Venous Thromboembolism Therapeutics Lecture 1 Flashcards
1
Q
Define hematology
A
the discipline concerned with the production, function, and disorders of blood cells and blood proteins
2
Q
Define blood
A
a liquid consisting of plasma in which RBC, platelets and other white cells are suspended
3
Q
What makes up plasma?
A
water, electrolytes, nutrients, waste products, and many soluble proteins
4
Q
What is the typical human blood volume?
A
70mL/kg or roughly 5L
5
Q
what % of blood volume is occupied by RBC?
A
40-50%
6
Q
The cellular components of blood include what 3 types of blood cells?
A
- erythrocytes
- thrombocytes
- Leukocytes
7
Q
what are thrombocytes?
A
platelets
8
Q
what are the 5 types of leukocytes? List in order of abundance
A
- neutrophils
- lymphocytes
- monocytes
- eosinophils
- basophils
9
Q
what is the most abundant WBC in peripheral blood?
A
neutrophil
10
Q
all of the cells in the peripheral blood originate in the ____
A
bone marrow
11
Q
what is a “thrombus”
A
a blood clot that forms in a vein or artery
12
Q
what is an “embolism”
A
anything that moves through the blood vessels until it reaches a vessel that is too small to let it through
13
Q
An embolus is often a thromboembolsim; what is a thromboembolism?
A
a small piece of a blood clot that breaks off
14
Q
VTE refers to what 2 types of embolisms?
A
deep vein thrombosis (DVT) & pulmonary embolism (PE)
15
Q
what is hemostasis?
A
complex process in which many componenets of blood clotting system activate due to vessel injury in order to control bleeding
16
Q
what is primary hemostasis?
A
vasoconstriction and platelet plug formation
17
Q
primary hemostasis is triggered by a vessel injury that exposes ____
A
collagen
18
Q
during primary coagulation, do vessels constrict or dilate?
A
constrict to reserve blood
19
Q
during primary coagulating platelets do what?
A
adhere and aggregate
20
Q
secondary coagulation brings on the activation of ____ and generation of ____
A
coagulation factors and thrombin generation
21
Q
tissue factor is released directly from the ____ and activates the ____ pathway during seconday coagulation
A
damaged vascular tissue & extrinsic coagulation pathway
22
Q
during 2 coagulation, tissue factor combines with and activates factor ____ to form a complex that activates factor ___
A
VII; X
23
Q
the intrinsic coagulation pathway is activated by contact with factor ____ with exposed ___ from damaged subendothelial vessels
A
XII; collagen
24
Q
all the clotting factors needed for the activation of the intrinsic coagulation pathway can be found in the ____
A
circulating blood
25
the intrinsic and extrinsic pathways meet and continue as the ____ pathway via factor ___
common; factor X
26
the common pathway ultimately leads to the formation of ____, which stabilizes the clot
fibrin
27
the coagulation cascade is broken down into what 3 phases?
1. initiation]
2. propogation
3. amplification
28
____ converts fibrinogen into fibrin monomers
thrombin
29
fibrin monomers polymerize to form a ____
soluble clot
30
after converting fibrinogen to fibrin, thrombin activates factor ___, which does what ti the fibrin monomers in order to stabilize the clot?
XIII; cross links
31
what enzyme is responsible for fibrinolysis when the clot is no longer needed?
plasmin
32
plasmin is made from which inactive blood protein?
plasminogen
33
after plasmin lyses the clot, new ___ and ___ cells colonize the wounded area
endothelial and collagen producing cells
34
what are D-Dimers?
breakdown products made by the action of plasmin on the cross-linked fibrin (by-products of fibrinolysis)
35
each D-Dimer contains 2 cross linked ____
D fragments
36
what converts plasminogen to plasmin?
tissue plasminogen activator (t-PA)
37
t/f D-dimers are the smallest fibrin degradation products
t
38
what factors are involved in the extrinsic pathway?
factor VII
39
what factors are involved in the intrinsic pathway?
factors XII, XI, IX and VIII
40
what factors are involved in teh common pathway?
factors X, V, II, fibrinogen
41
the PT is most sensitive to the ___ and ___ pathway factors
extrinsic and common
42
the aPTT is most sensitive to the ___ and ___ pathway factors
intrinsic and common
43
the thrombin time is most sensitive to ___ and presence of ___
fibrinogen and presence of thrombin inhibitors like factor IIA
44
the anti-XA assay only assesses the inhibition of ____
factor XA
45
what is ACtivated partial thromboplastin time (APTT) used to asses?
the deficiencies or inhibitors of the intrinsic pathway factors (factors XII, XI, VIII) and common pathway factors (factors X, V, II, fibrinogen)
46
what is prothrombin time (PT) used to assess?
deficiencies or inhibitors of the extrinsic pathway factors (VIi) and common pathway factors (X, V, II, fibrinogen)
47
anti-XA assay can be used to assess ___
the anticoagulant activity of an anticoagulant that inhibits clotting factor XA, such as heparin, LMWH, fondaparinox or direct XA inhibitors (rivaroxaban and apixaban)
48
The international normalized ratio (INR) was developed to standardize the ____ to allow for monitorong of oral _____ therapy across different labs
prothrombin time; vitamin K antagonists
49
the unit of time for PT when calculating INR is
seconds
50
each lot of PT reagent needs to have an _______ determined or assigned, which indicates how sensitive the reagent is to deficiencies in the vitamin K dependent factors compared to the WHO reference standard
international sensitivity index (ISI)
51
what is the formula for calculating INR?
(patient PT/mean normal PT) all multiplied by ISI
52
thrombosis can occur in the arms, especially under what circumstances?
when a catheter is in place for taking blood or receiving chemo
53
t/f thrombosis can occur in other organs such as the kidney, brain, or bowels
t
54
the 3 primary factors that influenece the formation of a clot are described as the _____ triad
Virchow's
55
venous stasis is characterized by ____
altered or decreased blood flow in the deep veins of the limbs
56
t/f venous stasis is a major predisposing factor to clot formation
t
57
venous stasis results in endothelial damage to ___ secondary to ___
venous valves; hypoxia
58
venous stasis prevents the dilution of ______ by blood flow, which leads to them collecting in the area of stasis
clotting factors
59
venous stasis results from several conditions including :
immobility, prolonged bed rest, massive obesity, venous obstruction, congestive heart failure, varicose veins
60
what are 2 typical etiologies of VTE?
vascular injury
| hypercoaguable states
61
explain the "vascular injury" etiology of VTE
there is a mechanical or chemical injury to the vessel, this evokes inflammatory response, which leads to clot formation. This might be caused by trauma, surgery, venipuncture, indwelling cannulas/catheters or chemical irrigation, forgein material in teh vessels (such as artificial valaves)
62
explain the "hypercoaguable state" etiology of VTE
occurs when the activation of the coagulation system exceeds the ability of the body's natural fibrinolysis to prevent thrombus formation . This may be caused by deficiencies in proteins C & S, or antithrombin III, pregnancy, use of oral contraceptives, malignancy etc. extra risk if >40 years old
63
what are the 3 sides of Virchow's triad?
1. venous stasis
2. vascular injury
3. hypercoagulabilty
64
what are the risk factors for venous stasis?
being >40, immobility, heart failure, stroke, paralysis, spinal cord injury, hyperviscosity, polychythemia vera, severe COPD, obesity, varicose veins
65
what are the risk factors for hypercoagulability?
cancer, high estrogen, IBD, nephrotic syndrome, sepsis, smoking, pregnancy, thrombophilia, lupus anticoagulant, anti-phospholipid antibodies, protein C/S deficiency, factor V leiden, sickle cell, antithrombin deficiency
66
what are the risk factors for vascular injury related thrombosis?
surgery, prior VTE, central lines, trauma
67
how does systemic estrogen increase risk for thrombosis?
by increasing markers of thrombin and fibrin production
68
how do oral contraceptives increase risk of thrombosis?
1. increase factor VII and factor X
2. increase fibrinogen
3. activate protein C resistance
69
how does tamoxifen increase risk of thrombosis?
1. decrease antithrombin
| 2. decrease protein C
70
how do corticosteroids increase the risk for thrombosis?
decrease clearance rate of clotting factors
71
how to serotonin inhibitors increase the risk for thrombosis?
potentiate plateler aggregation
72
how does cisplatin increase the risk for thrombosis?
1. increase von Willebrand factor
| 2. endothelial damage
73
how do thalidomide and lenalidomide increase risk fro thrombosis?
promote platelet activation and aggregation
74
VTE is the ____ most common cardiovascular disorder and affects up to ___% of the population in their lifetime
3rd; 5
75
the annual incidence of PE in 1 per ____ persons, but this increases sharply with age
1000
76
what is believed to be the most common mechanism of PE?
embolization of a DVT into the pulmonary arteries
77
VTE is associated with lower health-related QOL and long-term complications such as post-thrombotic syndrome in up to ___% of DVT patients and chronic pulmonary hypertension in up to ____% of PE patients
40; 1-4
78
t/f thromboprophylaxis in mediaclly ill patients has been shown to be safe and effective
t
79
what are some of the signs of a DVT?
when clots form in deep veins, there is reduced drainage of blood, which increases the pressure in the vessels below the clot, this results in swelling, pain, discolouration, and warmth in the affected limb. May also be difficult to draw blood, difficult to inject, veins on back of hand may stick out, aching shoulder/neck
80
what are some of teh signs of PE?
worsening fatigue, chest pain, unexpected SOB and tachycardia
81
up to ___% of time, there are no symptoms of VTE and they are discovered by chance on diagnostic imaging and other ways
50!!
82
what are the 3 common sites for lower extremity DVT?
1. ileo femoral veins
2, popliteal
3. calf veins (may extend proximally)
83
t/f there is a higher risk of PE with proximal DVT
t
84
upper extremity DVTs are often caused by ___ and ____ or ____
IV lines and pacemaker wires or thoracic outlet obstruction
85
what is the thoracic outlet?
the ring formed by the top ribs, just below the collar bones
86
what is thoracic outlet syndrome (TOS)?
occurs when nerves or blood vessels are compressed by the rib, collarbone or neck muscles at the top of the outlet
87
VTE diagnosis is based on assessment of the clinical probability of VTE prior to ____. This is called ____
diagnostic testing; pre-test probability (PTP)
88
the prevalence of VTE in a population influences the ___ of diagnostic tests
predictive value
89
diagnostic test accuracy is obtained from what 2 thinsg
1. studies evaluating diagnostic tests (CTPA, D-Dimer etc.) compared to reference standard
2. management studies
90
combining the pre-test probability with diagnostic test accuracy gives the ___
post-test probability of a VTE
91
what is the Wells Score for Leg DVT?
assigns points to various risk factors/symptoms (cancer, tenderness, swelling etc.) to assess probability of a leg VTE
92
what is Constans Score for Upper Extremity DVT?
assigns points to various risk factors and symptoms (central line, unilateral edema etc.) to assess the probability of an UE VTE
93
a score >/= 3 on the Wells leg DVT means
high PTP (>50%)
94
a score of 1-2 of the Wells leg DVT means
intermediate PTP (25%)
95
a score of 0 on the Wells leg DVT means
low PTP (<10%)
96
a score of 2-3 on the Constans upper extremity DVT means
likely PTP (~40%)
97
a score of 1/lower on the Constans upper extremity DVT means
unlikely DVT PTP (~10%)
98
what do the ASH clinical guidelines recommend as a starting point for patients suspected of DVT with a PTP 50%/higher?
proximal lower extremity or whole leg ultrasound followed by serial ultrasound if the initial ultrasound is negative and no alternative diagnosis is made
99
What do the ASH clinical guidelines recommend as the starting point for suspected DVT in patients with low PTP?
D-Dimer diagnostic test
100
if a 2-level decision rule (ie likely vs unlikely) is used, the recommendation corresponds to the _____ category
likely DVT
101
when assessing for recurrence of DVT, comparison of ____ and ___ is warranted to determine if radiographic findings are old or represent recurrence
prior and current imagine
102
Pre-test probablility for PE is determined using clinical prediction scores such as ___ or ___ scores
revised geneva score or wells score for PE
103
a high PTP for a PE is defined as what %
%50+
104
an intermediate PTP for a PE is defined as what %?
~20%
105
a low PTP for a PE is defined as what %?
5% or lower
106
a score of 11+ on the revised geneva score for PE is ranked as
high PTP for PE
107
a score of 4-10 on the revised geneva score for PE is rnaked as
intermediate PTP for a PE
108
a score of 0-3 on the revised geneva scale is ranked as
low PTP for a PE
109
a score of >6 on the wells PE scale is ranked as
high PTP for PE
110
a score of ___ is ranked as intermediate risk for a PE according to Wells
2-6
111
a score of ___ is ranked as low risk for a PE according to wells
<2
112
what is the ASH clinical guideline for patients with intermediate PTP for a PE?
start with a d-dimer, then VQ scan or CTPA in patients who need additional testing
113
if a d-dimer test is used to determine presence of a PE, what type of assay is required?
high sensitivity d-dimer assay
114
if the d-dimer comes back negative for PE, what is the ruling?
no PE, no additional testing or anticoagulation required
115
a d-dimer test has limited use in what 3 patient populations due to high frequency of positive results with standard thesholds
1. hospitalized patients
2. post-surgical
3. pregnancy
116
the use of _____ d-dimer cutoff in outpatients older than 50 years oldis as safe as the standard cutoff and increases diagnostic use
age-adjusted
117
how is age-adjusted d-dimer calculated?
age (years) x 10ug/L (using d-dimer assays with a cutoff of 500ug/L)
118
do the ASH guidelines recommend using a positive d-dimer alone to diagnose a PE?
np
119
if a suspected PE, patients who are likely to have a non-diagnostic VG scan should undergo ___
CTPA
120
the likelihood of a diagnostic VQ result (normal to high probablity) is LESS likley in which patient populations? What is the alternative?
older individuals, pre-existing lung disease, and those with abnormal chest x-ray; they should undergo CTPA
121
why is a VQ scan preferred over a CTPA as subsequent test to d-dimer as long as there are no complications?
this limits radiation exposure in patients
122
what is involved in a Lung Ventilation/Perfusion (VQ) scan for PE?
the injection and inhalation of radiolabeled compounds. Test results are expressed as high, intermediate, or low probability of PE
123
what is involved in a computed tomography pulmonary angiogram?
injection of contrast media into the right and left pulmonary arteries and radiographically detecting any filling defects on multiple magnification views. This is the gold standard, but is invasive
124
what is the ASH guideline recommendation for patients with high (50+%) chance of PE?
start with a CTPA (may have to use VQ scan if issues such as allergy to dye, renal impairment etc.)
125
what is the next step if a patient has high chance of PE and the results of the CTPA come back negative?
additional testing with VQ or proximal ultrasound or lower extremities
126
patients with a positive d-dimer or those who have a likley PTP should undergo a ___
CTPA
127
what are the 3 sections of PE risk stratification?
1. massive PE (high risk)
2. submassive PE (moderate risk)
3. minor/nonmassive PE (low risk)
128
what are the symptoms of massive PE?
sustained hypotension (systolic <90 for 15+ minutes), inotropic support, pulselessness, persistent profound bradycardia (HR ,40 bpm with signs of shock)
129
what are the symptoms of submassive PE?
systemically normotensive (systolic BP 90+) , RV dysfunction, myocardial necrosis
130
what is RV dysfunction?
RV/LV ratio >0.9 or RV systolic dysfunction on echo; RV/LV ratio >0.9 on CT; elevation of BNP (>90 pg/mL), elevation of NT pro-BNP (>500 pg/mL), ECG changes (new complete or incomplete RBBB, anteroseptal ST elevation or depression, anteroseptal t-wave inversion)
131
what are the symptoms of minor PE?
systemically normotensive, no RV dysfunction, no myocardial necrosis
132
massive PE occurs in __% of PE cases
5%
133
massive PE has a ___% 3 month mortality rate
58%
134
submassive PE occurs in ___% of PE cases
40%
135
submassive PEs have a ____% mortality rate (3 month)
2-3% initially and 21% at 3 months
136
minor PEs occur in ___% of PE cases
55%
137
what is the mortality rate for minor PEs?
low
138
what are the goals of therapy for a DVT?
1. prevent PE
2. prevent thrombus extension
3. prevent post-thrombotic syndrome
4. prevent bleeding from anticoagulation
139
what are the goals of therapy for PE?
1. prevent progression
2. prevent stroke
3. prevent death
4. prevent thromboembolic pulmonary hypertension
5. prevent bleeding from anticoagulation
140
what are some non-pharm managements for VTE?
1. mechanical thromboprophylaxis
2. IVC filter
3. early and frequent mobilization
141
what are some options for mechanical thromboprophylaxis
intermittent pneumatic compression (IPC) devices; calf length graduated compression stockings (gCS)
142
what is an IVC filter?
small device placed in vena cava to stop blood clots from traveling to the lungs
143
what are some parenteral anticoagulants used for VTE?
1. unfractioned heparin (UFH)
2. low molecular weight heparin (LMWH)
3. fondaparinux
4. argatroban
5. bivalrudin
144
what are some PO anticoaulants for treatment of VTE?
1. warfarin
2. dabigatran
3. rivaroxaban
4. apixaban
5. endoxapan
145
what is a thrombolysis treatment that can be used to treat VTE?
t-PA
146
what is an antiplatelet that can be used to treat VTE?
ASA
147
unfractionated heparin is a _____ (homo/heterogenous) mixture of polymers of varying molecular weights (____ daltons)
heterogenous ; 3000- 30 000
148
what animal is unfractionated from?
pig
149
what is the typical dosing of unfractionated heparin?
continuous infusion (therapeutic anticoagulation) to target aPTT or 5000 units SQ q 8-12h for prophylaxis
150
what needs to be monitored when giving unfractionated heparin
bleeding, HIT, hyperkalemia, osteoporosis
151
what is the antidote to unfractionated heparin?
protamine
152
what is the half life of unfractionated heparin?
50-90 minutes (a short half-life)
153
PTT targets for unfractionated heparin vary by the ___ and which ___ is used, whether it is ____heparin or ____ heparin
indication and lab reagnets used ; ACS heparin or non-ACS heparin
154
what is the MOA of unfractionated heparin?
binds to anti-thrombin 3, activated AT then inactivates thrombin and factor Xa to stop the clotting process
155
what are the indications for unfractionated heparin?
essentially any indication requiring anticoagulation
156
UFH is usually ordered, monitored, and adjusted using a _____
nomogram
157
the dose for UFH is in what unitis?
units/hr
158
what are some non-ACS UFH indications?
VTE
159
what is an indication for ACS UFH?
acute MI
160
t/f there can be lower aPTT targets for UGH treatment in special cases
t
161
LMWH is derived by what process?
chemical or enzymatic depolymerization of UFH
162
LMWH can inactivate ___, but have very reduced effect on ____ as compared to the larger UFH molecules
factor Xa; thrombin
163
of LMWH & UFH, which has more predictable pharmacokinetics? What does this predictability allow for?
LMWH; fixed dosing based on weight
164
t/f although there are several LMWHs available, they cannot be used interchangeably unit for unit with other LMWH or with UFH
t
165
what are indications for LMWH?
many indications both therapeutic and for prophylaxis
166
what is a newer use of LMWH?
circuit anticoagulation in hemodialysis (given IV into circuit -- not directly into patient)
167
what monitoring should be done when giving LMWH?
an anti XA assay, sometimes in renal failure patients and extreme weights (<40kg >10kg) extra monitoring is done. Monitoring is typically based on the institution
168
which has a longer half life, UFH or LMWH?
LMWH
169
how is LMWH cleared from the body?
renally
170
LMWH is not recommended if the CrCl is below_____ mL/min
30
171
what is the antidote for LMWH?
partially reversible with protamine
172
what is the contracted LMWH at NS hospitals?
dalteparin (Fragmin)
173
what is the prophylactic dosing of dalteparin for patients weighing less than 40 kg?
2500 units SQ daily
174
what is the prophylactic dosing of dalteparin for patients weighing 40-100 kg?
5000 units SQ daily
175
what is the prophylactic dosing of dalteparin for patients weighing >40kg?
7500 units SQ daily or 5000 units SQ BID
176
what is the therapeutic dosing for dalteparin?
200 units/kg SQ D or 100U/kg SQ bid
177
t/f dalteparin can be given through IV, but it is rarely given this way
t
178
dalteparin should not be used for ____
acute STEMI
179
t/f dlateparin is available as vials, ampoules, and prefilled syringes
t
180
what formulation of dalteparin contains a preservative?
vials
181
t/f there are teaching kits and patient support programs available for dalteparin
t
182
t/f the dose banding for dalteparin is safe and cost effective; you just round to the nearest pre-filled syringe size
t
183
lovenox is commonly used for prophylaxis and therapeutic indications in which provinces?
NB and PEI
184
lovenox is used in NS hospitals for what indication?
STEMI
185
the first dose of lovenox for treatment of STEMI is given by what route?
IV
186
what is the prophylactic dosing of lovenox?
30, 40, or 60 mg SQ daily or 40 mg SQ BID
187
what is teh therapeutic dosing for lovenox?
1mg/kg BID or 1.5mg/kg daily
188
lovenox is available in what formulations?
vials and prefilled syringes
189
t/f subsequent entry biologics to lovenox are now availanle
t
190
what is the brand name for tinzaparin?
Inohep
191
t/f Tinzaparin is rarely used in atlantic Canada
true
192
there is some evidence for the use of Tinzaparin when CrCL is as low as ____
20mL/min
193
what is the prophylactic dosing for Tinzaparin?
either 3500 or 4500 units SQ daily
194
what is the dosing for VTE treatment using Tinzaparin?
175 units/kg SQ daily
195
what is the brand name for Nadroparin?
Fraxiparin
196
t/f Nadroparin is rarely used
t
197
what is the prophylactic dosing for nadroparin?
2850 units daily (general surgery) or 38 units/kg daily for orthopedic surgery
198
what is the dosing fo nadroparin for VTE treatment?
171 units/kg SQ daily or 86 units/kg SQ BID
199
according to ASH guidelines, what is the recommendation for determining initial dosage of LMWH in obese patients for VTE treatment?
initial dose according to actual body weight rather than a fixed max daily dose
200
In obese patients receiving LMWH treatment for VTE, ASH suggests AGAINST using _____ monitoring to guide LMWH dose adjustment
factor Xa concentration (results found that there are more PEs, more DVTs and more bleeding risk with this monitoring)
201
Describe the steps a patient would use to administer LMWH
1. wash hands
2. clean and dry skin (alcohol swabs not needed at home)
3. You need to be in a position where you can see and pinch up the skin on your stomach, thighs, or back of arm. (Stomach is best spot typically, but NOT for infants or children)
4. Avoid area near navel, scars, or bruise from previous injection
5. Remove the needle cap by pulling it straight up and off the needle
6. hold the syringe in your dominant hand and pinch the skin with the other.
7. Insert the ENTIRE length of teh needle into the pinched skin at a 90 degree angle. Do not release the pinched skin until done injecting
8. while still holding the pinched skin, press down on the plunger to inject the contents of the syringe
9. while still holding the plunger, pull the needle out
10. release the pulnger and skin pinch
11. hold gentle pressure with a cotton ball on the injection site for 1-2 minutes to reduce bleeding and bruising (do not rub the skin)
12. put syringe into a sharps container that can be safely returned to the pharmacy
202
what is fondaparinux?
a synthetic and specific inhibitor of factor Xa
203
what is the MOA of fondaparinux?
inhibits factor Xa which reduced teh formation of thrombin and fibrin
204
what are the indications for fondaparinux?
VTE prophylaxis, VTE treatment, NSTEMI
205
what is the dosing of fondaparinux for prophylaxis or NSTEMI?
2.5 mg SQ daily
206
what is the therapeutic dosing for fondaparinux?
5, 7.5, or 10 mg SQ daily (weight based?)
207
fondaparinux is available only as what dosage form?
pre-filled syringe
208
what monitoring is required for fondaparinux?
anti-XA
209
where is fondaparinux metabolized?
renal
210
fondaparinux is not recommended if CrCL is below ____
30 mL/min
211
what is the antidote for fondaparinux?
no specific antidote?
212
what is the MOA of argatroban?
direct thrombin inhibitor
213
what are the indications for argatroban?
1. suspected or confirmed HIT
| 2. can be used as a substitute for UFH, but not commonly done.
214
what is the dosing for argatroban?
IV infusion as per the nomogram
215
what monitoring is required for argatroban?
PTT
216
why is it complex to switch from argatroban to warfarin?
argatroban prolongs INR
217
what is an ADR of argatroban?
bleeding
218
how is argatroban metabolzed?
hepatic
219
how is the dosage of argatroban changed in hepatic failure?
reduced
220
what is a major factor to consider with argatroban?
cost
221
what is the MOA of bivalrudin?
direct thrombin inhibitor
222
what are teh indications for bivalrudin?
1. suspected or confirmed HIT (off label)
| 2. UFH sub (not common)
223
Heparin induced thrombocytopenia (HIT) is a profoundly _____ state
hypercoagulable state
224
HIT is a ____ disorder that is usually mediated by ___ antibodies that bind to ___ complexes
iatrogenic; IgG; PF4-heparin
225
the IgG antibodies can cause a hypercoagulable state by activating ___ and ___
platelets and procoagulant microparticles
226
1/3 to 1/2 of patients with HIT will develop ___, ___ or ____
venous, arterial, or microvascular thrombosis
227
out of UFH and LMWH, which is 10x more likely to cause HIT?
UFH
228
HIT is reported in up to ___% of patients receiving UFH depending on teh patient population
5
229
the onset of HIT is typically ____ days after starting therapy, unless there has been recent exposure to UFH or LMWH, in which case it can happen sooner
5-10
230
t/f if HIT is suspected, all heparin must be stopped and a HIT-safe anticoagulant used instead
t
231
how is HIT diagnosed?
4T scoring
232
if the antibody assay is positive for HIT, what is the follow up lab to confirm?
functional assay
233
for bloodwork, day zero is teh ___ date
admission
234
In patients with suspected HIT, the ASH panel suggests usign the ____ score to estimate the probability of HIT, rather than a _____ approach
4Ts score; gestalt
235
if there is any missing information when perfomring a 4Ts score, it is safer to err on the side of a ____(higher / lower) score
higher
236
t/f the 4Ts score should be reassessed frequently. If there is a change in the clinical picture, it should be recalculated
t
237
HIT immunoassay tests detect the presence of ___ antibodies
anti-PF4/heparin
238
functional HIT assays detect ___
antibodies capable of binding and activating platelets
239
give examples of HIT immunoassay tests
1. ELISA to detect IgG
2. ELISA to detect polyspecific antibodies
3. IgG specific chemiluminescent assay
4. particle gel immunoassay (PaGIA)
5. latex agglutination assay
240
give examples of functional HIT assays
1. serotonin release assay (SRA)
2. heparin-induced platelet activation test (HIPA)
3. platelet aggregation test (PAT)
4. flow cytometry-based assays
241
if there is an intermediate or high probability 4Ts score, the ASH panel recommends what type of assay?
an immunoassay
242
if there is an intermediate or high probability 4Ts score and the immunoassay comes back positive, what is a next step that can be done (if resources are available)?
functional assay
243
liklihood of HIT increases with a higher ELISA ____
OD (Optical Density)
244
in patients with HIGH probability HIT 4Ts score, ASH recommends discontinuation of ____ anticoagulants and starting _____ type anticoagulants at therapeutic intensity
heparin; non-heparin
245
if a patient has an intermediate 4Ts HIT score, ASH recommedns stopping heparin and starting a non-heparin at prophlactic intensity if ____ and at therapeutic intensity if ____
patient is at high bleeding risk; patient is not at high bledding risk
246
why give HIT intermediate risk patients who have high bleeding risk dosed prophylactly with a non-heparin anticoag? ``
bc they are at high bleeding risk, making them lower risk for HIT and higher dosed anti-coags could cause harm (bleeding)
247
in patients with acute HITT or acute isolated HIT, the panel recommends against starting a VKA before doing a _____
platelet count recovery (platelets >/= 150 x 10^9 /L)
248
if a patient has already been started on VKA at onset of acute HITT or acute isolated HIT and a platelet count recovery has not been performed?
VKA should be stopped and in IV vitamin K given in combination with starting a non-heparin anticoagulant
249
what are some side effects of early initiation of VKA at onset of acute HITT or acute isolated HIT?
1. warfarin-induced skin necrosis
2. venous limb gangrene
3. recurrent thrombosis
4. limb amputation
250
In patients with HITT or isolated HIT, ASH recommends stopping ___ and starting ___
heparin; non-heparin anticoagulant
251
what is HITT?
acute HIT complicated by thrombosis
252
what is isolated HIT?
acute HIT without thrombosis
253
what are the non-heparin anticoagulants recommended by ASH to replace heparin in possible HIT patient?
argatroban, bivalirudin, fondaparinux, or a direct oral anticoagulant (DOAC)
254
what are 2 non-heparin anticoagulants recommended for patients with critical illness, increased bleeding risk, or for possibly urgent procedures? Why?
argatroban or bivaliruden because they have shorter duration of effect
255
what is something that needs to be accounted for when considering argatroban in a patient with moderate or severe hepatic dysfunction (Childs-Pugh B or C)?
might needed to decrease dose or avoid this drug altogether
256
what are the recommended non-heparin anticoagulants in life or limb threatening VTE (massive PE or venous limb ganagrene)?
parenteral preferred: argatroban, bivalirudin, fondaparinux; some (few) patients are treated with DOACs
257
what are the recommended non-heparin anticoagulants recommended in clinically stable patients at average bleeding risk?
fondaparinux or DOACs (most published research on the DOAC rivaroxaban)
258
how is argatroban cleared from the body?
hepatobiliary
259
how is bivalirudin cleared from the body?
enzymatic clearance
260
how is fondaparinux cleared from the body?
renal
261
how is rivaroxaban cleared?
renal
