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. 2021 Jan 22;10(3):427. doi: 10.3390/jcm10030427

Figure 2.

Figure 2

Different formulations of heme affect the results of standard coagulation diagnostic tests, (PT, aPTT, and TT) in vitro and in vivo. While PT is used to evaluate effects on the extrinsic and common pathway (violet), changes in the intrinsic and common pathways (yellow) can be determined using aPTT. With TT only the last step of fibrin generation and fibrin clot formation (turquoise) can be analyzed. Hemin (red symbol; concentration ranges: 50 mg/kg, 50 µmol/kg, 0.01–100 µM) either did not affect PT and aPTT or a slight prolongation was observed. TT was not determined (n.d.). In contrast, hematin (orange symbol; concentration ranges: 4–12 mg/kg, 3 nmol, 10–100 µg/mL) has been reported to induce significant prolongation of all clotting times. For Panhematin® (green symbol; concentration ranges: 4 mg/kg, 70–78 µg/mL), longer clotting times were also recorded, but to a lesser extent than with hematin. However, from detailed investigations of different researcher it can be assumed that just aged hematin and Panhematin® solutions can have such strong effects, whereas fresh hematin and Panhematin® solutions are ineffective (clock symbol) [156,157,175]. Heme arginate/Normosang® (blue symbol; concentration: 3 mg/kg) did not influence these diagnostic tests at all. FIIa = thrombin, FII = prothrombin, FV = factor V, FVa = activated factor V, FVIIa = activated factor VII, FVIII = factor VIII, FVIIIa = activated factor VIII, FIX = factor IX, FIXa = activated FIX, FX = factor X, FXa = activated FX, FXI = factor XI, FXIa = activated FXI, FXII = factor FXII, FXIIa = activated factor XII, FXIII = factor XIII, FXIIIa = activated factor XIII, n.d. = not determined, ~ = no effect, VWF = von Willebrand factor, ↓ = 30% decrease, ↑ = < 2-fold increase, ↑↑ > 2-fold increase, ↑↑↑ > 3-fold increase. * only observed in in vivo experiments; ** only observed in in vitro experiments.