Anti-coagulation

Anti-coagulation in
in critically
critically ill
ill
patient
patient
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By
By
Dr.
Dr. Moustafa
Moustafa AbdAbd Elhamid
Elhamid Elshal
Elshal
Specialist
Specialist of
of Vascular
Vascular Surgery
Surgery ,Endovascular
,Endovascular Surgery
Surgery and
and
Diabetic
Diabetic Foot
Foot management
management
National
National Institute
Institute Of
Of Diabetes
Diabetes and
and Endocrinology
Endocrinology
Cairo
Cairo -- Egypt
Egypt

Tele
Tele :: 0113437474
0113437474 -- 0106011656
0106011656
Member
Member
2010
2010
Problems of critically ill patient
• Immobilization
• Pulmonary Embolism

• Age > 65
•Thrombogenicity of associated illness
- Cancer - Surgery - Trauma

• Obesity
• Past hystory
- DVT - Varicose Vs
 Role of early mobilization
mobilization

Incidence of TED

Immobilization (1 week) 15 %

Immobilization (2 - 3 weeks) up to 80 %

Oral contraceptives 2.9 %

M.LEVINE et al, N Engl J M 1996; ,334:2, 677-681

Proximal Deep Vein
Thrombosis (DVT)
 Deep Vein Thrombosis (DVT)
Risk Factors in Outpatients

Clinical Condition Odds Ratio

Cancer 5.6
Obesity 3.9
Smoking 2.8
Oral contraceptives 2.75
Hormone replacement therapy 2.7
Varicose veins 2.6
Age >65 years 1.8
History of venous thromboembolism 1.7
 Deep Vein Thrombosis (DVT)
Risk Factors in Hospitalized Patients
Clinical Condition Odds Ratio
Surgery 21.7
Trauma 12.7
Confinement to nursing home or hospital 8.0
Cancer with chemotherapy 6.5
Cancer without chemotherapy 4.1
Central venous catheter or pacemaker 5.6
Superficial vein thrombosis 4.3
Neurologic disease with extremity paresis 3.0
Clin Council on DVT Management. Treatment of deep vein thrombosis in the outpatient setting (Part 1).
Home Health Care Consultant. July 2002;11-18
 S U R G I C A L  P A T I E N T S

Incidence of Incidence
 
TED (total) of fatal PE
Low risk
< 10 % 0.01 %
Minor surgery (<30 min)
Moderate risk
Major surgery (>30 min) 10 - 40 % 0.1 - 1 %
Abdominal, pelvic, neuro surgery
High risk
Orthopedic surgery of lower 40 - 80 % 1 - 10 %
limbs
Consensus Group. BMJ. 1992
 Pharmaco-dynamic
Pharmaco-dynamic effectiveness
effectiveness

UFH LMWH
Half life 60-90 minutes 24 hours

Mollecular weight 15.000 dalton 5.000 Dalton

Anti-thrombotic effect 1:1 4:1

Anti-coagulant effect 1:1 1:1

Bioavailability Low 2-3 SC inj/day High single dose

Blood tests Needed frequently Not needed

 International studies
HULL et al,N Engl J Med. 1992;326:975-982
Riguourus unbiased study
 400 pts randomized Tinzaparin 175 IU/kg Sc once/day or
UFH IV
 Control by a PTT by a third party and follow up for 3
months
 UFH Gr 6.9% new thrombo embolic event, 2.9% in group I
 Major bleeding 5% in UFH and 0.5% in Gr I
 Mortality 21/200 (1.05%) in UFH Gr and only 10/200
(0.5%) in GrI
 CONCLUSION: Tinzaparin has a definite superiority over
UFH
 Incidence of VTE and Death
(DVT±PE
DVT±PE) at Day
Day 90
14 LMWH 175 IU/kg/day
once daily SC (n=216†)*
12
UFH 5,000 IU bolus then
9.6
% of Patients

10 continuous infusion (n=219†)*

8 6.8
5.9
6 4.6
4.1
4 2.8 2.7
2 1.4 1.4 1.4

0
Total VTE DVT PE Death Abrupt Death

Hull et al. NEJM 1992;326:975-982, n=213, LMWH, n=219 UFH

 Major
Major Bleeding
Bleeding Events
Events ((DVT±PE
DVT±PE))
During or Immediately
Immediately After Initial
Treatment
Treatment
LMWH (n=216)
Major Bleeding Events

UFH (n=219)
% of Patients With

5.0

0.5

P=.006 LMWH vs UFH

Hull et al. NEJM 1992;326:975-82.
 Frequency of Recurrent VTE (DVT±PE)

30 Log-rank Analysis (Time-to-Event)

Number of Patients

20

UFH

10
LMWH*

0
0 10 20 30 40 50 60 70 80 90
Days
*P=.049 LMWH vs UFH
Hull et al. NEJM 1992;326:975-82.
 Conclusion (DVT±PE)

 LMWH given once daily is at least as safe and

effective as classic IV UFH therapy in patients
with acute proximal-vein thrombosis
 Patients treated by LMWH experienced
significantly fewer major bleeding complications
(P=.006)

Hull et al. NEJM 1992;326:975-82.

 Treatment
Treatment for PE
PE (Subset
(Subset Analysis
Analysis)
14
LMWH 175 IU/kg/day
12 once daily SC (n=97)*
% of Patients

UFH 5,000 IU bolus then

10 8.7
continuous infusion (n=103)*
8 6.8
6.2
6

4 2.9
1.9
2 1.0 1.0
0.0
0
Recurrent VTE Major Bleeding Minor Bleeding Death

Hull et al. Arch Intern Med 2000;160(2):229-36.

 Conclusion
Conclusion

 Tinzaparin
Tinzaparin given
given once
once daily
daily is
is at
at least
least as
as
safe
safe and
and effective
effective as
as classic
classic IV
IV heparin
heparin
therapy
therapy in
in treating
treating patients
patients with
with PEPE and
and
associated
associated proximal
proximal DVT
DVT

 No
No patient
patient treated
treated with
with tinzaparin
tinzaparin (n=97)
(n=97)
had
had aa new
new episode
episode ofof VTE
VTE compared
compared with
with 77
of
of 103
103 (6.8%)
(6.8%) patients
patients who
who received
received UFH
UFH
(95%
(95% CI:
CI: 1.9,
1.9, 11.7;
11.7; PP=.01)
=.01)
Hull et al. Arch Intern Med 2000;160(2):229-36.
 Simonneau et al
Events: Days
Days 1-8
1-8 (Acute
(Acute PE
PE))
14
LMWH
12

10 UFH 50 IU/Kg bolus then

% of Patients

continuous infusion (n=308)*

8

2 0.99 1.3 0.99 1.3 0.97

0.65
0
Recurrent VTE Major Bleeding Death

* Oral anticoagulant therapy (warfarin, fluindione, or acenocoumarol; dose adjusted

to achieve INR of 2-3) started on day 1, 2, or 3
Simonneau et al. NEJM 1997; 337(10):663-9.
 Events: Days 9-90 (Acute PE)
14
LMWH
12

10 UFH 50 IU/Kg bolus then

continuous infusion (n=308)*
8
% of Patients

6
3.6
4
2.6
1.9
2 1.3 1.3
0.66
0
Recurrent VTE Major Bleeding Death

* Oral anticoagulant therapy (warfarin, fluindione, or acenocoumarol; dose adjusted to

achieve INR of 2-3) started on day 1, 2, or 3

Simonneau et al. NEJM 1997; 337(10):663-9.

 Conclusions (Acute
(Acute PE
PE Trial)
Trial)

 The
The efficacy
efficacy of
of once-daily
once-daily SC
SC tinzaparin
tinzaparin was
was comparable
comparable to
to
continuous
continuous infusion
infusion IV
IV UFH
UFH inin patients
patients with
with symptomatic
symptomatic PE
PE

 Tinzaparin
Tinzaparin can
can be
be used
used safely
safely and
and effectively
effectively when
when given
given once
once
daily
daily to
to treat
treat DVT
DVT patients
patients with
with acute,
acute, symptomatic
symptomatic PE
PE

 In
In both
both groups,
groups, the
the rates
rates of
of recurrence,
recurrence, major
major bleeding,
bleeding, and
and death
death
were
were similar
similar and
and low
low

 During
During the
the first
first 88 days
days of
of treatment,
treatment, the
the overall
overall incidence
incidence of
of severe
severe
critical
critical events
events was
was similar
similar in
in both
both groups
groups (~3%)
(~3%)

 During
During the
the 33 months
months of
of follow-up,
follow-up, there
there was
was aa non
non significant
significant
trend
trend favoring
favoring tinzaparin
tinzaparin compared
compared with
with IV
IV UFH,
UFH, with
with rates
rates of
of the
the
combined
combined endpoint
endpoint of
of 5.9%
5.9% and
and 7.1
7.1 %
% respectively
respectively

Simonneau et al. NEJM 1997; 337(10):663-9.

Low-Molecular-Weight Heparin vs Heparin in the
Treatment of Patients With Pulmonary Embolism
Russell D. Hull, MBBS, MSc; Gary E. Raskob, PhD; Rollin F. Brant, PhD;
Graham F. Pineo, MD; Gregory Elliott, MD; Paul D. Stein, MD;
Alexander Gottschalk, MD; Karen A. Valentine, MD, PhD; Andrew F.
Mah; for the American-Canadian Thrombosis Study Group
Arch Intern Med. 2000;160:229-236.

Results  Of 200 patients with high-probability lung scan

findings at study entry, none of the 97 who received
low-molecular-weight heparin had new episodes of
venous thromboembolism compared with 7 (6.8%) of
103 patients who received intravenous heparin
 A comparaison of LMWH administered
primary at home with UFH administered at
hospital for proximal DVT
Mark Levine, MD, Michael Gent, …et al.
N Engl J M. 1996;334:11,676-681.

Results
LMWH(253 pts) UFH (247pts) 
Recurrent DVT 13(5.03%) 17 (6.7%)
Major bleeding 5 3
Hospital stay 1.1 day 6.5 days
Pharmaco-economic evaluation of outpatient
treatment with LMWH versus inpatient
treated with UFH
Alex C. Spyropoulos,MD. Judith Huley, et al.
Chest/122/1/July,2002: 108-114

Outpatient (LMWH) Inpatient (UFH)

9.347 $ 11.930 $
Difference = 2.583 $
 OBLIGATIONS
OBLIGATIONS FOR
FOR HOME
HOME THERAPY
THERAPY
 Patient
Patient geographically
geographically accessible
accessible
 Patient
Patient must
must bebe instructed
instructed for
for the
the proper
proper giving
giving
for
for LMWH
LMWH injections
injections
 Patient
Patient should
should not
not have
have other
other major
major conditioned
conditioned
as
as Hep
Hep cell
cell failure,
failure, peptic
peptic ulcer
ulcer
 Patient
Patient should
should provide
provide enough
enough quantity
quantity of
of ttt
ttt
 Patient
Patient stable
stable clinically
clinically
 Conclusion
• LMWH is as safe as UFH
• LMWH is as effective as UFH
• LMWH is easy to use, single shot, with no monitoring
• LMWH is cost effective
• LMWH allows us to treat patients with proximal DVT
and acute Pulmonary embolism at Home with results as
safe and effective as UFH
• Prevention program is the best treatment for TED