Heparin-induced thrombocytopenia (HIT)

What is heparin-induced thrombocytopenia (HIT)?

Heparin-induced thrombocytopenia, or HIT, occurs in some patients who have been taking the anticoagulant (blood thinner) heparin. Less commonly, drugs related to heparin called low-molecular-weight heparins (LMWHs) can cause HIT. Heparin and LMWH are used to treat clotting disorders, to prevent blood clots in certain heart conditions, and to prevent blood clots in patients who have undergone surgery or are hospitalized.

Thrombocytopenia is the medical term for low platelets, which are blood cell fragments that help with clotting the blood in response to injury. A normal platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. The platelet count is low if it is less than 150,000. Platelets are measured on a routine blood test called a ‘CBC’ or complete blood count.

Antibodies are blood proteins the body makes against substances it recognizes as foreign to help eliminate them. For example, people who catch the flu make antibodies that help fight the flu virus. In a similar way, vaccines trigger the body to make antibodies against infectious diseases like hepatitis or measles. Sometimes, though, the body makes antibodies to medications or, in the case of autoimmune diseases like rheumatoid arthritis and lupus, to parts of the body. HIT occurs when heparin or LMWH cause an immune reaction that creates antibodies that attach to platelets and heparin at the same time, causing platelets to stick together and be abnormally active, despite their low level in the bloodstream. When this occurs, the affected person is at high risk for developing blood clots in any blood vessel in the body.

Who is at risk for developing HIT?

Fortunately, HIT is rare, occurring in less than 2% of patients who are taking heparin. It is most common in patients who have undergone orthopedic surgery and are receiving heparin to prevent blood clots, and less common in those who are taking the related LMWHs, such as enoxaparin (Lovenox) or dalteparin (Fragmin). The other patients who may develop HIT are those undergoing open heart surgery, which requires large amounts of heparin during use of the heart-lung bypass machine that oxygenates the blood while the heart is stopped. Other surgical patients, medical patients, and obstetric (pregnant or post-partum) patients exposed to heparin and LMWH are at very low risk of HIT, though it does occur from time to time in these groups.

What are the signs and symptoms of HIT?

Patients with HIT may have no symptoms at all, or they may have symptoms related to blood clotting. The most common type of blood clots in patients with HIT are deep vein thrombosis (DVT) and pulmonary embolism (PE), which are blood clots affecting the vein side of the circulation (Figure 1). Veins are the blood vessels that carry blood back to the heart, in contrast to arteries, which carry blood from the heart to the tissues. Patients with DVT may have pain, swelling, or redness in the affected leg. Patients with PE often have a racing heartbeat, shortness of breath, or chest pain. Blood clots may also develop in other veins of the body, such as in the veins of the abdomen (Figure 1).

Figure 1.

This patient with heparin-induced thrombocytopenia (HIT) developed a deep vein thrombosis (DVT) in the vein that drains the left kidney, which is seen as a gray shape within the vein (panel A, arrow). She also had pulmonary embolism, or clots in the lungs, which is seen as gray material within the blood vessel (panel B, arrow).

Patients with HIT may also develop blood clots in the arteries. The symptoms depend on the artery that is affected; for instance, clots in the arteries of the arms or legs can cause severe pain, coldness, loss of pulses, and even gangrene in very severe cases (Figure 2). Clots in the arteries of the brain can cause a stroke, and clots in the coronary arteries can cause a heart attack.

Figure 2.

This patient had a severe form of heparin-induced thrombocytopenia (HIT) and developed gangrene of the toes and foot related to blood clots. Fortunately, this is a rare complication of HIT if it is detected promptly and managed with an alternative blood thinner. (Photograph courtesy of John R Bartholomew.)

Up to 20% of patients with HIT may have skin reactions at the site of heparin injections, with painful red patches or skin necrosis, which is a black, scabbed spot that results when skin tissue dies. Rarely, patients with HIT may have severe reactions immediately after a heparin dose, with shortness of breath, racing heartbeat, fever, chest tightness, and flushing.

Although patients with HIT have low platelet counts, they seldom have bleeding.

How is HIT diagnosed?

HIT is diagnosed using a combination of a clinical assessment by a health care provider and blood testing. HIT typically develops within 5 to 10 days of first exposure to heparin. The platelet counts usually fall by 30–50%. The health care team looks at the timing and the severity of the fall in the platelet count in combination with whether the patient has other reasons to have low platelets. If the patient is found to have blood clots, this further raises the suspicion of HIT. Then, a blood test is performed, which is a measurement of the HIT antibodies (also known as anti-PF4 antibodies) or other assessments of the immune reaction. In patients in whom the suspicion of HIT is moderate or low, a normal blood test rules out the diagnosis, and other causes of the low platelets must be sought. In patients who are suspected of HIT, a second confirmatory blood test is often performed if the first one comes back positive for the diagnosis.

How is HIT treated?

Patients with HIT are at high risk for getting blood clots over several weeks to months, so in addition to stopping heparin and strictly avoiding even small quantities of it, they must be put on an alternative blood thinning medication. In the hospital setting, the blood thinner most commonly used is an intravenous (IV) medication called a direct thrombin inhibitor (DTI), such as argatroban or bivalirudin. Occasionally, an injectable medication called fondaparinux is used. Patients cannot go home on IV medications, so they must switch to the oral medication warfarin (Coumadin). Warfarin takes several days to take effect. Warfarin must overlap with the DTI for a minimum of 5 days, which often results in longer hospital stays for patients diagnosed with HIT. HIT patients must stay on warfarin for a minimum of 3–6 months, depending on whether or not they developed blood clots around the time of diagnosis.

What are the long-term effects?

HIT tends not to recur, although patients should avoid any future exposure to heparin or LMWH, and it is important to have heparin and LMWHs listed in drug allergies on the medical record. Fortunately, there are several blood thinner options that do not contain heparin.

By about 100 days after the initial diagnosis, the vast majority of patients with HIT will no longer have the HIT antibodies in their bloodstream. The one exception to avoiding further heparin exposure is patients who need open heart surgery. After 100 days, if their antibody tests are normal, they may have a one-time exposure to heparin during the operation. This planning is usually made with a health care provider who has expertise in the management of HIT, such as a hematologist or vascular medicine specialist.

The long-term effects of HIT depend on the severity of the illness at the time of diagnosis. Patients with no blood clots or with small blood clots do quite well, although being on any blood thinner carries a risk of bleeding. Patients with large blood clots in the lungs or in the arteries may have substantial lasting problems related to the clots themselves. Nevertheless, unless patients with HIT have another reason to stay on a blood thinner (such as an abnormal heart rhythm like atrial fibrillation), their blood thinner is typically stopped after 3–6 months after HIT was diagnosed.

How can HIT be prevented?

Because HIT is more common with heparin than LMWH, avoiding heparin in favor of LMWH may cut down on instances of HIT. However, sometimes heparin is the preferred medication, such as in patients with advanced kidney disease.

Summary

HIT is an uncommon complication of heparin and LMWH use, which causes a low platelet count and can lead to blood clots in the veins or arteries. Treatment consists of alternative blood thinners, usually for a period of 3–6 months. Patients with HIT must avoid future exposure to heparin and related drugs.