Anticoagulation


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Rivaroxaban and bleeding risk. 
Called by nursing that tonight's surgery has been canceled due to elevated INR. 
The patient's last dose of rivaroxaban was 2/15 AM. The half life of this medication is about 12 hours in the elderly. In non-urgent procedures, guidelines suggest taking the last dose 48 hours before low bleeding risk surgeries and 72 hours before high bleeding risk surgeries. 

The judgement of the surgeon should definitely be taken into account when weighing the risks and benefits of delaying the surgery another day in order to allow further processing of the drug and further lowering bleeding risk. 

There is no need to further check the INR. This is not a reliable way to gauge the anticoagulation effect of rivaroxaban, and rivaroxaban can have variable effects on the INR which do not necessarily correlate with bleeding risk. Vit K was apparently ordered overnight but not given. Rivaroxaban is not a vitamin K antagonist and this will not be helpful.
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Surgical Management of stented patients.

DES - requires anti-platelet x 1 year
BMS - requires anti-platelet x 1 month

DES becomes metal at 6 month.

All elective surgeries to be postponed for 1 year following DES, 3-6 months following BMS.
If you miss 1 dose of ( brilinta , ticagrelor ) you're at the plavix level of anti-platelet efficacy. Prasugrel ( Effient ) can be used in place of brilinta.

Plavix has mixed efficacy because genetic variations dictate efficacy. However, it is plentiful and cheap.

Eliquis , apixaban not indicated for stents, only afib and PE

If a person comes during the active time for DES and BMS, start them on IV integrilin. (integrilin , eptifibatide )


- Pathophysiology: when a stent is implanted it causes micro-trauma to the endothelium and collagen expresses itself creating a site of immediate coagulation. This is the"endothelial damage" in Virchow's triad.

- Always consult Cardiology for these decisions.

Tags: ( eliquis , apixaban ),  ( brilinta , ticagrelor ),  (plavix clopidogrel )



Warfarin should started at <= 5 mg in the elderly.
tags: warfarin, coumadin, heparin, lovenox, LMWH, fondaparinux







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Lovenox Dosing for ACS - this was preceding a cath on the same day:
- wt 88.5 kg, using ABW 72 kg for dosing.
- last dose 1 mg/kg ~ 23:00 on 10/13, ppx dose held this AM.
- pending baseline aPTT
- 4000U initial bolus, start infusion at 8.6 ml/hr per low dose protocol.
- order APTT at 6 hrs based on start time

Post-thrombotic syndrome (PTS) is a complication of acute deep-vein thrombosis (DVT), and is characterized by chronic pain, swelling, and skin changes in the affected limb. Within 5 years of experiencing a DVT, one in three patients will develop PTS. REF


Antiphospholipid antibody syndrome in pregnancy is associated with an increased risk of thromboembolism, fetal loss, thrombocytopenia, and poor pregnancy outcome. Studies comparing aspirin alone versus aspirin and heparin suggest that the combination of aspirin and heparin is most effective for decreasing fetal loss.

Oral glycoprotein IIb/IIIa receptor inhibitors appear to increase the risk of mortality when compared with aspirin. REF

Indications for argatroban & desirudin (Iprivask). REF

V. important - recco duration of antiplatet therapy. REF

Bleeding time, activated partial thromboplastin time (aPTT), and prothrombin time (PT) are relatively poor predictors of bleeding risk. REF

Pre-surgical tx of pt with h/o postoperative venous thromboembolism. REF (Note that the dose listed here is 40 mg for prophylaxis, vs weight based dose for treatment: see PE)

Indirect Xa inhibitor: See the St Louis 2013 p. 2602 for more information
AriX(a)tra (FondaparinuXa) - inhibits Xa selectively via AIII (it is an indirect Xa inhibitor).
- monitor via chromogenic anti-Xa heparin assay but generally needs no monitoring.
- renal failure - can use if CrCl > 30
- indication - prophylaxis in orthopedic surgery
- at STEH Arixtra is the DOC for DVT prophylaxis.
- if < 50 kg our lab changes to Fragmin (LMWH)

Direct Xa inhibitors - inhibit Xa directly and do not use AIII as an intermediary
- pro - monitoring not required, oral dosing, predictable
- statin interaction via CYP3A4
- RivaroXaban (Xarelto), ApiXaban, -bans
- Rivaroxaban has not been tested in patients with liver ds and end stage liver disease.
- Can be rx'd for PE, DVT and non-valvular Afib.
- Dosing: 15 mg BID for 21 days then 20 mg QD (with food).
- greater risk for GI bleed than coumadin (confirm)
- stats: 12 million will have Afib in 2050 - increases stroke risk X 5.
- anticoagulation decreases mortality by 70% (xarelto  flier)
- 50% of those with afib aren't anticoagulated.
- x is 2/3 metab by liver, 1/3 excreted by Ks.
- ASA is not effective anti-coagulation.
- Afib anti-coag with Xarelto when CHADS > 2.
- simpler than Warfarin, no testing required, W requires 7-10 days to be therapeutic.
- DO NOT use in pts with mechanical heart valves.
- Use for non-valvular afib both rheumatic and non-rheumatic.
- ROCKET - mean CHADS 3.5 - result - X was not inferior to W.
- Hazard ratio 12% for X.
- Cerebral hemm has 50% chance of death and 2/3 of hemorrhagic strokes occur on W.


Direct Thrombin(IIa) Inhibitor:
DaBigatran (Pradaxa)
- monitor - requires none
- indication - stroke prophylaxis in those with atrial fibrillation due to non heart valve causes.
- non-reversibile in the event of major bleed
- greater risk for GI bleed than coumadin (confirm)

LMWH  - inhibits thrombin(IIa) & XIIa via AIII &  has affinity for PF-4
              - monitor via anti-factor Xa levels, but usually no routine monitoring unless renal failure.
              - CLOT study - Dalteparin superior to Warfarin to prevent clots in neoplasia.
              - Lovenox is Enoxaparin (in renal failure dose is cut in half).
              - Fragmin is Dalteparin    (ok in renal failure - does not accumulate).
              - Appropriate prophylaxis in a 72 yo F with ttl knee replacement ? REF

Heparin - inhibits thrombin(IIa), IXa, Xa, XIa, XIIa via AIII & has affinity for PF-4.
- monitor via aPTT

Warfarin - inhibits II, VII, IX, X via Vitamin K antagonism
- monitor via INR

More extensive notes regarding the foregoing:

AriX(a)tra (FondaparinuXa) - inhibits Xa selectively via AIII for Xa only.  REF
- A synthetic pentasaccharide (= 5 monomeric sugar) Factor Xa inhibitor. 
- Has same 5 monomeric sugar units as H/HS (After they are cleaved enzymatically)
- In H/HS this 5 monomeric sugar sequence binds ATIII which increases its anti-coag activity X 1000
- The difference between H/HS and Arixtra is that Arixtra doesn't inhibit thrombin(IIa).
- Structurally Fonda has an O-methyl at its reducing end.  H/HS don't.
- Indication - DVT prophylaxis in orthopedic surgery.
- Risk of HIT is lower than for H/HS and LMWH b/c it has no affinity for PF-4
- Can actually be used in HIT
- Unlike direct Xa inhibitors it mediates its effects indirectly through AIII but is selective for Xa

LMWH (Lovenox=Enoxaparin) - inhibits thrombin(IIa) & XIIa via AIII &  has affinity for PF-4 
- monitor via anti-factor Xa levels

Heparin - inhibits thrombin(IIa), IXa, Xa, XIa, XIIa via AIII & has affinity for PF-4.
- monitor via aPTT
- In H/HS its 5 monomeric sugar sequence binds ATIII which increases its anti-coag activity X 1000

Warfarin - inhibits II, VII, IX, X via Vitamin K antagonism
- monitor via INR

What does Xa do ?  It catalyzes the conversion of prothrombin to thrombin(IIa)

In the obese patients (>330 lb) and those with renal failure, LMWH (Levenox=Enoxaparin) therapy should be monitored with anti-factor Xa levels obtained 4 hours after injection. Most other patients do not need monitoring. The INR is used to monitor warfarin therapy, and the activated partial thromboplastin time (aPTT) is used to monitor therapy with unfractionated heparin. Factor VIII levels are not used to monitor anticoagulation therapy. REF

MC cause of bleeding at the circumcision site in a neonate ? REF

Who should and should not receive Lovenox ? (Very good)  REF

Medication, dose and length of tx for a person with first DVT ? REF

PE in pregnancy - how to tx ? REF
- Does Warfarin cross the placenta ?
- Does Heparin cross the placenta ?
- Can Warfarin be given after pregnancy ? 
- Does Warfarin appear in breast milk ?

PE is thought to be responsible for 5-10% of deaths in hospitalized patients. REF

218. An 80-year-old female is being started on warfarin (Coumadin) for atrial fibrillation. According to the American College of Chest Physicians guidelines, the initial dose in this patient should NOT exceed 
A) 2.5 mg 
B) 5 mg 
C) 7.5 mg 
D) 10 mg 
E) 12.5 mg 

Item 218 
ANSWER: B 
The American College of Chest Physicians recommends a starting warfarin dosage of * 5 mg/day in elderly patients, or in patients who have conditions such as heart failure, liver disease, or a history of recent surgery. The INR should be used to guide adjustments in the dosage. 
Ref: Ansell J, Hirsch J, Hylek E, et al: Pharmacology and management of the vitamin K antagonists. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133(6 Suppl):161S.

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