What is Heparin-Induced Thrombocytopenia?
Heparin-induced thrombocytopenia (HIT) is a serious side effect that can happen to patients who are given any type or amount of heparin, a commonly used medicine. This condition is marked by a drop in platelet counts, which are cells that help your body form clots to stop bleeding, and a higher risk of forming clots when not necessary. Those facing HIT may also see an increased chance of suffering from thromboembolic complications, conditions caused by blood clots traveling in the bloodstream and blocking blood vessels in other parts of the body. These complications can contribute to serious health problems and even death. This fact is particularly concerning because heparin is often used to prevent and treat blood clots, to clean out IV lines, and in heparin-coated catheters. This review will focus on how HIT occurs in the body, how it’s identified, and how patients with HIT are managed.
What Causes Heparin-Induced Thrombocytopenia?
Thrombocytopenia is a condition where your blood has a lower than normal number of platelets, which are blood cells that help your wounds stop bleeding. There are two types of thrombocytopenia that can happen after using a blood-thinning medication called heparin:
Type I, also known as Heparin-associated thrombocytopenia (HAT), is a reaction not related to immunity. It’s more common than the second type and can happen as soon as one day after starting the heparin medication. This is a mild reaction and doesn’t lead to any complications. Even if you continue the medication, your platelet count will get back to normal on its own.
Type II is a reaction related to the immune system and involves the creation of antibodies, which are proteins our bodies use to fight off foreign substances. This type of reaction usually happens 5 to 14 days after taking heparin. But, if you’ve used heparin in the last 100 days, these antibodies could still be in your system. This means that the reaction could happen as soon as the first day after taking heparin again. This reaction is serious and leads to a state where your blood clots more easily than normal. It can cause life-threatening complications. This summary will speak more on type II and how it’s managed.
Risk Factors and Frequency for Heparin-Induced Thrombocytopenia
Heparin-induced thrombocytopenia (HIT) is a serious condition that can happen to 5% of patients who are treated with heparin products. This can make their blood significantly more likely to clot, and half of these patients may then have complications due to these clots. It can be fatal in up to 30% of cases.
There are several things that can increase the risk of developing HIT. These include different factors related to the medication and patient. It is more common to get HIT from standard heparin (UFH) than from a shorter type of heparin (LMWH) because of differences in their structures. Fondaparinux, a drug similar to heparin, doesn’t cause HIT and can’t react with the antibodies of HIT either. UFH is a complex drug that has long chains of saccharides of different lengths and weights. On average, the UFH molecule has 45 saccharide units. LMWH also has varying saccharide chains, but it’s shorter in comparison, with an average of 15 saccharide units. Fondaparinux is a synthetic drug made up of only 5 sugars. The shorter the saccharide chain and the smaller the molecule, the less likely it is to bind to proteins and cells in the blood. Therefore, there’s a lower risk of getting HIT from LMWH than UFH, and no risk from fondaparinux. Fondaparinux can be safely used in patients with a history of HIT and potentially for treating acute HIT.
Even small doses of heparin can cause a reaction, but the risk of HIT is higher in patients exposed to larger doses, and the longer the treatment, the higher the risk goes. Additionally, women and older patients are at a higher risk of getting HIT. Surgeries can also raise the incidence of HIT, potentially because the physical injuries and interventions can increase activity in platelets and other molecules related to clot formation.
Signs and Symptoms of Heparin-Induced Thrombocytopenia
Heparin-induced thrombocytopenia (HIT) can exhibit various signs and symptoms. These might include sudden pain, redness, and swelling in an arm or leg. Some people might notice bruise-like spots or a rash near where a heparin shot was given. You might also experience weakness, numbness, or issues moving because of discomfort. It’s also possible that a clot or larger blood clot may form or grow, which can happen in both veins and arteries. If it happens in a vein, you may witness deep vein thrombosis in your arm or leg, or a lung clot known as a pulmonary embolism. Additional symptoms may come up if you are receiving heparin through an intravenous line, such as chills, fever, high blood pressure, fast heart rate, shortness of breath, and chest pain. Some people may even see a rash of red spots on their skin.
- Sudden pain, redness, and swelling in an arm or leg
- Bruise-like spots or a rash near where a heparin shot was given
- Weakness or numbness
- Difficulty moving because of pain
- Formation or growth of a blood clot
- Deep vein thrombosis in an arm or leg
- Pulmonary embolism
- Chills if receiving heparin via IV
- Fever
- High blood pressure
- Fast heart rate
- Shortness of breath
- Chest pain
- Rash of red spots on the skin
Testing for Heparin-Induced Thrombocytopenia
If you’re currently on medication known as heparin or have recently used it, and your platelet count mysteriously begins to drop, this could be a sign of heparin-induced thrombocytopenia (HIT). HIT usually manifests as a consistent drop in platelet counts, without much change in hemoglobin and hematocrit counts.
Your doctor will first use a diagnostic tool called the 4T score to figure out how likely you have HIT. This scoring system gives points depending on the presence or absence of specific signs. The following point ranges represent the probability of having HIT:
– 0 to 3: HIT is unlikely, and the doctor may continue your heparin therapy while looking for other reasons for your low platelet count.
– 4 to 5: HIT is a possible explanation, and the probability is intermediate.
– 6 to 8: There is a high probability that you have HIT.
If your 4T score is 4 or higher, your doctor will stop all forms of heparin and start an alternate blood thinning treatment for safety. To confirm the diagnosis of HIT, your doctor will resort to two more specific tests – PF4 ELISA and Serotonin Release Assay (SRA).
The PF4 ELISA test checks for the presence of certain antibodies in your blood. If the test comes out negative, it can effectively rule out HIT. However, it can also give false-positive results, meaning the test might say you have HIT when you actually do not. Because of this, if the PF4 ELISA comes out positive, it needs to be confirmed by the SRA test. The SRA test is currently considered the most reliable test for diagnosing HIT because it checks whether platelets (a type of blood cell) activate in the presence of heparin and antibodies. If the SRA test is positive, you definitely have HIT, and even if the PF4 ELISA result was positive, a negative SRA indicates that you do not have HIT.
Treatment Options for Heparin-Induced Thrombocytopenia
Heparin-induced thrombocytopenia (HIT) is a complication that can affect patients taking heparin, a blood-thinning drug. When someone has a score of 4 or more on a scale used to assess HIT risk (called the 4T score), treatment should begin swiftly. This most commonly includes stopping all types of heparin use.
Once heparin has been stopped, an alternative drug for preventing blood clots should be given, especially to prevent or treat any blood clots caused by HIT. If a patient was recently prescribed warfarin (another blood thinner), this medication would also be paused. Additionally, vitamin K may be given to help replenish protein C and S, which are crucial for preventing blood clotting. Two specific tests, PF4 ELISA and SRA, are usually done to confirm the diagnosis of HIT.
The American Society of Hematology (ASH) has guidelines for how to approach treating HIT. They suggest that most patients should be started on therapeutic doses of an alternative blood thinner. This includes patients with high or intermediate risk of getting HIT and no other reasons to avoid blood thinners, or who aren’t at high risk for bleeding. In select cases, patients at high risk of bleeding with an intermediate HIT risk score may only need a lower, or prophylactic, dose. If such a patient tests positive for HIT, they should be switched to therapeutic doses.
There are several choices for alternative blood thinners, including argatroban, bivalirudin, danaparoid, fondaparinux, or a direct oral anticoagulant (DOAC). Particular ones might be picked based on the individual patient’s condition. Argatroban and bivalirudin, for instance, act quickly and might be used for severely ill patients, those at risk for bleeding, or those who may need an urgent procedure. Both these drugs work by directly inhibiting thrombin, a protein involved in clotting, and don’t interact with the factors that cause HIT.
Fondaparinux, an injectable anticoagulant, is generally safe and effective for HIT, although it’s not specifically approved for this use by the US Food and Drug Administration. It’s cleared from the body by the kidneys, so it’s not recommended in patients with severe kidney impairment. Recently, direct oral anticoagulants (DOACs) have been suggested as a potentially effective and safe treatment for HIT, with rivaroxaban being the most commonly used in practice.
It’s crucial to remember that each patient’s condition is different and affects the choice and dosage of medication. The aim of treatment is to prevent the development of harmful blood clots while managing the risks of bleeding that come with anticoagulant use.
What else can Heparin-Induced Thrombocytopenia be?
When diagnosing HIT (heparin-induced thrombocytopenia), there are several other conditions that doctors must consider. These may include:
- Type I HIT (Heparin Associated Thrombocytopenia)
- Disseminated intravascular coagulation (a condition that causes small blood clots throughout the body)
- Liver disease
- Bleeding disorders
- Hemodilution (a decrease in the concentration of cells and solids in the blood)
- Immune thrombocytopenia (a disorder that results in easy or excessive bruising and bleeding)
- Myelosuppression (a decrease in bone marrow activity resulting in fewer blood cells)
- Drug-induced causes of blood disorders
- Bacterial sepsis (a severe infection that spreads through the bloodstream)
- Drug-induced thrombocytopenia (low platelet count caused by medication)
- Hemolytic-uremic syndrome (a condition that affects blood and blood vessels)
- Splenomegaly (an enlarged spleen)
- Thrombotic thrombocytopenic purpura (a rare disorder that causes blood clots in small vessels)
- Transfusion reactions (an adverse reaction to a blood transfusion)
