1. Parenteral Anticoagulant
BY : Maha khalid
Supervisor : Pro Dr Seham Hafez

2. Parenteral Anticoagulant
UFH & LMWH all
consist of high
MW molecules that
Are highly ionized (they don't
absorbed from GIT they must
given by
IV infusion or
deep SC injection.
( never IM )
LMWH
UFH
Fondaparinux

3. Objective of anticoagulation
To prevent death & recurrent event with acceptable rate of bleeding complications.
Considering the high mortality rate (30 %) in untreated patient with suspected PE anticoagulant treatment should be consider while a waiting definitive diagnostic confirmation.

4. Goals of anticoagulation therapy
1-The efficacy of heparin therapy depends on achieving a critical therapeutic level of heparin within the first 24 hours of treatment. The critical therapeutic level of heparin is 1.5 times the baseline control value or the upper limit of normal range of the activated partial thromboplastin time (aPTT).
This level of anticoagulation is expected to correspond to a heparin blood level of U/mL by the protamine sulfate titration assay and by the antifactor X assay.

5. UFH Vs LMWH
1-Standard heparin is comprised of an unfractionated heterogeneous mixture of polysaccharide chains with mean molecular weights ranging from to daltons.
2-LMWHs are formed by depolymerization of unfractionated heparin side chains, producing “smaller” heparin fragments, with mean molecular weights ranging from 1000 daltons to daltons.

7. UFH Vs LMWH
1- Both types of heparin inactivate factor Xa by interacting with antithrombin (AT)
2- unfractionated heparin (UFH) is able to inactivate factor IIa through formation of a tertiary complex.
3- UFH inactivates factors IIa and Xa and affects the apTT (activated partial thromboplastin time )
4-LMWH inhibits factor Xa and minimally affects factor IIa; thus activated partial thromboplastin time is not used to measure its anticoagulant activity

11. Anticoagulant Properties of UFH
1-Inhibits the thrombin-mediated
conversion of fibrinogen to fibrin
3-Inhibits activation of fibrin
stabilizing enzyme
2-Inhibits the aggregation
of platelets by thrombin
4-Inhibits activated factors XII, XI, IX, X and II

12. When unfractionated heparin is used, the aPTT should not be checked until 6 h after the initial heparin bolus because an extremely high or low value during this time should not provoke any action.
Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis

13. UFH weight based dose:

14. can give once or at the most
UFH Vs LMWH
LMWH have potential desirable PK
than heparin
, they excreted renally &
have longer half lives
1-Heparin half life is 1 hrs
but it shorter in patient
with PE It
excreted by
both hepatic & renal ways
it would take 5 hrs
( five half lives
to reach steady state
, a loading dose is
required to reduced
the time
to achieve adequate
anticoagulation
have more
predictable dose
response than UFH.,they
can give once or at the most
twice daily in fixed dose.

15. UFH Vs LMWH Hemorrhage Heparin LMWH risk commoner in of hemorrhage
may
produce
fewer
hemorrhagic
complication &
monitoring of
effect is
not
routinely
required
LMWH
risk
of hemorrhage is
increased
in those
given
heparin by
Intermittent
intravenous
bolus
rather than by
continuous
administration.
Heparin
commoner in
patients
with sever heart
or liver disease
,renal disease
, general debility
& women
aged over
60 years.
The risk of
hemorrhage
is increased
in those
with prolonged
clotting times
Hemorrhage
More
less

16. LMWH Heparin HIT Thrombocytopenia
LMWH are less likely to produce thrombocytopenia this complication only in :Patient only previoulsly developed thrombocytopenia after UFH .
Heparin
HIT
LMWH
Thrombocytopenia

17. Heparin induced thrombocytopenia “ HIT “
the second type occure
after 6 days
of FIRSTtreatment or
hours to 2-3 days
with re-exposure.
the first occurs
after 3-5 days
after initiate
of treatment
often result in much
more reduction in
plateletscount & increased risk
of thromboembolism .
doesnot result in
complication

18. HIT ( Mechanism )
HIT is the most common drug-induced thrombocytopenia in adults, complicating 1-4% of full-dose exposures to standard heparin. Unlike other thrombocytopenias, HIT carries a high thrombotic morbidity (30-50%) and mortality (10-15%) because it is a syndrome of platelet activation. Heparin forms a complex with platelet factor 4 (PF4) which is released from platelets by platelet activation. Antibody directed against the heparin-PF4 complex binds via its Fab region. The antibody-heparin-PF4 immune complex binds to the Fc receptor on the surface of the platelet leading to activation of the platelet.

20. Criteria for Diagnosing HIT

21. Complications of HIT 1-•Deep vein thrombosis• 2-Pulmonary embolism•
3-Myocardial infarction•
4-Occlusion of limb arteries (possibly resulting in amputation)•
5-Cerebrovascular accidents (stroke )
6-Skin necrosis•
7-End-organ damage (e.g., adrenal, bowel, spleen, gallbladder or hepatic infarction; renal failure)•
8-Death

22. Treatment of HIT : C/I must be stopped should be AVOIDED
1-ALL heparin (lines, flushes, heparin-coated catheters, LMWH )
should be AVOIDED
Platelet transfusion
(transfusion may precipitate thrombosis)
warfarin in the acute phase of HIT
(its use may precipitate venous gangrene and thrombosis).
C/I

23. highly specific direct in order to prevent further
[1-lepirudin (rDNA)
for injection
highly specific direct
inhibitor of thrombin
indicated as an
anticoagulant
for prophylaxis
or treatment of
thrombosis in
patients with HIT
and associated
thromboembolic
disease
in order to prevent further
complications.
Treatment of HIT :
2-Argatroban is a
synthetic direct
thrombin inhibitor
indicated as an
anticoagulant
for prophylaxis
or treatment
of thrombosis in
patients with HIT

24. For how long UFH &LMWH should be used ?
1-Heparin used in immediate stages of venous
thrombosis & PE until the effect of warfarin
become apparent .
In the past it has been continued for 7-10 days
but recent evidence indicate that 3-5 days of therapy maybe sufficient in many instances :
this will reduce the risk of HIT which normally occurred after 6 days.
2- LMWH are used for similar length but they are give SC without loading dose & without routinely monitoring.

25. Enoxaparin Only LMWH approved by FDA for both
treatment and prophylaxis of DVT and PE.
Dose
Adult :DVT/PE: 1 mg/kg SC q12h or 1.5 mg/kg SC qd Prophylaxis of DVT: 30 mg SC q12h Prophylaxis in abdominal surgery: 40 mg SC qd,
first dose given 2 h prior to surgery Pediatric
DVT/PE: 1 mg/kg SC q 12h
Interactions:
Platelet inhibitors or oral anticoagulants (eg, dipyridamole
, salicylates, aspirin, NSAIDs,
sulfinpyrazone, ticlopidine) may increase risk of bleeding

26. Enoxaparin(Con”d) Pregnancy
contraindication
Documented hypersensitivity; major bleeding; thrombocytopenia
Pregnancy
B - Usually safe but benefits must outweigh the risks
Precautions
If thromboembolic event occurs despite LMWH prophylaxis,
discontinue drug and initiate alternate therapy; elevation of
hepatic transaminases may occur but is reversible;
HIT may occur; 1 mg protamine sulfate
reverses effect of approximately 1 mg enoxaparin
if significant bleeding complications develop

27. When LMWH will need dose adjustment :
in patient with renal failure
dose adjustment according to
anti-Xa level.
If crcl less than 30ml/min
heparin is preferred
Also patient
at high risk of
bleeding
heparin should
be considering as
it effect
is easy to
reversed.
very thin or very
obese patient
dose
adjustment
According
to factor Xa
pregnancy.

28. FONDAPARINUX
Synthetic anticoagulant that works by inhibiting factor Xa
a key component involved in blood clotting. Provides
highly predictable response.
Bioavailability is 100%. Has a rapid onset of action and
a half-life of h,
allowing for sustained
antithrombotic activity over 24-h period
Does not affect prothrombin time or activated partial
Thromboplastin time, nor does it affect platelet function
Dose : 2.5 mg SC qd

29. administration of platelet inhibitors,
DRUG INTERACTIONS:
None reported; increased risk of bleeding possible
with concurrent
administration of platelet inhibitors,
oral anticoagulants, or thrombolytic agents
Contraindication
Documented hypersensitivity; seriously impaired kidney function
or in patients
who weigh <110 lb; patients given spinal anesthesia
or spinal puncture
Pregnancy
C - Safety for use during
pregnancy has not been established.
Precautions
When spinal anesthesia or spinal puncture
used, may develop blood clot in spine
, which can result in long-term or permanent paralysis

30. Finally which one is better UFH or LMWH ?

31. Several meta-analyses have indicated that:
1-LMWH
is associated
with less
bleeding
and fewer
episodes of
heparin-
Induced
thrombocytopenia
Than
UFH
2-patients
receiving
LMWH reported
a higher quality of
life in terms of
physical and
social
function
and sense
of well-being.
3- Treatment of DVT
with LMWH
was more
cost-effective
than therapy with
UFH
because
the length of
The hospital
stay was reduced by 60
to 70 percent without
an increase in the cost
of home health care

32. But Two recent studies of patients with DVT :
To compare the effect of LMWH given on an outpatient basis SC twice daily with that of UFH given by continuous IV infusion in the No significant different was hospital found in rates of recurrent venous thromboembolism, hemorrhagic complications, development of thrombocytopenia or mortality. LMWH were as safe and effective as UFH and most patients were managed at home immediately after diagnosis or a brief hospitalization.

33. With warfarin

34. THANK YOU