Evaluation of anemia

Consumptive coagulopathy may be due to repeated blood transfusions or to disseminated intravascular coagulation.

average delay of 3-4 days before reticulocyte response, after acute blood loss.

average delay of 3-4 days before reticulocyte response, after acute blood loss.

Intravascular ultrasound is more accurate if patient is stable.

Spiral CT or MRI are better if patient is stable.[Figure caption and citation for the preceding image starts]: CT scan of a ruptured abdominal aortic aneurysmUniversity of Michigan, specifically the cases of Dr Gilbert R. Upchurch reflecting the Departments of Vascular Surgery and Radiology [Citation ends].

[Figure caption and citation for the preceding image starts]: Chest x-ray showing a widened mediastinumFrom the collection of Professor James Brown; used with permission [Citation ends].

increased ferritin threshold may help to identify patients with iron deficiency anemia in whom inflammation due to rheumatologic disease, chronic infections, or malignancy gives rise to increased ferritin levels (>15 ng/mL).[22]Ko CW, Siddique SM, Patel A, et al. AGA clinical practice guidelines on the gastrointestinal evaluation of iron deficiency anemia. Gastroenterology. 2020 Sep;159(3):1085-94. https://www.doi.org/10.1053/j.gastro.2020.06.046 http://www.ncbi.nlm.nih.gov/pubmed/32810434?tool=bestpractice.com [86]The Royal College of Pathologists of Australasia​. Ferritin. 2024 [internet publication]. https://www.rcpa.edu.au/Manuals/RCPA-Manual/Pathology-Tests/F/Ferritin [87]World Health Organization. Serum ferritin concentrations for the assessment of iron status in individuals and populations: technical brief. Dec 2020 [internet publication]. https://www.who.int/publications/i/item/9789240008526 [88]Garcia-Casal MN, Pasricha SR, Martinez RX, et al. Serum or plasma ferritin concentration as an index of iron deficiency and overload. Cochrane Database Syst Rev. 2021 May 24;5(5):CD011817. https://www.doi.org/10.1002/14651858.CD011817.pub2 http://www.ncbi.nlm.nih.gov/pubmed/34028001?tool=bestpractice.com [ ] What is the accuracy of ferritin as a marker for iron deficiency in non‐healthy adults?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.3826/fullShow me the answer​​ The trade-off between higher sensitivity and lower specificity using the higher threshold of 45 ng/mL provides an acceptable balance of benefits (fewer missed diagnoses) compared with potential harms (additional diagnostic evaluations).​​[22]Ko CW, Siddique SM, Patel A, et al. AGA clinical practice guidelines on the gastrointestinal evaluation of iron deficiency anemia. Gastroenterology. 2020 Sep;159(3):1085-94. https://www.doi.org/10.1053/j.gastro.2020.06.046 http://www.ncbi.nlm.nih.gov/pubmed/32810434?tool=bestpractice.com

Endometrial carcinoma should be excluded in patients >40 years.

The UK's National Institute for Health and Care Excellence recommends that adults with a FIT result of at least 10 micrograms of hemoglobin per gram of feces should be referred using a suspected cancer pathway referral for colorectal cancer (for a diagnosis or ruling out of cancer within 28 days of being referred urgently)​​.[93]National Institute for Health and Care Excellence (UK). Suspected cancer: recognition and referral. Apr 2025 [internet publication]. https://www.nice.org.uk/guidance/ng12 [94]National Institute for Health and Care Excellence. Quantitative faecal immunochemical testing to guide colorectal cancer pathway referral in primary care. Aug 2023 [internet publication]. https://www.nice.org.uk/guidance/dg56 Refer to guidelines for an exhaustive list of signs and/or symptoms that may prompt assessment for suspected colorectal cancer.[93]National Institute for Health and Care Excellence (UK). Suspected cancer: recognition and referral. Apr 2025 [internet publication]. https://www.nice.org.uk/guidance/ng12 ​​[94]National Institute for Health and Care Excellence. Quantitative faecal immunochemical testing to guide colorectal cancer pathway referral in primary care. Aug 2023 [internet publication]. https://www.nice.org.uk/guidance/dg56 [95]Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: recommendations for physicians and patients from the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2017 Jul;112(7):1016-30. https://journals.lww.com/ajg/Fulltext/2017/07000/Colorectal_Cancer_Screening__Recommendations_for.13.aspx http://www.ncbi.nlm.nih.gov/pubmed/28555630?tool=bestpractice.com ​​​​ ​​​​  

Useful alternative for patients who cannot tolerate colonoscopy.

Endometrial carcinoma should be excluded in patients aged >40 years.

Following negative endoscopy in the setting of persistent iron deficiency anemia, H pylori testing may be considered when malignancies, B12 deficiency, and idiopathic thrombocytopenic purpura have been excluded.[96]Public Health England (UK). Helicobacter pylori in dyspepsia: test and treat. Sep 2019 [internet publication]. https://www.gov.uk/government/publications/helicobacter-pylori-diagnosis-and-treatment

About a third of patients with pernicious anemia may have spuriously normal B12 levels (because autoantibodies to anti-intrinsic factor interfere with the laboratory assay) and normocytic anemia, leading to a missed or delayed diagnosis.[113]Mohamed M, Thio J, Thomas RS, et al. Pernicious anaemia. BMJ. 2020 Apr 24;369:m1319. https://www.doi.org/10.1136/bmj.m1319 http://www.ncbi.nlm.nih.gov/pubmed/32332011?tool=bestpractice.com

About a third of patients with pernicious anemia may have spuriously normal B12 levels (because autoantibodies to anti-intrinsic factor interfere with the laboratory assay) and normocytic anemia, leading to a missed or delayed diagnosis.[113]Mohamed M, Thio J, Thomas RS, et al. Pernicious anaemia. BMJ. 2020 Apr 24;369:m1319. https://www.doi.org/10.1136/bmj.m1319 http://www.ncbi.nlm.nih.gov/pubmed/32332011?tool=bestpractice.com Determining the vitamin B12 levels is more relevant and cost-efficient than determining folate levels when investigating macrocytic anemia.

Confirms deficiency if B12 levels are borderline.

If recreational use of nitrous oxide is suspected to be the cause of vitamin B12 deficiency, plasma homocysteine or serum methylmalonic acid should be used as the initial test.[21]National Institute for Health and Care Excellence. Vitamin B12 deficiency in over 16s: diagnosis and management. Mar 2024 [internet publication]. https://www.nice.org.uk/guidance/ng239

Not as specific as methylmalonic acid for vitamin B12 deficiency.[114]Devalia V, Hamilton MS, Molloy AM, et al. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014 Aug;166(4):496-513. https://www.doi.org/10.1111/bjh.12959 http://www.ncbi.nlm.nih.gov/pubmed/24942828?tool=bestpractice.com

If recreational use of nitrous oxide is suspected to be the cause of vitamin B12 deficiency, plasma homocysteine or serum methylmalonic acid should be used as the initial test.[21]National Institute for Health and Care Excellence. Vitamin B12 deficiency in over 16s: diagnosis and management. Mar 2024 [internet publication]. https://www.nice.org.uk/guidance/ng239

Neurologic symptoms will worsen if folate is corrected in the presence of low vitamin B12. Determining the vitamin B12 levels is more relevant and cost-efficient than determining folate levels when investigating macrocytic anemia.

Serum folate is rapidly affected by diet and short term supplementation; RBC folate represents longer term body stores. In most cases, however, serum folate is preferred, and correlates well with RBC folate. Determining the vitamin B12 levels is more relevant and cost-efficient than determining folate levels when investigating macrocytic anemia.

Prussian blue iron staining of bone marrow aspirate can show ringed sideroblasts - abnormal erythroid precursor cells which have granules around the nucleus.

Determining the vitamin B12 levels is more relevant and cost-efficient than determining folate levels when investigating macrocytic anemia

serum folate is rapidly affected by diet and short term supplementation; RBC folate represents longer term body stores. In most cases, however, serum folate is preferred, and correlates well with RBC folate. Determining the vitamin B12 levels is more relevant and cost-efficient than determining folate levels when investigating macrocytic anemia.

Up to 10% of patients do not have peripherally circulating blasts.

Immunohistochemistry, cytochemistry, and cytogenetics help to further classify disease.

Cytoplasmic granules indicate myeloid lineage of blasts. May also see Auer rods.[Figure caption and citation for the preceding image starts]: Peripheral blood film of a patient with acute myeloid leukemia showing myeloid blasts with an Auer rodFrom the collection of Dr Kavita Raj and Dr Priyanka Mehta; used with patient consent [Citation ends].

Immunohistochemistry, cytochemistry, and cytogenetics help to further classify disease.[115]Mehta P, Telford N, Wragg C, et al. Recommendations for laboratory testing of UK patients with acute myeloid leukaemia. Br J Haematol. 2023 Jan;200(2):150-9. https://www.doi.org/10.1111/bjh.18516 http://www.ncbi.nlm.nih.gov/pubmed/36278472?tool=bestpractice.com

Due to elevated leukocyte count and turnover.

Characteristic mononuclear "hairy" cells, which stain positive for tartrate-resistant acid phosphatase

[Figure caption and citation for the preceding image starts]: Cytospin prepared from bone marrow aspirate illustrates the typical cell cytology, with oval- to bean-shaped nuclei and moderate amounts of cytoplasm with irregular cytoplasmic borders (Wright Giemsa 100x oil)From the collection of Lynn Moscinski, MD; used with permission [Citation ends].

Residual hematopoietic cells are morphologically normal

Determining the vitamin B12 levels is more relevant and cost-efficient than determining folate levels when investigating macrocytic anemia

serum folate is rapidly affected by diet and short term supplementation; RBC folate represents longer term body stores. In most cases, however, serum folate is preferred, and correlates well with RBC folate. Determining the vitamin B12 levels is more relevant and cost-efficient than determining folate levels when investigating macrocytic anemia.

if metastatic malignancy is suspected, provide history to the pathologist so appropriate stains can be ordered.

The most common infectious cause.

May be microcytic if anemia of chronic disease is coexistent with iron deficiency anemia.

When anemia of chronic disease is coexistent with iron deficiency anemia, these parameters may be different.

Elevation, if present, is usually inadequate to compensate for the degree of anemia.

Serum folate is rapidly affected by diet and short term supplementation; RBC folate represents longer term body stores. In most cases, however, serum folate is preferred, and correlates well with RBC folate.

Serum folate is rapidly affected by diet and short term supplementation; RBC folate represents longer term body stores. In most cases, however, serum folate is preferred, and correlates well with RBC folate.

Copper deficiency should be considered in patients on prolonged total parenteral nutrition.

Counts usually reach nadir 7 to 10 days after administration of chemotherapy. Cyclosporine, tacrolimus, clopidogrel, oral contraceptive pills, and some chemotherapy drugs may cause hemolytic uremic syndrome, in which case the anemia is hyperproliferative.

Cyclosporine, tacrolimus, clopidogrel, oral contraceptive pills, and some chemotherapy drugs may cause hemolytic uremic syndrome, in which case the reticulocyte count will initially be >2% until metabolites in the marrow are exhausted.

The elevated reticulocyte count may incorrectly increase MCV on automated counters.[Figure caption and citation for the preceding image starts]: Peripheral blood smear with spherocytes, reticulocytes, and a nucleated red blood cell (RBC)From the collection of John Densmore, Department of Medicine, University of Virginia; used with permission [Citation ends].

negative in 5% to 10% of cases[116]Kamesaki T. Diagnostic algorithm for classification and characterization of direct antiglobulin test-negative autoimmune hemolytic anemia with 1-year clinical follow-up. Transfusion. 2022 Jan;62(1):205-16. https://www.doi.org/10.1111/trf.16709 http://www.ncbi.nlm.nih.gov/pubmed/34668206?tool=bestpractice.com

Most commonly a clerical error. Stop transfusion immediately and stabilize the patient.

Malaria can cause both direct marrow suppression (low reticulocyte count) due to persistence of cytokines or occult parasitemia. However, the typical hemolytic picture with initial marrow compensatory response (elevated reticulocyte count) is seen in most other acute cases.

Banana-shaped gametocytes or multiple signet-ring forms in RBCs are typical for Plasmodium falciparum, which requires hospital admission.

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.[117]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 [118]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 [119]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.[120]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 [121]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 ​​​

IgM may persist long after infection; its absence excludes infection.

Recommended to confirm diagnosis of suspected visceral leishmaniasis (if definitive diagnostic tests for the parasite cannot be conducted or have negative results).​[122]Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Am J Trop Med Hyg. 2017 Jan 11;96(1):24-45. https://www.ajtmh.org/view/journals/tpmd/96/1/article-p24.xml

Considered the test of choice in immunocompetent patients with suspected visceral leishmaniasis, but it is less sensitive in immunosuppressed patients.

Recommended to confirm diagnosis of suspected cutaneous or visceral leishmaniasis, if available. Emerging as the most sensitive assays for the diagnosis of leishmaniasis.[122]Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Am J Trop Med Hyg. 2017 Jan 11;96(1):24-45. https://www.ajtmh.org/view/journals/tpmd/96/1/article-p24.xml

Sensitivity estimates range from 70% to 100% when using tissue biopsies for cutaneous leishmaniasis diagnosis and when using peripheral blood for visceral leishmaniasis diagnosis.[123]Reithinger R, Dujardin JC. Molecular diagnosis of leishmaniasis: current status and future applications. J Clin Microbiol. 2007 Jan;45(1):21-5. https://www.doi.org/10.1128/JCM.02029-06 http://www.ncbi.nlm.nih.gov/pubmed/17093038?tool=bestpractice.com

Splenic aspirate is most sensitive technique (>95%), but carries a 1:1000 risk of major bleeding; considerable technical expertise is required.[124]Kager PA, Rees PH. Splenic aspiration. Review of the literature. Trop Geogr Med. 1983 Jun;35(2):111-24. http://www.ncbi.nlm.nih.gov/pubmed/6351381?tool=bestpractice.com

Examination of bone marrow aspirate or lymph node fluid is safer, but is of lower sensitivity (70% to 96% and 58%, respectively).[125]Zijlstra EE, Ali MS, el-Hassan AM, et al. Kala-azar: a comparative study of parasitological methods and the direct agglutination test in diagnosis. Trans R Soc Trop Med Hyg. 1992 Sep-Oct;86(5):505-7. https://www.doi.org/10.1016/0035-9203(92)90086-r http://www.ncbi.nlm.nih.gov/pubmed/1475815?tool=bestpractice.com

Used to exclude parvovirus when typical clinical features are absent.

Rules out Epstein-Barr virus, which is clinically indistinguishable from CMV.

Pancytopenia occurs in aplastic crisis (usually self-limited).[Figure caption and citation for the preceding image starts]: Red cells in sickle cell diseaseFrom the personal collection of Sophie Lanzkron, MD; used with permission [Citation ends].

Although patients often exhibit an elevated reticulocyte count, generally the degree of reticulocyte output is inadequate to meet the degree of red blood cell destruction (hemolysis) occurring in the bone marrow and the patients remain anemic.

Excludes immune-mediated hemolytic anemias.

Heinz bodies are rapidly cleared by the spleen within 24 hours, resulting in "bite cells."

May be falsely negative during the acute hemolytic event, owing to the destruction of affected cells.

Distinguishes glucose-6-phosphate dehydrogenase deficiency from immune hemolytic anemias.

Aplastic anemia is the commonest cause of acquired bone marrow failure. The commonest cause of inherited aplastic anemia is Fanconi anemia,

Excludes disseminated intravascular coagulation.

Excludes immune-mediated hemolytic anemias.

Fibrinogen may be normal or elevated as an acute-phase reactant.

Excludes immune-mediated hemolytic anemias.

Platelet sequestration in enlarging hemangiomas (Kasabach-Merritt syndrome) can cause life-threatening bleeding.

Excludes immune-mediated hemolytic anemias.