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Anticoagulants
Outline
Available anticoagulants
Surgical prophylaxis
DVT and pulmonary embolus
Atrial fibrillation
Perioperative management of patients on
chronic anticoagulation
Arterial thromboembolism
Cerebral
Visceral
Extremity
Anticoagulation in pregnancy
Extrinsic system
Injury
IX
IXa
+
VIIa
+
Ca++
Tissue
thromboplastin
+
VII
Xa
+
Va + Ca++
Prothrombin
Thrombin
Fibrinogen
Fibrin
Available anticoagulants
Unfractionated heparin
Low Molecular Weight Heparins
Oral Anti-coagulants
Alternative agents
Unfractionated HeparinLimitations
Significant protein binding
Response is unpredictable (close
monitoring required)
<25% of patients in therapeutic range
12 hours after starting Rx
Inaccessibility of clot-bound thrombin
Unfractionated HeparinDosing
Loading 80-100 U/ kg IV
Then IV infusion at 18 U/kg/hr
Normogram available for most
hospitals
Therapeutic range 1.5-2.5 X control PTT
Unfractionated HeparinComplications
Heparin Induced
Thrombocytopenia
Incidence 1-5%
Can occur with all methods of
administration
No known risk factors
Increased incidence with Bovine
preparations
Dx- plt count < 100-150 000/uL
Heparin Induced
Thrombocytopenia I
HIT I
Heparin Induced
Thrombocytopenia II
HIT II (HITT)
Immunologically mediated
Ab to Heparin-PF 4 complex
More severe but less common
5-7 days after initiating Tx
PLT << 100 000/uL
Bleeding complications unusual
Diffuse thrombotic events
Separate and distinct from initial event requiring
heparin Rx
Heparin Induced
Thrombocytopenia II
Heparin Induced
Thrombocytopenia
Treatment
Withdrawal of ALL heparin and heparin
products
Plasmapheresis - anecdotal success
Further treatment should await confirmation
of Dx
Start anti-platelet therapy
? LMWH
Thrombin inhibitors
Ancrod
Conversion to Warfarin
Available Anticoagulants
Unfractionated heparin
Low Molecular Weight Heparins
Oral Anti-coagulants
Alternative agents
10,000
5,000
15,000
20,000
Smaller size
Available Anticoagulants
Unfractionated heparin
Low Molecular Weight Heparins
Oral Anti-coagulants
Alternative agents
Oral AnticoagulationLimitations
May create initial hypercoaguable state
3-5 days for anticoagulant effect
3-5 days to reverse effects
Reversed rapidly by FFP
Can reduce time of reversal with
supplemental Vit K (10mg IV or 3-5mg PO)
Oral AnticoagulationComplications
Hemorrhage
Skin necrosis
Protein C deficiency
Malignancy
Teratogenic
Available Anticoagulants
Unfractionated heparin
Low Molecular Weight Heparins
Oral Anti-coagulants
Alternative agents
Alternative Anticoagulants
Danaproid
Thrombin Inhibitors
Hirudin
Lepirudin
Argatroban
Ancrod
Alternative AnticoagulantsDanaproid
Heparinoid
Mixture heparin-like glycosaminoglycans and
chondroitins
Anti-factor Xa and anti-factor IIa activity
Can be used in patients with HIT
Approved for DVT prophylaxis
Longer duration than UF heparin
Measure by anti-factor Xa levels
Weight based dosing
Alternative AnticoagulantsAncrod
Venom of Malaysian Pit Viper
Defibrinating agent
Converts fibrinogen to soluble aggregate
removed by plasmin and RES
Increases FDP augments anticagulant
effect
Indirect micro-fibrinolytic by increasing TPA
release
Monitor fibrin levels
Venous Thromboembolism
Virchows Triad
Stasis
Intimal injury
Activation of coagulation
(hypercoaguable state)
Venous ThrombosisEpidemiology
Venous thromboembolism is the 3rd most
common vascular disease in the United
States
Mortality and morbidity associated with VTE
is enormous
Average cost per admission in the US:
PE = $12,595
DVT = $9,337
Additional long-term costs of morbidity > 75% of
initial therapy costs
Obesity
Varicose Veins
Cardiac dysfunction
Indwelling vascular
catheter
IBD
Nephrotic syndrome
Pregnancy or estrogen
use
Advanced age
Prolonged immobility
Stroke or Paralysis
Previous VTE
Cancer and its
treatment
Major Surgery
esp. abdomen,
pelvis, and lower
extremities
Trauma
esp. fractures of
pelvis, hip, or leg
Event rate
Recommended Regimens
2.0%
0.4%
0.2%
0.002%
Event Rates
Calf DVT
10-20%
Major surgery in
Recommended
Regimens
patients
with additional
Proximal DVT 2-4%
risk LMWH
factors
Clinical PE
1-2%
Non-major surgery in
Fatal PE
0.1-0.4%
Low
dose
UFH
patients 40-60 with no
Elastic
additional
risk stockings
factors
Intermittent
Pneumatic Compression
Major
surgery in
patients < 40 with no
additional risk factors
Event Rate
Non-major surgery
Calf DVT
20-40%
Recommended
in patients
> 60 or
Regimen
Proximal DVT 4-8%
additional risk
Clinical PE
2-4%
LMWH
factors
Fatal PE
0.4-1.0%
Major
surgery
inUFH q8h
Low
dose
patient < 40 or
IPC risk
additional
factors
Event Rate
Recommended
Major
surgery in
Regimen
Calf DVT
40-80%
patients > 40 plus
Proximal DVT 10-20%
priorLMWH
VTE, cancer,
Clinical PE
4-10%
hypercoaguable
Oral Anticoagulants
Fatal PE
0.2-5.0%
state
Hip IPC/ES
or knee + LMWH/LDUFH
arthroplasty
Major
Adjustable
trauma
dose UFH
Spinal cord injury
0.25
0.5
0.75
In Favor of LMWH
1.5
1.25
In Favor of UFH
0.75
Mortality
LMWH
UFH
5.1%
6.7%
0.02
Enoxaparin
sodium 1mg/kg
q12h SC
Clinical
endpoints
Adjusted-dose
heparin
infusion
Clinical
endpoints
Warfarin therapy
initiated on 2nd day
Warfarin 90 days
post randomization
Enoxaparin sodium
n=247 (%)
13 (5.3)
11 (4.5)
10 (4.0)
2 (0.8)
Heparin
n=254 (%)
17 (6.7)
14 (5.5)
12 (4.7)
3 (1.2)
Study Day
INR*
aPTT
(sec)
6
7
7
5
2.7
2.7
3.2
3.4
27
55
40
40
2.4
40
2
3
1
1.3
3.0
2.7
64
88
64
(n=3)
Heparin
Hematuria
Gastrointestinal bleeding
Hematemesis
Atrial Fibrillation
Most common arrythmia in adults
Responsible for 15% CVA
Better survival with combined rate
control and anticoagulation
IV heparin/ LMWH + coumadin
Administer anticoagulation before and
3 - 4 weeks after cardioversion
Atrial Fibrillation
Age
Risk Factors
For Stroke*
Therapy
< 65
None
ASA or none
>65-75
None
ASA or Warfarin
Any
1 or more
Warfarin
Perioperative Management Of
Patients on Chronic
Anticoagulation
Patients at low risk
VTE adequatelt treated for > 3 months, no
predisposing factors
Nonvalvular A. Fib without embolic events
Most bioprosthetic and mechanical heart
valves without thromboembolism
Perioperative Management Of
Patients on Chronic
Anticoagulation
Recommendations
Hold warfarin 4 days before surgery
Recheck PT day of surgery
Resume warfarin on post-op day 2
Perioperative Management Of
Patients on Chronic
Anticoagulation
Patients at intermediate risk
Venous or arterial embolism
In 2nd to 3rd month of Tx, no predisposing
factors
Recurrent VTE tx for 12 months
Perioperative Management Of
Patients on Chronic
Anticoagulation
Recommendations
Perioperative Management Of
Patients on Chronic
Anticoagulation
Patients at highest risk
Venous thromboembolism with specific
circumstances (consider IVC filter)
Onset within last month
Idiopathic, last 6 months
Recurrent VTE, within last 12 months
Perioperative Management Of
Patients on Chronic
Anticoagulation
Recommendations
Hold warfarin 4 days prior to surgery
Begin IV heparin or SC LMWH 2 days prior to
surgery
Recheck PT day of surgery
Hold heparin 6-12 hrs before surgery
Resume heparin 12 hours after surgery if
adequate hemostasis
Resume warfarin on post-op day 2
D/C heparin when INR > 2
Arterial ThromboembolismExtremity
Patient with
suspected ALI
History
PE
Doppler
Diagnosis confirmed
HEPARIN
Arterial ThromboembolismExtremity
Protection against clot propagation
Prevent embolus
IV HEPARIN
5000 u bolus
Titrate to PTT 60-80 sec
No clear
consensus
Start
Warfarin
after 24 hrs
Cerebral
embolism
study
group
INR 2.0-3.0
Arterial ThromboembolismVisceral
Acute mesenteric ischemia
Embolic
Thrombotic
Non-occlusive
Venous thrombosis
Arterial ThromboembolismVisceral
Diagnosis requires high index of suspicion
Angiography diagnostic
Treatment
Initiate IV heparin at time of diagnosis (bolus
and titrate to PTT 60-80 sec)
Thrombolysis if no evidence of peritonitis
Surgical thrombectomy/revascularization with
bowel resection
Arterial ThromboembolismVisceral
Non-occlusive mesenteric ischemia
Multi-system organ failure, low-flow states,
and visceral vasoconstriction
Rarely exists without severe cardiac
dysfunction
Abdominal pain 75%
Arterial ThromboembolismVisceral
Arteriography demonstrate mesenteric arterial
spasm
Reversible with intra-arterial papaverine infusion
or other vasodilating agents
Adjunctive use of IV heparin recommended
Arterial ThromboembolismVisceral
Venous thrombosis
Hypercoaguable state
Intraabdominal infection or inflammation
Asymptomatic state to catastrophic illness
Generalized abdominal pain out of proportion to physical
exam
Rigorous resuscitation
IV heparin anticoagulation (PTT 60-80)
Surgical exploration for peritonitis
Long-term therapy with warfarin (life-time if hypercoaguable
state identified)
Anticoagulation in Pregnancy
Sixfold risk of venous thrombembolism
PE most common cause of maternal
mortality in US
Gravid uterus compressing Vena Cava
Pregnancy related hypercoagulability
(increase II, VII, VIII, X)
Decreased fibrinolytic activity and AT III
Anticoagulation in Pregnancy
Coumadin during first trimester associated
with specific malformations in > 25% of
births
Fetal Warfarin Syndrome (nasal
hypoplasia, stippled epiphyses)
Increase CNS anomalies if used during
other time during pregnancy
Anticoagulation in Pregnancy
Drugs with molecular weight < 1000
daltons pass through placental
membranes
Fetus has already low levels of Vit-K
dependant factors- further depleted by
warfarin effect
Anticoagulation in PregnancyRecommendations
Initiate anticoagulation with intravenous heparin
Continue Tx with subcutaneous heparin or
LMWH
Continue Tx through delivery and post-partum
period
After delivery coumadin for 6 months
Prophylaxis (LMWH) recommended during
subsequent pregnancy
Acute iliofemoral DVT consider thrombectomy
or vena Caval filter placement