Leukogram Patterns Stress (cortisol-mediated) leukogram Expected CBC findings: • ± Mild neutrophilia (neutrophilia < 2x URL) • No left shift • Lymphopenia* (best support) Chemistry findings (may or may not be present): • Hyperglycemia (due to cortisol) • ± Monocytosis ± Eosinopenia • • Increased ALP activity (cortisol effects, dogs only) Excitement or physiologic (epinephrine-mediated) leukogram Expected CBC findings: • Mild neutrophilia (neutrophilia < 2x URL)* • Erythrocytosis (splenic contraction) • No left shift • Thromobocytosis (splenic contraction) • Mild lymphocytosis Chemistry findings (may or may not be present): • Hyperglycemia (related to epinephrine effects, multifactorial) Inflammatory leukogram Expected CBC findings to support an interpretation of an inflammatory leukogram: • Neutrophil count >2x URL • Concurrent left shift • Neutrophil toxic change (cytoplasmic basophilia, cytoplasmic foamy vacuolization, Dohle bodies, retained primary granules, donut-shaped nuclei) • Neutrophilia < 2x URL (without another obvious cause, i.e. stress or inflammation) – must be proven • Overwhelming inflammation causing neutropenia or a degenerative left shift • Lymphocytosis suggesting chronic inflammation – look for concurrent neutrophilia and/or left shift and/or neutrophil toxic change and/or monocytosis; See document on lymphocytosis for further information • Monocytosis (especially if > 2x URL) • Eosinophilia +/- Basophilia Stress Segmented neutrophils* ↑ Excitement/ Acute Chronic Overwhelming Physiologic inflammation inflammation inflammation ↑ N-↑-↑↑↑ ↑-↑↑↑↑ ↓-N ±↑ ±↑ ±↑ ± ± ± ±↓ (if stress) ±↑ ±↓ (if stress) Band neuts. or earlier Neutrophil toxic change Lymphocytes ↓ Monocytes ±↑ ±↑ (if stress) ±↑ ±↑ (if stress) Eosinophils ±↓ ±↓ (if stress) ±↑ ±↓ (if stress) ↑ *Magnitude of neutrophilia (segmented): ↑, Mild (< 2 x URL); ↑↑, Moderate (2-3 x URL); ↑↑↑, Marked (≥ 4 x URL) PVMA - November 2016 - Nicole Weinstein, DVM, DACVP – Penn Vet Clinical Pathology Specific terminology or cutoffs • • Acutevs.chronicinflammation–Thereisapproximatelya5-daysupplyofneutrophilsinthe storagepool.Themarrowisfirstdepletedofsegmentedneutrophils,thenbands,then metamyelocytes,andsoon.Neutrophilsarereleasedfromthematurationpoolintotheblood resultinginneutrophilia±leftshiftthatlastsabout2-5days.Depletionofstoragepoolneutrophils duringtheacutephasestimulatesgranulopoiesis,whichreplenishesthestoragepool.The leukogrammayrevealaneutrophiliawithorwithoutaleftshift,dependingonthedegreeoftissue inflammation.Productiontendstoequaldemand,andtheincreasedreleaseofneutrophilsfrom themarrowmayexceedthemigrationofneutrophilsintotheinflamedtissues.Thistakesovera weektoreachthischronicphase.Attimes,theneutrophiliamaypersistpasttheresolutionof inflammationuntilbonemarrowgranulopoiesisnormalizes.Oncegranulocytichyperplasiastarts,it mustcontinueuntilallofthesurplusneutrophilsarereleasedintoblood.Therefore,theWBCcount maycontinuetoincreaseornotdecrease,evenafterthesourceofinflammationhasbeen removed.Therewilloftenbeaconcurrentmonocytosiswithchronicinflammationasthe stimulatingfactoraffectsbothneutrophilandmonocytedevelopment. Overwhelminginflammation–identifiedbythepresenceofa‘degenerativeleftshift,’where immatureneutrophilsexceedmatureneutrophilsintheperipheryorthereisaneutropenia+aleft shift.Thistypicallyreflectsanacuteinflammatoryprocess,wherematureneutrophilsutilization exceedstheabilityofthemarrowto‘keepup.’Othercausesofneutropeniashouldbeexcluded,i.e. decreasedproductionofneutrophilsbythebonemarrow,immune-mediatedneutrophil destruction(rare),EDTA-inducedartifactualneutrophilclumping(incats),or,ifonlyamild decrease,duetonormalvariation,e.g.averycalmanimal. • Leukemoidresponse–neutrophilnumbers(any/alltypes)>50,000/uL o Subtypeofchronicinflammation o Calledleukemoid(leukemia-like)givennumbersofWBCsareincreasedsimilartoleukemia o Causes: § Immune-mediatedhemolyticanemia(IMHA)withresultingtissuenecrosis/death fromsevereanemia-inducedhypoxemia(e.g.centrilobularhepaticnecrosis)and/or thromboembolicdisease § The‘Ps’–Pyometra(&stumppyometra),pyothorax,peritonitis,pyelonephritis (lookforazotemia),pneumonia(chronic,notacutepneumonia),paraneoplastic (rare) § Neoplasiawithtumornecrosisorsevereassociatedtissueinflammation § Hepatozoonamericanuminfection(southernUSA,Texas) § Granulocyticorneutrophilicleukemia(atypeofchronicmyeloproliferativedisease) istheneoplasticdifferential–rare;othercausesmustberuledout Neoplastic leukogram Possible causes: • Acute leukemia – acute lymphoid leukemia; acute myeloid (i.e. non-lymphoid cells) with a variety of subclassifications, i.e. erythroid leukemia (cats); acute undifferentiated leukemia; etc. • Chronic leukemia – Chronic lymphocytic leukemia; Chronic myeloproliferative disease aka chronic myeloid leukemia (rare), e.g. polycythemia vera, essential thrombasthenia, chronic eosinophilic leukemia, etc • Circulating neoplastic cells – Secondary to circulating neoplastic lymphoid cells with lymphoma PVMA - November 2016 - Nicole Weinstein, DVM, DACVP – Penn Vet Clinical Pathology
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