Coagulation (secondary hemostasis)
Also referred to as factor IV, is an inorganic ion necessary for essentially all stages of coagulation.
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 3-year-old boy is brought to the emergency department for pain and swelling of the knee. The child was walking and talking one minute and crying inconsolably several minutes later. Aspiration of the joint space provides pain relief and produces a rusty-colored joint fluid that is heme positive. Laboratory serum studies are drawn and shown in the chart.
A mixing study corrects the prolonged prothrombin time. Which blood component that binds to tissue factor in the extrinsic coagulation pathway is most likely deficient in this patient?
Content Reviewers:Rishi Desai, MD, MPH, Yifan Xiao, MD, Sean Watts, Marisa Pedron, Sam Gillespie, Evan Debevec-McKenney
Hemostasis can be broken down into hemo referring to blood or bleeding and stasis meaning to stop - so together it means stopping bleeding.
Hemostasis has two phases: primary and secondary hemostasis.
In primary hemostasis, platelets aggregate to form a plug at the site of an injured blood vessel.
This is where numerous enzymes that are always floating around in the blood called clotting factors get proteolytically activated, meaning that activation happens when a small piece is chopped off - a bit like pulling the pin out of a grenade.
These factors activate one another, eventually leading to the activation of fibrin or factor Ia.
That results in a fibrin mesh which forms around the platelet plug to reinforce it and hold it together.
Without primary and secondary hemostasis, our body would suffer massive blood loss from even the most minor injuries--imagine losing all of your blood volume from something as simple as a pinprick!
So let’s get into the details of secondary hemostasis. The process of forming the fibrin mesh begins via two pathways --the extrinsic and intrinsic pathways.
The intrinsic pathway is called intrinsic because all of the factors required to activate it are intrinsic, or found within the blood.
Conversely, the extrinsic pathway is called extrinsic because it’s activated by tissue factor found extrinsically, or outside of the blood.
Both pathways can become activated independently and ultimately culminate in the activation of factor X, which then proceeds to activate the rest of the coagulation cascade via the common pathway.
Let's start with the extrinsic pathway. It starts when trauma damages the blood vessel, and exposes the cells under the endothelial layer, like smooth muscle cells, which have tissue factor or factor III in their membrane.
Now, it turns out that there’s an enzyme called factor VII floating around in the blood, and some of it is active, meaning that it’s already set to proteolytically cleave other proteins.
When it’s in that state, it’s called active factor VII or VIIa, “a” for active.
Factor VIIa binds to a tissue factor and a calcium ion -which get released by nearby activated platelets--and it forms a VIIa-TF complex on the surface of the smooth muscle cell.
Both the calcium ions and tissue factors are cofactors, meaning that they need to bind to the enzyme factor VIIa to allow it to really get going.
This complex then cleaves clotting factor X yielding the active form called factor Xa.
Once factor Xa is generated via the extrinsic pathway, it cleaves factor V into Va and then it uses factor Va and a calcium ion as the cofactors to form the prothrombinase complex which activates prothrombin or factor II, into thrombin or factor IIa.
In fact, each prothrombinase complex can activate thousands of thrombin, so there’s enormous amplification that occurs at this step.
Thrombin uses calcium ion as a cofactor and it has a number of pro-coagulative effects.
First, thrombin binds to receptors on platelets causing them to activate.