“Coagulation & Medications” – Clot Formation

24 Apr

joe_stevenson_bloody_mess-300x241

Welcome back on EMDutch, the Dutch Emergency Medicine website! Today starts the 1st of several posts about “Coagulation and Medications”. Today will only be a short summary about Clot Formation. Just a reminder of what you know from MedicalSchool. The following posts about “coagulation & medications” will look at certain antiplatelet medication, anticoagulation & thrombolysis which are often used in the ED for diseases like (N)STEMI, VTE (PE/DVT) and acute ischemic stroke. I will not just look at their mechanism, but more importantly at the evidence supporting their use. Here we go….

Clot Formation

First you need tissue damage, which releases Tissue Factor (a glycoprotein present on activated vascular cells, monocytes & macrophages) that starts the coagulation cascade when it is exposed to Factor VII (F VII) and calcium.  Von Willebrand Factor (vWF) is a blood glycoprotein which binds to collagen when the collagen is exposed in endothelial cells due to damage occurring to the blood vessel.  The vWF then binds to the platelet GPIb-receptor on the platelets.

In the coagulation cascade Thrombin gets produced. Thrombin has several mechanisms, one of which is Factor VIII (F VIII) to be released from vWF, which causes activation of F VIII (F VIIIa). Thrombin also activates the platelet, which results in GPIIb/IIIa-receptors on the surface of the platelets. The GPIIb/IIIa-receptors on the platelets bind to Fibrinogen. Thrombin (by activating F XIII) causes the Fibrinogen to be cleaved into monomers of fibrin, which then polymerizes to form a Fibrin matrix, that is the basis of the clot!

Clot Formation

http://upload.wikimedia.org/wikipedia/commons/a/a4/Coagulation_cascade.png

http://m.australianprescriber.com/magazine/30/4/92/6

http://ahdc.vet.cornell.edu/clinpath/modules/coags/primim.htm

Several medications have an inhibitory effect in this whole cascade of clot formation. The medications that we will look at on EMDutch are the ones that are often used in the ED:

Antiplatelets

* Aspirin –>  It irreversibly inactivates the Cyclooxgenase (COX) enzyme. COX is required for thromboxane synthesis that activates the platelet and causes GPIIb/IIIa receptors on the platelet.

* Clopidogrel –> It blocks platelet aggregration by irreversibly inhibiting an ADP chemoreceptor on platelet cell membranes. The ADP receptor is important for the activation of the platelets.

* Prasugrel –> Like clopidogrel it is a ADP receptor inhibitor.

Anticoagulation

* Heparin / Fragmin –> Heparin binds to antithrombin III (AT). The activated AT then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa. The rate of inactivation of these proteases by AT can increase by up to 1000-fold due to the binding of heparin. Low-molecular-weight heparins (fragmin)  target anti-factor Xa activity rather than anti-thrombin activity.

* Sintrom / Acenocoumarol –> It inhibits the vitamin K-dependent synthesis of biologically active forms of the calcium-dependent clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S, and protein Z.

Thrombolysis

* Thrombolysis (t-PA / streptokinase) –> Fibrin polymerizes and constitutes a “mesh” that acts as hemostatic clot (in conjunction with platelets) over a wounded site. This plasmin meshwork can be cleaved by plasmin, which derives from an inactive precursor: plasminogen. Plasminogen can be activated by the tissue plasminogen activator (t-PA) and streptokinase.

See you next time…Hope you will enjoy this bloody interesting topic!

Egon

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