anticoagulation 101
DESCRIPTION
Anticoagulation 101. Neil A. Lachant, MD Chief, Section of Hematology Director, Thrombosis Program Cooper Cancer Institute Professor of Medicine UMDNJ Robert Wood Johnson Medical School. Venous Thrombosis Magnitude of the Problem. No national data Incidence 1- 2/1,000 - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/1.jpg)
Anticoagulation 101Neil A. Lachant, MD
Chief, Section of Hematology
Director, Thrombosis Program
Cooper Cancer Institute
Professor of Medicine
UMDNJ Robert Wood Johnson Medical School
![Page 2: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/2.jpg)
Venous ThrombosisMagnitude of the Problem
• No national data• Incidence
– 1- 2/1,000– 300,000 - 600,000 new cases per year– increasing as population ages
• life expectancy 78 years
![Page 3: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/3.jpg)
Incidence of VTE
Age Incidence
<10 1:100,000
20 1:10,000
50 1:1,000
80 1:100
![Page 4: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/4.jpg)
Manifestations
• 2/3 DVT– 50- 80% post-phlebitic syndrome
• 1/3 pulmonary emboli– 30% mortality– 30,000 – 60,000 deaths per year
![Page 5: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/5.jpg)
![Page 6: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/6.jpg)
A 22 yo female presents with an iliofemoral DVT. Her aPTT is 37 sec (nl <32) and she is found to have a lupus anticoagulant. She weighs 55 kg and her creatinine is 0.5 mg/dl. She is started on weight -based UFH. Her aPTT at 4 hrs is 123 s. She could be anticoagulated by all of the following EXCEPT:
1. Decrease UFH with aPTT goal of 1.5-2.5 x her baseline
2. UFH monitoring heparin level
3. UFH correlating heparin level with the aPTT
4. LMWH without monitoring
5. Fondaparinux without monitoring
![Page 7: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/7.jpg)
A 22 yo female presents with an iliofemoral DVT. Her aPTT is 37 sec (nl <32) and she is found to have a lupus anticoagulant. She weighs 55 kg and her creatinine is 0.5 mg/dl. She is started on weight -based UFH. Her aPTT at 4 hrs is 123 s. She could be anticoagulated by all of the following EXCEPT:
1. Decrease UFH with aPTT goal of 1.5-2.5 x her baseline
2. UFH monitoring heparin level
3. UFH correlating heparin level with the aPTT
4. LMWH without monitoring
5. Fondaparinux without monitoring
![Page 8: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/8.jpg)
Heparin Therapy in APLS
• Lupus anticoagulant with prolonged baseline aPTT
– use LMWH– use standard weight-based unfractionated heparin
dosing
1. correlate aPTT with heparin level (3-4 points)
use aPTT range that corresponds to therapeutic heparin level (0.3 –
0.7 iu/ml)
2. follow thrombin time if standardized in your lab
![Page 9: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/9.jpg)
0
20
40
60
80
100
120
140
0 0.2 0.4 0.6 0.8
Heparin Level (u/ml)
aPT
T
Normal
Patient
![Page 10: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/10.jpg)
• A 34 year old African American male presents with a femoral DVT. He is given a 5000 u bolus of UFH and is started on a heparin drip at 1000 u/hr. The aPTT remains subtheraputic despite an increase to 1800 u/hr. A hematology consult is obtained on the 3rd hospital day for “inability to be anticoagulated”.
![Page 11: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/11.jpg)
• What is the most appropriate goal for UFH:
1. aPTT ratio 1.5 - 2.5 x baseline
2. aPTT that correlates with heparin level of 0.3 - 0.7 u/ml
3. Whatever the lab computer says the therapeutic range is
![Page 12: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/12.jpg)
• What is the most appropriate goal for UFH:
1. aPTT ratio 1.5 - 2.5
2. aPTT that correlates with heparin level of 0.3 - 0.7 u/ml
3. Whatever the lab computer says the therapeutic range is
![Page 13: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/13.jpg)
aPTT
20 40 60 80 100 120 140 160 180 200
aP
TT
Ra
tio
1
2
3
4
5
6
Effect of Thromboplastin on aPTT Ranges
(Anti-Xa 0.3 - 0.7 IU/ml)
![Page 14: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/14.jpg)
aPTT
20 40 60 80 100 120 140 160 180 200
aP
TT
Ra
tio
1
2
3
4
5
6
Effect of Thromboplastin on aPTT Ranges
(Anti-Xa 0.3 - 0.7 IU/ml)
![Page 15: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/15.jpg)
• Review of the patients records shows that he weighs 150 kg. His current aPTT is 38 sec (normal < 37.1) with an infusion rate of 1800 u/hr. The most appropriate rate for the UFH infusion is:
1. 2700 u/hr (18 u/kg/hr)
2. 2000 u/hr (18 u/kg/hr capped for patient size)
3. Continue at 1800 u/hr
4. Switch to LMWH because UFH doses above 2000 u/hr are too dangerous to use
![Page 16: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/16.jpg)
• Review of the patients records shows that he weighs 150 kg. His current aPTT is 38 sec (normal < 37.1) with an infusion rate of 1800 u/hr. The most appropriate rate for the UFH infusion is:
1. 2700 u/hr (18 u/kg/hr)
2. 2000 u/hr (18 u/kg/hr capped for patient size)
3. Continue at 1800 u/hr
4. Switch to LMWH because UFH doses above 2000 u/hr are too dangerous to use.
![Page 17: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/17.jpg)
UFH Dosing
Anti-Xa APTT
Initial dose 80 u/kg bolus, then 18 u/kg/hr
< 0.15 80 u/kg bolus, increase 4 u/kg/hr
0.15 – 0.29 40 u/kg bolus, increase 2 u/kg/hr
0.30 – 0.70 No change
0.71 – 0.85 Decrease infusion by 2 u/kg/hr
> 0.85 Hold 1 hr, decrease infusion by 3 u/kg/hr
Adopted from Raschke Arch Int Med 156:1645, 1996
![Page 18: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/18.jpg)
Utilization management is pushing for discharge, but his INR is only 1.6. The most appropriate recommendation for the use of enoxaparin would be:
1. 150 mg (1 mg/kg) sc q 12 hr
2. 150 mg sc q 12 hr and check a heparin level immediately before the third dose
3. 150 mg sc q 12 hr and check a heparin level 3.5 - 4 hours after the third dose
4. 225 mg (1.5 mg/kg) sc q 24 hr
5. Enoxaparin contraindicated in a patient this large
![Page 19: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/19.jpg)
Utilization management is pushing for discharge, but his INR is only 1.6. The most appropriate recommendation for the use of enoxaparin would be:
1. 150 mg (1 mg/kg) sc q 12 hr
2. 150 mg sc q 12 hr and check a heparin level immediately before the third dose
3. 150 mg sc q 12 hr and check a heparin level 3.5 - 4 hours after the third dose
4. 225 mg (1.5 mg/kg) sc q 24 hr
5. Enoxaparin contraindicated in a patient this large
![Page 20: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/20.jpg)
Kinetics of LMWH
• Different for each LMH
• Doses not interchangable
![Page 21: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/21.jpg)
Low Molecular Weight Heparin Dosing
Prophylactic
Therapeutic
Enoxaparin 40 mg q 24 h 1 mg/kg q12 h, or
1.5 mg/kg q 24 h Daltaparin 2,500 or 5,000 u
q 24 h
200 u/kg q 24 h
Tinzaparin 175u/kg q 24 h
![Page 22: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/22.jpg)
LMWH in Obesity
• Relationship of intravascular volume and TBW is not linear– adipose tissue has a relative decrease in
plasma volume compared to muscle– could lead to overdosing
![Page 23: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/23.jpg)
Weight in LMWH Studies
Enoxaparin <144 kg
Daltaparin <190 kg
Tinzaparin <165 kg
Actual weight dosed anti-Xa activity is not significantly increased in obesity
![Page 24: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/24.jpg)
Recommendations For the Use of LMWH in Obesity
• Patient should receive LMWH dose based on actual body weight– if < 150 kg,
• monitoring not necessary on a routine basis
– if > 150 kg, • check heparin level 3.5 - 4 hrs after 3rd or
4th dose• dose reduce if > 1.0 IU/ml
![Page 25: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/25.jpg)
• A 24 yo dialysis dependant female is paraplegic. She receives enoxaparin 1 mg/kg q 12h for an acute DVT. One week later in rehab, she develops pain in her right shoulder. She is brought to the emergency room during the night with a 20 cm hematoma in her right supraclavicular fossa. What is her correct enoxaparin dose?
A. 1 mg/kg q 12h
B. 1 mg/kg qd
C. Enoxaparin contraindicated with ESRD
![Page 26: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/26.jpg)
• A 24 yo dialysis dependant female is paraplegic. She enoxaparin 1 mg/kg q 12h for an acute DVT. One week later in rehab, she develops pain in her right shoulder. She is brought to the emergency room during the night with a 20 cm hematoma in her right supraclavicular fossa. What is her correct enoxaparin dose?
A. 1 mg/kg q 12h
B. 1 mg/kg qd
C. Enoxaparin contraindicated with ESRD
![Page 27: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/27.jpg)
LMWHDosing in Renal Dysfunction
• LMWH accumulates as Ccr decreases– cutoff point varies between different LMWHs
– Ccr 30 - 50
• monitor heparin level if concern about dosing or bleeding
– Ccr < 30
• dose reduce
• monitor heparin level
– Ccr < 10
• do not use LMWH under any circumstances
![Page 28: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/28.jpg)
Enoxaparin Dosing with Renal Dysfunction
Indication
Ccr > 30 ml/min
Ccr 10 - 30 ml/min
Abdominal Surgery Prophylaxis
40 mg qd 30 mg qd
Medical Prophylaxis 40 mg qd 30 mg qd
Orthopedic Prophylaxis 30 mg q 12h 30 mg qd
DVT and/or PE 1 mg/kg q 12h 1 mg/kg qd
![Page 29: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/29.jpg)
• A 24 year old Hispanic female presents to her local hospital with left calf pain. Duplex shows a popliteal DVT. Therapy with UFH is initiated on Saturday. She is discharged on Sunday. Her only anticoagulation is 12 mg warfarin which she is told to start at 6 PM that night. She presents to Cooper Hospital on Monday evening with a leg that is painful and swollen to the groin. Duplex shows a DVT extending to the iliac vein.
![Page 30: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/30.jpg)
• Which of the following statements about anticoagulation after VTE is/are true?1. Warfarin should only be given simultaneously
with a heparin, DTI or other rapid acting anticoagulant
2. Warfarin should be started at a dose of 5 - 7.5 mg 3. Warfarin should be overlapped with heparin for a
minimum of 5 days (no matter what the INR is)4. Heparin should be stopped when the INR > 2.0
for 2 days or INR > 2.5 5. All of the above
![Page 31: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/31.jpg)
• Which of the following statements about anticoagulation after VTE is/are true?1. Warfarin should only be given simultaneously
with a heparin, DTI or other rapid acting anticoagulant
2. Warfarin should be started at a dose of 5 - 7.5 mg3. Warfarin should be overlapped with heparin for a
minimum of 5 days (no matter what the INR is)4. Heparin should be stopped when the INR > 2.0
for 2 days or INR > 2.5 5. All of the above
![Page 32: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/32.jpg)
A 60 year old female is taking a stable dose of coumadin as prophylaxis for atrial fibrillation (INR 2.6). She develops a UTI and is treated with bactrim. Two weeks later her INR is 6.9. She has no clinical bleeding. Her coumadin is held. The most appropriate adjunctive therapy would be:
A. Transfuse 4-6 units FFP
B. Transfuse 15 bags cryoprecipitate
C. Vitamin K 0.5 mg sc x 1
D. Vitamin K 10 mg sc x 1
E. Vitamin K 10 mg sc x 3d
F. Vitamin K 2.5 mg po x 1
G. No additional therapy is needed
![Page 33: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/33.jpg)
A 60 year old female is taking a stable dose of coumadin as prophylaxis for atrial fibrillation (INR 2.6). She develops a UTI and is treated with bactrim. Two weeks later her INR is 6.9. She has no clinical bleeding. Her coumadin is held. The most appropriate adjunctive therapy would be:
A. Transfuse 4-6 units FFP
B. Transfuse 15 bags cryoprecipitate
C. Vitamin K 0.5 mg sc x 1
D. Vitamin K 10 mg sc x 1
E. Vitamin K 10 mg sc x 3d
F. Vitamin K 2.5 mg po x 1
G. No additional therapy is needed
![Page 34: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/34.jpg)
Reversal of Warfarin
• INR < 5.0, no bleeding– lower dose or – omit dose, restart at lower dose
Chest June, 2008
![Page 35: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/35.jpg)
Reversal of Warfarin
• INR > 5.0 but < 9.0, no significant bleeding– omit 1 or 2 doses and restart at lower dose, or– omit dose, give vitamin k 1-2.5 mg po, or– for rapid reversal (i.e., surgery) 3 - 5 mg po
(INR should decrease in 24 hr)• can repeat vitamin k 1-2 mg po if goal not
reached
![Page 36: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/36.jpg)
Reversal of Warfarin
• INR > 9.0, no significant bleeding– hold warfarin– give vitamin K 2.5 - 5 mg po (INR should be
significantly reduced in 24 - 48 hrs)– additional vitamin k po if needed– resume warfarin when INR therapeutic
![Page 37: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/37.jpg)
Reversal of Warfarin
• Any INR > 3.0, serious bleeding– hold warfarin– vitamin k 10 mg slow iv infusion– repeat every 12 hours as needed– FFP, r-VIIa or prothrombin complex depending
upon urgency of the situation
![Page 38: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/38.jpg)
Reversal of Warfarin
• Any INR > 3.0, life threatening bleeding– hold warfarin– fresh frozen plasma, r-VIIa or prothrombin
complex– vitamin k 10 mg slow iv infusion
![Page 39: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/39.jpg)
Warfarin Pearls
• Coumadin if possible– If generic, keep track of brands
• Dose adjustment– Think in terms of a week– New warfarin dose = current dose x goal INR
current INR– New dose = 35 mg x 2.5/5.0– New dose = 17.5 mg/week = 2.5 mg/day
![Page 40: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/40.jpg)
IVC FilterIndications
• Recent proximal DVT, and– Contraindication to anticoagulation
• current or recent active GI bleed • intracranial bleed in last 5 days• recent neurologic or ophthalmologic surgery• cerebral metasteses at risk for bleeding
– seminoma, melanoma, renal cell, choriocarcinoma
• planned major surgery in next 4 weeks• severe, prolonged thrombocytopenia
• Recurrent pulmonary emboli while fully anticoagulated
![Page 41: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/41.jpg)
New Anticoagulants
• Pentasaccharide– Fondaprinux (Arixtra)
• Oral IIa inhibitors– ximelagatran
• Oral Xa-inhibitors
![Page 42: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/42.jpg)
Fondaparinux (Arixtra)
![Page 43: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/43.jpg)
Theoretical Models for Differential Effects of Heparin and LMWH on Thrombin and
Factor Xa
Fondaparinux: 5 Saccharide Units
Fondaparinux
XaATIIaAT55
Binds to AT but not to Thrombin
Binds to AT
![Page 44: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/44.jpg)
New Anticoagulants
• Fondaparinux (Arixtra)– Synthetic pentasaccharide– Selective anti-Xa inhibitor
• no anti-IIa activity• PT or PTT are insensitive
– Renal excretion– T1/2 17 – 20 hrs– Does not bind PF4
• One reported case of HIT
![Page 45: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/45.jpg)
• FDA Approved– hip and knee surgery prophylaxis– treatment of DVT– treatment of PE when started in hospital– surgical DVT prophylaxis
![Page 46: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/46.jpg)
• Fondaparinux dosing for DVT or PE– < 50 kg 5 mg qd sc– 50 – 100 kg 7.5 mg qd sc– >100 kg 10 mg qd sc
• Dose modification– Ccr 30 – 50, use with caution– Ccr < 30, contraindicated
![Page 47: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/47.jpg)
• Because of long half-life, anticoagulant effect may last for 2 – 4 days after stopping fondaparinux with normal renal function
• Anti-Xa activity can be measured– ? <0.3 u/ml safe
• R-VIIa if severe bleeding
![Page 48: Anticoagulation 101](https://reader035.vdocuments.site/reader035/viewer/2022081504/56812f70550346895d94f880/html5/thumbnails/48.jpg)