VTE Flashcards by Jessyka Yard

what are the precursor diseases related to VTE that are important to have under control

HTN
DM
Dyslipidemia
Metabolic Syndrome

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this is a stationary blood clot that remains at its point of origin

thrombus

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production of thrombus

thrombosis

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the is a blood clot which has traveled from its point of origin to another location which occludes a vessel

embolus

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this is obstruction or occlusions of a vessel by an embolus

embolism

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these are agents that affect the process of thrombosis; includes both anticoagulants (affects the coagulation pathway) and anti platelet agents (affect the function of platelets)

antithrombotic agents

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does the arterial or venous thrombosis result from atherosclerotic disease; acute plaque rupture initiates clotting process

arterial

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what is a thrombus composed of

fibrin
platelets
RBCs

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does this describe the types of thrombus in arteries or veins?
lots of fibrin and platelets with some RBCs

arteries - therefore anti-platelets work best in arteries due to the high number of platelets

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does this describe the types of thrombus in arteries or veins?
lots of fibrin and RBCs with some platelets

veins - therefore antiplatelet agents would not work the best in the veins due to the low number of platelets

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what are the two main types of venous thromboembolism (VTE)?

deep vein thrombosis (DVT) and pulmonary embolism (PE)

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this occurs in the superficial veins (either upper or lower extremity).
- lower extremity ___ is often related to varicose veins.
- may require anti-coagulant tx depending on size, location, and other patient risk factors

superficial vein thrombosis (SVT)

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this is a thrombus formation, usually in the deep veins of the legs. can also have upper extremity DVT which is less common

deep vein thrombosis (DVT)

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what are the two classes of DVT?

distal - confined to the veins elwoe the popliteal vein (below the knee) most common location

proximal - involves the popliteal and/or a more proximal veins (above the knee) more risk of embolism

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this is a clot (embolus) that lodges into the pulmonary artery (or one of its branches), causing complete to partial obstruction of pulmonary blood flow

pulmonary embolism (PE)

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list some VTE risk factors according to Virchow’s Triad

Hypercoagulability
- drugs (estrogen, SERMs)
- malignancy
- pregnancy
- genetic abnormalities
Vascular Injury
- major orthopaedic surgery (e.g. knee and hip replacements)
- major trauma
- indwelling venous catheters (e.g. pt getting chemo and blood clot originates from the IV line)
Stasis
- major medical illness
- immobility (e.g. bedrest for at least 3 days during hospital admission)
- major surgery

extra risk factors:
- age (risk doubles with each decade after age 50)
- prior history of VTE (once you have an event, your risk will never go back to 0 - biggest risk factor)

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diagnosis of DVT

signs/symptoms:
- extremity pain, tenderness, swelling, eryhtema, warmth, cyanosis/discoloration, palpable cord & Homan’s sign (if flex foot will cause pain)

clinical probability scoring tools:
- Wells DVT risk score
- D-dimer (measures amount of D-dimer protein your body makes to break down clots - high D-dimer may suggest you have a blood clot or clotting problem)

diagnosis testing
- Doppler ultrasound

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diagnosis of PE

signs/symptoms:
- dyspnea (SOB), tachypnea/tachycardia, pleuritic chest pain/palpitations, cough, diaphoresis,

clinical probability scoring tools:
- Wells PE risk score
- D-dimer (measures amount of D-dimer protein your body makes to break down clots - high D-dimer may suggest you have a blood clot or clotting problem)

diagnostic testing:
- CTPA (CT scan) *main test for diagnosing PE
- V/Q scan

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what is the route for Unfractionated Heparin (UFH)

sc or iv

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what class do these agents fall into:
- Dalteparin (Fragmin)
- Enoxaparin (Lovenox + biosimilars)
- Tinzaparin (Innohep)
- Nadroparin (Fraxiparine)

low molecular weight heparins (LMWH)

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what class of medication is Warfarin

Vitamin K antagonist

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what class do these medications fall into:
- Fondaparinux (Arixtra) -> indirect
- Rivaroxaban (Xarelto) -> DOAC
- Apixiban (Eliquis) -> DOAC
- Edoxaban (Lixiana) -> DOAC

Anti Factor Xa Inhibitors

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what class of medication does Dabigitran (Pradaxa), Agratroban and Bivalirudin (Angiomax) fall into

Direct Thrombin Inhibitors (DOAC)

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what class of medication does Alteplase (tPA / Activate) fall into

Fibrinolytics / Thrombolytics

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this lab test measures the time it takes for a clot to form when not on anticoagulant tx / measures effect of intrinsic and common pathway

Activated Partial Thromboplastic time (aPTT)

this lab test is a measure of the integrity of the extrinsic and final common pathways

Prothrombin Time (PT)

this lab test is a ratio of a patients prothrombin time (PT) to a normal control sample

International Normalized Ratio (INR)

this lab test indirectly measures the amount of LMWH in the blood by measuring its inhibition of factor Xa activity

anti-Xa levels (for LMWH)

with regards to thrombosis what are we looking for on a CBC

platelets and Hemoglobin

this lab test may be important for the dosing of some of the anticoagulant agents

SCr

this agent used for treatment of VTE potentiates the action of antithrombin III and thereby inactivates thrombin. is given SC (onset of 1-2 hr) or IV (onset within mins).

UFH

what baseline testing is needed for UFH

weight, CBC, INR and aPTT

true or false: UFH uses weight based dosing

true

true or false: UFH needs to be dose adjusted for reduced renal function

false

what should be monitored in patients on UFH

*EFFICACY & BLEEDING* - aPTT (as per protocol) - CBC/platelets q 2-3 days while on tx ADE's: heparin induced thrombocytopenia (drop in platelets)

true or false: UFH is safe in pregnancy

true

this agent used for treatment of VTE inhibits primarily factor Xa. it has a longer plasma half-life and has a more predictable pharmacokinetic profile. it is given SC with a peak onset of 3-5 hours

LMWH e.g. enoxaparin

true or false: LMWH uses weight based dosing

true

true or false: LMWH is safe in pregnancy

true

what baseline testing is required before initiating LMWH

weight, Scr, CBC, INR and aPTT

true or false: LMWH needs to be dose adjusted for reduced renal function

true

what should be monitored in a patient who is on LMWH

*EFFICACY & BLEEDING* - CBC/platelets, SCr periodically - Anti-Xa levels ADE's: heparin induced thrombocytopenia (drop in platelets)

this agent used to treat VTE is a synthetic indirect inhibitor of factor Xa; contains the five-saccarhide sequence of UFH responsible for its activity. is given SC with an onset of 1-3 hrs

Fondaparinux

true or false: Fondaparinux is safe to use in pregnancy

true

what baseline testing is required before starting a patient on Fondaparinux

weight, CBC, SCr, INR and aPTT

true or false: Fondaparinux uses weight based dosing

true

true or false: Fondaparinux needs to be dose adjusted for reduced renal function

true

what should be monitored in patients on Fondaparinux

*EFFICACY & BLEEDING* - CBC/SCr periodically (note: ADE other than bleeding is uncommon)

this agent used to treat VTE inhibits Vitamin K dependant clotting facts in the liver. has 100% bioavailability and is highly protein bound. it is taken PO and can take 3-7 days to see an effect so cannot make changes to doses to quickly here

Warfarin

what baseline testing is required before starting a patient on Warfarin

CBC, INR!!!!! (aPTT)

true or false: Warfarin is safe to use in pregnancy

false

true or false: Warfarin uses weight based dosing

false

true or false: Warfarin needs to be dose adjusted based on renal function

false

what should be monitored in patients on Warfarin

*EFFICACY & BLEEDING* - INR!!!!!! (target 2.0-3.0); monitor q3days until stable INR for 2-3 readings then extend duration between tests - CBC periodically - drug interactions (LOTS) + some meds can affect INR readings!

if a patient gets a new clot and is started on Warfarin, what other agent should be overlapped with Warfarin to avoid hypercoagubility, and how long should the overlap last

overlap with short acting agent (UFH, LMWH, Fondaparinux) for at least five days AND until 2 consecutive INR readings in target

how is Warfarin usually dose adjusted if INR is out of range

based on WEEKLY dose

if patients INR is < 2.0, how should the patients dose be adjusted and when should INR be checked

increase weekly dose by 10-15% and repeat INR within 1 week

if the patients INR is between 3.1 and 3.5, how should the patients dose be adjusted and when should the INR be checked

decrease weekly dose by 0-10% and repeat INR within 2 weeks

if the patients INR is between 3.6 and 4.0, how should the patients dose be adjusted an when should the INR be checked

decrease weekly dose baby 10-15% and repeat INR within 2 weeks

if the patients INR is between 4.1 and 6.0, how should the patients dose be adjusted and when should the INR be checked

hold 1 dose of Warfarin, and decrease the weekly dose by 10-15% and repeat INR in 2-3 days

if the patients INR is between 6.1 and 10, how should the patients dose be adjusted and when should the INR be checked

hold 2 doses of Warfarin and decrease weekly dose by 10-15% and repeat INR in 2 days

if a patients INR is > 10, how should the patients dose be adjusted and when should the INR be checked

hold 2 doses, decrease weekly dose by 10-15% and administer Vitamin K (2.5-5mg PO); Repeat INR next day

when are the two situations when Vitamin K should be administered to a patient on Warfarin with an INR out of range?

if INR > 10 or patient is showing signs of bleeding

these agents that are used to treat VTE are direct inhibitors of thrombin or factor Xa. these are taken PO therefore have an onset of 3-4 hrs

direct oral anticoagulants (DOACs)

what baseline testing is required before starting a patient on a DOAC

weight, CBC, SCr, INR and aPTT

true or false: DOACs need to be dose adjusted with reduced renal function

true/false lol - no dose adjustment is CrCl is 25 mL/min but AVOID if less then 15-30 mL/min

true or false: DOACs use weight based dosing

false

true or false: DOACs are safe in pregnancy

false

what should be monitored in a patient who is on a DOAC

*EFFICACY & BLEEDING* - CBC, SCr, INR, aPTT periodically - DOACs are generally well tolerated but Dabigitran can cause some dyspepsia/gastritis

this agent used to treat VTE breaks down the clot - only used in eligible patients (e.g. limb or life threatneing situations with no bleeding contraindications); single dose! Given IV therefore immediate onset it converts plasminogen to the natural fibrinolytic agent plasmin. Plasmin lyses clot by breaking down the fibrinogen and fibrin contained in a clot.

Fibrinolytics (Alteplase)

true or false: Fibrinolytics use weight based dosing

false - certain bolus dose then IV infusion for 2 hours

what is the main adverse effect of anticoagulants

bleeding

this type of bleeding includes fatal bleeding and/or symptomatic bleeding in a critical area or organ, such as intracranial, instraspinal, intraocular, retroperitoneal, intraarticular or pericardial or intramuscular with compartment syndrome and/or bleeding causing a fall in hemoglobin leading to transfusion of two or more units of whole blood or RBCs

major bleeding

this type of bleeding does not meet the criteria for major bleeding but still requires intervention.

clinically relevant non-major bleeding

this type of bleeding has generally little or no clinical significant and may not require further tx or investigations

minor bleeding

which oral anticoagulant has a slightly increased of bleeding during the first 6 months of tx a) DOACs b) warfarin

b) warfarin

true or false: DOACs have a 50% decrease in intracranial hemorrhage versus warfarin

true

true or false: dabigatran, rivaroxaban and endoxaban have a decreased GI bleeding risk compared to warfarin

false - dabigatran, rivaroxaban and endoxaban have similar or increased risk of GI bleeds compared to warfarin

what are some signs or symptoms of bleeding

*blood where its not supposed to be* - blood in stool, urine, vomit - gingival bleeding - excessive menstrual bleeding - change or blurred vision, falls or head trauma - unexplained joint pain, stiffness or swelling - continuing or severe headache with or without confusion, dizziness, n/v, weakness or parasthesias (pins and needles)

what are some risk factors that put patients at an increased risk for bleeding

- hepatic or renal failure - alcohol abuse - cancer - older age - reduced platelet count or function - uncontrolled HTN - anemia - frequent falls - previous stroke - DM - anticoagulant tx - poor anticoagulant control (e.g. warfarin) - comorbidity and reduced function capacity

bleeding management

1. supportive care 2. Stop anticoagulant tx 3. antidotes - vitamin K or Prothrombin Complex Concentrate (PCC) for warfarin - Idarucizumab for Dabigitran - protamine for UFH and LMWH

this is used for bleeding management. it is a humanized monoclonal antibody fragment that specifically binds to dabigitran and its metabolites to completely reverse its anticoagulant effect. it is not effective for other anticoagulants. standard one time dose is 5g IV

Idarucizumab

what therapy option may be used if anticoagulant therapy is contraindicated

vena cava filter

what therapy should be used if a patient has a massive PE with shock and/or has a high risk for PE morbidity or has extensive proximal DVT?

thrombolytic therapy (e.g. Alteplase) if bleeding risk is acceptable

what are the therapy options if the patient has no PE and no extensive proximal DVT

- Apixiban as single drug therapy - Rivaroxaban as single drug therapy - LMWH as single drug therapy - LMWH or UFH overlap with warfarin - LMWH for 5-10 days then dabigitran (no overlap) - LMWH for 5-10 days then edoxaban (no overlap)

what should be done if VTE is provoked by a reversible risk factor

stop anticoagulation

what should be done if VTE is not provoked by a reversible risk factor

long-term anticoagulation therapy periodically reassess risk-to-benefit ratio of and patient preference for continued anticoagulation

if a patient had adequate liver & renal function, expected to have good adherence to medications, unable/unwilling to undergo SC injections and/or INR testing, has medication insurance coverage, what would be the preferred option for this patient?

DOAC! if had VTE with active malignancy: use edoxaban, apixiban or rivaroxaban

if a patient had severe renal dysfunction (CrCl less than 30 mL/min), had a severe drug-drug interaction with a DOAC, has a weight > 140-150 kg (308 - 330 lbs), is unable to obtain a DOAC, has known antiphospholipid syndrome and has no history of HIT, what is the preferred option fort this patient

LMWH bridging to warfarin

if a patient has an active malignancy and DOAC is not an option, or is pregnant, or has a high bleeding risk AND has no history of HIT, what is the preferred option for this patient

LMWH alone

what is the general time frame to treat VTE episode

3 months - therapy beyond 3 months would be used to prevent VTE

if a patient had a provoked VTE (know the reason the VTE occurred), and has a persistent risk factor, what action in terms of anticoagulant therapy should be done

usually continue therapy until risk factor is no longer present as long as VTE risk outweighs bleeding risk

if a patient has a provoked VTE (know the reason the VTE occurred), and has a transient risk factor, what action in terms of anticoagulation therapy should be done

usually d/c after 3-6 months

true or false: DOACs can be dose reduced and still be effective for VTE prevention after 6 months of treatment

true

this is a complication of VTE; occurs in 20-50% of patients after acute DVT. cluster of leg signs and symptoms in patients with a previous DVT including - chronic postural dependant swelling and pain - ambulatory discomfort - skin pigmentation - itching & burning severity of symptoms cary over time. the most extreme manifestation of this is a venous leg ulcer. there is no strategy proven effective for decreasing occurrence. elastic stocking/compression bandages to provide an ankle pressure gradient of 30-40 mmHg if feasible may help with edema or treatment of this

post thrombotic syndrome

this complication of VTE is defined by suboptimal cardiac function, pulmonary artery flow dynamics, or pulmonary gas exchange at rest or during exercise, in combination with dyspnea, exercise intolerance, or diminished function status or QoL, without an alternative explanation

Post PE Syndrome

this is the most severe manifestation of post PE syndrome

chronic thromboembolic pulmonary hypertension (CTEPH)

this is the gold standard treatment for CTEPH which has been proven to reduce morbidity and mortality, improve right circulation hemodynamics, and improve exercise tolerance

pulmonary endarterectomy (PEA)

list the non Pharm options used to prevent VTE

- ambulation - gradual compression stockings - intermittent pneumatic compression - inferior vena cava (IVC) filters

what pharmacological options are available for prevention of VTE

- low dose UFH - LMWH (lower dose) - Fondaparinux - DOACs *warfarin not usually used for prevention

what are the roles for the pharmacist in treatment and prevention of VTE

- recommend appropriate choice of therapy, follow up and monitoring - assess adherence to therapy, provide advice on adherence/missed doses, utilize adherence aids, aid in access issues (e.g. special auth, compassionate access) - educate patients about their disease, avoidance of OTC NSAIDs with anticoagulants - monitor for bleeding and risk factors, assess renal function, assess and manage drug interactions, monitor and interpret INR for warfarin and recommend dosage alterations, assess reasons for poor/increase/variable response to therapy (adherence, excessive alcohol usage, drug interactions, dietary changes)