Heme/Onc - First Aid Flashcards Preview

► USMLE 1 > Heme/Onc - First Aid > Flashcards

Flashcards in Heme/Onc - First Aid Deck (309):
1

Erythrocyte Features

-carries O2 to tissues and CO2 to lungs -anucleate, biconcave -large surface area to volume ratio for rapid gas exchange -life span = 120 days -uses glucose for energy

2

The membrane of erythrocytes contains...

chloride-HCO3- antiporter which allows RBCs to export HCO3- and transport CO2 from the periphery to the lungs for excretion.

3

A reticulocyte is...

an immature erythrocyte; a marker of erythroid proliferation.

4

Anisocytosis

varying size

5

Poikilocytosis

varying shape

6

Platelet (thrombocyte) features

-invovled in primary hemostasis -small cytoplasmic fragment derived from megakaryocytes -life span = 8-10 days

7

When a platelet is activated by endothelial injury, it will...

aggregate with other platelets and interact with fibrinogen to form a platelet plug.

8

Platelets contain...

dens granules (ADP and calcium) and alpha granules (vWF and fibrinogen).

9

Thrombocytopenia or decreased platelet function results in...

petechiae.

10

vWF receptor

GPIb

11

Fibrinogen receptor

GPIIb/IIIa

12

Leukocytes are divided into...

granulocytes (neutrophils, eosinophils, basophils) and mononuclear cells (monocytes and lymphocytes).

13

Normal Leukocyte level

4000-10000

14

WBC differential from highest to lowest

Neutrophils Like Making Everything Better Neutrophils (54-62%) Lymphocytes (25-33%) Monocytes (3-7%) Eosinophils (1-3%) Basophils (0-.75%)

15

Neutrophils are...

an acute inflammatory response cell seen in bacterial infections. -phagocytic -multilobed

16

Small neutrophils with more numerous specific granules contain...

ALP, collagenase, lysozyme and lactoferrin.

17

Larger neutrophils with less numerous azurophilic granules contain...

proteinases, acid phophatase, myeloperoxidase and beta-glucoronidase.

18

Hypersegmented PMNs (5 or more lobes) are seen in...

vitamin B12/folate deficiency.

19

Increased band cells (immature neutrophils) reflect states of...

myeloid proliferation (bacterial infections, CML).

20

Monocytes differentiate into...

macrophages in tissues.

21

Monocyte features

-large, kidney-shpaed nucleus -"frosted glass" cytoplasm

22

Macrophages act to...

phagocytose bacteria, cellular debris and senescent RBCs and scavenge damaged cells and tissue.

23

Macrophages are activated from monocytes via...

gamma-interferon.

24

Macrophages can function as...

antigen presenting cells via MHC II.

25

Surface marker for macrophages

CD14

26

Macrophages are an important component of...

granuloma formation.

27

Eosinophils defend against...

helminthic infections (w/ major basic protein).

28

Eosinophils features

-bilobate nucleus -packed with large eosinophilic granules -highly phagocytic for Ag-Ab complexes

29

Eosinophils produce..

histaminase and arylsulfatase (these help limit rxn following mast cell degranulation).

30

Causes of eosinophilia

NAACP N: neoplasia A: asthma A: allergies C: CT disorders P: parasites

31

Basophils mediate...

allergic rxns.

32

Basophil features

densely basophilic granules containing heparin (anticoagulant), histamine (vasodilator) and leukotrienes.

33

Isolated basophilia is rare but can be a sign of...

myeloproliferative disease (particularly CML).

34

Mast cells mediate...

allergic rxn in local tissue. (resemble basophils)

35

Mast cells can bind...

the Fc portion of IgE to the membrane. IgE cross-links upon Ag binding, causing degranulation, which releases heparin, histamine, and eosinophilic chemotactic factors.

36

Mast cells are involved in...

type I HSR.

37

Mast cell degranulation is prevented by...

cromolyn sodium (used for asthma prophylaxis).

38

Dendritic cells are...

highly phagocytic APCs that function as the link between the innate and adaptive immune systems.

39

Dendritic cells express...

MHC class II and Fc receptors on the surface.

40

Dendritic cells of the skin are called...

Langerhans cells.

41

Lymphocyte appearance

round, densely staining nucleus with a small amount of pale cytoplasm

42

B lymphocytes arise from...

stem cells in bone marrow, mature there and then migrate to peripheral lymphoid tissue (follicles of LNs, white pulp of spleen).

43

When Ag is encountered, B cells will...

differentiate into plasma cells that produce Abs and memory cells.

44

B cells can function as...

an APC via MHC II.

45

T lymphocytes originate from...

stem cells in the bone marrow but mature in the thymus.

46

The costimulatory signal necessary for T-cell activation is...

CD28.

47

The primary target of HIV is...

CD4+ helper T cells.

48

Plasma cell appearance

eccentric nucleus clock-face chromatin abundant RER well-developed Golgi apparatus

49

Universal recipient of RBCs

AB blood group

50

Universal donor of plasma

AB blood group

51

Universal donor of RBCs

O blood group

52

Universal recipient of plasma

O blood group

53

Rh- mothers who are exposed to fetal Rh+ blood (oftenduring delivery) may make...

anti-Rh IgG. In subsequent pregnancies, anti-Rh IgG crosses the placenta causing hemolytic disease of the newborn (erythroblastosis fetalis).

54

Rho(D) immune globulin is given for...

mothers during every pregnancy to prevent intial sensitizaiton of Rh- mother to Rh antigen.

55

Warfarin acts by...

inhibiting the enzyme vitamin K epoxide reductase to prevent maturation of coagulation factors.

56

Neonates lack enteric bacteria which produce...

vitamin K.

57

Vitamin K deficiency leads to...

decreasd synthesis of factors II, VII, IX, X, protein C and S.

58

vWF carries/protects...

factor VIII.

59

Antithrombin inhibits...

activated forms of factors II, VII, IX, X, XI, XII.

60

Heparin enhances...

the activity of antithrombin.

61

Principal targets of antithrombin

thrombin and factor Xa

62

Factor V Leiden mutation produces...

a factor V resistant to inhibition by activated protein C.

63

tPA is used clinically as...

a thrombolytic. It converts plasminogen to plasmin which then causes fibrinolysis.

64

A normal platelet aggregation response is not seen in...

von Willebrand disease.

65

Acute phase reactants in plasma (fibrinogen) can cause...

RBC aggregation, thereby increasing RBC sedimentation rate.

66

Increased ESR (erythrocyte sedimentation rate) is seen in...

infxns autoimmune diseases malignant neoplasms GI disease (UC) pregnancy

67

Decreased ESR is seen in...

polycythemia sickle cell anemia CHF microcytosis hypofibrinogenemia

68

Acanthocyte (spur cell)

-liver disease -abetalipoproteinemia (states of cholesterol dysregulation)

69

Basophilic stippling

-anemia of chronic disease -alcohol abuse -lead poisoning -thalassemias

70

Bite cell

G6PD deficiency

71

Elliptocyte

Hereditary elliptocytosis

72

Macro-ovalocyte

megaloblastic anemia (also hypersegmented PMNs) marrow failure

73

Ringed sideroblast

sideroblastic anemia (excess iron in mitochondria)

74

Schistocyte/helmet cell

DIC TTP/HUS traumatic hemolysis (mechanical heart valve prosthesis)

75

Spherocyte

hereditary spherocytosis autoimmune hemolysis

76

Teradrop cell

bone marrow infiltration (myelofibrosis) *RBCs shed a tear bc they have been forced out of their home in the bone marrow.

77

Target cells

HbC disease Asplenia Liver disease Thalassemia

78

Heinz bodies are seen in...

G6PD deficiency; Heinz body-like inclusions are seen in alpha-thalassemia.

79

Heinz bodies cause....

oxidation of Hb sulfhydryl groups leading to denatured Hb precipitation and phagocytic damage to the RBC membrane forming bite cells.

80

Heinz bodies are visualized with...

special stains such as crystal violet.

81

Howell-Jolly bodies are seen in pts with...

functionl hyposplenia or asplenia.

82

Howell-Jolly bodies are...

basophilic nuclear remnants found in RBCs. They are normally removed from RBCs by splenic macrophages.

83

Iron deficiency can be caused by...

chronic bleeding, malnutrition/absorption disorders, pregnancy

84

Iron deficiency decreases...

the final step in heme synthesis leading to a microcytic, hypochromic anemia.

85

Findings in Iron Deficiency Anemia

-decreased iron -increased TIBC -decreased ferritin -fatigue -conjunctival pallor

86

Iron Deficiency Anemia may manifest as...

Plummer-Vinson syndrome which is a triad of: 1. iron deficiency anemia 2. esophageal webs 3. atrophic glossitis

87

alpha-thalassemia has a defect in...

alpha-globin gene (deletions) leading to decreased synthesis.

88

cis alpha-thalassemia deletion is prevalent in...

Asian populations. The trans deletion is prevalent in African populations.

89

alpha-thalassemia (4 allele deletion):

-no alpha-globin -excess gamma globin forms gamma4 (Hb Barts) -incompatible with life (hydrops fetalis)

90

alpha-thalassemia (3 allele deletion):

-HbH diseae -very little alpha globin -excess beta-globin forms beta4 (HbH)

91

alpha-thalassemia (1-2 allele deletion):

no clinically significant anemia

92

Beta-thalassemia is...

a microcytic, hypochrmoic anemia due to point mutations in splice sites and promoter sites leading to decreased beta-globin synthesis; prevalent in mediterranean populations

93

Beta-thalassemia minor (heterozygote) features

-beta chain underproduced -usually asymptomatic -diagnosis confirmed by increased HbA2 (> 3.5%) on electrophoresis

94

Beta-thalassemia major (homozygote) features

-beta chain absent (severe anemia requiring blood transfusion) -marrow expansion ("crew cut" on skull x-ray) leading to skeletal deformities (chipmunk facies) -extramedullary hematopoiesis (hepatosplenomegaly)

95

Beta-thalassemia major pts are at increased risk for...

parvovirus B-19 induced aplastic crisis.

96

Beta-thalassemia major has increased...

HbF which is protective for the 1st 6 months of life (no symptoms).

97

HbS/beta-thalassemia heterozygote

mild/moderate sickle cell depending on amount of beta-globin production

98

Lead inhibits...

ferrochelatase and ALA dehydratase leading to decreased heme synthesis and increased RBC protoprophyrin;

99

Lead also inhibits...

rRNA degradation causing RBCs to retain aggregates of rRNA (basophilic stippling).

100

High risk of lead poisoning in...

old houses with chipped paint.

101

Lead poisoning findings

-lead lines on gingivae and long bones -encephalopathy -erythocyte basophilic stippling -abdominal colic -sideroblastic anemia -wrist and foot drop

102

1st line treatment for lead poisoning is...

Dimercaprol and EDTA.

103

In kids with lead poisoning, treatment is...

Succimer for chelation. (It SUCks to be a kid who eats lead.)

104

Sideroblastic Anemia is due to...

a defect in heme synthesis.

105

Hereditary sideroblastic anemia

X-linked defect in delta-ALA synthase gene

106

Causes of sideroblastic anemia

-genetic -acquired -alcohol -lead -vitamin B6 deficiency -copper deficiency -isoniazid

107

Sideroblastic Anemia presents with

-increased iron -normal TIBC -increased ferriting -ringed sideroblasts (w/ iron-laden mitochondria)

108

Treatment for sideroblastic anemia

pyridoxine (B6 - cofactor for delta-ALA synthase)

109

Megaloblastic anemia is due to...

impaired DNA synthesis. This causes the maturation of the nucleus of precursor cells in bone marrow to be delayed relative to the maturation of the cytoplasm. This causes abnormal cell division leading to pancytopenia.

110

3 types of megaloblastic anemia

-folate deficiency -B12 deficiency -orotic aciduria

111

Causes of folate deficiency megaloblastic anemia

-malnutrition (alcoholics) -malabsorption -anifolates (methotrexate, trimethoprim, phenytoin) -increased requirement (hemolytic anemia, pregnancy)

112

Findings of Folate deficiency

-hypersegmented neutrophils -glossitis -decreased folate -increased homocysteine but normal methylmalonic acid -NO neuro symptoms (distinguishes from B12 deficiency)

113

Causes of B12 deficiency anemia

-insufficient intake (vegans) -malabsorption -pernicious anemia -Diphyllobothrium latum -proton pump inhibitors

114

Findings of B12 Deficiency

-hypersegmented neutrophils -glossitis -decreased B12 -increased homocysteine -increased methylmalonic acid -neuro symptoms

115

Neurologic symptoms of B12 deficiency are due to..

subacute combined degeneration due to involvement of B12 in fatty acid pathways and myelin synthesis.

116

Neuro symptoms of B12 Deficiency

1. peripheral neuropathy w/ sensorimotor dysfunction 2. dorsal columns (vibration/proprioception) 3. lateral corticospinal (spasticity) 4. dementia

117

Orotic aciduria is due to...

the inability to convert orotic acid to UMP because of a defect in UMP synthase.

118

Orotic aciduria presents in...

children as megalobastic anemia that cannot be cured by folate or B12 with FTT.

119

Orotic aciduria does not have...

hyperammonemia (which distinguishes it from ornithine transcarbamylase deficiency).

120

Findings of Orotic Aciduria

-hypersegmented neutrophils -glossitis -orotic acid in urine

121

Treatment for Orotic Aciduria

uridine monophosphate to bypass the mutated enzyme

122

Causes of nonmegaloblatic, macrocytic anemia

-liver disease -alcoholism -reticulocytosis -drugs (5-FU, zidovudine, hydroxyurea)

123

Findings of nonmegaloblastic, macrocytic anemias

macrocytosis bone marrow suppression

124

Normocytic, normochromic anemias are classified as either...

hemolytic or nonhemolytic.

125

Findings of Intravascular Hemolysis

-decreased haptoglobin -increaesed LDH -schistocytes -increased reticulocytes -urobilinogen in the urine

126

Finings of Extravascular Hemolysis

-macrophages in the spleen clear RBCs -spherocytes -increased LDH -increased unconjugated bilirubin

127

Nonhemolytic, hormocytic anemias (3)

1. anemia of chronic disease 2. aplastic anemia 3. chronic kidney disease

128

In Anemia of Chronic Disease, inflammation leads to..

increased hepcidin (released by the liver, binds ferroportin on intestinal mucosal cells, thus inhibiting iron transport) leading to decreased release of iron from macrophages.

129

Findings of Anemia of Chronic Disease

-decreased iron -decreased TIBC -increased ferritin

130

Aplastic anemia is caused by...

failure or destruction of myeloid stem cells due to: -radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites) -viral agents (parvovirus B19, EBV, HIV, HCV) -Fanconi anemia -

131

Findings of Aplastic Anemia

-pancytopenia characterized by severe anemia, leukopenia and thrombocytopenia -normal cell morphology -hypocellular bone marrow with fatty infilration (dry bonemarrow tap)

132

Symptoms of Aplastic Anemia

-fatigue -malaise -purpura -mucosal bleeding -petechiae -infxn

133

Treatment of aplastic anemia

-immunosuppressive regimens -allogeneic bone marrow transplant -RBC/platelet transfusion -G-CSF -GM-CSF

134

Chronic kidney disease causes anemia because...

decreaed EPO leads to decreased hematopoiesis.

135

Types of Intrinsic Hemolytic Normocytic Anemia

-Hereditary spherocytosis (E) -G6PD deficiency (I/E) -Pyruvate kinase deficiency (E) -HbC defect (E) -Paroxysmal nocturnal hemoglobinuria (I) -Sickle Cell Anemia (E)

136

Hereditary spherocytosis is due to a defect in...

proteins interacting with RBC membrane skeleton and plasma membrane (ankyrin, band 3, protein 4.2, spectrin)

137

In hereditary spherocytosis, less membrane causes...

small and round RBCs with no central pallor (increased MCHC and increased red cell distribution width) leading to premature removal of RBCs by the spleen.

138

Findings in hereditary spherocytosis

-splenomegaly -aplastic crisis (w/ parvovirus B19 infxn)

139

Labs of Hereditary spherocytosis

-osmotic fragility test positive -eosin-5-maleimide binding test useful for screening -normal/decreased MCV with abundance of cells

140

Hereditary spherocytosis masks...

microcytia.

141

Treatment for hereditary spherocytosis

splenectomy

142

The most common enzymatic disorder of RBCs is...

G6PD deficiency (X-linked).

143

In G6PD deficiency, a defect in G6PD leads to...

decreased glutathione leading to increased RBC susceptibility to oxidant stress. Then there is hemolytic anemia followng oxidant stress.

144

In G6PD deficiency, classic causes of oxidant stress are...

sulfa drugs, antimalarials, infxns, fava beans.

145

Findings of G6PD deficiency

-back pain -hemoglobinuria a few days after oxidant stress

146

Labs for G6PD deficiency

RBCs with Heniz bodies and bite cells

147

Pyruvate kinase deficiency has a defect in...

pyruvate kinase which leads to decreased ATP and rigid RBCs.

148

Pyruvate kinase deficiency presents as...

hemolytic anemia in a newborn.

149

HbC defect is due to a...

glutamic acid to lysine mutation at residue 6 in the beta-globin.

150

HbC defect pts with HbSC (1 of each mutant gene) have...

milder disease than HbSS pts have.

151

Paroxysmal nocturnal hemoglobinuria is an...

acquired mutation in a hematopoietic stem cell leading to increased complement-mediated RBC lysis (there is impaired synthesis of GPI anchor for decay-accelerating factor that protects RBC membrane from complement).

152

Paroxysmal nocturnal hemoglobinuria has increased incidence of...

acute leukemias.

153

Triad of Paroxysmal nocturnal hemoglobinuria

-Coombs negative hemolytic anemia -pancytopenia -venous thrombosis

154

Labs for Paroxysmal Nocturanl Hemoglobinuria

-CD55/59 negative RBCs on flow cytometry

155

Treatment for Paroxysmal Nocturnal Hemoglobinuria

Eculizumab

156

Sickle Cell Anemia has a...

HbS point mutation that causes a single amino acid replacement in the beta-chain (substitution of gluatmic acid with valine) at position 6.

157

Pathogenesis of Sickle Cell Anemia

low O2, dehydration or acidosis preciptates sickling (deoxygenated HbS polymerizes) which results in amemia and vaso-occlusive disease

158

Newborns with sickle cell are initially...

asymptomatic because of increased HbF and decreased HbS.

159

Heterozygotes (sickle cell trait) have...

resistance to malaria.

160

On skull x-ray, sickle cell shows...

"crew cut" due to marrow expansion from increased erythropoiesis (also in thalassemias).

161

Complications in sickle cell

-aplastic crisis (due to parvovirus B19) -autosplenectomy (increased risk of infxn with encapsulated organisms) -splenic sequestration crisis -salmonella osteomyelitis -dactylitis (painful hand swelling) -acute chest syndrome -avascular necrosis -stroke -renal papillary necrosis -microhematuria

162

Diagnosis of sickle cell is made with...

hemoglobin electrophoresis

163

Treatment of sickle cells

hydroxyurea (increases HbF) bone marrow transplant

164

Extrinsic Hemolytic normocytic anemias

1. autoimmune hemolytic anemia 2. microangiopathic anemia 3. macroangiopathic anemia 4. infxn

165

Autoimmune hemolytic anemia with warm agglutinin is...

chronic anemia seen in SLE, CLL or with certain drugs (alpha-methyldopa). IgG mediated.

166

Autoimmune hemolytic anemia (AIHA) with cold agglutinin is seen with...

acute anemia triggered by cold; seen in CLL, mycoplasma penumonia infections or infectious mononucleosis

167

AIHAs are usually positive for...

Coombs.

168

Direct Coombs Test

anti-Ig antibody added to pts blood; RBCs agglutinate if RBCs are coated with Ig

169

Indirect Coombs Test

normal RBCs added to pts serum; if serum has anti-RBC surface Ig, RBCs agglutinate when anti-Ig antibodies are added.

170

Microangiopathic anemia pathogenesis

RBCs are damaged when passing through obstructed or narrowed vessel lumina

171

Microangiopathic anemia is seen in...

DIC, TTP-HUS, SLE and malignant HTN.

172

On blood smear of microangiopathic anemia, there are...

schistocytes (helmet cells) due to mechanical destruction of RBCs.

173

Macroangiopathic anemia is due to...

prosthetic heart valves and aortic stenosis secondary to mechanical damage. Show schistocytes.

174

Infections can increase the...

destruction of RBCs (malaria, Babesia).

175

Transferrin

transports iron in the blood

176

Ferritin

primary iron storage protein of the body

177

Neutropenia definition

absolute neutrophil count

178

Neutropenia causes

-sepsis/postinfection -drugs -aplastic anemia -SLE -radiation

179

Lymphopenia definition

absolute lymphocyte count

180

Causes of lymphopenia

-HIV -DiGeorge syndrome -SCID -SLE -corticosteroids -radiation -sepsis -postoperative

181

Eosinopenia causes

-cushing syndrome -corticosteroids

182

Corticosteroids cause neutrophilia because they...

decrease activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation.

183

Corticosteroids cause eosinopenia and lymphopenia becasue they...

sequester eosinophils in LNs and cause apoptosis of lymphocytes.

184

The porphyrias are...

conditions of defective heme synthesis that lead to accumulation of heme precursor. (lead inhibits enzymes of heme synthesis, leading to similar conditions)

185

Affected enzyme in lead poisoning

-ferrochelatase -ALA dehydratase

186

Accumulated substrate in lead posioning

-protoporphyrin -delta-ALA (in blood)

187

Presenting symptoms of Lead poisoning

-microcytic anemia -GI/kidney disease

188

Common presentation of lead poisoning in children

Exposure to lead point leads to mental deterioration.

189

Common presentation of lead poisoning in adults

environmental exposure (battery/ammunition/radiator factory) leads to HA, memory loss, demyelination)

190

Affected enzyme in acute intermittent porphyria

porphobilinogen deaminase

191

Accumulated substrate in acute intermittent porphyria

-porphobilinogen -delta-ALA -coporphobilinogen (urine)

192

Presenting symptoms of acute intermittent porphyria

-painful abdomen -port-wine colored urine -polyneuropathy -pscyhological disorders -precipitated by drugs, alcohol and starvation (5 Ps)

193

Treatment for acute intermittent porphyria

-glucose and heme (which inhibit ALA synthase)

194

Affected enzyme in Porphyria cutanea tarda

uroporphyrinogen decarboxylase

195

Accumulated substrate in Porphyria cutanea tarda

uroporphyrin (tea-colored urine)

196

Presenting symptom of Porphyria cutanea tarda

blistering cutaneous photosensitivity tea-colored urine

197

Prothrombin Time (PT) tests...

the function of the common and extrinsic pathway (factors I, II, V, VII, and X); a defect will increase PT.

198

PTT tests...

function of common and intrinsic pathway (all factors exceptr VII and XIII); defect will increase PTT.

199

Hemophilia A features

-increased PTT -deficiency of factor VIII

200

Hemophilia B features

-increased PTT -deficiency of factor IX

201

Clinical findings of Hemophilia A and B

-hemarthroses (bleeding into joints) -easy bruising

202

Treatment for Hemophilia A

-recmobinant factor VIII

203

Vitamin K deficiency features

-increased PT -increased PTT -bleeding time is normal -decreased synthesis of factors II, VII, IX, X, protein C and protein S

204

Defects in platelet plug formation leads to...

increased bleeding time

205

Platelet abnormalities lead to...

microhemorrhage: mucous membrane bleeding (epistaxis), petechiae/purpura, increased bleeding time, decreased platelet count

206

Bernard-Soulier Syndrome Featuers

-increaed bleeding time -decreased platelets -decreased GpIb (leads to defect in platelet to vWF adhesion)

207

Glanzmann thrombasthenia features

-increased bleeding time -decreased GpIIb/IIIa (defect in platelet to platelet aggregation) -blood smear shows no platelet clumping

208

Immune thrombocytopenia

-decreased platelets -increased bleeding time -anti-GpIIb/IIIa antibodies (splenic macrophage consumes platelet/Ab complex) -may be triggered by viral illness -increased megakaryocytes on bone marrow biopsy

209

Thrombotic thrombocytopenic pupura (TTP) features

-decreased platelets -increased bleeding time -deficiency of ADAMTS 13 leads to decreased degradation of vWF multimers

210

In TTP, with the increased large vWF multimers, it leads to...

increased platelet adhesion and increased platelet aggregation and thrombosis.

211

Labs of TTP

schistocytes, increased LDH

212

Symptoms of TTP

-pentad of neurologic and renal symptoms, fever, thrombocytopenia and microangiopathic hemolytic anemia (FATRN)

213

Treatment for TTP

exchange transfusion and steroids

214

von Willebrand Disease features

-increased bleeding time -normal/increased PTT -decreased vWF causes a defect in platelet-to-vWF adhesion

215

Characteristics of von Willebrand Disease

-mild -autosomal dominant

216

Diagnose von Willebrand Disease with...

ristocetin cofactor assay (decreased agglutination is diagonistic).

217

Treatment for von Willebrand Disease

DDAVP (desmopressin) which releases vWF stored in endothelium

218

DIC features

-decreased platelets -increased bleeding time -increased PT -increased PTT

219

DIC is...

widespread activation of clotting which leads to a deficiency in clotting factors which creates a bleeding state.

220

Causes of DIC

Sepsis (gram-negative) Trauma Obstetric complications acute Pancreatitis Malignancy Nephrotic syndrome Transfusion (STOP Making New Thrombi)

221

Labs for DIC

-schistocytes -increased fibrin split products (D-dimers) -decreased fibrinogen -decreased factors V and VIII

222

vWF acts to...

carry/protect factor VIII

223

Factor V Leiden is production of...

mutatn factor V that is resistant to degradation by activated protein C.

224

Hereditary thrombosis sydnromes leading to hypercoaguability

1. Factor V Leiden 2. Prothrombin gene mutation 3. Antithrombin deficiency 4. Protein C or S deficiency

225

Prothrombin Gene Mutation is in the...

3' untranslated region leading to increased production of prothrombin leading to venous clots.

226

Antithrombin deficiency is inherited and has no direct effect on...

PT, PTT or thrombin time but diminshes the increase in PTT following heparin administration.

227

Antithrombin deficiency can also be acquired when...

renal failure leads to antithrombin loss in the urine leading to increased factors II and X.

228

Protein C or S deficiency leads to decreased ability to...

inactivate factors V and VIII leading to increased risk of thrombotic skin necrosis with hemorrhage following administration of warfarin.

229

Packed RBCs effect

increase Hb and O2 carrying capacity

230

Packed RBCs clinical use

acute blood loss severe anemia

231

Platelets transfusion clinical use

stop significant bleeding (thrombocytopenia)

232

Fresh frozen plasma transfusion effect

increase coagulation factors

233

FFP transfusion clinical use

DIC cirrhosis warfarin overdose exchange transfusion in TTP/HUS

234

Cryoprecipitate transfusion effect

contains fibrinogen, factor VIII, factor XIII, vWF and fibronectin

235

Clincial use of cryoprecipitate transfusion

treat coagulation factor deficiencies involving fibrinogen and factor VIII

236

Blood transfusion risks include..

infection transmission transfuscion reactions iron overload hypocalcemia hyperkalemia

237

Leukemia

lymphoi or myeloid neoplasms with widespread involvement of bone marrow; tumor cells are usually found in peripheral blood

238

Lymphoma

discrete tumor masses arising from LNs

239

Leukemoid rxn is an...

acute inflammatory response to infection.

240

Features of the Leukemoid Reaction

-increased WBC -increased neutrophils and band cells -increased leukocyte ALP

241

Hodgkin Lymphoma

localized, single group of nodes; extranodal is rare; contiguous spread; better prognosis

242

Hodgkin Lymphoma is characterized by...

Reed-Sternberg cells.

243

Distribution of Hodgkin Lymphoma is...

bimodal: young adulthood and greater than 55. Usually in men.

244

50% of Hodgkin Lymphoma is associated with...

EBV.

245

Symptoms of Hodgkin's

-contitutional (B) symptoms - low fever, night sweats, weight loss

246

Non-Hodgkin lymphoma

-multiple, peripheral nodes -extranodal involvement common -noncontiguous spread

247

The majority of Non-Hodgkin lymphomas involve...

B cells.

248

Peak incidence for Non-Hodgkin's is...

20-40.

249

Non-Hodgkin's lymphom may be associated with...

HIV and immunosuppression.

250

Reed-Sternberg cells

-binucleate -CD15 and CD30 + -B cell origin -necessary for diagnosis of Hodgkin Lymphoma

251

Forms of Hodgkin lymphoma

-nodular sclerosing form most common -lymphocyte-rich has best prognosis

252

Neoplasms of mature B cells (Non-Hodgkin lymphomas)

1. Burkitt 2. Diffuse large B-cell 3. Mantle Cell 4. Follicular

253

Burkitt lymphoma occurs in...

adolescents.

254

Burkitt lymphoma genetics

t(8;14) translocation of c-myc and heavy-chain Ig

255

Histology of Burkitt

-"starry sky" appearance -sheets of lymphocytes w/ interspersed macrophages

256

Burkitt is associated with...

EBV

257

Different forms of Burkitt

Endemic form: jaw lesion, Africa Sporadic form: pelvis or abdomen

258

Diffuse large B-cell lymphoma (DLBL) occurs in...

older adults usually.

259

Genetics of Diffuse large B-cell lymphoma

t(14;18)

260

Mantle cell lymphoma occurs in...

older males.

261

Mantle cell lymphoma genetics

t(11;14) translocation of cyclin D1 and heavy chain Ig

262

Mantle cell lymphoma cell marker

CD5+

263

Follicular lymphoma is seen in...

adults.

264

Genetics of follicular lymphoma

t(14;18) translocation of heavy chain Ig and bcl-2

265

bcl-2 inhibits...

apoptosis.

266

Follicular lymphoma presents with...

painless "waxing and waning" lymphadenopathy.

267

Neoplasms of mature T cells (non-hodgkin lymphoma)

*see cutaneous lesions in adults 1. Adult T-cell lymphoma 2. Mycosis fungoides/Sezary syndrome

268

Adult T-cell lymphoma is caused by...

HTLV-1 and is associated with IV drug abuse.

269

Presentation of Adult T-cell lymphoma

-cutaneous lesions -esp. in Japan, West Africa and Caribbean -lytic bone lesions and hypercalcemia

270

Presentation of Mycosis fungoides/Sezary syndrome

-adults present with cutaneous patches/plaques/tumors with potential to spread to LNs and viscera -circulating malignant cells -CD4+

271

Multiple myeloma is a...

monoclonal plasma cell ("fried egg" appearance) cancer that arises in the marrow and produces large amounts of IgG and IgA.

272

Multiple myeloma is associated with...

-increased susceptiblity to infection -primary amyloidosis -punched out lytic bone lesions -M spike on serum protein electrophoresis -Ig light chains in urine (Bence Jones protein) -Rouleaux formation (stacked RBCs)

273

Histology of Multiple myeloma

-numerous plasma cells with "clock face" chromatin -intracytoplasmic inclusions containing Ig

274

Waldenstrom macroglobulinemia is similar to Multiple myeloma except...

M spike is from IgM and there are no lytic bone lesions.

275

Monoclonal gammopathy of undetermined significance (MGUS)

monoclonal expansion of plasma cells with M spike and decreased plamsa cells in bone marrow **asymptomatic precursor to multiple myeloma

276

Myelodysplastic syndromes are...

stem cell disorders involving ineffective hematopoiesis leading to defects in cell maturation of all non-lymphoid lineages.

277

Myelodysplastic syndromes are caused by...

de novo mutations or environmental exposure (radiation, benzene, chemo).

278

Myelodysplastic syndrome has a risk of trasnformation to..

AML.

279

Pseudo-Pelger-Huet anomaly

neutrophils with bilobed nuclei typically seen after chemo

280

Acute lymphoblastic leukemia/lymphoma (ALL) is seen in those...

less than 15.

281

T-cell ALL can present as a...

mediastinal mass (leukemic infiltration of the thymus).

282

ALL is associated with...

Down Syndrome.

283

Markers of ALL

-increased lymphoblasts in blood and marrow -TdT+ -CD10+

284

ALL other features

-responsive to therapy -may spread to CNS and testes -t(12;21) = better prognosis

285

In leukemias, unregulated growth of...

leukocytes in bone marrow leads to anemia, infxns and hemorrhage.

286

Small lymphocytic lymphoma or Chronic lymphocytic lymphoma (SLL/CLL) features

-age > 60 yrs -CD20+ -CD5+ -B cells -progresses slowly -smudge cells -AIHA

287

SLL is the same as CLL except CLL has...

increased peripheral blood lymphocytosis or bone marrow invovlement.

288

Hairy Cell Leukemia features

-adults -B cells -cells have filamentous, hair-like projections

289

Hairy cell leukemia stains...

TRAP positive.

290

Hairy cell leukemia causes...

marrow fibrosis (dry tap).

291

Treatment for Hairy cell

-cladribine (an adenosine analog that inhibits adenosine deaminase)

292

Acute myelogenous leukemia (AML) features

-65 yrs -auer rods -peroxidase + -increased circulating myeloblasts

293

Risk factors for AML

-alkylating chemo -radiation -myeloproliferative disorders -down syndrome

294

M3 type of AML has...

a t(15;17) translocation.

295

M3 subtype of AML responds to...

all trans retinoic acid (vitamin A) which induces differentiation of myeloblasts.

296

Common presentation of AML is...

DIC which is induced by chemo due to release of Auer rods.

297

Chronic myelogenous leukemia (CML)

-45-85 yrs -philadelphia chromosome t(9;22) - bcr-abl -myeloid stem cell proliferation -increased neutrophils, metamyeloctyes and basophils -splenomegaly

298

CML may progress to...

AML or ALL ("blast crisis").

299

As a result of low activity in the granulocytes, CML has a very low level of...

leukocyte alkaline phosphatase.

300

CML responds to...

imatinib (an inhibitor of the bcr-abl tyrosine kinase).

301

Langerhans cell histiocytosis is a proliferative disorder of...

dendritic cells from a monocyte lineage that presents in a child as lytic bone lesions and skin rash. Or recurrent otitis media with a mass involving the mastoid bone.

302

In langerhans cell histiocytosis, the cells are...

functionally immature and do not efficiently stimulate the primary T lymphocytes via Ag presentation.

303

Langerhans cell histiocytosis cells express...

S-100 (mesodermal origin) and CD1a. Birbeck granules (tennis rackets) are characteristic.

304

Polycythemia vera features

-hematocrit > 55% -mutation in JAK2

305

Polycythemia vera presents as...

intense itching after hot shower. Classic symptom is erythromelalgia (severe, burning pain and red/blue color) due to episodic clots in extremities.

306

Secondary polycythemia is via...

natural or artificial increase in EPO.

307

Essential thrombocytosis is similar to polycythemia vera but is specific for...

overproduction of abnormal platelets leading to... bleedign and thrombosis. The bone marrow contains enlarged megakaryocytes.

308

Myelofibrosis is...

fibrotic obliteration of the bone marrow. Teardrop RBCs and immature forms of the myeloid line are seen.

309

bcr-abl transformation in CML leads to...

increased cell division and inhibition of apoptosis.