Haematology

Question 0

What tests are required for defining tehe nature, duration and severity of anaemia?

Answer 0

Packed cell volume - normal: dog:38% to 57%, cat: 24% to 45%
Total serum protein -normal: dog 58-76, cat - 60-80g/l
Examination of direct smear: air dried, stained blood smear under high power (oil immersion).
Reticulocyte count (immature red cells) quantities erythrocyte regenerative responses. Can be presented as a percentage of RBCs or a total count.

Question 1

What is Anaemia?

Answer 1

A reflection of a diseased state characterised by a decreease in the number o red blood cells and or haemoglobin. As anaemia is the presenting sign of a disease, it is important to search for and treat the underlying cause. An animal whose mucous membranes are pale may have anaemia or may have decreased blood perfusion.

Question 2

How are anaemias described?

Answer 2

Tests should be done to determine if it is regenerative or non regenerative. Most cases of haemolysis or haemorrhage are regenerative. Anaemias are described as macro-, normo- or microocytic based on the cell size, or mean corpuscular volume, and as hypo or normochromic based on their mean cell haemoglobin concentration. Macrocytosis and hypochromia ocur during regeneration. Macrocytosis an also occur in some normal poodles and in cats with FeLV. Microcytosis occurs during iron deficency with hypocrhomia, in animals with portosystemic shunts and in some normal akitas.

Question 3

Which three classifications can anaemia be split into?

Answer 3

Haemorrhagic, haemolytic, non regenerative.

Question 4

Describe acute blood loss causing haemorrhagic anaemia?

Answer 4

Acute, severe blood loss causes hypovolaemic shock rather than anaemia, proportional loss of all blood components means that initially PCV nd TSP appear normal. volume expansion during recovery then progressively dilutes PCV and TSP. Loss of over 30% of blood volume in a single episode of haemorrhage can cause death due to hypovolaemic shock. Patients that survive are therefore unlikely to have lost more than 30% of circulating red cells and will not be severely aenamic unless bleeding continues at slower rate. Erythrocyte regneration featuring rising reticulocyte count, anisocytosis, polychromasia and sometimes nucleated red cells, is not evident for 3-4 days. Acute blood loss can therefore initially mimic non regenerative anaemia. Subsequent regenerative responses peak at one week, although CV may take up to 2-3 weeks to return to normal.

Question 5

Describe chronic blood loss causing haemorrhagic anaemia?

Answer 5

Reduced oxygenation of the kidneys secondary to anaemia stimulates erythropoietin release which then stimulates the bone marrow to incraese red cell production. Patients also eventually compensate for anaemia by increasing levels of red cell 2,3-diphosphoglycerate which improves the release of oxygen from haemoglobin into the tissues. Patients with chronic anaemia can compensate remarkably well and may only exhibit obvious clinical signs when the anaemia is extreme.

Question 6

What are the clinical signs of anaemia?

Answer 6

They reflect both the presence of insufficient circulating haemoglobin to oxygenate tissues (pale mucus membranes, lethargy, weakness) and compensatory sympathetic stimulation (tachypnoea, tachycardia and frequently bounding pulses). Chronic blood loss anaemia is usually very regenerative, featuring aisocytosis, polychromasia, reticulocytosis and sometimes nucleate red cells. Chronic external haemorrhage especially GI losses, may however cause eventual iron deficiency resulting in a non regenerative and microcytic hypochromic anaemia.

Question 7

How is blood loss anaemia investigated?

Answer 7

blood loss as a cause o anaemia can usually be confirmed or excluded via simple diagnostic tests. Haemostasis should be evaluated via tests such as platelet count, prothrombin time, activated partial thromboplastin time or activated coagulation test and buccal mucosal bleeding time. Potential gastrointestinal, urinary and body cavity haemorrhage can be investigated via faecal occult blood, endoparasitic faecal flotation, urine dipstick/sedimentation and thoracic/abdominal radiographs. Suspected iron deficiency may be investigated by measuring serum iron, total iron binding capacity and ferritin and possibly bone marrow stores.

Question 8

How is acute/chronic blood loss treated?

Answer 8

Identify and remove underlying cause. Vigorous volume replacement with isotonic crystalloid fluids is the initial supportive treatment of choice. Refractory cases may benefit from synthetic colloids or plasma. Packed red blood cells or whole blood is indicated in patients with moderate/severe anaemia without hypovolaemia which may occur in patients with acute severe haemorrhage following fluid therapy. Iron deficiency is treated by removing the underlying cause o blood loss and giving oral ferrous uslphate at 4-6mg of iron daily for several months it may be needed up to a year to replete stores. Only give iron supplementation if you are sure there is an iron deficiency and no infection present.

Question 9

What is a haemolytic anaemia?

Answer 9

Haemolysis destroys only erythrocytes, so blood volume, leukocytes, platelets and serum protein are usually not decreased. Acute haemolytic anaemia will appear non regenerative until the marrow responds in 3-5 days. Iron deficiency does not occur because there is no external blood loss. Haemoglobin releases from haemolysed red cells is eventually metabolised by the tissues into unconjugated bilirubin, and is then taken up by hepatocytes conjugated and excreted into ble. Massive acute haemolysis may overwhelm this process and result in jaundice.

Question 10

What is intravascular haemolysis?

Answer 10

Intravascular haemolysis releases haemoglobin directly into the circulation. Haemoglobin binds avidly to plasma haptoglobin which prevents the haemoglobin from spilling into the urine. Massive release of haemoglobin during acute severe intravascular haemolysis overwhelms haptoglobin binding leading to haemoglobinaemia and haemoglobinuria.

Question 11

What is extravascular haemolysis?

Answer 11

Since extravascular haemolysis does not release haemoglobin directly into the circulation, haemoglobinaemia and haemoglobinuria do not occur. Furthermore, jaundice occurs during acute severe haemolytic crises. haemolytic anaemia in small animals is more often extravascular. Extravascular Haemolysis is often sub acute or chronic and in the presence of normal liver function will not cause severe or persistent jaundice.

Question 12

What are some causes of haemolytic anaemia?

Answer 12

Immune mediated haemolytic anaemia, microangiopathic haemolysis, babesia infection, heinz body haemolytic anaemia, copper toxicity associated with hepatic necrosis in bedlington terriers, zinc induced haemolytic anaemia, severe hypophosphataemia, inherited erythrocyte defects (e.g pyruvate kinase deficiency in the basenji). In cats also consider FeLV associated haemolytic anaemia, mycoplasma haemofelis.

Question 13

What are Heinz body anaemias?

Answer 13

These occur due to oxidative damage to the RBC globin and subsequent damage to the RBC membrane and are more common in cats. Causes include toxicities due to paracetamol, onions, zinc and propylene glycol.

Question 14

How are haemolytic anaemias investigated?

Answer 14

Non immunologic causes of haemolytic anaemia may be investigated by obtaining a complete history and performing thoracic and abdominal radiographs to look for neoplasia or zinc foreign bodies. In the cat, FeLV testing and examination of blood smears for M. haemofelis should also be considered.

Question 15

What is the treatment of haemolytic anaemias?

Answer 15

The most effective means of treating haemolytic anaemia is to identify and treat the primary cause: surgical removal of zinc foreign bodies and operable tumours, immunosuppressive drugs, heparin and plasma, tetracyclines and phosphorous. Cage rest and standard therapy alone are sucesful in many patients with haemolytic anaemia. Blood transfusion is indicated if the patient is very affected by anaemia. Transfused red cells have a short lifespan in patients with haemolytic anaemia. Since patients with haemolytic anaemia have a normal blood volume, fluid therapy is of no benefit and may contribute to volume overload. Oxygen supplementation is also of minimal benefit. a synthetic haemoglobin has been used to treat haemolytic and blood loss anaemias.

Question 16

What Is IMHA?

Answer 16

Immune mediated haemolytic anaemia - most common cause of canine Haemolysis and can be intra or extravascular. It may occur with concurrent thrombocytopenia. It can be secondary to many causes, or occur as a primary auto immune disorder. Diagnosis is by slide agglutination, presence of spherocytes and coombs test. Cats show spherocytosis less commonly than dogs. Treatment is based on treatment of underlying disease, immunosuppressive drugs, transfusions or oxyglobin should be given as needed.

Question 17

What are non regenerative Anaemias?

Answer 17

Circulating erythrocyte lifespan in small animals is approximately 2-3 months. Non regenerative anaemia therefore develops gradually as the diseased marrow fails to replace ageing erythrocytes. Compensatory mechanisms are well established so patients intially cope despite having anaemia.

Question 18

What are the causes of non regenerative anaemias?

Answer 18

Many of the systemic disorders that cause non regenerative anaemia only produce mild anaemia whereas primary bone marrow disorders typically cause moderate to severe anaemia.
moderate/severe - iron deficiency anaemia, chronic renal failure (erythropoietin deficiency), endogenous hyperoestrogenism( gonadal tumour) feLV associated non regenerative anaemia, drug induced marrow failure (eg oestrogens, some chemotherapeutics.) IMHA of RBC precursors in the bone marrow.
Milder anaemia: anaemia of chronic disease, lead poisoning chronic liver disease, hypothyroidism, hypoadreocorticism.

Question 19

Which bone marrow disorders cause non regenerative anaemias?

Answer 19

Pure red cell aplasia, aplastic anaemia, myelophthisis: marrow replaced by fibrous tissue/collagen/ may be impossible to collect marrow aspiration and will need core biopsy. Myelodysplasia - includes a collection of haemopoietic stem cell disorders. May be a form of chronic leukaemia. haemopoetic neoplasia, ineffective erythropoiesis.

Question 20

What are the typical features of a non regenerative anaemia?

Answer 20

Minimal anisocytosis or polychromasia and has a low reticulocyte count. Erythrocytes usually appear normal (normocytic normocrhomic anaemia) serum protein is usually normal. Iron deficiency anaemia will often be microcytic hypochromic RBCS. Bone marrow disorders often cause concurrent leukopaenia and thrombocytopenia.

Question 21

How is a non regenerative anaemia investigated?

Answer 21

systemic illnesses causing depression of red cell production can usually be identified by history, physical examination and results of haematology/biochemistry. Mild to moderate non regenerative anaemia is often anaemia of chronic disease, associated with such processes as chronic inflammatory disease infection and neoplasia. Serological testing for retroviruses (immunodeficiency and leukaemia viruses) is indicated in cats with non regenerative anaemia. Bone marrow aspiration cytology and or core biopsy histopathology is essential for establishing a definitive diagnosis in patients with non regenerative anaemia due to primary marrow disorders.

Question 22

how is a systemic non regenerative anaemia treated?

Answer 22

The best method of treating non regenerative anaemia secondary to systemic disorders is to eliminate the underlying aetiology. Iron deficiency anaemia is best treated by removing the cause of chronic blood loss and administering oral ferrous sulphate. The anaemia associated with chronic kidney disease is most effectively treated with recombinant erythropoietin. Many animals develop antibodies to this erythropoietin causing an eventual failure of treatment. Treatment of the anaemia of CKD with androgens may be considered but is usually ineffective.

Question 23

How are primary bone marrow disorders treated?

Answer 23

Pure red cell aplasia and aplastic anaemia are forms of marrow failure that have been regarded as incurable without marrow transplantation. Some cases are immunological diseases with antibodies against haematopoeitic precursors in the marrow and such patients may respond to immunosuppressive therapy. Despite isolated anecdotal reports of successful responses to chemotherapy or radiotherapy, marrow neoplasia is typically an incurable disease. Myelofibrosis is also often in curable.

Question 24

Describe transfusion in patients with non regenerative anaemia?

Answer 24

Since both recipient and donor erythrocytes in animals with non regenerative anaemia often have a normal circulating lifespan, transfusion is an effective method of temporary supportive treatment and a single blood transfusion may stabilise an anaemic patient for a couple of months. The ideal transufsion end point is probably the conversion of severe anaemia into mild to moderate anaemia. Endogenous erythropoietin release may fail to be stimulated if an anaemic patient is transfused to a PCV volume of over 30% with a consequent delay in the recovery of nromal haematopoiesis. Refractory non regenerative anaemia may necessitate repeat blood transfusions every few months. Multiple transfusions over a prolonged period greatly increase the risk of transfusion reactions. Even subtle incompatibilities will decrease the circulating lifespan of donor erythrocytes, necessitating progressively more transfusions in order to maintain an adequate PCV. Blood typing dogs for dog erythrocyte antigen 1.1 Is commonly performed and recommended where available. Cross matching should always be performed prior to transfusion inc ats, and prior to a second transfusion in dogs receiving additional blood transfusions more than 5 to 7 days after the initial transfusion.

Question 25

What is haemostasis?

Answer 25

A complex process involving blood vessels, platelet and coagulation proteins. It is divided into a vascular platelet phase and a subsequent coagulation phase. The end product of haemostasis is a solid clot composed of fused platelets enclosed in a mesh of fibrin strands. Excessive clot formation is prevented by the fibrinolytic system, which acts to breakdown fibrin within blood cots.

Question 26

Describe Primary haemostasis?

Answer 26

Primary haemostasis starts with vasoconstriction triggered by vessel injury and continues ntil vessel integrity is restored and bleeding stops. As well as lacrations, vascular damage may result from trauma, excessive turbulence, indwelling catheters or inflammation. Platelets respond to vessel injury by adhering to vascular subendothelium and to other platelets, changing shape and releasing substances which promote vasoconstriction and activate more platelets. Platelet contraction and aggregation triggered by the substances released by the platelets continue until injury is sealed by a fragile platelet plug.

Question 27

Describe secondary haemostasis?

Answer 27

Primary haemostasis alone will only be temporarily beneficial unless the platelet plug is reinforced by fibrin assembled by the clotting cascade. (secondary haemostasis). Secondary haemostasis is dependent on the interacctions of a number of proteins within the intrinsi, extrinsic and common pathways of the cascade. The clotting factors are synthesised in the liver which functions in the primary plug formation rather than the clotting cascad.e The factors circulate in the plasma in an inactive form. Factors II, VII, IX and X are dependent upon vitamin K to become active.

Question 28

What is fibrinolysis?

Answer 28

The process of plasmin induced fibrin breakdown, prevents uncontrolled and wide spread clotting and is comprised of a number of mechnisms. The two most important naturally occurring anticoagulant proteins are antithrombin and protein C. when complexed with heparin sulphate, AT inactivates thrombin and can also inactivate factors X and IX. Fibrin degradation products FDP are the end products of fibrinolysis.

Question 29

What are clinical signs of disordered primary haemostasis?

Answer 29

patients with defective primary haemostasis typically present with pinpoint haemorrhage affecting the skin and mucous membranes because platelets fail to seal even tiny capillary defects. Occular haemorrhage is common. Intact secondary haemostasis often prevents major haemorrhage. Disorders of primary haemostasis typically present with multiple minor bleeds and prolonged bleeding.

Question 30

What are the clinical signs of disordered secondary haemostasis?

Answer 30

Typically causes haemorrhage into joints and body cavities. haemothorax, haemoperitoneum or haemarthrosis may cause dyspnoea, abdominomegaly or joint swelling and lameness. Although subcutaneous and intramuscular haemorrhages occur, intact primary haemostasis prevents minor capillary bleeding. Disorders of secondary haemostasis typically present with large bleeds.

Question 31

What are the clinical signs of disorders of fibrinolysis?

Answer 31

may result in thrombus formation and loss of blood supply. The formation of thrombi is promoted by: local endothelial injury, circulatory stasis and changes in anticoagulants or procoagulants. The most common mechanisms for AT deficiency are glomerular disease and accelerated consumption which occurs with disseminated intravascular coagulation or sepsis.

Question 32

How is platelet number evaluated?

Answer 32

Platelet numbers may be rapidly estimated by examination of a stained blood smear or quantified by manual counting techniques or automated haematology analysers. when estimating the numer using a blood smear, count and average the number of platelets on 10 immersion oil fields and multiply the mean by 15. Thrombocytopaenia rarely causes clinical signs until platelet count drops below 40 -50x10^9. spontaneous bleeding is more likely with counts of less than 20 to 30. clinical signs may occur at higher counts if there is a concurrent disease affecting platelet function e.g NSAID use.

Question 33

How is platelet function evaluated?

Answer 33

Via the buccal mucosa bleeeding time. BMBT should be performed only if platelet count is not low. The BMBT is the time elapsed until cessation of bleeding from a small standardised incision made in the buccal mucosa. More specialised tests of a primary haemostasis evaluate platelet aggregation, adhesion and release and meassurement of levels of Von willebrands factor.

Question 34

what is activated clotting time and how can it be evaluated?

Answer 34

Secondary haemostasis can be rapidly evaluated via the activated clotting time. the ACT is the time taken for fresh whole blood to clot in a glass tube containing a contact activator. A prolonged ACt indicated an abnormality affecting the intrinsic and common pathways of secondary homeostasis.

Question 35

What are the prothrombin and partial thromboplastin times?

Answer 35

Secondary haemostasis can be more precisely evaluated by laboratories via analysis of prothrombin time, which tests the extrinsic and common pathways and activated partial thrombopastin time, which tests the intrinsic and common pathways.

Question 36

What is the PIVKA test?

Answer 36

Proteins induced by vitamin K antagonists or absence. When there is a relative deficiency of vitamin K, the protein precursors to the vitamin K dependent coagulation factors accumulate and spill into the circulation. This test will show deficiency in these factors earlier and is more sensitive than the PT test.

Question 37

How can fibrinolysis be evaluated?

Answer 37

Evidence of excessive fibrinolytic activity can be obtained by the detection of low levels of fibrinogen and high levels of fibrinogen degradation products, the end products of fibrin breakdown. D dimer tests for specific FDPs have also been used. Evidence of pathological thrombus formation is by clinical signs relevant to the part of the body affected e.g the lungs or hindlimbs. Primary and secondary haemostasis can be adequately evaluated in most patients by initil measurement of platelet number, BMBT and ACT followed by subsequent analysis of PT, PTT, FDP and levels of vwf and specific clotting factors if indicated.

Question 38

What are vascular disorders abnormalities of primary haemostasis?

Answer 38

uncommon cause of significant haemostatic defects. Infectious diseases such as leishmania, Rocky Mountain spotted fever or dirofilaria are among potential causes of vasculitis. Pancreatitis can also cause vasculitis.

Question 39

What causes thrombocytopaenia?

Answer 39

Most common cause of defective primary haemostasis. i) decreased platelet production - aplastic anaemia, myeloproliferative disorders, megakaryocyte hypoplasia, neoplasia, chemotherapy, myelofibrosis, drugs (eg oestrogens). Increased platelet destruction - immune mediated thrombocytopaenia, consumptive coagulopathies e.g disseminated intravascular coagulation. Defective platelet function - congenital defects, uraemia, DIC, drugs - nsaids, hepatic diseases.

Question 40

What are clotting factor deficiencies?

Answer 40

Most common cause of defective secondary haemostasis - decreased production of clotting factors - deficiency of active vitamin K (anticoagulant rodenticide toxicity), hepatic failure, hereditary (haemophilia A, factor VIII deficiency). Increased consumption of clotting factors - disseminated intravascular coagulation (DIC).

Question 41

What are circulating inhibitors of coagulation?

Answer 41

Heparin, fibrin degradation products (produced as end result of DIC), lupus anticoagulant antibody against clotting factors.

Question 42

What is the management for bleeding disorders?

Answer 42

Supportive treatment - strict rest, small boer needles, catheters, avoid jugular venepuncture, avoid IM injections, body cavity haemorrhage often does not require drainage, thoracocentesis or abdominocentesis. avoid drugs that decrease platelet function.

Question 43

Which drugs should be avoided in bleeding disorders?

Answer 43

Narcotics are preferred and NsaIDs should be avoided. Penicillins aggravate clinical haemorrhage in thrombocytopenic patients and should be avoided. Tetracyclines gentamicin and sulfa drugs impair platelet function in vitro. Cefazolin and enrofloxacin have minimal effect on platelets and are recommended. Anaesthetic and sedative agents such as acepromazine, diazepam ketamine and propofol impair platelet aggregation while barbiturates and isoflurane do not. Antihistamines : H1 and H2 blockers impair platelet aggregation. H2 blockers are frequently given to thrombocytopenic animals with GIT haemorrhage. Famotidine has less of an effect on platelets than either cimetidine or ranitidine.

Question 44

when should transfusion be considered?

Answer 44

In emergencies. Transfusion of patents with bleeding disorders is used either to address the life threatening effects of blood loss such as anaemia and hypovolaemia or to replace missing platelets and or clotting factos. ALthough stored whoole blood, packed rd cells or fluids may be sufficient to treat anaemia and or hypovolaemiia, the replacement of specific haemostatic components requires transfusion with either fresh whole food or products derived from fresh blood such as platelet rich plasma, fresh plasma, fresh frozen plasma or cryoprecipitate.

Question 45

What is Von wille brands disease?

Answer 45

An autosomally inherited haemostatic disorder caused by deficiency of von willebrand factor, a large glycoprotein that facilitates platelet function (adhesion and aggregation) and is needed for primary haemostasis. Affected patients have a prolonged BMbt and decreased plasma level of vwf. Desmopressin sometimes useful for treatment - increases levels of factor VIII and vwF.

Question 46

What is Haemophilia A?

Answer 46

A sex linked hereditary disorder caused by a deficiency of factor VIII, a component of the intrinsic pathway of the clotting cascae. Affected patients have a prolonged ACt and APTT and a normal PT. Specific treatment of vwD or haemophilia A during life threatening bleeding episodes Consists of transfusion with fresh whole blood, fresh or frozen plasma or cryoprecipitate. Desmopressin may also transiently boost plasma levels.

Question 47

Describe anticoagulant rodenticide poisoning?

Answer 47

Anticoagulant rodenticides inhibit the enzyme that regenerates active vitamin K. Clotting factors II, VII, IX and X require active vitamin K n order to function. Major clotting pathways are typically all affected by anticoagulant toxicity, ACT PT and PTT are all prolonged. PIVKA test most sensitive. followed by PT, parameters of primary haemostasis wil be normal. Vitamin K1 is specific antidote for the anticoagulant toxicity and must initially be given subcutaneously then orally until the toxin is cleared from the body. Vitamin K1 can take up to 24 hours to correct clotting defects, prompt transfusion with fresh whole blood or fresh frozen plasma to immediately replenish clotting factors is indicated.

Question 48

What is disseminated intravascular coagulation?

Answer 48

Characterised by accelerated clotting leading to wide spread formation of microthrombi. Paradoxically although DIC is caused by accelerated coagulation, the condition is often only recognised when uncontrolled thrombus formation leads to defective haemostasis and bleeding. Wide spread formation of microthrombi causes depletion of platelets and clotting factors and thereby predisposes to haemorrhage. Excessive quantities of FDP may be released as the fibrinolytic system attempts t break fibrin within microthrombi. FDP inhibit both platelet function and various factors in the

Question 49

When should DIC be suspected?

Answer 49

It is one of the few disease processes that can simultaneously affect primary haemostasis, secondary haemostasis and fibrinolysis. DIC should be strongly suspected if haemostatic testing revels thrombocytopenia, elevated FDP, decreased fibrinogen and prolonged BMBT, ACT, PT and APTT.

Question 50

What is canine immune mediated thrombocytopenia?

Answer 50

Glucocorticoid therapy main treatment initial and chronic. Immunosuppressive therapy decreases antibody synthesis, decreases the binding affinity between antibodies and blood cells and decreases the destruction of antibody coated cells by the mononuclear phagocytic system. May respond to vincristine bolus. The vinca alkaloids have both mild immunosuppresive and thrombocytic properties.

Question 51

Describe acute lymphoblastic leukaemia

Answer 51

Clones of poorly differentiated neoplastic lymphoblasts proliferate with great rapidity within the bone marrow. diagnosis is based upon haematology and bone marrow aspiration. These may be so poorly diifferentiated that they cannot be distinguished from myeloid blast cells. Treatment of these cases fis fraught with difficulties as any cytotoxic drugs may exacerbate cytopenias in the short term due to their myelosuppressive effects. the prognosis is poor even with aggressive chemotherapy regimes.

Question 52

What is chronic lymphocytic leukaemia?

Answer 52

there is an uncontrolled proliferation of morphologically normal small lymphocytes in the bone marrow and blood. these cells are functionally abnormal. again, they may secondarily infiltrate the liver, spleen and lymph nodes. diagnosis is usually suggested by a lymphocytosis o of 5 to 100x10^9 or more. Bone marrow aspiration is necessary for diagnosis. treatment - chlorambucil, prednisolone. Maintainance dose can be gradually reduced based on haematological monitoring, aiming to keep the lymphocyte count wihthin normal limits and eliminate the cytopenias.

Question 53

What is multiple myeloma?

Answer 53

This form of lymphoproliferative disease encountered does not represent common diagnosis. the disease arises as a result of malignant transformation of plasma cells in the bone marrow. clinical features - hypergammaglobulinaemia - a relatively consistent feature of multiple myeloma and arises because the neoplastic cells retain their secretory ability and cause a monoclonal gammopathy. IgG gammopathies often have no effect on blood viscosity but the IgM/igA gammopathies can increase the viscosity of the blood because they are multimeric molecules. Osteolytic bone lesions - osteolysis can result in pain and may ultimately lead to fracture. collapse of affected vertebrae can result in paralysis/paresis. these lytic lesions are often poorly defined or sharply punched out. Bone marrow infiltration with plasma cells. Hypercalcaemia. Diagnosis of myeloma requires two of the following criteria - plasmacytosis of bone marrow, serum monocloncal gammopathyy, osteolytic lesons, bence jones proteinuria. Multiple myeloma is characterised by plasmacytosis of the bone marrow. examination of marrow reveals clusters of plasma cells. these plasma cells can be well differentiated or poorly differentiated.

Question 54

Describe splenic haemangiosarcomas

Answer 54

A malignant tumour arising from the vascular endothelium. the spleen is the most ocmmon primary site of haemangiosarcoma. the classical presentation is a solitary cavitated lesion which bleeds causing haemoperitoneum and hypovolaemic colapse. the tumour readily metastasised to liver and other areas of abdominal cavity and to lungs. cutaneous metastasis can be seen but this tumour also has primary cutaneous form. splenic lesions are found concurrently with right atrial lesions in some case.s haemangiosarcoma is seen more commonly in large breed dogs. The median age of affected animal is 10 years old. Dogs frequently have coagulation abnormalities such as DIC or thrombocytopenia and are often anaemic. CBC and coagulation profile, serum biochem, ultrasound, haematology may show polychromasia, hypochromasia, reticulocytosis, schistocytes, and nucleated RBCS on blood smears.

Question 55

Describe multiple myeloma

Answer 55

The pathophysiology is actually d ue to abnomrality in B lymphocytes that have an abnormal increase inproduction of anti body producing plasma cells in the bone marrow. clinical features are hypergammaglobinaemia: very consistent feature due to increase in production of IgM igA antibody production in blood leading to hyperviscosity syndrome. Osteolytic bone lesions: osteolysis can be seen in radiographs which lead to pathological fractures and ones on vertebrae lead to paralysis if severe enough. bone marrow infiltration with plasma cells:cytopenias affecting neutrophils, platelets and red blood cells. hypercalcaemia common paraneoplastic syndrome along with anorexia, vomiting, constipation, PU PD and neurological signs. diagnosis - plasmacytosis of the bone marrow, serum monoclonal gammopathy, occasionally biclonal, osteolytic bone lesions, bence jones proteinuria. treatment with melphalan and prednisolone.

Question 56

What are the possible causes of haemolytic anaemia in the cat

Answer 56

iron deficiency, chroniic renal failure, endogenous and exogenous oestrogens, FELV combined with mycoplasma haemoflies, IMHA. Mild: anaemia of chronic disease, lead poisoning, chronic liver disease, hypothyroidism, hypoadrenocorticism.

Question 57

How is non regenerative anaemia diagnosed in the dog?

Answer 57

Do a slide agglutination test should come out positive, spherocytes, positive coombs test, increased WBC, anaemia of RBC, looking at old normal looking RBC without ay sign of erythroblast formation (no anicytosis), normcytic, normochromic looking RBC, no polychromasia, no nucleated RBCC, low erythropoietin production, PCV, total serum protein, examination of blood smear, reticulocyte count. Causes: iron deficiency, chronic renal failure, endogenous and exogenous oestrogens, FELV combined with mycoplasma haemoflis, IMHA on rbc precursors, anaemia of chronic disease, lead poisonig, chronic liver disease, hypothyroidism, hypoadrenocorticism.

Question 58

What are the likely presenting signs of autoimmune haemolytic anaemia, immune mediated thrombocytopenia and systemic lupus erythematosus.

Answer 58

IMHA: most common cause of canine haemolysis - lethargic, weak, pale mucous membranes, prolonged CRT, tachypnaeia, tachycardia, high pulse, possible jaundice if severe enough on mucous membranes and sclera. Thrombocytopenia: primary haemostatic problem shows petechial to ecchymotic haemorrhagic on skin and mucosal surfaces, increased bleeding time, other than that need to do a BMBT or ACT. SLE : multisystemic auto immune disorder affecting three or more body systems, dermatology shows erosions, ulcers, scaling, IHA, IMTH, glomerulonephritis. To diagnose IMHA: do an agglutination test, check for spherocytes, do a Coombs test, check STSP, reticulocyte count (high reticulocyte count means regenerative)

Question 59

What signs are suggestive of flea infestation in an adult cat and her litter of eight week old kittens? what tests would you do to support the diagnosis?

Answer 59

Flea comb and paper to see flea dirt, magniiifying loop, look for miliary dermatitis, eosinophillic complex, symmetrical alopecia, head and neck pruritis, put cats on anti flea medication (selamectin, fipronil, imidocloprid, moxidectin). Management: kill adult fleas on contact and in contact animals (all kitetns and queen) eliminate environmental reservoir using sprays and vacuuming, alleviate pruritis in queen with short term glucocorticoids.

Question 60

What is lymphoma?

Answer 60

Lymphoma is common, malignant proliferation of lymphoid cells which can arise in any organ containing lymphoid tissue. (malignant lymphoma, lymphosarcoma same thing) Occurs most commonly in middle age animals. Bassets, boxers, bulldogs, st bernards and scottish terriers at increased risk.

Question 61

Describe the different types of lymphoma

Answer 61

The presence of a solid mass - multicentric: localised or generalised lymphadenopathy, hepatosplenomegaly, can cause respiratory embarrassment or oedema formation if lymph nodes are reducing venous flow. Thymic - anterior mediastinal mass & pleural effusion leading to respiratory signs e.g dyspnoea. Alimentary : vomiting, diarrhoea, weight loss, palpable mass. Cutaneous frms: cutaneous tumours which rapidly progress to cause systemic disease. hepatosplenic: vomiting, diarrhoea, weight loss, hepatosplenomegaly. Nasal: nasal discharge, epistaxis, epiphora, facial deformity. Ocular: uveitis, hyphaema. Systemic effects of tumour - anaemia, thrombocytopaenia, hypercalcaemia, organ failure due to lymphoid infiltration. The most frequent form is multicentric.

Question 62

What should your minimum diagnostic data base be for diagnosing lymphoma?

Answer 62

History and physical examination, complete blood count and serum chemistry, urinalysis, thoracic radiography, cytology - lymph nodes FNA, thymus - ultrasound guided FNA or tru cut needle biopsy, alimentary tract - endoscopic biopsy, cutaneous - Punch biopsy. additionally - abdominal ultrasound if a clinical examination reveals a potential abnormality, bone marrow biopsy if haematology revels unexplained cytopaenias or abnormal circulating cells.

Question 63

What are the treatment options of lymphoma

Answer 63

Give as good a possible a quality of life by putting the lymphoma into remission for as long as possible. without treatment most dogs succumb to disease 4-6 weeks. 1. no treatment. 2. Single agent therapy. Prednisolone doxorubicin and CCNU (lomustine). Multi drug chemotherapy - COP protocol cytotoxan (cyclophosphamide) oncovin (vincristine), prednisolone or CHOP, which also includes hydroxydaunorubicin (doxorubicin).

Question 64

Describe feline lymphoma

Answer 64

Systemic neoplasm of the lymphoid system that can involve multiple anatomic sites. aetiology often unknown but retroviral infection can increase risk. the anatomic site of origin important in prognosis. can include, GI, renal, CNS, nasal, mediastinal, extranodal, multicentric. Small cell lymphoma is a gastrointestinal lymphoma an indolent neoplasm that carries a good prognosis with treatment compared to GI large cell lymphoma. Biopsy needed to distinguish but important because treatment regimes differ. mitigating side effects of therapy vs disease recurrence more complicated in cats than dogs. systemic chemotherapy is indicated for treatment in diffuse disease or multi organ involvement.

Question 65

What is the role of FeLV in lymphoma?

Answer 65

Felv A is ecotropic and can only infect feline cells. FeLV b is polytropic. felv A and feline endogenous sequences present in the feline genome. felv C is also thought to arise de novo by mutation. persistemtly viraemic cats are the main source of infection the virus is secreted continuously in saliva. Lymphoma is the most common tumour of cats and can present most commonly in thymic, multicentric and alimentary forms. The mechanism of tumourogenesis includes both immunosuppression of the host and insertional effects of pro viral DNA on cellular oncogenes such as Myc. It is important to note that FELV is not isolated from all cats with lymphoma only 80% with thymic lymphoma are viraemic whilst only 60% with multicentric. These viruses may be involved as an initiating event before being cleared by the animals immune system.

Question 66

How does FIV cause tumourogenesis?

Answer 66

FIV is a lentivirus. associated with neoplastic disease in cats especially lymphoma. can be largely explained by the immunosuppression caused by the virus however a direct effect associated with viral insertional mutagenesis has been postulated.

Question 67

Hw is low grade GI lymphoma best treated? how is high grade lymphoma treated?

Answer 67

Low garde - oral prednisolone and chlorambucil. Multicentric, renal, high grade and gastointestinal and thymic forms - COP regimes provide extended remission. Doxorubicin nephrotoxic in cats.

Question 68

What is canine leukaemia?

Answer 68

a malignant neolastic disease affecting the cells of the bone marrow but sometimes originating in the spleen. neoplastic cells may or may not circulate in the peripheral blood stream. the classification of leukaemias is often difficult in dogs becaue they are often associated with mixed lineages. the clinical signs of leukaemia in dogs are referable to marrow replacement with neoplastic cells and infiltration of organs systems - mainly liver spleen and sometimes lymph nodes. the important distinction is whether the disease is acute or chroniic. acute leukaemia refers to a disease in which the majority of neoplastic cells are immature or blastic. this disease carries a grave prognosis. chronic leukaemia refers to a disease in which the majority of the neoplastic cells are mature and well differentiated. better prognosis.

Question 69

Describe the pathophysiology of leukaemia

Answer 69

Normal bone marrow contains stem cells that divide and differentiate through either the myeloid lineage (red cells, platelets, neutrophils, eosinophils, basophils and monocytes ) or lymphoid linage (T cells, B cells, BK cells, Plasma cells).. myeloid stem cells differentiate into commited colony forming units from which arise neutrophils eosinophils, monocytes, basophils, RBCs and platelets. in normal adults haematopoeisis is restricted to bone marrow within the proximal ends of long bones, the pelbic, the vertebrae and the sternum but when necessary can take place in the spleen and liver. the complex process requires, the stem cell pool, haematopoietic cytokines which are hormones that regulate haematopoiesis through both endocrine and paracrine mechanisms and the haematopoietic inductive microenvironment which is made up of the bone marrow stroma and vasculature. in leukaemia marrow infiltration due to uncontrolled proliferation results in crowding out of normal marrow elements, competition for nutrients, the failure of the marrow to elaborate normal stimulatory factors and the build up of inhibiitory factors released by the neoplastic cells. as a result normal blood cell production is reduced, the first manifestation of this is neutropenia followed by thrombocytopenia. it is considered that leukaemia is a true stem cell disease i.e malignant transformation takes place in the stem cell. The nature of that change will dictate the lineage affected and the degree by which differentiation is blocked.

Question 70

What are the general haematological features of leukaemia

Answer 70

Non regenerative anaemia due to myelopthesis and effects of chronic disease or a regenerative anaemia - immune mediated secondary to tumour. Neutropenia, leukocytosis, thrombocytopenia, usually due to marrow ablation or secondary immune mediated mechanisms, bleeding diathesis - DIC as a terminal event, as a complication of elevated gammaglobulins, liver failure, thrombocytopaenia. Hyperviscosity of the blood can occur when there are vastly elevated numbers of cells int he circulation or due to hypergammaglobulinaemia which results from aberrant production of immunoglobulins by neoplastic B cells. IgA and igM producing tumours cause more severe hyperviscosity than igG as the former are multimeric molecules. clinical consequences include - bleeding diathesis due to interference of para proteins with platelet function and clotting factors, occular changes, neurological signs due to poor perfusion, PUPD due to poor perfusion and renal tubular and glomerular damage, thromboembolism.

Question 71

What are the general biochemical abnormalities associated with leukaemia?

Answer 71

Hypercalccaemia - most common. azotaemia- secondary to Hypercalcaemia or hyper viscosity which can result in renal tubular and glomerular damage or poor renal perfusion. monoclonal gammopathy - associated with multiple myeloma and some b lymphoid leukaemias and lymphomas. hypoproteinaemia, gastrointestinal protein loss du to tumour infiltration of the gut. elevated enzyme liver activity - consequence of hepatic infiltration. hyperkaaemia - large numbers of atypical lymphoid cells in the circulation, potassium may become artefactually increased due to release from firable cells, hypoglycaemia - large numbers of abnormal white blood cells may metabolize glucose

Question 72

What are the main clinical features of leukeamia?

Answer 72

Acute onset of clinical signs, dullness and lethargy, acute leukaemic patients often present quite sick with marked clinical signs. dogs with chronic leukaemias often feel quite well and is an incidental finding. anorexia, anaemia, pallor of mucous embranes, splenoegaly, hepatomegaly, lymphadenopathy. In chronic leukaemias - mild anaemia, more indolent in nature, splenomegaly, often no clinical signs.

Question 73

Describe the classifications of leukaemia

Answer 73

For simplicity they can be divided as either lymphoid or myeoid. Lymphoid tumours - acute lymphoblastic leukaemia (poorly differentiated lymphoblasts in blood and bone marrow), chronic lymphocytic leukaemia (abnormally elevated numbers of mature lymphocytes in blood and bone marrow.) and multiple myeloma (malignant transformation and clonal expansion of a plasma cell (B lymphocytes) become antibody secreting plasma cells.)

Question 74

What is myeloproliferative diease?

Answer 74

Myeloproliferative disease encompasses all the non lymphoid dysplastic and neoplastic conditions arising from the haemapoietic stem cells or their progeny. including: granulocytic leukaemia, monocytic leukaemia, myelomonocytic leukaemia, eosinophilic leukaemia, basophilic leukaemia, polycythaemia rubra vera, erythroleukaemia, thrombocytothaeemia, myelodysplasia ETC.

Question 75

Describe acute lymphoblastic leukaemia

Answer 75

Clones of poorly differentiated neoplastic lymphoblasts proliferate with great rapidity within the bone marrow. diagnosis based o haematomoology and bone marrow aspiration. treatment is difficult as many cytotoxic drugs exacerbate cytopaenias.

Question 76

What is chronic lymphocytiic leukaemia

Answer 76

There is an uncontrolled proliferration of morphologically normal small lymphocytes int he bone marrow and blood. they are functionally abnormal. they may secondarily infiltrate the liver spleen and lymph nodes. diagnosis usually suggested by lymphocytosis of 5to100x10^9 or more. Bone marrow aspiration required for diagnosis. treatmeent with chlorambucil and prednisolone.

Question 77

Describe multiple myeloma

Answer 77

A result of malignant transformation of plasma cells in the bone marrow. clinical features are hypergammaglobulinaemia because the neoplastic cells cause a monoclonal gammopathy. Osteolytic bone lesions & bone marrow infiltration with plasma cells, hypercalcaemia. Diagnosis requires - plasmacytosis of the bone marrow, serum monoclonal gammopathy, osteolytic lesions, bence jones proteinuria. multiple myeloma is characterised by plasmacytosis of the bone marrow. examination of marrow reveals clusters of plasma cells. these plasma cells can be well differentiated or poorly differentiated.

Question 78

How is multiple myeloma treated?

Answer 78

Melphalan & prednisolon. Treat hyperviscosity if present. Bisphosphonates may be considered to alleviate dis comfort associated with osteolytic lesions and to reduce paraneoplastic hypercalcaemia.

Question 79

Describe treatment of chronic granulocytic leukaemia

Answer 79

The aim of treatment is to reduce the granulocyte count to normal levels and attempt to correct any other haematological abnormality. the drug of choice is busulphan. this is an alkylating agent which is specific to granulocytic series. given at 2-6mg/m2 daily.

Question 80

Describe leukaemia in the cat

Answer 80

Acute lymphoid leukaemia - most common leukaemia. poorly differentiated lymphoblasts in blood and bone marrow. usually T cell. 75% are FeLV positive. Chronic lymphoid leukaemia rare. mature lymphocytes in blood and bone marrow. Granulocytic leukaemia - rare. Myelofibrosis - abnormal growth and diifferentiation of erythroid myeloid and megakarycytic cell types.

Question 81

Describe tumours of the spleen

Answer 81

Canine spleen can be the site for both malignant and benign tumours and non neoplastic disease. splenic tumours tend to occur in middle aged to older patients. clinical signs can be vague or non existant or dramatic. approximately two thirds of canine splenic lesions are neoplasstic. 50% of feline splenic lesions are neoplastic. splenic lesions may be generalised or localised. ultrasound will give better categorisation. Cytology not always accurate. haemangiosarcoma frequently has areas of haemorrhage and fibrosis. Benign - haematoma, abscess, nodular hyperplasia, extarmedullary haemapoeisis, myelolipoma, haemangioma, malignant - haemangiosarcoma, fibrosarcoma, leiomyosarcoma, histiocytic sarcoma, metastatic disease.

Question 82

Describe haemangiosarcoma of the spleen

Answer 82

Malignant tumour arising from the vascular endothelium. the spleen is the most common primary site of Haemangiosarcoma. the classical presentation is a solitary cavitated lesion which bleeds causing haemoperitoneum and hypovolaemic collapse. this tumour readily metastasises to the liver and other areas. splenic lesions found concurrently with right atrial lesions in a quarter of cases. Dogs with haemangiosarcoma frequently have coagulation abnormalities such as DIC or thrombocytopenia and often are anaemic. Cbc and coagulation profile, serum biochemistry, ultrasonography of the abdomen, liver and spleen. haematology may show polychromasia, hypochromasia, reticulocytosis, schistocytes and nucleated RBCS on blood smears.