venous stasis

vascular injury

hypercoagulability

Unfractionated Heparin (UFH)

mechanism

-potentiates anti-thrombin, thereby inactivationg thrombin

-Inactivates Factors 9-12a

-prevents conversion of fibrinogen to fibrin

-prevents coag, pts own thrombolytic system degrades clot

1.  venousthromboembolism tx/prophylaxis

2.  unstable angina/acute MI

3.  coronary bypass surgery

4.  hemodialysis

5.  angioplasty

6.  IV line flushes

must be monitored for:

1.  hemorrhage

2.  heparin-induced throbocytopenia (HIT)

3.  Heparin Associated Thrombocytopenia (HAT)

4.  Osteoporosis (long term use)

5.  Hyperkalemia (long term use)

heparin-induced throbocytopenia (HIT):

-platelets <100,000 or < 50% baseline

*if this happens:  d/c and start alt anti-coag w/ Direct Thrombin Inhibitor

heparin associated thrombocytopenia (HAT):

-mild thrombocytopenia, platelets rarely drop < 100,000

-no antibody formation

-manage by observation (platelets will recover with cont tx)

category C

does not crsoss placenta but caution maternal hemorrhage, osteoporosis

OK to breast fee with too as it does not enter the breast milk

loading dose:  IV push

                                                       followed by:

continuous infusion

-elderly doses usu lower

-can be administered SubQ for non-acute situations (VTE)

aPTT in 6 hrs

reference range: 25-39sec

historical tx range:  1.5-2.5 X control aPTT

(for control of 30sec, 45-75 sec tx range)

platelets check qod x 14days or until UFH stopped, whichever first

Protamine (heparine antidote):  binds heparin to inhibit it from affecting clotting cascade

-1mg protamine neutralizes 90units heparin (impt to know so do not overshoot and increase risk of clotting!)

-max dose:  50mg, infused over 10min

caution hypotension and anaphylactoid rxns

c/cx of low molecular weight heparin

(LMWH)

Enoxaparin (Lovenox):  for DVT prophylaxis and VTE tx

-1/3 size of UFH

-subQ bioavailability 92%

-inhibits only clotting factor 10a (vs 9-12a)

-predictable dose response

-longer half life:  q12hr

-reduced need for lab monitoring

-hemorrhage

-thrombocytopenia

*lower incidence of HIT than with heparin; check platelets on day 3 of tx

-injection site hematoma

-osteoporosis (may be less than with heparin)

-routine monitoring not neccessary

-anti-factor 10a activity:  in pts w/ CrCl <30ml/min, weight <50kg, morbid obesity, prolonged tx >14days, during pregnancy

-draw steady state level 4 hrs after subq dose

VTE dose much higher than prophylaxis

protamine

cannot completely neutralize anti-coag effect

1mg protamine/1mg enoxaparin

Fondaparinux (Arixtra)

FDA-approved for VTE prophylaxis in lower extremity ortho procedures

-indicated for VTE tx

-unapproved use for pt where heparin forms caused HIT

-no reversal agents!

-cautions:  renal function, weight- dose adjust

requiring aPTT monitoring:  Lepirudin, Argatroban

others:  bivalirudin, desirudin

-potential for use in many indications

-relatively high incidence of bleeding and high cost

-no reversal agents!

Lepirudin use

Argatroban use

Lepirudin:  HIT pts

Argatroban:  HIT pts, HIT w/ PTCA

Bivalirudin:  pt undergoing PTCA

Desirudin:  VTE prophylaxis in pts undergoing elective hip surgery

Warfarin (Coumadin)

mechanism of action

-does not affect established thrombus

-interferes with hepatic synthesis of vitamin K-dependent clotting factors

*specifically 2, 7, 9, 10

-onset of anti-coag effect 36-72hrs, peak effect 5-7days (d/t clotting factor half life: 6hr-72hr)

-does not affect already formed clotting factors

1.  venous thromboembolism tx/prophylaxis

2.  prosthetic heart valves

3.  a. fib

4.  TIA/stroke

5.  acute MI

6.  hypercoagulable states

7.  peripheral arterial occlusive dz

contraindicated in pregnancy

BUT

inactive form in breast milk, so OK to breastfeed when taking

-hemorrhage (2-10%)

-skin necrosis (rare, appears early (3-8days after initiation))

*pt w/ protein C deficiency at most risk- D/C, administer Vitamin K or fresh frozen plasma and heparin

-purple toe syndrome (rare, occurs later (3-10wks))

*D/C drug to prevent progression to necrosis

-spinal anesthesia or spinal injections

-pregnancy category X

-pt w/ additional risk for hemorrhage

-noncompliance w/ drug therapy or monitoring

-EtOH

-surgery, dental work

-average dose:  4-5mg, however patient specific and can range from 1-15mg

-dosed qday, usu overlap w/ heparin for 4-5days (takes 5-7days for warfarin to peak)

-higher the INR ratio, more likely to bleed- less likely to give warfarin

-lower the INR ratio, more likely to clot- more likely to give warfarin

give vitamin K! antagonizes warfarin

-induces metabolism of warfarin:  therefore decreases the serum conc. of warfarin, therefore decreases the INR (low INR- faster clotting time, high INR- slower clotting time)

green vegetables MC source of dietary vitamin K

multivitamins

consistent intake to stabilize INR

assume an intrxn until proven otherwise

increases bleeding risk (does not effect INR):  ASA, NSAIDS

increases anti-coag effect (inc INR (takes longer to clot)):  sulfamethoxazole

decreases anti-coag effect (dec INR (quicker to clot)):  vitamin K

CONTRAINDICATED:  pt taking sulfamethoxazole (septra, bactrim)

acute ingestion:  increases INR

*metabolism is slowed because acute ingestion inhibits CytP450

chronic ingestion:  decreases INR

*induces CytP450

cirrhosis:  increases INR

-heparin

-LMWH

-compression stockings/intermittent pneumatic compression device

measure of prevention varies with degree of risk

continuous infusion heparin 5-7days

warfarin begins on day 1 or 2

must have therapeutic INR for 2 days in a row before stopping heparin

subcutaneous LMWH 5-7days

warfarin tx begins on day 1 or 2

must have therapeutic INR for 2 days in a row before stopping heparin

systemic lytic tx NOT recommended for most pt

intracranial bleed 0.5-1% of pt

contraindicated if major surgery w/in 10 days, active internal bleeding, stroke w/in 3 months, intracranial tumor

genetic variations of CYP2C9 lead to significant differences in pt response to warfarin

study found that CYP2C9*2 and CYP2C9*3 are associated with:

1.  warfarin maintenance dose

2.  time to stable warfarin dose

3.  rate of above range INRs

4.  bleeding events

-identifies pt who need lower doses d/t inc risk for bleeding

-tests for variations in CYP2C9 and VKORC1 genes

*help determine pt sensitivity to warfarin metabolism and anti-coag process

-specifically overanticoagulation

-help achieve maintenance dose faster and likely increase safety and efficacy