VTE - Porter

venous thromboembolism

blood clots that start in vein, require immediate medical attention

DVT, PE

deep vein thrombosis (DVT)

blood clot in deep vein (usually leg)

sx: swelling, warmth, redness, pain/tenderness, unilateral

pulmonary embolism (PE)

occurs when DVT clot breaks free from vein wall, travels to lungs and blocks blood flow

sx: chest pain, SOB, wheezing, cough, tachycardia

arterial thrombus

forms from plaque that ruptures causing altered vessel wall

platelet heavy

venous thrombus

irregular clotting caused by vessel wall damage, blood flow changes, alterations in the blood

fibrin rich

VTE risk factors

thrombophilia, increased estrogen, cancer, lung/kidney dz, decreased blood flow, hospitalization, age, pregnancy/postpartum

thrombophilia

usually genetic

abnormal clotting causes by deficiencies in antithrombin III, protein C/S, etc.

VTE medication risk factors

oral/TD contraceptives, HRT, testosterone, certain cancer therapies (tamoxifen, , thalidomide, lenalidomide), glucocorticoids

COVID and VTE

hyper coagulability in lungs → clot forms directly in lungs

DVT diagnosis

ultrasound, physical exam, imaging

D-dimer

D-dimer

degradation product of cross-linked fibrin

• is elevated in all DVT pts BUT not diagnostic for DVT (need other tests)

DVT differential diagnosis

muscle strain/tear, lymph obstruction, venous insufficiency, edema

PE diagnosis

Hx and examination, EKG, chest X-ray, ventilation perfusion scanning, imaging

PE lab tests for diagnosis

CBC, arterial blood gas, D-dimer, BNP and troponin

PE differential diagnosis

HF, pneumonia, MI, pericarditis, MSK pain, exacerbation of lung disease

antithrombotic

meds used to prevent and treat thrombosis

both anticoagulants AND antiplatelets

anticoagulant

slow down clotting, reducing fibrin formation to prevent growing and clot formation

no direct effect on pre-existing clot

anti platelet

prevents platelets from clumping to prevent clots from forming

thrombolytic

dissolves existing clots

common and rare anticoagulant SE

common: bleeding, increased bruising, nose bleeds

rare: hematuria, GI bleeding, intracranial hemorrhage

anticoagulant monitoring

CBC (hemoglobin, hematocrit, platelets)

FIT (fecal immunochemical test): stool test looking for blood in stool

anticoagulant drug interactions

anti platelet agents, thrombolytics, NSAIDs (GI bleeding), SSRIs

dabigatran class

direct thrombin inhibitor

rivaroxaban class

factor Xa inhibitor

apixaban class

factor Xa inhibitor

edoxaban class

factor Xa inhibitor

dabigatran metabolism

prodrug, no CYP involvement

Rivaroxaban/Apixaban metabolism

CYP3A4

edoxaban metabolism

minimal CYP

order of DOAC renal CL (high to low)

dabigatran, rivaroxaban, edoxaban, apixaban

rivaroxaban counseling pearl

has to be taken WITH FOOD (full meal) → 15/20 mg only

Which DOAC is best for poor kidney function?

apixaban

dabigatran other indications

stroke prevention, pediatrics

rivaroxaban other indications

stroke prevention, CAD, PAD, pediatrics

apixaban other indications

stroke prevention

edoxaban other indications

stroke prevention

What DOAC should be used with hepatic impairment?

dabigatran

dabigatrin SE

bleeding, GI (dyspepsia, heartburn)

rivaroxaban SE

bleeding

apixaban SE

bleeding

edoxaban SE

bleeding, rash

Important dabigatran info

store in ORIGINAL container (4 months once opened)

rivaroxaban missed dose

15 mg BID → double up if same day

20 mg bid → 6 hour rule

What is idarucizumab?

reversal agent for dabigatran

drug activity assay for rivaroxaban, apixaban, edoxaban

drug specific anti-Xa assay

DOAC black box warning

stopping early = ischemic risk increased

epidural/spinal procedure (paralysis)

Edoxaban: CrCL > 95 mL/min for non-valvular Afib

warfarin MOA

inhibits vit K oxide reductase

INR monitoring and frequency

q2-3 days, then q week, q 2 weeks, q 4 weeks

warfarin monitoring

INR

CBC (baseline then q6 months)

LFTs (baselines, yearly)

pregnancy test (baseline, prn)

what does INR > 3 indicate?

bleeding risk

what does INR < 2 indicate?

clotting risk

causes of supratherapeutic INR

nonadherence, low vit K, wrong strength, excessive alcohol intake, drug/diet interaction, poor nutritional intake, acute illness, decompensation of cardiac disease

causes of subtherapeutic INR

nonadherence, large amts vit K, drug/diet interaction, follow-up too soon

warfarin reversal

stop warfarin (4-5 days), vitamin K (oral/IV)

• alternatives = fresh frozen plasma, factor VII, prothrombin complex concentrates

prothrombin complex concentrates

vit-K dependent coagulation factors

given to help produce more thrombin

What to do with INR above therapeutic range but <4.5, no evidence of bleeding?

lower or omit dose

monitor more frequently and resume at lower dose when INR in range

What to do with INR > 4.5 but <10, no evidence of bleeding?

omit 1-2 doses

monitor more frequently and resume at lower dose when INR in range

vitamin K not recommended

What to do with INR > 10, no evidence of bleeding?

Hold warfarin therapy and give vitamin K (oral)

resume warfarin at appropriate adjusted dose when INR in range

What to do with serious bleeding at any INR elevation?

hold warfarin

give vitamin K by IV supplemented with PCC, FFP, or VIIa

stereoselective warfarin metabolism

affect oxidative metabolism of either S/R isomer

• S more important

S-isomer warfarin interacting drugs

amiodacrone, antibiotics, antifungals, antiepileptics

mechanisms of warfarin drug interactions

altered platelet functions, direct Gi injury, altered gut vitamin K synthesis, interference with vit K cycle (APAP), impaired absorption

warfarin and amiodarone

inhibits 2C9 and 1A2

increases warfarin concentration → decrease dose (30-50% of weekly dose) when starting amiodarone

monitor q7-10 days

meds that cause increased risk of bleeding

herbals (garlic, ginkgo biloba)

antiplatelets

NSAIDs

thrombolytics

warfarin adverse effects

bleeding complications, tetragonicity, skin necrosis and limb gangrene, “purple toe” syndrome

UFH MOA

interacts with ATIII to inactivate Factor Xa and inhibits conversion of prothrombin to thrombin

UFH indications

acute VTE and PE

prevention VTE

UFH monitoring

activated partial thromboplastin time (aPTT)

chromogenic antifactor Xa heparin assay

activated clotting time (ACT)

CBC

UFH adverse effects

bleeding

osteoporosis

increased LFTs

HIT

HIT

prothrombotic condition associated with increased thrombin

• occurs 5-10 days after starting heparin

HIT signs and sx

platelets decrease by >50% and/or thrombotic event occurs in pts being treated with heparin, thrombocytopenia

How to monitor for HIT?

platelets → baseline, q2-3 days from day 4-14

for pts whose risk of HIT > 1%

if HIT is suspected?

Ag assay to detect HIT Ab

functional assays that detect evidence of platelet activation in presence of heparin

4 Ts probability score

HIT tx

D/C all forms of heparin (flushes, dialysis, heparin-coated catheters)

avoid prophylactic platelet infusions

anticoagulant

• DTI

• indirect thrombin inhibitor

DTI (3) and indirect factor Xa inhibitor (1) for HIT tx

DTI: Lepirudin, Argatroban, Bivalirudin

indirect: Fondaparinux

UFH reversal

stop heparin and give protamine sulfate

monitor aPTT

adverse effects: hypotension, bradycardia

LMWH MOA

similar to UFH but less activity against IIa relative to Xa

LMWH indications

prevention VTE following surgery

prevention VTE in immobilized pts

Tx of acute VTE and PE

Tx VTE in cancer pts long-term

LMWH monitoring

anti-factor Xa level

CBC

renal function

weight

which heparin preferred in renal impairement?

UFH

fondaparinux MOA

indirect factor Xa inhibitor

prevents conversion of prothrombin to thrombin

fondaparinux indication

VTE prophylaxis

HIT tx

fondaparinux monitoring

CBC, antifactor Xa, renal function

IV direct thrombin inhibitors

lepirudin (HIT)

Bivalirudin (PCI)

Argatroban (PCI, HIT)

problems with warfarin

slow onset/offset of action

bridging

variable dosing

genetic variation

risk of bleeding

frequent lab monitoring

food/drug interactions

considerations for selecting oral anticoagulant

cost

pt preference

accessibility to health care (labs)

adherence

once vs BID dosing

IV therapy needed or not

HAS-BLED (for bleeding risk assessment)

HTN

Abnormal renal/liver fxn

Stroke

Bleeding tendency

Labile INR (unstable)

elderly (> 65 years)

drugs

prevention for GI bleeding

PPIs or H2RAs for high risk patients

pt safety and counseling pearls for anticoagulants

trauma, falls, cuts and seeking care

ID card/med-alert tag

emergency phone #

pregnancy issues

safe storage

proper disposal

3 things to consider when switching between anticoagulant agents

half-life/time to onset/offset

renal function

effect of med on labs (riva can increase INR)

VTE primary prophylaxis

prevention before a clot forms

VTE secondary prophylaxis

prevent another clot from happening

mechanical thromboprophylaxis methods

for pts at high risk of bleeding or who can’t use anticoagulants (brain bleed)

• intermittent pneumatic compression (IPC)

  • graduated compression stockings, venous foot pump

pharmacologic thromboprophylaxis

LMWH

UFH

Fondaparinux

Warfarin

DOACs

Aspirin

Aspirin in VTE prevention

more evidence for VTE prevention in ortho surgery

meds for acutely ill hospitalized patients and duration

LMWH, UFH, fondaparinux, rivaroxaban

warfarin and aspirin not recommended

until discharged

COVID-19 Hospitalized Patients VTE Prophylaxis

UFH/LMWH most common

what anticoagulant is not used in cancer patients?

warfarin

orthopedic surgery VTE prophylaxis

duration of therapy is 3-6 weeks after

ASA or anticoagulant (riva/apix)

VTE prophylaxis long-distance travel

avoid constricting clothings around legs/waist

hydrate

calf-muscle contraction

get up (q1-2 hours)