Blood
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Calreticulin mutations (CALR(MUT)) are found in a significant proportion of patients with essential thrombocythemia (ET) lacking JAK2(V617F) or MPL mutations. They are associated with substantially different hematological and clinical features and define a distinct subtype of ET. ⋯ Neutrophil CALR(MUT) level was significantly higher than JAK2(V617F) level (median, 50% vs 18%; P < .0001), and wild-type myelopoiesis was suppressed in CALR(MUT) but not JAK2(V617F) patients. These data are suggestive of truly monoclonal hematopoiesis in CALR(MUT) patients and provide further evidence that the biology associated with CALR mutations is markedly different from that of JAK2(V617F) mutations.
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Multiple myeloma is a plasma cell malignancy in which significant advances have been observed during the last 15 years. Our understanding of the disease has been advanced through its molecular characterization. We have also seen improvements in patient care with the development of 2 new classes of active agents, proteasome inhibitors and immunomodulatory drugs (IMiDs), resulting in a significant improvement in overall survival of myeloma patients such that it can now be debated as to whether some subsets of myeloma patients can be cured. ⋯ Moreover, the molecular characterization of malignant plasma cells would not have predicted the effectiveness of these novel therapies. We hypothesize that proteasome inhibitors and IMiDs are highly active because malignant plasma cells are constrained by many of the characteristics of their normal counterparts and these novel therapies target both normal plasma cell biology and the cancer biology of myeloma. Thus, a better understanding of normal plasma cell biology will likely yield as many actionable targets as mapping the genomic landscape of this disease.
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Multicenter Study Clinical Trial
Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study.
This prospective, observational study investigated the utility of Fibtem A5 and Clauss fibrinogen as predictors of progression of postpartum hemorrhage (PPH). A consecutive cohort of 356 women experiencing 1000 to 1500 mL PPH was recruited. Fibtem and fibrinogen were measured and subsequent transfusions, invasive procedures, and bleed volume recorded. ⋯ Receiver operating characteristic area under the curve (95% CI) for progression to RBC transfusion was 0.67 (0.60-0.74) for fibrinogen and 0.61 (0.54-0.68) for Fibtem, and progression to >2500 mL was 0.71 (0.61-0.81) and 0.75 (0.66-0.85) for fibrinogen and Fibtem, respectively. Fibtem A5 <10 mm was associated with more prolonged bleeds (median [95% CI], 127 [44-210] compared with 65 [59-71] minutes; P = .018) and longer stay in the high-dependency unit (23.5 [18.4-28.5] compared with 10.8 [9.7-11.8] hours). Fibtem is a rapidly available early biomarker for progression of PPH.