Pharmacotherapy of heparin-induced thrombocytopenia

Abstract

Heparin-induced thrombocytopenia (HIT) is a life-and-limb threatening condition that is associated with the development of antibodies that activate platelets and the coagulation system in the presence of unfractionated heparin or low molecular weight heparin. The binding of antibody to heparin-PF-4 complexes can activate platelets, leading to an acute, often catastrophic, thrombotic diathesis. The most common laboratory finding is the development of thrombocytopenia 5 or more days after beginning heparin treatment, which occur in up to 1 - 5% of patients exposed to heparin, depending on type of heparin and indication for anticoagulation. The onset of thrombocytopenia can be immediate or delayed for several weeks after the exposure to heparin. Approximately 50 - 60% of patients who develop HIT manifest acute venous or arterial thrombosis and a significant percentage of these patients die or develop vascular gangrene of a limb that requires amputation. Given the severe sequelae associated with HIT, recognition and immediate medical management is essential. Treatment of a patient with HIT is complex, as there are several different anticoagulants now available which have been shown to be useful. Optimal management depends on each patient's individual clinical manifestations, as well as the need for ongoing anticoagulation therapy. No single agent or treatment approach can be considered to be 'standard practice' as very few clinical trials have been completed, compare different treatment options. The use of warfarin alone in a patient with HIT, must be avoided in order to avoid the possibility of further activating coagulation, which may hasten the development of venous limb gangrene. There are several different tests available that detect HIT antibodies and each has different sensitivity and specificity for HIT. In this review we discuss the epidemiology and natural history of HIT, risk factors associated with the development of HIT and the clinical and laboratory tests that aid in the diagnosis and treatment. Special emphasis is given to addressing the management of HIT in special populations, particularly patients with renal or liver disease, acute coronary syndromes, pregnancy, paediatrics and patients who require cardiopulmonary bypass surgery.

Functional divergence between 2 chemokines is conferred by single amino acid change

“…8 CXCL4 has also been proposed to play critical role in other human diseases including heparin-induced thrombocytopenia (HIT) and progression of multiple myeloma. 29,30 During evolution, recent gene duplication gave rise to a second CXCL4 form, named PF4alt/PF4V1 or CXCL4L1. 31 CXCL4L1 is only found in some primates.…”

Heparin-induced thrombocytopenia in the critical care setting: Diagnosis and management^

“…These clinical study data showed significant risk reductions in clinical outcomes (all-cause death, all-cause amputation, and new thrombosis within 37 days of baseline) relative to historical controls (Table 7) (66). Rates of death in argatroban-treated patients ranged from 16.9% to 23.1% compared with 20.9% to 28.3% in the historical control groups.…”

“…The ELISA can be performed relatively quickly and has high sensitivity (90 -98%) and high negative predictive value (95%); however, it has a low specificity with a moderately high false-positive rate in patients who have received heparin between 5 days to a few weeks earlier. The presence of HIT antibodies does not necessarily predict the development of clinical HIT (66). A positive ELISA test for HIT antibodies occurs in approximately 3-20% of patients treated with heparin (37), and this percentage is even higher (40 -60%) after open heart surgery, yet relatively few of these patients develop HIT (67)(68)(69).…”

Thrombocytopenia Associated With Antithrombotic Therapy in Acute Coronary Syndrome

“…In the emergent intervention of acute coronary syndromes and myocardial infarction, heparin is often given. It is important to distinguish the cause of thrombocytopenia because heparin itself may also induce this effect 16 . Heparin may elicit a direct or enhancing effect of other platelet‐aggregating substances, resulting in mild platelet aggregation.…”

“…Nadir platelet counts usually fall to <100×10 9 /L or to 50% below baseline. Heparin‐PF4 antibody—as well as serotonin‐releasing assay—may differentiate between the types of heparin‐induced thrombocytopenia and definitively rule out heparin as the suspect in the cause of profound thrombocytopenia 16 …”