HIT, Valvular heart disease, Anticoagulation reversal

where is the tricuspid valve

between RA and RV

where is the mitral valve

between the LA and the LV

what is stenosis

calcification and narrowing of the valve (decreases ability to push blood forward), primarily a disease of aging

what is regurgitation

blood flowing backwards through the valves

what is aortic stenosis?

most common valvular disease, often occurs as patients age, decreases cardiac output

decreased cardiac output aortic stenosis can cause:

chest pain, fatigue, shortness of breath, and syncope

Treatment for aortic stenosis

minimal drug therapy, if procedural/surgical correct of valve, antithrombotic therapy is likely necessary

Types of aortic valve replacements

surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR)

what is SAVR

requires open heart surgery (invasive) and can replace with a mechanical or bioprosthetic valve

what is TAVR

percutaneous access (similar to a catheterization procedure, less invasive than surgical replacement), only bioprosthetic valve

types of aortic valves:

mechanical valve and bioprosthetic

what is a mechanical valve

lasts 20-30 years; risk of thromboembolism is higher; requires lifelong anticoagulation with warfarin (INR goal 2-3)

what is a bioprosthetic valve

lasts ~10 years; risk of thromboembolism is lower; requires ~3 months of anticoagulation or antiplatelet therapy

what is mitral regurgitation?

most common mitral valve disease that is often due to heart failure (increase blood volume and pressure in left ventricle pushes blood backwards from the left ventricle to the left atrium)

how can we often treat mitral valve disease

can often treat this with adequate diuresis

does mitral valve disease require a valve replacement

it may require a valve replacement if too severe

what is mitral stenosis

most commonly from rheumatic fever (incidence is decreasing); may require mitral valve replacement if too severe

which valve is at higher risk for clotting?

the mitral valve (compared to the aortic valve)

The mitral valve has mainly ______________ blood flow from left atrium to left ventricle

passive/low pressure

the aortic valve has mainly ______________ pressure blood flow from left ventricle to aorta (left ventricle creates your blood pressure)

high

why does the mitral valve have an increase clot risk compared to the aortic valve?

the mitral valve has passive blood flow whereas the aortic valve has forceful/high pressure blood flow

what does HIT stand for

heparin induced thrombocytopenia

what is HIT

a prothrombotic disorder associated with unfractionated heparin (UFH) or low molecular weight heparin (LMWH)

epidemiology of HIT

UFH - 5% of patients and LMWH - 0.5-1% of patients

Types of HIT

HIT and HITT

difference between HIT and HITT

HIT is ‘isolated HIT’ where labs are positive but the patient doesn’t have a clot. HITT is HIT complicated by thrombosis

risk factors for HIT

source of heparin (bovine increased risk over porcine), type of heparin used (UFH higher risk than LMWHH), patient population, longer duration of exposure, and IV administration has higher risk than SQ

which patient population has a higher risk for HIT

surgical patients have a higher risk than medical and obstetric patients

which test is used to assess the likelihood of HIT?

4T’s Pretest Score

how many points on the 4T’s Pretest score indicate low probability for HIT?

<= 3 points

how many points on the 4T’s Pretest score indicate intermediate probability for HIT?

4-5 points

how many points on the 4T’s Pretest score indicate high probability for HIT?

6-8

How is HIT diagnosed?

Once a patient receiving heparin or LMWH has platelet decreasing, a pretest probability score is calculated (4T score or HEP score). If the score is not low, stop all heparin, consider alternative anticoagulant, and send for testing.

Which tests are recommended for HIT after patient has a high pre-test probability score?

PF 4 IgG ELISA Immunoassay and Serotonin Release Assay (SRA)

what is PF 4 IgG ELISA Immunoassay?

it is not diagnostic; detects heparin-dependent IgG antibody; has potential for false positives

what is Serotonin Release Assay?

a validation test and detects actual pathologic response.

In patients with acute HIT or HITT, what is the guideline recommendation for treatment?

discontinuation of heparin and initiation of a non-heparin anticoagulant

What are non-heparin anticoagulant options?

argatroban, bivalirudin, fondaparinux, or a direct oral anticoagulant (DOAC)

DOAC selection for HIT or HITT?

rivaroxaban has the most evidence, but any can be used

rivaroxaban dosing for HIT

15 mg BID until platelet count recovery (platelet count > 150 k), then 20 mg daily

rivaroxaban dosing for HITT

15 mg twice daily for three weeks then 20 mg daily.

Alternative IV anticoagulants after stopping heparin during HIT/HITT

argatroban and bivalirudin

MOA for argatroban and bivalirudin

direct thrombin inhibitors

half-life of argatroban

39-51 minutes

half-life of bivalirudin

10-24 minutes

renal adjustments for argatroban

since ~15% is renally eliminated, will likely need lower infusion rate; not dialyzable

renal adjustments for bivalirubin

~15% is renally eliminated, so it requires initial infusion rate decrease

monitoring for argatroban and bivalirudin

aPTT 1.5-3x ULN; monitor hemoglobin, hematocrit, and platelets

Pearls for argatroban

~85% hepatobiliary elimination and will elevate INR

Pearls for bivalirudin

~85% proteolytic elimination and will elevate INR

when to transition from DTI to warfarin

after platelets >= 150,000

T/F: argatroban and bivalirudin increase INR, but this is not necessarily a reflection of the degree of anticoagulation

True

Which effects INR more, argatroban or bivalirudin?

Argatroban

First step in transitioning from agatroban or bivalirudin to warfarin

administer 5 doses of warfarin

After giving 5 doses of warfarin, if the INR is > 4 what should be done to the argatroban dose?

consider stopping it!

After giving 5 doses of warfarin, if the INR is > 3 what should be done to the bivalirudin dose?

consider stopping

when to recheck PTT/INR after the 5 doses of warfarin and first INR check?

2-4 hours

for patients swapping from DTI to warfarin, if the PTT baseline and INR are in range after follow up (2-4 hrs later) what should be done to the infusion?

leave the drip off

for patients swapping from DTI to warfarin, if the PTT baseline and INR are below range after follow up (2-4 hrs later) what should be done to the infusion?

restart drip

transition from DTI to DOAC?

stop the DTI and start the DOAC !!

duration of therapy for HIT

30 days

duration of therapy for HITT

3 months

when do we reverse anticoagulation

generally, only reverse anticoagulation for life-threatening bleeds or a BIG or URGENT surgery/procedure that requires reversal

T/F: it is preferred to reverse anticoagulation instead of doing a wash-out period for a few days (3-5 half-lives)

False

for renally eliminated anticoagulants, is the hold time longer in patients with poor renal function?

yes, it may be longer

if we reverse anticoagulation, what state do we put the patient in?

a prothrombotic state

what should be done with anticoagulants if the patient has minor or non life-threatening bleeding?

supportive measures, and may hold anticoagulant until hemostasis is achieved

specific reversal agent for warfarin

Vitamin K (Phytonadione)

non-specific reversal agent for warfarin

Fresh frozen plasma; prothrombin complex concentrate

specific reversal agent for apixaban, rivaroxaban, and edoxaban

Andexanet Alfa (Andexxa)

non-specific reversal agent for apixaban, rivaroxaban, and edoxaban

Prothrombin complex concentrate

specific reversal agent for dabigatran

Idarucizumab

non-specific reversal agent for dabigatran

Activated prothrombin complex concentrate

specific reversal agent for heparin and LMWH

Protamine

reversal of factor Xa inhibitors

Andexanet Alfa (if available) OR 4-factor PCC

reversal of dabigatran

Idarucizumab (if available) OR activated PCC

reversal of warfarin

4-factor PCC and IV vitamin K

Class of Andexanet Alfa

recombinant modified human factor Xa protein binding and sequestering of factor Xa inhibitor

FDA indication for Andexanet Alfa

apixaban and rivaroxaban reversal

off-label indications of Andexanet Alfa

edoxaban reversal

onset for andexanet alfa

2 minutes

duration for Andexanet alfa

2 hours

class of 4-factor PCC (Kcentra, Belfaxar)

coagulation factors II, VII, IX, and X, and anticoagulants protein C and S

FDA indication for 4-factor PCC

life-threatening bleeding on warfarin

off-label indication for 4-factor PCC

life-threatening bleeding on factor Xa inhibitors

onset for 4-factor PCC

10 minutes

duration for 4-factor PCC

8 hours

class for Idarucizumab (Praxbind)

humanized monoclonal antibody fragment that binds to dabigatran and neutralizes effects

FDA indications for Idarucizumab (Praxbind)

dabigatran reversal

onset for Idarucizumab (Praxbind)

5 minutes

duration for Idarucizumab (Praxbind)

12-24 hours

class for Activated PCC (Feiba)

non activated factors II, IX, X, and activated VII

FDA indications for Activated PCC (Feiba)

bleeding with hemophilia A or B

off-label indications for for Activated PCC (Feiba)

life-threatening bleeding on dabigatran

onset for Activated PCC (Feiba)

30 minutes

duration for Activated PCC (Feiba)

12 hours

class of vitamin K (Phytonadione)

promotes liver synthesis of factors II, IV, IX, and X

FDA indication of vitamin K (Phytonadione)

reversal of warfarin

off-label indication of vitamin K (Phytonadione)

liver disease

onset of vitamin K (Phytonadione)

10-12 hours