Fibrinolytic drugs

Fibrinolysis

STEMI receiving fibrinolytic therapy

Antiplatelet

ASA 162-325 mg PO Plus

Clopidogrel 300 mg PO (Age 75 years or younger)

Clopidogrel 75 mg PO (Age > 75 year old)

Tenecteplase (Mnemonic "Table dose")

Single bolus over 5 seconds

Patient Weight (kg)	TNKase Dose (mg)	Volume to be Administered (ml)
< 60	30	6
>=60 to < 70	35	7
>= 70 to < 80	40	8
>=80 to < 90	45	9
>=90	50	10

Reteplase (Mnemonic "Repeat dose")

10 units bolus in 10 min then repeat in 30 mins

Alteplase (Mnemonic "Alternating dose")

Weight (Kg.)

15 mg IV bolus, then 0.75 mg/kg (not to exceed 50 mg) over 30 min,

then 0.5 mg/kg (not to exceed 35 mg) over 60 min.

(maximum dose is 100 mg over 90 min.)

Streptokinase

1.5 M units V in 30-60 min.

Contraindication

Absolute Contraindication

Any prior intracranial hemorrhage

Known intracranial malformation or neoplasm

Ischemic stroke < 3 months (Except within 4.5 hours)

Suspected aortic dissection

Gastrointestinal bleeding within the last month

Bleeding diathesis (Excluding Menses)

Significant closed head or facial trauma < 3 months

Relative Contraindication

History of chronic severe poorly controlled hypertension

Severe uncontrolled hypertension on presentation (SBP> 180 mmHg or DBP > 110 mmHg)

History of previous TIA in preceding 6 months

Traumatic or prolonged (> 10 min) CPR or major surgery (< 3 weeks)

Recent (within 2-4 weeks) internal bleeding

Noncompressible vascular punctures

For Streptokinase, anistreplase: previous exposure (> 5 days earlier) or previous allergic reaction to these agents

Pregnancy or within 1 week post partum (* Me: Beware of spontaneous coronary artery dissection)

Active peptic ulcer

Current use of anticoagulants: The higher the INR, the higher the risk of bleeding

Infective endocarditis

Advanced liver disease

Acute ischemic stroke (fast track < 4.5 h)

rtPA

Weight (Kg.)

Total dose: 0.9 mg/kg (Not exceed 90 mg)

10% Bolus in 1 minute then

90% One hour IV infusion

BP management

Patients eligible for treatment with IV alteplase

Labetalol 10 - 20 mg IV over 2 min.

Nicardipine 2 mg +D5W up to 4 ml IV bolus 1 ml

Nicardipine 20 mg +5D/W up to 100 ml IV 25 ml/h titrate

Before IV alteplase: SBP <185 and DBP < 110 mmHg.

After IV alteplase: SBP < 180 and DBP < 105 mmHg.

Patients who undergo/successfully mechanical thrombectomy

Not receive thrombolytic, planned mechanical thrombectomy : </=185/110 mmHg

After reperfusion Target BP: </=180/105 mmHg

Indication

Diagnosis of ischemic stroke causing measurable neurological deficit

The onset of symptoms <3 h before treatment begins (See additional contraindication to tPA at 3-4.5hr below)

Age ≥18 y

Additional contraindication for 3-4.5 h

Age ≥ 80 years

History of prior stroke and diabetes

Any active anticoagulant use (even INR< 1.7)

NIHSS > 25

CT shows multilobar infarction (hypodensity > 1/3 of the cerebral hemisphere)

Contraindication

Absolute Contraindication

Significant head trauma or prior stroke in the previous 3 mo
Symptoms suggest SAH
Arterial puncture at a non-compressible site in previous 7 d
History of previous intracranial hemorrhage Intracranial neoplasm, AVM, or aneurysm
Recent intracranial or intraspinal surgery
Elevated blood pressure (systolic >185 mmHg or diastolic >110 mmHg)
Active internal bleeding
Acute bleeding diathesis, including but not limited to
- Platelet count < 100,000 mm3
- Heparin was received within 48 hours, resulting in abnormally elevated aPTT above the upper limit of normal.
- Current use of anticoagulant with INR >1.7 or PT >15 s
- Current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated sensitive laboratory tests (e.g., aPTT, INR, platelet count, ECT, TT, or appropriate factor Xa activity assays)
Blood glucose concentration < 50 mg/dL
CT demonstrates multilobar infarction (hypodensity >1/3 cerebral hemisphere)

Relative Contraindication

The weighting of risk to benefit patients may receive fibrinolytic therapy despite ≥1 relative contraindication. Consider the risk to the benefit of intravenous rtPA administration carefully if any of these relative contraindications are present. Only minor or rapidly improving stroke symptoms (clearing spontaneously)

Pregnancy
Seizure at onset with postictal residual neurological impairments
Major surgery or serious trauma within the previous 14 d
Recent gastrointestinal or urinary tract hemorrhage (within the previous 21 days)
Recent acute myocardial infarction (within previous 3 mo)

Onset time is defined as either the witnessed onset of symptoms or the time last known normal if symptom onset was not witnessed.

In patients without recent use of OACs or heparin, treatment with intravenous rtPA can be initiated before availability of coagulation test results but should be discontinued if INR is >1.7 or PT is abnormally elevated by local laboratory standards.

In patients without a history of thrombocytopenia, treatment with intravenous rtPA can be initiated before availability of platelet count but should be discontinued if platelet count is <100,000/mm3

Acute pulmonary embolism

rtPA

100 mg over 2 h

Weight (Kg.)

Although not officially approved, the accelerated rtPA regimen for pulmonary embolism is occasionally utilized in cases of severe hemodynamic instability, such as cardiac arrest.

0.6 mg/kg over 15 min (maximum dose 50 mg)

Streptokinase

Accelerated regimen: 1.5 million IU over 2 h

250 000 IU as a loading dose over 30 min, followed by 100 000 IU/h over 12-24 h

Urokinase

Accelerated regimen: 3 million IU over 2 h

Weight (Kg.)

4400 IU/kg as a loading dose over 10 min, followed by 4400 IU/kg/h over 12 - 24 h

Contraindication

Absolute

History of haemorrhagic stroke or stroke of unknown origin

Ischaemic stroke in previous 6 months

Central nervous system neoplasm

Major trauma, surgery, or head injury in previous 3 weeks

Bleeding diathesis

Active bleeding

Relative

Transient ischaemic attack in previous 6 months

Oral anticoagulation

Pregnancy or first post-partum week

Non-compressible puncture sites

Traumatic resuscitation

Refractory hypertension (systolic BP >180 mmHg)

Advanced liver disease

Infective endocarditis

Active peptic ulcer

References

1) Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK, Ornato JP. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004 Aug 4;44(3):E1-E211.

2) Authors/Task Force Members, Steg PhG, James SK, Atar D, Badano LP, Lundqvist CB, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). European Heart Journal. 2012 Oct 1;33(20):2569–619.

2) Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, et al. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke. Stroke. 2016 Feb 1;47(2):581–641.

3) Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec 1;50(12):e344–418.

4) Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). European Heart Journal. 2020 Jan 21;41(4):543–603.