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BLOOD COMMENTARIES

HOW I TREAT

Stanworth and Shah use clinical vignettes to highlight challenges in deciding when to transfuse patients with platelets. The authors review the latest data on the drawbacks and benefits of platelet transfusion and focus particularly on the use of platelet transfusions as prophylaxis against bleeding and in critically ill patients with bleeding. They succinctly place the best evidence into context and propose a risk-adapted approach in different scenarios.

LYMPHOID NEOPLASIA

The second most common peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), arises from T-follicular helper cells in the context of age-related clonal hematopoiesis. Fujisawa and colleagues utilized single cell analyses of primary samples and murine models to reveal that TET methylcytosine dioxygenase 2 (TET2) mutations within clonal B cells in the tumor microenvironment are necessary for facilitating TET2-mutated AITL. Their data also suggest a novel therapeutic possibility.

Cardiac involvement with immunoglobulin light chain amyloidosis is associated with a dismal prognosis. Basset et al report on an analysis of 249 patients with newly diagnosed stage IIIb cardiac amyloidosis, identifying that early cardiac response is possible in some patients with advanced disease and that survival can be predicted by grading cardiac and hematological response at 90 days.

RED CELLS, IRON, AND ERYTHROPOIESIS

Patients with sickle cell disease (SCD) have more inflammation than patients with other hemoglobinopathies associated with intravascular hemolysis. Allali and colleagues address this conundrum, demonstrating that free hemoglobin S (HbS) leads to substantially greater toll-like receptor 4 (TLR4)-mediated monocyte activation and inflammatory cytokine production than hemoglobin A, despite differing by only 1 amino acid. In vivo, free HbS activates both NF-κB and the type I interferon pathways, and this can be blocked by TLR4 inhibitors.

THROMBOSIS AND HEMOSTASIS

In acquired hemophilia A, autoantibodies block factor VIII leading to severe bleeding requiring expensive hemostatic therapy. Immunosuppression is needed. However, this regimen can be slow to resolve the problem, and it is associated with substantial toxicity. Simon et al describe a novel regimen comprising of standard immunosuppressive drugs that yields excellent results (97% complete response rate), including control of bleeding within a median of 16 days and with acceptable toxicity.

LETTERS TO BLOOD

Two Letters to Blood address the risks of COVID-19 in populations with precursors of hematological disease. In the first article, Miller and colleagues report on whether clonal hematopoiesis of intermediate potential (CHIP) is associated with adverse outcomes with COVID-19, finding no association between CHIP and 28-day mortality while providing data indirectly linking IL-6 signaling and patient outcomes. In the second article, Ho and colleagues investigate the outcomes of patients with monoclonal gammopathy of undetermined significance (MGUS) with COVID-19, reporting that one-fourth had a severe infection and that on multivariable analysis, adverse outcomes are more likely if immunoparesis is present.

Two Letters to Blood address the risks of COVID-19 in populations with precursors of hematological disease. In the first article, Miller and colleagues report on whether clonal hematopoiesis of intermediate potential (CHIP) is associated with adverse outcomes with COVID-19, finding no association between CHIP and 28-day mortality while providing data indirectly linking IL-6 signaling and patient outcomes. In the second article, Ho and colleagues investigate the outcomes of patients with monoclonal gammopathy of undetermined significance (MGUS) with COVID-19, reporting that one-fourth had a severe infection and that on multivariable analysis, adverse outcomes are more likely if immunoparesis is present.

BLOOD WORK

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