Week 5 Flashcards
1
Q
Quinidine
A
Drug that causes drug induced thrombocytopenia
2
Q
Quinine
A
Drug that causes drug induced thrombocytopenia
3
Q
Sulfa drugs
A
Drugs that cause drug induced thrombocytopenia
4
Q
Rifampin
A
Drug that causes drug induced thrombocytopenia
5
Q
heparin
A
Does not cause drug induced thrombocytopenia-more likely to causes thrombosis
6
Q
Tx for ITP
A
Corticosteroids, IV IgG, antibody against RhD, splenectomy (not in children), or thrombopoesis
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.
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
9
Q
What are the thrombopoeitic drugs?
A
Romiplostim and Eltromopag
10
Q
What is the most common treatment for drug induced thrombocytopenia?
A
Stop using the drug that is causing it.
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).
12
Q
What drugs causes platelet dysfunction?
A
Aspirin, clopidogrel, others
13
Q
What is the most common cause of platelet dysfunction?
A
Drugs
14
Q
What are the inherited disorders of platelet dysfunction?
A
Glanzmann’s thrombasthenia and Bernard-Soulier syndrome
15
Q
Glanzmanns thrombasthenia
A
autosomal recessive disorder where platelets lack GP IIb/IIIa receptor so there is no aggregation
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
17
Q
Aspirin
A
Irreversibly inhibits cyclooxyrgenase which blocks thromboxane synthesis (a prothrombotic molecule)
18
Q
Clopidogrel
A
blocks ADP receptor (ADP is a platelet agonist)
19
Q
Abciximab, eptifibatide, trifoban
A
block the IIb/IIIa receptor which prevents aggregation
20
Q
What is the most common inherited bleeding disorder?
A
Von Willebrand Disease
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)
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
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
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.
25
Cofactors
non protein cellular components that are key for enzyme activity: metals (1/3), coenzymes, and prosthetic groups
26
Coenzymes and Prosthetic groups
Cofactors that are low molecular organic compounds that bind either weakly (coenzymes) or tightly *prosthetics) to the protein.
27
Rate or product formation is determined by
catalytic speed (how fast E can convert S to P), availability of substrate, and concentration of product.
28
At very high substrate concentration, how is the reaction velocity influenced?
The enzyme has a high turnover number and the reaction approaches Vmax.
29
Vmax
is constant for a given enzyme
30
What is Km
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
31
Michaelis menton kinetics
v=Vmax[S]/(Km+[S]
32
Lineweaver Burke plots
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
33
Competitive Inhibitors
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
34
Non competitive inhibitors
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
35
Mixed inhibitions
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.
36
Uncompetitive inhibitors
Reversible inhibitor that reacts only with enzyme substrate complex. Reduce Vmax and Km via stabilizing of the ES complex.
37
Irreversible Inhibitors
covalently bind enzyme which continually lowers Vmax oil all enzymes have reacted with inhibitor. jSuicide substrates.
38
proteolysis
irreversible hydrolytic cleavage of peptide bond in ap protein to either activate it or inactive it
39
Serine proteases
active site pocket is formed by aspartate, histidine, and serine.
40
Thrombin activation via serine proteases
Inactive thrombin zygmogen is called Prothrombin. Prothrombin is converted to thrombin via cleavage at Arg 271 and 320 by serine protease called Xa
41
Serpins
Serine Protease Inhibitors bind and inhibit serine proteases. Antithrombin III inhibits thrombin and factors Xa, IXa, XIa, XIIa (stimulated by heparin)
42
Thrombin cleaves:
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
43
Fibrin and soft clot formation
Fibrin spontaneously polymerizes to form soft clots through docking of newly exposed beta chains
44
Hard clot formation
Factor XIIIa catalyzes cross linking between fibrin molecules in soft clots to form polymerized fibrin (hard clots) via glutamyl-lysine crosslinks
45
Intrinsice pathway
XII-->XIIa
XIIa catalyzes XI-->XIa
XIa catalyzes IX-->IXa
IXa catalyzes X-->Xa
46
X--->Xa
requires Ca++, PL, and helper protein VIIIa
47
Extrinsic Pathway
TF found on adventitia of blood vessels activates VII to VIIaxTF. In low TF concentrations, IX-->IXa. In high TF concentrations, X-->Xa
48
Vitamin K Dependent factors
IX, VII, X, Prothrombin are zymogens that are modified by vitamin K dependent processes in liver
49
Vitamin K dependent processes
post translational modification of glutamate side chains (-1) to gamma carboxyglutamate side chains (-2)--allows binding to multiple Ca++ ions.
50
Membrane localization
These negative charges create a specific place for enzymes to attack their substrates on membrane surface.
51
Amplification
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.
52
Things that acerbate initial phase of clotting
Xa, thrombin, Ca, PL
53
Things that terminate clot formation
thrombin, Protein C/S,
54
Thrombin-thrombomodulin complex
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)
55
Serpin Antithrombin and heparin
inhibit thrombin and factor Xa (faster when Xa is not bound to endothelium)
56
Platelet Adhesion
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
57
Platelet Aggregation
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
58
IIb/IIIa Receptors On/Off
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
59
Adherent activated platelet
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.
60
vWF and ADAMTS13
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
61
Problems with ADAMTS13
leads to platelet aggregation causing TTP. Red cells will get torn on fibrin--schistocytes.
62
Engaging the Platelets
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)
63
Warfarin
competitive inhibitor of vitamin K--prevents post translational modifications of vitamin K dependent coagulation factors. Can not generate as much thrombin
64
Prostacycin and ADPase anticoagulant features of endothelium
inhibit platelet recruitment and activation
65
Factor V leiden
specific sequence of Amino acids on factor Va is messed up so that it takes longer for APC to cleave. Predisposes to clot formation
66
Increase amount of coagulation factors
Increases the reaction rate
67
Normal Thrombin levels
Can differ by 28 fold in people
68
Fibrinolysis
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
D dimers
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
VTE Risk
risk factors differ in magnitude and are additive, FH is more important.
71
Thrombocytopenia
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
Petechiae
bleeding due to lack of vessel integrity: plt maintain vessel integrity
73
Inhibiting platelets vs thrombin
Inhibiting plates causes leaky vessels, thrombin does not
74
Immune Thrombocytopenia purpura ITP
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
Drug induced thrombocytopenia
drug binds plasmas protein-->form ab/drug/protein complex which associates with platelets. Complement reaction destroys platelet.
76
Clotting factor deficiencies
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
Inherited factor deficiency
```
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
Hemophilia A or B
severity depends on factor level, only severe if <1%.
Joint and muscle bleeding, can cause join damage
Tx: with missing factor replacement.
79
Amplification loop in Hemophilia
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
Acute complications of hemophilia
Muscle hematoma
| Hemarthrosis
81
Long term complications of hemophilia
Joint destruction and nerve damage
82
Prophylaxis in hemophilia
Port put in and administer clotting factor concentrate--reduces bleeding incidents and frequency of long term joint damage
83
Hemophilia lab findings
Long aPTT, normal PT/INR
Long aPTT corrects with mixing
low level of factor VIII or IX
84
Acquired Clotting factor deficiencies
```
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
Vitamin K deficiency
Inadequate supply (Newborn, hospitalized patient not eating or on antibiotics)
Poor absorption (biliary obstruction, generalized malabsorption)
Vitamin K inhibitors (warfarin)
86
Lab findings in Vitamin K deficiency
Long PT/INR and aPTT
PT/INR more sensitive
long clotting times correct with mixing
low levels of vitamin K dependent factors
87
Tx of vitamin K deficiency
fresh frozen plasma or prothrombin complex concentration
| Newborns get prophylactic vitamin K on day one of life
88
Coagulation inhibitors--immune
antibodies to clotting factors (usually VIII) especially in hemophiliacs due to alloimmunity
89
Other coagulation inhibitors
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
Direct thrombin and Xa inhibitory drugs
argatroban
dabigtran
rivaraxaban
apixaban
91
Coagulation inhibitor lab effects
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
Disseminated Intravascular Coagulation
Uncontrolled disorganization of clotting/fibrinolytic systems (coag factors, inhibitors, and platelets)
due to exposure of excessive tissue factor
associated with diffuse endothelial injury
93
DIC Lab results
thrombocytopenia, long PTT, long PT/INR, high d dimer, and low fibrinogen.
Associated with underlying debilitating disease (sepsis, disseminated cancer, obstetric complications)
94
Tx of DIC
Control of underlying disease biggest factor
| Can use FFP and platelet transfusion for blood issues
95
DIC Purpura fulminans
tissue necrosis seen in DIC due to underlying factors like sepsis
96
Thrombotic thrombocytopenic purpura
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
Lab findings in TTP
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
Hemolytic Uremic syndrome
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
Tx of TTP
Plasma exchange and concomitant immunosuppressive therapy
100
Measuring fibrin formation
```
Prothrombin time
INR
aPTT
fibrinogen level
mixing study
```
101
Measuring fibrinolysis
d dimer
| alpha 2 antiplasmin
102
Measuring regulation
Antightombin activity
| protein C/S activity
103
Prothrombin time (PT)
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
activated partial thromboplastin time aPTT
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
Thrombin time
thrombin and plasma--see how long it takes to clot (see if anything is inhibiting thrombin)
106
Mixing study
mix plasma 1:1 with normal plasma and measure aPTT. Should correct any deficiency. If not, inhibitory
107
Bleeding time and PFA 100
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
Pathologic thrombosis is due to what three factors
Virchows triangle:
| vessel wall injury, hyper coagulability, and stasis of blood vessel
109
Arterial Thrombosis
interrupting blood flow causes ischemic necrosis of downstream organ/limb
110
Arterial Thrombosis causes
vessel wall injury (atheroma), emboli may cause downstream small vessel infarction
Ex: MI, stroke, limb, ischemia/gangrene
111
Arterial thrombosis and platelets
arterial circulation is high shear--platelets play bigger role than thrombin.
112
Arterial thrombosis pathophysiology
linked to atherosclerotic vessel disease (endothelial injury and inflammation processes)
113
Arterial thrombosis RF
smoking, HTN, hperchoesterolemia, diabetes, FH, age, obesity, sedentary
114
Arterial thrombosis treatment
antiplatelets
115
Venous Thrombosis
obstruction to outflow, usually in deep veins of legs/pelvis, associated with venous stasis
edema, swelling, pain, inflammation
116
Venous thrombosis and PE
PE is where thrombus breaks free and follows venous return through right heart into PAs. Can cause hypoxemia, shock and death (5%).
117
Paradoxical embolus
enters arterial circulation via patent ductus areriosus or ASD, causing arterial occlusion (usually don't have PE in arterial blood)
118
Venous thrombosis and fibrin
Low shear stress in veins allows accumulation of activated clotting factors--Fibrin rich
119
Venous thrombosis treatment
Drugs that block thrombin generation (not anti platelet)
120
VTE formation
forms in valve pockets of deep vein because lowest shear area
121
Causes of venous stasis
```
Surgery/major trauma
Cancer
Immobilization (bedrest, paralysis, long airplane)
Obesity
Preganncy
CHF
Venous insufficiency or obstruction
```
122
Causes of acquired hypercoaguability
```
age (increased VWB factor and VIII)
surgery or trauma
cancer
myeloproiferative disorders (polycythemia vera)
pregnancy
estrogen oral contraceptives
```
123
Disease of hypercoagulability
Antiphospholipid syndrome
| Heparin induced thrombocytopenia
124
Antiphospholipid Antibodies (APA)
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
Lupus anticoagulants (LAC)
subset of APA that inhibit IN VITRO coagulation. prolong aPTT (misleading name)
126
Antiphospholipid syndrome
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
Genetic Risk factors for VTE
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
VTE is multigenic
Gene defect does not mean disease
FV leiden is most common
multiple genes act synergistically
relative risk seems high, use absolute risk
129
VTE risk
determined by genetic and acquired causes (number of prothrombotic alleles varies in population)
130
FH vs lab testing for thrombophilia
FH predicts just as well
| thrombophilic mutations do not predict thrombotic risk in absence of FH
131
Idiopathic VTE versus Provoked VTE
Idiopathic more likely to recur (20-30%)
| risk of recurrent VTE not strongly influenced by presence of inherited thrombophilia
132
Diagnosis of VTE
```
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
Objective testing for VTE
DVT: duplex doppler ultrasonagraphy, contrast or MR venography
PE: spiral computed tomography, VQ scan, MR angiography
134
DVT Doppler ultrasound
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
DVT MR vs contrast venography
Veins with black areas-clot
136
Unfractionated Heparin UFH
```
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
UFH antidote
protamine sulfate
138
Low molecular weight heparin LMWH
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
LMWH vs UFH
lower HIT risk (do not use to treat)
preferred during pregancy
less sticky, more predictable dose response
Safer, can be outpatient
140
UFH uses
acute coronary syndrome, peripheral artery occlusive disease, cardiopulmonary bypass, extracorpeal membrane oxygenation ECMO, dialysis circuits
141
Fondaparinux
```
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
How heparin works
5 pentasaccharide binds AT
AT binds Xa
tail of heparin binds thrombin
143
Heparin Induced thrombocytopenia
```
>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
HIT mechanism
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
HIT and smaller heparin molecules
smaller heparin molecules (LMWH or Fonda) result in less IgG binding-less platelet activation, decreasing HIT risk
146
Testing for HIT
anti platelet 4 test
147
HIT Tx
```
Stop heparin
DON"T USE WARFARIN
screen for thrombosis
give thrombin inhibitors (argatroban, bivalidrudin)
give fondaparinux
give DOACs
```
148
Warfarin
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
Warfarin mechanism
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
Variability in warfarin effect
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
Warfarin uses
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
Warfarin and Protein C
warfarin lowers protein C faster than levels of vitamin K dependent factors
153
Warfarin associated skin necrosis
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
Tx warfarin OVERDOSE
Vitamin K oral/IV (takes time)
fresh frozen plasma (excess volume
prothrombin complex concentrate (FVII, IX,X,II, less volume)
155
Direct Oral Anticoagulants (DOACs)
small molecules that inhibit specific clotting factors
156
DOAC Thrombin inhibitor
Dabigatran
157
DOAC Factor Xa inhibitors
Rivaroxaban (single use agent), apixaban (single use agent), edoxaban
158
DOAC use
stroke prevention in non valvular atrial fib
Tx and prophylaxis of VTE
VTE prophylaxis in orthopedic surgery
159
Direct vs Indirect anticoagulants
Direct binds Xa itself, do not need antithrombin (no cofactor required)
160
Advantages of DOACs
```
oral administration (only 1-2x day)
No monitoring
rapid onset and single agent
no hospitilization
safer
```
161
Disadvantages of DOACs
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
Antiplatelet drugs
Asprin
ADP receptor antagonist (clopidogrel)
IIb/IIIa antagonists: abciximab, eptifibatide, tirofiban
163
Fibrinolytic drugs
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
TX of VTE overall
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
IVC filters
linked to injuries and can actually cause thrombosis
166
VTE treat longer if
treat longer than 6 mo if recurrent VTE, unprovoked VTE, Antiphopholipid syndrome, other irreversible store RF for recurrence
167
VTE common in hospitalized patients
VTE prophylaxis is routine part of admission now
168
High risk patients for VTE
```
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
procogulants of endothelium
endothelin-1, VWB and collagen
