Why does sepsis cause leukopenia

Nonetheless, select patients may undergo radiologic and nuclear imaging as adjunctive tests to aid in elucidating a particular cause of the leukocytosis or leukopenia. Plain radiography has a limited role; however, adenopathy noted on a chest x-ray may occur in sarcoid or lymphoma. In a patient with a leukemoid reaction, the presence of a thickened, inflamed colon is compatible with C. Also, splenomegaly on computed tomography could indicate lymphoma or chronic myelogenous leukemia.

Nuclear imaging such as a gallium scan, positron emission tomography PET scan, bone scan, or indium-labeled leukocyte scan may be helpful in certain clinical scenarios in patients with leukocytosis or leukopenia.

For instance, gallium scanning may indicate lymphoma; PET scanning may help assess for malignancy or recurrence of malignancy; bone scanning may indicate osteomyelitis or metastases; and indium-labeled imaging may help locate occult infection.

Even though imaging may be helpful in the diagnostic armamentarium for quantitative leukocyte disorders, these tests are no substitute for a thorough history, physical exam including lymph nodes and spleen , and careful review of a peripheral blood smear and occasionally, the bone marrow. Often, the clinician will need to make a rather timely decision regarding the possibility of infection and the subsequent need for systemic antibiotics in patients with leukocyctosis or leukopenia.

In patients with leukocytosis, the possibility of infection always exists, especially with neutrophilia and no prior documentation of leukocytosis. If the patients is febrile, has unstable vital signs e. For instance, in an elderly female nursing home patient, antibiotics directed at urosepsis should be considered. Furthermore, a community-dwelling patient with fever, cough, sputum, and fatigue should have antibiotics directed against common pneumonic pathogens.

Leukopenic patients pose a greater challenge. Often, patients with febrile neutropenia develop common bacterial infections such as pyelonephritis, pneumonia, or skin and soft tissue infections. However, the risk of aggressive and overwhelming infection and sepsis is increased due to the paucity of neutrophils. As such, patients with febrile neutropenia due to chemotherapy, drug reactions, or sometimes bone marrow disease, require prompt administration of broad-spectrum antibiotics to cover the most likely pathogens.

Some recommend the use of filgrastim G-CSF to aid in neutrophil recovery. Granulocyte colony stimulating factor G-CSF or filgrastim, is an agent often utilized in the setting of chemotherapy administration for malignancy, in hopes to avoid the morbidity and mortality associated with neutropenia.

Studies have revealed variable benefit in patients with established febrile neutropenia in hopes of raising the neutrophil count thereby increasing the phagocytic and bactericidal effects of circulating and tissue-based neutrophils. Meticulous supportive care should be provided to all neutropenic patients.

It should be appreciated that the leukocyte count can rise dramatically, sometimes into the leukemoid reaction range. Also, monocytosis may appear as the bone marrow recovers, and is an expected finding in this situation. Patients with leukocytosis should be monitored with frequent blood counts and clinical assessment, but treatment depends on the underlying diagnosis. Abramson N, Melton B. Leukocytosis: Basics of clinical assessment.

Am Fam Physician ; Leukemoid reactions associated with Clostridium difficile colitis. South Med J ; Marinella MA. Extreme leukemoid reaction associated with retroperitoneal hemorrhage. Arch Intern Med ; Approach to the microscopic evaluation of blood and bone marrow. Philadelphia: Lippincott Williams and Wilkins, , pp. Drug-associated disease: hematologic dysfunction. Crit Care Clin ; Yo CH, et al.

Comparison of the test characteristics of procalcitonin to C-reactive protein and leukocytosis for the detection of serious bacterial infections in children presenting with fever without source: a systematic review and meta-analysis.

Ann Emerg Med ; Clinical Manifestations. Laboratory Diagnosis. Ramaprasad C, Pursell K. Cytopenias after Solid Organ Transplantation.

George TI. Malignant or benign leukocytosis. Clinical Manifestation. It can take days to receive microbiologic culture results, and successful resolution of sepsis requires the early administration of general antibiotics. Therefore, as soon as culture samples have been taken, patients are started on wide spectrum antibiotics, with the plan of reassessing the effectiveness daily and customizing the antibiotic once the cultures are available.

Not all patients with sepsis-like symptoms have an infection. The same reaction, SIRS, can be triggered by noninfectious causes, and in such cases it is risky to expose the patient to unnecessary nephrotoxic antibiotics.

For decades, scientists have been trying to find a rapid laboratory test that will give a quick and reliable diagnosis of sepsis. Sepsis is a complex syndrome. To date, however, no single physiologic change has been found to be a specific and sensitive identifier for sepsis.

Among the many molecules being studied, three that appear to be the most useful are C-reactive protein, complement C3a, and procalcitonin. An elevated level of C-reactive protein CRP, a different molecule from protein C , is a useful marker for systemic inflammation in general. Systemic infections raise the levels of molecules in the complement cascade. An elevated level of procalcitonin the precursor molecule to the hormone calcitonin will also distinguish sepsis from noninfectious SIRS.

Blood molecules useful to identify sepsis include all but one of the following:. At times the diagnosis of sepsis is straightforward. A patient can present with tachycardia, hypotension, tachypnea, fever, leukocytosis, metabolic acidosis, and signs of a serious infection such as pneumonia, acute pyelonephritis, or acute peritonitis.

At other times, however, sepsis presents with only a few classic symptoms. This is especially true in the early stages of the disease when the patient may not yet look severely ill and the underlying infection may not be obvious. Another confusing initial presentation occurs in the patient with sepsis who has acute and dramatic dysfunction of an organ. There can also be diagnostic difficulties when a patient presents with a mix of complaints.

Sepsis tends to take hold in patients who already have illnesses, injuries, or infirmities. If you are attending a virtual event or viewing video content, you must meet the minimum participation requirement to proceed.

If you think this message was received in error, please contact an administrator. Return to Course Home. Sepsis: Immune Response Meltdown Page 7 of Septic patients should look ill and should have the classic signs of a systemic infection: Fever Tachypnea Tachycardia High white blood cell count The severity of the septic reaction should also produce other warning signs, such as: Hot, flushed skin Newly altered mental status Hypotension Widened pulse pressure Pulse pressure is the difference between the systolic and the diastolic blood pressure values.

Elevated blood lactate level Thrombocytopenia It is important to stress that few if any patients in the early stages of the inflammatory responses to infection are diagnosed via the four SIRS criteria. Clinical experience by identifying signs and symptoms. Clinical Signs of Sepsis A septic patient has an infection and a number of the following signs.

Test Your Knowledge Fever is a classic sign of a systemic infection. In Sepsis: Patients with sepsis always have a fever.

Older patients tend to have a fever, but most patients have a normal or near-normal temperature. Patients often have a fever, although some septic patients can have normal temperatures or even hypothermia.

Fever is rare in all sepsis patients. Clinical Assessment of Cardiac Output Cardiac output is the volume of blood that the heart pumps per minute. Clinically, a reduced cardiac output will produce: Narrow pulse pressure Cool extremities Weak pulse Delayed capillary refill An increased cardiac output will produce: Widened pulse pressure Warm extremities Bounding pulse Rapid capillary refill The classic presentation of sepsis includes an increased cardiac output.

Volume of blood that the heart pumps per minute. Heart rate plus the respiratory rate. A significant proportion of patients who overcome the initial sepsis die in the further course of their ICU stay. In particular, patients with remaining organ dysfunction are at increased risk. Microbiological findings imply that all measures should be undertaken to preserve integrity of the gastrointestinal mucosa, for example, by early enteral feeding and central venous access should be replaced or removed following ICU admission.

Adding antimicrobials with activity against Gram-positive cocci resistant to beta-lactam antibiotics early in the course of disease may have a significant impact on outcome. Kruse, Thomas Jenning, Philipp Enghard, and Michael Oppert participated in the design of the study and performed statistical analysis.

All authors read and approved the final paper. Kruse et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. Special Issues. Academic Editor: Djillali Annane.

Received 29 Nov Revised 01 Feb Accepted 07 Feb Published 18 Apr Abstract Objective. Methods 2. Antibiotic Regimen Due to the retrospective nature of the study, the choice of antibiotics was made by the intensivist in charge. Data Collection Data were collected from the electronic patient files. Statistical Analysis Parameters were recorded as median and interquartile range 25th—75th percentile.

Results 3. General Patient Characteristics Among the Figure 1. Context-dependent mortality of leukopenic patients admitted to the ICU. Patients after stem cell transplantation have an inferior prognosis. Patients with leukopenia after chemotherapy have a significantly better ICU survival. Figure 2. Number of patients deceased per ICU day. There is a concentration of fatalities in the first 6 days. Figure 3. Overview of the number of analyzed patients. Of the patients admitted to the ICU, 39 patients deceased in the initial sepsis phase, while 63 patients overcame it.

Of these 63 patients, 17 deceased in the ICU in the recovery phase, while 46 patients survived and were discharged from the ICU. Table 1. Characteristics of patients who manage to overcome the initial sepsis compared to those who decease in the initial septic episode. Table 2. Comparison of patients in the recovery phase after overcoming the initial sepsis. Figure 4.

Microbiologic findings in the initial sepsis phase. References K. Cooper, J. Madan, S. Whyte, M. Stevenson, and R. Sprung, M. Danis, M. Baily et al. Azoulay and B. Brunet, J. Lanore, J. Dhainaut et al. Groeger and P. Benoit, K. Vandewoude, J. Decruyenaere, E. Hoste, and F. Darmon, E. Azoulay, C. Using ICD-9 codes to exclude patients with etiologies of leukopenia other than sepsis may have imperfect sensitivity. Additionally, our data set only includes data on the day of arrival to ICU and after ICU admission, without the ability to evaluate laboratory values prior to ICU admission that may aid in prognostic evaluation.

Among critically ill patients with suspected infection, leukopenia was rare, but associated with increased risk of death as compared with leukocytosis. Although leukopenia did not independently add to prognostic validity of the SOFA score above platelet count, the correlation of leukopenia with thrombocytopenia and association of neutropenia with mortality suggest that future studies should whether leukopenia or neutropenia may prospectively identify a larger group of patients earlier than current Sepsis-3 definitions.

We would like to acknowledge the work of researchers at the MIT Laboratory for Computational Physiology, collaborating research groups, patients and funders for making MIMIC a publicly available research resource.

Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Abstract Background Although both leukocytosis and leukopenia have been considered Systemic Inflammatory Response Syndrome criteria, leukopenia is not generally considered a normal response to infection. Methods We performed a retrospective cohort study using the Medical Information Mart v1. Results We identified 5, ICU patients with suspected infection; 4. Conclusions Among ICU patients with suspected infection, leukopenia was associated with increased risk of death compared with leukocytosis.

Funding: The authors received no specific funding for this work. Background Prior to , [ 1 ] consensus definitions conceptualized sepsis as suspected infection with evidence of systemic inflammatory response syndrome SIRS [ 2 ]. Download: PPT. Exposures, covariates, and outcomes of interest We determined exposures and covariates in the time window from 48 hours before to 24 hours after the onset of suspected infection.

Sensitivity analysis We conducted a sensitivity analysis where we restricted our cohort to patients with an ICD-9 code for infection, to increase the likelihood that the cohort included patients with confirmed, rather than suspected, infection. Table 1. Fig 2. Exploratory analysis: Sequential analysis of individual organ dysfunction scores, leukopenia, and mortality The coagulation component of the SOFA score platelet count was most responsible for attenuating the association between leukopenia and mortality Table 3.

Fig 3. Correlation of platelet count with white blood cell count. Table 3. Beta-estimates before and after adjustment for specific organ dysfunction. Discussion In order to evaluate the potential role of leukopenia as a marker of life threating organ dysfunction within the conceptual model of Sepsis-3, we determined the association between leukopenia and mortality among patients admitted to the ICU with suspected infection.

Conclusions Among critically ill patients with suspected infection, leukopenia was rare, but associated with increased risk of death as compared with leukocytosis.

Supporting information. S1 Table. Odds ratios for neutropenia models. S2 Table. Odds ratios for Lymphopenia models.