What are the signs of Heparin (unfractionated heparin) induced thrombocytopenia (HIT)?

From the Guidelines

Heparin-induced thrombocytopenia (HIT) is characterized by a drop in platelet count by 50% or more from baseline, typically occurring 5-14 days after starting heparin therapy, and is often accompanied by thrombotic events rather than bleeding. The diagnosis of HIT should be made in the presence of a platelet count < 100 G.L and a decrease in the platelet count > 50% compared to a previous value, most often obtained at the beginning of treatment 1. Thrombocytopenia is the most common clinical manifestation of HIT, occurring in 85% to 90% of patients, and can be defined as a platelet count < 150 x 10^9/L or a proportional fall in the platelet count (e.g., 30%-50% fall even if the nadir remains > 150 x 10^9/L) 1.

Key Signs of HIT

• A drop in platelet count by 50% or more from baseline
• Thrombotic events, such as deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, and limb ischemia
• Skin lesions at heparin injection sites, including erythema, necrosis, or painful nodules
• Acute systemic reactions, such as fever, chills, hypertension, tachycardia, chest pain, dyspnea, or cardiopulmonary arrest, which can occur within 30 minutes of IV heparin bolus

Diagnosis and Management

The diagnosis of HIT should be suspected in patients who develop thrombocytopenia or thrombosis after heparin therapy, and should be confirmed with both immunoassay and functional assays 1. If HIT is suspected, all heparin products should be immediately discontinued and alternative anticoagulation started (argatroban, bivalirudin, or fondaparinux) while awaiting confirmatory testing 1. The pathophysiology of HIT involves antibody formation against platelet factor 4-heparin complexes, leading to platelet activation, consumption, and a prothrombotic state.

From the FDA Drug Label

Thrombocytopenia has been reported to occur in patients receiving heparin with a reported incidence of up to 30%. Heparin-induced Thrombocytopenia (HIT) is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets. HIT may progress to the development of venous and arterial thromboses, a condition referred to as Heparin-induced Thrombocytopenia and 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

The signs of Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia and Thrombosis (HITT) include:

• Thrombocytopenia (platelet count falls below 100,000/mm3)
• Thrombotic events such as:
  • 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
  • Possibly death If the platelet count falls below 100,000/mm3 or if recurrent thrombosis develops, the heparin product should be promptly discontinued and alternative anticoagulants considered, if patients require continued anticoagulation 2

From the Research

Signs of Heparin-Induced Thrombocytopenia

The signs of heparin-induced thrombocytopenia (HIT) include:

• A drop in platelet count, typically to less than 50% of the basal level, with or without the appearance of thrombotic complications 3
• Thrombocytopenia usually manifests 5-10 days after starting heparin therapy, but can occur sooner with recent heparin exposure or rarely have a delayed onset 4, 5
• The platelet count usually decreases to less than 100 x 10(3)/mm3, and generally normalizes within 5-7 days after discontinuing heparin therapy 6
• Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported 4
• Thrombotic episodes can occur simultaneously or shortly after the onset of thrombocytopenia 5

Key Characteristics of HIT

Some key characteristics of HIT include:

• The development of antibodies to platelet factor 4 (PF4) and heparin, which cause secondary activation of platelets, coagulation, and increased thrombin production 3
• An increased risk for thromboembolic complications, primarily venous thromboembolism 4
• The need for prompt management, including discontinuation of heparin and initiation of non-heparin anticoagulant therapy, to prevent complications 4, 7

Diagnostic Considerations

Diagnostic considerations for HIT include:

• Monitoring the platelet count in patients receiving heparin to detect early signs of thrombocytopenia 3
• Demonstration of heparin-dependent platelet activation using an antigen or functional assay to confirm the clinical diagnosis 3
• The use of alternative anticoagulants, such as argatroban, bivalirudin, and fondaparinux, in the treatment of HIT 4, 7