3. Coagulation
• Platelets and clotting factors are responsible for
initiating coagulation. When an injury occurs,
platelets (thrombocytes) immediately migrate to the
damaged area. Because platelets stick to each other
(aggregation) and to the vessel walls (adhesion), they
form a plug around the injured tissue. Plasma
clotting factors reach the platelet plug and interact
with each other to form a stable blood clot.
Hemostasis is the balance between clot formation
and clot breakdown that occurs throughout the day.
1-3
4. Coagulation
• Intrinsic Pathway:
– Damage to vessels
– Physical/chemical activation within the blood
(blood components within the vessels)
• Extrinsic Pathway
– Damage outside of vessels
– Tissue factor released by damaged cells activation
outside the blood (blood escaped from vessels)
1-4
7. Stage 1
• A substance known as thromboplastin is produced.
• The intrinsic system requires many clotting factors
and platelets to stimulate production of
thromboplastin.
• The extrinsic system requires factor VII and tissue
extract, a substance that is released from injured
cells. Regardless of the pathway involved, once
thromboplastin is produced, clotting proceeds
automatically.
1-7
8. Stage 2 & 3
• Stage 2. Thromboplastin converts prothrombins to
thrombin.
• Stage 3. Thrombin converts fibrinogen to fibrin and
activates several clotting factors (V, VIII, XIII, and
protein C).
– Fibrin is the primary element of a blood clot, and these
activated factors build a fibrin mesh that holds the
platelets (developing clot) together.
– Require calcium ions in order to function efficiently.
Vitamin K is required for the synthesis of many of the
factors in the coagulation pathway.
– Usually, the clot is dissolved once its function has ended.
1-8
9. Stage 4
• Stage 4: Plasmin is formed from the
conversion of plasminogen by tissue
plasminogen activator (tPA). Plasmin is an
enzyme that acts upon the fibrin elements to
produce a more soluble product.
1-9
10. Drug Class Prototype Action Effect
Anticoagulant
Parenteral Heparin Inactivation of clotting
factors
Prevent DVT
Oral Warfarin Decrease synthesis of
clotting factors
Prevent DVT
11. Anticoagulants
Heparin
Structure
Mucopolysaccharide
Metabolism
Partially in the liver by heparinase to uroheparin, which has
only slight antithrombin activity.
20-50 % is excreted unchanged.
{The heparin polysaccharide chain is degraded in the gastric
acid} administered IV or SC.
Heparin should not be given IM }danger of hematoma
formation{.
12. Unfractionated heparin (UFH)
Mol weight:
3000-30000
Mechanism of action:
•Primarily: interaction with antithrombin III: alters the molecular
configuration of antithrombin III, making it 1,000 to 4,000 times more
potent as an inhibitor of thrombin formation: limits conversion of
fibrinogen to fibrin: prolongs aPTT
•Also inhibits the effects of factor Xa on the coagulation cascade &
limits platelet aggregation.
Half-life:
IV: 1 hr
SC: 3 hrs.
13. Dosing options.
Preoperative: 5,000U 2 hours before surgery.
{The single preoperative dose seems to be as effective as multiple
preoperative doses}.
Postoperative: 8 to 12 hrs after surgery & every 8
to 12 hrs until the patient is fully ambulatory.
Antidote:
Protamine sulphate
Monitor:
aPTT
Use in pregnancy: {does not cross the placenta}
safe
15. Half-life:
4 hrs, by any route: longer dosing interval.
Bioavailability
More consistent than that of UFH: dosing is based on
lean body mass & Less thrombocytopenia.
Use in pregnancy:
Does not cross the placenta: safe.
Dosing options.
Prophylaxis: Once a day
Therapy: Twice-daily.
Enoxaparin is an LMWH
Moderate risk: 20 mg/d
High risk: 40 mg/d.
•Advantage
Decreased need for monitoring
16.
17. Oral anticoagulants
Warfarin
Structure:
small, lipid-soluble molecules, Structurally related to vitamin K,
isolated from clover leaves
Mechanism:
• Inhibits production of active clotting factors
• blocks the Vitamin K-dependent glutamate carboxylation of
precursor clotting factors e.g. FII, VII, IX , X
Metabolism:
• Absorption: rapid
• Binds to albumin
• Clearance is slow: 36 hrs
• Delayed onset: 8-12 hr {T1/2 of clotting factors in plasma}
18. WarfarinHeparin
OralParentral onlyAbsorption
7.6-13.9 LPlasma vol (0.07 L/kg)Vol of distribution
HepaticHepatic metabolism & uptake by reticulo
endothelial system
Also by thrombin & other clotting factors
Metabolism/Clearance
36-42 hr50-90 minElimination t1/2
99.4% bound to albuminBound to antithrombin III & other serine
proteases
Protein binding
1.5 mg/L0.2-0.4 U/mlPlasma concentration
(therapeutic)
Bleeding
Skin necrosis
Drug interactions
Bleeding
Thrmbocytopenia
Osteoporosis
Side effects
•Mild: hold 1-2 doses,
observe, restart at lower
dose
•Severe: Vit K or fresh
frozen plasma
•Mild: Slow or stop infusion
•Severe: Protamine 1 mg/100 u of
estimated heparin remaining in body
Treatment of
bleeding
20. Effective Patient Education
• Teach basic concepts of safe, effective
anticoagulation
• Discuss importance of regular INR
monitoring
• Counsel on use of other medications,
alcohol
• Develop creative strategies for improving
compliance
–Evening, same time
–Dosettes, blisterpacks
21. Warfarin Tablets
• 1mg – pink
• 2mg – lavendar
• 2.5mg – green
• 3mg – tan
• 4mg – blue
• 5mg – peach
• 6mg – teal
• 7.5mg – yellow
• 10mg - white
22. Warfarin Management
• Serious bleeding,
– Hold Warfarin
– Give Vitamin K1 10mg slow IV plus fresh plasma or
prothrombin complex concentrate, depending on
urgency
– Repeat Vitamin K1 every 12 hours as needed
• Life-threatening bleeding,
– Hold warfarin
– Give prothrombin complex concentrate (or
recombinant factor VIIa as an alternative)
supplemented with vitamin K1 10mg slow IV; repeat
as needed
23. Clexane (enoxaparin)
• Clexane injection contains the active ingredient
enoxaparin, which is a type of medicine called a
low molecular weight heparin. It is used to stop
blood clots forming within the blood vessels.
• Blood clots normally only form to stop bleeding
that has occurred as a result of injury to the
tissues. The clotting process is complicated and
begins when blood cells called platelets clump
together and produce chemicals that activate the
clotting process. The final part of this process
involves a substance called thrombin being
activated to produce a protein called fibrin. Fibrin
binds the platelets together, forming a blood clot.
This is the body’s natural way of repairing itself.
24. • Sometimes, however, a blood clot can form
abnormally within the blood vessels. This is
known as a thrombus. It can be dangerous
because the clot may detach and travel in
the bloodstream, where it becomes known
as an embolus. The embolus may
eventually get lodged in a blood vessel,
thereby blocking the blood supply to a vital
organ such as the heart, brain or lungs. This
is known as a thromboembolism.
25. • Enoxaparin is used to prevent and treat these types
of abnormal blood clots. It works by inactivating
thrombin in the clotting process described above.
This stops the formation of fibrin, the essential
component of blood clots. The medicine is
administered by injection under the skin
(subcutaneous injection).
• Enoxaparin can also be used to prevent blood clotting
when it is filtered through a kidney dialysis machine.
26. What is it used for?
• Treatment of blood clots in the veins of the leg (deep
vein thrombosis).
• Treatment of blood clots that travel to the lungs
(pulmonary embolism).
• Preventing these types of blood clots (thromboembolic
disorders), particularly following general surgery or
surgery on the bones (orthopaedic surgery), or in
people bedridden due to illness.
• Treating blood clots in the coronary arteries in unstable
angina and heart attack (myocardial infarction).
• Preventing blood from clotting when it is filtered
through an 'artificial kidney' (haemodialysis) machine
as part of the management of kidney failure.
•
27. • Warning!
• During treatment with this medicine you
should have regular blood tests to monitor
the numbers of blood cells called platelets in
your blood.
• Your doctor may also want to monitor the
level of potassium in your blood while you
are having this medicine, particularly if
treatment lasts for longer than 7 days.
28. Use with caution in
• People over 80 years of age.
• People who are underweight or overweight.
• Decreased kidney function.
• Chronic kidney failure.
• Decreased liver function.
• People who have previously developed a reduced platelet count in the blood due to treatment
with heparin or low molecular weight heparin (heparin-associated thrombocytopenia).
• People with problems stopping bleeding.
• History of peptic ulcer.
• Recent stroke caused by a blood clot in the brain (ischaemic stroke).
• Severe uncontrolled high blood pressure (hypertension).
• Diabetes.
• Diabetes affecting the eyes (diabetic retinopathy).
• People who have recently had eye surgery.
• People who have recently had surgery on the brain or spinal cord (neurosurgery).
• People having spinal or epidural anaesthesia.
• High level of potassium in the blood (hyperkalaemia).
• Increase in the acidity of the blood (metabolic acidosis).
•
29. Not to be used in
• Allergy to heparin or other low molecular weight
heparins.
• Bacterial infection of the heart valves and the lining
surrounding the heart (bacterial endocarditis).
• Active major bleeding.
• Conditions with a high risk of uncontrolled bleeding,
for example the blood clotting disorder haemophilia,
or the conditions listed below.
• Active peptic ulcer.
• Recent stroke caused by bleeding in the brain
(haemorrhagic stroke).
• Reduced platelet count in the blood
(thrombocytopenia).
• This medicine is not recommended for use in children.
30. Side effects
• Bleeding.
• Pain and irritation at the injection site.
• Blood clots which form a solid swelling at the injection site
(haematoma).
• Decrease in the number of platelets in the blood (thrombocytopenia).
• Major bleeding (haemorrhage), for example in the abdomen or inside
the skull.
• Alteration in results of liver function tests.
• High blood potassium level (hyperkalaemia).
• Death of skin cells (necrosis) at the site of injection.
• Blood clots in the spinal cord (intraspinal haematoma) in people also
having spinal or epidural anaesthesia.
• Osteoporosis (a reduction in bone density leading to bones which may
fracture easily) has occurred after long-term treatment with a similar
medicine called heparin. It is possible that this could happen with
Clexane.
31. ANTICOAGULATION DRUGS: WHAT
NURSES NEED TO KNOW
• The goal of activity is to provide nurses and
nurse practitioners with knowledge and skills to
manage patients on anticoagulant drugs. After
reading this article, you will be able to:
• Identify common indications for use of
anticoagulants
• Describe monitoring requirements
• Consider important safety implications to help
prevent complications
• Discuss patient/family educational needs related
to anticoagulants
32. • Monitoring and Safety Implications
Heparin requires close monitoring because of its
narrow therapeutic index, increased risk for bleeding,
and potential for heparin-induced thrombocytopenia
(HIT). Monitoring includes thorough head-to-toe
patient assessments for potential side effects, and
laboratory monitoring.
• Bleeding is the most common side effect, and may
present in a variety of ways: epistaxis, gum bleeding,
hemoptysis, hematuria, melena or hemorrhage.
Undiagnosed and uncontrolled bleeding may lead to
cardiovascular collapse or cardiac tamponade. In the
event of major bleeding, heparin should be stopped,
and, if necessary, protamine sulfate may be
administered.
33. • Patient Education
• Patients on anticoagulant therapy must be educated
about their increased risk for bleeding, monitoring for
bleeding, managing bleeding if it occurs, and drug-
specific information.
• Monitoring and Safety Implications
Warfarin has a narrow therapeutic index, so monitoring
includes assessment for potential side effects,
laboratory tests for dose titration, and vigilance for
potential drug and food interactions.
• Bleeding is the most common side effect, most
frequently in the GI tract. Warfarin may cause skin
necrosis, or cholesterol embolus syndrome. Specific
patient variables may impact drug metabolism. For
example, active hepatic disease, certain drugs, and old
age are likely to enhance the response to warfarin.
34. Conclusion
Anticoagulation drugs can be life-saving.
Nurses must carefully assess, closely
monitor, and comprehensively educate
the patient receiving anticoagulation
drugs to ensure the full benefit of
anticoagulation therapy and to minimize
potential harm.
