Heparin-Induced Thrombocytopenia (HIT)

How HIT works

Heparin binds to a protein released by platelets called platelet factor 4 (PF4). In some people, the immune system makes IgG antibodies against this heparin-PF4 complex. The antibody complexes bind to platelets and activate them, causing them to clump and release substances that trigger clotting. Activated platelets are removed from circulation, so the count falls (thrombocytopenia), while widespread activation causes clots.

This is why HIT is a clotting disorder, not a bleeding disorder, despite low platelets.

HIT is more common with unfractionated heparin than with low-molecular-weight heparin (such as enoxaparin), and after heart and orthopedic surgery. It is rare in children and in pregnancy.

A related syndrome, vaccine-induced immune thrombotic thrombocytopenia (VITT), involved similar PF4 antibodies after some adenovirus-vector COVID-19 vaccines, but without heparin.

Symptoms

Many people have no symptoms at first apart from a falling platelet count on routine blood tests. When clots form:

• deep vein thrombosis: leg or arm swelling, pain and warmth
• pulmonary embolism: chest pain, breathlessness, fast heart rate
• arterial clots: stroke, heart attack, or a cold, painful limb (acute limb ischemia) that can lead to amputation
• skin necrosis: painful red or black patches at injection sites
• adrenal hemorrhage: belly or flank pain and low blood pressure
• acute systemic reaction: fever, chills, high blood pressure, breathlessness or chest pain within 30 minutes of an IV heparin bolus

Bleeding is uncommon, even when platelets are low.

Diagnosis

The 4Ts score

Doctors first estimate the probability of HIT using the 4Ts score:

Each category scores 0 to 2 points. A total of 0 to 3 means low probability, 4 to 5 intermediate and 6 to 8 high. A low score makes HIT very unlikely.

Laboratory tests

• PF4-heparin antibody test (immunoassay): sensitive, so a negative result largely excludes HIT, but many positive results are not true HIT
• functional test (serotonin release assay or heparin-induced platelet activation assay): confirms that antibodies activate platelets
• ultrasound of the legs and arms to look for silent clots, recommended in confirmed HIT

Treatment

Immediate steps

• stop all heparin, including heparin flushes and heparin-coated catheters
• start a non-heparin anticoagulant right away for intermediate or high probability, even before test results: argatroban, bivalirudin, fondaparinux or a direct oral anticoagulant such as rivaroxaban or apixaban in suitable patients
• do not start warfarin until the platelet count has recovered, because it can cause venous limb gangrene in acute HIT. If warfarin was started, it is reversed with vitamin K
• avoid platelet transfusions unless there is serious bleeding, because they may fuel clotting

Duration

• HIT without clots: anticoagulation usually continues until platelets recover, and often for up to about 3 months
• HIT with clots: anticoagulation for at least 3 months

Future heparin exposure

HIT antibodies usually disappear within about 3 months. Heparin should generally be avoided in the future. In special situations, such as heart surgery, a short exposure may be allowed after antibodies disappear, under specialist guidance. HIT should be recorded as a serious adverse reaction on your medical record.

Outlook

With prompt recognition and treatment, most people recover. Untreated HIT carries a high risk of clots, amputation and death. Platelet counts usually recover within about a week of stopping heparin.

Frequently asked questions

What is heparin-induced thrombocytopenia?

HIT is an immune reaction to heparin in which antibodies activate platelets. This lowers the platelet count but greatly raises the risk of blood clots in veins and arteries. It usually develops 5 to 10 days after starting heparin.

What are the symptoms of HIT?

Often the only early sign is a drop in platelets on a blood test. Symptoms come from clots: leg or arm swelling, chest pain or breathlessness, stroke symptoms, a cold painful limb, or painful dark skin patches at injection sites. Bleeding is uncommon.

What is the 4Ts score?

The 4Ts score is a bedside tool that estimates the likelihood of HIT based on the degree of platelet fall, its timing, the presence of new clots, and other possible causes of low platelets. A low score makes HIT very unlikely and often avoids unnecessary testing.

How is HIT treated?

All heparin is stopped immediately and a non-heparin blood thinner such as argatroban, bivalirudin, fondaparinux or a direct oral anticoagulant is started. Warfarin is delayed until platelets recover. Platelet transfusions are generally avoided.

Can I ever have heparin again after HIT?

Heparin is usually avoided for life. In some situations, such as cardiac surgery, specialists may allow brief heparin use once antibodies have disappeared, typically after about 3 months. Always tell your healthcare team you have had HIT.