What is Heparin-Induced Thrombocytopenia (HIT)?

From the Guidelines

Heparin-induced thrombocytopenia (HIT) is a serious immune-mediated adverse drug reaction caused by heparin therapy, characterized by a significant drop in platelet count and an increased risk of venous and arterial thrombosis, and should be managed by immediately discontinuing heparin products and initiating alternative anticoagulation with direct thrombin inhibitors like argatroban or bivalirudin, as recommended by the American Society of Hematology guidelines 1.

Key Characteristics of HIT

• HIT typically develops 5-10 days after starting heparin therapy (or sooner with recent heparin exposure) 1
• Characterized by a significant drop in platelet count (usually >50% from baseline) and an increased risk of venous and arterial thrombosis 1
• Diagnosis is confirmed with both clinical assessment (using the 4T score) and laboratory testing (anti-PF4/heparin antibody ELISA and/or functional assays) 1

Management of HIT

• Discontinue all heparin products, including heparin flushes and heparin-coated catheters, immediately if HIT is suspected 1
• Initiate alternative anticoagulation with direct thrombin inhibitors like argatroban (starting dose 2 mcg/kg/min adjusted to target aPTT 1.5-3 times baseline) or bivalirudin, as patients remain at high thrombotic risk 1
• Fondaparinux or direct oral anticoagulants may be used in stable patients without critical illness, although their use is not universally recommended 1
• Warfarin should not be started until platelet counts recover (>150,000/μL) to avoid warfarin-induced skin necrosis, and patients with a history of HIT should avoid heparin exposure in the future when possible 1

Special Considerations

• Patients with a history of HIT should be closely monitored for signs of thrombosis and bleeding, and alternative anticoagulation strategies should be considered 1
• Pregnant patients, patients requiring urgent cardiac surgery or PCI, and patients requiring renal replacement therapy require special consideration and may benefit from consultation with a hematologist or other specialist 1

From the FDA Drug Label

Heparin-induced thrombocytopenia (HIT) is a serious antibody-mediated reaction. HIT occurs in patients treated with heparin and is due to the development of antibodies to a platelet Factor 4-heparin complex that induce in vivo platelet aggregation HIT may progress to the development of venous and arterial thromboses, a condition referred to as heparin-induced thrombocytopenia with thrombosis (HITT). Thrombotic events may also be the initial presentation for HITT These serious thromboembolic events include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, mesenteric thrombosis, renal arterial thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and possibly death If the platelet count falls below 100,000/mm3 or if recurrent thrombosis develops, promptly discontinue heparin, evaluate for HIT and HITT, and, if necessary, administer an alternative anticoagulant.

Heparin-Induced Thrombocytopenia (HIT) is a serious reaction that can occur in patients treated with heparin. It is caused by the development of antibodies to a platelet Factor 4-heparin complex, leading to in vivo platelet aggregation. HIT can progress to venous and arterial thromboses, known as Heparin-Induced Thrombocytopenia with Thrombosis (HITT).

• Key features of HIT include:
  • Thrombocytopenia (low platelet count)
  • Thrombotic events, such as deep vein thrombosis, pulmonary embolism, and stroke
  • Risk of death or serious complications, such as amputation or organ failure
• Management of HIT involves:
  • Prompt discontinuation of heparin
  • Evaluation for HIT and HITT
  • Administration of an alternative anticoagulant, if necessary 2

From the Research

Definition and Pathophysiology of HIT

• Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin 3, 4, 5, 6, 7.
• The thrombocytopenia is typically moderate, with a median platelet count nadir of approximately 50 to 60 x 10(9) platelets/L 5.
• HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism 5.

Diagnosis of HIT

• Diagnosis of HIT is essential to guide treatment strategies using non-heparin anticoagulants and to avoid unwanted and potential fatal thromboembolic complications 4.
• A 4Ts score is recommended for all patients with suspected HIT prior to laboratory testing 4.
• Further laboratory testing with a screening immunoassay or confirmatory functional assay is not recommended in individuals with a low 4Ts score, but should be performed if there are missing or unreliable clinical data 4.
• A positive functional assay result confirms the diagnosis of HIT and should be performed to confirm a positive immunoassay result 4.

Treatment of HIT

• Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated 3, 4, 5, 6, 7.
• Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid 3, 5, 6.
• Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe 5, 6.
• Direct oral anticoagulants (DOACs) may be used in place of warfarin after patients with HIT have responded to alternative parenteral anticoagulants with platelet count recovery 4, 6.
• Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT 3, 5.

Monitoring and Management

• Platelet count monitoring is recommended for patients receiving heparin in whom the clinician considers the risk of HIT to be > 1.0% 3.
• For patients who are receiving heparin or have received heparin within the previous 2 weeks, investigation for a diagnosis of HIT is recommended if the platelet count falls by >/= 50%, and/or a thrombotic event occurs, between days 5 and 14 (inclusive) following initiation of heparin 3.
• The nonheparin anticoagulant should be continued until the platelet count has reached a stable plateau, the international normalized ratio (INR) has reached the intended target range, and after a minimum overlap of at least 5 days between nonheparin anticoagulation and VKA therapy 3.