Ch. 4 - Hemostasis and Related Disorders Flashcards Preview

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Flashcards in Ch. 4 - Hemostasis and Related Disorders Deck (261):
1

primary hemostasis forms a..

weak PLT plug

2

secondary hemostasis stabilizes the PLT plug with...

fibrin

3

PLTs bind vwF via what receptor?

GPIb

4

vwF binds exposed..

subendothelial collagen

5

What is the FIRST thing that happens when the endo has been damaged?

reflexive vasoconstriction via neural response and endothelin

6

What are the two sources of vWF?

Weibel-Palade bodies of endo and a-granules of PLTs

7

What are the two mediators that are released from PLTs adhesed to vWF?

ADPTXA2

8

ADP is released from what granule in the PLT?

dense granules

9

ADP release from PLTs promotes the exposure of what receptor on the PLT?

GPIIb

10

how do PLTs aggregate together?

via GPIIb

11

TXA2 is synthed by what enzyme?

COX

12

what is the linker molecule between GPIIb/IIIa receptors?

fibrinogen

13

What are the major symptoms of disorders in PRIMARY hemostasis?

MUCOSAL BLEEDINGepistaxis, hemoptysis, GI bleeding, hematuria, meorrhagia

14

what is a severe complication o thrombocytopenia?

intracranial bleed

15

Describe the size of petehcia, purprua and echymoses

petechiae: 1-2mmpurpura: >3mmecchymoses: >1cm

16

Are petechiae seen in QUALITATIVE d/o of bleeding?

NO just when PLTs are low!!!

17

what is the most common cause of thrombocytopenia in adults and kids?

ITPimmune thrombocytopenic purpura

18

Describe the general process of ITP

autoAbs produced by the spleen; coat PLTs, the spleen then eats the complex

19

what cell in the spleen produces the autoAbs in ITP?

plasma cells

20

after what event does acute ITP surface?

acute viral infection or IMMUNIZATION; self limited

21

What type of Ig is involved in ITP?

IgG

22

Chronic ITP is assc'd with other autoDz like....

SLE

23

how can newborns get ITP?

IgG can cross the placenta from mom with ITP/SLE

24

What is the PT/PTT like in ITP?

NORMAL; just not ENOUGH PLTs!

25

how does the bone marrow look in ITP?

increased megakaryocytes

26

what is the initial Tx for ITP?

corticosteroids

27

What is the Tx for symptomatic bleeding in ITP?

IVIG; just buys you time

28

What is the ultimate Tx for ITP?

splenectomy; removes the source of Abs and cuase of PLT destruction

29

What is the ultimate Tx for ITP?

splenectomy; removes the source of Abs and cuase of PLT destruction

30

What causes the shearing of RBCs in MAHA?

formation of microthrombi

31

TTP is due to decreased (blank), an enzyme that cleaves vWF for degradation

ADAMTS13

32

TTP is due to decreased (blank), an enzyme that cleaves vWF for degradation

ADAMTS13

33

MAHA is seen in what two qualitative PLT disorders?

TTP and HUS

34

Is decreased ADAMTS13 levels a congenital or acquired def?

acquired strangely enough!; seen in adult females

35

(TTP/HUS) is caused by drugs or infection

HUS

36

What E. coli toxin damages endothelial cells in the kidney and brain in HUS?

E. coli verotoxin

37

What are the common clinical findings in TTP/HUS?

1. skin and mucosal bleeding2. MAHA3. fever

38

What clinical finding lets you know you have HUS and TTP?

renal insufficiency

39

What clinical finding lets you know you have TTP and not HUS?

CNS abnormalities

40

What are the lab values for TTP and HUS:PLTbleeding timePT/PTTHgbPeripheral smearBone marrow biopsy

low PLTincreased bleeding timenomral PT/PTT; coag cascade not involved!!!low Hgb aka anemiaschistocytes on smearincreased megakaryocytes on bone marrow biopsy

41

Bernard-Soulier syndrome is due to a genetic (blank) deficiency causing impaIred platelet ADHESION

GPIb

42

What finding do you see on smear in Bernard-Soulier syndrome?

enlarged PLTs; Big-Suckers

43

Glanzmann thrombasthenia is a genetic (blank) deficiency causing impaired PLT AGGREGATION

GPIIb/IIIa

44

Aspiriin irreversibly inhibits COX leading to a lack of (blank) and impairs aggregation

TXA2

45

T/F: both adhesion and aggregation are impaired in uremia

TRUE

46

secondary hemostasis generates (blank) which stabilizes the PLT plug

thrombin

47

Thrombin converts fibrinogen to (blank)

fibrin

48

The formation of fibrin allows it to be (blanked) to generate strength

cross-linked

49

Where are the coagulation factors produced?

in the liver

50

T/F: coag factors are produced in an inactive state

TRUE

51

What is the activating substance for the extrinsic (activates VII) pathway?

tissue thromboplastin (TT)

52

What is the activating substance for the intrinsic (activates XII) pathway?

subendothelial collagen (SEC)

53

What are the three things needed to activate the coag cascade?

1. activating factor (SEC or TT)2. phospholipid surface of PLTs3. Calcium from PLT dense granules

54

What distinguishes 2ry hemostatic disease from 1ry?

2ry causes deept tissue bleeding into muscles and joints (hemarthrosis) and rebleeding after surgical procedures (circumcision and tooth extraction common)

55

What factors are in the intrinsic pathway?

12, 11, 9, 8

56

What factors are in the extrinsic (tissue factor) pathway?

7; 7 is lucky, luck is extrinsic

57

What factors are in the common pathway?

5, 2, 1

58

What factors are activated by Vit. K?

2, 7, 9, 10, C, S

59

(PT/PTT) measures the extrinsic pathway (7)

PT; TT activates 7, PT and TT both have 2 letters

60

(PT/PTT) measures the intrinsic pathway (12)

PTT; SEC activates 12, PTT and SEC both have 3 letters

61

Hemophilia A is caused by a def of what factor?

AAAAAAAAA-8!

62

What is the mode of inheritance in males of hemophilia A?

x-linked

63

T/F: hemophilia A can present with no family history

TRUE

64

What is the most common presentation of hemophilia a?

deep tissue bleeding after surgery

65

T/F: severity of hemophilia A is in a range depending on how def you are

TRUE

66

What are the lab values for hemophilia a?PT/PTTfactor levelsPLTbleeding time

HI PTTnormal PTlow FVIIINORMAL PLTnormal bleeding time (if superficial can use primary hemostasis)

67

How do you treat hemophilia A?

recombinant FVIII

68

What is Christmas disease ?

hemophilia B, factor 9 def

69

What is the only difference between hemophilia A and B?

B has a 9 def

70

T/F: a mixing study will normalize the PTT in both hemophilia a and B

TRUE

71

T/F: a mixing study will normalize PTTT in a coagulation factor inhibitor

FALSE; factor will overwhelm the mixed serum

72

What is the most common anti-factor inhibitor?

anti-8

73

T/F: inhibitor disorders can cause qualitative and quantitative disorders

TRUE

74

What is the most common INHERITED coag disorder?

vW disease

75

How does vW disease normally present?

mild skin and mucosal bleeding

76

vW disease is due to impaired PLT (adhesion/aggregation)

adhesion

77

Describe the lab values for vW diseasebleeding time PT/PTTPLT Ristocetin test

increased bleeding timeincreased PTT: decreased FV8 b/c vWF stabilizes 8normal PTabnormal ristocetin leading to NO agglutination

78

What is the Tx for vW disease?

desmopressin

79

Desmopressin increases vWF release from the (blank) bodies of endothelial cells

weibel-palade

80

Vit. K is activated by (blank) in the liver

epoxide reductase

81

Vit. K gamma carboxylates what factors?

2 7 9 10 C S

82

PT is used to test (heparin/coumadin) levels

PT = coumadin/warfrintwo letters, two drug names

83

PTT is used to test (heparin/coumadin)

PTT = heparin; HEParin has three letters like PTT

84

Coumadin blocks (blank) activity resulting in less activated Vit. K

epoxide reductase

85

what are the three scenarios in which you see a Vit. K def?

1. newborns --lack of GI bacteria to make vit. K2. long term abx therapy3. malabsorption

86

How does liver failure lead to problems with the coag cascade?

Liver is the source of all the factors AND of Vit. K activation. DECREASED PRODUCTIONDECREASED ACTIVATION

87

How does a large volume transfusion mimmic a coag cascade def?

Works to dilute the factors

88

WHat is another name for factor I?

fibrinogen

89

What is another name for prothrombin?

factor II

90

What coag factor is made by the Kuppfer cells in the liver?

FVIII

91

WHere is Prekalikrein made?

liver

92

Where is high molecular weight kininogen made?

liver

93

What is another name for factor XIII

fibrin stabilizing factor

94

What is Hagemann factor?

FXII

95

What is christmas factor

FIX

96

What is antihemophilic factor?

FVIII

97

What two factors make up the prothrombinase complex?

Va and Xa

98

What three factors make up the tenase complex?

VIIIa, Xa, and Ca

99

What two factors are needed to convert XII to XIIa?

prekallikrein and high molecular weight kininogen

100

What ion is needed to transform VIIIa to X?

Ca

101

What factor is needed to take cross link fibrin?

XIIIa

102

What factor is needed to take Fibrinogen to fibrin?

IIa

103

Plasmin degrades what end product of the coag cascade?

fibrin

104

what coag path is activated by tissue injury?

Extrinisc via 7

105

Which coag path is activated by contact?

Intrinsic path

106

What test is done by adding phospholipid (contact activator) to calcium and plasma?

PTT

107

What test is done by adding tissue factor and phospholipid to plasma?

PT

108

What test screens for qualitative PLT disorders?

bleeding time

109

What disease presents with this PENTAD of symptoms:1. thrombocytopenia2. hemolytic anemia3. neurologic abn.4. renal abn.5. fever

TTP

110

what is the mode of inheritance of activated protein C resistance?

Auto Dom

111

(blank) is responsible for 50% of hereditary thrombophilia

activated protein C resistance

112

What is the MOA of activated protein C resistance? (think Factor V)

heterozygosity of FV Leidin which makes FVL resistance to inactivation via protein C

113

An anthithrombin deficiency leads to no inactivation of what factors?

II, IXa, Xa, XIa, XIIIa2 9a 10a 11a 12a

114

what is the MOA of anthithrombin?

auto dom

115

Protein C is activated by the (blank) complex

thrombin-thrombomodulin complex

116

What is the cofactor for the thrombin-thrombomodulin complex?

protein S

117

Acquired (blank) deficiency may be due to coumadin therapy, liver disease, and pregnancy

protein C

118

Antiphospholipid syndrome includes what two antibodies?

lupus anticoagulant syndromeanti-cardiolipin syndrome

119

In what diseases do you seen antiphospholipid syndrome?

lupus, primary APL syndrome, HIV, malignancy, collagen vascular disorders, and with drugs

120

What is the second most common causes of inherited thrombophilia?

prothrombin variant

121

thrombin can act on what activated factors?

2a 9a 10a 11a 12a

122

Is the protein C receptor antithrombotic or prothrombotic?

anithrombotic

123

Is tPA antithrombotic or prothrombotic?

antithrombotic

124

Is Thromboxane antithrombotic or prothrombotic?

prothrombotic

125

Are NO and prostacyclin antithrombotic or prothrombotic?

anithrombotic

126

What platelet receptor binds vWF?

GP1b

127

What platelet receptor binds fibrinogen?

GpIIb/IIIa

128

What platelet receptor binds fibronectin?

GPIc/IIa

129

What platelet receptor is an adhesion molecule?

CD62P (P-selectin)

130

What platelet receptor binds initiates platelet activation when bound by thrombin?

thrombin receptor

131

What platelet receptor binds initiates PLT activation when bound by ADP?

ADP receptor

132

What platelet receptor binds collagen?

GPIa/IIa

133

T/F: PLTs contain red cell antigens

TRUE

134

T/F: PLTs contain Rh factor

FALSE

135

What class of MHC ag is present on PLTs?

MHC I

136

What particular MHCs are present on PLTs?

HLA-A, B, and C

137

What is contained within the dense granules of PLTs?

ATPADPCaSerotonin

138

What is contained within the a-granules of PLTs?

vWFFibrinogenFVVEGF, EGF, PDGFAngiostatin, thrombospondin, endostatinPF-4, IL-8, CCL5

139

PGI2 released by endothelial cells has a (pos/neg) effect on the coag cascade

negative

140

Tissue Factor Pathway Inhibitor blocks what conversion?

7 to 7a

141

tPA prevents what final step of stabilizing the PLT plug?

cross linking of fibrin;tpA converts plasminogen to plasmin, and plasmin blocks the cross linking

142

What test do you use to screen for vW disease?

bleeding time

143

T/F: bleeding time is useful to predict the risk of bleeding during surgery

FALSE

144

What test uses ADP, epi, arachidonate, collagen, and ristocetin to determin PLT aggregation?

PLT aggregometry

145

What is PLT flow cytometry used to Dx?

def. of PLT surface glycoproteins and disorders of PLT activation

146

INR is used to monitor (heparin/coumadin) therapy

coumadin

147

INR references the (PT/PTT)

PT

148

What test is used to monitor heparin, hirudin, or argatroban therapy?

aPTT

149

What test is used to test the presence of functional fibrinogen?

TT

150

What causes prolongation of the thrombin time?

heparin, hirudin, argatroban and dysfribrinogenemia

151

What does a mixing study screen for?

presence of inhibitors

152

T/F: mixing studies excludes the presence of heparin

TRUE

153

If there is at least 50% activity on the mixing study, then you know that the prolongation is due to (blank)

a factor deficiency

154

If there is less than 50% activity in the mixing study, then you know that the prolongation is due to (blank)

presence of an inhibitor

155

D-dimers are formed by the degradation of what molecule in the clot?

fibrin

156

The fuck do you use an Anti-Xa assay for?

monitor unfractionated or LMWH therapy

157

Males tend to have (coag/PLT) bleeding disorders

coag

158

females tend to have (coag/PLT) bleeding disorders

PLT

159

Type I vW disease is (quantitative/qualitative) disorder

quantitative; not enough vWF

160

Describe the lab values for Type I vW disease:PTPTTBT (bleeding time)FVIII levels

normal PTincreased PTTincreased bleeding timedecreased FVIII

161

Type II vW disease is (quantitative/qualitative)

qualitative

162

Type IIM vW prevents vWF from binding to (blank)

GpIb

163

Type IIN vW is shows reduced binding of vWF to (blank)

FVIII

164

Type IIa vW is absence of (blank)

high molecular wt. vWF multimers

165

What is the only lab value that is markedly changed in vWF IIa?

ristocetin agglutination decreased

166

vW disease IIb is spontaneous binding of vWF to (blank)

PLTs

167

T/F: vW IIa and IIb both have decreased high molecular wt. vWF multimers

TRUE

168

What should you not give to someone with vW IIb?

DDAVP: profound thrombocytopenia and bleeding

169

What is wonky about the ristocetin test in vW IIb>?

it is increased since there is spontaneous PLT binding

170

In what disease do PLTs lack the PLA1 ag?

Glanzmann thrombasthenia

171

IN what disorder to PLTs fail to aggregate with all agonists except risocetin?

Glanzmann thrombasthenia

172

Hermansky-PudlakChediak-HigashiWiskott-AldrichAre all (blank) diseases with no second wave of aggregation

dense granule

173

In alpha granule disease, aggregation is blunted with all agents except (blank)

ADP

174

Gray PLT syndrome is a (a/dense) granule disorder

alpha

175

ASA and NSAIDS inhibit what enzyme?

COX-1

176

What molecule released by first wave PLTs from the dense granules signal for the second wave aggregation?

tXA2

177

Is the effect of ASA or NSAIDS on COX-1 irreversible?

ASA

178

Ticlopidine and Clopidogrel inhibit (blank) mediated PLT activation

ADP

179

Abciximab, Eptifibatide, Tirofiban inhibit the (blank) receptor, aka fibrinogen receptor

GpIIb/IIIa

180

Abciximab, Eptifibatide, Tirofiban will cause impaired aggregation to which agonists?

all except ristocetin

181

Ticlopidine & Clopidogrel will cause impaired aggregation against which agonist?

ADP

182

What bleeding disease is made by a diagnosis of exclusion?

ITP

183

Heparin induced thrombocytopenia is IgG binding to what complex?

Heparin-PF4 between the drug and the PLT

184

T/F: bleeding is rare in HIT

TRUE

185

T/F: thrombosis is likely in HIT

true, as strange as it is considering the name; PLTs will aggregate and activate the fucking cascade

186

Liver disease results in chronic DIC from an impaired clearance of (blank)

d-dimer

187

anti-thrombin def. results in (arterial/venous) thromboses

venous

188

T/F: homozygous anti-thrombin def is incompatible with life

TRUE

189

antibodies against B2 glycoproteins and prothrombin are most likely what type of Ab?

antiphospholipid; can be classified as lupus anticoagulant or anticardiolipin

190

phenytoin, quinidine, hydralazine, procainamide, phenothiazines, IFN, cocainecan all cause secondary (blank)

antiphospholipid syndrome

191

Coumadin therapy may result in an acquired (blank and blank) def

protein C and S

192

Ca is necessary in the conversion of what factor from the intrinsic pathway to the common pathway?

8a to X

193

What PLT surface marker can HEP bind to?

PF4

194

What causes PLT destruction in heparin induced thrombocytopenia?

IgG binding to HEP-PF4

195

What activates the PLTs in HIT?

the fragments of the destroyed PLTs, leading to thrombosis

196

DIC can lead to (blank) of downstream tissue

infarction and ischemia

197

Where do you see bleeding in DIC?

IV sites and mucosal surfaces

198

How does pregnancy cause DIC?

TT from the amniotic fluid may initiate coag cascade

199

Sepsis from what two bugs can cause DIC?

E. coli and N. meningitidis

200

Macrophages release what two cytokines during sepsis that can lead to DIC?

TNF-a and IL-1

201

What is is about infx with E. coli and N. meningitidis that leads to DIC?

release of endotoxins

202

(blank) from adenocarcinoma can lead to DIC

mucin

203

Primary granules that go on to form Auer rods in (blank) can cause DIC

Acute promyelocytic leukemia

204

what kind of snake bite can cause DIC?

rattlesnake

205

What are the lab values for DIC?PLTPT/PTTfibrinogenwhat type of anemia

LOW PLT (lots of little clots)INCREASED PT AND PTT (consumption of cascade)decreased fibrinogen (making clots)MAHA

206

What is the best test to screen for DIC?

D-dimer

207

Are d-dimers formed from the splitting of fibrin or fibrinogen?

fibrin; FROM LYSIS OF ALREADY PRESENT CLOT

208

Besides addressing the underlying condition causing the DIC, what supportive care can you give the patient?

transfusion of cryoprecipitate

209

What converts plasminogen to plasmin?

tPA

210

Plasmin cleaves (blank) and serum (blank), destroys coagulatoin factors, and blocks platelet (aggregation/adhesion)

cleaves fibrin and serum fibrinogenblocks PLT aggregation

211

What inactivates plasmin?

a2-antiplasmin

212

A radical prostatectomy resulting in large releases of urokinase or cirrhosis of the liver resulting in decreased a2-antiplasmin can both result in increased (blank)

bleeding

213

What other disorder do issues of fibrinolysis resemble clincally?

DIC

214

Describe the labs for fibrinolytic disorders:PT/PTTbleeding timePLTD-dimers (present/absent)

increased PT/PTTincreased bleeding timeNORMAL PLTS; THERE ARE NO CLOTS, JUST ACTIVATION OF CLOT BUSTERNO D-DIMER BECAUSE NO ACTUAL CLOTS

215

What is the Tx for issues of tPA overdose or fibrinolytic disorders?

aminocaproic acid, blocks activation of plasminogen

216

T/F: a thrombus may occur in an artery or vein

TRUE

217

Where do DVTs normally occur?

below the knee

218

DVTs are characterized by lines of (blank) and attachment to the vessel wall

lines of Zahn

219

what are the three risk factors for thrombus that makeup Virchow's triangle?

1. disruption in blood flow2. endothelial cell damage3. hypercoagulable state

220

T/F: turbulent non-laminar blood flow can cause clot formation

TRUE

221

Immobilization, cardiac wall dysfunction, and anuerysm are all things that cause a (blank) in blood flow

disruption

222

Endothelial cells prevent thrombosis by protecting expsoure to subendothelial (blank) and underlying tissue factor

SEC

223

What two molecules do the endothelial cells produce that prevent thrombosis?

PGI2 and NO; PGI2 is opposite of TXA2 and NO causes vasodilation

224

Endothelial cells secrete heparin-like molecules that augment (blank) which inactivates thrombin and coag factors

ATIII

225

What are the three actions of tPA?

1. converts plasminogen to plasmin2. cleaves fibrin and serum fibrinogen and destroys coag factors3. blocks PLT aggregation

226

Atherosclerosis, vasculitis, and high levels of (blank) can cause endothelial damage

homocysteine

227

What two vitamin defs can lead to high homocysteine?

Vit. B12 and folate def

228

What enzyme deficiency can lead to homocysteine buildup?

Chystathionine beta synthase (CBS)

229

Vessel thrombosis, mental retardation, lens dislocation, long slender fingers, and high levels of homocysteine are indicative of what congential enzyme def?

CBS

230

Hypercoagulable states are due to excess (blank) or deficiencies of (blank)

excess procoagulants or def. anticoags

231

DVTs normally ocurr below the knee or in what two arteries?

hepatic and cerebral

232

Protein C or S def decreases (neg/pos) feedback on the coag cascade

negative, they are ANTICOAGS

233

What factor do proteins C and S inactivate?

FVIII

234

Protein C and S def has an increased risk of what drug reaction?

warfarin skin necrosis

235

Warfarin works by decreasing Vit. K dependent factors. Why does a protein C or S deficiency cause concern at the beginning of warfarin Tx?

The half life of C and S is shorter than that of the 2 7 9 10; therefore the anticoags disappear faster than the coags and the pt is at risk of a microvessel thrombus

236

What is Factor V Leidin?

FV that lacks the cleavage site for C and S

237

What is the most common cause of hypercoagulable state?

Factor V Leidin

238

An inherited point mutation that increases prothrombin expression is caused by (blank)

Prothrombin 20210A;

239

ATIII def decreases the effect of what class of molecules released by the endothelium?

heparin like molecules

240

What is unique about the PT/PTT in ATIII def when treating with heparin?

PTT does not rise with standard heparin dosing ATIII def; since aTIII is bound by HEPARIN-like molecules, the action of heparin is going to be limited!!

241

Once high doses of heparin are given to acheive an anticoag'd state in ATIII def pts, what is given to maintain their blood viscosity?

coumadin

242

The pill increases a hypercoagulable state via what mechanism?

estrogen increases the production of coagulation factors.

243

What is the most common type of embolus?

thromboembolus

244

What histo finding is characteristic of an atherosclerotic embolus?

cholesterol clefts in the embolus

245

a (blank) embolus is common after traumatic bone fractures (long bones) and soft tissue trauma

soft tissue trauma

246

in relation to the trauma, when does a fat embolus form?

while trauma is still present or during repair

247

What clinical findings are associated with a fat emoblus/

SOB, and skin petechiae on the CHEST

248

(blank) emobolus is seen in decompression sickness

gas embolus

249

What is the chronic form of gas embolus that causes multifocal ischemic necrosis of bone/

Caisson disease

250

Gas embolus may also form during what type surgery?

laparoscopic

251

Amniotic fluid is rich in what coagulation precursor?

TT

252

Amniotic fluid emboli present with what symptoms as they travel the lung, brain, and systemically?

SOB, neurologic symptoms, DIC

253

Squamous cells and keratin debris in the embolus is characteristic of what?

amniotic fluid embolus

254

PE normally arises from a DVT in the lower extremity involving what three veins?

1. femoral2. iliac3. popliteal

255

T/F: PE is normally clinically silent

true, b/c the lung has dual blood supply

256

What percent of PEs result in infarction?

10%; need pre-existing compromise!

257

what symptoms do pts with PE have?

SOB, hemoptysis, pleuritic chest pain, pleural effusion

258

Describe the labs for PE:V/Qspiral CTLower extremity USD-dimer

V/Q mismatch; perfusion is abnormalCT shows vascular filling defectUS shows a DVTelevated D-dimer because they are trying to lyse the PE AND the DVT!!

259

What type of embolus in PE causes sudden death?

saddle embolus; death by electromechanical dissociation

260

WHat happens with chronic pulmonary emboli?

plumonary HTN

261

Where do most systemic emoboli come from?

left heart, normally go to lower extremities