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1976   Part XII  Hemostasis and Thrombosis


                                                 First day of antibody detection


                                                     Beginning of HIT-related platelet count fall
                                      Summary
                                       of 12 HIT
                                        patient
                                        profiles                    Platelet count fall ≥50%

                        3.0                                                 Thrombotic event

                              Start of heparin
                        2.5   Non-HIT (mean day 1.21)                        **   **   **
                       EIA-GAM OD (mean +/– SEM)  1.5  GAM  (n = 12) (n = 36)  *  **  **
                              HIT (mean day 1.38)
                        2.0


                                           Non-HIT
                                      HIT


                        1.0
                                 HIT vs. Non-HIT

                        0.5     **p < .005, *p < .05       *
                                                                EIA OD cut-off

                          0
                              0    1   2    3    4    5   6    7    8    9   10   11   12  13   14
                      A                                  Days after surgery

                        1.6

                        1.4
                                        HIT  Non-HIT
                                      (n = 12) (n = 36)
                        1.2      IgG                                **  **   **   *    *
                       EIA-Ig OD (mean +/– SEM)  0.8  IgM      **
                                 IgA
                        1.0
                                   HIT vs. Non-HIT
                                  **p < .005, *p < .05


                        0.6

                        0.4                               **
                                                      *
                                                                                              EIA OD
                        0.2                                                                   cut-off

                          0
                              0    1   2    3    4    5   6    7    8    9   10   11   12  13   14
                      B                                  Days after surgery
        Fig. 133.2  CHARACTERISTIC TIMELINE OF HEPARIN-INDUCED THROMBOCYTOPENIA. Antiplatelet 4 (PF4)/heparin antibodies (by enzyme
        immunoassay [EIA]) per postoperative day in 12 patients with heparin-induced thrombocytopenia (HIT) and 36 seropositive non-HIT control patients. (A)
        Mean (± standard error of the mean [SEM]) optical density (OD) of anti-PF4/heparin antibodies detected using commercial immunoassay (EIA-GAM) that
        detects antibodies of all three immunoglobulin classes (IgG, IgA, IgM). HIT patients are indicated by blue squares, and seropositive non-HIT controls by green
        squares. On each day beginning on postoperative day 6, there is a significant difference in the mean of the OD levels between the patients with HIT and the
        seropositive non-HIT controls (p < .05 by nonpaired t-test). At the top of the figure, summary data for 12 HIT patient profiles are shown for four key events
        (first day of antibody detection, beginning of HIT-related platelet count fall, platelet count fall ≥50%, and thrombotic event), summarized as median (small
        purple squares within rectangles), interquartile range (rectangles), and range (ends of thin black lines). (B) Mean (±SEM) OD values of anti-PF4/heparin antibodies
        detected using an in-house immunoassay (EIA-Ig) that detects antibodies of the individual immunoglobulin classes, IgG (red circles), IgA (green triangles), and
        IgM (blue inverted triangles) for HIT (solid symbols) and non-HIT (open symbols). On each postoperative day beginning on day 5, there is a significant difference
        in the mean of the OD units for the IgG immunoassay between the patients with HIT and the seropositive non-HIT controls (**p < .005 for days 6–10; *p <
        .05 for days 5, 11, and 12). (From Warkentin TE, Sheppard JI, Moore JC, et al: Studies of the immune response in heparin-induced thrombocytopenia. Blood 113:4693, 2009.)
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