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Agents Affecting Blood
Clotting
Introduction
 Thromboemboli (blood clot that blocks the blood vessel)
 Causes many deaths per year
 Anticoagulants prevents the formation of a thrombus
Anticoagulants
 Inhibits the formation of clots
 Heparin- found in mast cells throughout the body
 Action- inhibits the clotting process
 Incapable of exerting a fibrinolytic effect on existing clots
Heparin
 Used in prophylaxis and treatment of clotting
disorders:
Coronary occlusion, cerebral thrombosis, CVAs,
thromboembolism
Indirectly interferes with the conversion of
prothrombin to thrombin
Deficiency of thrombin prevents the conversion of
fibrinogen to fibrin
Heparin
 Not effective in oral administration & not advised in IM (hematoma)
 Administered SC (long acting) or IV (continuous infusion preferred)
Measured in units
Units vary from product to product and dosing should be closely
monitored
Do not aspirate after SC injection
 Inactivates prothrombin, prevents of thromboplastin
 Effectiveness determined through clotting times
Most commonly used test activated partial thromboplastin time (APTT)
Heparin
 Continuous IV-coagulation tests every 4 hours
 Intermittent IV or deep SC injection- coagulation test done before
each injection
 Caution with diseases: severer HTN, dissecting aneurysm,
idiopathic thrombocytopenic purpura, hemophilia, peptic ulcer,
ulcerative colitis, threatened abortion
Heparin
 Complications:
Hemorrhage-constantly observed for evidence (subcutaneous bleeding,
bloody stool, bleeding gums, hematemesis)
Allergy- hypersensitivity
Heparin induced thrombocytopenia (HIT) after discontinuation
Caution-do not administer to patients with coagulation disorders
Antidote- 1% Protamine sulfate
0.5-1mg of protamine required for each 100 USP units of
Heparin
Drugs & Herbals That Increase or
Decrease The Effects of Heparin pg 642
 Increase Effects
 Decrease Effects
 Feverfew
• Antihistamines
 Ginger
• Ginseng
 Aspirin
• Nitroglycerin
 Other Anticoagulants
• Tetracycline's
 NSAIDs
• Digitalis
 Penicillilns
 Salicylates
 Ibuprofen
Low Molecular Weight Heparin
(LMWH)
 Enoxaparin (Lovenox)
Anticoagulant drug related to heparin
Minor risk for bleeding
Increases clotting time
Used for prophylaxis of DVT for hip or knee replacement &
DVT/pulmonary embolus
 7-10 post-op in joint replacement
 1mg/kg q12h for embolus
Administered only through SC ( though IV Bolus available in single dose)
Risk of epidural or spinal hematoma- can result in long term or
permanent paralysis
Low Molecular Weight Heparin
(LMWH) cont.
 Indicated in prophylaxis of ischemic complications
 Prevent thromboembolic complications
 Some Adverse Effects: Anemia, dyspnea, edema
 Interactions: increased risk of bleeding if used Aspirin, NSAIDs, or
some herbals
 Administered with tuberculin syringe
Oral Anticoagulants
 Warfarin (Coumadin)
Inhibits blood clotting by interfering with the synthesis of vitamin
K-dependent clotting factors
Has the most predictable action and a lower incidence of side
effects
Monitor client closely
Individualized dosing
International normalized ratio (INR) prothrombin time should be
monitored every 4-6 weeks once stabilized
Prothrombin time should be maintained from 1.5-2.5 times the
control volume
Oral Anticoagulants
 Primarily metabolized in the liver
 Use with caution in trauma, HTN, diabetes, or major surgery
 Drugs that increase Warfarin : Box 20-3 pg 651 include
acetaminophen, NSAIDs…
 Drugs that decrease Warfarin: Alcohol, rifampin, vitamin k
 If over dosage omit anticoagulant until bleeding stops. If
unsuccessful administer vitamin k (phytonadione) in doses of 110 mg or more for more serious cases
Antiplatelet Agents
 Useful in treating clients who have experienced ischemic
or embolic CVAs or myocardial infarctions
 May help to prevent recurrence of such disorders
 Aspirin and dipyridamole (Persantine) are commonly
used for this purpose
 Results in a decrease of the synthesis of endoperoxides and
thromboxanes
 Substances that mediate platelet aggregation
Oral Antiplatelet Agents
 Clopidogrel bisulfate (Plavix)
 used for acute coronary syndrome, reduction of myocardial
infarction, ischemic or embolic stroke, vascular mortality, and
following cardiac surgeries
 Acts by inhibiting the binding of adenosine diphosphate to its
platelet receptor and subsequent ADP-mediative activation of
glycoprotein GPIIb/IIIa complex
 Irreversibly alters the receptor life of the platelet
 Onset is 1 hour and elimination is 8 hours
 Caution: should not be taken with other OTC medications unless
specifically prescribed, PPIs increase risk for AMI (except
pantoprazole/protonix)
Oral Antiplatelet Agents
 Cilostazol (Pletal
 Interferes with cellular phosphodiesterase (PDE) and inhibits cyclic adenosine monophosphate
(AMP)/PDE III complex
 Levels of AMP increase, resulting in vasodilation and decreased platelet aggregation
 Primarily used for treatment of intermittent claudication
 Prasugrel HCl (Effient)
 Used to reduce thrombotic events for clients with acute coronary syndrome, including stent
thrombosis
 Most common adverse effect is bleeding, use of warfarin increases risk
 For bleeding events or overdose, platelet transfusing may restore clotting ability
 Ticlopidine (Ticlid)
 Inhibitor of platelet aggregation
 Used to prevent recurrence of stroke or in clients who are susceptible to strokes
 CBC and white cell differentials should be performed every 2 weeks starting on the second week and
continuing to the third month of therapy
 If neutropenia occurs, discontinue the drug
Parenteral Antiplatelet Agents
 Abciximab
 Injectable antiplatelet drug used with aspirin and heparin to prevent coronary vessel occlusion in
clients undergoing percutaneous transluminal coronary angioplasty or atherectomy
 IV administered
 Caution when performing arterial or venous punctures, IM injections, or insertion of catheter or
nasogastric tubes
 Eptifibatide (Integrilin)
 A cyclic heptapeptide fashioned after the protein found in the venom of rattlesnakes
 Usually used in conjunction with aspirin and heparin to treat unstable angina and acute myocardial
infarction
 IV bolus administered followed by a continuous infusion
 Contraindicated in clients with creatinine levels above 2.0 mg/dL
 Stored in refridgerator and away from light
 Triofiban HCl (Aggrastat)
 Nonpeptide synthetic molecule and has smaller range of uses
 Indicated for use in treating unstable angina and AMI in conjunction with heparin
 IV administered for 30 minutes, then continuously infused
 Should not be used in the presence of acute pericarditis
Nursing Practice
 Obtain a complete medication history for the client receiving warfarin to
avoid the numerous drug interactions associated with this agent
 Vitamin K (phytonadione) is used as an antidote for oral anticoagulants
 Contact the prescriber before administering the next dose or an oral
anticoagulant if the INR is greater than the prescribed level or if the
prothrombin time is 30 seconds or greater
 Avoid the use of aspirin, NSAIDs, other anticoagulants, and antiplatelet
products
 Report abnormal bleeding or indications of internal bleeding, such as
headache, tarry stools, and changes in neurological status
Client Teaching about Anticoagulants
 Clients are advised to avoid situations that could lead to trauma
 Clients are instructed to talk with the primary care provider before adding
or subtracting any drug from their treatment program including OTC
products and herbals
 Drastic changes in diet, laxatives, and mineral oil should be avoided
 Identification and information about treatment should always be carried or
a Medic-Alert tag worn
 Women receiving anticoagulants who are considering pregnancy must be
referred to an obstetrician
 The importance of follow-up with the health care provider for monitoring
and laboratory testing should be stressed
Antithrombin agent/ Thrombin inhibitors
Antithrombin agents act by reversibly binding to an active thrombin site,
inhibiting effects of thrombin
Examples: Argatroban, synthetic direct thrombin inhibitor, binds to thrombin
site & requires no antithrombin III for its antithrombin action, Bivalirudin,
anticoagulant effects for clients with unstable angina undergoing PTCA, also
used for preventative/treatment of heparin-induced thrombocytopenia,
Desirudin, subcutaneously administered thrombin inhibitor used for the
prophlylaxis of DVT in clients undergoing hip replacement surgery
Thrombolytic Agentspg655
 Thrombolytic enzymes dissolves fibrin clots, as well as other plasma proteins
Action: Convert plasminogen to enzyme fibrinolysin; fibrinolysin dissolves clots
Indication: Lysis of acute massive pulmonary emboli and central line sepsis caused by
fibrin formation
urokinase used to clear fibrin from central venous catheters
Example
Urokinase/Abbokinase
Streptokinase/Streptase
Caution
Hemorrhage
Tissue Plasminogen Activatorspg657-658
Used in the management of Acute MI and the acute phase of CVA
(stroke)
Causes local fibrinolysis and disintegration of the clot
Effectiveness is related to how soon it is administered after the onset of
symptoms of MI (within 6 ours of onset of symptoms)
Common side effect: bleeding
Other agents that alter platelet formation should not be used before,
during or after treatment because of their additive affect and risk for
bleeding
Examples: Alteplase-recombinant (Activase), Reteplase
recombinant (Retavase), Tenecteplase ( TNKase)
Tissus Plasminogen Activators (cont.)
Alteplase, is considedered the drug of choice for the management of acute
ischemic stroke in adults to improve neurologic recovery and limit disability; t-PA
(tissue plasminogen activators) need to be initiated within 3hours of CVA
manifestations; effectiveness of treatment with t-PA is related to how soon it is
administered after the onset of symptoms of AMI.
Recteplase, is indicated for use in adult clients experiencing AMI to improve
ventricular function, reduce incidence of HF and decrease mortality;1st dose
administered over 2mins and them 30mins later 2nd dose administered; monitor
clients for bleeding and reprofusion reactions (arrhythmias); agents that alter
coagulation should not be given during recteplase therapy because of increased
risk for bleeding
Tenecplase, similar in action to alteplase, reteplase and streptokinase, indicated in
the treatment of AMI, administered in single dose IV bolus rather than multiple
doses or continuous infusion required with other agents,
Nursing implicationspg658
Regarding Alteplase, monitor for superficial bleeding at needle
insertion sites or areas recently involved in surgery.
Regarding Reteplase, it is administered by IV bolus and should be
injected into a dedicated IV line
Regarding Tenecteplase recombinant administrating: reconstitute as
directed; flush line well before/after administration with normal saline
because dextrose-containing fluids may cause precipitate; avoid IM
injections, monitor potential bleeding sites (art. & ven. sites), monitor
client for arrhythmias. Does not contain bacteriostatic preservatives, so
reconstitute immediately before administering.
Hemorheologic Agents
A hemoreologic agent is one that
improves blood flow by decreasing
blood viscosity.
Uses of Hemorheologic Agents
 This agent is useful in the treatment of intermittent claudification, a chronic
condition categorized by occlusion of the arteries of the limbs.
 These agents increases the flexibility of red blood cells and reduces their
aggregation.
 Homerheologic agents also reduce the concentration of fibrinogen,
thereby reducing the likelihood of blood clotting.
Side Effects of Hemorheologic Agents
 Common adverse effect of some common drugs include:
-Insomnia
-Nasal congestion
-Abdominal bloating
-Flatulence
-Dyspepsia
-Headache
-Elevated liver enzymes.
Best Example of Hemorheologic
Agents
Pentoxifylline (Trental)
Nursing Care
 Check effectiveness of medicine in affected area by looking at common
signs, example:
-Pain at the affected area
-Skin color in the affected area
-Presence of pulses in the affected area
-Temperature of the affected area
-Paralysis of the affected area
Drug Interactions
 Pentoxifylline if used concurrently with antihypertensive agents, a decrease
in blood pressure may occur.
 Use with cimetidine increases pentoxifylline effects.
 Pentoxifylline increases affects in both theophylline and warfarin.
Antihemorrhagic Agents
These agents are used to stop the
flow of blood in excessive bleeding
-Trauma
-Surgery
Most Common Examples
 Aminocaproic acid
 Tranexamic acid
 Aprotinin
 Desmopressin acetate
 Gelatin (Gelfoam)
 Absorbable gelatin film
 Recothrom
 Oxidized cellulose
Aminocaproic Acid
 Uses:
-To treat excessive bleeding resulting from systemic hyperfibrinolysis and urinary
fibrinolysis.
 Adverse effects:
-Development of blood clots
-Thrombophlebitis
 Contraindications:
-Oral contraceptives
-Renal failure/renal insufficiency
-Elevated potassium levels
Tranexamic Acid
 Uses:
-Short acting agent used in hemophilia to prevent hemorrhage during and
after tooth extraction.
 Adverse effects
-Hypotension
-Diarrhea, nausea, vomiting
-Behavior changes
 Contraindications:
-Use with factor IX complex or anti-inhibitor anticoagulant complex
Aprotinin
 Uses:
-Preventing blood loss in clients undergoing cardiopulmonary bypass
during coronary artery bypass surgery.
 Adverse effects:
-Hypersensitivity/allergic reaction because of bovine origin.
 Contraindications:
-Decreases effects of fibrinolytic agents
-Blocks the effect of captopril (antihypertensive drug)
Desmopressin Acetate
 Uses:
-Treats hemophelia A and von Willebrand disease
-Treats diabetes insipidus
 Adverse effects
-Infrequent
-Headache, hypertension
-Nausea and abdominal pain
 Contraindication:
-Caution with other pressor agents
-Caution with carbamazepine or chlorpropamide
Gelatin, Gelfoam, Gelfilm
 Uses:
 Gelfoam: applied on to the bleeding tissue, quickly stops the flow of blood, used
in surgical procedures.
 Gelfilm: used in neurosurgery, thoracic surgery, ophthalmic surgery, to prevent
excessive bleeding.
 Contraindications:
-Gelfilms made of pork are contraindicated with religious reasons.
Recothrom, Oxidized Cellulose
 Uses:
 Recothrom: used as an aid to hemostasis whenever oozing blood and minor bleeding from
capillaries and small venules occur during surgery and standard bleeding control methods.
 Oxidized Cellulose: used as sterile packing material at surgical sites to control bleeding.
Clotting Factor Replacement
 Born with either hereditary or genetic deficiencies in certain
clotting factors including:
Thrombin
Factor VIII
Factor IX
Factor XI
Antithrombin III
•
Human Thrombin (Evithrom) derived from human plasma
• Purified human thrombin used as an aid in homeostasis
• Applied locally to bleeding tissue
Hemophilia
 Hereditary bleeding disorder
 Classified according to type
Hemophilia A
Most common
Deficiency in factor VIII
Hemophilia B
Christmas Disease
Deficiency in factor IX
Hemophilia C
Least common
Deficiency in factor XI
Hemophilia (cont.)
Treatment
IV Human factor concentrated for factor VIII or factor IX
Purified donor blood
Synthetic
Recombinant antihemophilia factors
(Ex. Xyntha, Corifact)
Adverse Effects
Human blood- hypersensitivity
Synthetic factors reduce chance of hypersensitivity
Hemophilia (cont.)
Other agents for treatment
Desmopressin acetate (DDAVP)
Stimulates production of factor VIII
Results in increase of concentration of factors VIII & von
Willebrand
Tranexamic acid & aminocaproic acid
Used with factor replacement therapy
Antihemophilic factor-von Willebrand factor complex
(Alphanate)
Treatment of Willebrand diseases ( type 1 &2)
Pooled human plasma
Antithrombin III Deficiency
Inactivates thrombin and factors IX & X
Increases risk fir pulmonary emboli, MI, & CVA
Antithrombin Recombinant (ATryn)
Preventative therapy of intraoperative and intrapartal
thromboembolitic event
A recombinant form of human antithrombin
Congenital Fibrinogen & Protein C
Deficiency
 Fibrinogen
 Human fibrinogen concentrate
(RiaSTAP)
 Lyophilized fibrinogen for acute
bleeding
 Protein C
 Results in hypercoagulation state
(life threatening clots) leading to
brain damage
 Protein C concentrate
(Ceprotin) for severe deficiency
 Plasma derived for replacement
therapy
Oral Anti coagulants inhibit clotting by
interfering with the synthesis of what?
Where are 2 places they are located?
Oral Anti coagulants inhibit clotting by
interfering with the synthesis of what?
Where are 2 places they are located?
Vitamin k- dependent clotting factors
Liver & Intestines
pg. 644
What is the antidote for Heparin and
recommended dosage of the antidote?
What is the antidote for Heparin and
recommended dosage of the antidote?
Antidote- 1% Protamine sulfate
0.5-1mg of protamine required for each 100
USP units of Heparin
pg. 644
Question
Which tissue plasminogen activator is the simplest and most convenient?
A.
Alteplase
B.
Tenecteplase
C.
Reteplase