Ver el código de «Peripheral blood smear»

==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/>

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