Peripheral blood smear - Revision history

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2026-03-19T16:15:12Z

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Ostermayer: Created page with "==Background== The peripheral blood smear (PBS), also called a blood film, involves microscopic examination of a stained blood sample to evaluate cell morphology across all three cell lines (red blood cells, white blood cells, and platelets)Lynch EC. Peripheral Blood Smear. In: Walker HK, Hall WD, Hurst JW, eds. ''Clinical Methods: The History, Physical, and Laboratory Examinations''. 3rd ed. Boston: Butterworths; 1990. Chapter 155. PMID 21250105.
2026-03-12T17:19:34Z

Created page with "==Background== The peripheral blood smear (PBS), also called a blood film, involves microscopic examination of a stained blood sample to evaluate cell morphology across all three cell lines (red blood cells, white blood cells, and platelets)<ref name="lynch">Lynch EC. Peripheral Blood Smear. In: Walker HK, Hall WD, Hurst JW, eds. ''Clinical Methods: The History, Physical, and Laboratory Examinations''. 3rd ed. Boston: Butterworths; 1990. Chapter 155. PMID 21250105.</ref..."

New page
==Background==
The peripheral blood smear (PBS), also called a blood film, involves microscopic examination of a stained blood sample to evaluate cell morphology across all three cell lines (red blood cells, white blood cells, and platelets)<ref name="lynch">Lynch EC. Peripheral Blood Smear. In: Walker HK, Hall WD, Hurst JW, eds. ''Clinical Methods: The History, Physical, and Laboratory Examinations''. 3rd ed. Boston: Butterworths; 1990. Chapter 155. PMID 21250105.</ref>
Follows the [[CBC|complete blood count (CBC)]] as the second most performed test in the hematology laboratory<ref name="bain">Bain BJ. Diagnosis from the blood smear. ''N Engl J Med''. 2005;353(5):498-507. PMID 16079373.</ref>
Provides morphologic information that automated hematology analyzers cannot — including cell shape abnormalities, inclusions, parasites, and immature/atypical cells<ref name="adewoyin">Adewoyin AS, Nwogoh B. Peripheral blood film — a review. ''Ann Ib Postgrad Med''. 2014;12(2):71-79. PMID 25960697.</ref>
Stained using Wright or Wright-Giemsa stain; examined under light microscopy at 100× (oil immersion) for morphologic detail
Collected in an EDTA (purple/lavender top) tube; smear should ideally be prepared within 2 hours of collection to minimize artifact
Approximately 10–25% of CBC samples trigger a manual smear review based on abnormal automated flags or institutional criteria<ref name="craig">Craig FE, Roth CG. The utility of peripheral blood smear review for identifying specimens for flow cytometric immunophenotyping. ''Int J Lab Hematol''. 2017;39(4):363-368. PMID 28444824.</ref>

==Clinical Features==
The PBS is a diagnostic tool, not a clinical condition. It is ordered when the clinical picture or CBC abnormalities suggest a diagnosis requiring morphologic confirmation. Key morphologic findings and their clinical associations are outlined below.

===Red Blood Cell Morphology===
{| class="wikitable"
|-
! Finding !! Description !! Clinical Association
|-
| '''Schistocytes''' || Fragmented RBCs (helmet cells, triangles, crescents) || [[TTP]]/[[HUS]], [[DIC]], [[HELLP Syndrome|HELLP]], mechanical heart valves, malignant hypertension; ≥ 1% is suggestive of thrombotic microangiopathy (TMA)<ref name="zini">Zini G, d'Onofrio G, Briggs C, et al. ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes. ''Int J Lab Hematol''. 2012;34(2):107-116. PMID 22081912.</ref>
|-
| '''Spherocytes''' || Small, round RBCs lacking central pallor || [[Hereditary Spherocytosis|Hereditary spherocytosis]], autoimmune hemolytic anemia (warm AIHA), transfusion reactions, burns
|-
| '''Sickle cells (drepanocytes)''' || Crescent/sickle-shaped RBCs || [[Sickle Cell Disease|Sickle cell disease]]
|-
| '''Target cells (codocytes)''' || Bull's-eye appearance with central and peripheral hemoglobin || Thalassemia, hemoglobin C disease, liver disease, iron deficiency, post-splenectomy
|-
| '''Tear-drop cells (dacrocytes)''' || Drop-shaped RBCs || Myelofibrosis, bone marrow infiltration (myelophthisis), thalassemia major, megaloblastic anemia
|-
| '''Burr cells (echinocytes)''' || Evenly spaced short spicules with preserved central pallor || Uremia/renal failure, artifact (drying, EDTA); may be seen in liver disease
|-
| '''Acanthocytes (spur cells)''' || Irregularly spaced thorny projections || Severe liver disease (spur cell anemia), abetalipoproteinemia, post-splenectomy
|-
| '''Rouleaux formation''' || RBCs stacked like coins || Multiple myeloma, Waldenström macroglobulinemia, chronic inflammation, elevated ESR
|-
| '''Howell-Jolly bodies''' || Nuclear remnants (dark inclusions) within RBCs || Post-splenectomy, functional asplenia (e.g. sickle cell disease), megaloblastic anemia
|-
| '''Basophilic stippling''' || Aggregated ribosomal RNA appearing as blue dots || [[Lead Poisoning|Lead poisoning]], thalassemia, sideroblastic anemia, myelodysplastic syndrome
|-
| '''Heinz bodies''' || Denatured hemoglobin inclusions (require supravital stain) || G6PD deficiency (during hemolytic crisis), unstable hemoglobin variants, oxidant drug exposure
|-
| '''Polychromasia''' || Bluish-gray tint to RBCs (reticulocytes) || Active bone marrow response to anemia (hemolysis, acute blood loss)
|-
| '''Hypersegmented neutrophils''' || Neutrophils with ≥ 5 lobes (or > 5% with 5 lobes) || Vitamin B12 or folate deficiency (megaloblastic anemia)
|-
| '''Nucleated RBCs''' || RBCs with retained nuclei (normoblasts) || Severe anemia, hemolysis, myelophthisic processes (bone marrow infiltration), extramedullary hematopoiesis, neonates (normal finding)
|}

===White Blood Cell Morphology===
{| class="wikitable"
|-
! Finding !! Description !! Clinical Association
|-
| '''Blasts''' || Large immature cells with high nuclear-to-cytoplasmic ratio, fine chromatin, prominent nucleoli || Acute leukemia (AML, ALL) — '''hematologic emergency''' requiring immediate consultation<ref name="bain"/>
|-
| '''Left shift''' || Increased immature granulocytes (bands, metamyelocytes, myelocytes) || Severe bacterial infection, sepsis, physiologic stress, myeloproliferative disorders
|-
| '''Toxic granulation''' || Prominent dark granules in neutrophil cytoplasm || Severe infection/sepsis, inflammation
|-
| '''Döhle bodies''' || Light blue cytoplasmic inclusions in neutrophils || Severe infection, burns, May-Hegglin anomaly
|-
| '''Toxic vacuolization''' || Cytoplasmic vacuoles in neutrophils || Severe sepsis/bacteremia (associated with high specificity for bacteremia)
|-
| '''Auer rods''' || Pink rod-shaped crystalline inclusions in blast cytoplasm || '''Pathognomonic for AML''' (especially APL/M3); '''hematologic emergency'''
|-
| '''Atypical lymphocytes''' || Large lymphocytes with abundant pale blue cytoplasm and scalloped borders ("Downey cells") || Infectious mononucleosis (EBV), CMV, other viral infections, drug reactions
|-
| '''Smudge cells''' || Fragile lymphocytes that rupture during smear preparation || [[Chronic Lymphocytic Leukemia|CLL]] (when numerous)
|-
| '''Pelger-Huët anomaly''' || Bilobed neutrophils || Inherited (benign); acquired (pseudo-Pelger-Huët) in myelodysplastic syndrome
|-
| '''Hypersegmented neutrophils''' || ≥ 5 nuclear lobes || Megaloblastic anemia (B12/folate deficiency)
|}

===Platelet Morphology===
{| class="wikitable"
|-
! Finding !! Description !! Clinical Association
|-
| '''Platelet clumps''' || Aggregated platelets on smear || Pseudothrombocytopenia (EDTA-dependent clumping) — falsely low automated platelet count; re-draw in citrate tube to confirm<ref name="bain"/>
|-
| '''Giant platelets''' || Platelets approaching or exceeding RBC size || Bernard-Soulier syndrome, May-Hegglin anomaly, [[ITP]] (young active platelets), myeloproliferative disorders
|-
| '''Decreased platelets on smear''' || < 1 platelet per oil-immersion field || True thrombocytopenia (each platelet per OIF ≈ 10,000–15,000/μL)
|}

===Infectious Organisms===
{| class="wikitable"
|-
! Finding !! Clinical Association
|-
| '''Malaria parasites''' (intra-erythrocytic rings, gametocytes, schizonts) || [[Malaria]] — thick smear for detection, thin smear for speciation; gold standard diagnostic test<ref name="adewoyin"/>
|-
| '''Babesia''' (intra-erythrocytic ring forms, Maltese cross/tetrad) || [[Babesiosis]] — may resemble ''Plasmodium falciparum''
|-
| '''Anaplasma/Ehrlichia morulae''' (intracytoplasmic inclusions in granulocytes or monocytes) || [[Anaplasmosis]]/[[Ehrlichiosis]]
|-
| '''Borrelia spirochetes''' (rare) || [[Relapsing Fever]]
|-
| '''Trypanosomes''' || [[Trypanosomiasis]]
|}

==Differential Diagnosis==
===Conditions Diagnosed or Strongly Suggested by PBS===
'''Thrombotic microangiopathy (TTP/HUS/DIC):''' Schistocytes + thrombocytopenia<ref name="zini"/>
'''Acute leukemia:''' Circulating blasts; Auer rods pathognomonic for AML
'''Malaria/Babesiosis:''' Intra-erythrocytic parasites
'''Sickle cell disease:''' Sickle cells on smear
'''DIC:''' Schistocytes + thrombocytopenia + abnormal coagulation studies
'''Myelofibrosis/Marrow infiltration:''' Tear-drop cells + nucleated RBCs + left shift (leukoerythroblastic picture)
'''CLL:''' Absolute lymphocytosis + smudge cells
'''Megaloblastic anemia:''' Macro-ovalocytes + hypersegmented neutrophils
'''AIHA:''' Spherocytes + polychromasia + positive Coombs test

==Evaluation==
===ED Indications for Ordering a Peripheral Blood Smear===
Unexplained anemia, especially when etiology is unclear from CBC indices alone
Thrombocytopenia — to rule out pseudothrombocytopenia (platelet clumps) and evaluate for schistocytes (TMA)<ref name="zini"/>
Suspected [[TTP]], [[HUS]], [[DIC]], or [[HELLP Syndrome|HELLP]] — '''schistocyte identification is essential for TMA diagnosis and should not be delayed'''
Suspected acute [[Leukemia|leukemia]] — blasts on smear → emergent hematology consultation
Suspected [[Malaria|malaria]] or [[Babesiosis|babesiosis]] — thick and thin smear remain the gold standard<ref name="adewoyin"/>
Pancytopenia or leukoerythroblastic picture
Unexplained leukocytosis with concern for malignancy
Clinical suspicion of [[Sickle Cell Disease|sickle cell crisis]] in an undiagnosed patient
Fever in a returning traveler

===How to Order===
Order "peripheral blood smear with pathologist review" or "manual differential with smear" — terminology varies by institution
Specify clinical question (e.g. "evaluate for schistocytes" or "rule out blasts") to guide the reviewing pathologist or technologist
If malaria is suspected, order "thick and thin blood smears for malaria parasites" — standard Wright-stained smear may not be optimized for parasite detection

===Interpreting Results===
Smear results should always be interpreted alongside the CBC, clinical context, and other labs<ref name="adewoyin"/>
A single negative malaria smear does not exclude infection; repeat every 12–24 hours for 3 sets if clinical suspicion is high
Absence of schistocytes does not definitively exclude TMA; a threshold of ≥ 1% schistocytes supports the diagnosis, but clinical judgment should prevail<ref name="zini"/>
Smear artifacts (echinocyte formation from alkaline stain, stomatocytes from acidic stain, crenated cells from drying) should be recognized and not misinterpreted

==Management==
Management is directed by the underlying diagnosis suggested or confirmed by the PBS:

'''Schistocytes identified + thrombocytopenia:'''
Assume TMA until proven otherwise — calculate '''PLASMIC score''' if TTP is suspected
Send ADAMTS13 activity level (results take days; do not delay treatment)
Emergent hematology consultation for [[TTP]] (plasma exchange is lifesaving and should not be delayed)<ref name="scully">Scully M, Cataland S, Coppo P, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. ''J Thromb Haemost''. 2017;15(2):312-322. PMID 27868334.</ref>
'''Do NOT transfuse platelets''' in suspected TTP (may worsen microvascular thrombosis)
**Evaluate for DIC (PT/INR, PTT, fibrinogen, D-dimer) — abnormal coagulation studies favor DIC over TTP
'''Blasts on smear:'''
Emergent hematology/oncology consultation
Evaluate for [[Tumor Lysis Syndrome|tumor lysis syndrome]] (potassium, phosphorus, uric acid, calcium, LDH, creatinine)
If WBC > 100,000/μL with blasts → concern for [[Leukostasis|leukostasis]]; may require emergent leukapheresis
'''Do not delay flow cytometry and bone marrow biopsy'''
'''Malaria parasites:'''
Calculate percent parasitemia from thin smear
> 5% parasitemia or any evidence of severe malaria (altered mentation, renal failure, severe anemia, ARDS) → IV artesunate<ref name="rosenthal">Rosenthal PJ. Artesunate for the treatment of severe falciparum malaria. ''N Engl J Med''. 2008;358(17):1829-1836. PMID 18434654.</ref>
**Infectious disease consultation
*'''Spherocytes + hemolysis labs:'''
Send direct Coombs (direct antiglobulin test)
If positive → autoimmune hemolytic anemia; consider steroids
**If negative → consider hereditary spherocytosis, delayed transfusion reaction
'''Leukoerythroblastic picture''' (tear-drop cells + nucleated RBCs + immature granulocytes):
Suggests marrow infiltration (myelofibrosis, metastatic disease, granulomatous disease)
Hematology consultation for bone marrow biopsy

==Disposition==
'''Admit:'''
Schistocytes with thrombocytopenia (suspected TMA) — often to ICU; emergent plasma exchange for TTP
Blasts on peripheral smear (suspected acute leukemia)
Severe parasitemia (malaria > 5% or any signs of severe malaria)
Symptomatic anemia requiring transfusion with unclear etiology
**Pancytopenia with fever
*'''Discharge with urgent follow-up may be appropriate for:'''
Mild morphologic abnormalities (e.g. target cells, mild poikilocytosis) with stable CBC and known chronic condition
Confirmed pseudothrombocytopenia with normal citrate platelet count
**Stable atypical lymphocytosis consistent with viral syndrome
Communicate critical smear findings (blasts, schistocytes, parasites) directly with the consulting service — do not rely solely on electronic result notification

==See Also==
[[CBC]]
[[Anemia]]
[[TTP]]
[[Hemolytic Uremic Syndrome]]
[[DIC]]
[[Leukemia]]
[[Neutropenic fever]]
[[Malaria]]
[[Babesiosis]]
[[Sickle Cell Disease]]
[[HELLP Syndrome]]
[[Thrombocytopenia]]
[[Pancytopenia]]

==External Links==
[https://www.ncbi.nlm.nih.gov/books/NBK263/ Peripheral Blood Smear - Clinical Methods (NCBI Bookshelf)]
[https://pmc.ncbi.nlm.nih.gov/articles/PMC4415389/ Peripheral Blood Film — A Review (Ann Ib Postgrad Med 2014)]
[https://pubmed.ncbi.nlm.nih.gov/22081912/ ICSH recommendations for schistocyte identification and quantitation (Int J Lab Hematol 2012)]
[https://pubmed.ncbi.nlm.nih.gov/16079373/ Diagnosis from the blood smear (N Engl J Med 2005)]
*[https://pubmed.ncbi.nlm.nih.gov/28444824/ Utility of PBS review for identifying specimens for flow cytometry (Int J Lab Hematol 2017)]

==References==
<references/>

[[Category:Labs]]
[[Category:Heme/Onc]]

← Older revision		Revision as of 16:15, 19 March 2026
Line 100:		Line 100:
	==Differential Diagnosis==		==Differential Diagnosis==
	===Conditions Diagnosed or Strongly Suggested by PBS===		===Conditions Diagnosed or Strongly Suggested by PBS===
	*~~'''~~Thrombotic microangiopathy (TTP/HUS/DIC):~~'''~~ Schistocytes + thrombocytopenia<ref name="zini"/>		*Thrombotic microangiopathy (TTP/HUS/DIC): Schistocytes + thrombocytopenia<ref name="zini"/>
	*~~'''~~Acute leukemia:~~'''~~ Circulating blasts; Auer rods pathognomonic for AML		*Acute leukemia: Circulating blasts; Auer rods pathognomonic for AML
	*~~'''~~Malaria/Babesiosis:~~'''~~ Intra-erythrocytic parasites		*Malaria/Babesiosis: Intra-erythrocytic parasites
	*~~'''~~Sickle cell disease:~~'''~~ Sickle cells on smear		*Sickle cell disease: Sickle cells on smear
	*~~'''~~DIC:~~'''~~ Schistocytes + thrombocytopenia + abnormal coagulation studies		*DIC: Schistocytes + thrombocytopenia + abnormal coagulation studies
	*~~'''~~Myelofibrosis/Marrow infiltration:~~'''~~ Tear-drop cells + nucleated RBCs + left shift (leukoerythroblastic picture)		*Myelofibrosis/Marrow infiltration: Tear-drop cells + nucleated RBCs + left shift (leukoerythroblastic picture)
	*~~'''~~CLL:~~'''~~ Absolute lymphocytosis + smudge cells		*CLL: Absolute lymphocytosis + smudge cells
	*~~'''~~Megaloblastic anemia:~~'''~~ Macro-ovalocytes + hypersegmented neutrophils		*Megaloblastic anemia: Macro-ovalocytes + hypersegmented neutrophils
	*~~'''~~AIHA:~~'''~~ Spherocytes + polychromasia + positive Coombs test		*AIHA: Spherocytes + polychromasia + positive Coombs test

	==Evaluation==		==Evaluation==
Line 136:		Line 136:
	Management is directed by the underlying diagnosis suggested or confirmed by the PBS:		Management is directed by the underlying diagnosis suggested or confirmed by the PBS:

	*~~'''~~Schistocytes identified + thrombocytopenia:~~'''~~		*Schistocytes identified + thrombocytopenia:
	**Assume TMA until proven otherwise — calculate '''PLASMIC score''' if TTP is suspected		**Assume TMA until proven otherwise — calculate '''PLASMIC score''' if TTP is suspected
	**Send ADAMTS13 activity level (results take days; do not delay treatment)		**Send ADAMTS13 activity level (results take days; do not delay treatment)
Line 142:		Line 142:
	**'''Do NOT transfuse platelets''' in suspected TTP (may worsen microvascular thrombosis)		**'''Do NOT transfuse platelets''' in suspected TTP (may worsen microvascular thrombosis)
	**Evaluate for DIC (PT/INR, PTT, fibrinogen, D-dimer) — abnormal coagulation studies favor DIC over TTP		**Evaluate for DIC (PT/INR, PTT, fibrinogen, D-dimer) — abnormal coagulation studies favor DIC over TTP
	*~~'''~~Blasts on smear:~~'''~~		*Blasts on smear:
	**Emergent hematology/oncology consultation		**Emergent hematology/oncology consultation
	**Evaluate for [[Tumor Lysis Syndrome\|tumor lysis syndrome]] (potassium, phosphorus, uric acid, calcium, LDH, creatinine)		**Evaluate for [[Tumor Lysis Syndrome\|tumor lysis syndrome]] (potassium, phosphorus, uric acid, calcium, LDH, creatinine)
	**If WBC > 100,000/μL with blasts → concern for [[Leukostasis\|leukostasis]]; may require emergent leukapheresis		**If WBC > 100,000/μL with blasts → concern for [[Leukostasis\|leukostasis]]; may require emergent leukapheresis
	**'''Do not delay flow cytometry and bone marrow biopsy'''		**'''Do not delay flow cytometry and bone marrow biopsy'''
	*~~'''~~Malaria parasites:~~'''~~		*Malaria parasites:
	**Calculate percent parasitemia from thin smear		**Calculate percent parasitemia from thin smear
	**> 5% parasitemia or any evidence of severe malaria (altered mentation, renal failure, severe anemia, ARDS) → IV artesunate<ref name="rosenthal">Rosenthal PJ. Artesunate for the treatment of severe falciparum malaria. ''N Engl J Med''. 2008;358(17):1829-1836. PMID 18434654.</ref>		**> 5% parasitemia or any evidence of severe malaria (altered mentation, renal failure, severe anemia, ARDS) → IV artesunate<ref name="rosenthal">Rosenthal PJ. Artesunate for the treatment of severe falciparum malaria. ''N Engl J Med''. 2008;358(17):1829-1836. PMID 18434654.</ref>
	**Infectious disease consultation		**Infectious disease consultation
	*~~'''~~Spherocytes + hemolysis labs:~~'''~~		*Spherocytes + hemolysis labs:
	**Send direct Coombs (direct antiglobulin test)		**Send direct Coombs (direct antiglobulin test)
	**If positive → autoimmune hemolytic anemia; consider steroids		**If positive → autoimmune hemolytic anemia; consider steroids
	**If negative → consider hereditary spherocytosis, delayed transfusion reaction		**If negative → consider hereditary spherocytosis, delayed transfusion reaction
	*~~'''~~Leukoerythroblastic picture~~'''~~ (tear-drop cells + nucleated RBCs + immature granulocytes):		*Leukoerythroblastic picture (tear-drop cells + nucleated RBCs + immature granulocytes):
	**Suggests marrow infiltration (myelofibrosis, metastatic disease, granulomatous disease)		**Suggests marrow infiltration (myelofibrosis, metastatic disease, granulomatous disease)
	**Hematology consultation for bone marrow biopsy		**Hematology consultation for bone marrow biopsy

	==Disposition==		==Disposition==
	*~~'''~~Admit:~~'''~~		*Admit:
	**Schistocytes with thrombocytopenia (suspected TMA) — often to ICU; emergent plasma exchange for TTP		**Schistocytes with thrombocytopenia (suspected TMA) — often to ICU; emergent plasma exchange for TTP
	**Blasts on peripheral smear (suspected acute leukemia)		**Blasts on peripheral smear (suspected acute leukemia)
Line 166:		Line 166:
	**Symptomatic anemia requiring transfusion with unclear etiology		**Symptomatic anemia requiring transfusion with unclear etiology
	**Pancytopenia with fever		**Pancytopenia with fever
	*~~'''~~Discharge with urgent follow-up may be appropriate for:~~'''~~		*Discharge with urgent follow-up may be appropriate for:
	**Mild morphologic abnormalities (e.g. target cells, mild poikilocytosis) with stable CBC and known chronic condition		**Mild morphologic abnormalities (e.g. target cells, mild poikilocytosis) with stable CBC and known chronic condition
	**Confirmed pseudothrombocytopenia with normal citrate platelet count		**Confirmed pseudothrombocytopenia with normal citrate platelet count