Fibrinolytic agents are plasminogen activators(PA) that act by converting plasminogen to plasmin. Plasmin then degrades the fibrin matrix of thrombi and produces soluble fibrin degradation products resulting in clot lysis.
PAs that preferentially activate fibrin-bound plasminogen are fibrin-specific. Nonspecific PAs do not discriminate between fibrin-bound and circulating plasminogen. Activation of circulating plasminogen generates unopposed plasmin & can trigger a systemic lytic state.
Fibrinolytics are used for intravenous thrombolysis(IVT) in ST Elevation MI, Massive Pulmonary embolism, and Acute Ischemic stroke. Peripheral arterial thrombi and thrombi in the proximal deep veins of the leg are most often treated using catheter-directed thrombolytic therapy.
Indications and contraindications are to be throughly vetted before considering fibrinolytic therapy owing to their propensity to cause hemorrhage.
Urokinase is not prefered. Aanistreplase is costly to manufacture and is not commonly used. Only nonspecific fibrinolytic used is streptokinase that too not commonly. It is still used because it has mortality benefit in MI and is cheap compared to fibrin specific fibrinolytics.
IVT in STEMI:
Primary PCI is the preferred mode of reperfusion in a PCI-capable facility. For IVT, bolus fibrinolytics (Tenecteplase) are preferred as there is ⬇️chance of medication errors and are associated with ⬇️ noncerebral bleeding and has potential for prehospital Rx
For Thrombolysis in STEMI the treatment time window is within 30min to up to 12hrs of onset of symptoms. Best results if given within 1-2 hrs.
Thrombolysis in Acute Ischemic Stroke (AIS):
Eligible patients should receive thrombolysis as soon as possible, ideally within 60 minutes of hospital arrival. Only Alteplase and Tenecteplase are recommended for IVT in AIS.
Thrombolysis in pulmonary embolism (PE):
Patients with massive PE or high-risk submassive PE (with both right ventricular dysfunction and troponin elevation due to right ventricular injury) are candidates for IVT.
Patients who receive thrombolysis up to 14 days after onset of new symptoms or signs in PE can derive benefit, probably because of the effects on the bronchial collateral circulation.
There is a 1% to 3% rate of intracranial hemorrhage in patients with PE receiving full-dose IVT. Off-label half dose of alteplase(50mg) infusion over 2hrs is sometimes used to mitigate the risk of bleeds. Catheter-directed pharmacomechanical therapy has lower rates of bleeding.
Source
1.Harrisons Principles of Internal Medicine, 21e
2.Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 11e
3.2021,European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke
Drug of choice for ANAPHYLAXIS in a patient with no response to Epinephrine?
Patient is on Propranolol 60 mg BD for essential tremors. #MedTwitter#emergencymedicine#CriticalCare
Anaphylaxis is a severe, life threatening systemic hypersensitivity reaction characterized by being rapid in onset with potentially life threatening airway, breathing, or circulatory problems and is usually, although not always, associated with skin and mucosal changes.( ICD-11)
27 yrs old patient, detected to be pregnant when she missed her periods one day back. She has Graves disease on Rx for past 3 years, presently on Carbimazole 5mg daily and not on propranolol. She was euthyroid with Rx for past 1 year. Best strategy ?
Present reports 👇
A. Stop carbimazole and monitor by weekly/fortnightly TSH, FT4 levels and follow up.
B. Switch to PTU 50mg bd and do FT4, TSH after 2 weeks and review
C. Switch to PTU 50 mg bd + LT4 50mcg OD. TSH, FT4- 4wkly
D. PTU 50mg BD and Propranolol XL 20mg , Monthly TSH,FT4-followup