Review
The Hematologic System as a Marker of Organ Dysfunction in Sepsis

https://doi.org/10.4065/78.7.869Get rights and content

Sepsis with acute organ dysfunction (severe sepsis) results from a systemic proinflammatory and procoagulant response to infection. Organ dysfunction in the patient with sepsis is associated with increased mortality. Although most organs have discrete anatomical boundaries and carry out unified functions, the hematologic system is poorly circumscribed and serves several unrelated functions. This review addresses the hematologic changes associated with sepsis and provides a framework for prompt diagnosis and rational drug therapy. Data sources used include published research and review articles in the English language related to hematologic alterations in animal models of sepsis and in critically ill patients. Hematologic changes are present in virtually every patient with severe sepsis. Leukocytosis, anemia, thrombocytopenia, and activation of the coagulation cascade are the most common abnormalities. Despite theoretical advantages of using granulocyte colony-stimulating factor to enhance leukocyte function and/or circulating numbers, large clinical trials with these growth factors are lacking. Recent studies support a reduction in the red blood cell transfusion threshold and the use of erythropoietin treatment to reduce transfusion requirements. Treatment of thrombocytopenia depends on the cause and clinical context but may include platelet transfusions and discontinuation of heparin or other inciting drugs. The use of activated protein C may provide a survival benefit in subsets of patients with severe sepsis. The hematologic system should not be overlooked when assessing a patient with severe sepsis. A thorough clinical evaluation and panel of laboratory tests that relate to this organ system should be as much a part of the work-up as taking the patient's blood pressure, monitoring renal function, or measuring liver enzymes.

Section snippets

HEMATOLOGIC CHANGES IN SEPSIS-ADAPTATION VS DYSFUNCTION

There are 2 components to the host response, a nonspecific innate immune response and a specific or acquired immune response. The innate immune response (or acute phase response) is a highly evolutionarily conserved mechanism that serves to combat pathogens, minimize tissue injury, promote host recovery, and set the stage for the acquired immune response.3, 4 Innate immunity involves the coordinated activity of both cells and proteins (Figure 1). The principal cellular and soluble effectors are

Incidence

In patients with sepsis, the white blood cell count is normally elevated (leukocytosis). This observation is sup-ported in animal models of sepsis in which administration of endotoxin results in pronounced leukocytosis.5 The leukocyte differential count typically reveals increased numbers of neutrophils (neutrophilia).6 Occasionally, the degree of leukocytosis is extreme, with white blood cell counts of more than 50 × 109/L (leukemoid reaction). In some cases, sepsis is associated with a

Red Blood Cell Deformability

Sepsis-induced changes in the mechanical and membrane properties of red blood cells lead to decreased deformability.29, 30, 31 The mechanism is unclear but may involve membrane damage from reactive oxygen species derived from circulating leukocytes and ischemic tissues.32, 33 Red blood cell deformability is an important determinant of blood flow, particularly in the microcirculation.34, 35 Indeed, decreased deformability results in increased transit time and reduced flow. These changes may

Platelet Function

Platelets are activated during sepsis.75, 76 Activated platelets aggregate, provide a phospholipid-rich surface for coagulation complexes, release proinflammatory mediators, and interact with leukocytes and endothelial cells.75 In addition, platelets may generate procoagulant-rich microparticles, which contribute to a prothrombotic state.77, 78 At the present time, platelet function assays provide little diagnostic or therapeutic value and are not routinely performed in these patients.

Thrombocytopenia

Incidence.

CONCLUSION

Patients with sepsis who develop organ failure have an increased mortality rate. Prompt diagnosis of organ dysfunction is critical in identifying patients who may benefit from therapeutic intervention. In assessing patients for organ dysfunction, the hematologic system should not be overlooked. A thorough clinical evaluation and panel of laboratory tests that relate to this organ system should be as much a part of the work-up as taking the blood pressure, monitoring renal function, or measuring

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    1

    Dr Aird is a member of the advisory board of the National Initiative in Sepsis Education, an educational initiative that is sponsored by Vanderbilt University School of Medicine and Thomson Advanced Therapeutics Communications and supported in part by an unrestricted educational grant from Eli Lilly and Company.

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