Aktuell Anämie Englisch einzeln - Laboklin · induce regenerative, hemolytic anaemia. The ... Aktuell Nr.6Englisch: ... o drug-ortoxin-induced o neoplastic(e.g.lymphoma)

Anemia in dogs and cats – guidelines forthe veterinary practice

LABOR FÜR KLINISCHE DIAGNOSTIK GMBH & CO.KG Info 6/2010 Page 1Steubenstraße 4 • 97688 Bad Kissingen • Phone: +49(0)971/72020 • Fax: +49(0)971/68546 • www. laboklin.com


Increased travelling with pets and the import ofrescued animals from all over the world createnew challenges for the veterinary practitioner.A frequently found clinical and laboratory diagnosisin these patients is anaemia. Sometimes theexact classification of anaemia can be difficult.Anaemia is a decrease of the erythrocyte contentof blood. The typical clinical signs are palemucous membranes, the laboratory characteri-stics of anaemia are decreased values of theerythrogramm.

There are different classification systems ofanaemia, each with its advantages and limitati-ons.The classification used in this article is based onbone marrow responsiveness, assessed by thenumber of reticulocytes in the peripheral blood.The major advantage of this method is its practi-

procariotic bacteria.Babesia, rickettsia and hemotropic mycoplasmaspecies cause direct damage of the erythrocytesby parasitizing in the red blood cells or in theirmembrane.Blood parasites can also provoke immune-mediated hemolytic anaemia.Ehrlichia canis and anaplasma spp. parasitizein monocytes or neutrophilic granulocytes,respectively and lead to anaemia by productionof antibodies against the erythrocyte membrane.

Confirmation by microscopic examination orPCR is only reliable in acute disease, whereas inchronic cases the antibody detection should bepreferred.

In both monocytic or granulocytic ehrlichiosisthrombocytopenia is frequent and prominent,while anemia can be mild to moderate, in casesof chronic e. canis infections severe anemia andhemostasis problems can occur.Thrombocytopenia is easily recognized byexamination of a blood smear and is of good dia-gnostic value.

cability. By means of a stained blood smear anda microscope the presence of reticulocytosis caneasily be estimated in every in-house lab.

Intoxication

A variety of toxins can provoke regenerative ornon regenerative anaemia.Intoxications by zinc or other heavy metalsinduce regenerative, hemolytic anaemia. Thecausative mechanism is the integration of themetal into the hemoglobin instead of iron. As aconsequence of this erythrocytes are destroyed.The bone marrow however is capable of maintai-ning erythropoesis, even though an incompleteone.Concerning non regenerative anaemia leadintoxication and estrogen toxicosis have to bementioned. High serum levels of estrogeninduced e.g. by sertoli cell tumour or granulosacell tumour sometimes cause severe bonemarrow hypoplasia in dogs.

Final remark

This article makes no claim to be complete,because it is not always possible to „press“ thepathogenesis of anaemia into certain schemes.It is supposed to provide a quick guide for theveterinary practitioner and support the reader inachieving a precise and efficient diagnostic pro-cess.In case of doubt however further medical proce-dures like imaging techniques are necessary tomake a diagnosis.

Diagrams adapted from Willard, Tvedten, Turnwald:Small Animal Clinical Diagnosis by LaboratoryMethods 2nd Edition

Fig. 1: Pale mucous membranes of an anaemic dog

Fig. 5: Anaplasma phagozytophilum (morula)

Fig. 4: Hemotropic mycoplasms

Aktuell Nr. 6 Englisch:Layout 1 03.11.2010 13:13 Uhr Seite 1



CAVE: sometimes there is immunmediatedhemolytic anaemia that does not show signs ofregeneration!

Non Regenerative Anaemia

The etiology of non regenerative anaemia ismuch more divers. In various chronic diseasesthere is a reactive decrease of erythropoesis.(Table 2).

In this case an organ screening especially of thekidneys and liver is recommended. Chronic renalinsufficiency decreases erythropoesis in bonemarrow via decreased erythropoetin production.

Increased activity of liver enzymes and elevatedliver function tests may indicate a decreasedsynthesis of proteins, in particular gobulins, thatare essential for hemoglobin synthesis in bonemarrow.Increased unconjugated Bilirubin can also besuggestive of hemolytic anaemia and may berecognized by yellow colouration of plasma.

Nutrient deficiency

With conventional feeding malnutrition is a rarecondition nowadays, nevertheless it should beconsidered as differential diagnosis, if othercauses of anaemia have been ruled out.In iron deficiency there is not enough iron to beincorporated into hemoglobin and a hypochro-mic, in later stages even microcytic anaemiadevelops.This can be verified by determining the CHR,which is consistent with the hemoglobin contentin reticulocytes.A shortage in copper also causes defectivehemoglobin sythesis. Evaluation of copper statusin serum is the method of choice to confirmcopper deficiency.

Indication for bone marrow aspiration

In non regenerative anaemia without detectablesystemic cause a bone marrow examination isthe best way to find a diagnosis.Especially when pancytopenia is present and forthe diagnosis and staging of hematopoeticneoplasia, but also to provide samples for PCRof infectious agents (leishmania, ehrlichia,…) abiopsy of bone marrow is indicated.

Diagnosis

After determining the severity of the anaemia byassessing the erythrocyte count, the hematocritand hemoglobin, the regenerative capability ofthe bone marrow is evaluated.For this purpose the enumeration of reticulocytesis gold standard. A regenerative anaemia ischaracterized by reticulocytosis (dog > 60,0 /nland cat > 30,0 /nl). It may take up to 96 hoursuntil reticulocytosis becomes detectable inperipheral blood.The estimation of bone marrow responsivenessby examination of a blood smear is easily perfor-med in the in-house lab. Polychromasia oferythrocytes (Fig. 2) is evidence of regenerationin properly stained smears. Polychromasia isless pronounced in cats than in dogs.

Regenerative Anaemia

Regenerative anaemia is caused by blood lossor a shortened life span of the erythrocytes(hemolysis).A low total protein is suggestive rather of bloodloss anaemia than of hemolysis, becausebleeding patients loose erythrocytes togetherwith plasma proteins.

When blood loss anaemia is suspected it is advi-sable to assess furthermore the platelet concen-tration and the coagulation times (thromboplastintime, partial thromboplastin time, thrombin time).The determination of the buccal mucosalbleeding time (BMBT) is an easily performed testof platelet function in practice.

Infectious causes of anaemia

In this etiologic group regenerative as well asnon regenerative anaemias are comprised.For quite some time the terminus feline/canineinfectious anaemia is encountered in literaturefrequently. The infectious agents in this case arehemotropic mycoplasma species (formerlyhemobartonalla spp.). But there are far moreinfectious causes of anaemia in dogs and cats.

Infectious disease in general

In every febrile disease a temporary, often mildanaemia may be caused by the elevated bodytemperature. In other cases the infectious agentitself is able to induce amaemia e.g. by suppres-sion of the bone marrow. In this context the FeLVand FIV induced anaemia in the cat has to bementioned above all.

Blood parasites

The term „blood parasites“ covers a heteroge-nous group of microorganisms, e.g. babesia andhepatozoon are eucariotic protozoa, while ricett-sia or hemotropic mycoplasma species are

In chronic cases of blood loss bone marrowresponsiveness decreases because irondeficiency develops over time. The hemoglobinconcentration of reticulocytes (CHR) is a newlyavailable parameter that detects iron deficiencyearlier and more sensitive than microcytosisand hypochromasia, which develop at a laterstage of iron deficiency anaemia. Determinationof CHR is included in the reticulocyte count atLABOKLIN.

Highly regenerative anaemias – > 100 /nl in catsand > 120 /nl in dogs – are normally caused byhemolytic anaemia or acute blood loss. If blee-ding is ruled out, the list of differential diagnosisof hemolyses has to be reviewed.

Etiology of hemolytic anaemia:

� Reduced membrane stabilitye.g. PK deficiency, PFK deficiency

� Mechanic destructiono In capillaries e.g. glomerulonephritis,

DIC, neoplasia...o Turbulences in large vessels e.g. in

massive dirofilariosis� Toxic lysis

(e.g. Heinz body anaemia, hypophosphatemia)� Blood parasites (lysis by infectious agent

directly) frequently in combination with� IMHA (=immunmediated haemolytic anaemia)

o infectious (blood parasites but also ohterinfectious disease)

o drug- or toxin-inducedo neoplastic (e.g. lymphoma)o idiopathic (autoimmune)

Immunemediated hemolysis is confirmed if thecoombs-test gives a positive result.The coombs-test detects antibodies againsterythrocytes. In vivo these are recognized on theerythrocyte surface by cells of the mononuclearphagocyte system that subsequentlyphagocytize affected erythrocytes. The directcoombs test detects antibodies on theerythrocyte surface, the indirect one circulatingantibodies in serum.

In the course of hemolytic anaemia occasionallyvery small, spherical erythrocytes may be foundon blood smears, so called spherocytes. A highnumber of spherocytes is considered diagnosticfor IMHA.

Fig. 2: Polychromatic erythrocytes

Fig. 3: Babesia canis




CAVE: sometimes there is immunmediatedhemolytic anaemia that does not show signs ofregeneration!

Non Regenerative Anaemia

The etiology of non regenerative anaemia ismuch more divers. In various chronic diseasesthere is a reactive decrease of erythropoesis.(Table 2).

In this case an organ screening especially of thekidneys and liver is recommended. Chronic renalinsufficiency decreases erythropoesis in bonemarrow via decreased erythropoetin production.

Increased activity of liver enzymes and elevatedliver function tests may indicate a decreasedsynthesis of proteins, in particular gobulins, thatare essential for hemoglobin synthesis in bonemarrow.Increased unconjugated Bilirubin can also besuggestive of hemolytic anaemia and may berecognized by yellow colouration of plasma.

Nutrient deficiency

With conventional feeding malnutrition is a rarecondition nowadays, nevertheless it should beconsidered as differential diagnosis, if othercauses of anaemia have been ruled out.In iron deficiency there is not enough iron to beincorporated into hemoglobin and a hypochro-mic, in later stages even microcytic anaemiadevelops.This can be verified by determining the CHR,which is consistent with the hemoglobin contentin reticulocytes.A shortage in copper also causes defectivehemoglobin sythesis. Evaluation of copper statusin serum is the method of choice to confirmcopper deficiency.

Indication for bone marrow aspiration

In non regenerative anaemia without detectablesystemic cause a bone marrow examination isthe best way to find a diagnosis.Especially when pancytopenia is present and forthe diagnosis and staging of hematopoeticneoplasia, but also to provide samples for PCRof infectious agents (leishmania, ehrlichia,…) abiopsy of bone marrow is indicated.

Diagnosis

After determining the severity of the anaemia byassessing the erythrocyte count, the hematocritand hemoglobin, the regenerative capability ofthe bone marrow is evaluated.For this purpose the enumeration of reticulocytesis gold standard. A regenerative anaemia ischaracterized by reticulocytosis (dog > 60,0 /nland cat > 30,0 /nl). It may take up to 96 hoursuntil reticulocytosis becomes detectable inperipheral blood.The estimation of bone marrow responsivenessby examination of a blood smear is easily perfor-med in the in-house lab. Polychromasia oferythrocytes (Fig. 2) is evidence of regenerationin properly stained smears. Polychromasia isless pronounced in cats than in dogs.

Regenerative Anaemia

Regenerative anaemia is caused by blood lossor a shortened life span of the erythrocytes(hemolysis).A low total protein is suggestive rather of bloodloss anaemia than of hemolysis, becausebleeding patients loose erythrocytes togetherwith plasma proteins.

When blood loss anaemia is suspected it is advi-sable to assess furthermore the platelet concen-tration and the coagulation times (thromboplastintime, partial thromboplastin time, thrombin time).The determination of the buccal mucosalbleeding time (BMBT) is an easily performed testof platelet function in practice.

Infectious causes of anaemia

In this etiologic group regenerative as well asnon regenerative anaemias are comprised.For quite some time the terminus feline/canineinfectious anaemia is encountered in literaturefrequently. The infectious agents in this case arehemotropic mycoplasma species (formerlyhemobartonalla spp.). But there are far moreinfectious causes of anaemia in dogs and cats.

Infectious disease in general

In every febrile disease a temporary, often mildanaemia may be caused by the elevated bodytemperature. In other cases the infectious agentitself is able to induce amaemia e.g. by suppres-sion of the bone marrow. In this context the FeLVand FIV induced anaemia in the cat has to bementioned above all.

Blood parasites

The term „blood parasites“ covers a heteroge-nous group of microorganisms, e.g. babesia andhepatozoon are eucariotic protozoa, while ricett-sia or hemotropic mycoplasma species are

In chronic cases of blood loss bone marrowresponsiveness decreases because irondeficiency develops over time. The hemoglobinconcentration of reticulocytes (CHR) is a newlyavailable parameter that detects iron deficiencyearlier and more sensitive than microcytosisand hypochromasia, which develop at a laterstage of iron deficiency anaemia. Determinationof CHR is included in the reticulocyte count atLABOKLIN.

Highly regenerative anaemias – > 100 /nl in catsand > 120 /nl in dogs – are normally caused byhemolytic anaemia or acute blood loss. If blee-ding is ruled out, the list of differential diagnosisof hemolyses has to be reviewed.

Etiology of hemolytic anaemia:

� Reduced membrane stabilitye.g. PK deficiency, PFK deficiency

� Mechanic destructiono In capillaries e.g. glomerulonephritis,

DIC, neoplasia...o Turbulences in large vessels e.g. in

massive dirofilariosis� Toxic lysis

(e.g. Heinz body anaemia, hypophosphatemia)� Blood parasites (lysis by infectious agent

directly) frequently in combination with� IMHA (=immunmediated haemolytic anaemia)

o infectious (blood parasites but also ohterinfectious disease)

o drug- or toxin-inducedo neoplastic (e.g. lymphoma)o idiopathic (autoimmune)

Immunemediated hemolysis is confirmed if thecoombs-test gives a positive result.The coombs-test detects antibodies againsterythrocytes. In vivo these are recognized on theerythrocyte surface by cells of the mononuclearphagocyte system that subsequentlyphagocytize affected erythrocytes. The directcoombs test detects antibodies on theerythrocyte surface, the indirect one circulatingantibodies in serum.

In the course of hemolytic anaemia occasionallyvery small, spherical erythrocytes may be foundon blood smears, so called spherocytes. A highnumber of spherocytes is considered diagnosticfor IMHA.

Fig. 2: Polychromatic erythrocytes

Fig. 3: Babesia canis


Anemia in dogs and cats – guidelines forthe veterinary practice



Increased travelling with pets and the import ofrescued animals from all over the world createnew challenges for the veterinary practitioner.A frequently found clinical and laboratory diagnosisin these patients is anaemia. Sometimes theexact classification of anaemia can be difficult.Anaemia is a decrease of the erythrocyte contentof blood. The typical clinical signs are palemucous membranes, the laboratory characteri-stics of anaemia are decreased values of theerythrogramm.

There are different classification systems ofanaemia, each with its advantages and limitati-ons.The classification used in this article is based onbone marrow responsiveness, assessed by thenumber of reticulocytes in the peripheral blood.The major advantage of this method is its practi-

procariotic bacteria.Babesia, rickettsia and hemotropic mycoplasmaspecies cause direct damage of the erythrocytesby parasitizing in the red blood cells or in theirmembrane.Blood parasites can also provoke immune-mediated hemolytic anaemia.Ehrlichia canis and anaplasma spp. parasitizein monocytes or neutrophilic granulocytes,respectively and lead to anaemia by productionof antibodies against the erythrocyte membrane.

Confirmation by microscopic examination orPCR is only reliable in acute disease, whereas inchronic cases the antibody detection should bepreferred.

In both monocytic or granulocytic ehrlichiosisthrombocytopenia is frequent and prominent,while anemia can be mild to moderate, in casesof chronic e. canis infections severe anemia andhemostasis problems can occur.Thrombocytopenia is easily recognized byexamination of a blood smear and is of good dia-gnostic value.

cability. By means of a stained blood smear anda microscope the presence of reticulocytosis caneasily be estimated in every in-house lab.

Intoxication

A variety of toxins can provoke regenerative ornon regenerative anaemia.Intoxications by zinc or other heavy metalsinduce regenerative, hemolytic anaemia. Thecausative mechanism is the integration of themetal into the hemoglobin instead of iron. As aconsequence of this erythrocytes are destroyed.The bone marrow however is capable of maintai-ning erythropoesis, even though an incompleteone.Concerning non regenerative anaemia leadintoxication and estrogen toxicosis have to bementioned. High serum levels of estrogeninduced e.g. by sertoli cell tumour or granulosacell tumour sometimes cause severe bonemarrow hypoplasia in dogs.

Final remark

This article makes no claim to be complete,because it is not always possible to „press“ thepathogenesis of anaemia into certain schemes.It is supposed to provide a quick guide for theveterinary practitioner and support the reader inachieving a precise and efficient diagnostic pro-cess.In case of doubt however further medical proce-dures like imaging techniques are necessary tomake a diagnosis.

Diagrams adapted from Willard, Tvedten, Turnwald:Small Animal Clinical Diagnosis by LaboratoryMethods 2nd Edition

Fig. 1: Pale mucous membranes of an anaemic dog

Fig. 5: Anaplasma phagozytophilum (morula)

Fig. 4: Hemotropic mycoplasms


Documents

Aktuell Anämie Englisch einzeln - Laboklin · induce regenerative, hemolytic anaemia. The ... Aktuell Nr.6Englisch: ... o drug-ortoxin-induced o neoplastic(e.g.lymphoma)