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BLOOD COMMENTARIES

PLENARY PAPER

Sepsis stimulates both innate immunity and the coagulation cascade, and overactivation of coagulation can lead to disseminated intravascular coagulation (DIC). In a study reported in this Plenary Paper, Yang et al demonstrated the role of type 1 interferons in increasing the procoagulant activity of tissue factor, elucidating the pathophysiology of sepsis-related DIC and a pathway for novel preventive therapies.

CLINICAL TRIALS AND OBSERVATIONS

Scleromyxedema is a rare skin and systemic disorder associated with monoclonal gammopathy. In a retrospective study of 33 patients, the authors documented the efficacy of intravenous immunoglobulin in the treatment of mild and moderate cases of scleromyxedema and of antimyeloma therapy in severe cases.

HEMATOPOIESIS AND STEM CELLS

Hematopoietic stem cell transplantation (HSCT) depends on engraftment and proliferation of donor HSCs. Morales-Hernández and colleagues report that GPRASP proteins are negative regulators of HSCs and that silencing of Gprasp1 or Gprasp2 increases HSC survival, engraftment, and proliferation through downregulation of CXCR4. These findings suggest that disruption of this pathway could enhance HSCT.

LYMPHOID NEOPLASIA

While survival for pediatric, adolescent, and young-adult Burkitt lymphoma/leukemia (BL) is over 90%, the prognosis for those with relapsed or primary refractory disease is extremely poor. Woessmann et al reviewed the 3-year survival of 157 out of 1979 children (8%) and adolescents with relapsed or refractory BL and identified risk factors for the failure of intensive salvage therapy and stem cell transplantation.

MYELOID NEOPLASIA

PLATELETS AND THROMBOPOIESIS

RED CELLS, IRON, AND ERYTHROPOIESIS

Anemia increases with age and one-third of cases are unexplained. The authors examined the relationship of clonal hematopoiesis (CH) to the anemia of aging. While common age-related mutations were not increased in the anemia population, deleterious mutations, including TP53 and SF3B1, were increased. However, the higher prevalence of CH was insufficient to account for unexplained anemia, the etiology of which remains elusive.

THROMBOSIS AND HEMOSTASIS

Rapid diagnosis of heparin-induced thrombocytopenia (HIT) improves patient management and avoids unnecessary exposure to direct thrombin inhibitors. Marchetti et al present a diagnostic algorithm for HIT using a Bayesian combination of pretest probability and rapid immunoassay results. This algorithm allows identification of HIT within 60 minutes.

LETTER TO BLOOD

The authors report on 3 patients who developed leukemia following allogeneic HSCT for sickle cell disease (SCD). All 3 patients had experienced graft failure; the 2 for whom DNA was available for next-generation sequencing were found to have preexisting TP53 mutations with a variant allele fraction that increased following HSCT graft failure.

BLOOD WORK

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