Both disseminated intravascular coagulation (DIC) and thrombotic microangiopathy (TMA) cause microvascular thrombosis associated with thrombocytopenia, bleeding tendency and organ failure. The frequency of DIC is higher than that of thrombotic thrombocytopenic purpura (TTP). Many patients with TMA are diagnosed with DIC, but only about 15% of DIC patients are diagnosed with TMA. Hyperfibrinolysis is observed in most patients with DIC, and microangiopathic hemolytic anemia is observed in most patients with TMA. Markedly decreased ADAMTS13 activity, the presence of Shiga-toxin-producing Escherichia coli (STEC) and abnormality of the complement system are useful for the diagnosis of TTP, STEC-hemolytic uremic syndrome (HUS)and atypical HUS, respectively. However, there are no specific biomarkers for the diagnosis of DIC. Although DIC and TMA are similar appearances, all coagulation, fibrinolysis and platelet systems are activated in DIC, and only platelets are markedly activated in TMA.

Clinical application of platelet-rich plasma is gaining popularity in treating low back pain (LBP). This study investigated the efficacy and safety of platelet-rich plasma releasate (PRPr) injection into degenerated discs of patients with discogenic LBP. A randomized, double-blind, active-controlled clinical trial was conducted. Sixteen patients with discogenic LBP received an intradiscal injection of either autologous PRPr or corticosteroid (CS). Patients in both groups who wished to have PRPr treatment received an optional injection of PRPr eight weeks later. The primary outcome was change in VAS from baseline at eight weeks. Secondary outcomes were pain, disability, quality of life (QOL), image analyses of disc degeneration, and safety for up to 60 weeks. The VAS change at eight weeks did not significantly differ between the two groups. Fifteen patients received the optional injection. Compared to the CS group, the PRPr group had a significantly improved disability score at 26 weeks and walking ability scores at four and eight weeks. Radiographic disc height and MRI grading score were unchanged from baseline. PRPr caused no clinically important adverse events. PRPr injection showed clinically significant improvements in LBP intensity equal to that of CS. PRPr treatment relieved pain, and improved disability and QOL during 60 weeks of observation.

Object: Although thrombin burst has attracted attention as a physiological coagulation mechanism, clinical evidence from a routine assay for it is scarce. This mechanism was therefore evaluated by a clot waveform analysis (CWA) to assess the thrombin time (TT). Material and Methods: The TT with a low concentration of thrombin was evaluated using a CWA. We evaluated the CWA-TT of plasma deficient in various clotting factors, calibration plasma, platelet-poor plasma (PPP), and platelet-rich plasma (PRP) obtained from healthy volunteers, patients with thrombocytopenia, and patients with malignant disease. Results: Although the TT-CWA of calibration plasma was able to be evaluated with 0.01 IU/mL of thrombin, that of FVIII-deficient plasma could not be evaluated. The peak time of CWA-TT was significantly longer, and the peak height significantly lower, in various deficient plasma, especially in FVIII-deficient plasma compared to calibration plasma. The second peak of the first derivative (1st DP-2) was detected in PPP from healthy volunteers, and was shorter and higher in PRP than in PPP. The 1st DP-2 was not detected in PPP from patients with thrombocytopenia, and the 1st DP-2 in PRP was significantly lower in patients with thrombocytopenia and significantly higher in patients with malignant disease than in healthy volunteers. Conclusion: The CWA-TT became abnormal in plasma deficient in various clotting factors, and was significantly affected by platelets, suggesting that the CWA-TT may be a useful test for hemostatic abnormalities.

We investigated the involvement of CXCL12–CXCR4 interactions in human lymphohematopoiesis by coculture with telomerized human stromal cells. CXCR4 expression was low in CD34⁺CD38⁻CD45RA⁻CD10⁻CD7⁻CD19⁻ immature hematopoietic stem/precursor cells (HSPCs) but higher in CD34⁺CD38⁻CD45RA⁺CD10⁺CD7^+/−CD19⁻ early lymphoid precursors and even higher in CD34⁺CD38⁺CD45RA⁺CD10⁺CD7⁻CD19⁺ pro-B cells. Inhibition of the effect of stromal cell–produced CXCL12 by an anti-CXCR4–blocking Ab suppressed the generation of CD45RA⁺CD10⁻CD7⁺CD19⁻ early T lymphoid precursors (ETPs) and CD45RA⁺CD10⁺CD7⁻CD19^+/− B lymphoid precursors on stromal cells, but it did not affect the generation of ETPs in conditioned medium of stromal cell cultures. Replating assays showed that contact with stromal cells was critical for HSPC-derived CD45RA⁺CD10⁺CD7⁻CD19⁻ B lineage–biased precursors to differentiate into CD19⁺ pro-B cells, which was suppressed by the anti-CXCR4 Ab. Conversely, HSPC-derived ETPs possessed T and B lymphoid and monocytic differentiation potential; stromal cell contact was not required for their growth but rather promoted B lymphoid differentiation. The anti-CXCR4 Ab did not affect the growth of ETPs in conditioned medium, but it suppressed their B lymphoid differentiation on stromal cells. CD14⁻CD11c⁻HLA-DR⁺CD123^highCD303⁺ plasmacytoid dendritic cells developed from HSPCs and ETPs exclusively in contact with stromal cells, which was suppressed by the anti-CXCR4 Ab. These data indicate that CXCL12 plays an essential role in stromal cell contact–mediated B lymphoid and plasmacytoid dendritic cell differentiation from immature hematopoietic and early T lymphoid precursors with a multilineage differentiation potential, but it does not participate in contact-independent generation of early T lymphoid precursors.

Disseminated intravascular coagulation (DIC) is induced by excess activation coagulation, and activated platelets are also involved in pathogenesis. Therefore, plasma levels of soluble C-type lectin-like receptor 2 (sCLEC-2), a new marker for platelet activation, can be expected as a marker of DIC in critically ill patients. Plasma levels of sCLEC-2 and D-dimer were measured using the STACIA system. Plasma sCLEC-2 and D-dimer levels were significantly higher in patients with underlying diseases of DIC than in those with unidentified clinical syndrome (UCS). Plasma sCLEC-2 levels were significantly higher in the patients with DIC and Pre-DIC than in those without DIC or Pre-DIC. Similarly, plasma D-dimer levels were also significantly higher in patients with DIC and Pre-DIC than in those without DIC or Pre-DIC. The plasma sCLEC-2 levels in all patients and those with a DIC score ≤ 4 were significantly higher in non-survivors than survivors. The plasma D-dimer levels in all patients, those with a DIC score ≥ 5 and those with a DIC score ≤ 4, were significantly higher in non-survivors than in survivors. The plasma sCLEC-2 is expected as a marker for DIC/Pre-DIC as well as the prognostic marker in critically ill patients.