Figure 3.
Platelets are crucial for VT that follows inhibition of antithrombin and protein C. (A) Blood platelet numbers in mice not receiving siRNAs 3 days after injection with saline (–αGP1b; open circles) or a rat monoclonal antibody targeting mouse GP1b (+αGP1b; filled circles). P = .036, Mann-Whitney rank sum test. (B) Scoring of the clinical phenotype in mice treated with siRNAs targeting Serpinc1 and Proc. Mice showing characteristic clinical coagulopathy (blue bar) and mice unaffected (red bars) 3 days after siRNA treatment (end of experiment). One of the mice from the –αGP1b group died as a result of the thrombotic coagulopathy. P = .001, Fisher’s exact test. (C-D) Representative thrombus in a vein in the mandibular area in the control group (–αGP1b, panel C) and a representative vein in the platelet-depleted group (+αGP1b, panel D) in the hematoxylin and eosin–stained sections. thr, thrombus, with typical fibrin layers; rbc, postmortem clotted blood, rich in red blood cells; mus, striated muscle tissue. White bars represent 100 μm. Supplemental Figure 7 presents enlargement of the images from both panels. (E) Descriptive scoring for the type of detected thrombi. 0: no thrombi found; I + II: thrombus categories were based on structure and layering. Blue bars: –αGP1b (n = 10); red bar: +αGP1b (n = 16). n.d., not detected. (F) Levels of fibrin deposition in the liver of the platelet-depleted group (+αGP1b) and the control group (–αGP1b). P = .001, Mann-Whitney rank sum test. Solid and dashed lines represent fibrin levels found in siNEG-injected C57BL/6J female mice (median and range, respectively, 4.5 ng/mg [3.1, 5.7]).