The Incidence of Heparin-Induced Thrombocytopenia (HIT) After Prophylactic Heparin Exposure in Pediatric Intensive Care and Congenital Cardiology Patients: A Single Center, Prospective and Phase-IV Study: Turkish Experience

Abstract 4365

Heparin is the standard therapy for the prevention and the treatment of venous thromboembolism in children. Heparin-induced thrombocytopenia (HIT) is a well-known serious adverse effect related with heparin therapy or prophylaxis. HIT affects up to %5 of patients treated with unfractionated heparin (UFH). However, prospective studies are so rare in children for technical and ethical reasons.

Aim of this study was to determine the incidence of HIT in UFH-exposed children for prohylaxis. Patients who used treatment doses of UFH were excluded. Only ICU and cardiology patients were included. We performed a prospective single center phase-IV study in Ege University Children's Hospital after approved by Ethics Commitee and Ministry of Health. Children who exposed to UFH for any time were eligible for study. Study group consists of intensive care (ICU) patients (n=28) and congenital heart disorders who will undergo catheter operation (n=25). Mean age was 52 mo (range:1–204). Thirty of patients were female and others were male. All ICU patients used diluted UFH for flushing to maintain patency of central lines. All cardiology cases received only one bolus dose of UFH (50 IU/kg) for prophylaxis. In all patients (n=53) blood samples were collected for platelet counts (CELL DYN 3700 counter, Abbott), anti-Heparin/PF4 antibody (ELISA)(Asserachrom HPIA-Ig G, Diagnostica Stago) and heparin-induced platelet agregation tests (APACT-4004, Tokra) prior to and after 10 days (median) (range: 7–15) of first UFH exposure.

After 2 years of observation, we have not found any single patient diagnosed as HIT by clinical findings and confirmed by laboratory analysis. Significant dropping (>50%) of platelet count was observed in only 4 ICU patients. Only one patient had below <150.000/mm3. However, ELISA and agregation tests were negative for these patients. Reasons for thrombocytopenia were evaluated as underlying medical conditions (trauma, pneumonia and sepsis) not for HIT. In only one ICU case, ELISA test was found border-line positive (O.D: 1.374)(positive controls: 1.35±0.34). However, no thrombocytopenia and no activation in agregation related heparin studies were found. This result was evaluated as false-positivity for ELISA. However, mean OD values for ELISA test was found significantly elevated after heparin exposure (before heparin: 0.119±0.061 versus after heparin: 0.258±0.262)(Wilcoxon test; p<0.0001). Elevated heparin-induced agregation response (more than >20% after heparin exposure) was found only in three cardiology patients (diagnosed as ASD, VSD and PDA). However, there was no thrombocytopenia and ELISA seropositivity in these patients. This hyperactivity was evaluated as “non-specific” heparin-induced agregation.

In literature, infants with congenital heart disease or children requiring admission to ICU are particularly at risk of venous thromboembolism and likely to be exposed to heparins for prevention and treatment. However, in this single center phase-IV study, we have not found prospectively any HIT patients among 53 risky patients. Reasons may be prophylaxis versus treatment doses, short exposure time versus long-term exposures and medical versus surgical interventions and lower count of patients for low incidence. However significant ELISA activity after heparin exposure was noted as interesting finding. This point might supported for mild heparin activity in patient group who has lower immunogenicity of heparin.