VWF multimer analysis in patients with CALI who were not treated with bevacizumab.

<p>VWF multimer analysis was performed in 4 representative patients out of 6 patients with CALI not treated with bevacizumab. These patients developed CALI during month 3 or 4. UL-VWFMs were found before and during CALI in all patients. Decreased levels of H-VWFMs were found in Patient 4 at months 0 and 1, and in Patient 17 at month 2. VWF von Willebrand factor, CALI chemotherapy-associated liver injury, UL-VWFMs unusually-large VWF multimers, H-VWFM high molecular weight VWF multimers, AST aspartate transaminase, T-Bil total bilirubin, VWF:Ag VWF antigen, VWF:CB VWF collagen binding activity.</p

Comparison of platelet count, VWF:Ag, ADAMTS13:AC, AST, and T-Bil between patients treated with and not treated with bevacizumab.

<p>(A) Platelet counts decreased until months 3 as the number of chemotherapy cycles increased in both patients who received and did not receive bevacizumab. However, platelet counts in patients not treated with bevacizumab decreased much less in patients who received bevacizumab in months 5. (B) Plasma levels of VWF:Ag increased as the number of chemotherapy cycles increased in patients not treated with bevacizumab, but did not change in patients treated with bevacizumab. (C) Plasma levels of ADAMTS13:AC were unchanged in both groups. (D) Serum AST levels increased as the number of chemotherapy cycles in patients who did not receive bevacizumab, but they were unchanged in patients with bevacizumab. (E) Plasma levels of T-Bil did not change significantly in either group. VWF:Ag von Willebrand factor antigen, ADAMTS13:AC ADAMTS13 activity, AST Aspartate transaminase, T-Bil total bilirubin.</p

Clinical characteristics, chemotherapy regimen, response of chemotherapy and spleen size ratio.

<p>^# tumor response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). (response)</p><p>^## the spleen size ratio was the ratio of spleen size after chemotherapy to those before chemotherapy (spleen size ratio)</p><p>* unresectable metastatic colorectal cancer (UMCRC)</p><p>** recurrence (rec.)</p><p>Patients 18 through 23 were treated without bevacizumab.</p><p>Clinical characteristics, chemotherapy regimen, response of chemotherapy and spleen size ratio.</p

VWF multimer analysis in patients without CALI who were not treated with bevacizumab.

<p>Results of VWF multimer analysis in 4 representative patients out of 11 patients without CALI not treated with bevacizumab are shown. UL-VWFMs were found in Patients 10, 14, and 15, who did not develop CALI. In Patient 10, decreased levels of H-VWFMs were observed during months 1 and 4. VWF von Willebrand factor, CALI chemotherapy-associated liver injury, UL-VWFMs unusually-large VWF multimers, H-VWFM high molecular weight VWF multimers, AST aspartate transaminase, T-Bil total bilirubin, VWF:Ag VWF antigen, VWF:CB VWF collagen binding activity.</p

Immunohistochemical analysis of liver specimens in patients with SOS.

<p>Histological findings in the liver with hematoxylin and eosin (H. E.) staining in Patient 4 included extensive Grade 2 sinusoidal dilatation (A) and platelet thrombi in the liver sinusoids, as indicated with white arrows (B). Many of these thrombi were positive for both platelet-specific anti-IIb/IIIa (C, D) and anti-VWF (E), which showed that they are platelet thrombi, as indicated with arrows. Some thrombi were positive for fibrinogen (F), which indicated that they are fibrinogen thrombi, but there were much less frequently observed than platelet thrombi.</p

Comparison of platelet count, VWF:Ag, ADAMTS13:AC, and AST between patients with splenomegaly and those without splenomegaly.

<p>(A) Platelet counts decreased as the number of chemotherapy cycles increased in patients with and without splenomegaly. (B) Plasma levels of VWF antigen (:Ag) increased as the number of chemotherapy cycles increased in patients with splenomegaly. (C) Plasma levels of ADAMTS13:AC were unchanged in both groups. (D) Plasma levels of aspartate transaminase (AST) increased as the number of chemotherapy cycles increased in patients with splenomegaly, but not in patients without splenomegaly. VWF:Ag von Willebrand factor antigen, ADAMTS13:AC ADAMTS13 activity, AST Aspartate transaminase.</p