The anaemic cancer patient

11 The anaemic cancer patient


Anaemic animals can have many underlying conditions causing the problem, so it is vital that a logical, stepwise clinical approach is taken to ensure an accurate diagnosis is reached. The first question to ask once a patient is diagnosed with anaemia is whether the anaemia is regenerative or non-regenerative, as the differential diagnoses to be considered and the diagnostic evaluations to be undertaken will differ once this question has been answered. The determination as to whether a patient has regenerative anaemia or not can be indicated by the presence of polychromasia and anisocytosis on blood smear examination, but the most accurate way is made by assessing the reticulocyte count using a supravital stain such as a new methylene blue (NMB) on a freshly made blood smear. To undertake a reticulocyte count, the clinician should:







Absolute reticulocyte counts are generally the most useful assessment to make, as percentage reticulocyte values will always be affected by the total red cell count (already low in an anaemic patient). The corrected reticulocyte percentage can help determine whether or not the degree of regeneration is appropriate for the degree of anaemia but this is not always a reliable assessment. The reticulocyte production index, likewise, is a tool to help determine whether or not the degree of response seen is appropriate (Box 11.1).



If the clinician does not have a supravital stain available a regenerative anaemia can also be assessed by simply looking at a normally stained blood smear and looking for anisocytosis and polychromasia. Routine blood smears are also very useful to look for other erythrocyte changes, such as microcytosis or hypochromasia, both of which may suggest iron deficiency and therefore a possible chronic blood loss problem. However, the presence of polychromasia or anisocytosis does not truly define whether an anaemia is regenerative or not, so an absolute reticulocyte count should be obtained in all anaemic animals.



CLINICAL CASE EXAMPLE 11.1 – A HAEMORRHAGING SPLENIC MASS IN A DOG










Theory refresher


Haemangiosarcoma (HSA) is a malignant mesenchymal tumour that arises within the vascular endothelium and most commonly develops (in dogs) within the spleen where it accounts for approximately half of all splenic neoplasms. The other predilection sites include the right atrium, skin, pericardium, liver, lungs, kidneys, oral cavity, muscle, bones, the urinary bladder and peritoneum. The predilection sites in cats are different in that there is an approximately even incidence of 50% occurrence between the visceral form (which includes disease in the spleen, liver and/or intestines) and the skin form.


HSA is a tumour generally seen in older animals, with most studies reporting a mean age of occurrence of between 8 and 13 years of age. However, as the case reported here illustrates, the tumour can occur in much younger animals. Large-breed dogs appear to be over-represented with the German shepherd dog seemingly the most commonly affected breed and some studies suggest that male dogs may be more frequently affected than females. Non-cutaneous HSA in dogs is usually associated with having aggressive metastatic behaviour, probably somewhat in part due to the close approximation of the tumour cells with the vasculature and patients presenting with signs that could be consistent with a splenic mass should always undergo careful clinical staging prior to excision of any mass whenever possible. Splenic HSAs that bleed are also at risk for developing serosal metastasis, as the primary tumour is often very friable and many cases appear to have bled before the problem is diagnosed, meaning that metastatic disease can develop in places such as the omentum, mesentery and diaphragm as well as the more expected locations such as the liver and lungs. HSA also has a relatively high rate of metastasis to the brain and has been cited as the mesenchymal tumour most likely to spread to the CNS in dogs, with an incidence figure of 14% being reported in one study. Visceral HSA in cats can also behave aggressively, but the cutaneous form in either species is usually not so aggressive.


HSA patients can present with variable clinical signs depending upon the location and size of the tumour. Common signs include (episodic) weakness, pallor, weight loss, abdominal distension and signs of right-sided heart failure due to the presence of a pericardial effusion. In particular, a history of note is a large-breed dog that presents with signs of acute collapse that seems to correct spontaneously, as was described in this case. It is thought that in such cases the collapse is caused by acute hypotension following a haemorrhagic episode which then corrects as the red cells are reabsorbed into the circulation. Collapse could also be due to the presence of a tumour within the heart, causing either a physical obstructive effect to right-sided cardiac output, the development of a cardiac arrhythmia or cardiac tamponade caused by haemorrhage within the pericardial sac. However, some cases will simply present with vague signs of waxing and waning lethargy, or simply of abdominal distension.



Cutaneous HSA presents as discrete firm, raised, dark red to purple papules or nodules, or possibly also subcutaneous haemorrhaging masses.



The diagnosis is therefore usually made based on a combination of clinical history, clinical examination findings and diagnostic imaging findings. If a mass is found within the spleen, then it is often best to recommend not obtaining fine needle aspirates, as if the mass proves to be an HSA, then the act of aspiration itself is likely to cause haemorrhage, thereby substantially increasing the risk of seeding tumour cells throughout the abdomen and establishing metastatic lesions. It is very important to remember that there is a long differential diagnosis list for masses within the spleen (haematoma, haemangioma, splenic nodular hyperplasia, leiomyosarcoma, lymphoma, malignant fibrous histiocytoma) and some studies have suggested that up to 45% of splenic masses may NOT be malignant, so obtaining biopsies for histopathology is mandatory. The mainstay of treatment therefore is complete surgical splenectomy, performed via a midline celiotomy but prior to surgery it is prudent to undertake a full coagulation profile (manual platelet count, one-stage prothrombin time and activated partial thromboplastin time or an activated clotting time if available in an emergency, and a d-dimer assessment) as HSA is a tumour that is associated with paraneoplastic coagulopathies such as disseminated intravascular coagulation (DIC). The reason for this is that the blood vessels within the tumour itself are anatomically abnormal, which causes platelet aggregation and also significant shear-stress to the red cells as they pass through, which results in erythrocyte damage, such as the formation of schistocytes and/or acanthocytes. In addition to these structural changes, the blood vessels within the tumour often have incomplete endothelial linings, thereby exposing underlying collagen and stimulating the coagulation cascade. All of these changes can lead to inappropriate coagulation and the eventual deregulation of the cascade, causing DIC. A full coagulation assessment therefore is vital. However, once this has been found to be normal, surgery can proceed. The incision should be large (extending from the xyphoid to the pubis) to allow removal of very large splenic tumours and also provide access for a full abdominal exploration which must include the liver, mesentery and local lymph nodes. Any suspicious lesions in these areas should be either aspirated or biopsied at the time of surgery as well. A complete splenectomy rather than a partial splenectomy is indicated with either suspected or confirmed malignant neoplasia.



Splenectomy can be performed either by ligating individual hilar vessels close to the spleen as they enter the parenchyma or it can be performed by ligation of the major splenic vessels (including the short gastric arteries). The latter technique is a much faster and simpler technique and has been shown not to compromise the vascular supply to the stomach. Omental adhesions to the spleen can be bunch ligated and divided (Fig. 11.3). Ligation of the splenic artery and vein is best achieved using a double-ligation technique. A suture material that has good handling properties (e.g. silk) or forms secure ligatures is appropriate for performing this surgery.



An alternative to suture material is to use vascular clips or a mechanical stapler. The ligating dividing stapler (LDS) is a device that simultaneously places two clips (made of stainless steel or titanium) on a vessel as a blade cuts between them. Each cartridge contains 15 pairs of ‘U’-shaped staples. Vessels that need to be double ligated need to have a single ligature placement before the LDS is applied (Fig. 11.4). This device decreases surgical time by performing rapid vascular occlusion and is extremely useful in splenectomies.



After the splenectomy is complete and exploratory laparotomy performed, the abdominal cavity is lavaged and closed routinely. If possible the entire spleen should be submitted for histopathology; however, if this is not feasible then a representative sample should be submitted and the remainder stored in formalin in case the need for further sample submission becomes necessary.




Postoperative chemotherapy has been considered in many studies and the general conclusion of these is that adjunctive chemotherapy using a doxorubicin-containing protocol definitely improves the outcome for all cases except for small, simple cutaneous tumours for which the prognosis is good anyway. The prognosis for all other forms of haemangiosarcoma is still guarded even with good chemotherapy. Doxorubin has been administered as a single-agent treatment given either at 2- or 3-weekly intervals or in combination with vincristine and cyclophosphamide (the so-called ‘VAC’ protocol) and survival times of between 172 and 250 days are reported, compared with other publications reporting postoperative survival times of 65 days or less without adjunctive chemotherapy. What does become apparent on reading these reports is that the tumour burden and clinical tumour stage are the most important prognostic factors, so as with the other tumours described in this text, it is good clinical practice to establish the clinical stage of the disease using the TNM system (Box 11.2).



The study which evaluated the use of doxorubicin given every 2 weeks for a total of five cycles showed that clinical stage related to median survival times in the following manner: stage I disease, 257 days; stage II disease, 210 days; stage III disease, 107 days. The prognosis for dogs with non-cutaneous HSA is therefore guarded and even with adjunctive chemotherapy and surgery the 1-year survival rate is no better than 10%. The prognosis for visceral HSA in cats is also generally poor. However, the prognosis for the cutaneous form of the disease is a little better. If the tumour is restricted solely to the dermis without deeper invasion, a study of 25 dogs showed that the median survival time was 780 days, compared to a median survival time of 172 days if the tumour was invading into the subcutaneous tissue. Good histopathology is therefore required in these cases, as adjunctive therapy should certainly be considered in invasive dermal HSA but not necessarily for superficial dermal HSA if complete margins have been achieved.



CLINICAL CASE EXAMPLE 11.2 – A HAEMORRHAGING INTESTINAL MASS IN A DOG





Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on The anaemic cancer patient

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