Objectives: To characterize the prevalence, incidence, and temporal evolution of thrombocytopenia (platelets < 100 × 109/L) in septic shock and to investigate the independent association of thrombocytopenia on clinical outcomes. Design: Retrospective, propensity-matched, cohort study. Setting: Two academic ICUs in Winnipeg, Canada. Patients: Nine-hundred eighty adult patients diagnosed with septic shock between 2007 and 2012. Interventions: Propensity-matched cohort analysis and Cox proportional hazard model evaluating thrombocytopenia over time. Measurements and Main Results: Of 980 adults, 165 patients (16.8%) had thrombocytopenia at ICU admission (prevalent), whereas 271 (27.7%) developed thrombocytopenia during ICU admission (incident). Among patients with incident thrombocytopenia, the median time from ICU admission to thrombocytopenia was 2 days (interquartile range, 1–3 d). Among survivors, the median time from incident thrombocytopenia to platelet recovery was 6 days (interquartile range, 4–8 d). The median time from liberation of vasopressors to recovery of platelets concentration (≥ 100 × 109/L) was 2 days (interquartile range, 0–4 d). In a propensity-matched analysis, thrombocytopenia was associated with increased durations of ICU length of stay (9 vs 6 d; p < 0.01), mechanical ventilation (7 vs 4 d; p < 0.01), and vasopressor use (4 vs 3 d; p < 0.01), as well as increased major bleeding events (41% vs 18%; p < 0.01). In an adjusted Cox proportional hazards model, thrombocytopenia was significantly associated with both increased ICU mortality (hazard ratio, 1.99; 95% CI, 1.51–2.63) and hospital mortality (hazard ratio, 1.93; 95% CI, 1.48–2.51). Conclusions: Both the prevalence and incidence of thrombocytopenia are high in septic shock. Incident thrombocytopenia occurs early in septic shock, and platelet recovery lags behind clinical recovery. In septic shock, thrombocytopenia is associated with increased length of stay, longer duration of organ support, major bleeding events, and mortality.

Early administration of intravenous therapeutic dose unfractionated heparin may be associated with decreased mortality when administered to patients diagnosed with septic shock, especially in patients with higher severity of illness. Prospective randomized trials are needed to further define the role of this agent in sepsis and septic shock.

Heparin-induced thrombocytopenia is a serious complication of heparin therapy that can lead to thromboembolism, cardiovascular events, and death. Hemodialysis patients are repeatedly exposed to heparin and are at risk for developing antibodies to the platelet factor 4-heparin (PF4-H) complex. We sought to determine the association between PF4-H antibodies and mortality in a prospective cohort of 419 asymptomatic hemodialysis patients. Pre-dialysis blood samples were screened for nonspecific PF4-H antibodies, and all positive and indeterminate samples were subsequently tested using immunoglobulin (Ig)G-specific PF4-H and platelet serotonin-release assays. During a median follow-up of 2.5 years there were 129 all-cause deaths. After controlling for potential confounding variables, the relative risk of death was significantly increased for patients with IgG-specific PF4-H antibodies and further elevated with an indeterminate serotonin-release assay. Our study suggests that IgG-specific PF4-H antibody formation is associated with increased mortality in hemodialysis patients.

Genetic factors are thought to contribute to the pathogenesis of acute myocardial infarction (AMI). A common variant of factor XIII (FXIII), FXIII Val34Leu, may be protective against developing an AMI, but various studies show conflicting results. We performed a meta-analysis to determine whether the FXIII Val34Leu variant is associated with a decreased risk of AMI. One hundred ninety-five articles were reviewed and 12 case-control studies were selected. We included studies involving patients with objectively diagnosed AMIs (WHO criteria), provided that FXIII Val34Leu genotyping data were available. Inclusion decisions, quality assessment, and data extraction were conducted by two reviewers. Hypothesizing that the Leu allele was protective, we performed three analyses with the Val/Val genotype as the reference group. Pooled odds ratios (OR) and their 95% confidence intervals (95% CI) were determined. Prior to pooling, heterogeneity testing was performed using the I(2) statistic. These studies included a total of 8,743 patients, of which 3,663 were AMI patients and 5,080 were healthy controls. Using the random effects methods, protective effects were seen with the Leu/Val genotype alone (OR 0.79, 95% CI 0.68-0.93) and with Leu/Val and Leu/Leu genotypes combined (OR 0.79, 95% CI 0.66-0.93). There was also a protective effect with the Leu/Leu genotype alone, (not statistically significant: OR 0.83, 95% CI 0.61-1.12), likely due to the low frequency of this genotype. These results suggest that there is an association between the factor XIII Leu allele and a modest protective effect against AMI and may provide useful information in profiling susceptibility to myocardial infarction.

Early administration of low-dose corticosteroid is not associated with decreased mortality when it is administered to unselected patients with septic shock. A beneficial effect of low-dose corticosteroid on mortality may exist in patients with the highest severity of illness. Future trials of low-dose corticosteroid in septic shock should consider restricting the study population to this cohort.