Haematological Consequences of Systemic Inflammation: A Critical Narrative Review of Pathophysiology, Clinical Manifestations, Biomarkers and Therapeutic Implications

Abstract

Inflammation is inseparable from blood-cell biology: circulating cells detect inflammatory cues, bone-marrow progenitors alter lineage output, erythroid iron supply is actively restricted, and haemostatic pathways can be recruited as components of host defence. Yet the expression “haematological inflammation” is used inconsistently and can obscure the distinction between adaptive haematopoietic responses, secondary cytopenias or cytoses, thrombo-inflammation, and primary haematological disease. This critical narrative review integrates mechanistic, translational and clinical evidence on the major ways systemic inflammation remodels haematopoiesis and peripheral blood phenotypes. Literature indexed from 1 January 2000 to 11 June 2026 was considered, with earlier work retained only when conceptually indispensable. The evidence indicates that acute inflammatory signalling can beneficially accelerate myeloid production and mobilise innate effector functions, whereas persistent interferon, interleukin-1, tumour necrosis factor and related signals can impose lineage bias, impaired stem-cell fitness and a marrow environment permissive to clonal selection. In erythropoiesis, the interleukin-6–hepcidin–ferroportin axis provides the strongest mechanistic link between inflammation and functional iron restriction, although shortened erythrocyte survival and direct cytokine-mediated suppression of erythropoiesis remain important. Platelets and neutrophil extracellular traps connect inflammation to coagulation, providing a biological continuum from protective immunothrombosis to sepsis-induced coagulopathy and disseminated intravascular coagulation. Common biomarkers, including C-reactive protein, erythrocyte sedimentation rate, ferritin, procalcitonin and cell-count ratios, are clinically useful only when interpreted as context-dependent signals rather than disease-specific tests. Therapeutic implications therefore differ by mechanism: control of the initiating disease remains primary, while cytokine blockade, manipulation of the hepcidin–ferroportin axis, and selective anti-thrombo-inflammatory strategies may be useful in defined phenotypes. The most important unresolved challenge is to distinguish adaptive, reversible inflammatory haematopoiesis from maladaptive programmes that become self-sustaining, clonal or organ-damaging.