Haematology Flashcards
What tests are required for defining tehe nature, duration and severity of anaemia?
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.
What is Anaemia?
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.
How are anaemias described?
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.
Which three classifications can anaemia be split into?
Haemorrhagic, haemolytic, non regenerative.
Describe acute blood loss causing haemorrhagic anaemia?
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.
Describe chronic blood loss causing haemorrhagic anaemia?
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.
What are the clinical signs of anaemia?
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.
How is blood loss anaemia investigated?
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.
How is acute/chronic blood loss treated?
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.
What is a haemolytic anaemia?
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.
What is intravascular haemolysis?
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.
What is extravascular haemolysis?
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.
What are some causes of haemolytic anaemia?
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.
What are Heinz body anaemias?
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.
How are haemolytic anaemias investigated?
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.
What is the treatment of haemolytic anaemias?
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.
What Is IMHA?
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.
What are non regenerative Anaemias?
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.
What are the causes of non regenerative anaemias?
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.
Which bone marrow disorders cause non regenerative anaemias?
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.
What are the typical features of a non regenerative anaemia?
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.
How is a non regenerative anaemia investigated?
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.
how is a systemic non regenerative anaemia treated?
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.
How are primary bone marrow disorders treated?
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.
Describe transfusion in patients with non regenerative anaemia?
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.
What is haemostasis?
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.
Describe Primary haemostasis?
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.
Describe secondary haemostasis?
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.
What is fibrinolysis?
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.
What are clinical signs of disordered primary haemostasis?
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.
What are the clinical signs of disordered secondary haemostasis?
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.
What are the clinical signs of disorders of fibrinolysis?
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.
How is platelet number evaluated?
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.
