Anticoag VTE Flashcards
Pathogenesis of Thrombosis
Describe Virchow’s Triad
1) Abnormal Blood Flow
2) Endothelial Injury
3) Hypercoagulability
What can cause endothelial injury?
How does this predispose to thrombus formation?
-Shear stress due to HTN
-HLD
-Elevated blood glucose in diabetes
-traumatic vascular injury
-some infections
1) Platelet activators like collagen promoting platelet adhesion
2) Exposure of tissue factor initiates coag cascade
3)Depletion of natural antithrombotics(t-PA) at site of injury occurs due to fractured endothelial lining
Abnormal blood flow:
Name 2 examples
How does this promote thrombosis formation?
1) Atherosclerotic lesions
2) Bifurcation of vessels
Absence of laminar flow allows platelets to flow close to vessel wall
-stasis inhibits flow of fresh blood into region preventing dilution of activated clotting factors
Hypercoagulability
Name 2 Primary Genetic Disorders
Name 2 secondary (acquired) disorders
1) Mutation in gene encoding factor V (Leiden Mutation)
2) Prothrombin G20210A mutation leads to 30% incr in circulating thrombin levels
1) Heparin exposure leading to heparin :PF4 complex
2) Immune system generates circulating Ab’s to clear platelets that have the heparin:PF4 co plex
Name Primary Hypercoagulable Conditions (7)
-Antithrombin (ATIII) deficiency
* Protein C deficiency
* Protein S deficiency
* Factor V Leiden
* Elevated factor VIII levels
* Factor XII deficiency
* Prothrombin G20210A
mutation
Name Secondary Hypercoagulable Conditions (7)
-Pregnancy
* Immobility
* Trauma
* Oral contraceptives
* Antiphospholipid syndrome
* Malignancy
* HITTS
Who is at higher risk for developing VTE? (4)
trauma, multiple surgeries of lower extremities, metastatic cancer, previous history of VTE
Risk Factors for VTE (DVT/PE)
(12)
- Age
- Previous VTE
- Surgery (hip / knee
replacement) - Trauma
- Immobility
- Malignancy
- Pregnancy
- Oral contraceptives /
hormone replacement
therapy - Hypercoagulable state
- Indwelling venous
catheter - Acute major illness
- Obesity
Signs and Sx’s of a DVT?
1) What kind of leg swelling?
2) Pain located where and when foot is doing what?
3) ____ in superficial veins
1) Unilateral leg swelling (warmth, tenderness, discoloration)
2) behind knee or calf when foot is flexed (+ Homan’s sign)
3) Palpable cord
What’s signs and sx’s of PE?
List the major ones first (5)
(D,C,C,T,T)
-Dyspnea
-Tachypnea
-Chest pain
-Chest tightness
-Tachycardia
-Diaphoretic
* Cough
* Dizziness
-Hemoptysis
* Palpitations
* Light-headedness
How to diagnose DVT?
-Clinical suspicion based on?
-Compression Ultrasound
Doppler =
B Mode =?
-Elevated ????
-Venography
-Wells score of?
risk factors
sound, visual
D Dimer (Normal is <= 240 ng/mL)
> =2 points
How to diagnose PE:
What kind of Scan? If mismatch this means high probablity of?
What kind of CT?
Elevated What?
What kind of angiogram?
Simplified Wells PE score that is ?
Ventilation/Perfusion (V/Q) scan which is less invasive.
-If mismatch, PE
SPIRAL
D-dimer
Pulmonary angiogram (contrast, expensive)
> 4 points
Risk factors for major bleeding while taking anticoag therapy
-Higher anticoagulation intensity
* Initiation of therapy (first few
days and weeks)
* Unstable anticoagulation
response
* Age > 65 years old
* Concurrent aspirin or other
antiplatelet therapy
* Concurrent NSAID use
* History of GI bleeding
* Recent surgery or trauma
* High risk for fall / trauma
* Heavy alcohol use
* Renal failure
* Cerebrovascular disease
* Malignancy
Fibrinolytic Drugs
-Used to ?
-Has the potential to dissolve not only pathologic thrombi but also ___ which could lead to ?
1) Lyse already formed clots, and thereby to restore the patency of an obstructed vessel
2) physiologically appropriate fibrin clots, which could lead to hemorrhage of varying severity
Indications for Fibrinolytic Drugs : (3)
1) Massive ileo-femoral DVT at risk for limb gangrene due to venous occlusion
2) Hemodynamically unstable PE patients (ie. SBP < 90 mm Hg, shock)
3) Select high-risk PE patients without hypotension or shock providing the risk of
bleeding is acceptable (gray-area)
What are some factors associated with high risk for adverse PE outcomes? (4)
1) Ill appearing patients with marked dyspnea, anxiety and low oxygen saturation
2) Elevated cardiac troponin levels
3) right ventricular dysfunction on echocardiography
4) right ventricular enlargement on chest CT
CI’s for Fibrinolytic Drugs
Memorize this list
-Active internal bleeding (not including menses)
* Previous intracranial hemorrhage (ICH) at any time
* Ischemic stroke within 3 months (except ischemic stroke within 4.5 hours)
* Known malignant intracranial cancer (primary or metastatic)
* Known structural vascular lesion (e.g., arteriovenous malformation, AVM)
* Suspected aortic dissection
* Significant closed head or facial trauma within 3 months
* Intracranial or intraspinal surgery within 2 months
* Severe uncontrolled hypertension (unresponsive to emergency therapy)
* For streptokinase, prior streptokinase treatment within the previous 6
months
Before fibrinolytic therapy begins, administer what?
For High Intensity Heparin
-use which weight?
Loading dose?
Maintenance dose?
During fibrinolytic therapy, either __ or ___ for duration of fibrinolytic administration
IV heparin in full therapeutic Doses
-Actual body weight
-LD : 80 units/kg bolus IV x 1 (max initial bolus = 10k units)
-MD : 18 units/kg/hr continuous IV (max initial rate = 2150 units/hr)
continue, suspend heparin
For Fibrinolytic Drugs and Dosing, Refer to Printout
Kim Printout
Initial Acute Phase Tx (Days 0-7)
-What options can you use? (4)
1) UFH IV or SC
2) SC LMWH
3) SC FONDAPARINUX
4) Oral Rivaroxaban or apixaban
If you use oral dabigatran or edoxaban , what do they require?
5-10 days of parenteral therapy first
Transitioning from Parenteral to Orals :
Continue for at least ___ AND until ____ (inr of ___) for at least 24 hrs, then continue on PO warfarin alone (Best practice)
No overlap is necessary if switching from parenteral therapy to ?
5 days, warfarin is therapeutic , 2-3
rapid acting DOAC (Rivarox or apixaban)
Note, Heparin will not ___ only ___
dissolve a clot, prevent new clot propagation and growth
Heparin, LMWH, and Fondaparinux don’t cross the __, which means they’re an ideal choice for anticoag during ?
Placenta
pregnancy
Monitoring Heparin :
Which baseline labs to collect? (5)
Which ongoing/routine labs should be done? State timing as well (2)
Kim, Know Heparin IV and SQ dosing, know goal aPTT and anti xa values
-CBC with platelets
* PT/INR
* aPTT
* BUN
* Serum creatinine
aPTT or Anti Xa
-6 hrs after initial bolus, every 6 hrs until 2 consecutive values are therapeutic, and then daily
-Get aPTT/AntiXa 6 hrs after ANY rate change or subsequent bolus
CBC with Platelets
-Daily if pretx platelet count < 100,000 mm^3
-every 72 hrs if pre tx platelet count >100,000 mm^3
Heparin : Precautions and AE’s
1) has a narrow what?
2) HIT?
3) ___ (minor to major)
4) What kind of rxns?
5) ___ (rare) due to heparin induced inhib of aldosterone synthesis
6) ___ (rare) - asocciated with long term SC use
7) Reverse anticoag by stopping infusion +/- admin of ___
1) therapeutic window
2) Heparin induced thrombocytopenia
3) Hemorrhage
4) Hypersensitivity (fever, chills, urticaria)
5) Hyperkalemia
6)Osteoporosis
7) Protamine
LMWH
What are your two options?
Potency is assessed using?
Describe the Xa:thrombin inactivation ratio
refer to chart for dosing
enoxaparin (Lovenox)
Dalteparin (Fragmin)
Anti factor Xa assays
3-4:1 , this is bc LMWH has sacch unit of 17, which is too short to inactivate thrombin fully.
LMWH -Monitoring
Higher risk patients that may require monitoring include? (4)
Use which assay to monitor?
Sample how many hours post SC dose?
What occurs less often with LMWH than UFH? but can still occur
Obese pt’s, renal impairment CrCl<30 mL/min, elderly + children, cancer
Anti factor Xa
4 hrs
HIT
Recognizing HIT : Any of the following scenarios in the presence of in vitro detected “HIT ANTIBODIES”
1) Platelet count drop of ?
2) ___ or arterial ___
3) ___ @ heparin injection sites
4) _____ that occur after a bolus of IV heparin
1) 50% (even if nadir >150,000) from baseline
2) Venous, thrombosis
3) Skin lesions
4) Acute systemic (anaphylactoid) rxns
Heparin-Induced Thrombocytopenia (HIT)
Description (What type and kind of reaction)
Typical Onset?
Incidence?
Platelet drop ?
Complications?
TX?
Type2, severe immune mediated reaction
4-14 days or <=1 day if pt had been exposed to heparin in past 3 months
<=5%
Significant, usually >50% from baseline; absolute nadir moderately low (median of 60,000 mm^3)
Thrombosis can occur before platelet nadir as a result of a consumptive process
prompt discontinuation of ALL heparin products
-initiation of an alternative anticoag like argatroban, bivalirudin, or fondaparinux. Platelets usually recovers in 4-7 days
HIT Risk Factors
-Duration of Hep admin
-Which type?
-Which type of pt?
-Which gender?
UFH>LMWH
Postsurg> medical>obstetric/pediatric
females > males
Managing Confirmed HIT :
-Discontinue what?
-Initiate non-heparin anticoag at thera doses
A. For clinical stable pt’s at low average risk of bleeding?
B. ICU, dialysis or CrCl<30 mL/min, incr bleeding risk life or limb threatening thromboembolism or potential need for urgent procedure?
C. Transition to oral agents after platelet recovery to >= ?
D. Continue anti coag for ___ if
-no acute thrombosis
-acute thrombosis
- if another indication for anticoag
All heparin products
A. Fondaparinux (Use total body weight)
B. Bivalirudin, argatroban
C. 150x10
D. 1 month, or platelet recovery to >= 150 x10
3-6 months
> 6 months
Fondaparinux :
- MOA?
- Has no effect on ___ inhibition because?
- Potency asessed with ?
- Indirect factor Xa inhibitor
- thrombin inhibition, it’s too short to bridge antithrombin to thrombin
- Anti-factor Xa assays
Direct Thrombin Inhibitors : Bivalirudin
-Administered ?
-Indications?? (2)
-How is it cleaved and how is it excreted?
-Half life with normal renal function?
-What’s necessary for mod to severe renal dysfunction?
IV
-As alternative to heparin when undergoing CABG
-As alternative to heparin in presumed or confirmed HIT
proteolytically cleaved and renally excreted
25 mins
dose reductions
DTI : Argatroban
-Used as alternative to heparin in which pt’s?
-Administered?
-Metabolized by?
-Excreted in ?
-Half life?
-Need dose reduction for?
pt’s with or at risk of developing HIT
IV
CYP
Bile
40-50 mins
Hepatic Dysfunction
See sheet for DOAC’s and dosing
See sheet
Pt Education for DOAC’s
1.DO NOT DO WHAT?
2.REPORT ANY WHAT?
3.YOU MAY HAVE HIGHER RISK OF WHAT?
4.TAKE RIVAROXABAN WITH?
5.AFTER OPENING A BOTTLE OF DABIGATRAN WHAT MUST YOU DO?
1.dont abruptly stop taking your blood thinner w/o talking to your healthcare provider
- Report unexpected bleeding or bleeding that lasts long time (from gums, nose bleeds, heavier menses) , any bleeding you cant control (pink or brown urine, red or black stools, coughing up blood)
- bleeding if u take other meds such as aspirin, nsaids, warfarin
- evening meal
- use within 4 months and keep capsules in original bottle
MOA of warfarin?
Warfarin is antag of Vitamin K dependent factors + proteins.
-Coag factors 2, 7, 9 and 10 + proteins C and S are bio inactive unless carboxylation occurs which requires reduced vitamin K
-Warfarin blocks vit K epoxide reductase which converts vit K to reduced vit K –> no coag
Why is the half life of each factor important?
When will the full antithrombotic effects of warfarin be reached?
It’s important because fully carboxylated factors/proteins arent influenced by warfarin!
Several days
Monitoring Warfarin
What do u use?
What exactly is INR?
Typical INR goal range?
What can be prolonged by warfarin?
INR
-Normalized prothrombin time ratio bt pt’s on warfarin and persons who are not
- (2-3) (2.5-3.5 for high risk mechanical prosthetic heart valves)
aPTT
Warfarin ADME
Food?
Protein bound?
Crosses ___ but not ___
Which enantiomer is more potent?
food in GI tract decr rate of absorption
-99% protein bound (albumin)
-crosses placenta but not milk so breastfeeding is ok
-S enantiomer
Which enzyme affects warfarin PK?
Pt’s with allele 2 and 3 require how much warfarin because?
VKORC1
Affects warfarin ___
-Encodes for what?
-Warfarin dose requirements will be changed how?
CYP2C9
-less warfarin bc they encode an enzyme with decr metabolic activity
PD
-vitamin K epoxide reductase complex
-reduced by 25% in hetero and by 50% in homozygotes
Warfarin Dose
-Should be tailored to?
-Goal INR?
-Which baseline labs are needed?
-Starting daily dose for the following
A. AGE < 70 : AA, Cauc/Hispanic, Asian
B. AGE >= 70 AA, Cauc/Hispanic, Asian
In all scenarios, how would u reduce or increase a dose?
Patient
-INR = 2-3
-PT/INR, cbc, liver panel, albumin
A. 7.5, 5, 2.5
B. 5 mg, Females 2.5, Males 5 , 2.5
Incr/decr dose by 2.5 mg or 50% whichever is less
Warfarin Dose Lowering Factors ?
Weight < 45 kg
* Baseline INR > 1.3
* Malnourishment
* Albumin < 3 gm/dL
* Liver disease
* Catabolic conditions (recent
surgery, hyperthyroidism, ADHF,
pneumonia)
* Taking azole antifungals,
metronidazole, Septra,
amiodarone
Warfarin Dose RAISING FACTORS?
-Weight > 90 kg
* Untreated hypothyroidism
* Receiving enteral feeds
* Taking rifampin, carbamazepine,
dicloxacillin, phenobarbital,
bosentan
Study which drugs incr and decr war metabolism
Sheet
Major Toxicity with Warfarin? (2)
-Bleeding
-Risk of intracranial hemorrhage incr dramatically with INR > 4
OTHER toxicities? (3)
Birth defects, skin necrosis, purple toe syndrome
When treating DVT/PE what must u do with warfarin?
-Tx with BOTH for how long?
Must have therapeutic INR for how long?
Overlap UFH/LMWH treatment
at least 5 days
2 consecutive days
Reversal Agents : Protamine
-Binds only ___ therefore only partially neutralizes __ and has no effect on ___
-1 mg protamine corresponds to?
-Half life ?
-ADmin?
-No more than __ should be administered in 10 min period
long heparin molecules, LMWH, fondaparinux
100 units circulating heparin
60 mins
slow IV push over 1-3 mins
50 mg
Protamine and LMWH (Enoxaparin)
what’s the ratio of protamine to enox if enox given < 8 hrs ago ?
Whats ratio of protamine to enox if enox given >8 hrs ago?
1 mg protamine : 1 mg enox
0.5 mg prot : 1 mg enox
Protamine ae’s?
-Dyspnea, wheezing, cyanosis
– Flushing, urticaria
– Chills
– Chest pain
– Nausea / vomiting
– Bradycardia, severe hypotension, anaphylactoid reactions have
occurred from too rapid administration
Vitamin K :
-Source?
-Vitamin K deficiecny signs?
-Used to therapeutically correct what?
-Its inexpensive!
-Preferred route? how long is max effect?
-SC has erratic absorption
-IV is associated with ___ so reserve for ? Effects seen?
Green plants, Phytonadione is only natural Vit k avail for therapeut use
- tendency to bleed
-Bleeding tendency or hemorrhage associated w/deficiency
-PO, 24 hrs
-Anaphylaxis, life threatening bleeds . 6-12 hrs
For other reversal agents see sheet
Kim, make the sheet
