Evaluation of neutropenia

Blood cultures should be taken immediately, and preferably before antibiotics are started, provided their sampling will not delay administration of antibiotics. Other cultures (for example, sputum, stool, and urine) should be taken as clinically indicated.

Elevated serum lactate indicates tissue hypoperfusion, and is most reliably assessed using an arterial sample.

WBC count is sensitive but not specific for the diagnosis of sepsis.

Elevated creatinine may occur in sepsis associated with renal dysfunction.

Sepsis can originate from hepatic or peri-hepatic infections.

Comorbid hepatic disease can affect drug metabolism.

Septic shock can compromise hepatic blood flow and metabolism.

An ECG should be arranged to help exclude other differential diagnoses, including myocardial infarction, pericarditis, and myocarditis. Sepsis also predisposes to myocardial dysfunction and arrhythmias.

Performed if meningitis suspected.

Should be considered if antibiotic therapy was started prior to sample collection.

Not useful in the initial diagnosis as repeated weekly culture is required to identify the organism.

Used at the point of care by properly trained staff. False-negatives may occur before antibodies to HIV appear. A positive result should be confirmed with a second rapid test.

p24 protein is detectable during acute infection and again during late stages of infection. It is used as a supplementary test during the window period.

Used as a confirmatory test if rapid test or ELISA are positive.

IgM is more useful in the acute infection.

IgM is more useful in the acute infection.

IgM is more useful in the acute infection.

Acceptable specimens include nasopharyngeal swab, nasal wash, bronchial wash, nasal aspirate, and sputum.

Acceptable specimens include nasopharyngeal swab, nasal wash, bronchial wash, nasal aspirate, and sputum.

Reserved for patients in whom serology is indeterminate.

Used to exclude parvovirus when typical clinical features are absent.

A positive result will usually not appear until 7 to 10 days into the infection.

The test should be repeated if negative, as several tests are often required to obtain a positive result.

Can also see thrombocytopenia, anemia, and neutropenia.

Cytogenetics should be performed on the bone marrow biopsy.

Can also see thrombocytopenia, anemia, and neutropenia.

Cytogenetics should be performed on the bone marrow biopsy.

Cytogenetics should be performed on the bone marrow biopsy.

Fine needle aspiration is not adequate. Full excision of lymph node should be done.

Fine needle aspiration is not adequate. Full excision of lymph node should be done.

Provide history to pathologist so appropriate stains can be ordered if metastatic malignancy is suspected.

Neutropenia is usually due to vitamin B12 or folate deficiency.

Alcohol can cause or aggravate copper deficiency.

Indicated if nutritional status is excluded as a cause. If alcohol is stopped, this should resolve in days to weeks.

IgM is more useful during the acute infection.

The test quantifies the number of pp65-positive cells/150,000-200,000 cells.

Paired samples should be obtained during the acute and convalescent phases (i.e., 2-4 weeks later) to demonstrate rising antibody titers. A fourfold or greater increase in antibody titer is diagnostic.[63]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: rocky mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016 May 13;65(2):1-44. http://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com

Thick films are more sensitive for detection of parasites than thin films, as they allow for a greater volume of blood to be examined. Nonimmune individuals may be symptomatic at very low parasite densities that may initially be undetectable. Therefore, if clinical suspicion is high, smears should be repeated daily on three separate occasions over 48 hours. Thin blood smears permit species identification and calculation of the parasitemia (percentage of parasitized red blood cells). A high parasitemia (>2% of erythrocytes parasitized) is itself a sign of more severe disease, although severe disease may occur at any level of parasitemia. In addition, the presence of schizonts on the blood smear may indicate a patient with the potential to suddenly deteriorate.

These immunochromatographic tests detect the presence of malaria antigen or enzyme and typically give a visible band after 15 minutes if positive.

Problems have included poor detection of species other than Plasmodium falciparum and false-negative results at lower parasite burden.[64]Pattanasin S, Proux S, Chompasuk D, et al. Evaluation of a new plasmodium lactate dehydrogenase assay (OptiMAL-IT) for the detection of malaria. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):672-4. https://www.doi.org/10.1016/s0035-9203(03)80100-1 http://www.ncbi.nlm.nih.gov/pubmed/16117960?tool=bestpractice.com [65]Ashley EA, Touabi M, Ahrer M, et al. Evaluation of three parasite lactate dehydrogenase-based rapid diagnostic tests for the diagnosis of falciparum and vivax malaria. Malar J. 2009 Oct 27;8:241. https://www.doi.org/10.1186/1475-2875-8-241 http://www.ncbi.nlm.nih.gov/pubmed/19860920?tool=bestpractice.com [66]Yerlikaya S, Campillo A, Gonzalez IJ. A systematic review: performance of rapid diagnostic tests for the detection of plasmodium knowlesi, plasmodium malariae, and plasmodium ovale monoinfections in human blood. J Infect Dis. 2018 Jun 20;218(2):265-76. https://www.doi.org/10.1093/infdis/jiy150 http://www.ncbi.nlm.nih.gov/pubmed/29554284?tool=bestpractice.com However, some studies have shown that performance of RDTs can be equivalent to expert microscopy.[67]Stauffer WM, Cartwright CP, Olson DA, et al. Diagnostic performance of rapid diagnostic tests versus blood smears for malaria in US clinical practice. Clin Infect Dis. 2009 Sep 15;49(6):908-13. https://www.doi.org/10.1086/605436 http://www.ncbi.nlm.nih.gov/pubmed/19686072?tool=bestpractice.com [68]Nicastri E, Bevilacqua N, Sañé Schepisi M, et al. Accuracy of malaria diagnosis by microscopy, rapid diagnostic test, and PCR methods and evidence of antimalarial overprescription in non-severe febrile patients in two Tanzanian hospitals. Am J Trop Med Hyg. 2009 May;80(5):712-7. http://www.ncbi.nlm.nih.gov/pubmed/19407111?tool=bestpractice.com

RDTs should be used if quality-assured malaria microscopy is not readily available.[59]World Health Organization. WHO Guidelines for malaria. Oct 2023 [internet publication]. https://www.who.int/publications/i/item/guidelines-for-malaria

Used in active cutaneous disease.

Used in active cutaneous or visceral disease.

Used in healing cutaneous disease.

Various highly sensitive and specific tests are available, and the choice depends mainly on availability and imaging expertize.[69]Chappuis F, Sundar S, Hailu A, et al. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbiol. 2007 Nov;5(11):873-82. https://www.nature.com/articles/nrmicro1748 http://www.ncbi.nlm.nih.gov/pubmed/17938629?tool=bestpractice.com ​

Used in suspected visceral disease; can be used to confirm relapse.

A useful test in immunocompetent patients with suspected visceral leishmaniasis, but less sensitive in patients who are immunosuppressed. However, it may be used in patients who are immunosuppressed if parasitologic diagnosis is not feasible.[70]Cota GF, de Sousa MR, Demarqui FN, et al. The diagnostic accuracy of serologic and molecular methods for detecting visceral leishmaniasis in HIV infected patients: meta-analysis. PLoS Negl Trop Dis. 2012;6(5):e1665. https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001665 http://www.ncbi.nlm.nih.gov/pubmed/22666514?tool=bestpractice.com

When hemolysis is brisk and all of the transfused red cells are rapidly destroyed, the posttransfusion direct antiglobulin test may be negative.

Should be done on a sample of blood from both the patient and the transfused component.

Dysplastic features resolve with copper supplementation.

May need to be repeated to get a positive result. If a negative result is found on the first test, it should be repeated.

May need to be repeated to get a positive result. If a negative result is found on the first test, it should be repeated.

May need to be repeated to get a positive result. If a negative result is found on the first test, it should be repeated.

Quantitatively measures tears.

May need to be repeated to get a positive result. If a negative result is found on the first test, it should be repeated.

Pseudoneutropenia is a diagnosis of exclusion in an asymptomatic patient.

If a biopsy obtained for the investigation of another condition is normal, pseudoneutropenia is the diagnosis of exclusion.

Bone marrow failure syndromes include severe congenital neutropenia/Kostmann syndrome, Fanconi anemia, Shwachman-Diamond syndrome, Pearson syndrome, dyskeratosis congenita, Griscelli syndrome, and Barth syndrome.

Detects Fanconi anemia.

Seen in Griscelli syndrome.

Congenital isolated neutropenia syndromes include cyclic neutropenia, chronic idiopathic neutropenia (a diagnosis of exclusion), myelokathexis, Cohen syndrome, Hermansky-Pudlak syndrome type II, and P14 deficiency.

Congenital immunodeficiency syndromes include common variable immunodeficiency, X-linked agammaglobulinemia, hyper IgM syndrome, cartilage-hair hypoplasia, reticular dysgenesis, WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, Chediak-Higashi syndrome, Schimke immuno-osseous dysplasia, and Wiskott-Aldrich syndrome.

It is important to check with the imaging before sending the sample. The result needs to be considered in light of detailed clinical information and data on enzyme activity.