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Platelet and Bleeding Disorders > Week 5 > Flashcards

Week 5 Flashcards

1
Q

Quinidine

A

Drug that causes drug induced thrombocytopenia

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2
Q

Quinine

A

Drug that causes drug induced thrombocytopenia

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3
Q

Sulfa drugs

A

Drugs that cause drug induced thrombocytopenia

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4
Q

Rifampin

A

Drug that causes drug induced thrombocytopenia

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5
Q

heparin

A

Does not cause drug induced thrombocytopenia-more likely to causes thrombosis

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6
Q

Tx for ITP

A

Corticosteroids, IV IgG, antibody against RhD, splenectomy (not in children), or thrombopoesis

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7
Q

Why do we use IV IgG and anti D IgG to treat ITP?

A

They causes an abundance of IgG clogging receptors on macrophages and confuse macrophages to go for RBCs rather than platelets–can causes hemolysis.

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8
Q

Thrombopoeitic drugs

A

Promote platelet production via stimulation of TPO receptor. They increase marrow production, but do not fix the underlying autoimmune process

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9
Q

What are the thrombopoeitic drugs?

A

Romiplostim and Eltromopag

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10
Q

What is the most common treatment for drug induced thrombocytopenia?

A

Stop using the drug that is causing it.

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11
Q

Causes of Platelet dysfunction

A

Inherited disorders, drug, uremia, monoclonal gammopathy (protein interferes with platelet adherence/aggregation), myelodsyplasia and myeloproliferative disorders (abnormal hematopoietic stem cell).

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12
Q

What drugs causes platelet dysfunction?

A

Aspirin, clopidogrel, others

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13
Q

What is the most common cause of platelet dysfunction?

A

Drugs

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14
Q

What are the inherited disorders of platelet dysfunction?

A

Glanzmann’s thrombasthenia and Bernard-Soulier syndrome

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15
Q

Glanzmanns thrombasthenia

A

autosomal recessive disorder where platelets lack GP IIb/IIIa receptor so there is no aggregation

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16
Q

Bernard-Soulier syndrome

A

autosomal recessive disorder where platelets lack VWB factor GPIb so there is no adherence and a low platelet count

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17
Q

Aspirin

A

Irreversibly inhibits cyclooxyrgenase which blocks thromboxane synthesis (a prothrombotic molecule)

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18
Q

Clopidogrel

A

blocks ADP receptor (ADP is a platelet agonist)

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19
Q

Abciximab, eptifibatide, trifoban

A

block the IIb/IIIa receptor which prevents aggregation

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20
Q

What is the most common inherited bleeding disorder?

A

Von Willebrand Disease

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21
Q

Von Willebrand disease

A

Autosomal Dominant but with variable penetrance.
Can be quantitative or qualitative. Can have low factor VIII levels. Usually mild/moderate bleeding (menorrhagia, surgical bleeding, bruising)

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22
Q

Lab values in VWB disease

A 
low levels of VWB and VIII (if quantitative defect)
low activity (less platelet adherence) if quantitative expressed in PFA-100
PTT may be long if low enough VIII
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23
Q

catalyst

A

simple inorganic compound or an enzyme (protein or mRNA) that stabilizes the transition state of a reaction by lowering the activation energy

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24
Q

How does enzyme concentration influence reaction velocity

A

if enzyme concentration is living and the uncatilizated reaction rate is zero, then the enzyme concentration changes reaction velocity in a linear fashion.

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25
Q

Cofactors

A

non protein cellular components that are key for enzyme activity: metals (1/3), coenzymes, and prosthetic groups

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26
Q

Coenzymes and Prosthetic groups

A

Cofactors that are low molecular organic compounds that bind either weakly (coenzymes) or tightly *prosthetics) to the protein.

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27
Q

Rate or product formation is determined by

A

catalytic speed (how fast E can convert S to P), availability of substrate, and concentration of product.

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28
Q

At very high substrate concentration, how is the reaction velocity influenced?

A

The enzyme has a high turnover number and the reaction approaches Vmax.

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29
Q

Vmax

A

is constant for a given enzyme

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30
Q

What is Km

A

the substrate concentration at which reaction proceeds at 1/3 Vmax. It does not depend on enzyme concentration. Its s inversely related to the affinity of an enzyme for its substrate. the higher the affinity, the lower the Km

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31
Q

Michaelis menton kinetics

A

v=Vmax[S]/(Km+[S]

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32
Q

Lineweaver Burke plots

A

take the Michaelis Menton kinetics and put it in linear form. 1/v=(Km/Vmax)(1/[S]+1/Vmax)
y intercept: 1/Vmax
x intercept: -1/Km
slope: Km/Vmax

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33
Q

Competitive Inhibitors

A

Reversible inhibitor that react only with free enzyme at active site. Need higher [S] to get to 1/2 vMax so Km is larger, Vmax is the same

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34
Q

Non competitive inhibitors

A

Revserible inhibitor that reacts with free enzyme and enzyme/substrate complex. Usually bind away from the active site. Vmax is decreased, but the Km stays the same

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35
Q

Mixed inhibitions

A

When Ki1 does not equal Ki2 in a non competitive situation then both the slope and y intercept of the line weaver burke plot is affected. In addition, lines do not intersection x axis.

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36
Q

Uncompetitive inhibitors

A

Reversible inhibitor that reacts only with enzyme substrate complex. Reduce Vmax and Km via stabilizing of the ES complex.

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37
Q

Irreversible Inhibitors

A

covalently bind enzyme which continually lowers Vmax oil all enzymes have reacted with inhibitor. jSuicide substrates.

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38
Q

proteolysis

A

irreversible hydrolytic cleavage of peptide bond in ap protein to either activate it or inactive it

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39
Q

Serine proteases

A

active site pocket is formed by aspartate, histidine, and serine.

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40
Q

Thrombin activation via serine proteases

A

Inactive thrombin zygmogen is called Prothrombin. Prothrombin is converted to thrombin via cleavage at Arg 271 and 320 by serine protease called Xa

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41
Q

Serpins

A

Serine Protease Inhibitors bind and inhibit serine proteases. Antithrombin III inhibits thrombin and factors Xa, IXa, XIa, XIIa (stimulated by heparin)

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42
Q

Thrombin cleaves:

A

Fibrinogen into fibrin via cleavage of 1 bond in both alpha chains and 1 bond in each beta chain

Thrombin also aids the reaction of VIII–>VIIIa

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43
Q

Fibrin and soft clot formation

A

Fibrin spontaneously polymerizes to form soft clots through docking of newly exposed beta chains

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44
Q

Hard clot formation

A

Factor XIIIa catalyzes cross linking between fibrin molecules in soft clots to form polymerized fibrin (hard clots) via glutamyl-lysine crosslinks

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45
Q

Intrinsice pathway

A

XII–>XIIa
XIIa catalyzes XI–>XIa
XIa catalyzes IX–>IXa
IXa catalyzes X–>Xa

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46
Q

X—>Xa

A

requires Ca++, PL, and helper protein VIIIa

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47
Q

Extrinsic Pathway

A

TF found on adventitia of blood vessels activates VII to VIIaxTF. In low TF concentrations, IX–>IXa. In high TF concentrations, X–>Xa

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48
Q

Vitamin K Dependent factors

A

IX, VII, X, Prothrombin are zymogens that are modified by vitamin K dependent processes in liver

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49
Q

Vitamin K dependent processes

A

post translational modification of glutamate side chains (-1) to gamma carboxyglutamate side chains (-2)–allows binding to multiple Ca++ ions.

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50
Q

Membrane localization

A

These negative charges create a specific place for enzymes to attack their substrates on membrane surface.

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51
Q

Amplification

A

II–>IIa
increased by 278,000 fold when Xa, Ca, PL, and Va are present

Overall the entire clotting process–3x10 to the 19th fold increase in. acceleration.

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52
Q

Things that acerbate initial phase of clotting

A

Xa, thrombin, Ca, PL

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53
Q

Things that terminate clot formation

A

thrombin, Protein C/S,

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54
Q

Thrombin-thrombomodulin complex

A

Thrombin and thrombomodulin on endothelium from T/Tm complex which activates the zymogen protein C to protein Ca–>Protein Ca forms complex with Protein S

Inactivates Va and VIIIa (cleave the arm via specific amino acid sequence)

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55
Q

Serpin Antithrombin and heparin

A

inhibit thrombin and factor Xa (faster when Xa is not bound to endothelium)

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56
Q

Platelet Adhesion

A

In normal: platelets bounce off endothelium in random fashion

In injury: VWB factor and collage are exposed and can bind VWBR on platelet and stick

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57
Q

Platelet Aggregation

A

When VWBR and Collage R are engaged, undergo conformational changes resulting in outside in signaling. Insie out signaling activates the normal non activated R for fibrinogen called the IIb/IIIa R

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58
Q

IIb/IIIa Receptors On/Off

A

Off may not be default setting. There is an inhibitory protein on the receptor. Lack of this, results in half/on/half off hypersensitive receptor.

Inhibitor is displaced by A1 and A2 proteins to turn it on

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59
Q

Adherent activated platelet

A

Negative PL heads turn outward, ADP allows granules to extrude contents, IIb/IIIa activated and can bind bivalent fibrinogen. Need to engage coagulation proteins which PL are essential for.

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60
Q

vWF and ADAMTS13

A

Platelet binds VWBF and gets stuck on endothelium, fibrinogen can bind platelet and so can vWBF and platelets keep aggregating. ADAMTS13 cleaves large vWB factor strands to limit clot buildup

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61
Q

Problems with ADAMTS13

A

leads to platelet aggregation causing TTP. Red cells will get torn on fibrin–schistocytes.

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62
Q

Engaging the Platelets

A

VWBF binds to endothelium
Negative PL heads bind positive Ca
Vitamin K coagulation factors bind Ca.

creates a 2D surface for Xa to cleave II
Va holds them in a certain orientation (holds II and Xa)

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63
Q

Warfarin

A

competitive inhibitor of vitamin K–prevents post translational modifications of vitamin K dependent coagulation factors. Can not generate as much thrombin

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64
Q

Prostacycin and ADPase anticoagulant features of endothelium

A

inhibit platelet recruitment and activation

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65
Q

Factor V leiden

A

specific sequence of Amino acids on factor Va is messed up so that it takes longer for APC to cleave. Predisposes to clot formation

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66
Q

Increase amount of coagulation factors

A

Increases the reaction rate

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67
Q

Normal Thrombin levels

A

Can differ by 28 fold in people

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68
Q

Fibrinolysis

A

Getting rid of clots
fibrin has binding site for plasminogen and its helper to cleave it

When lysine is present in fibrinogen, helper t-Pa can cleave it

69
Q

D dimers

A

Fibrinogen contains D domains–form cross linking during clot formation. Pasmin cleaves clot–leaves you with d dimers. D dimers are indicators that a clot has formed. Sensitive but not specific.

70
Q

VTE Risk

A

risk factors differ in magnitude and are additive, FH is more important.

71
Q

Thrombocytopenia

A

decreased production (marrow), increased consumption (immune, increased clotting DIC, MAHA-TTP, HUS, and multifactorial), sequestration in spleen,

severe if <10-20K put–petechaie, purpura, and mucosal bleeding

72
Q

Petechiae

A

bleeding due to lack of vessel integrity: plt maintain vessel integrity

73
Q

Inhibiting platelets vs thrombin

A

Inhibiting plates causes leaky vessels, thrombin does not

74
Q

Immune Thrombocytopenia purpura ITP

A

Ab coat platelets-destroyed by spleen and liver.
Childhood-virus attaches to platelet, IgG complement
Adult: chronic, recurring–antiplatelet autobodies
Treat only if low platelet <30K

75
Q

Drug induced thrombocytopenia

A

drug binds plasmas protein–>form ab/drug/protein complex which associates with platelets. Complement reaction destroys platelet.

76
Q

Clotting factor deficiencies

A

level below 30% of normal. Most that are inherited are autosomal recessive with exception of VIII and IX which are sex linked.

If acquired: usually liver disease, vitamin K deficiency ofr DIC

77
Q

Inherited factor deficiency

A 
Hemophilia A or B (VIII and IX respectively) sex linked
Factor XI (hemophilia C) autosomal recessive
Contact factor deficiency (XIII) does not cause bleeding
78
Q

Hemophilia A or B

A

severity depends on factor level, only severe if <1%.
Joint and muscle bleeding, can cause join damage
Tx: with missing factor replacement.

79
Q

Amplification loop in Hemophilia

A

Low VIII and IX-problem with intrinsic pathway
can bypass if there is a lot of tissue factor
Not a lot of tissue factor in joints and muscles–most bleeding occurs there.

80
Q

Acute complications of hemophilia

A

Muscle hematoma

Hemarthrosis

81
Q

Long term complications of hemophilia

A

Joint destruction and nerve damage

82
Q

Prophylaxis in hemophilia

A

Port put in and administer clotting factor concentrate–reduces bleeding incidents and frequency of long term joint damage

83
Q

Hemophilia lab findings

A

Long aPTT, normal PT/INR
Long aPTT corrects with mixing
low level of factor VIII or IX

84
Q

Acquired Clotting factor deficiencies

A 
Vitamin K deficiency (II, VII, IX, X, protein C)
autoimmune destruction of single factor
liver disease (all factors and inhibitors)
DIC (all factors, inhibitors, and platelet)
85
Q

Vitamin K deficiency

A

Inadequate supply (Newborn, hospitalized patient not eating or on antibiotics)

Poor absorption (biliary obstruction, generalized malabsorption)

Vitamin K inhibitors (warfarin)

86
Q

Lab findings in Vitamin K deficiency

A

Long PT/INR and aPTT
PT/INR more sensitive
long clotting times correct with mixing
low levels of vitamin K dependent factors

87
Q

Tx of vitamin K deficiency

A

fresh frozen plasma or prothrombin complex concentration

Newborns get prophylactic vitamin K on day one of life

88
Q

Coagulation inhibitors–immune

A

antibodies to clotting factors (usually VIII) especially in hemophiliacs due to alloimmunity

89
Q

Other coagulation inhibitors

A

drugs (heparin) which accelerate inhibition of thrombin/Xa via antithrombin
Direct thrombin inhibitors and Xa inhibitors.
Lupus anticoagulants: binds PL and prevents catalysis of cascade (in vitro only–thrombosis in vivo by uncertain mechanism)

90
Q

Direct thrombin and Xa inhibitory drugs

A

argatroban
dabigtran
rivaraxaban
apixaban

91
Q

Coagulation inhibitor lab effects

A

Heparin: long aPTT, long PT/INR, long thrombin time (most sensitive)
Factor VIII inhibitors: long aPTT
LAC: long aPTT, occasionally long PT/INR

NO CORRECTION WITH MIXING

92
Q

Disseminated Intravascular Coagulation

A

Uncontrolled disorganization of clotting/fibrinolytic systems (coag factors, inhibitors, and platelets)

due to exposure of excessive tissue factor
associated with diffuse endothelial injury

93
Q

DIC Lab results

A

thrombocytopenia, long PTT, long PT/INR, high d dimer, and low fibrinogen.

Associated with underlying debilitating disease (sepsis, disseminated cancer, obstetric complications)

94
Q

Tx of DIC

A

Control of underlying disease biggest factor

Can use FFP and platelet transfusion for blood issues

95
Q

DIC Purpura fulminans

A

tissue necrosis seen in DIC due to underlying factors like sepsis

96
Q

Thrombotic thrombocytopenic purpura

A

ADAMTS13 autoimmune destruction–platelet aggregates in small vessels
fibrin shears cause schistocytes and low platelet count

MAHA, thrombocytopenia, and organ dysfunction
primarily neurologic effects

97
Q

Lab findings in TTP

A

thrombocytopenia and anemia
normal fibrinogen and clotting factors
intravascular hemolysis: high LDH, low haptoglobin
high reticulocyte count
Coag tests are normal
renal dysfunction: high creatinine, proteinuria, hematuria
very low <5% ADAMTS13

98
Q

Hemolytic Uremic syndrome

A

MAHA where kidneys are the primary organ affected
GI prodrome due to infection with toxin producing E coli–injures endothelium.

Atypical HUS not associated with infection; associated with inherited defects in complement regulation

99
Q

Tx of TTP

A

Plasma exchange and concomitant immunosuppressive therapy

100
Q

Measuring fibrin formation

A 
Prothrombin time
INR
aPTT
fibrinogen level
mixing study
101
Q

Measuring fibrinolysis

A

d dimer

alpha 2 antiplasmin

102
Q

Measuring regulation

A

Antightombin activity

protein C/S activity

103
Q

Prothrombin time (PT)

A

add thromboplastin (excess of TF, PL, Ca) to citrated plasma. Allows to bypass amplification step mediated by VIII and IX.

Sensitive to VII, X, IX, VIII or contact factor levels–how long it takes to form fibrin

Detects ACQUIRED coagulapthies

104
Q

activated partial thromboplastin time aPTT

A

incubate citrated plasma withPL and contact system activator which generates XIIa–>XIa–>IXa, then add Ca to allow clotting and proceed to completion

Sensitive to contact factors XI, IX, VIII, common.

detects INHERITED coagulaopahty

105
Q

Thrombin time

A

thrombin and plasma–see how long it takes to clot (see if anything is inhibiting thrombin)

106
Q

Mixing study

A

mix plasma 1:1 with normal plasma and measure aPTT. Should correct any deficiency. If not, inhibitory

107
Q

Bleeding time and PFA 100

A

cut someone and measure bleeding time–not standardized

Measure how long it takes flowing blood to clot in collage coated tube in presence of ADP or EPI

108
Q

Pathologic thrombosis is due to what three factors

A

Virchows triangle:

vessel wall injury, hyper coagulability, and stasis of blood vessel

109
Q

Arterial Thrombosis

A

interrupting blood flow causes ischemic necrosis of downstream organ/limb

110
Q

Arterial Thrombosis causes

A

vessel wall injury (atheroma), emboli may cause downstream small vessel infarction
Ex: MI, stroke, limb, ischemia/gangrene

111
Q

Arterial thrombosis and platelets

A

arterial circulation is high shear–platelets play bigger role than thrombin.

112
Q

Arterial thrombosis pathophysiology

A

linked to atherosclerotic vessel disease (endothelial injury and inflammation processes)

113
Q

Arterial thrombosis RF

A

smoking, HTN, hperchoesterolemia, diabetes, FH, age, obesity, sedentary

114
Q

Arterial thrombosis treatment

A

antiplatelets

115
Q

Venous Thrombosis

A

obstruction to outflow, usually in deep veins of legs/pelvis, associated with venous stasis

edema, swelling, pain, inflammation

116
Q

Venous thrombosis and PE

A

PE is where thrombus breaks free and follows venous return through right heart into PAs. Can cause hypoxemia, shock and death (5%).

117
Q

Paradoxical embolus

A

enters arterial circulation via patent ductus areriosus or ASD, causing arterial occlusion (usually don’t have PE in arterial blood)

118
Q

Venous thrombosis and fibrin

A

Low shear stress in veins allows accumulation of activated clotting factors–Fibrin rich

119
Q

Venous thrombosis treatment

A

Drugs that block thrombin generation (not anti platelet)

120
Q

VTE formation

A

forms in valve pockets of deep vein because lowest shear area

121
Q

Causes of venous stasis

A 
Surgery/major trauma
Cancer
Immobilization (bedrest, paralysis, long airplane)
Obesity
Preganncy
CHF
Venous insufficiency or obstruction
122
Q

Causes of acquired hypercoaguability

A 
age (increased VWB factor and VIII)
surgery or trauma
cancer
myeloproiferative disorders (polycythemia vera)
pregnancy
estrogen oral contraceptives
123
Q

Disease of hypercoagulability

A

Antiphospholipid syndrome

Heparin induced thrombocytopenia

124
Q

Antiphospholipid Antibodies (APA)

A

antibodies directed against a variety of epitopes present on phospholipid/protein complexes (anticardiolipin Ab, antibeta 2, glycoprotein I ab)

common-mostly asymptomatic, only disease if high titer

125
Q

Lupus anticoagulants (LAC)

A

subset of APA that inhibit IN VITRO coagulation. prolong aPTT (misleading name)

126
Q

Antiphospholipid syndrome

A

persistently positive test for APA (LAC and other APA)
uncertain pathophys
increased risk of arterial/venous thrombosis, recurrent fetal loss, autoimmune thrombocytopenia/hemolytic anemia

occasional catastrophic presentation with organ failure
lifelong anticoagulation

127
Q

Genetic Risk factors for VTE

A

deficiency of major coagulation inhibitors (uncommon, 20 fold increase)

  1. Antithrombin deficiency (make more thrombin)
  2. protein C deficiency (more Va and VIIIa)
  3. Protein S deficiency

Other conditions (more common, but less risky)

  1. Factor V Leiden
  2. Prothrombin G20210A polymorphism
128
Q

VTE is multigenic

A

Gene defect does not mean disease
FV leiden is most common
multiple genes act synergistically
relative risk seems high, use absolute risk

129
Q

VTE risk

A

determined by genetic and acquired causes (number of prothrombotic alleles varies in population)

130
Q

FH vs lab testing for thrombophilia

A

FH predicts just as well

thrombophilic mutations do not predict thrombotic risk in absence of FH

131
Q

Idiopathic VTE versus Provoked VTE

A

Idiopathic more likely to recur (20-30%)

risk of recurrent VTE not strongly influenced by presence of inherited thrombophilia

132
Q

Diagnosis of VTE

A 
Symptoms and physical exam NOT sufficient
D dimer (cross linked fibrin released from clot) is sensitive but not specific
Objective documentation of thrombus necessary
133
Q

Objective testing for VTE

A

DVT: duplex doppler ultrasonagraphy, contrast or MR venography
PE: spiral computed tomography, VQ scan, MR angiography

134
Q

DVT Doppler ultrasound

A

Veins are normally compressible, arteries are not
If a vein is not compressible, that means a clot

Can also show blood flow (color0, if black, no blood flow

135
Q

DVT MR vs contrast venography

A

Veins with black areas-clot

136
Q

Unfractionated Heparin UFH

A 
large molecular wight (16,000)
Inhibits IIa, Xa, IXa, XIa in presence of antithrombin
relative anti Xa: anti II activity 1:1
eliminated by liver and kidney
IV unless prophylaxis, then SQ
MUST BE MONITORED via aPTTT or anti Xa
137
Q

UFH antidote

A

protamine sulfate

138
Q

Low molecular weight heparin LMWH

A

MW 5000
relative anti Xa: anti II activity 2:1 to 4:1
eliminated mainly kidney (careful with renal failure)
longer half life
less off target binding to cells and other plasma proteins
monitor via anti Xa levels if needed
ONLY Partially neutralized via protamine sulfate

139
Q

LMWH vs UFH

A

lower HIT risk (do not use to treat)
preferred during pregancy
less sticky, more predictable dose response
Safer, can be outpatient

140
Q

UFH uses

A

acute coronary syndrome, peripheral artery occlusive disease, cardiopulmonary bypass, extracorpeal membrane oxygenation ECMO, dialysis circuits

141
Q

Fondaparinux

A 
pentasaccharide (MW 1200) 
Inhiibits ONLY Xa
eliminated by kidney (avoid in renal failure)
long ass half life
No monitoring
No HIT risk, can beat HIT
no antidote
142
Q

How heparin works

A

5 pentasaccharide binds AT
AT binds Xa
tail of heparin binds thrombin

143
Q

Heparin Induced thrombocytopenia

A 
>50% drop in platelet count when receiving heparin but paradoxically leads to blood clots. 5-7 days after heparin
Intensely prothrombotic (30 day incidence of arterial and venous thrombosis 50%), 20% mortality
144
Q

HIT mechanism

A

Platelet 4 factor in platelet granules released when platelet is activated. They are heparin neutralizers–bind heparin to form PF4/heparin complex, which stimulates an immune response. IgG binds to form a pF4/heprain/IgG immune complex which binds Fc receptor on platelets. This stimulates removal via macrophage (thrombocytopenia) or platelet activation/release/aggregation (thrombosis)

145
Q

HIT and smaller heparin molecules

A

smaller heparin molecules (LMWH or Fonda) result in less IgG binding-less platelet activation, decreasing HIT risk

146
Q

Testing for HIT

A

anti platelet 4 test

147
Q

HIT Tx

A 
Stop heparin
DON"T USE WARFARIN
screen for thrombosis
give thrombin inhibitors (argatroban, bivalidrudin)
give fondaparinux
give DOACs
148
Q

Warfarin

A

Vitamin K antagonist-inhibits vitamin K dependent carboxylation of the Gla domains (VII,IX,X,PT)
monitor via INR
Usual INR 2.0-3.0, takes several days to get to therapeutic range
DO NOT USE IN PREGNANCY

149
Q

Warfarin mechanism

A

inhibits enzyme (vitamin K epoxide reductase) that takes oxidized vitamin K back to usuable reduced form. It can’t modify the coag factors in oxidized form

150
Q

Variability in warfarin effect

A

Genetic polymorphisms in target enzymes
Variation in dietary vitamin K
Increase metabolism (barbiturates, chronic alcohol)
Decrease metabolism (phenytoin, acute alcohol, some antibiotics)
drugs that decrease vitamin K synthesis by gut (antibiotics)
Drugs that displace warfarin from albumin (aspirin)

151
Q

Warfarin uses

A

Prevent recurrent VTE (3-6 mo dose)
Prevent stroke in atrial fib
Prevent stroke/embolism in patents with artificial heart valves (INR 2.5-3.5)

152
Q

Warfarin and Protein C

A

warfarin lowers protein C faster than levels of vitamin K dependent factors

153
Q

Warfarin associated skin necrosis

A

microvascular skin necrosis-breast, butt, thighs, abs

rare, in first week of VKA exposure. Because warfarin decreases levels of protein C faster coag factors

154
Q

Tx warfarin OVERDOSE

A

Vitamin K oral/IV (takes time)
fresh frozen plasma (excess volume
prothrombin complex concentrate (FVII, IX,X,II, less volume)

155
Q

Direct Oral Anticoagulants (DOACs)

A

small molecules that inhibit specific clotting factors

156
Q

DOAC Thrombin inhibitor

A

Dabigatran

157
Q

DOAC Factor Xa inhibitors

A

Rivaroxaban (single use agent), apixaban (single use agent), edoxaban

158
Q

DOAC use

A

stroke prevention in non valvular atrial fib
Tx and prophylaxis of VTE
VTE prophylaxis in orthopedic surgery

159
Q

Direct vs Indirect anticoagulants

A

Direct binds Xa itself, do not need antithrombin (no cofactor required)

160
Q

Advantages of DOACs

A 
oral administration (only 1-2x day)
No monitoring
rapid onset and single agent
no hospitilization
safer
161
Q

Disadvantages of DOACs

A

cost 10x warfarin
no method to determine drug level
no reversal agent for Xa inhibitors
potential for accumulation in liver/kidney disease
not suitable for all warfarin indications (prosthetic valves)

162
Q

Antiplatelet drugs

A

Asprin
ADP receptor antagonist (clopidogrel)
IIb/IIIa antagonists: abciximab, eptifibatide, tirofiban

163
Q

Fibrinolytic drugs

A

activate plasminogen to plasmin–chews up clots
recombinant t-Pa
use in MI, Peripheral vascular thrombosis, ischemic stroke, massive PE

most effective for arterial clot if given within 90 min
Not indicated in routine treatment of VTE
significant risk of hemorrhage

164
Q

TX of VTE overall

A
  1. rapid acting anticoagulant: heparin, LMWH, DOAC
    **if using warfarin overlap with initial anticoagulant drug for 4-5 days, INR 2-3 before stopping heparin
    Continue for 3-6 mo (longer if needed)
    exceptions are HIT (direct thrombin inhibitor or fondaparunix), cancer VTE (better to do LMWH), placement of IVC filter if anticoagulant fails
165
Q

IVC filters

A

linked to injuries and can actually cause thrombosis

166
Q

VTE treat longer if

A

treat longer than 6 mo if recurrent VTE, unprovoked VTE, Antiphopholipid syndrome, other irreversible store RF for recurrence

167
Q

VTE common in hospitalized patients

A

VTE prophylaxis is routine part of admission now

168
Q

High risk patients for VTE

A 
orthopedic and surgical
trauma
stroke,
acutely ill medical
Hx of VTE
known thrombophilia

Tx: UFH, LMWH, fondaparinux, or DOAC (at lower doses than Tx), elastic stockings or pneumatic compression devices

169
Q

procogulants of endothelium

A

endothelin-1, VWB and collagen

Platelet and Bleeding Disorders (4 decks)

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