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Anti-PF4/heparin antibodies associated with repeated hemofiltration-filter clotting: a retrospective study.

Lasocki S, Piednoir P, Ajzenberg N, Geffroy A, Benbara A, Montravers P - Crit Care (2008)

Bottom Line: CVVH duration was significantly decreased in antibody-positive patients (5.0 [2.5 to 7.5] versus 12.0 [7.5 to 24.0] hours; P = 0.007) as was CVVH efficiency (urea reduction ratio 17% [10% to 37%] versus 44% [30% to 52%]; P = 0.04) on heparin infusion.The receiver operating characteristic curve showed that a 6-hour cutoff was the best CVVH session duration to predict a positive antibody test (sensitivity 71%, specificity 85%, and area under the curve 0.83).CVVH duration (32 [22 to 37] hours; P < 0.05) and urea reduction (55% [36% to 68%]; P < 0.03) were restored by danaparoid sodium infusion.

View Article: PubMed Central - HTML - PubMed

Affiliation: Département d'Anesthésie - Réanimation Chirurgicale, APHP, CHU Bichat-Claude Bernard, Université Paris 7, Paris, France. sigismond@lasocki.com

ABSTRACT

Introduction: Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction that is associated with a procoagulant state and both arterial and venous thrombosis. After observing two cases of repeated hemofiltration-filter clotting associated with high anti-PF4/heparin antibody concentrations, we systematically measured the anti-PF4/heparin antibody concentration in all cases of unexpected and repeated hemofiltration-filter clotting during continuous veno-venous hemofiltration (CVVH). The aim of this study was to identify factors associated with positive anti-PF4/heparin antibody in the case of repeated hemofiltration-filter clotting.

Methods: We reviewed the charts of all patients who had an anti-PF4/heparin antibody assay performed for repeated hemofiltration-filter clotting between November 2004 and May 2006 in our surgical intensive care unit. We used an enzyme-linked immunoabsorbent assay (heparin-platelet factor 4-induced antibody) with an optical density (OD) of greater than 1 IU considered positive.

Results: During the study period, anti-PF4/heparin antibody assay was performed in 28 out of 87 patients receiving CVVH. Seven patients were positive for anti-PF4/heparin antibodies (OD 2.00 [1.36 to 2.22] IU) and 21 were antibody-negative (OD 0.20 [0.10 to 0.32] IU). Baseline characteristics, platelet counts, and activated partial thromboplastin time ratios were not different between the two groups. CVVH duration was significantly decreased in antibody-positive patients (5.0 [2.5 to 7.5] versus 12.0 [7.5 to 24.0] hours; P = 0.007) as was CVVH efficiency (urea reduction ratio 17% [10% to 37%] versus 44% [30% to 52%]; P = 0.04) on heparin infusion. Anti-PF4/heparin antibody concentration was inversely correlated with CVVH duration. The receiver operating characteristic curve showed that a 6-hour cutoff was the best CVVH session duration to predict a positive antibody test (sensitivity 71%, specificity 85%, and area under the curve 0.83). CVVH duration (32 [22 to 37] hours; P < 0.05) and urea reduction (55% [36% to 68%]; P < 0.03) were restored by danaparoid sodium infusion.

Conclusion: Repeated hemofiltration-filter clotting in less than 6 hours was often associated with the presence of anti-PF4/heparin antibodies, regardless of the platelet count. In antibody-positive patients, replacement of heparin by danaparoid sodium allowed the restoration of CVVH duration and efficiency.

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Duration and efficiency of continuous veno-venous hemofiltration (CVVH) sessions. Boxes represent medians, interquartile ranges, and 10th and 90th percentiles of mean duration of CVVH sessions (upper panel) and urea reduction ratios ([(urea before – urea after)/urea before] × 100, lower panel) observed in PF4+ (n = 7) and PF4- (n = 21) patients when using unfractionated heparin (50 and 132 sessions for PF4+ and PF4- patients, respectively) and in PF4+ patients when using danaparoid sodium for anticoagulation (17 sessions). *P < 0.05 compared with PF4+ (using a Mann-Whitney test); #P = 0.027 compared with PF4+ (using a Wilcoxon rank test). There was no difference between PF4- and danaparoid CVVH durations (P = 0.17) or urea reduction (P = 0.27). PF4-, anti-PF4/heparin antibody-negative; PF4+, anti-PF4/heparin antibody-positive.
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Figure 2: Duration and efficiency of continuous veno-venous hemofiltration (CVVH) sessions. Boxes represent medians, interquartile ranges, and 10th and 90th percentiles of mean duration of CVVH sessions (upper panel) and urea reduction ratios ([(urea before – urea after)/urea before] × 100, lower panel) observed in PF4+ (n = 7) and PF4- (n = 21) patients when using unfractionated heparin (50 and 132 sessions for PF4+ and PF4- patients, respectively) and in PF4+ patients when using danaparoid sodium for anticoagulation (17 sessions). *P < 0.05 compared with PF4+ (using a Mann-Whitney test); #P = 0.027 compared with PF4+ (using a Wilcoxon rank test). There was no difference between PF4- and danaparoid CVVH durations (P = 0.17) or urea reduction (P = 0.27). PF4-, anti-PF4/heparin antibody-negative; PF4+, anti-PF4/heparin antibody-positive.

Mentions: The main CVVH session characteristics are summarized in Tables 1 and 2. No significant difference was observed in terms of aPTT ratios, regardless of the value considered. The duration of CVVH sessions was significantly decreased in PF4+ patients (Table 1; P = 0.007). An inverse correlation was observed between the anti-PF4/heparin antibody concentration (OD) and the duration of CVVH sessions (r2 = 0.24; P = 0.01). As CVVH session duration was the only parameter associated with positive antibodies, we assessed the most relevant duration to predict a positive test. The ROC curve analysis showed that 6 hours was the best cutoff to predict a positive anti-PF4/heparin antibody test (with a sensitivity of 71%, a specificity of 85%, and an area under the curve of 0.83) (Figure 1). The efficiency of CVVH sessions (assessed by the urea reduction ratio) was also decreased in PF4+ patients (Figure 2). The use of danaparoid sodium as a replacement for UFH allowed the restoration of adequate CVVH duration (32 [22 to 37] hours; P < 0.05) and efficiency (urea reduction 55% [36% to 68%]; P < 0.03) for PF4+ patients (Figure 2).


Anti-PF4/heparin antibodies associated with repeated hemofiltration-filter clotting: a retrospective study.

Lasocki S, Piednoir P, Ajzenberg N, Geffroy A, Benbara A, Montravers P - Crit Care (2008)

Duration and efficiency of continuous veno-venous hemofiltration (CVVH) sessions. Boxes represent medians, interquartile ranges, and 10th and 90th percentiles of mean duration of CVVH sessions (upper panel) and urea reduction ratios ([(urea before – urea after)/urea before] × 100, lower panel) observed in PF4+ (n = 7) and PF4- (n = 21) patients when using unfractionated heparin (50 and 132 sessions for PF4+ and PF4- patients, respectively) and in PF4+ patients when using danaparoid sodium for anticoagulation (17 sessions). *P < 0.05 compared with PF4+ (using a Mann-Whitney test); #P = 0.027 compared with PF4+ (using a Wilcoxon rank test). There was no difference between PF4- and danaparoid CVVH durations (P = 0.17) or urea reduction (P = 0.27). PF4-, anti-PF4/heparin antibody-negative; PF4+, anti-PF4/heparin antibody-positive.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2481483&req=5

Figure 2: Duration and efficiency of continuous veno-venous hemofiltration (CVVH) sessions. Boxes represent medians, interquartile ranges, and 10th and 90th percentiles of mean duration of CVVH sessions (upper panel) and urea reduction ratios ([(urea before – urea after)/urea before] × 100, lower panel) observed in PF4+ (n = 7) and PF4- (n = 21) patients when using unfractionated heparin (50 and 132 sessions for PF4+ and PF4- patients, respectively) and in PF4+ patients when using danaparoid sodium for anticoagulation (17 sessions). *P < 0.05 compared with PF4+ (using a Mann-Whitney test); #P = 0.027 compared with PF4+ (using a Wilcoxon rank test). There was no difference between PF4- and danaparoid CVVH durations (P = 0.17) or urea reduction (P = 0.27). PF4-, anti-PF4/heparin antibody-negative; PF4+, anti-PF4/heparin antibody-positive.
Mentions: The main CVVH session characteristics are summarized in Tables 1 and 2. No significant difference was observed in terms of aPTT ratios, regardless of the value considered. The duration of CVVH sessions was significantly decreased in PF4+ patients (Table 1; P = 0.007). An inverse correlation was observed between the anti-PF4/heparin antibody concentration (OD) and the duration of CVVH sessions (r2 = 0.24; P = 0.01). As CVVH session duration was the only parameter associated with positive antibodies, we assessed the most relevant duration to predict a positive test. The ROC curve analysis showed that 6 hours was the best cutoff to predict a positive anti-PF4/heparin antibody test (with a sensitivity of 71%, a specificity of 85%, and an area under the curve of 0.83) (Figure 1). The efficiency of CVVH sessions (assessed by the urea reduction ratio) was also decreased in PF4+ patients (Figure 2). The use of danaparoid sodium as a replacement for UFH allowed the restoration of adequate CVVH duration (32 [22 to 37] hours; P < 0.05) and efficiency (urea reduction 55% [36% to 68%]; P < 0.03) for PF4+ patients (Figure 2).

Bottom Line: CVVH duration was significantly decreased in antibody-positive patients (5.0 [2.5 to 7.5] versus 12.0 [7.5 to 24.0] hours; P = 0.007) as was CVVH efficiency (urea reduction ratio 17% [10% to 37%] versus 44% [30% to 52%]; P = 0.04) on heparin infusion.The receiver operating characteristic curve showed that a 6-hour cutoff was the best CVVH session duration to predict a positive antibody test (sensitivity 71%, specificity 85%, and area under the curve 0.83).CVVH duration (32 [22 to 37] hours; P < 0.05) and urea reduction (55% [36% to 68%]; P < 0.03) were restored by danaparoid sodium infusion.

View Article: PubMed Central - HTML - PubMed

Affiliation: Département d'Anesthésie - Réanimation Chirurgicale, APHP, CHU Bichat-Claude Bernard, Université Paris 7, Paris, France. sigismond@lasocki.com

ABSTRACT

Introduction: Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction that is associated with a procoagulant state and both arterial and venous thrombosis. After observing two cases of repeated hemofiltration-filter clotting associated with high anti-PF4/heparin antibody concentrations, we systematically measured the anti-PF4/heparin antibody concentration in all cases of unexpected and repeated hemofiltration-filter clotting during continuous veno-venous hemofiltration (CVVH). The aim of this study was to identify factors associated with positive anti-PF4/heparin antibody in the case of repeated hemofiltration-filter clotting.

Methods: We reviewed the charts of all patients who had an anti-PF4/heparin antibody assay performed for repeated hemofiltration-filter clotting between November 2004 and May 2006 in our surgical intensive care unit. We used an enzyme-linked immunoabsorbent assay (heparin-platelet factor 4-induced antibody) with an optical density (OD) of greater than 1 IU considered positive.

Results: During the study period, anti-PF4/heparin antibody assay was performed in 28 out of 87 patients receiving CVVH. Seven patients were positive for anti-PF4/heparin antibodies (OD 2.00 [1.36 to 2.22] IU) and 21 were antibody-negative (OD 0.20 [0.10 to 0.32] IU). Baseline characteristics, platelet counts, and activated partial thromboplastin time ratios were not different between the two groups. CVVH duration was significantly decreased in antibody-positive patients (5.0 [2.5 to 7.5] versus 12.0 [7.5 to 24.0] hours; P = 0.007) as was CVVH efficiency (urea reduction ratio 17% [10% to 37%] versus 44% [30% to 52%]; P = 0.04) on heparin infusion. Anti-PF4/heparin antibody concentration was inversely correlated with CVVH duration. The receiver operating characteristic curve showed that a 6-hour cutoff was the best CVVH session duration to predict a positive antibody test (sensitivity 71%, specificity 85%, and area under the curve 0.83). CVVH duration (32 [22 to 37] hours; P < 0.05) and urea reduction (55% [36% to 68%]; P < 0.03) were restored by danaparoid sodium infusion.

Conclusion: Repeated hemofiltration-filter clotting in less than 6 hours was often associated with the presence of anti-PF4/heparin antibodies, regardless of the platelet count. In antibody-positive patients, replacement of heparin by danaparoid sodium allowed the restoration of CVVH duration and efficiency.

Show MeSH
Related in: MedlinePlus