THROMBOLYTIC

THERAPY

Submitted to Submitted by

Prof. Agnet Beena Mani Nice Mathew

H.O.D Medical Surgical Nursing 2nd year M.Sc. Nursing

BMCON BMCON

Calicut Calicut
 INTRODUCTION

Thrombosis is an important part of the normal hemostatic response that limits

hemorrhage caused by microscopic or macroscopic vascular injury. Physiologic thrombosis is
counterbalanced by intrinsic antithrombotic properties and fibrinolysis. Under normal
conditions, a thrombus is confined to the immediate area of injury and does not obstruct flow
to critical areas, unless the blood vessel lumen is already diminished, as it is
in atherosclerosis.

Under pathologic conditions, a thrombus can propagate into otherwise normal vessels. A
thrombus that has propagated where it is not needed can obstruct flow in critical vessels; it
can also obliterate valves and other structures that are essential to normal hemodynamic
function. The principal clinical syndromes that result are as follows:

 Acute myocardial infarction (AMI)

 Deep vein thrombosis (DVT)
 Pulmonary embolism (PE)
 Acute ischemic stroke (AIS)
 Acute peripheral arterial occlusion
 Occlusion of indwelling catheters

THROMBOLYTIC THERAPY/ FIBRINOLYTIC THERAPY

MEANING

Thrombolysis (fibrinolysis), also known as thrombolytic (fibrinolytic) therapy, is a

treatment to dissolve dangerous clots in blood vessels, improve blood flow, and prevent
damage to tissues and organs.

HISTORY

Fibrinolytic therapy dates to 1958 when the first description of a prolonged infusion
of streptokinase for patients with acute MI was published. Rentrop and colleagues reported
the use of intracoronary streptokinase for acute MI in 1979. This was the dawning of the age
of fibrinolytic therapy. Use of intracoronary streptokinase was found to salvage ischemic
myocardium, resulting in less myocardial damage and greater preservation of left ventricular
function. Many trails using IV fibrinolytic therapy followed, demonstrating improvement in
mortality after acute STEMI.

INDICATIONS OF THROBOLYTIC THERAPY

 AMI especially STEMI patients who have onset of symptoms within the previous 12
hours and ST segment elevation greater than 0.1mV in at least two contagious
precordial leads or at least two adjacent limb leads or new or presumably new LBBB.
 Acute ischemic stroke
 Acute, massive PE
 Acute, extensive DVT
 Acute arterial thrombosis or embolism
 Occlusion of arteriovenous cannula
 Unlabeled use: to clear thrombi in central venous catheters (2mg into blocked
catheter).

AMERICAN COLLEGE OF CARDIOLOGY/ AHA GUIDELINES FOR SELECTING

THROMBOLYTIC THERAPY

Step 1: Assess time and risk

 Time since onset of symptoms
 Risk of STEMI
 Risk of fibrinolysis
 Time required for transport to a skilled PCI laboratory.
Step 2: Determine if fibrinolysis or invasive strategy is preferred.
 Early presentation (3 hours from symptom onset and delay to invasive strategy)
 Invasive strategy is not an option
 Catheterization laboratory occupied/not available
 Lack of access to a skilled PCI laboratory
 Delay to invasive strategy
 Prolonged treatment
 ( Door to balloon)- ( door to needle) is < 1hr.
Golden hour- with in 3 hrs of symptoms.
Patients with STEMI who receive fibrinolytic therapy have better short- and
long term survival when treatment is instituted rapidly, with early reestablishment of
flow within 2 to 3 hrs after onset of symptoms. Little benefit is seen with fibrinolytic
therapy after 12 hrs, which is theorized to be related to thrombus organization within
the coronary artery over time and loss of an opportunity for restoration of blood flow
and myocardial salvage.
The administration of tPA in the time period between 2.5 and 3h after the
stroke was of less value.

CONTRA INDICATIONS TO THROMBOLYTIC THERAPY

Absolute Contraindications
 Any prior intracranial hemorrhage
 Known structural cerebral vascular lesion (e.g., AVM)
 Known malignant intracranial neoplasm (primary or metastatic)
 Ischemic stroke within 3 months EXCEPT acute ischemic stroke within 3 hours
 Suspected aortic dissection
 Active bleeding or bleeding diathesis (excluding menses)
 Significant closed head or facial trauma within 3 months
Relative Contraindications
 History of chronic severe, poorly controlled hypertension
 Severe uncontrolled hypertension on presentation (SBP > 180 mm Hg or DBP >110
mm Hg)
History of prior ischemic stroke greater than 3 months, dementia, or known intracranial
pathology not covered in contraindications
 Traumatic or prolonged (greater than 10 minutes) CPR or major surgery (less than 3
weeks)
 Recent (within 2 to 4 weeks) internal bleeding
 Non compressible vascular punctures
 For streptokinase/anistreplase: prior exposure (more than 5 days ago) or prior allergic
reaction to these agents
 Pregnancy
 Active peptic ulcer
Current use of anticoagulants: the higher the 1NR, the higher the risk of bleeding

PREHOSPITAL FIBRINOLYTICS

Prehospital fibrinolysis protocols are reasonable if physicians are present in the

ambulance or if well organized EMS systems are in place and meet the following criteria:
(1) Paramedics are full time employees, can transmit 12-lead ECGs, and have initial and
ongoing training in ECHG interpretation and STEMI treatment
(2) Online medical command and a medical director with training /experience in STEMI
management are available
(3) An ongoing continuous quality improvement program has been implemented. If the
EMS are capable of providing fibrinolysis, and if the patient qualifies for fibrinolytic
therapy, fibrinolysis should begin within 30 minutes of EMS arrival on scene.

THROBOLYTIC AGENTS

Thrombolytic agents are proteins that activate a plasma proenzyme, plasminogen, to

the active enzyme plasmin. Plasmin then solubilizes fibrin and degrades a number of other
plasma proteins, most notably fibrogen.
In 1980, Dewood and colleagues published a paper on the prevalence of coronary
artery thrombosis in acute MI. Today it is widely accepted that STEMI is a result of
vulnerable plaque rupture. A vulnerable plaque is described as a nonobstructive plaque
composed of a large lipid core covered by a thin fibrous cap. Plaque rupture results in
endothelial cell injury, which causes platelet adhesion, activation, and aggregation and leads
to accelerated thrombin production. Thrombin in turn converts fibrinogen to fibrin. The
resulting thrombus includes a high concentration of platelets and fibrin. The thin fibrin
strands form a matrix, traping more platelets and plasminogen at or near the clot surface. The
body produces and breaks down physiological thrombi (those that heal avessel) and
pathological thrombi (those that occlude a vessel). Fibrinolytic agents use the intrinsic
thromboresistant defense mechanism of the vascular system to break down the thrombi. In
the presence of the fibrinthe endogenous tissue plasminogen activator binds to fibrin in the
thrombus, converting the inactivate precursor, plasminogen, to the active enzyme, plamin.
Plasmin in turn breaks down the fibrin matrix, causing lysis of the clot.
Early fibrinolytic agents are referred to as fibrin non specific agents because they
targeted not only newly formed fibrin-rich pathological thrombi but also normal
physiological thrombi. This results in a systemic lytic state, which can cause serious systemic
bleeding. Newer fibrinolytic agents have been developed, referred to as fibrin specific agents,
that target newly formed fibrin present in pathological thrombi while limiting the effect on
physiological thrombi.

Strptokinase

First-generation nonselective fibrinolytics include streptokinase and urokinase, which

activate plasminogen systemically and are not fibrin specific. IV urokinase is not approved
for STEMI. Tillet and Garner discovered in 1933 that several strains of Streptococcus
hemolyticus could dissolve human thrombus. Streptokinase is a single chain polypeptide
protein derived from l3-hemolytic streptococcus. It binds to plasminogen to form the
streptokinase-plasminogen activator complex and then converts plasminogen to plasmin,
which initiates fibrinolysis. As described by Bates, 40 early studies of IV streptokinase
showed inconsistent improvement in LV function and mortality, likely because doses were
inconsistent and administered too late. With improvements in both time-to-administration and
consistent dosing protocol (I.5 million units of streptokinase infused over 60 minutes),
patency rates at 60 to 90 minutes and at 2 to 3 hours of approximately 50% and 70%
respectively were attained.
Streptokinase is antigenic and can cause immunologic sensitization with repeat
administration. Patient who receive streptokinase or streptococcal infection develop
antistreptokinase antibodies. Major reactions of anaphylaxis are rare and occur in <0.5% of
cases. Less severe symptoms with administration include shivering, pyrexia, rash, or
hypotension that may occur in 10% of patients. Bleeding is the most common complication,
with minor bleeding at puncture sites occurring in 3% to 4% of patients; major bleeding and
stroke occurs in < 1 % and 1.6%, respectively, in patients older than 70 years.

Tissue plasminogen activator (t-PA) and recombinant t-PA (rt-PA; Alteplase)

 The second-generation fibrinolytics are fibrin selective and have demonstrated
improved patency rates for reperfusion in STEMI. The fibrinolytic t-PA occurs as a serine
protease that is secreted naturally by vascular endothelium. rt-PA is known as alteplase. Both
native t-PA and rt-PA (alteplase) preferentially activate plasminogen at the fibrin clot and
cause lysis of thrombus, although systemic plasminogen activation occurs at clinical doses.
Accelerated or front-loaded alteplase, weight adjusted and administered with heparin
for 24 to 48 hours, has proven to be the best fibrinolytic strategy of the second-generation
agents with 90 minute patency rates of approximately 82%. Alteplase has a short half-life
(3 to 4 minutes), requiring heparin infusion for at least 24 hours after administration.
Alteplase has not been associated with allergic reactions or hypotensive reactions.

Reteplase (r-PA), Tenecteplase (TNK-t-PA), and Lanoteplase (n-PA)

The third-generation fibrinolytics include reteplase, tenecteplase, and

lanoteplase. STEMI treatment advancement with these third-generation agents
has been in the finetuning of protocols and administration of adjunctive
treatments rather than in the synthesis of new compounds. Reteplase, a
nonglycosylated deletion mutant of wild-type t-PA, has preferential activation
of fibrin-bound plasminogen, a longer half-life, enhanced fibrinolytic potency,
and lower affinity for endothelial cells than does t-PA. Tenecteplase is a
genetically engineered, multiple point mutant of t-PA that has a longer plasma
half-life, allowing single IV bolus injection and more fibrin specificity than
standard t-PA. Clinical trials involving reteplase and tenecteplase have found
similar efficacy and safety results as with alteplase, but these agents are easier
and more convenient to use because of bolus administration rather than
infusion.

THROMBOLYTIC THERAPY FOR ACUTE ISCHEMIC STROKE

The direct administration of a throbolytic into a vessel is an alternative to IV t-PA.

Such administration is effective in acute ischemic stroke and can be given upto 6 hrs after
the onset of the symptoms. A limiting factor is that the patient must be admitted to a
speciality centre in which localized intra-arterial infusion of thrombolytic agents is
possible. Through this approach, an occluded cerebral artery can be reopened. For intra
arterial therapy, a femoral arterial sheath is usually inserted, through which a microcatheter
can be threaded, under fluoroscopy. The catheter tip is positioned into the clot and
advanced as the clot dissolves. The femoral sheath usually remains in place for 24 hours in
case of recurrent vessel occlusion. The advantage of this approach is that the medication
can be delivered directly to its target.

Eligibilty criteria for thrombolytic therapy

Inclusion criteria
 Symptoms onset of less than 3 hours.
 Clinical diagnosis of ischemic stroke with measurable deficit on NIHSS
 Older than 38 yrs
 CT criteria: absence of high density lesion consistent with intracerebral hemorrhage;
sbsence of significant mass effect or midline shift; absence of parenchymal
hypodensity; or effacement of cerebral sulci in more than 33% of the middle cerebral
artery terrirtory.
Exclusion criteria
 Stroke or serious head trauma within past 3 months
 Systolic BP more than 185mm Hg or diastolic BP more than 110 mmHg or BP
readings that require aggressive treatment.
 Conditions that could precipitate or suggest parenchymal bleeding (subarachnoid
and intracerbral hemorrhage; recent onset MI, seizures at onset, major surgery within
past 14 days; gastrointestinal or urinary tract hemorrhage within previous 21 days;
and arterial puncture of a non compressible site or LP within previous 7 days.
 Glucose less than 50mg /dL or more than 400 mg/dL; INR more than1.7; platelet
count less than 100000/mm3
 Rapidly improving or deteriorating neurological signs or minor symptoms
 Recent MI
 Recent treatment with IV or SC heparin within past 48 hours and elevated PTT.
 Women of child bearing age who have a positive pregnancy test result.

THROMBOLYTIC THERAPY FOR PULMONARY EMBOLISM

 Pulmonary emboli often arise from thrombi originating in the deep venous system of
the lower extremities or pelvis. A blood clot dislodges and is swept into the pulmonary
circulation and lodges in a pulmonary artery. If the clot is large enough to obstruct large
vessels in the lung, it can cause hemodynamic instability, along with right ventricular failure
and possibly death. Currently, thrombolytic therapy for PE is still controversial.

PE ranges in severity from acute massive PE to acute pulmonary infarction to acute embolism
without infarction to multiple emboli.

Indication

 Only patients with acute massive PE (ie, those at the highest risk of immediate death)
are eligible for fibrinolytic therapy if no contraindications are present. Other types are
treated with anticoagulants or antithrombotic therapy.
 Nevertheless, there is a subgroup of patients who are hemodynamically stable at
presentation but have right ventricular (RV) dysfunction; these patients have an
increased risk of death and thus might benefit from fibrinolytic therapy.
 In addition to generalized, nonspecific symptoms, patients with acute massive PE
also present with systemic hypotension, systolic blood pressure below 90 mm Hg or a
decrease in systolic arterial pressure of at least 40 mm Hg for at least 15 minutes, or
cardiogenic shock.

Unfractionated heparin (UFH) should not be given concomitantly with fibrinolytic therapy in
acute massive PE. After fibrinolytic therapy, anticoagulation treatment is recommended to
prevent recurrent thrombosis. Do not begin heparin until the activated partial thromboplastin
time (aPTT) has decreased to less than twice the normal control value.

In the worst clinical scenario, PE can cause cardiac arrest. The most common cardiac arrest
initial rhythms documented include pulseless electrical activity and asystole.

Numerous case reports state the use of thrombolytic boluses in cardiac arrest due to PE, with
apparent heroic results. According to the British Thoracic Society 2003 recommendations,
immediate administration of 50 mg of alteplase may be life saving for patients in cardiac
arrest believed to be caused by PE. The clinician’s focus should be on preventing the cardiac
arrest and identifying patients who are candidates for thrombolytic therapy in the event of a
PE.
The 3 thrombolytic agents currently approved by the FDA for use in patients with acute PE
are alteplase, urokinase, and streptokinase. Tenecteplase is currently being studied for use in
PE; however, it is not yet approved for this indication.

Thrombolytic regimens

Drug Systemic administration

Strepokinase 250000 U over 30 minutes followed by 100000U/h for 24 hrs
Urokinase 4400U/Kg over 10 minutes followed by 4400U/Kg/h for 12-24 hrs
t-PA 100mg over 2hrs

Alteplase

The FDA-approved alteplase regimen for PE is 100 mg as a continuous infusion over 2 hours.
A 15-mg bolus is administered first, followed by 85 mg administered over 2 hours. Heparin
drip must be discontinued during alteplase infusion.

Some centers prefer to use an accelerated 90-minute regimen that appears to be faster-acting,
safer, and more efficacious than the 2-hour infusion. For patients weighing less than 67 kg,
the drug is administered as a 15-mg IV bolus followed by 0.75 mg/kg over the next 30
minutes (maximum, 50 mg) and then 0.50 mg/kg over the next 60 minutes (maximum, 35
mg). For patients weighing more than 67 kg, 100 mg is administered as an 15-mg IV bolus
followed by 50 mg over the next 30 minutes and then 35 mg over the next 60 minutes.

Urokinase

The FDA-approved urokinase regimen for PE consists of 4400 U/kg as a loading dose given
at a rate of 90 mL/h over a period of 10 minutes, followed by continuous infusion of 4400
U/kg/h at a rate of 15 mL/h for 12-24 hours.

Streptokinase

The FDA-approved streptokinase regimen for PE consists of 250,000 U as a loading dose

over 30 minutes, followed by 100,000 U/h over 12-24 hours.

Reteplase
Reteplase has not been approved by the FDA for any indication except AMI, but it is widely
used for acute deep vein thrombosis and PE. The dosing used is the same as that approved for
patients with AMI: 2 IV boluses of 10 U each, administered 30 minutes apart.

THROMBOLYTIC THERAPY FOR DEEP VEIN THROMBOSIS

Deep vein thrombosis (DVT) occurs when clots form in the extremities. If pieces of these
clots break off and travel to the lungs, pulmonary embolism (PE) can occur.. Early diagnosis
and treatment are crucial for preventing morbidity and mortality. Death from DVT is
attributed to massive PE.

The main stay of initial treatment for DVT is anticoagulation. Nonetheless, anticoagulation
therapy does not actually treat DVT by dissolution of thrombus but instead prevents the
propagation of the existing acute DVT.

Indication

 In selected patients with extensive acute proximal DVT (eg, those with iliofemoral
DVT, upper-extremity DVT, symptoms of less than 14 days’ duration, good
functional status, or a life expectancy exceeding 1 y)
 whose bleeding risk is low, catheter-directed thrombolysis (CDT) may be used to
reduce symptoms and postthrombotic

CDT is performed under imaging guidance; the procedure delivers the thrombolytic agent
directly to the clot through a catheter inserted in the vein. Intraclot injection of the thrombus
with a fibrin-specific thrombolytic agent such as alteplase is an alternative to continuous
infusion and minimizes the duration of systemic exposure to thrombolytic agents.

Limitations

Despite the known effectiveness of thrombolysis, widespread use of thrombolytics in the

treatment of DVT is limited by the long infusion times required and the substantial risk of
hemorrhagic complications associated with large doses of these agents.

These limitations have led to the development of adjunctive endovascular techniques

for the treatment of DVT, such as ultrasound (US)-accelerated thrombolysis, which involves
simultaneous delivery of low-intensity US and a thrombolytic agent into a thrombosed vessel.
A multicenter retrospective study demonstrated that US-accelerated thrombolysis had a
considerable advantage over CDT alone for the treatment of DVT, with fewer complications,
reduced drug doses, and shorter infusion times.

Thrombolytic regimens

Alteplase

For lysis of venous thrombus, catheter-directed infusion of alteplase 1-1.5 mg/h for 12-24
hours has been used; regimens may vary, depending on local expertise.

Urokinase

The usual systemic urokinase regimen for DVT consists of 4400 U/kg as an IV bolus
followed by a maintenance drip of 4,400 U/kg/h. The drip is continued for 1-3 days, until
clinical or laboratory investigations demonstrate thrombus resolution. When available,
intrathrombus delivery of urokinase can avoid a systemic lytic state. Via this route, the drug
is given in a loading dose of 250,000 U IV followed by infusion of 500 U/kg/h. If clot lysis is
inadequate, the infusion rate can be gradually increased up to 2000 U/kg/h.

Streptokinase

The usual streptokinase regimen for DVT consists of an IV bolus of 250,000 U followed by a
maintenance drip at 100,000 U/h. The drip is continued for 1-3 days, until clinical or
laboratory investigation shows thrombus resolution.

Reteplase

Reteplase is not approved by the US Food and Drug Administration (FDA) for lysis of
venous thrombus in DVT but is often used off label. Catheter-directed infusion of 1 U/h is
maintained for 18-36 hours.

THROMBOLYTIC THERAPY FOR BLOCKED CATHETERS

Central venous access devices (CVADs) are an important component of long-term

treatments that require ongoing venous access and regular maintenance. Risk factors include
type of malignancy, type of chemotherapy, type of CVAD, insertion site, and type of catheter
tip. Mechanical central venous catheter occlusions call for cause-specific treatment, whereas
thrombotic occlusions usually resolve with thrombolytic treatment.

Thrombolytic therapy has reopened occluded catheters in 85-90% of episodes, and

removal of the catheter is not usually required. Alteplase, urokinase, and streptokinase have
all been used. Streptokinase is not commonly used, because of its antigenic properties and
allergic reactions. Urokinase was off the market for a time; it is now available again but is not
approved for clearance of occluded catheters. A randomized trial comparing urokinase
10,000 U with alteplase 2 mg suggested that the latter was markedly superior.[39]

Thrombolytic regimens

Alteplase

Alteplase is approved by the US Food and Drug Administration (FDA) for clearance of
thrombotically occluded CVADs. It is available in a 2 mg/2 mL vial, which suffices to fill
most catheter lumens. For patients weighing 30 kg or more, give 2 mg in 2 mL saline. For
those weighing less than 30 kg, fill 100% of the internal lumen volume of the catheter (but do
not exceed 2 mg in 2 mL saline). Leave the agent for 30 minutes to 2 hours, then withdraw it.
The dose may be repeated. If this is unsuccessful, 2 mg/50 mL infused over 4 hours may be
given.

Urokinase

The urokinase dose for catheter clearance is 5000 U in each lumen over 1-2 minutes; this is
left in in the lumen for 1-4 hours and then aspirated. If 5000 U fails to clear the catheter, the
process may be repeated with 10,000 U in each lumen. The volume to be instilled into the
catheter is equal to the volume of the catheter. For patients undergoing dialysis, instill 5000 U
into each lumen over 1-2 minutes, leave the agent in the lumen for 1-2 days, and then
aspirate.

Streptokinase

Slowly instill 250,000 U of streptokinase in 2 mL of solution into each occluded limb of the
cannula, and clamp off the cannula limb(s) for 2 hours. After treatment, aspirate the contents
of the cannula limb(s), flush with saline, and reconnect the cannula.

THROMBOLYTIC THERAPY FOR PERIPHERAL ARTERIAL DISEASE

Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis and may
present as an obstruction of arterial blood flow to an extremity. The clinical manifestation of
acute arterial occlusion will vary, depending on the location of the obstruction and the extent
of collateral circulation.

Accepted treatments for prompt revascularization consist of catheter-directed thrombolysis

(CDT), percutaneous mechanical thrombus extraction with or without thrombolytic therapy,
and surgical thrombectomy or bypass.

Primary fibrinolysis is the initial treatment of choice for many patients with acute peripheral
arterial occlusions. The ability to perform CDT with subsequent angioplasty and stenting has
reduced the need for arterial surgery in many settings.

Patients with limb-threatening ischemia are not candidates for local fibrinolysis, which
usually takes between 6 and 72 hours to achieve clot lysis. These patients require emergency
embolectomy. CDT is reserved for patients with non–life-threatening limb ischemia due to in
situ thrombosis of less than 14 days’ duration. Consider that patients with thrombosis of
more than 30 days duration are not likely to respond to local fibrinolysis.

Streptokinase was once the most widely used agent but has since been supplanted by
urokinase and alteplase; prourokinase (not currently available), reteplase, and tenecteplase
have been studied as well. Reteplase and tenecteplase are as safe and efficacious as tissue
plasminogen activator. The optimal dosages and concentrations of reteplase, alteplase, and
tenecteplase are still under investigation. .

Thrombolytic regimens

The standard regimen for reteplase in PAD consists of 0.5 U/h by intra-arterial infusion.

The standard regimen for alteplase consists of 0.05-0.1 mg/kg/h intra-arterially. The high-
dose regimen consists of 3 doses of 5 mg over 30 minutes followed by 3.5 mg/h for up to 4
hours.

The regimen for urokinase consists of 4000 U/min intra-arterially until initial recanalization,
then 1,000-2,000 U/min intra-arterially until complete lysis.

The regimen for streptokinase consists of 5000-10,000 U/h intra-arterially.

 RATIONALE FOR BOLUS DOSE FIBRINOLYTIC THERAPY VERSUS
INFUSION OF FIBRINOLYTIC THERAPY

Reteplase and tenecteplase) have several advantages in the clinical arena.

1. bolus dosing allows easier and safer administration and may facilitate more rapid
treatment of STEMI. Door-to-drug time may be reduced with a simple bolus
fibrinolytic agent that does not require time to perform drug calculations.
Reducing door-to-drug time is critical to myocardial preservation and reduction
in mortality.
2. prehospital administration may be facilitated using bolus dose therapy for the
same reasons. This approach could reduce medical contact-to drug time, again to
preserve myocardium and reduce mortality.
3. bolus dosing is more attractive is that it could decrease medication errors,
particularly when rapid mathematical calculations are needed in an intense
situation. Decreasing medication errors is a high priority in the health care arena.

COMPARISON OF THROBOLYTIC AGENTS

Streptokinase Alteplase Reteplase Tenecteplase-tPA

Action Binds with Binds to fibrin Catalyzes the Binds to fibrin and
plasminogen to in a thrombus cleavage of converts
produce a and converts plasminogen plasminogen to
complex that plasminogen to to generate plasmin
converts plasmin plasmin
plaminogen to
plasmin.
Indications AMI AMI AMI AMI
Acute PE Acuteischemic
Acute, extensive stroke
DVT Acute massive
Acute arterial PE
thrombosis or Unlabeled use:
 embolism to clear
Occulsion of thrombi in
arteriovenous central venous
cannula catheters

Dose 1,500000IU IV 100mg IV over 10U+ 10U IV Weight based dose

within 60min 90 min (15mg bolus ( each IV over 5 sec:
IV bolus; 50 10 U given >60kg =30mg
mg IV over 30 over 2min; ≥60to<70kg=35mg
min; 35mg IV second bolus ≥70to<80kg=40mg
over 60 min) given 30 min ≥80to<90kg=45mg
after first ≥90kg=50mg
bolus
Half-life 23 min <5min 13-16min 20-24 min
Bolus administration No No Yes Yes
Antigenic Yes No No No
Allergic Yes No No No
reaction(hypotensio
n most common)
Syetemic fibrinogen Marked Mild Moderate Minimal
depletion
90 min patency 50 75 7 75
rates, approximate
%
TMI grade 3 flow, 32 54 60 63
%

MANIFESTATIONS OF REPERFUSION
 Decreased or resolved ST segment elevation.
 Abrupt cessation of chest pain
 Early peak of serum cardiac markers
 Reperfusion dysrrhythmias such as VT, PVCs, accelerated idioventricular rhythm and
AV block.
MANIFESTATIONS OF OCCLUSION AFTER THROMBOLYTIC THERAPY
 Recurrent chest pain
 ST segment elevation
  Further myocardial ischemia
 Lethal dysrrhythmias
 Cardiogenic shock or death.

ANCILLARY ANTICOAGULATION TO SUPPORT REPERFUSION THERAPY

To prevent reocclusion of the infarct vessel, the ACC/AHA STEMI fibrinolysis

guidelines recommend ancillary anticoagulant therapy for a minimum of 48 hours but op-
timally for the duration of hospitalization. Unfractionated heparin (UFH) is recommended
only for the first 48 hours because of the risk of heparin-induced thrombocytopenia with
prolonged UFH exposure unless there are ongoing indications for anticoagulation. The 2004
ACC/AHA STEMI ancillary anticoagulation recommendations are:
1. Patients undergoing percutaneous or surgical revascularization should receive UFH.
2. UFH should be given intravenously to patients undergoing reperfusion therapy with
alteplase, retaplase, or tenecteplase.
3. UFH should be given intravenously to patients treated with nonselective fibrinolytic
agents (streptokinase, anistreplase, urokinase) who are at high risk for systemic emboli
(large anterior MI, atrial fibrillation, previous embolus, or known LV thrombus).
4. Platelet counts should be monitored daily in patients taking UFH.

A number of studies have compared alternative anticoagulant protocols with UFH or

placebo. According to the 2007 ACC/AHA STEMI focused update: there are three
currently recommended ancillary anticoagulant regimens that have established efficacy:

1. UFH as initial bolus (60 U/kg, with maximum of 4,000 U) followed by 12 U/kg/h
(maximum 1000 U/h), adjusted to maintain activated partial thromboplastin time (aPTT) at
1.5 to 2 times (approximately 50 to 70 seconds) .
2. Enoxaparin (if serum creatinine level <2.5 mg/dL in men or <2.0 mg/dL in women):
for patients younger than 75 years, as initial 30 mg IV bolus followed 15 minutes later by
subcutaneous (SC) injection of 1.0 mg/kg every 12 hours. : or patients at least 75 years old,
initial IV bolus is eliminated and SC injection is reduced to 0.75 mg/kg every 12 hours.
Regardless of patient age, if creatinine clearance is <30 mL/min, SC protocol is 1.0 mg/kg
every 24 hours. Continue enoxaparin for duration of index hospitalization (up to 8 days)
3. Fondaparinux (if serum creatinine level <3.0 mg/dl.): initial dose 2.5 IV, followed by
2.5 mg SC daily. Continue fondaparinux for duration of index hospitalization (up to 8
days).

COMPLICATIONS OF THROMBOLYTIC THERAPY

 Bleeding such as ICH, GI bleeding
 Stroke
 Bruising or bleeding at the access site
 Damage to the blood vessel
 Migration of the blood clot to another part of vascular system
 Kidney damage in patients with diabetes or other pre-existing kidney disease
 Reperfusion dysrrhythmia

If a patient who was treated with fibrinolytic medications develops serious bleeding
complications, the first step is to stop the fibrinolytic agent and any anticoagulants. The
next step is to institute supportive therapy, often including volume repletion and
transfusion of blood factors. When possible, direct pressure should be used to control
bleeding. If the patient has also been receiving heparin, protamine sulfate may be used to
reverse the heparin effect. Each 1 mg of protamine sulfate neutralizes approximately 100
U of heparin.

 Aminocaproic acid is a specific antidote to fibrinolytic agents. In adults, 4-5 g of

aminocaproic acid in 250 mL of diluent is administered by infusion during the first
hour of treatment, followed by a continuing infusion at the rate of 4 mL (1 g) per hour
in 50 mL of diluent. Infusion is continued for about 8 hours or until the bleeding
situation has been controlled. Fresh frozen plasma, cryoprecipitate, or both may be
used to replenish fibrin and clotting factors.
 Aminocaproic acid should not be given unless hemorrhage is life-threatening, because
it inhibits intrinsic fibrinolytic activity and can precipitate runaway thrombosis with
end-organ damage at many sites. The drug worsens disseminated intravascular
coagulation (DIC), including that associated with heparin-induced thrombocytopenia.
ADVANTAGES OF FIBRINOLYTIC THERAPY

 Does not require access to catheterization laboratory facilities.

 Treats the underlying problem of a central occluding thrombus
 Documented efficacy in large, well-controlled trials

DISADVANTAGES OF FIBRINOLYTIC THERAPY

 Despite widespread availability, fibrinolytic therapy is given only in

approximately 30 to 40 percent of patients with acute myocardial infarction;
absolute or relative contraindications are frequent
 Not effective for hemodynamic instability
 Early reperfusion rates range from 55 to 80 percent depending on agent used
 Achievement of TIMI-3 flow in less than 50 to 60 percent of patients
 Reliable assessment of reperfusion often not possible
 Residual stenosis

THE THROBOLYSIS IN MI(TIMI) FLOW SCALE

SCALE COMMENT
TIMI grade 0 No perfusion
Absence of antegrade flow beyond the
point of occlusion

TIMI grade 1 Penetration without perfusion

Partial penetration of contrast medium
beyond the obstruction with absence of
filling of the distal vessel

TIMI grade 2 Partial perfusion

Patency of the vessel but with
delayed filling
TIMI grade 3 Complete perfusion
Normal brisk antegrade flow

NURSING CARE OF THE PATIENT UNDERGOING FIBRINOLYTIC THERAPY

 Most institutions have protocols in place to provide rapid reperfusion when a
patient has STEMI. Protocols usually include giving aspirin and oxygen,
obtaining a 12-lead electrocardiogram and blood work, and placing the patient
on a cardiac monitor.
 Blood work should include a complete blood count, electrolytes, blood urea
nitrogen, creatinine, PT, PTT, and cardiac biochemical markers [CK, CK-MB,
and troponin]. A blood type and crossmatch may be obtained because bleeding
is a potential complication of fibrinolytic therapy.
 Obtaining a focused history and physical examination is critical. In obtaining
the history, it is essential to determine the time of symptom onset. Also
important is to determine whether there are any relative or absolute
contraindications to fibrinolytic therapy.
 Whenever possible, all arterial and venous lines should be placed before
fibrinolytic therapy is delivered in order to decrease the risk of bleeding from
puncture sites.
 Before initiation of fibrinolytic therapy, insertion of two to three intravenous
catheters is recommended. One line should be dedicated to the fibrinolytic
medication (especially when a fibrinolytic medication requiring a continuous
infusion is used). One line should be used for concomitant intravenous heparin
therapy and intravenous fluids. That line also may be used for any intravenous
medications compatible with heparin. The third intravenous catheter should be
connected to a saline lock and used as needed (with any intravenous
medications not compatible with heparin, as a backup intravenous access, or
for blood sampling).
 An arterial line may be placed for continuous blood pressure monitoring and
for blood sampling during and after the course of fibrinolytic therapy.
 Intravenous or arterial catheters should be placed at sites where firm
compression can be accomplished if bleeding should occur at the insertion site
(subclavian and jugular sites should be avoided because they are difficult areas
to apply firm manual compression).
 Intramuscular and subcutaneous injections should be avoided for 24 hours after
fibrinolytic therapy, if possible, to prevent hematoma formation.
 If venepuncture must be performed within the first 24 hours, manual pressure
 should be applied for 20 to 30 minutes after withdrawal of the needle followed
by placement of a secure pressure dressing. The access site must be monitored
closely for development of bleeding or a hematoma.
 Intravenous and arterial lines should not be discontinued for 24 hours after
fibrinolytic therapy in order to reduce the risk of bleeding.
 Education also incudes the purpose of the medication, information about
moderate consumption of leafy green vegetables containing vitamin K, and the
importance of having blood drawn regularly to monitor PT and INR.
 For safety patients should be instructed to obtain Media alert cards and
bracelets so they can be identified as taking an anticoagulant in the event of a
medical emergency.
 Patients and families must be informed that bleeding and bruising are common
with fibrinolytic therapy. Provide reassurance that precautions to prevent
bleeding and bruising will be taken (i.e., padding side rails and limiting
injections and venepuncturesj
 Nursing care in the intensive care unit or coronary care unit includes frequent
monitoring of vital signs for assessment of hemodynamic stability. The use of
noninvasive blood pressure monitoring has caused concern that it may increase
the risk of bruising on the extremity. One study compared the safety of using
noninvasive blood cuff measurements to manual blood pressure cuff
measurements during fibrinolytic therapy and 24 hours after therapy. The 96
patients in the study received streptokinase or alteplase after presenting with
STEMI. The investigators found no significant difference in frequency of
petechiae, ecchymosis, or hematoma formation between patients who had
blood pressure measured with a noninvasive cuff and those who had blood
pressure measured manually. There are several markers of successful
reperfusion after fibrinolytic therapy. Ongoing evaluation of chest pain
(resolution or recurrence) is one way to assess reperfusion.
 If fibrinolytic therapy is successful, chest pain usually improves within 90
minutes of treatment. However, analgesics or nitrates given concomitantly may
mask true relief of pain from fibrinolytic therapy; therefore, other markers of
reperfusion should be assessed.
 Serial 12-lead electrocardiograms should be performed to monitor ST segments
for evidence of recurrent ischemia or extension of the STEMI. Within the first
 few hours after fibrinolytic therapy, a downward trend of the ST segments back
to baseline in the leads facing the area of infarction is an indication of success -
ful reperfusion of the occluded coronary artery.
 If the bedside monitoring system has continuous ST segment monitoring
capability, it should be used to monitor for recurrent ischemia or extension of
the STEMI, in addition to serial 12-lead electrocardiograms. For patients who
have STEMI, the AHA practice standards recommend monitoring ST segments
in the lead(s) facing the area of infarction for a minimum of 24 hours and
continuing until the patient remains event-free for 12 to 24 hours.
 Cardiac monitoring is used to observe for reperfusion dysrhythmias, another
potential marker of successful therapy. Reperfusion dysrhythmias occur
because of the sudden influx of oxygenated blood to an injured, ischemic, and
irritable myocardium. This causes electrical instability and often manifests as
accelerated idioventricular rhythm, ventricular tachydysrhythmias, and
bradydysrhythmias. Reperfusion dysrhythmias are treated with standard
therapies if the patient exhibits hemodynamic instabiliry
 Serial blood work samples should be drawn per protocol, including a complete
blood count, electrolytes, magnesium, and cardiac biochemical markers (CK,
CKMB, and troponin). The complete blood count is compared with pre-
fibrinolytic therapy values to assess for occult bleeding.
 Stool and urine should be checked for occult blood. If significant blood loss is
noted, a blood transfusion may be required.
 If hypokalemia or hypomagnesemia is noted, the potassium and magnesium
should be replaced to decrease myocardial irritability.
 Successful reperfusion with fibrinolysis causes a rapid rise in the CK and CK-
MB (usually within 4 hours) from the sudden influx of oxygenated blood into
necrotic myocardial tissue. Without reperfusion therapy, the CK and CK-MB
normally peak at 24 hours after an acute myocardial infarction.
 Ongoing assessment of the patient's neurological status is important to assess
for early signs of intracranial hemorrhage (sudden onset of a focal neurological
deficit that progresses quickly, accompanied by headache, nausea, vomiting,
altered level of consciousness, and elevated blood pressure). If the patient's
neurological status changes, consider obtaining a neurology consult and
computed tomography scan of the head.
  Once the acute phase of the STEMI is over, focus should turn to patient and
family education about secondary prevention measures (risk factor
modification and medications).
 A cardiac catheterization may be recommended during the index
hospitalization to better assess coronary anatomy. If obstructive coronary dis-
ease is found on coronary angiography, PCI or coronary artery bypass grafting
surgery may be recommended.

CONCLUSION

Although thrombolysis is usually successful, the treatment is not able to dissolve the blood
clot in up to 25% of patients. Another 12% of patients subsequently redevelop the clot or
blockage in the blood vessel. In addition, thrombolysis alone -- even when successful --
cannot treat tissue that has already been damaged by compromised blood circulation. So
further treatment may be needed to address the underlying causes of the blood clot and repair
damaged tissues and organs.

BOOK REFERENCE

1. Woods SL and etal (2010); Cardiac nursing; Lippincott Williams and wilkins, 6 th
edition, China.
2. Moser and Riegel (2008); Cardiac nursing; Saunders Elsevier publications; Missouri.
3. Chatterjee and etal (2013); Cardiology an illustrated textbook; Jaypee publications; 1 st
edition;New delhi.
4. Morton and etal (1994); Critical care nursing; Lippincott Williams Wilkins; 8 th
edition, Philadelphia.
5. Hickey JV; (2003);The clinical practice of neurological and neurosurgical nursing; 5 th
edition;Lippincott Williams and wilkins;Philadelphia.
6. Ropper AH and Samuels MA( 2009); Adams and Victor’s Principles of Neurology;
9th edition; Mc Graw Hill;Philadelphia.
7. Fink MP and etal (2005); Critical care; 5th edition’ Saunders publication;Philadelphia.

WEB REFERENCE
 emedicine.medscape.com/article/811234-overview
 atvb.ahajournals.org/content/30/4/669.full
 www.ncbi.nlm.nih.gov/pubmed/12556743
 www.vascularweb.org › VascularWeb › Vascular Health
 link.springer.com/article/10.1007%2Fs11936-009-0013-9