From the Guidelines
Heparin-induced thrombocytopenia (HIT) typically presents with a significant drop in platelet count, usually a decrease of 50% or more from baseline, and paradoxically causes thrombosis rather than bleeding, with symptoms including new blood clots, deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, or limb ischemia 1. The primary symptom of HIT is a significant drop in platelet count, which can occur 5-10 days after starting heparin therapy, or sooner in patients previously exposed to heparin. Despite this thrombocytopenia, HIT causes thrombosis rather than bleeding, which can manifest as:
- Deep vein thrombosis
- Pulmonary embolism
- Stroke
- Myocardial infarction
- Limb ischemia with symptoms like swelling, pain, warmth, and discoloration in affected areas Skin lesions at heparin injection sites, including erythema, pain, necrosis, or a palpable rash, may also occur. Systemic reactions such as fever, chills, hypertension, tachycardia, dyspnea, or chest pain can develop shortly after intravenous heparin administration. HIT occurs when heparin binds to platelet factor 4, forming complexes that trigger antibody production, leading to platelet activation, aggregation, and subsequent thrombosis 1. If HIT is suspected, all heparin products should be immediately discontinued and alternative anticoagulation started, as the condition can be life-threatening if not promptly addressed 1. Some key points to consider in the management of HIT include:
- Discontinuing heparin therapy and switching to a nonheparin anticoagulant
- Using approved alternative anticoagulants such as direct thrombin inhibitors or heparinoids
- Considering the use of direct oral anticoagulants (DOACs) in select cases, although they are not currently licensed for patients with HIT 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. HIT or HITT can occur up to several weeks after the discontinuation of heparin therapy Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin sodium should be evaluated for HIT or HITT.
The symptoms of Heparin-Induced Thrombocytopenia (HIT) from heparin (unfractionated heparin) include:
- Thrombocytopenia (low platelet count)
- Thrombosis (blood clots)
- Venous and arterial thromboses, including:
- Deep vein thrombosis
- Pulmonary embolism
- Cerebral vein thrombosis
- Limb ischemia
- Stroke
- Myocardial infarction
- Mesenteric thrombosis
- Renal arterial thrombosis
- Skin necrosis
- Gangrene of the extremities 2
From the Research
Symptoms of Heparin-Induced Thrombocytopenia (HIT)
The symptoms of Heparin-Induced Thrombocytopenia (HIT) from heparin (unfractionated heparin) include:
- A decrease in platelet count by 50% or to less than 100,000, from 5 to 14 days of therapy 3
- Thrombotic complications, such as venous/arterial thrombosis, skin gangrene, and acute platelet activation syndrome 3
- A prothrombotic hypercoagulable state due to the combined effect of various factors, such as platelet activation, mainly the formation of PF4/heparin/IgG complex, stimulation of the intrinsic factor, and loss of anticoagulant effect of heparin 3
- Catastrophic arterial and venous thrombosis, with a mortality rate of 20%, without early recognition 4
- Moderate thrombocytopenia, with a median platelet count nadir of approximately 50 to 60 x 10(9) platelets/L 5
- Severe thrombocytopenia, with high antibody levels and severe clinical outcomes, such as disseminated intravascular coagulation with microvascular thrombosis 5
Clinical Manifestations
The clinical manifestations of HIT include:
- A fall in platelet count and a high incidence of thromboembolic complications 6
- Venous thromboembolism (VTE) and arterial thrombosis 7
- Delayed-onset HIT, which occurs several days following heparin discontinuation 7
- Skin gangrene and acute platelet activation syndrome 3
Diagnosis and Treatment
The diagnosis of HIT is done by clinical condition, heparin use, and timing of thrombocytopenia, and it is confirmed by either serotonin release assay or ELISA assay 3. The treatment of HIT involves:
- Discontinuation of heparin and the use of an alternative anticoagulant, such as danaparoid, lepirudin, argatroban, or bivalirudin 6, 5
- Fondaparinux, a synthetic pentasaccharide and indirect-acting factor-Xa inhibitor, which has little to no cross-reactivity with the heparin-platelet factor 4 antibody in in vitro testing 7
- Warfarin therapy, which should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated 5