PHRX 5040 Cardio Module - Exam #2 (Dr. Bessada's Section)

what are the 3 categories of Virchow's triad contributing to the etiology of VTE?

- hyper coagulable state

- vascular wall injury

- circulatory stasis

what are 8 contributing factors to a hyper coagulable state

- malignancy

- pregnancy

- hormonal therapy

- trauma or surgery of lower extremity

- nephrotic syndorme

- IBS

- sepsis

- thrombophilia

what are 6 contributing factors to vascular wall injury?

- trauma or surgery

- venipuncture

- chemical irritation

- heart valve disease or replacement

- atherosclerosis

- indwelling catheters

what are 5 contributing factors to circulatory stasis?

- A fib

- left ventricular dysfunction

- immobility or paralysis

- venous insufficiency or varicose veins

- venous obstruction form tumor, obesity or pregnancy

overall, describe reversible risk factors of VTE

- resolve after provoking VTE

- dont need long term anticoagulation

what are 5 reversible VTE risk factors

- surgery within 3 months requiring general anesthesia

- confined to hospital bed for 72+ hours

- C section

- medication use, especially with estrogen therapy

- long stretches of immobility

overall, describe persistent risk factors of VTE

- persist after provoking VTE

- cannot remove risk factor

- requires longer term anticoagulation therapy

what are 4 examples of persistent VTE risk factors?

- active cancer

- autoimmune disorders = antiphospolipid syndrome

- chronic immobility

- ongoing hyper coagulable disease = IBS

describe pts who are at low risk of VTE

- ambulatory pt without VTE risk factors

- observation pt with LOS 2 days or less

- same day or minor surgery

describe pts who are at moderate risk of VTE

most medical/surgical pts = medically ill

describe pts who are at high risk of VTE

- lower extremity arthroplasty

- hip, pelvic or severe lower extremity fracture/surgery

- abdominal or pelvic cancer surgery

- multiple major trauma

- orthopedic trauma

- non orthopedic trauma

describe the use of mechanical ppx for VTE prevention

indication = pts at high bleed risk

what is the duration of VTE prevention treatment for pts with major general surgery?

until hospital discharge

what is the duration of VTE prevention treatment for pts with major general surgery with prior VTE?

28 days

what is the duration of VTE prevention treatment for pts with major trauma?

while immobile, up to 8 weeks

if using a DOAC for VTE ppx inpatient for a medically ill pt (mod risk), which agent is preferred?

rivaroxaban

- if using DOAC ppx inpatient, give rivaroxaban not apixaban

describe the duration of VTE prevention for medically ill pts (moderate risk_

6-14 days during acute illness, typically depends on:

- length of immobility

- chronic risk factors

overall, describe the VTE prevention measures taken in pts high risk = ortho surgery

- mechanical ppx if high bleed risk

- pharmacologic therapy = LMWH or DOAC

overall, describe the VTE prevention measures taken in pts high risk = non-ortho surgery

- mechanical ppx if high bleed risk

- pharmacologic therapy = UFH or LMWH, no DOAC use

overall, describe the VTE prevention measures taken in pts medically ill = moderate risk

- mechanical ppx if high bleed risk

- pharmacologic therapy = UFH or LMWH or rivaroxaban

- continue pharm therapy for length of immobility, and no longer

overall, describe the VTE prevention measures taken in pts low risk = ambulatory pts and same day surgery

typically, nothing is needed

what are 7 factors that increase a pts risk of bleed?

- age 65+

- severe liver disease

- severe renal disease

- thrombocytopenia

- cancer

- meds = other anticoagulants, anti platelets and NSAIDs

- previous bleeds (important)

overall, describe the clinical symptoms of DVT

- edema

- leg pain

- calf tenderness

- swelling

- discoloration

- increased leg warmth

what is key to note about symptoms of DVT?

- symptoms are generally unilateral

- generally imapacts ONE leg

overall, describe the symptoms of PE

very broad, requires further testing

- tachycardia

- tachypnea

- hemoptysis

- dyspnea

- cough

- chest pain

describe the role of D-dimer in diagnosis of VTE

- if there is increased D-dimer then it indicates that there MAY be a clot and pts should go to imaging

- positive D dimer = great than 500

describe the role of imagining in VTE

- allows you to see the clot

- this then allows for a definitive diagnosis of VTE

what helps you determine where/how VTE pts should be initially treated?

- depends on hemodynamics stability

- an unstable pt requires hospitalization

- severity of VTE increases as embolism occurs and increased severity will impact pt hemodynamics

what lab values indicate a pt is unstable?

- HR greater than 120

- systolic BP less than 90

- RR greater than 22

where should the pt be treated if they are stable with good prognosis?

outpatient treatment

where should the pt be treated if they are stable with poor prognosis?

hospitalization

where should the pt be treated if they are unstable

hospitalization

what are 4 agents that may be used as parental VTE treatment?

- LMWH

- heparin

- pentasaccharides = fondaparinux

- direct thrombin inhibitors = agratroban

what are 2 agents that may be used as oral VTE treatment?

- DOACs

- vitamin K antagonist = warfarin

describe the general course of treatment for subclinical acute PE

start DOAC monotherapy

describe the general course of treatment for symptomatic = low clinical severity score acute PE

start DOAC monotherapy

describe the general course of treatment for symptomatic = elevated clinical severity score acute PE

- start parenteral AC

- LMWH preferred over UFH

describe the general course of treatment for incipient cardio failure acute PE

consider thrombolytics

describe the general course of treatment for cardiopulmonary failure acute PE

consider thrombolytics

- key point = once lungs and heart deteriorate it becomes an emergency and fast acting thrombolytics are needed

what are the 3 techniques for acute VTE treatment?

- overlap

- switch

- mono therapy = preferred

overall, describe the overlap technique for acute VTE treatment

- start with parenteral AC (UFH, LMWH, Fonda) and warfarin

- continue for 5 days and INR 2-3

- then use ONLY warfarin daily

- the overlap is needed due to the initial warfarin lag period

what is the LMWH treatment dose for acute phase VTE (seen in overlapping method)?

- SC LMWH BID

- enoxaparin 1 mg/kg BID

overall, describe the switch technique for acute VTE treatment

- start ONLY with parenteral AC = UFH, LMWH or Fonda

- continue for 5-10 days

- switch to one of the following DOACs only = dabigatran, edoxaban

what are the 2 DOACs that can be used when using the switch technique?

- dabigatran

- edoxaban

overall, describe the monotherapy technique for acute VTE treatment

- preferred treatment technique

- start with either apixaban or rivoroxaban once VTE is diagnosed

what is the standard rivaroxaban dosing for treatment of acute VTE?

- 15 mg BID with food x 21 days

- then 20 mg daily with food

what is the standard apixaban dosing for treatment of acute VTE?

- 10 mg BID x 7 days

- then 5 mg BID

what oral agents are preferred in treatment of acute VTE? why?

- DOACs are the preferred agents over warfarin for acute VTE

- because they prevent clots and have a lower bleed risk than warfarin

how long should VTE treatment last when it is a provoked VTE that is reversible?

3-6 month anticoagulation

how long should VTE treatment last when it is provoked VTE that is persistent?

indefinite anticoagulation

how long should VTE treatment last when it is unprovoked VTE

indefinite anticoagulation

describe the use of IVC filters for VTE

IVC filters are only suggested to use in pts with acute VTE where anticoagulants are contraindicated

for advanced treatment of PE, what pts are candidates for systemic thromobolytic therapy?

cardiopulmonary failure = category E

- present with hypotension and do NOT have high bleed risk

- deteriorate after starting anticoagulation therapy, but have not developed hypotension and acceptable bleed risk

what is the main side effect of all anticoagulants? what is our goal?

- main ADE = bleeding

- goal = hemostasis, maintain a balance between bleed and thrombosis risk

describe the dosing of UFH for VTE

- IV infusion only

- dosing is weight based

- adjusted via nomogram

describe the therapeutic monitoring requirements for UFH for VTE

- close monitoring is required

- monitor either aPTT or anti-Xa

- anti-Xa = gold standard for monitoring

describe the monitoring of Anti-Xa levels with UFH use for VTE

- gold standard for monitoring

- tends to be more accurate in hospitalized, acute medically ill pts

- should NOT be used after LMWH or DOAC

what is the most common ADE seen with UFH?

thrombocytopenia

- can cause heparin indued thrombocytopenia = HIT

how is HIT diagnosed?

- diagnostic screening = 4T's

- this score will determine if the drop ion platelets is caused by heparin

what dosage form of UFH is used for VTE treatment?

- IV only for VTE treatment

- VTE ppx = SC

why would UFH be considered over LMWH for VTE?

- in general, LMWJ is preferred over UFH for VTE

unless the pt has:

- poor kidney function

- has upcoming surgeries/procedures

what is the preferred LMWH used for VTE?

enoxaparin (Lovenox)

what is the enoxaparin dose for VTE treatment?

- 1 mg/kg BID

- note that this is the TREATMENT dose not the ppx dose

- admin SC

describe the monitoring parameters for LMWH for VTE

frequent anti-Xa monitoring is NOT necessary due to predictable anticoagulant response with SC admin

what is important to note about the safety of enoxaparin?

- safe to use in pregnancy, does NOT cross the placenta

- preferred anticoagulant in pregnancy

overall, which parental AC is 1st line in VTE treatment?

LMWH preferred over UFH unless procedures planned or kidney injury

what 6 reasons are there that make LMWH 1st line parental AC for VTE treatment?

- predictable anticoagulation dose response

- lower incidence of thrombocytopenia

- reduced need for lab monitoring

- improved SC bioavailability

- dose independent clearance

- longer biological t1/2 = 3-6 hrs

in what cases is UFH preferred over LMWH for VTE? why?

- UFH is not renally cleared = helpful in poor kidney function

- UFH IV can be easily turned off = fast offset, helpful when there are upcoming procedures

when is fondaparinux considered for VTE?

- generally for VTE treatment or ppx

- used only in the setting of HIT

when are IV direct thrombin inhibitors considered for VTE?

- used for VTE treatment

- only in the setting of HIT

in general, why does warfarin require continuous monitoring and pt education?

- narrow therapeutic index

- many food and drug interactions

describe the warfarin SNOT factors

SNOT factors = 7, 9, 10, 2

- this is the order by which warfarin diminishes and inhibits activity of specific clotting factors

- 7 = 4-6 hrs

- 9 = 21-30 hrs

- 10 = 27-48 hrs

- 2 = 42-72 hrs

ALSO inhibits the body's natural anticoagulants:

- protein C = 8 hrs

- protein S = 30 hrs

how long does it take to see the full effects of warfarin?

- 49-72 hrs

- time required to inhibit factor IIa

when is the most thrombotic period of warfarin initiation?

- within the first 30 hrs

- not yet at full treatment efficacy AND the body's natural anticoagulants are inhibited

- this increases thrombosis risk, so the overlap period is very important

what is the target INR for warfarin?

- target = 2.5

- range = 2-3 for most indications

describe the balance of safety and efficacy with warfarin INR values

goal range = 2-3

- less than 2 = increased clot risk

- more than 3 = increased bleed risk

describe the dosing strategy generally sued for warfarin

- individualized dosing is used

- based on desired target INR range and pt response

which 2 enzymes cause the majority of PK interactions with warfarin?

2C9 and 3A4

describe the diet considerations that need to be taken with pts taking warfarin

- pts must be consistent with diet

- then can adjust their warfarin dose to their normal eating habits, do NOT take greens out

what effect do 3A4/2C9 inhibitors have on warfarin metabolism?

increase anticoagulation = increase INR = increase bleed risk

what are 3 specific 3A4/2C9 inhibitors that interact with warfarin?

- amiodarone

- fluconazole

- sulfamethaxzole

what effect do 3A4/2C9 inducers have on warfarin metabolism?

decrease anticoagulation = decrease INR = increase clot risk

what are 4 specific 3A4/2C9 inducers that interact with warfarin?

- carbamazepine

- phenytoin

- rifampin

- vitamin K

what are 3 agents that have PD interactions with warfarin? what do they do?

increase bleed risk

- aspirin

- NSAIDs

- blood thinners

what is a notable drug-food interaction seen with warfarin? what is its effect?

- green leafy vegetables

- decrease INR = increase clot risk

what are 2 specific ADEs seen with warfarin? when are they most likely to occur?

most likely to occur with new initiation within the first 24-42 hrs = increased thrombotic risk

- warfarin induced skin necrosis

- purple toe syndrome

describe the monitoring required with DOACs

do NOT require routine INR monitoring BUT still require monitoring every 3-6 months of the following:

- kidney function

- liver function

- CBC

- body weight

- DDIs

what are 3 special populations where DOACs need to be used carefully?

- renal disease

- liver disease

- extreme body weight

what are the 2 DDI types seen with DOACs?

- P-gp

- 3A4

what impact do p-gp/3A4 inhibitors have on DOACs? what are 4 specific examples?

increase bleed risk

- amiodarone

- propafenone

- quinidine

- verapamil

what impact do p-gp/3A4 inducers have on DOACs? what are 2 specific examples?

decrease concentration = increase clot risk

- carbamazepine

- rifampin

what are 4 reasons as to why DOACs would be sued 1st line for VTE?

- 1st line therapy for acute VTE

- normal renal and hepatic function

- less frequent monitoring

- insurance coverage

what are 5 contraindications to DOAC use?

- strong 3A4 interactions

- mechanical heart valves

- rheumatic heart disease

- pregnancy

- triple positive antiphospholipid syndrome

what are 2 health disparities that may increase a pts risk of developing PAD?

- race = increased risk for black pts

- socioeconomic status

what are 7 PAD related risk amplifiers?

- 75+

- diabetes

- ongoing smokers

- CKD and end stage kidney disease

- polyvascular disease

- microvascular disease

- depression

describe the relationship between PAD and ASCVD

PAD is an ASCVD event

- should be treated with secondary prevention = high intensity statin etc

define claudication

- pain in legs associated with periphery astherosclerosis

- seen in PAD pts

what test is the key diagnostic tool for diagnosing PAD?

ankle brachial index = ABI

describe how ABI can be interpreted to diagnose PAD

- compares leg and arm BPs to calculate ratio to diagnose PAD

- ABI interpretation = abnormal is 0.90 or less

what are the 5 pillars of PAD management?

- lipid management

- glycemic control

- BP management

- smoking cessation

- antithrombotic use