Clinical significance of heparin/platelet factor 4 antibody in maintenance hemodialysis patients / 第二军医大学学报

Objective To investigate the positive rate of heparin/platelet factor 4 (H/PF4) antibody in maintenance hemodialysis (MHD) patients, and to explore its clinical significance. Methods Fifty-four MHD patients treated in the Department of Nephrology of Changzheng Hospital of Naval Medical University (Second Military Medical University) were selected. The dialysis duration (unfractionated heparin/low-molecular-weight heparin) of all patients was more than 3 months, with no infections or other active diseases. Serum samples were collected from the MHD patients before dialysis, and IgG H/PF4 antibody was detected by particle immunofiltration assay. The general condition, hemoglobin level, platelet count, anticoagulant method (unfractionated heparin/low-molecular-weight heparin), anticoagulant dosage, and dialysis mode (conventional hemodialysis/nocturnal extended hemodialysis) were compared between the H/PF4 antibody-positive group and H/PF4 antibody-negative group. After 3 years' follow-up, the change of platelets, the incidence of vascular access thrombosis, cardio-cerebral vascular events, hospitalization rates and mortality were compared between the two groups. Results The positive rate of H/PF4 antibody was 63.0% (34/54) in MHD patients. There were no significant differences in gender, age, dialysis age, hemoglobin level or platelet count between the H/PF4 antibody-positive group and H/PF4 antibody-negative group (P0.05). The positive H/PF4 antibody was not correlated with primary kidney disease, anticoagulant method, anticoagulant dosage, or dialysis mode (all P0.05). After 3 years' follow-up, there were no significant differences in the change of platelet, the incidence of vascular access thrombosis (14.7%5/34vs 25.0%5/20), cardiovascular events, cerebrovascular events, hospitalization rates, or mortality between the two groups (all P0.05). Conclusion The positive rate of H/PF4 antibody is high in MHD patients. The production of H/PF4 antibody is not related to the heparin type, heparin dosage, or dialysis mode. The positive H/PF4 antibody has no significant effect on platelet counts or adverse events, including thrombosis and cardiovascular events.

Utility of ELISA Optical Density Values and Clinical Scores for the Diagnosis of and Thrombosis Prediction in Heparin-induced Thrombocytopenia / 대한진단검사의학회지

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction caused by antibodies to the heparin/platelet factor 4 (PF4) complex, resulting in thrombocytopenia and prothrombotic state. HIT diagnosis is challenging and depends on clinical presentation and laboratory tests. We investigated the usefulness of clinical scores and heparin/PF4 ELISA optical density (OD) as a diagnostic marker and thrombosis predictor in HIT. METHODS: We analyzed 92 patients with suspected HIT. The heparin/PF4 antibody was measured using a commercial ELISA kit (GTI, USA). For each patient, the 4 T's score and Chong's score were calculated. RESULTS: Of the 92 patients, 28 were anti-heparin/PF4-seropositive. The 4 T's score and Chong's score showed good correlation (r=0.874). The 4 T's score and OD values showed good performance for diagnosis of the definite and unlikely HIT groups; however, OD levels showed better sensitivity (93.8%) than the 4 T's score used alone (62.5%). Of the 92 patients, 26 developed thrombosis. The OD values were significantly higher in patients with thrombosis than in those without thrombosis (0.52 vs. 0.22, P0.4) had an increased risk of thrombosis (adjusted odds ratio 9.44 [3.35-26.6], P<0.001) and a shorter 250-day thrombosis-free survival (32.1% vs. 54.7%, P=0.012). CONCLUSIONS: ELISA OD values in combination with clinical scoring can improve the diagnosis of and thrombosis prediction in HIT. More attention should be paid to the use of clinical scores and OD values as thrombosis predictors in HIT.

Anti-Heparin-Platelet Factor 4 Antibody is a Risk Factor for Vascular Access Obstruction in Patients Undergoing Hemodialysis

Since heparin is an anticoagulant commonly used in hemodialysis and the patients on hemodialysis are repeatedly exposed to heparin, heparin may be the cause of the development of heparin-dependent antibodies and thrombotic complications in patients on hemodialysis. The purpose of this study was to determine the prevalence and the clinical significance of the antibodies against heparin-platelet factor 4 complexes as determined by enzyme immunoassay in patients on maintenance hemodialysis. The prevalence of anti-heparin-platelet factor 4 antibodies was higher in hemodialysis patients than in normal subjects (8.8 vs 0.0%, p<0.05). The number of past episodes of vascular access obstruction per year was significantly higher in the anti-heparin-platelet factor 4 antibody positive group than antibody negative group. Anti-heparin-platelet factor 4 antibody positive patients experienced more frequent vascular access obstructions than control subjects. In conclusion, anti-heparin-platelet factor 4 antibody might be a risk factor for vascular access obstructions in patients with end-stage renal disease on maintenance hemodialysis.