Effect of therapeutic plasma exchange on tissue factor and tissue factor pathway inhibitor in septic shock. Critical care (London, England) BACKGROUND:Coagulopathy is part of the pathological host response to infection in sepsis. Higher plasma concentrations of both tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are associated with occurrence of disseminated intravascular coagulation (DIC), multi-organ dysfunction and increased mortality in patients with sepsis. Currently no treatment approaches specifically targeting this axis are available. We hypothesize that therapeutic plasma exchange (TPE) might limit this coagulopathy by restoring the balance of plasma proteins. METHODS:This was a pooled post-hoc biobank analysis including 51 patients with early (shock onset < 24 h) and severe (norepinephrine dose > 0.4 μg/kg/min) septic shock, who were either receiving standard of care treatment (SOC, n = 14) or SOC + one single TPE (n = 37). Plasma concentrations of TF and TFPI were measured both at- and 6 h after study inclusion. The effect of TPE on concentrations of TF and TFPI was investigated and compared to SOC patients. Further, baseline TF and TFPI concentrations were used to modulate and predict clinical response to adjunctive TPE, indicated by longitudinal reduction of lactate concentrations over the first 24 h following study inclusion. RESULTS:TPE led to a significant reduction in circulating concentrations of both TF and TFPI while no difference was observed in the SOC group. Relative change of TF within 6 h was + 14 (-0.8 to + 30.4) % (p = 0.089) in the SOC and -18.3 (-32.6 to -2.2) % (p < 0.001) in the TPE group (between group p < 0.001). Similarly, relative change of TFPI was + 14.4 (-2.3 to + 30.9) % (p = 0.076) in the SOC and -20 (-32.8 to -7.9) % (p < 0.001) in the TPE group (between group p = 0.022). The ratio of TF to TFPI remained unchanged in both SOC and TPE groups. SOC patients exhibited an increase in lactate over the initial 24 h when TF and TFPI concentrations were higher at baseline. In contrast, patients undergoing TPE experienced a sustained longitudinal reduction of lactate concentrations across all levels of baseline TF and TFPI elevations. In a multivariate mixed-effects model, higher baseline TF (p = 0.003) and TFPI (p = 0.053) levels led to greater longitudinal lactate concentration reduction effects in the TPE group. CONCLUSIONS:Adjunctive TPE in septic shock is associated with a significant removal of both TF and TFPI, which may contribute to the early hemodynamic improvement observed in septic shock patients receiving TPE. Higher baseline TF (and TFPI) plasma concentrations were identified as a putative predictor of treatment response that could be useful for predictive enrichment strategies in future clinical trials. 10.1186/s13054-024-05142-4

Coagulation and fibrinolysis balance in disseminated intravascular coagulation. Onishi Tomoko,Ishihara Takashi,Nogami Keiji Pediatrics international : official journal of the Japan Pediatric Society BACKGROUND:Sepsis is a common underlying disease associated with disseminated intravascular coagulation (DIC). We have recently determined hemostatic pathological states at diagnosis through simultaneous assessment of coagulation and fibrinolysis potentials in sepsis-associated DIC using clot-fibrinolysis waveform analysis. Here we aimed to investigate hemostatic pathological states, focusing on the balance between coagulation and fibrinolysis dynamics during the clinical course in pediatric sepsis-associated DIC. METHODS:Coagulation and fibrinolysis potential functions in three pediatric patients with sepsis-associated DIC during their clinical course were quantified using clot-fibrinolysis waveform analysis. A maximum coagulation velocity (|min1|) and maximum fibrinolysis velocity (|FL-min1|) was calculated as a ratio relative to normal plasma. RESULTS:In case 1, coagulation-enhanced and fibrinolysis-depressed state (|min1|-ratio 2.22 and |FL-min1|-ratio 0.42) was observed on day 1. This discrepancy significantly reduced after anticoagulant therapy and plasma exchange on day 2. A well-balanced hemostatic state (0.70 and 0.62, respectively) was restored on day 7. In case 2, fibrinolysis-impaired state (|min1|-ratio 1.09 and |FL-min1|-ratio 0.21) was seen on day 1. The |min1| ratio was slightly prolonged and the |FL-min1| ratio was severely decreased. Both were restored on day 7 and returned to normal levels on day 12. In case 3, twofold coagulation- and fibrinolysis-enhanced states (|min1|-ratio 1.99 and |FL-min1|-ratio 1.11) were seen on day 1. However, both potentials rapidly decreased on day 2 (0.49 and 0.0, respectively). She died on day 5. CONCLUSIONS:The hemostatic pathological states in sepsis-associated DIC depend on disease progression. Comprehensive assessment of coagulation-fibrinolysis potentials over time may therefore be helpful in considering optimal treatment plans for sepsis-associated DIC. 10.1111/ped.14684

Cytokine Storm and Sepsis-Induced Multiple Organ Dysfunction Syndrome. Advances in experimental medicine and biology There is extensive overlap of clinical features among familial or primary HLH (pHLH), reactive or secondary hemophagocytic lymphohistiocytosis (sHLH) [including macrophage activation syndrome (MAS) related to rheumatic diseases], and hyperferritinemic sepsis-induced multiple organ dysfunction syndrome (MODS); however, the distinctive pathobiology that causes hyperinflammatory process in each condition requires careful considerations for therapeutic decision-making. pHLH is defined by five or more of eight HLH-2004 criteria [1], where genetic impairment of natural killer (NK) cells or CD8+ cytolytic T cells results in interferon gamma (IFN-γ)-induced hyperinflammation regardless of triggering factors. Cytolytic treatments (e.g., etoposide) or anti-IFN-γ monoclonal antibody (emapalumab) has been effectively used to bridge the affected patients to hematopoietic stem cell transplant. Secondary forms of HLH also have normal NK cell number with decreased cytolytic function of varying degrees depending on the underlying and triggering factors. Although etoposide was uniformly used in sHLH/MAS in the past, the treatment strategy in different types of sHLH/MAS is increasingly streamlined to reflect the triggering/predisposing conditions, severity/progression, and comorbidities. Accordingly, in hyperferritinemic sepsis, the combination of hepatobiliary dysfunction (HBD) and disseminated intravascular coagulation (DIC) reflects reticuloendothelial system dysfunction and defines sepsis-associated MAS. It is demonstrated that as the innate immune response to infectious organism prolongs, it results in reduction in T cells and NK cells with subsequent lymphopenia even though normal cytolytic activity continues (Figs. 30.1, 30.2, 30.3, and 30.4). These changes allow free hemoglobin and pathogens to stimulate inflammasome activation in the absence of interferon-γ (IFN-γ) production that often responds to source control, intravenous immunoglobulin (IVIg), plasma exchange, and interleukin 1 receptor antagonist (IL-1Ra), similar to non-EBV, infection-induced HLH. 10.1007/978-3-031-59815-9_30

Plasma exchange in acute hemolytic reaction due to ABO-incompatible erythrocyte concentrate transfusions: Single center experience. Transfusion medicine (Oxford, England) OBJECTIVES:Acute hemolytic transfusion reaction (AHTR) due to ABO-incompatible erythrocyte concentrate (EC) is one of the most catastrophic complications of transfusion. Since the hemolysis is intravascular; hemoglobinemia and hemoglobinuria result in disseminated intravascular coagulation (DIC), acute renal failure, shock, and sometimes death. BACKGROUND:Treatment of AHTR is mostly supportive measures. Today there are no clear suggestions about plasma exchange (PE) in these patients. METHODS/MATERIALS:Here we report our experience with six patients diagnosed with AHTR due to ABO-incompatible EC transfusion. RESULTS:We performed PE in 5 of these patients. Although all of our patients were geriatric and most of them had significant comorbidities four out of five patients recovered without an incident. CONCLUSION:Although PE is considered a last-chance treatment when other measures fail in the literature, our experience above indicates that it must be evaluated in every patient with AHTR early in the course. If the patient has cardiac and renal comorbidities, large volume EC is transfused, DAT is negative, plasma color is red and there is macroscopic hemoglobinuria, we suggest performing PE. 10.1111/tme.12982

Therapeutic Plasma Exchange Protects Patients with Sepsis-Associated Disseminated Intravascular Coagulation by Improving Endothelial Function. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis The mortality rate of sepsis-associated disseminated intravascular coagulation (DIC) is high. This study aimed to explore the efficacy of therapeutic plasma exchange (TPE) in sepsis-associated DIC patients by improving endothelial function. A total of 112 sepsis-associated DIC patients were randomly divided into the TPE group (n = 40), the heparin (HP) group (n = 36), and the SHAM group (n = 36). The SHAM group received conventional treatment; the HP group was treated with HP based on conventional treatment; and the TPE group received conventional treatment plus TPE. The differences in thromboelastogram (TEG), platelet (PLT), coagulation function, and the endothelial cell (EC) injury biomarkers at 6 h, 24 h, 48 h, 72 h, and 7 days after TPE were compared among the three groups, and the three groups were compared in terms of Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sepsis-Related Organ Failure Assessment (SOFA) score, the length of intensive care unit (ICU) hospitalization, 28-day mortality rate, 28-day cumulative survival rate, the incidence of bleeding events, the incidence of acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS). The efficacy of TPE is superior to the HP in increasing PLT, improving coagulation function, increasing the 28-day cumulative survival rate, and reducing the length of ICU hospitalization, 28-day mortality, and the incidence of bleeding events, AKI, and ARDS with statistically significant differences (  .05). Moreover, the effect of TPE outperforms HP on the EC injury biomarkers with statistically significant differences (  .05). Our results suggest that TPE may be more effective than HP in the treatment of patients with sepsis-associated DIC. The possible mechanism is via improving endothelial function. 10.1177/10760296211053313