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Pathoma > Hemostasis and Related Disorders > Flashcards

Hemostasis and Related Disorders Flashcards

1
Q

What molecule mediates the transient vasoconstriction of primary hemostasis? What cell type releases this molecule?

A

endothelin

endothelial cells

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2
Q

What clotting factor binds subendothelial collagen?

A

vWF

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3
Q

Platelets bind vWF via what receptor?

A

GpIb

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4
Q

What two molecules are contained within Weibel Palade bodies?

A

vWF and P-selectin

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5
Q

What is contained in dense granules? What cell type?

A

ADP and calcium

platelets

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6
Q

GpIIb/IIIa is upregulated on the surface of platelets by what signal?

A

ADP binding ADP receptor

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7
Q

What molecule binds to GpIIb/IIIa?

A

fibrinogen

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8
Q

What are petechiae indicative of?

A

thrombocytopenia

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9
Q

What is a normal platelet count? Below what level can lead to petechiae?

A

150 - 400

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10
Q

What isotype of immunoglobulin is produced during Immune Thrombocytopenia? Against what?

A

IgG

GpIIb/IIIa

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11
Q

What cell type produces the Ab during Immune Thrombocytopenia? What organ is this cell located? What organ consumes these RBCs?

A

Plasma cells

spleen

spleen

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12
Q

Acute Immune Thrombocytopenia arises in what patient population? After what two happenings?

A

children

viral infection or vaccination

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13
Q

Chronic Immune Thrombocytopenia arises in what patient population?

A

women of childbearing age

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14
Q

Are any coagulation factors affected during Immune Thrombocytopenia? Why?

A

no . only destruction of GpIIb/IIIa

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15
Q

What is the initial treatment of Immune Thrombocytopenia?

A

corticosteroids = initial Tx

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16
Q

What two reasons is a splenectomy used as treatment for Immune Thrombocytopenia?

A

removes source of auto-Ab (splenic plasma)

removes site of platelet destruction (splenic macrophages)

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17
Q

What is microangiopathic hemolytic anemia?

A

pathological formation of platelet microthrombi in small vessels

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18
Q

What cellular happening is seen during MAHA?

A

schistocytes

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19
Q

What are the two classic disorders that will produce Microangiopathic Hemolytic Anemia?

A

TTP and HUS

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20
Q

Lack of what enzyme causes TTP? What is the normal function of this enzyme?

A

ADAMTS13

cleave vWF

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21
Q

What patient population most often develops auto-ADMATS13 Ab’s?

A

adult female

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22
Q

What specifc bacterial strain produces HUS? Where is this strain found?

A

E. coli O157:H7

undercooked beef

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23
Q

Does HUS cause renal or CNS defects?

A

renal

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24
Q

Does TTP cause renal or CNS defects?

A

CNS

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25
Q

Are coagulation factors effected during HUS or TTP? What does this mean?

A

no

PT/PTT = normal

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26
Q

What cellular happening is observed during TTP/HUS?

A

schistocytes

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27
Q

What would be observed on a bone marrow biopsy of during TTP/HUS?

A

schistocytes

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28
Q

What are the two treatments of TTP and HUS?

A

plasmapheresis and corticosteroids

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29
Q

What is defective/absent during Bernard-Soulier syndrome? What is impaired?

A

GpIb

adhesion = impaired

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30
Q

What two cellular happenings are seen during during Bernard-Soulier syndrome?

A

mild thrombocytopenia and enlarged platelets

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31
Q

What is defective during Glanzmann thrombasthenia? What is impaired?

A

GpIIb/IIIa

aggregation = impaired

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32
Q

What activates factor VII?

A

tissue thromboplastin

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33
Q

What activates factor XII?

A

subendothelial collagen

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34
Q

Defects in primary homeostasis manifest as what? Where?

A

skin and mucosal bleeding

nose bleeds (Epistaxis)

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35
Q

Defects in secondary homeostasis manifest as what two conditions?

A

deep tissue bleeding

rebleeding after surgical procedures

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36
Q

PT measures which arm of the coagulation cascade?

A

extrinsic

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37
Q

Which clotting factors does PT measure?

A

I (fibrinogen), two, five, seven and ten

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38
Q

PTT measures which arm of the coagulation cascade?

A

intrinsic

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39
Q

What is the mode of inheritance of hemophilia A?

A

X-linked recessive

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40
Q

What are of the coagulation cascade would be effected during hemophilia A?

A

PTT

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41
Q

What coagulation factor is absent during Hemophilia B?

A

nine

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42
Q

What coagulation factor is most likely to develop an autoantibody against it? How would this be diagnosed?

A

eight

PTT does not correct upon mixing with normal serum

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43
Q

Will PTT be corrected if a patient with Hemophilia A is given normal serum?

A

yes

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44
Q

Will PTT be corrected if a patient with Coagulation Factor Inhibitor is given normal serum?

A

no

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45
Q

What two sites will bleed during vWF Disease?

A

skin and mucosa

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46
Q

What branch of the coagulation cascade will vWF Disease effect? Why?

A

PTT

vWF binds and protects factor eight

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47
Q

What drug is used to Dx vWF Disease? What is the MOA of this drug?

A

Ristocetin

causes vWF to bind GpIb

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48
Q

What drug is used to Tx vWF Disease? What is the MOA of this drug?

A

Desmopressin (DDAVP)

desmopressin causes endothelial cells to release vWF from Weibel-Palade bodies

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49
Q

What factors are regenerated by Vitamin K?

A

two, seven, nine, ten, C and S

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50
Q

What branch of the coagulation cascade is used to follow liver failure?

A

PT

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51
Q

What protein do platelets bind during HIT?

A

PF4

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52
Q

What isotype of Ab is involved during HIT?

A

PF4

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53
Q

What pro-coagulant is contained in amniotic fluid?

A

tissue thromboplastin

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54
Q

What two bacteria are the most common causes of septic DIC?

A

E. coli

N. meningitidis

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55
Q

Why does sepsis cause DIC? Why?

A

endotoxin

influences endothelial cells to make tissue factor

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56
Q

What coagulation factor is tissue factor?

A

III

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57
Q

What type of neoplasia can result in DIC? What specific product causes this?

A

adenocarcinoma

mucin

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58
Q

What type of leukemia can cause DIC? Why?

A

acute promyelocytic leukemia

primary granules

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59
Q

What type of bite can cause DIC?

A

rattlesnake

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60
Q

What is the serologic marker for DIC? What is D-Dimer derived from?

A

D_DIMER

fibrin split products

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61
Q

What surgery can cause a disorder of fibrinolysis? Why?

A

radical prostatectomy

release of urokinase

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62
Q

What if the function of urokinase?

A

activate plasmin

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63
Q

Why can liver failure result with a defect in fibrinolysis?

A

decrease production of α2 anti-plasmin during liver failure

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64
Q

Why do errors in fibrinolysis produce an increase in PT and PTT?

A

plasmin degrades coagulation factors

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65
Q

Is the platelet count normal during errors of fibrinolysis?

A

yes

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66
Q

What is the Tx of disorders of fibrinolysis? What is the MOA of this drug?

A

aminocaproic acid

blocks activation of plasminogen

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67
Q

What is the histological pathological finding of thombosis? What are the three components?

A

Lines of Zahn

platelets and fibrin and RBCs

68
Q

What is Virchows triad?

A

stasis, endothelial damage, hypercoaguable state

69
Q

What two anti-coagulant molecules are produced by healthy endothelial cells?

A

PGI2 and NO

70
Q

What fibrinolytic molecule is secreted by a healthy endothelium?

71
Q

What are the three functions of plasmin?

A
  1. cleave fibrin and fibrinogen
  2. destroy coagulation factors
  3. block platelet aggregation
72
Q

Does thrombomodulin activate Protein C or does Protein C activate thromobomodulin?

A

thrombomodulin activates Protein C

73
Q

What coagulation factors are destroyed by Actiated Protein C?

A

five and eight

74
Q

Deficiency of what vitamin can lead to endothelial damage?

75
Q

Deficiency of what enzyme can result in homocystinuria?

A

cystathione beta-synthase

76
Q

What are the four defects of CBS deficiency?

A

vessel thrombosis

dislocated lens

mental retardation

long slender fingers

77
Q

Deficiency of what two proteins predispose to warfarin induced necrosis? Why?

A

Protein C or Protein S

C and S have shorter half-lifes than two, seven, nine or ten

78
Q

Why does warfarin induced skin necrosis happen?

A

microthrombi form in vessels

79
Q

Why does Factor V Leiden produce hypercoaguable states?

A

Factor V lacks cleavage site for APC

80
Q

How is antithrombin deficiency diagnosed?

A

heparin does not produce increase in PTT

81
Q

What type of drug is associated with an increase in coagulation factor synthesis?

A

oral contraceptives

82
Q

What is the characteristic histological feature of emboli?

A

cholesterol clefts

83
Q

Fracture of what type of bones are indicative of a fat embolus?

A

long bones

84
Q

What are the two gross manifestations of fat emboli?

A

dyspnea

petechiae on skin over chest

85
Q

Pain from what two locations are characteristic of the bends?

A

joint and muscle

86
Q

What happens to bones during Caisson disease?

A

multifocal ischemic necrosis of bone

87
Q

Gestational emboli has what two histological components located inside of it?

A

squamous cells

keratin

88
Q

What three veins does a PE most often arise from?

A

femoral, iliac and popliteal

89
Q

What is elevated during a pulmonary embolism?

90
Q

In what part of the heart do systemic emboli usually arise?

A

left heart

91
Q

What is the first step of primary hemostasis?

A

transient vasoconstriction

92
Q

What cell synthesizes TXA2 during the clottign cascade?

93
Q

What organ is the most at risk of bleeding during severe thrombocytopenia?

94
Q

What is a normal bleeding time?

A

2-7 minutes

95
Q

Which immunoglobulin can cross the placenta?

96
Q

What cell undergoes hyperplasia during Immune Thrombocytopenia? Where?

A

Megakaryocytes

on bone marrow biopsy

97
Q

What is the secondary Tx of immune thrombocytopenia?

A

IV immunoglobulin = secondary

gives splenic macrophages something to chew on rather than IgG anti-GpIIb/IIIa

98
Q

What cell is depleted during Microangiopathic Hemolytic Anemia?

99
Q

Where is E. coli O157:H7 found?

A

undercooked hamburger

100
Q

What cell type is damaged that leads to HUS?

A

endothelial

101
Q

Other than HUS, what can E. coli O157:H7 cause? What specific toxin?

A

Dysentery

verotoxin

102
Q

What is the mnemonic to remeber the five clinical finding of TTP and HUS?

103
Q

What does the C of CRSMF stand for?

A

CNS abnormalities

104
Q

What does the R of CRSMF stand for?

A

renal insufficiency

105
Q

What does the S of CRSMF stand for?

A

skin and mucosal bleeding

106
Q

What does the M of CRSMF stand for?

A

Microangiopathic hemolytic uremia

107
Q

What does the F of CRSMF stand for?

108
Q

Why does TTP and HUS cause skin and mucosal bleeding?

A

low platelets due to microthrombi formation

109
Q

What myeloid cell would increase in number on a PBS during TTP or HUS?

A

Megakaryocyte

110
Q

Why are corticosteroids used to treat TTP?

A

corticosteroids decrease number of antibody producing cells

111
Q

What do platelets look like in Bernard-Soulier syndrome?

112
Q

What drug can expose Glanzmann-Thrombasthenia? Why?

A

Aspirin

lack of TXA2 prevents aggregation

113
Q

What cell contributes the phospholipid surface to the coagulation cascade?

114
Q

What two locations body does a patient with Hemophilia A present with bleeding?

A

deep tissue

post-surgical

115
Q

What is the treatment for Hemophilia A?

A

Recombinant Factor 8

116
Q

How does von Willebrand Disease typically present?

A

mucosal and skin bleeding

117
Q

What is the most common disorder of coagulation?

A

vWF disease

118
Q

What coagulation factor does vWF bind to and stabilize?

119
Q

Regarding coagulation, what specific chemical reaction does Vitamin K catalyze?

A

gamma carboxylation

120
Q

Regarding coagulation, what enzyme is located in the lilver?

A

Vitamin K epoxide reductase

121
Q

What is the feared result of HIT?

A

thrombosis

122
Q

What are the two common bleeding sites of DIS?

A

mucosal surfaces

IV sites

123
Q

Regarding DIC, what in amniotic fluid can activate the coagulation cascade?

A

tissue thromboplastin

124
Q

What specific type of cancer can cause DIC? Why?

A

acute promyelocytic leukemia

expansion of platelets and their release of primary granules

125
Q

What type of histological feature is present in Acute Promyelocytic Leukemia?

126
Q

What is the Tx for DIC? What is contained in this?

A

Cryoprecipitate

fibrinogen

127
Q

What protein inactivates plasmin?

A

α2 anti-plasmin

128
Q

What factor is used to differentiate a disorder of fibrinolysis vs. DIC?

A

fibrinolysis disorder = normal platelet count

DIC = low platelets

129
Q

What cell type produces anti-Thrombin III?

A

endothelial cells

130
Q

What cell type produces tPA?

A

endothelial

131
Q

What cell type produces thrombomodulin?

A

endothelial cells

132
Q

What are the three causes of endothelial damage?

A

atherosclerosis, vasculitis, high serum homocysteine

133
Q

Initial warfarin therapy results in a deficiency of what two anti-coagulants?

A

Protein C and Protein S

134
Q

What is the mutated version of prothrombin? What mutation is present?

A

20210A

point mutation

135
Q

What is the key histological fidning of an atherosclerotic embolus?

A

cholesterol clefts

136
Q

What is the chronic form of a gas embolus?

A

Caisson Disease

137
Q

What is Caissons disease characterized by?

A

multifocal ischemic necrosis of bone

138
Q

What is the main complication of chronic pulmonary emboli?

A

pulmonary hypertension

139
Q

How can anemia present in an individual with already poor coronary vascular function?

140
Q

Where in the GI tract does absorption of ironn occur?

141
Q

What is contained within α-granules of platelets?

A

vWF and fibrinogen

142
Q

Why can oral contraceptives result in a hypercoaguable state?

A

estrogen promotes synthesis of clotting factors

143
Q

What type of neoplasia can cause iron deficient anemia?

A

colonic carcinoma

144
Q

What is the most common cause of a decrease in ADAMTS13?

A

acquired autoantibody

145
Q

Would a disorder of fibrinolysis present with D-dimers? Why or why not?

A

no

decreased fibrinolysis only–> no degradation of D-dimers to begin with

146
Q

What is lysed during a disorder of fibrinolysis?

A

fibrinogen

147
Q

What is the most common cause of thrombocytopenia in children and adults?

A

Immune Thrombocytopenia

148
Q

What is the most common inherited coagulation disorder?

A

Bernard soulier disease

149
Q

Why does Prothrombin 20210A result in a hyper-coaguable state?

A

too high of levels of prothrombin

150
Q

Which granule of platelets is vWF contained?

A

α-granules

151
Q

What is a normal bleeding time?

A

2-7 minutes

152
Q

Which myeloid cell does uremia interrupt?

153
Q

Which four clotting factors does the PT follow?

A

two

five

seven

ten

154
Q

PTT follows all factors except which two?

A

seven and thirteen

155
Q

Does HIT produce a hypocoaguable or hypercoaguable state?

156
Q

Which two cytokines are involved during DIC? Via wat mechanism?

A

TNF and IL1

induce endothelial cells to release tissue factor

157
Q

Does use of lytics increase or decrease BT?

158
Q

Which cell type synthesizes AT III?

A

endothelial

159
Q

What does plasmin do to platelets?

A

blocks their aggregation

160
Q

Which cell type secretes tPA?

A

endothelial

161
Q

What gets transferred from THF to B12? What is the fate of this molecule?

A

methyl group

homocysteine to methionine

162
Q

Is GpIb involved with adhesion or aggregation?

163
Q

Is GpIIb/IIIa involved with adhesion or aggregation?

A

aggregation

164
Q

What is the key difference between DIC and disorders of fibrinolysis?

A

no D-dimer with fibrinolysis problems

165
Q

What type of surgery can cause a gas emboli?

A

laproscopic

Pathoma (19 decks)

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