Page 544 - Cardiac Nursing

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520 PA R T I V / Pathophysiology and Management of Heart Disease
thrombus. Streptokinase is a single chain polypeptide protein de- dications for anticoagulation. 2,46,47 The 2004 ACC/AHA STEMI
2
rived from -hemolytic streptococcus. It binds to plasminogen to ancillary anticoagulation recommendations are :
form the streptokinase–plasminogen activator complex and then 1. Patients undergoing percutaneous or surgical revascularization
converts plasminogen to plasmin, which initiates fibrinolysis. As de- should receive UFH. (Class I, level of evidence: C)
40
scribed by Bates, early studies of IV streptokinase showed incon- 2. UFH should be given intravenously to patients undergoing
sistent improvement in LV function and mortality, likely because reperfusion therapy with alteplase, retaplase, or tenecteplase.
doses were inconsistent and administered too late. With improve- (Class I, level of evidence: C)
ments in both time-to-administration and consistent dosing pro- 3. UFH should be given intravenously to patients treated with
tocol (1.5 million units of streptokinase infused over 60 minutes), nonselective fibrinolytic agents (streptokinase, anistreplase,
patency rates at 60 to 90 minutes and at 2 to 3 hours of approxi- urokinase) who are at high risk for systemic emboli (large ante-
mately 50% and 70%, respectively, were attained. rior MI, atrial fibrillation, previous embolus, or known LV
Streptokinase is antigenic and can cause immunologic sensiti- thrombus). (Class I, level of evidence: B)
zation with repeat administration. Major reactions of anaphylaxis 4. Platelet counts should be monitored daily in patients taking
are rare and occur in 0.5% of cases. Less severe symptoms with UFH. (Class I, level of evidence: C)
administration include shivering, pyrexia, rash, or hypotension
that may occur in 10% of patients. 41 Bleeding is the most com- A number of studies 48–52 have compared alternative anticoag-
mon complication, with minor bleeding at puncture sites occur- ulant protocols with UFH or placebo. According to the 2007
3
ring in 3% to 4% of patients; major bleeding and stroke occurs in ACC/AHA STEMI focused update there are three currently rec-
1% and 1.6%, respectively, in patients older than 70 years. 42 ommended ancillary anticoagulant regimens that have established
efficacy:
Tissue Plasminogen Activator (t-PA) and Recombinant
t-PA (rt-PA; Alteplase). The second-generation fibrinolytics are 1. UFH as initial bolus (60 U/kg, with maximum of 4,000 U) fol-
fibrin selective and have demonstrated improved patency rates for lowed by 12 U/kg/h (maximum 1000 U/h), adjusted to main-
reperfusion in STEMI. The fibrinolytic t-PA occurs as a serine tain activated partial thromboplastin time (aPTT) at 1.5 to
protease that is secreted naturally by vascular endothelium. rt-PA 2 times (approximately 50 to 70 seconds) (level of evidence: C).
is known as alteplase. Both native t-PA and rt-PA (alteplase) pref- 2. Enoxaparin (if serum creatinine level 2.5 mg/dL in men or
erentially activate plasminogen at the fibrin clot and cause lysis of 2.0 mg/dL in women): for patients younger than 75 years, as
thrombus, although systemic plasminogen activation occurs at initial 30 mg IV bolus followed 15 minutes later by subcuta-
clinical doses. 41 neous (SC) injection of 1.0 mg/kg every 12 hours. For patients
Accelerated or front-loaded alteplase, weight adjusted and ad- at least 75 years old, initial IV bolus is eliminated and SC injec-
ministered with heparin for 24 to 48 hours, has proven to be the tion is reduced to 0.75 mg/kg every 12 hours. Regardless of pa-
best fibrinolytic strategy of the second-generation agents with 90- tient age, if creatinine clearance is 30 mL/min, SC protocol is
41
minute patency rates of approximately 82%. Alteplase has a short 1.0 mg/kg every 24 hours. Continue enoxaparin for duration of
half-life (3 to 4 minutes), requiring heparin infusion for at least index hospitalization (up to 8 days). (level of evidence: A)
24 hours after administration. Alteplase has not been associated 3. Fondaparinux (if serum creatinine level 3.0 mg/dL): initial
with allergic reactions or hypotensive reactions. dose 2.5 IV, followed by 2.5 mg SC daily. Continue fonda-
parinux for duration of index hospitalization (up to 8 days).
Reteplase (r-PA), Tenecteplase (TNK-t-PA), and Lan- (level of evidence: B)
oteplase (n-PA). The third-generation fibrinolytics include
reteplase, tenecteplase, and lanoteplase. STEMI treatment ad- Cautions, Complications, and
vancement with these third-generation agents has been in the fine- Contraindications for Fibrinolytic Agents
tuning of protocols and administration of adjunctive treatments
rather than in the synthesis of new compounds. 43 Reteplase, a The ACC/AHA STEMI Guidelines recommend the following ac-
2
nonglycosylated deletion mutant of wild-type t-PA, 43,44 has pref- tions to prevent complications :
erential activation of fibrin-bound plasminogen, a longer half-life, 1. Health care providers should ascertain whether the patient has
enhanced fibrinolytic potency, and lower affinity for endothelial neurological contraindications to fibrinolytic therapy, includ-
cells than does t-PA. 43 Tenecteplase is a genetically engineered, ing any history of intracranial hemorrhage (ICH) or significant
multiple point mutant of t-PA that has a longer plasma half-life, closed head or facial trauma within the past 3 months, uncon-
allowing single IV bolus injection and more fibrin specificity than trolled hypertension, or ischemic stroke within the past
standard t-PA. Clinical trials involving reteplase and tenecteplase 3 months. (Class I, level of evidence: A)
have found similar efficacy and safety results as with alteplase, but 2. Patients with STEMI at substantial ( 4%) risk of ICH should
these agents are easier and more convenient to use because of bo- be treated with PCI rather than fibrinolytic therapy. (Class I,
lus administration rather than infusion. 44,45 level of evidence: A)
Ancillary Anticoagulation to Support Complications of Fibrinolytic Therapy. Most complica-
Reperfusion Therapy tions associated with second- and third-generation fibrinolytic agents
To prevent reocclusion of the infarct vessel, the ACC/AHA are minor bleeding. Major bleeding occurs in approximately 5% to
STEMI fibrinolysis guidelines recommend ancillary anticoagulant 6% of patients treated with fibrinolytics. Although the fibrin-specific
therapy for a minimum of 48 hours (level of evidence: C) but op- agents were expected to result in fewer bleeding complications, the
timally for the duration of hospitalization. Unfractionated he- larger comparative studies showed no difference in bleeding or trans-
parin (UFH) is recommended only for the first 48 hours because fusion rates compared with streptokinase. Severe bleeding complica-
of the risk of heparin-induced thrombocytopenia with prolonged tions such as ICH occur in 1% to 2% of patients and more com-
3
UFH exposure (level of evidence: A) unless there are ongoing in- monly in the elderly. 12