### Date : 2024-12-03 16:40 ### Topic : Heparin-Induced Thrombocytopenia (HIT) #hematology ---- ### **Heparin-Induced Thrombocytopenia (HIT)** **Heparin-induced thrombocytopenia (HIT)** is a **rare but serious** immune-mediated reaction to **heparin**, a commonly used **anticoagulant**. HIT is characterized by a **decrease in platelet count** (thrombocytopenia) and an **increased risk of thrombosis**, paradoxically leading to **blood clots** despite being on an anticoagulant. There are two types of HIT: **Type 1 HIT** (non-immune, mild) and **Type 2 HIT** (immune-mediated, severe), with **Type 2** being the clinically significant form that can lead to **thrombosis** and **life-threatening complications**. --- ### **Pathophysiology** - **Type 1 HIT** (non-immune-mediated): - This is a **mild and transient** condition that occurs within **2 days** of starting heparin therapy. It is due to **direct platelet aggregation** caused by the **heparin-platelet factor 4 (PF4)** complex. - Platelet count usually **normalizes** without the need for discontinuing heparin therapy. - **Type 2 HIT** (immune-mediated): - This is the **severe form** of HIT and is caused by an **autoimmune response**. The immune system forms **IgG antibodies** against the **heparin-platelet factor 4 (PF4)** complex. - When **heparin** binds to **PF4** (a protein released from platelets), it causes a conformational change, allowing the immune system to recognize this complex as foreign. - The **IgG antibodies** bind to the **heparin-PF4 complex** on platelets and activate them, leading to **platelet aggregation** and **thrombosis**. This results in a **thrombocytopenia** (low platelet count) but also an **increased risk of clot formation**. - The activated platelets release more **PF4**, creating a vicious cycle of **platelet activation** and **thrombosis**. --- ### **Clinical Features of HIT** 1. **Thrombocytopenia**: - A **drop in platelet count** typically occurs **5-10 days after starting heparin** (but can occur earlier if the patient has been on heparin recently). - Platelet count may drop by **50% or more** from baseline. 2. **Thrombosis**: - **Paradoxical thrombosis** occurs in HIT, despite the presence of low platelets. This is the hallmark feature of **Type 2 HIT**. - **Venous thromboembolism (VTE)**: Common sites of thrombosis include the **deep veins** (leading to **deep vein thrombosis [DVT]**) and **lungs** (causing **pulmonary embolism [PE]**). - **Arterial thrombosis**: HIT can also cause **stroke**, **myocardial infarction**, or **limb ischemia** due to clot formation in the arteries. 3. **Skin lesions**: - In **Type 2 HIT**, skin lesions can occur at the **heparin injection sites** due to platelet aggregation and thrombosis in the small blood vessels. - These lesions can appear as **ecchymoses**, **erythematous patches**, or **necrotic ulcers**. 4. **Acute systemic symptoms**: - **Fever**, **chills**, **malaise**, and **shortness of breath** may occur due to the thrombotic complications. --- ### **Diagnosis of HIT** 1. **Clinical Suspicion**: - The diagnosis is primarily **clinical**, with a strong suspicion raised if a patient on **heparin** therapy develops **thrombocytopenia** and **thrombosis**. 2. **4Ts Score**: - The **4Ts score** is a clinical scoring system used to assess the **likelihood** of HIT based on the following criteria: 1. **Thrombocytopenia** (platelet count drop) 2. **Timing of platelet count drop** (occurring 5-10 days after heparin initiation) 3. **Thrombosis** (presence of new or worsening thrombotic events) 4. **Other causes of thrombocytopenia** (whether another cause of low platelets can be identified) - A **4Ts score** ≥4 suggests a high probability of HIT, and further testing is warranted. 3. **Laboratory Tests**: - **Serotonin Release Assay (SRA)**: This is the **gold standard test** for diagnosing **Type 2 HIT**, which detects platelet activation by heparin-PF4 antibodies. However, it is not widely available. - **Enzyme-Linked Immunosorbent Assay (ELISA)**: This test detects **anti-PF4/heparin antibodies** but cannot distinguish between the antibodies that cause HIT and those that do not. A **positive ELISA** suggests the presence of the antibodies, but further confirmation with a functional assay (e.g., SRA) is needed. 4. **Platelet Count**: - **A significant drop** in platelet count, typically by **50%** from baseline, should raise suspicion for HIT. --- ### **Management of HIT** 1. **Discontinue Heparin**: - The first step in treating **HIT** is to **immediately discontinue all forms of heparin** (including low-molecular-weight heparin [LMWH]). - This helps prevent further platelet activation and thrombus formation. 2. **Alternative Anticoagulation**: - **Non-heparin anticoagulants** should be used instead, such as: - **Direct thrombin inhibitors** (e.g., **argatroban** or **bivalirudin**) are the most commonly used agents in the acute setting. - **Fondaparinux**, an indirect factor Xa inhibitor, can also be used. - These agents provide anticoagulation without activating platelets or causing further thrombosis. 3. **Platelet Count Monitoring**: - **Monitor platelet counts** regularly to assess the progression of thrombocytopenia and the effectiveness of the anticoagulant therapy. 4. **Thrombosis Management**: - Treatment of any thrombotic events (e.g., **deep vein thrombosis**, **pulmonary embolism**, **stroke**) should be considered as part of the overall management of HIT. 5. **Avoid Re-exposure to Heparin**: - Once a patient has developed HIT, they should never be re-exposed to **heparin** or **low-molecular-weight heparin** due to the risk of recurrent HIT. --- ### **Prognosis** - **Type 1 HIT** generally has a **mild course** with **no long-term complications**, and platelet counts usually return to normal with discontinuation of heparin. - **Type 2 HIT** is much more serious, with **paradoxical thrombosis** being a significant risk. Without appropriate treatment, it can result in **severe thrombotic complications** or even death. - With **early recognition**, **discontinuation of heparin**, and **appropriate anticoagulation therapy**, the prognosis for **Type 2 HIT** has improved significantly. --- ### **Summary** - **Heparin-induced thrombocytopenia (HIT)** is an **immune-mediated disorder** that occurs in response to **heparin** therapy, leading to **thrombocytopenia** and an increased risk of **thrombosis**. - **Type 2 HIT** is the severe, **clinically significant** form, characterized by **platelet activation** and **paradoxical thrombosis**. - The diagnosis involves clinical suspicion (using the **4Ts score**) and laboratory tests like **serotonin release assay** or **ELISA** for detecting **heparin-PF4 antibodies**. - Treatment includes **discontinuing heparin**, **using alternative anticoagulants** (e.g., **argatroban**, **bivalirudin**), and **monitoring platelet counts** and **thrombotic events**. - Early detection and appropriate management are crucial to prevent complications and improve outcomes. ### Reference: - ### Connected Documents: -