The hematologic consequences of obesity

Abstract

The prevalence of obesity is increasing and progressively influencing physician-patient interactions. While there is a sizable amount of data demonstrating that obesity is a state of low-grade inflammation, to our knowledge, there is no single review summarizing its effects on hematologic parameters and thrombotic risk. We performed a literature search which largely surfaced observational studies, with a few systematic reviews and meta-analyses of these studies. We took care to review the mechanisms driving an inflammatory state and obesity's effect on white blood cells, red blood cells, platelets, and thrombotic risk. There is an observed relative, and sometimes absolute leukocytosis driven by this inflammatory state. Obesity is also associated with increased platelet counts and an increased risk for venous thromboembolism (VTE). Lastly, the association between obesity, iron deficiency (ID), and red blood cell counts may be present but remains uncertain. Recognizing the above associations may provide clinicians with reassurance regarding otherwise unexplained hematologic abnormalities in obese individuals. We hope this review will prompt future studies to further understand the underlying mechanisms driving these abnormalities and identify modifiable risk factors and potential therapeutic targets to prevent the development of probable obesity-associated conditions with significant morbidity and mortality, such as ID and VTE.

Keywords: anemia; iron deficiency; leukocytosis; thrombocytosis; venous thromboembolism.

Conflict of interest statement

Conflict-of-interest disclosure: J.J.S. is a consultant for Aronora, Inc. The remaining authors declare no potential conflict of interest.

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Figures

Figure 1:

In hematopoiesis, leptin significantly stimulates the appearance of granulocyte-macrophage colonies (CFU-GM), the precursor for monocytes and granulocytes. CFU-EO = colony forming uniteosinophils; CFU-GM = colony forming unit-granulocyte, macrophage; CFU-MEG = colony forming unitmegakaryocyte; BFU-E, burst-forming unit-erythroid; LepR = leptin receptor. All figures were created with BioRender.com

Figure 2:

Hepcidin expression has been shown to be increased in obese individuals and correlates with inflammation, mainly driven by IL-6. Leptin also stimulates hepcidin expression. Additionally, adipose tissue has been shown to express hepcidin itself, marking hepcidin as an adipokine. Fpn-1 = ferroportin-1. All figures were created withBioRender.com

Figure 3:

PAI-1, which blocks the activation of fibrinolysis, correlates with BMI and has been shown to be produced in adipose tissue. PAI-1 = Plasminogen activator inhibitor-1; tPA = tissue plasminogen activator; FDP = fibrin degradation products. All figures were created withBioRender.com

Figure 4:

Platelet hyperactivity has been noted in obese individuals, as reflected by urinary excretion of 11-dehyhdro-TxB2, the major metabolite of TXA2. BMI has been associated with increased levels of CD40-L and P-selectin, as well as positively correlated with mean platelet volume, an emerging risk factor for thrombotic disease, and pMPs, markers of platelet activation. GPIb = Glycoprotein Ib; vWF = von Willebrand factor; ADP = Adenosine diphosphate; GPIIB/IIIa = glycoprotein IIb/IIIa; pMP = platelet-derived microparticles; MPV = mean platelet volume; TXA2 = Thromboxane A2; AA = arachidonic acid; COX-1 = Cyclooxygenase-1; 11-dehydro-TXB2 = 11-Dehydrothromboxane B2. All figures were created withBioRender.com