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Auburn ECC > Coag/Transfusion > Flashcards

Flashcards in Coag/Transfusion Deck (273):
1

What are three alpha 2b beta 3 (GIIb/IIIIa) receptor antagonists?

Abciximab eptifibatide tirofiban

2

Thrombomodulin MOA? Where does it come from?

Binds thrombin > ACTIVATES PROTEIN C > inactivates Va and VIIIa (with cofactor protein S) & promotes fibrinolysis (inactivates PAI-1 & inhibits TAFI)Thrombomodulin from endothelium

3

What is the platelet receptor for collagen?

GPVI

4

Antiinflammatory effects of aPC

Inhibits apoptosisDecrease NF-kBDecrease inducible TFDecrease adhesion molecules

5

What suppresses fibrinolysis?

PAI-1TAFI

6

PAI-1 upregulated by

TNF-a and CRP

7

Heparin MOA

Facilitates AT-mediated inactivation of thrombin and factor Xa (also 7, 9, 11, 12)Facilitates release of TFPI from endothelial cellsPS binds to heparin-binding domain of endothelial cell matrix protein, thrombospondinInhibits complement and hemolysis induced thrombin generation

8

What accumulates in stored blood?

IL-1, IL-6, IL-8, bactericidal permeability increasing protein, phospholipase A2, TNF-a

9

TFPI MOA

inhibits EXTRINSIC pathwayTFPI from endothelium

10

How long can FWB be stored?

8h

11

How long can PC and PRP be stored?

5 d at 22C with gentle agitation

12

What are platelet storage lesions?

Change in shape from discoid to spherical, generation of lactate from glycolysis with decrease in pH, release of platelet granules, decrease in fxn, reduction in posttransfusion recovery and survival

13

Why should you not chill platelets?

chilling causes vWF receptors (GP1balpha-IX complex) on platelet surface. The integrin receptor alphaMbeta2 (C3R) of hepatic macrophages recognizes the receptor and eats the platelet

14

Half life of factor II (in dogs)?

41 h

15

Half life of factor VII (in dogs)?

6.2 h

16

What is the platelet receptor for VWF?

GP 1b-IX-V

17

How can giving pRBCs help with hemostasis?

1. dispersion of platelets to periphery 2. increase plt contact with endothelium 3. release ADP 4. scavenge NO (which inhibits plts) 5. increase production of TXA2 by platelets at bleeding site

18

The platelet receptor alpha 2b beta 3 (GIIb/IIIIa) binds?

FIBRINOGENalso vWf

19

HES-induced hypocoagulability is due to?

1. Reduced availability of alpha 2b beta 3 (GIIb/IIIIa) platelet receptors.2. Decreased vWF (and VIII)3. Altered FXIIIa fibrin crosslinking4. HES molecules coat surface of platelet limiting binding of ligands

20

LMWH MOA?

augments inhibitory effect of antithrombin on FXa.

21

What is the test of choice to monitor LMWH?

Anti-Xa activity

22

What is the test of choice to monitor warfarin?

Prothrombin time (PT) / INR

23

What is INR?

PT results vary from different manufacturers (different tissue factor properties), so INR developed to standardize results.

24

What is the test of choice to monitor unfractionated heparin?

activated partial thromboplastin time (aPTT) or anti-Xa activity

25

How many subunits must UFH have in order to bind AT and thrombin?

18

26

A patient with an increased risk of bleeding from LMWH overdose would have a low, normal, or high anti-Xa level?

high anti-Xa level

27

List 3 secondary agonists released by activated platelets to recruit additional platelets, amplifying the initial response

Thromboxane A2, ADP, and serotonin

28

Describe 2 mechanisms for platelet adhesion

Sub endothelial collagen via Platelet glycoprotein VI, or collagen bound vWF via glycoprotein 1b receptor

29

The final common pathway for all platelet agonists is the activation of?

Platelet integrin alphaIIbbeta3 receptor (aka glycoprotein IIbIIIa receptor); this induces a conformational change and exposes binding domains for fibrinogen

30

What factors does the PT test?

II, VII, X, V, and fibrinogen

31

What is tested with an aPTT?

Factors II, V, VIII, IX, X, XI, XII, prekallikrein, HMWK, or fibrinogen

32

What are FDP's?

Fibrinogen degradation products, generated when fibrinogen, soluable fibrin, or cross-linked fibrin is lysed by plasmin.

33

List 10 causes of elevated FDPs

Neoplasia, sepsis, SIRS, DIC, hepatic dysfunction, heart failure, thromboembolism, IMHA, heat stroke, trauma, and GDV

34

What is a D-dimer?

Neo-epitope produced when soluable fibrin is crosslinked by fXIIIa. The epitope is exposed by plasmin-induced cleavage of cross-linked fibrin

35

How do D-dimers differ from FDPs?

D-dimers are specific for active coagulation and fibrinolysis; indicate the activation of thrombin and plasmin (not just plasmin like FDPs)

36

List 6 acquired causes of hypofibrinogenemia

Hemodilution, massive transfusion, hepatic dysfunction, DIC, sepsis, and after thrombolytic therapy

37

What is the thrombin time a measure of?

Tests functional fibrinogen via a measure of the time taken for a standardized thrombin solution to convert fibrinogen to fibrin

38

List 3 causes of a prolonged thrombin time

Hypofibrinogenemia, dysfibrinogenemia, or presence of factors (heparin, FSPs) that inhibit fibrin polymerization

39

What is R and what does it represent?

Reaction time; represents enzymatic portion of coagulation (secondary homeostasis)

40

What is K? What does it represent?

Clotting time; represents clot kinetics, largely determined by clotting factors, fibrinogen, and platelets

41

What is the angle? What does it represent?

The angle represents the rapidity of fibrin accumulation and cross-linking and depends largely on fibrinogen, as well as platelets and factors.

42

What is MA and what does it represent?

Maximum amplitude; it represents the ultimate strength of the fibrin clot, dependent primarily on platelet aggregation (number and function) and to a lesser extent, fibrinogen

43

What is G and what does it represent?

Clot shear elastic modulus; represents overall coagulant status

44

What is the formula to calculate G?

G= 5000XMA/(100-MA)

45

What is LY60 and what does it represent?

Extent of clot lysis at 60 minutes after MA determined by the percentage decrease in amplitude at that time after MA. Measures fibrinolysis

46

List 8 causes of thrombocytopenia from decreased platelet production

Drug induced, IM megakaryocytic hypoplasia, viral (FeLV/FIV), chronic rickettsial disease, estrogen secreting neoplasia, myelodysplasia, megakaryocytic leukemia, cyclic thrombocytopenia, radiation, idiopathic bone marrow aplasia, post vaccination

47

List 7 causes of consumption/sequestration thrombocytopenia

DIC, microangiopathies, splenic torsion/hypersplenism, sepsis, hepatic disease, severe acute hemorrhage, severe hypothermia, HUS

48

List 9 causes of acquired thrombopathia

Drugs, uremia, anemia, hepatic disease, hypothermia, colloid hemodilution, myeloproliferative disorders and paraproteinemias, erhlichiosis, snake venom, DIC

49

List 10 drugs associated with thrombocytopathia

NSAIDs (aspirin and non aspirin), carbenicillin, cephalothin, moxalactam, sulfonamides, CCB, methylxanthines, B blockers, barbiturates, heparin, HES

50

List 3 causes of acquired vascular disorders and 1 cause of inherited

Acquired- vasculitis, cushings, arteriosclerosis Inherited - Ehlers-Danlos syndrome

51

List 8 inherited causes of thrombopathia

vWD, signal transduction disorders, Glanzmann's thrombasthenia, Chediak-Higashi syndrome, selective ADP deficiency, cyclic hematopoiesis, procoagulant expression disorders, macrothrombocytopenia

52

What is vWD, what breeds are affected?

Deficiency in vWF (type 1), decreased function of large proteins (type 2), or a complete absence of vWF (type 3). Affects many dog breeds (dobies!) rare in cats

53

What breeds have signal transduction disorders been reported in?

Bassett hound, Eskimo spitz

54

What is Glanzmann's thrombasthenia and what breeds does it affect?

Otter hound, Great Pyrenees

55

What is Chediak-Higashi syndrome? Whom does it affect?

Grey Persian cats

56

Whom is affected by selective ADP deficiency?

American Cocker Spaniel

57

In what breed is cyclic hematopoiesis inherited?

Grey collie

58

In what breed is Scott syndrome reported, what is another name for this?

GSD, procoagulant expression disorder

59

In what breed is macrothrombocytopenia reported?

CKCS

60

List 8 causes of acquired secondary homeostasis disorders

Vit K deficiency, hepatic failure, DIC, pharmacologic anticoagulants, hemodilution, severe hypothermia, acidemia, shock, massive trauma

61

Hypofibrinogenemia and dysfibrinogenemia are caused by a deficiency in what factor and this is inherited in what breeds?

FI deficiency; Bernese, Borzoi, Lhasa Apso, Vizla, Saint Bernard among others

62

Factor II deficiency causes what and is inherited in what breeds?

Hypoprothrombinemia, boxer, otter hound, English cocker spaniel

63

Factor VII deficiency causes what and in what breeds?

Hypoproconvertinemia; beagle, malamute, boxer, bulldog, miniature schnauzer, mixed breeds

64

What is hemophilia A and what animals does it affect?

FVIII deficiency; GSD, mixed breed dogs, other breeds, cats; X linked, mostly males affected

65

What is hemophilia B and whom does it affect?

FIX deficiency; numerous dog breeds, cats

66

What is Stuart-Power trait and whom does it affect?

FX deficiency; American cocker spaniel, JRT, mixed breed dogs

67

FXI deficiency causes what and in what breeds?

Plasma thromboplastin antecedent deficiency; English springer Spanial, Kerry blue terrier, Great Pyrenees

68

What animals have an inherited Vit K dependent factor deficiency been reported in?

Devon Rex cats

69

What is Hageman factor deficiency, whom does it affect, and is it a pathological condition?

FXII deficiency, min poodle, standard poodle, GSP, Shar Pei, cats; no

70

What is Chediak-Higashi syndrome?

An intrinsic platelet storage pool deficiency. Patients with this have prolonged bleeding times with normal platelet concentrations. Also have altered lysosomal granule formation and abnormal degranulation in neutrophils and platelets so aggregation response to collagen is absent.

71

What is Glanzmann's thrombasthenia?

Inherited intrinsic platelet functional defect which leads to a deficiency in alphaIIbbeta3 integrin and causes lack of fibrinogen binding. Corrected with experimental bone marrow transplantation and gene therapy

72

In what breed had a P2Y12 deficiency been reported and what does this cause?

Greater Swiss Mountain Dog; prevents activation via ADP induced outside in signaling for fibrinogen binding on the platelet surface at the alphaIIbBeta3 integrin

73

What is the mutation that alters protein signal transduction in inside out-outside in integrin signaling events in Landseers, Bassetts, and Spitz dogs?

Defect in the calcium-diacylglycerol guanine nucleotide exchange factor 1 gene (CalDAG-GEF1)

74

What is Canine Scott syndrome?

A defect so the phosphatidylserine is unable to be externalized for creation of a procoagulant surface. There is also decreased micro particle release. Diagnosis requires flow cytometry to show a difference in platelet function.

75

How is Canine Scott Syndrome treated?

Peri operative dimethylsulfoxide cryopreserved PRP transfusion plus a post operative antifibrinolytic

76

Thrombin has been shown to activate which members of the PAR family?

1,3,4

77

What does PAR mean?

Protease-activated receptors

78

According to The role of tissue factor in health and disease (JVECC 2009), what are the 4 coagulation proteases that activate PARs? PARs then mediate cell activation via what?

FVIIa, FXa, thrombin, TFG-proteins

79

TF activates what PAR receptor?

PAR 2

80

FXa activates what PAR receptor?

1, and 2

81

What are the 3 main endogenous anticoagulants?

TFPI, AT, and aPC

82

How does inflammation affect protein C production?

Down regulates PC pathway through inhibition of thrombomodulin and endothelial cell protein C receptor (EPCR) transcription so reduced ability to generate aPC. Neut elastases cleave TM from endothelial cells greatly reducing thrombomodulins activity. PC also dec in severe inflamm due to increased consumption and compromised ability to synthesize PC d/t hepatic dysfunction.

83

List the anti-inflammatory effects of TFPI

Decreased leukocyte activation and dampening expression of TNF alpha

84

Describe AT's anti-inflammatory effects

AT binds to endogenous endothelial cell GAGs (heparin sulfate and dermatan sulfate) which causes increased prostacyclin formation, decreased NF KB activation and decreased leukocyte activation and adhesion to endothelial cells.

85

Thrombophilia is...

Hypercoagulability as a result of inherited or acquired causes

86

What are some causes of thrombophilia in humans?

Factor V Leiden mutation or protein C deficiency

87

What is Virchow's triad?

Hypercoagulability, blood stasis/altered blood flow, endothelial dysfunction

88

What makes up the glycocalyx?

GAG's, proteoglycans, and glycoproteins

89

Vascular endothelial cells can be activated by what?

TNF-alpha, bradykinin, histamine, thrombin, and vascular endothelial growth factor (VEGF)

90

What anticoagulants rely on the glycocalyx?

Thrombomodulin, protein C, tissue factor pathway inhibitor,heparin cofactor II

91

How does the glycocalyx function as a mechanoreceptor?

Sensing altered blood flow and releasing nitric oxide during conditions of increased sheer stress to maintain appropriate organ perfusion.

92

List 3 important effects nitric oxide has in relation to the glycocalyx

Inflammatory response, leukocyte adhesion to the endothelium, and inhibition of platelet aggregation

93

List 5 substances contained in Weibel-Palade bodies

Ultra large multimers of vWF, P-selectin, IL-8, tPA, fVIII

94

How are UL-vWF usually dealt with in health?

Quickly cleaved by ADAMTS13, a metalloproteinase and disintegrin-like with thrombospondin type 1 repeats

95

What is the function of UL vWF?

Bind platelet GP 1balpha receptors and initiate platelet tethering and activation; are more active for platelet adhesion and activation than smaller vWF multimers

96

How does tissue factor promote inflammation?

Through the activation of nuclear factor kB, leading to production of TNF-alpha

97

What happens to platelets upon activation?

Shuffle negatively charged phospholipids (phosphatidylserine and phosphatidylethanolamine) to the surface. These provide catalytic surface needed for tenase and prothrombinase complexes for the propagation phase of clot formation

98

With activation platelets greatly increase the number of copies of what on their surface?

Active fibrinogen receptor - glycoprotein IIbIIIa, aka integrin alphaIIb beta3

99

What are the contents of alpha and dense granules secreted when platelets are activated

Calcium, factor Va, serotonin, fibrinogen, P-selectin, and ADP. Feline alpha granules also release vWF

100

How does AT act?

To inhibit thrombin and fXa, lesser inhibitory effects on fIXa and the fVIIa-TF complex

101

How can AT activity be increased?

Heparins, or, in their absence, by binding to Thrombomodulin in the presence of thrombin

102

List the 3 mechanisms that can decrease AT in systemic inflammation

Consumption (due to thrombin generation), decreased production, degradation by neutrophil elastase

103

Where is TFPI found?

Endothelial cells, platelets, mononuclear cells, vascular smooth muscle, cardiac myocytes, fibroblasts and megakaryocytes

104

What is the function of the protein C system?

Important inhibitor of fVa and fVIIIa

105

How is protein C activated?

When trace amounts of thrombin bind TM located on the endothelium, predominantly in microcirculation; accelerated in presence of EPCR and cofactor protein S

106

What 3 electrolyte abnormalities might be expected with massive transfusion?

Hypocalcemia, hypomagnesemia, and hyperkalemia

107

What hemostatic defects might be associated with massive transfusion?

Thrombocytopenia, secondary dilutional coagulopathy, and hypofibrinogenemia

108

Other than electrolyte and hemostatic abnormalities, list 4 other abnormalities associated with massive transfusion

Metabolic acidosis, TRALI, hypothermia, immunosuppression, other transfusion reactions, transmission of infectious diseases

109

Describe how massive transfusion causes hypocalcemia and hypomagnesemia

Citrate (anticoag added to blood products) binds rapidly to Ca and Mg with equal affinity resulting in decreases in iCa and iMg. ICa reported to resolve quickly once perfusion is restored as citrate is rapidly metabolized by the liver

110

When is treatment with calcium glauconate indicated in regards to massive transfusion?

When hypocalcemia is severe or when hypotension, muscle tremors, arrhythmias, or prolonged QT interval are present

111

What causes hyperkalemia associated with massive transfusion?

K levels rise over time d/t inactivation of Na-K-ATPase pumps by cold storage temperatures (less likely in dogs due to lower intracellular K stores). More likely K leakage from damaged tissues, extra cellular K shift secondary to acidosis, and reduced K excretion from oliguria

112

What is the cause of thrombocytopenia associated with massive transfusion?

Blood loss and dilution (blood products devoid of platelets after 2 days due to cold storage temperatures causing cell oxidation and death

113

Why is thrombocytopenia from dilution generally less severe than what would be predicted by the degree of dilution?

Platelets are released from stores in the lungs and spleen

114

Other than dilution, list 2 other causes of thrombocytopenia related to MT

Consumption of platelets and clotting factors (secondary to shock, sepsis, SIRS, blunt trauma); platelet dysfunction resulting from acidosis or hypothermia

115

Hemostasis is generally maintained as long as clotting factors are at least _____% of normal and PT and aPTT are not prolonged above ______.

30%; 1.5 times normal

116

Loss and replacement of 1 blood volume removes ______% of circulating factors in plasma

Slightly less than 70%

117

Acute coagulopathy of trauma is believed to result from what?

Altered coagulation enzyme activity, hyperfibrinolysis, and release of activated protein C secondary to tissue hypoperfusion, tissue injury, and acidosis.

118

Ratios of FFP/platelet to RBC ratios of what have been associated with decreased mortality in human patients?

Increased (at least 2:1, up to 1:1)

119

Describe 2 ways hypothermia can lead to coagulopathy in MT

Inactivates the enzymes that initiate the intrinsic and extrinsic coag cascades and to enhance fibrinolysis. Severe hypothermia can result in decreased platelet activity.

120

What is the 'bloody viscous cycle' being recognized increasingly in human medicine as a leading cause of death after blunt trauma?

Progressive hypothermia, persistent acidosis, and inability to establish hemostasis

121

What are the 3 definitions of massive transfusion?

1. Transfusion of > 1 blood volume of blood or blood products within a 24 hour period2. Transfusion of 1/2 estimated blood volume in 3-4 hours3. Administration of 1.5 ml/kg/min of blood products over a period of 20 minutes

122

List the factor numbers and their descriptive names

I-fibrinogenII-prothrombinIII-tissue factorV- labile factorVII- proconvertinVIII- antihaemophilic factorIX- Christmas factorX- Stuart prower factorXI- plasma thromboplastin antecedentXII- hageman factorXIII fibrin-stabilizing factor, prekallikrein (fletcher factor), HMWK (fitzgerald factor)

123

What is the plasma half life of factor II?

65 hrs

124

what is the half life of factor VII?

5 hrs

125

what is the half life of factor IX?

25 hrs

126

what is the half life of factor X?

40 hrs

127

what is the half life of factor I?

90 hrs

128

what is the half life of factor V?

15 hrs

129

what is the half life of factor VIII?

10 hrs

130

what is the half life of factor XI?

45 hrs

131

what is the half life of factor XIII?

200 hrs

132

which coagulation factors require vitamin K for synthesis and Ca2+ for activation?

II, VII, IX, X

133

What is the role of endothelin?

It promotes vasoconstriction and decreases local blood flow

134

What substances other than tissue plasmin activator, act as plasminogen activators?

urokinasebradykininkallikreinsoluble fibrin (non cross linked)

135

When are D-Dimers produced?

Plasmin cleaves cross-linked fibrin into x-oligomers that are then broken down into D-dimers. They are only produced with active coagulation and subsequent fibrinolysis

136

What are the three main mechanisms that limit thrombus formation?

AntithrombinProtein CFibrinolytic system

137

What anticoagulant substances are synthesized by the intact endothelium?

ThrombomodulinProtein SHeparan sulfateTissue factor pathway inhibitor

138

Where is tissue factor pathway inhibitor synthesized?

LiverEndothelial cells

139

Name 5 causes of endothelial disruption that may result in thrombus formation

SepsisSystemic inflammatory diseaseHeartwormNeoplasiaTraumaShockIV catheterizationReperfusion injury

140

Name 5 conditions that may lead to abnormal blood flow and subsequent thrombus formation

Vascular obstructionCardiomyopathyEndocarditisCHFShockHypovolemiaProlonged recumbencyHyperviscosityHypoviscosityAnatomic abnormality

141

Name 5 conditions that may lead to increased coagulability and subsequent thrombus formation

PLNCushingsIMHAPancreatitisPLESepsisNeoplasiaDICHeart disease

142

Why are animals with PLE less prone to clot formation than animals with PLN?

PLE also causes loss of AT however they cause a concurrent loss of larger proteins maintains more of a balance between procoagulant and anticoagulant factors

143

Other than obstructing flow in a vessel, what other local effects do thromboemboli have?

They release vasoactive substances (thromboxane A2 and serotonin) that induce vasoconstriction and compromise collateral blood flow development around the obstructed vessel

144

Sonoclot ACT correlates with what on TEG

R time, K time, angle

145

CR on sonoclot correlates with what on TEG

all parameters

146

What does the Sonoclot do?

Measures changes in blood viscosity by detecting a change in mechanical impendance of a tubular, disposable, plastic probe oscillating vertically in a cuvette containing whole blood or plasma

147

How is platelet function determined on Sonoclot?

Not directly, calculated value based on both teh time it takes for the signature to peak, as well as degree of clot retraction

148

What 3 variables determined on Sonoclot

ACT, clot rate (CR), and platelet function (indirectly)

149

What does CR measure on Sonoclot?

rate of fibrin formation

150

Sonoclot correlated to several TEG parameters, platelet count, and fibrinogen, but not to other commonly used coagulation tests. T/F

T

151

MOA thrombomodulin

binds thrombin changing its substrate specificity and becomes an anticoagulant by activating protein C, with its cofactor, protein S, inactivates Va and VIIIathrombomodulin from endothelium

152

MOA TFPI

inhibits extrinsic pathwayTFPI from endothelium

153

What is the initiation stage of coagulation?

TF-VIIa makes a small amount of thrombin

154

What is the prothrombinase complex?

Va-Xa

155

What is the tenase complex?

VIIIa-IXaFxn: activates X to Xa which then binds with Va on platelet surface forming the prothrombinase complex to create thrombin burst

156

Antithrombin inhibits what factors?

2, 7, 9, 10, 11, 12

157

What dramatically increases AT activity?

heparan sulfate from endothelial cells (or heparin exogenously)

158

Effects of plasmin.

cleaves fibrin creating FDPsinactivates 5, 8, 9, 11, cleaves complement C3, enhances conversion of 12 to 12a and conversion of prekallikrein to kallikrein

159

What are inhibitors of plasmin generation

a2-antiplasmin, a-2 macroglobulin

160

Heparin MOA

Facilitates AT-mediated inactivation of thrombin and factor Xa (also 7, 9, 11, 12)Facilitates release of TFPI from endothelial cellsPS binds to heparin-binding domain of endothelial cell matrix protein, thrombospondinInhibits complement and hemolysis induced thrombin generation

161

How do you monitor heparin therapy?

anti-factor Xa (gold standard) or APTT (want 1.5-2.5 x normal)

162

What can affect APTT measurement with heparin therapy?

reagent used, high fibrinogen levels, antiphospholipid antibodies, increased circulating VIII, steroids, more low molecular weight multimers (can still have anti-factor Xa activity, but reduced ability to complex with thrombin, so APTT may appear subtherapeutic when it really is)

163

How do you monitor LMWH (enoxaparin, dalteparin)?

anti Xa only - b/c they are LMW do not complex to thrombin

164

What is the vWF platelet receptor?

Gb1b-IX-V

165

What's the difference between platelet rich plasma and platelet concetrate?

PRP is made by a soft spin at 1000 x 4 min of FWB (200 mls). If you spin again (hard spin, 2000 x 10 min), get platelet concentrate (40-70 mls)

166

How many platelets are in PRP and PC?

>100 x 10^9/L

167

Non immunologic complications of blood transfusion

pyrogen-mediated fever (most common), transmission of infectious agents, vomiting, mechanical hemolysis, CHF, hypothermia, citrate toxicity, pulmonary complications

168

Immunologic reactions to blood

acute and delayed hemolytic transfusion reactions manifesting as urticaria, anaphylaxis, graft vs host dz

169

Virchows triad

blood stasis, hypercoagulable state, endothelial damage

170

What coag factors increased in cushings?

5, 10, fibrinogen

171

What IL stimulates TF?

6 - predominantly

172

Where does heparan sulfate come from?

endothelial cells

173

When AT bound to heparan sulfate on endothelium, stimulates what factors regarding inflammation?

prostacyclin I2 and NF-kB

174

Negatively charged proteins on platelet surfaces when activated.

phosphatidylserine and phosphatidylethanolamine

175

What lives in Weibel Palade bodies

vWF, VIII, p-selectin, IL-8, TPA

176

What activates endothelial cells?

TNFa, bradykinin, thrombin, histamine, VEGF

177

What is the prothrombinase complex?

Va and Xa and prothrombin (II)

178

Feline platelet alpha granules have what that is special...

vWF (not in dog alpha granules)

179

What supports decrease in fibrinolysis?

decreased tPA, increased a2 antiplasmin, PAI-1, TAFI

180

What is MPC on Advia 120?

mean platelet component - granularity of platelets, activated platelets will have released their granules, so decreased MPC may indicate hypercoagulable state

181

G =

5000 x MA / (100-MA); higher = more hypercoagulable

182

Anticoagulant effects of aPC

inactivates Va and VIIIaenhances fibrinolysis

183

Antiinflammatory effects of aPC

Inhibits apoptosis, decreases NF-kB, decreases inducible TF, decreases adhesion molecules

184

How does inflammation alter the protein C pathway?

Inhibits thrombomodulin and endothelial cell protein C receptor transcription resulting in a decreased ability to generated APC

185

PAI-1 upregulated by

TNF-a and CRP

186

What is usually elevated with chronic end stage liver dz?

fVIII and vWF

187

What does thrombomodulin do?

activates protein C

188

Where is thrombomodulin at?

endothelial cells - its a transmembrane protein

189

What converts plasminogen to plasmin?

fibrin

190

What are antifibrinolytic drivers?

PAI-1, TAFI

191

Underlying conditions that explain the bleeding tendency in patients with decompensated chronic liver disease.

1. Portal hypertension causing hemodynamic alterations2. Endothelial dysfxn3. Development of endogenous heparin-like substances from bacterial infection4. Renal failure

192

What are the PAR receptors?

PAR1 binds TFVIIa, Xa, thrombinPAR2 binds TF-VIIa, Xa, trypsinPAR 3 and 4 bind thrombin

193

Bentley, JVECC, 2013 on coagulation with septic peritonitis, findings?

Preop PC >60% and AT >41.5% sensitive predictors of survival.TEG survivors were more hypercoagulable

194

TRALI

Occurs within 2-6 h of blood product, no pre-existing ALI, and no temporal relationship to alternative risk factors for ALIDue to anti-leukocyte antibodies, resolves rapidly, low mortality

195

Delayed TRALI

Occurs w/i 6-72 h after transfusion, occurs in 25% of critically ill transfused patients, mortality up to 40%Trauma, burns, sepsis increased riskRisk increased with transfusion of plasma-rich products, frozen plasma, and platelets, than transfusion with pRBC

196

Massive tranfusion risk of...

ARDS/ALI

197

TRALI theories:

1. Donor antibodies to antigens on recipient leukocytes, or less likely the other way around (in humans at least)2. mediated by an interaction b/t biologically active mediators in banked blood products and the lung (classic 2 hit theory - lung endothelium of recipient primed with neutrophils from critical dz, then transfuse blood with inflammatory mediators causing endothelial damage, capillary leak, and TRALI)

198

What accumulates in stored blood?

IL-1, IL-6, IL-8, bactericidal permeability increasing protein, phospholipase A2, TNF-a

199

Leukoreduction helps to prevent..

delayed TRALI

200

Plateletpheresis yield

3-4.5 x 10^11 vs. <1 x 10^11 for whole blood derived platelets

201

DMSO cryopreserved platelets yield

50%, half life 2 days

202

What is plateletpheresis?

selective removal of platelets from the donor's blood via an automated cell separator with return of RBCs and plasma to the donorReduces exposure of recipient to multiple donors

203

Platelets in PC?

8 x 10^10 per PC unit

204

Donor concern for plateletpheresis

citrate toxicity, hypocalcemia

205

How long can FWB be stored?

8 h

206

How long can PC and PRP be stored?

5 d at 22 C with gentle agitation

207

What are platelet storage lesions?

Change in shape from discoid to spherical, generation of lactate from glycolysis with decrease in pH, release of platelet granules, decrease in fxn, reduction in posttransfusion recovery and survival

208

Why can't you chill platelets?

chilling causes vWF receptors (GP1balpha-IX complex) on platelet surface. The integrin receptor alphaMbeta2 (C3R) of hepatic macrophages recognizes the receptor and eats the plateletGalactosylation decreases

209

What is thrombosol?

mixture of amiloride, adenoseine, and sodium nitroprusside to inhibit platelets - used with DMSO to improve platelet survival

210

DMSO platelet half life

2 d, vs. 3.5 d for fresh platelets

211

DMSO plt storage life

1 year

212

pRBC mechanism for the role in hemostasis

1. dispersion of platelets to periphery2. increase plt contact with endothelium3. release ADP4. scavenge NO (which inhibits plts)5. increase production of TXA2 by platelets at bleeding site

213

FWB contains how many platelets?

10 x 10^9 /L

214

Methods to decrease lymphocytotoxic antibodies.

leukoreductionultraviolet B irradiation

215

What diseases are most common in cats with DIC

cancer, pancreatitis, sepsis

216

What % cats have hemorrhage with DIC?

15%

217

Other findings, DIC cats, JVIM 2009.

All DIC cats had high PTTMedian PT of nonsurivors * higher than survivorsNo effect of heparin or transfusion on outcomeMost cats died or euth (7% survival)

218

Incidence of prolonged PT in dogs following GI decontamination for acute anticoagulant rodenticide ingestion. JVECC, 2008, Pachtinger, findings....

Dogs presenting w/i 6 ingestion, then PT done w/i 2-6 days. Only 8.3% developed prolonged PT needing treatment (none had bleeding or needed transfusion). No diff in age, wt, time elapsed b/t treated and untreated patients found.No assc'n w/ type of anticoagulant.Trend towards smaller dogs needing vitamin K.

219

Half life of factor VII

6.2 h

220

Half life of factor II (prothrombin)

41 hShould take a minimum of 2 prothrombin half lives, or 3.5 days, to express the antithrombotic effect in patients

221

TFPI inhibits...

VIIa and XaTFPI lives in endothelial cells and platelets

222

What effect does LPS have on monocytes related to coagulation?

De novo synthesis of TF on surface

223

P-selectin

tethers platelets to surfacesP-selectin + PSGL-1 (leukocytes binding)

224

Firm adhesion of plts to neuts is fibrinogen binding, which couples the platelet...

alpha2b beta3 to CD11b/CD18 counterreceptor (MAC-1)

225

vWF platelet receptor

GP 1b-V-IX

226

collagen platelet receptor

GPVI

227

thrombin platelet receptors

PAR-1 and PAR-4

228

Alpha 2b Beta3 receptor antagonists

abciximabeptifibatidetirofiban

229

Drug that blocks PAR1 receptor

vorapaxar and atopaxar

230

Drugs that block P2Y12 receptor by blocking ADP from binding

thienopyridines (prodrugs): clopidogrel, prasugrel, ticlodipineirreversible: ticagrelorreversible: cangrelor

231

Endothelial prostaglandins

PGD2, PGE2, PGF2, PGI2

232

Acetylation of COX-1 is ___ more effective than COX-2 by aspirin

166Xvia acetylation of Ser529 preventing binding of AA to catalytic site on COX-1

233

Other effects of aspirin besides inhibition of COX-1

stimulates NO release via 15-epoxylipoxin A4 and inhibiting leukocyte endothelial reactions, enhances fibrin clot permeability and lysis by acetylating lysine residues on fibrin

234

Clopidogrel action decreased by what drug?

PPIs - omeprazole

235

Replacement of chlorine with ___ enhances prasugrels action.

fluorine

236

What drug class is ticagrelor in?

cyclopentyltriazolopyrimidine

237

Picotamide MOA

dual inhibitor of TxA2 receptors and TxA2 synthesis

238

20% of blood content of FV is where

alpha granules

239

What is the protein C/protein S/thrombomodulin (TM) system?

thrombin binds thrombomodulin, which activates protein C which binds with its cofactor, protein S, and intactivates any factors Va and VIIIa

240

Protease inhibitors TFPI and ATIII are always present bound to...

heparan sulfates on endothelial surfaces

241

TFPI inhibits

Xa and VIIa

242

What is the only coagulation protein that routinely circulates in its active form?

VII (about 1% VIIa)

243

What two effects does thrombin bound thrombomodulin have?

1. activates TAFI which modifies fibrin molecules by removing their terminal lysine residue making them more resistant to fibrinolysis2. activates Protein C which then binds cofactor Protein S to inactivate Va and VIIIa

244

How does the Sonoclot work?

Measures changes in blood viscosity using a vertically oscillating probe immersed in a cuvette of whole blood. Glass beads in the cuvette activate coagulation. Results are Sonoclot Signature graphically and quantitative results are ACT, clot rate, and platelet function

245

Recommended heparin levels for anticoagulation

0.35-0.7 U/ml

246

aPTT goal with heparin

1.5-2 X baseline

247

Babski, JVIM, 2012. Sonoclot evaluation of UFH dogs

ACT prolonged, CR decreased, aPTT correlated well with AXA; however, aPTT ratio did not correlate as strongly with AXA, Sonoclot equivalent to aPTT

248

Extrinsic platelets disorders are characterized by a lack of a functional protein needed for what?

Platelet adhesion and aggregation

249

Name the most common thrombocytopathy in dogs

Von Willebrands

250

What contacts more von willebrand factor, platelets or endothelial cells?

endothelial cells (richest source of vwb)

251

How many forms of von willebrands are there?

3

252

describe type 1 von willebrands

quantitative reduction in vWF - all multimers are present. however the concentration is less than needed for hemostasis

253

Describe type 2 von willebrands

measurable reductions in vWF, but the subset of large multimers is scant. This causes qualitative reduction in vWF because the large multimers are essentials for hemostasis

254

Describe type 3 von willebrands

Absolute lack of vWF all together

255

Clinical signs of vWF disease

Mucosal bleeding (epistaxis, melena, hematuria, gingival hemorrhage) or excessive cavity bleeding

256

T/F - Petechia and ecchymosis in dogs with von willebrands is common

false

257

What is the best in vivo diagnostic for primary hemostasis

buccal mucosal bleeding time BMBT

258

Normal BMBT times are less than ______

3 minutes

259

Which blood products are recommended to treat von willebrands

plasma containing VWF (fresh frozen plasma, cryoprecipitate or fresh whole blood)

260

T/F - Patients with Chediak higashi syndrome have a normal number of platelets

true - these patients have prolonged bleeding time in the presence of normal platelet concentrations

261

Describe the platelet defect in Chediak Higashi Syndrome

Patients with CHS have altered lysosomalgranuale formation, and abnormal degranulation in neutrophils/platelets. Because of this, aggregation to collagen is absent.

262

Describe the primary defect in patients with Glanzmanns thrombasthenia

Primary defect leads to a deficiency in the number of the alpha 2b beta 3 integrin. Prolonged bleeding time occurs because of the lack of fibrinogen beinding to this integrin.

263

Describe the mechanism behind the platelet membrane disorder in greater swiss mountain dogs

mutation is presnt on P2y12 receptor which prevents activation via ADP induced outside in signaling for fibrinogen binding on the platelet surface

264

How does clopidogrel work

Clopidogrel blocks ADP from binding at the P2Y12 receptor - reducing platelet activation

265

In which breed do we most often see Canine Scott Syndrome

German shepherd dogs

266

Describe the mechansim behind Canine Scott Syndrome

Defect lies in the inability for phosphatidylserine to be externalied from the creation of a procoagulant surface

267

Name the inherited autosomal recessive platelet defect seen in Cavaliers

Idiopathic asymptomatic macrothrombocytopenia

268

Describe the mutation in idiopathic asymtopmatic macrothrombocytopenia

A mutation in B1 tubulin leads to altered proplatelet formation in megakaryocytes

269

In humans, acquired von willebrands disease can occur through what mechanisms

autoimmune disease, increased shear-induced proteolysis of vWF (cardiovascualr lesions/pulmonary hypertension, etc), or increased binding of vWF to platelets on other cell surfaces

270

In humans, name three drugs that can cause acquired von willebrands

ciprfloxacin, griseofulvin, valproic acid

271

Name two molecules in the blood of uremic patients that become increased, resulting in altered vascualr tone and platelet function

nitric oxide and prostacylin

272

Recommended dosing of cryoprecipitate for dogs with clinical bleeding secondary to von willebrands dsiease

1 unit/10 kg IV

273

Recommended dosing of fresh frozen plasma

10-20mL/kg IV