Limits...
Utility of ELISA optical density values and clinical scores for the diagnosis of and thrombosis prediction in heparin-induced thrombocytopenia.

Kim SY, Kim HK, Han KS, Kim I, Yoon SS, Park S, Kim BK - Korean J Lab Med (2011)

Bottom Line: 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%).

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT

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, P<0.001). Patients with high OD values (OD>0.4) 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.

Show MeSH

Related in: MedlinePlus

ROC curve relating heparin/PF4 ELISA (A) optical density (OD) value and (B) 4 T's scores to occurrence of thromboembolic complication. (A) When the OD cut-off is 0.427, the sensitivity is 65.4%, and the specificity is 88.4%. (B) When the 4 T's score is greater than or equal to 4, the sensitivity is 69.2%, and the specificity is 84.8%.Abbreviation: AUC, area under curve.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC3111042&req=5

Figure 3: ROC curve relating heparin/PF4 ELISA (A) optical density (OD) value and (B) 4 T's scores to occurrence of thromboembolic complication. (A) When the OD cut-off is 0.427, the sensitivity is 65.4%, and the specificity is 88.4%. (B) When the 4 T's score is greater than or equal to 4, the sensitivity is 69.2%, and the specificity is 84.8%.Abbreviation: AUC, area under curve.

Mentions: Thromboembolic events were observed in 26 patients (28.3%). In 17 patients (65.4%), arterial thrombosis occurred (6 had thrombosis involving peripheral arteries, 5 intra-atrial or intraventricular thrombi, 4 brain infarction, and 2 splenic infarction), and 9 patients developed venous thrombosis (4 experienced new or progressive pulmonary embolism, 4 peripheral venous stasis or venous gangrene, and 1 recurrent extracorporeal circuit thrombosis). The clinical and laboratory characteristics of all patients who experienced thromboembolic complications were summarized in Table 5. Of the 26 patients, 17 patients (65.4%) tested positive for heparin/PF4 antibody (OD value>0.4), while 9 patients (34.6%) tested negative for heparin/PF4 antibody (OD≤0.4). Thrombocytopenia was more severe in patients who developed thrombosis (platelet nadir 21×109/L, P=0.015). OD values were significantly higher in patients with thrombosis (median, 0.52), compared to those without thrombosis (0.22, P<0.001). More patients in the 4 T's category of intermediate or high pretest probability experienced thromboembolic complication (Table 5). As the OD value increased, the frequency of thromboembolic complication tended to increase (Fig. 2). When the OD cut-offs of 0.4 and 1.0 were considered, 60.7% (17/28) patients with OD>0.4 subsequently developed thromboembolic complications, while 14.1% (9/64) of patients with OD≤0.4 developed thrombosis. Among patients with OD>1.0, 77.8% (7/9) developed thrombosis, and 22.9% (19/83) of patients with OD≤1.0 developed thrombosis. Thus, differences of the thrombosis risk between patients with OD>1.0 and those who with OD≤1.0 were greater, compared with differences between patients with OD>0.4 and those who with OD≤0.4. When the combination of OD values and 4 T's scores were considered, among 22 patients with 4 T's score ≥4 and OD>0.4, 11 patients (68.2%) developed thrombosis, a higher frequency than when 4 T's score ≥4 alone (22/44, 50.0%), or OD>0.4 alone (17/28, 60.7%) were considered. Meanwhile, among 4 patients with 4 T's score ≥6 (high probability) and OD>1.0, 3 patients (75.0%) developed thrombotic complication, the frequency for which was between 72.7% (8/11) when high probability patients were considered alone and 77.8% (7/9) when patients with OD>1.0 considered alone. ROC curves were constructed to determine the best cut-offs for the OD value and 4 T's score for the prediction of thrombosis (Fig. 3). The OD value of 0.427 and 4 T's score of 4 had the best performance as cut-off values. At the OD value of 0.427, the sensitivity to predict thrombosis was 65.4%, and specificity was 88.4%.


Utility of ELISA optical density values and clinical scores for the diagnosis of and thrombosis prediction in heparin-induced thrombocytopenia.

Kim SY, Kim HK, Han KS, Kim I, Yoon SS, Park S, Kim BK - Korean J Lab Med (2011)

ROC curve relating heparin/PF4 ELISA (A) optical density (OD) value and (B) 4 T's scores to occurrence of thromboembolic complication. (A) When the OD cut-off is 0.427, the sensitivity is 65.4%, and the specificity is 88.4%. (B) When the 4 T's score is greater than or equal to 4, the sensitivity is 69.2%, and the specificity is 84.8%.Abbreviation: AUC, area under curve.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3111042&req=5

Figure 3: ROC curve relating heparin/PF4 ELISA (A) optical density (OD) value and (B) 4 T's scores to occurrence of thromboembolic complication. (A) When the OD cut-off is 0.427, the sensitivity is 65.4%, and the specificity is 88.4%. (B) When the 4 T's score is greater than or equal to 4, the sensitivity is 69.2%, and the specificity is 84.8%.Abbreviation: AUC, area under curve.
Mentions: Thromboembolic events were observed in 26 patients (28.3%). In 17 patients (65.4%), arterial thrombosis occurred (6 had thrombosis involving peripheral arteries, 5 intra-atrial or intraventricular thrombi, 4 brain infarction, and 2 splenic infarction), and 9 patients developed venous thrombosis (4 experienced new or progressive pulmonary embolism, 4 peripheral venous stasis or venous gangrene, and 1 recurrent extracorporeal circuit thrombosis). The clinical and laboratory characteristics of all patients who experienced thromboembolic complications were summarized in Table 5. Of the 26 patients, 17 patients (65.4%) tested positive for heparin/PF4 antibody (OD value>0.4), while 9 patients (34.6%) tested negative for heparin/PF4 antibody (OD≤0.4). Thrombocytopenia was more severe in patients who developed thrombosis (platelet nadir 21×109/L, P=0.015). OD values were significantly higher in patients with thrombosis (median, 0.52), compared to those without thrombosis (0.22, P<0.001). More patients in the 4 T's category of intermediate or high pretest probability experienced thromboembolic complication (Table 5). As the OD value increased, the frequency of thromboembolic complication tended to increase (Fig. 2). When the OD cut-offs of 0.4 and 1.0 were considered, 60.7% (17/28) patients with OD>0.4 subsequently developed thromboembolic complications, while 14.1% (9/64) of patients with OD≤0.4 developed thrombosis. Among patients with OD>1.0, 77.8% (7/9) developed thrombosis, and 22.9% (19/83) of patients with OD≤1.0 developed thrombosis. Thus, differences of the thrombosis risk between patients with OD>1.0 and those who with OD≤1.0 were greater, compared with differences between patients with OD>0.4 and those who with OD≤0.4. When the combination of OD values and 4 T's scores were considered, among 22 patients with 4 T's score ≥4 and OD>0.4, 11 patients (68.2%) developed thrombosis, a higher frequency than when 4 T's score ≥4 alone (22/44, 50.0%), or OD>0.4 alone (17/28, 60.7%) were considered. Meanwhile, among 4 patients with 4 T's score ≥6 (high probability) and OD>1.0, 3 patients (75.0%) developed thrombotic complication, the frequency for which was between 72.7% (8/11) when high probability patients were considered alone and 77.8% (7/9) when patients with OD>1.0 considered alone. ROC curves were constructed to determine the best cut-offs for the OD value and 4 T's score for the prediction of thrombosis (Fig. 3). The OD value of 0.427 and 4 T's score of 4 had the best performance as cut-off values. At the OD value of 0.427, the sensitivity to predict thrombosis was 65.4%, and specificity was 88.4%.

Bottom Line: 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%).

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT

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, P<0.001). Patients with high OD values (OD>0.4) 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.

Show MeSH
Related in: MedlinePlus