) with or without chemo or radiation

351
Q

Why are biopsies of tissue so important fordetermining cancer treatment?

A

Staging, histology/grading, treatment, gene therapy

352
Q

At which stage(s) of cancer is radiation therapy themost likely to be useful?

A

When it is still localized, so stages I, II and III.

353
Q

If the patient has a stage IV cancer, which treatmentis most likely to be effective?

A

Chemo and/or radiation to shrink the tumor, then resection if possible

354
Q

What are the sequential steps thatarrest bleeding?

A
  • vascular reaction - vasoconstriction
  • formation of platelet plug (primary hemo)
  • activation of the coagulation cascase (stable fibrin clot - secondary hemo)
355
Q

Describe what happens during primary hemostasis?

A
  • collagen and von Willebrand factor is exposed due to injury to endothelial cell wall
  • platelets roll over that and stick
356
Q

What are the factors of the extrinsic pathway?

A

7–>X–>5–>2 (Prothrombin)–>2a (Thrombin) –>1 (Fibrinogen)–>Fibrin–>13 (Tight clot)NB: X marks the spot for the common pathwayNB2: 13 is not measured in PTT or PT

357
Q

What are the vitamin K dependent factors?

A

10, 9, 7, 2 (1972 - it was a good year!)NB: Vitamin K is more associated with the extrinsic pathway, but really, there are factors on both sides of the pathway. Mortier told me it is more important for 7 than 9.

358
Q

What happens if you are deficient in Protein C or Protein S?

A

You clot out of control (predisposed to major thrombosis)

359
Q

What are the factors of the intrinsic pathway?

A

TENET - Twelve, Eleven, Nine, Eight, Ten (common)Then remainder of common pathway - 5, 2, 2a, 1, Fibrin, 13

360
Q

aPTT/PTT measures coagulation in which pathway?

A

Instrinsic (PITT)

361
Q

PT measures coagulation in which pathway?

A

Extrinsic (PET)

362
Q

What are the important PMH and FH questions to ask a patient regarding bleeding?

A
  • Bleeding Hx - bruises, petechhaie, gingival bleeding, etc.
  • deep muscle and joint bleeding
  • hematemesis, melena, hematuria, hemotypsis
  • liver or kidney disease
  • aspirin, NSAIDs, Plavix, warfarin, heparin use?
  • menstrual bleeding hx
  • bleeding during or after surgery that was hard to control
  • blood relative with bleeding disorder
  • anemia
363
Q

What are the common pitfalls of laboratory studies?

A
  • heparin in sample
  • traumatic venipuncture (slow draw)
  • too little sample in tube
  • polycythemia (too much anticoag in vaccutainer)
  • anemia (too little anticoag)
  • specimen sits at room temperature
  • PFA shaken and stirred (too much disruption)
364
Q

What is PT used for?

A
  • extrinsic and common factors

* used to monitor Coumadin patients

365
Q

What happens to PT with a Vitamin K deficiency?

A

It is prolonged

366
Q

When is PTT prolonged?

A
  • von Willebrand disease
  • hemophilia
  • lupus anticoagulant
  • NB: sensitive to Heparin contamination
367
Q

What does a 1:1 mixing study tell you?

A
  • if it corrects into the normal range, a factor deficiency is the likely culprit
  • if it fails to correct, an inhibitor or anticoagulant is the likely suspect
  • NB: 30% activity is the threshold to correct clotting times
368
Q

What is the Platelet Function Assay (PFA-100)?

A
  • modern test that replaces old “bleeding time” test
  • push blood through a coated filter and watch the clot formation time on the filter
  • need platelets at least 100 x 109/L
369
Q

When will the Platelet Function Assay be prolonged?

A
  • von Willebrand disease
  • aspirin
  • platelet function defects
370
Q

What does a Normal PT/PTT indciate in the presence of a bleeding disorder?

A

Factor XIII deficiencyRemember, it is not measured by PT/PTT

371
Q

What does both an abornmal PT and PTT suggest?

A
  • fibrinogen deficiency/problem
  • Vitamin K deficiency
  • DIC
  • Liver disease (PT abnormal first)
372
Q

What does an abnormal PTT with normal mixing result suggest?

A
  • Hemophilia A or B
  • Von Willebrand disease
  • Factor XI deficiency
  • Factor XII deficiency
373
Q

What might cause a fibrinogen deficiency?

A
  • liver dysfunction

* DIC

374
Q

Can a reduced level of fibrinogen cause a prolonged PT, PTT or Thrombin Clot Time?

A
  • Generally, no unless fibrinogen is less than 100 mg/dL
375
Q

What does Thrombin Clot Time (TT) measure?

A

Measures the time for conversion of fibriongoen to fibrinHeparin can contaminate

376
Q

What is von Willebrand disease?

A
  • Caused by a deficiency or reduced functioning of von Willebrand factor
  • carries and stabilizes factor VIII
  • mediates platelet adhesion and aggregation
377
Q

What is the most common inherited bleeding disorder?

A

von Willebrand disease

378
Q

What is the mechanism of inheritance of von Willebrand disease?

A

Usually autosomal dominant

379
Q

What kind of bleeding do you see in von Willebrand disease?

A

platelet bleeding or primary hemostasis bleeding

380
Q

What is the Rx for von Willebrand’s disease?

A
  • DDAVP (Arginine vasopression) - releases stored vWf from endothelial cells
  • reduced efficacy with repeated dosing (tachyphylaxis)
  • Humate-P - factor VIII product that contains vWf
  • Cryoprecipitate - life-threatening bleeds (infectious transmission risks)
  • Aminocaproic acid - Amicar -supportive, effective for mucosal bleeding. acts by stabilizing clot. No for hematuria
381
Q

What is Hemophilia A?

A

Deficiency or lack of Factor VIII

382
Q

What is Hemophilia B?

A

Lack or deficiency of Factor IX

383
Q

How are Hemophilia A and B transmitted?

A

X-linked recessive disorders

384
Q

Hemophilia - Epidemiology

A
  • Factor VIII (80%)
  • Factor IX (15%)
  • Expressed in males, carried in females (some females can have prolonged bleeding in surgery or trauma)
  • approx. 30% new mutations
385
Q

What are the three degrees of severity of hemophilia?

A
  • Mild Hemophilia (30-40% of cases)- Factor level 6-50%/uncommon spontaneous bleeding/see sx after major trauma or surgery
  • Moderate hemophilia (10% cases) - factor level 1-5%/see sx after minor trauma/4-6 bleeding episodes per year
  • severe hemophilia (50-70%) - Factor level <1%/spontaneous bleeding occurs/2-4 x month
386
Q

What are some of the history questions to ask about hemophilia?

A
  • family history
  • bleeding with circumcision
  • prolonged bleeding with heel stick or vaccination
  • easy bruising
  • intracranial hemorrhage (esp. during childbirth)
  • milder phenotypes may not present until later ages
387
Q

What type of bleeding episode is most common in hemophila?

A

joint bleeding (60%)most common sites are knee, ankle, elbow

388
Q

What should you avoid when treating a joint bleed?

A

NSAIDS and Aspirin (you know why)

389
Q

Where are common sites for muscle bleeds in hemophilia?

A
  • gluteus
  • hamstrings
  • iliopsoas
  • calf
  • quadriceps
  • deltoid
  • biceps
390
Q

What are the possiblecomplications of untreated muscle bleeds?

A
  • foot drop
  • flexed hip
  • volkmann’s contracture (hand arm)
  • compartment syndrome
391
Q

What are the key points of assessment for a joint/muscle bleed?

A
  • pain - tingling or burning
  • disuse or immobility
  • abnormal appearance - circumference
  • tenderness and heat
  • nerve involvement
392
Q

What is the treatment for Hemophilia?

A
  • replacement of missing factor concentrate (on demand/prophylaxis)
  • DDAVP/ Stimate
  • Antifibrionolytic agents - Amicar
  • Supportive measures - RICE and pain control
393
Q

What are factor inhibitors and how do you identify when they exist?

A
  • these are antibodies that develop against “foreign” infused factors in hemophilias. They exist in 15-25% of Factor VIII pts and 1.5-3% of Factor IX pts.
  • median of 9-12 exposure days
  • consider when pt. is unresponsive to Rx
  • prolonged PTT after mixing 1:1
  • one BU of activity causes 50% loss of Factor VIII activity
394
Q

How do you treat inhibitors in hemophilia?

A
  • recombinant FVIIa - push clotting through extrinsic pathway
  • High-dose VIII or IX
  • prothrombin complex concentrates
  • can try to desensitize the immune systemto the factor
395
Q

What do you do first when a pt. with hemophilia presents with major bleed symptoms?

A
  • TREAT FIRST
396
Q

What is DIC?

A
  • A disorder of secondary hemostasis caused by consumption of factors in the coagulation system
  • triggered by exposure of blood to tissue factor
  • present with bleeding, petechiae and purpura
  • causes include: infection; major trauma; malignancy
397
Q

What is the Rx for DIC?

A
  • Most important: TREAT UNDERLYING CAUSE
  • hydration
  • RBC transfusion
  • if bleeding, fresh frozen plasma, cryoprecipitate, orplatelets
398
Q

What are conditions that can lead to thrombosis?

A 
Virchow's Triad	
* alterations in blood flow (stasis)	
* vascular endothelial injury	
* alterations in constituents of blood
50% of thrombotic events in pts with inherited thrombophilia are affiliated with additional risk factor
399
Q

What are the causes of inheritied thrombophilia?

A
  • Factor V (Leiden) - most common inherited in causasians 3-8%
  • prothrombin gene mutation (G20210A)
  • Protein S deficiency
  • Protein C deficiency
  • antithrombin deficiency
400
Q

What is the Rx for venous thromboembolism?

A
  • LMW heparin, vondaparinaux, unfractioned IV heparin
  • overlap with and transition to Vitamin K antagonist
  • Target INR 2.5
401
Q

Who should be screened for thrombophilia?

A
  • initial thrombus occuring before 40 without provoking factor
  • FH of 1st degree relatives with VTE
  • recurrent VTE
  • thrombosis in unusual vascular beds - liver, cerebral, mesenteric
402
Q

What are secondary hypercoagulable states?

A
  • pregnancy
  • contraceptive use/HT
  • malignancy
  • systemic inflammation
  • post-operative state
  • immobilization
  • trauma
403
Q

von Willebrand Disease Panel has what tests?

A
  • vWF:RCo (Ristocetin) - decreased in vW
  • vWF:Ag (Antigen) - decreased (but can be normal with non-functional vW)
  • FVIII (can be normal)
404
Q

prevalence of acute in leukemia in children vs adults

A

30% of childhood cancers2.3% of adult cancers

405
Q

define leukemia

A

neoplastic disease, abnormal proliferation of WBCs

406
Q

name the 4 types of leukemia (that we need to know)

A

acute lymphoblastic leukemiachronic lymphoblastic leukemiaacute myelogenous leukemiachronic myelogenour leukemia

407
Q

difference between acute and chronic leukemia

A

acute is associated with proliferation of immature precursors in blood and marrow, chronic is associated with mature precursors

408
Q

which genetic conditions predispose you to leukemia

A

down syndrome, neurofibromatosis, BMF syndromes

409
Q

what environmental/iatrogenic factors predispose you to leukemia?

A

ionizing radiation, occupational exposure (benzene), prior radiation therapy, prior malignancy

410
Q

in acute leukemia, what is the outcome of malignancy in immature precursors/ early hematopoietic precursors?

A

cell progeny does not differentiate/mature but proliferates uncontrollably. These “blasts” overtake the bone marrow, peripheral blood stream, lymph nodes

411
Q

what is a typical WBC count with leukemia

A

varies widely50% have normal-mild elevation25% very high25% decreased

412
Q

what does a bone marrow biopsy show in leukemia

A

hypercellular marrowmarrow fibrosis (AML)

413
Q

when do you order a lumbar puncture?

A

with ALL alwaysif there are neurologic symptoms in a patient with AML

414
Q

what disease presents with a mediastinal mass? (50%)

A

T-cell ALL

415
Q

What is the characteristic histology finding with AML?

A

Auer rods (found in 30% of patients)

416
Q

How long is induction with AML

A

10 days

417
Q

What is the most common form of cancer in children

A

acute lymphoblastic leukemia (ALL)

418
Q

associates symptoms common with ALL

A

splenomegaly, lymphadenopathy, bone pain

419
Q

How long is induction with ALL

A

4 weeks

420
Q

what is the management of ALL after induction?

A

post-remission consolidation for 6-8 weeksmaintenance doses daily or weekly for 2-3 yearsCNS prophylaxis (intrathecal chemo)

421
Q

What disease is associated with the Philadelphia Chromosome

A

Characteristic finding of CML, but also seen in ALL- means worse prognosis- lower remission rates

422
Q

major sequelae of leukemia

A

subsequent cancers

423
Q

complications associated with chemo

A

osteopenia, endcrine abnormalities, poor cardiac function

424
Q

how does treatment of children with ALL differ from adults?

A

intensive multi-agent inductionless intensive maintenancebone marrow transplant in 5%

425
Q

treatment of children with AML?

A

6 months inpatients treatment- intensive and toxicbone marrow transplant in 30%

426
Q

Chronic lymphocytic leukemia (CLL) epidemiology

A

most common adult leukemia (western world)male to female 2:1median age of onset 72

427
Q

CLL definition

A

proliferation of mature B cells, accumulation of long-lived mature lymphocytes, hypogammaglobulinemia

428
Q

CLL clinical presentation

A

often asymptomatic- incidental findingfatigueappetite losslymphadenopathyhepatosplenomegaly

429
Q

CLL immunologic abnormalities

A

auto-immune hemolytic anemiaauto-immune thrombocytopenic purpuramonoclonal spikehypogammaglobulinemia

430
Q

how do you Dx CLL?

A

Flow cytometry

431
Q

CLL staging

A

Rai StageStage 0 Lymphocytosis onlyStage I LymphadenopathyStage II SplenomegalyStage III AnemiaStage IV Thrombocytopenia

432
Q

CLL staging- ABC

A

Binet StageA: <3 areas of lymphadenopathy. No anemia/ thrombocytopeniaB: 3 or more involved LN areas. No anemia/ thrombocytopeniaC: Hemoglobin <10 g/dl or <100,000 platelets

433
Q

Treatment of CLL

A

usually none, only if progressive/severe symptoms

434
Q

Define CML

A

proliferative hematopoeitic stem cells

435
Q

characteristic abnormalities

A

Philadelphia chromosomeBCR-ABL tyrosine kinase

436
Q

epi of CML

A

median age 45-65slightly maleincrease risk with age

437
Q

3 phases of CML

A

chronicacceleratedblastic crisis

438
Q

presentation of CML

A

often asymptomaticfatigueanorexiaabdominal fullnesssplenomegaly

439
Q

CML CBC findings

A

leukocytosisthrombocytosisanemiabasophilia

440
Q

lymphoma symptoms

A

painless lymphadenopathyconstitutional symptomsextranodal involvement

441
Q

hodgkin lymphoma epi

A

bimodal- 15-34 years and >60maleassociated with viral infections

442
Q

key finding to suggest hodgkin lymphoma

A

painless, mobile, rubbery lymph nodesworse/painful with alcoholB symptomsReed Sternberg Cells

443
Q

how to Dx hodgkin lymphoma

A

biopsy- see Reed Sternberg cell

444
Q

treatment of hodgkin lymphoma

A

radiotherapy and chemotherapy, length depends on stage

445
Q

complications of hodgkin lymphoma treatment

A

immunologic deficitthyroid dysfunctioncardiac dysfunctionsecondary malignancies

446
Q

non-hodgkin lymphoma epi

A

increasing prevalence- unknown whycommon in AIDS patientsaverage age at Dx- 42risk groups- occupational exposure to hazardous material, viral exposure, low veggie/high red meat dietdrink a little wine to protect yourselves ladies

447
Q

clinical presentation of non-hodgkin lymphoma

A

lymph node involvementsplenomegalyB symptoms

448
Q

non-hodgkin lymphoma staging

A

Stage I– Involvement of single lymph node (LN) regionStage II– >2 LN regions on same side of diaphragmStage III– LNs on both sides of diaphragmStage IV– Multifocal involvement of >1 extra-lymphatic sites (e.g., liver, bone marrow, lung)

449
Q

non-hodgkin treatment

A

chemotherapy +/- radiation depending on stagingprognosis variable depending on staging

450
Q

what is multiple myeloma characterized by

A

neoplastic proliferation of plasma cells that produce an abnormal monoclonal immunoglobulin or light chain kappa or lambda (IgG, IgM, IgA…and rarely IgD or IgE)

451
Q

examples of the extensive skeletal destruction caused by plasma cells proliferating in the bone marrow

A

osteolytic lesionsosteopeniapathologic fracturesbone painhypercalcemiaanemia

452
Q

median age to present with multiple myeloma

A

70

453
Q

who is more likely to get multiple myeloma

A

occurs in all racesblacks 2x higher than whites3.7x more likely to get if 1st degree relative with MM

454
Q

clinical presentation of multiple myeloma

A

normocytic anemiabone painelevated creatininefatigue/general weaknesshypercalcemiaweight lossparesthesis

455
Q

how many people with multiple myeloma are asymptomatic

A

up to 1/3

456
Q

initial testing for multiple myeloma

A

CBC with diffserum chemistries (Ca, Cr, BUN, albumin)

457
Q

confirmatory testing for multiple myeloma

A

24 hr urine proteinbeta 2 microglobulinLDHserum free light chain assayserum protein electrophoresisurine protein electrophoresisserum immunofixation electrophoresisquantitative immunoglobulinsskeletal survey

458
Q

testing with oncology consult for multiple myeloma

A

bone marrow aspirate and biopsyBM cytogeneticsflow cytometryFISHimmunohistochemistry

459
Q

97% of patients with MM will have a monoclonal (M) protein produced and secreted by the malignant plasma cells…this M protein spike is detected on what region on electrophoresis

A

gamma region

460
Q

key test in diagnosis of MM

A

bone marrow aspirate and biopsy

461
Q

what two criteria must be met to diagnose MM

A

clonal bone marrow plasma cells greater than or equal to 10% or biopsy proven extra medullary plasmacytoma AND one or more myeloma-defining events (listed on diff flashcard)

462
Q

what are the myeloma-defining events

A

evidence of end organ damage attributed to underlying plasma cell proliferative disorder (listed on diff flashcard)clonal bone marrow plasma cells greater than or equal to 60%serum free light chain ratio greater than or equal to 100more than one focal lesion on MRI studies

463
Q

plasma cell proliferative disorder (CRAB)

A

hyperCalcemiaRenal insufficiencyAnemiaBone lesions: one or more lytic lesions

464
Q

treatment if not a transplant candidate

A

chemotherapy

465
Q

treatment if a transplant candidate

A

myeloablative chemotherapyautologous stem cell transplant then consolidation and maintenance chemotherapy

466
Q

treatment of bone disease

A

IV zoledronic acid (Recast)pamidronatecalcium and vit D supplements

467
Q

treatment of thromboembolic events

A

thromboprophylaxis: heparin or warfarin

468
Q

treatment of infection

A

prophylactic antibiotics

469
Q

what is MGUS (monoclonal gammopathy of undetermined significance)

A

clinically asymptomatic premalignant clonal plasma cell or lymphoplasmacytic proliferative disorderserum monoclonal protein M less than 3 gm/dL, bone marrow with less than 10% monoclonal plasma cells, and NO CRAB

470
Q

why should patients with MGUS be monitored

A

associated with small risk of progressing to malignant plasma cell dyscrasia or lymphoproliferative disorder

Clin Med I - Comprehensive (6 decks)

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