Heparin-induced thrombocytopenia

Definitions & Key takeaways

Heparin-induced thrombocytopenia (HIT) is a rare but potentially life-threatening complication that can occur during the treatment course with heparin. HIT occurs when the body produces antibodies against heparin, which then attach to and damage platelets (the cells that help the blood clot). This can decrease the number of platelets in the blood (thrombocytopenia), which can cause easy bruising and bleeding.

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Introduction0:00–0:25

The term heparin-induced thrombocytopenia can be divided into two parts. Heparin refers to an anticoagulant medication which prevents blood clots from forming, and thrombocytopenia refers to decreased number of thrombocytes, or platelets, in the blood.
So, heparin-induced thrombocytopenia or, HIT, is a complication caused by heparin that results in decreased platelets in the blood.

Physiology0:25–1:33

Okay, so imagine you’re making dinner and accidentally cut one of your fingers. Now, if your body doesn’t stop the bleeding, you will keep losing blood until there’s not enough to supply the vital organs like the heart and brain.
Now to prevent this from happening the body has a process called hemostasis. This process has two phases: primary and secondary hemostasis.In primary hemostasis, platelets aggregate to form a plug at the site of an injured blood vessel.
While these platelets are aggregating, coagulation, or secondary hemostasis starts. 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 from something as simple as a pinprick!
Okay, so heparin induced thrombocytopenia is caused by heparin. This medication works by activating an enzyme called antithrombin III, which inhibits coagulation factors Xa, also known as thrombin.

Pathology1:33–3:21

This halts secondary hemostasis and prevents existing blood clots from growing larger, so it’s often given to people who suffer from pulmonary embolisms, strokes, and myocardial infarctions.
Now, the main mechanism behind the development of HIT is actually an immune response, which starts when heparin binds to a protein on the surface of inactivated platelets called platelet factor 4 or PF-4.
Together they form a complex called heparin-PF4 complex. This complex is immunogenic in certain people, meaning they have circulating IgG antibodies that recognize the complex as foreign pathogens.
So these antibodies will bind to the heparin-PF4 complex and mark it for destruction within the spleen. Now when the antibody binds, it causes the platelet to activate.
The activated platelets release procoagulant chemicals like thromboxane A2 or TXA2, which causes other platelets to activate.
At the same time, the original platelet will also release more PF-4s so more antibodies will bind and keep it activated.
These events leads to more and more platelets getting activated and they start forming clots throughout the body. This way, a lot of the remaining platelets also get consumed, which results in a low platelet count.
Normally, it generally takes a week for the body to make IgG antibodies that target the heparin-PF4 complex. Thus thrombocytopenia typically develop one or two week after starting heparin therapy.
The exception is that if heparin is given to someone who was already treated with heparin previously, they would already have the antibodies against the complex so thrombocytopenia may develop within a day!Now, the widespread formation of abnormal clots can lead to life-threatening thrombotic events, which are most often venous - causing deep vein thrombosis.

Complications3:21–4:00

Sometimes, this thrombus can break down and part of the thrombus, also known as emboli, can lodge into the pulmonary circulation, leading to pulmonary embolism, which is often life-threatening.
Thrombus can also develop in cerebral veins leading to cerebral venous sinus thrombosis. Compared to the venous thrombosis, arterial thrombosis is less frequent.
Arterial thrombosis can block the arteries supplying limbs causing limb gangrene, or brain causing stroke, or heart causing myocardial infarction.Now, the diagnosis of HIT is often made clinically along with the help of some laboratory tests.

Diagnosis and treatment4:00–5:20

For example, individuals who recently started heparin therapy and experience a decrease in platelet count either within 1-2 weeks or within a day suggests HIT.
The level of platelets can be found by using a complete blood count, or CBC.Other diagnostic tests include an ELISA serological assay to detect the IgG antibodies.
However, many individuals that have received heparin previously will have these antibodies, but not all of them will develop HIT, so the test is not very specific.A more specific test is the serotonin release assay, which is the gold-standard for diagnosing HIT.
In the serotonin release assay, the patient’s serum is mixed with heparin and donor platelets.Activated platelets release serotonin.
So in a positive test, the patient’s serum has antibodies that activates the platelets and the serotonin level will increase.While confirming the diagnosis, it’s important to immediately stop giving the patient heparin and to start anticoagulation with a non-heparin anticoagulant, like argatroban, which is a thrombin inhibitor.
If the patient has a thrombotic event, anticoagulation is continued for three to six months. If there was no thrombotic event, then anticoagulation continues until the platelet count normalizes.##SummaryAlright, as a quick recap, heparin induced thrombocytopenia or HIT is a condition where individuals on heparin therapy develops thrombocytopenia or low platelet count in the blood.

Review5:20–5:51

HIT occurs as a result of an immune response which ultimately causes the platelets to get activated and used up during the formation of abnormal clots.
These clots can block veins and arteries leading to life-threatening thrombotic events like deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis and less commonly limb