Platelets, 2011, 1–2, Early Online Copyright ! 2011 Informa UK Ltd. ISSN: 0953-7104 print/1369-1635 online DOI: 10.3109/09537104.2011.553970
LETTER TO THE EDITOR
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The correlation between platelet activation markers and HMGB1 in patients with disseminated intravascular coagulation and hematologic malignancy SHOSAKU NOMURA1, SHINYA FUJITA1, RYOTARO OZASA1, TAKAHISA NAKANISHI1, MICHIHIKO MIYAJI1, SHINICHIRO MORI1, TOMOKI ITO1, & KAZUYOSHI ISHII2 1
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan and 2Division of Hematology, Kishiwada City Hospital, Osaka, Japan
Keywords: Microparticle, HMGB1, DIC, hematologic malignancy, recombinant, thrombomodulin
To the editor Disseminated intravascular coagulation (DIC) frequently complicates hematologic malignancy and infections [1]. Coagulation abnormalities and thrombocytopenia are common in DIC, and the extent of hemostatic disorders appears to correlate with disease severity [2]. In particular, low platelet count is predictive of poor outcome [3, 4]. In DIC patients, the thrombin generated may react with thrombin receptors (PAR-1) located on the platelets and result in platelet activation. On the other hand, high mobility group-B1 DNA binding protein (HMGB1) is a nuclear architectural chromatin binding protein released by necrotic cells that has been identified as a mediator of endotoxin-induced lethality, and acts at least in part as a proinflammatory cytokine [5–7]. Moreover, HMGB1 also plays a role in the pathogenesis of DIC because plasma HMGB1 levels correlate with DIC scores [8]. However, the significance of activated platelets related to HMGB1 in DIC patients is poorly understood. Here, we describe the correlation between platelet activation markers and HMGB1 in DIC patients with hematologic malignancy. In addition, we investigated the effect of recombinant thrombomodulin (rTM) on these markers. Patients with DIC associated with hematologic malignancy were recruited. DIC was diagnosed according to the diagnostic criteria established by
the Japanese Ministry of Health, Labor and Welfare [9]. In total, 45 patients comprised of 27 males and 18 females were enrolled. The median age was 54 years (range 21–78 years). Serum samples collected at baseline and 14 days after rTM therapy were tested by ELISA for antibodies against the markers. All ELISA kits were used according to the manufacture’s instructions. For DIC patients with hematologic malignancy, univariate analysis showed that prothrombin time (PT), fibrinogen, C-reactive protein (CRP), plateletderived microparticle (PDMP), soluble CD40 ligand (sCD40L), interleukin (IL)-6, and tissue necrotizing factor (TNF)! regulated on activation of normal T-cell expressed and secreted (RANTES) and monocyte chemotactic peptide-1 (MCP-1) were significantly associated with HMGB1 (Table I). In addition, fibrinogen, CRP, PDMP, sCD40L, TNF! and RANTES were significant factors in the multivariate model with HMGB1 (Table I). DIC patients exhibited a significant decrease in HMGB1 levels after rTM therapy (before vs. after, 26.3 ! 8.4 vs. 12.1 ! 5.9 ng/ ml, p < 0.001). In addition, the levels of platelet activation markers and cytokines were significantly decreased after rTM therapy in DIC patients (before vs. after, PDMP: 19.9 ! 3.3 vs. 11.7 ! 2.9 U/ml, p < 0.001; sCD40L: 3.45 ! 1.18 vs. 2.00 ! 0.79 ng/ml, p < 0.001; RANTES: 92.6 ! 14.5 vs.
Correspondence: Shosaku Nomura, First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8507, Japan. E-mail:
[email protected] (received 9 January 2011; accepted 10 January 2011)
2
S. Nomura et al.
Table I. Univariate and multivariate analysis on HMGB1. Univariate
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Analysis Age (years) PLT("104/ml) WBC (/ml) PT (%) APTT (sec) Fbg (mg/dl) FDP (mg/dl) D-dimer (mg/dl) ATIII (mg/dl) LDH (mg/dl) CRP (mg/dl) PDMP (U/ml) SCD40L (ng/ml) IL-6 (pg/ml) TNF ! (pg/ml) RANTES (ng/ml) MCP-1 (pg/ml)
"
p value
0.0533 #0.0395 #0.0240 #0.1125 0.0037 0.4396 #0.0654 #0.0356 #0.0034 0.1702 0.6506 0.3971 0.4826 0.4071 0.4303 0.3896 0.2295
0.21824 0.25213 0.30808 0.04915* 0.74391 0.00014* 0.23196 0.37801 0.78381 0.31774
