2. Megan 13yo Female Border Collie
Presentation: worsening lethargy. With a history of
intermittent anemia over the last few weeks.
Clinical Findings:
QAR
Slightly pale MM, Normal CRT
Fluid thrill noted on abdominal palpation
HR 120 bpm, Temperature and RR wnl.
3. Investigations
Abdominal Ultrasound: revealed large volume of free fluid. Small
cavitated mass adjacent to the spleen, and a larger mass arising in
cd abdomen.
Abdomenocentesis: Blood (PCV 32%)
Orthogonal thoracic radiographs: unremarkable
Cardiac scan: No obvious masses
Hematology:
Moderate Anemia (HCT 28%) (ref 37-55%)
Neutrophilia (15x10^9/L) (ref 6-12x10^9/L)
Thrombocytopenia (60x10^9/L) (ref 200-500x10^9/L)
Mildly prolonged APTT (37 seconds) (ref 17-24sec)
4. Diagnosis
Haemoabdomen, likely secondary to abdominal
neoplasia.
Non Traumatic/Spontaneous Causes of
Haemoabdomen
• Neoplasia***
• Splenic hematoma
• Splenic torsion
• Coagulopathies
• Vena caval syndrome secondary to Dirofilariasis
5. Plan
Referred to Soft Tissue service for an emergency
exploratory laparotomy.
Findings of Exlap:
Small mass on falciform fat
Larger caudal abdominal mass
800ml of free blood
Grossly abnormal liver
Both masses, and a liver biopsy were sent for histopathology.
6. Histopathology
The histological appearance of the two masses was
consistent with an haemangiosarcoma.
No normal tissue is present in the examined sections to
suggest a site of origin.
7. Haemangiosarcoma (HSA)
Highly malignant tumor of endothelial cells.
Occurs more frequently in dogs than in any other species and
is characterized by a high fatality rate (1)
The overall prevalence is reported to be 0.3% to 2.0% of all
tumors in dogs; German shepherds, golden retrievers, and
Labrador retrievers are overrepresented (2).
The etiology of HSA is still unknown, although the strong breed
association suggests an inherited or familial predisposition.
8. Haemangiosarcoma (HSA) cont.
The 3 most common primary sites of HSA are the spleen
(28% to 50%), right atrium/auricle (up to 50%), and skin or
subcutaneous tissue (13%) (1,3).
Most common sites of metastasis of HSA:
Lungs (65%)
Spleen (36-60%)
Kidneys (55%)
Liver (41-55%)
which can occur via haematogenous spread or by local
seeding after tumor rupture (1).
9. Common Laboratory Findings
Hematology:
Anemia
morphological changes to red blood cells:
nucleated erythrocytes
Polychromasia
poikilocytes, anisocytes, shistocytes, and
reticulocytes
Neutrophilia
due to either stress or tumor rupture and necrosis
thrombocytopenia
10. Common Diagnostic Imaging
Findings
Thoracic Radiographs
Metastatic patterns in dogs with HSA:
widely disseminated nodular pattern (common)
diffuse interstitial pattern (uncommon)
Abdominal US
primary HSA: mixed pattern of anechoic and hyperechoic regions
metastatic HSA: diffusely anechoic or hypoechoic appearance
Echocardiography
Helps detect structural abnormalities, presence of tumours, clots or fluid.
Electrocardiography
ventricular arrhythmias are commonly associated with HSA due to hypoxia, anemia, or
hypovolemia
11. Treatment of HSA
Usually a combination of:
Chemotherapy:
Doxorubicin
+/- Cyclophosphamide (AC)
+/-Vincristine (VAC)
Metronomic Chemotherapy
Continuous low dose oral cyclophosphamide.
Surgical:
Try to remove the primary tumour.
Ex: SPLENECTOMY:
Historically the treatment of SPLENIC HSA.
12. HSA Staging
Clinical Stage Tumour Node Metastasis
I T0-1 N0 M0
II T1-2 N0-1 M0
III T2-3 N0-2 M1
T (Primary Tumour)
T0 No evidence of neoplasia
T1 <5cm diameter, confined to primary site
T2 >5cm diameter, ruptured, or invading
subcutaneous tissue
T3 Invading adjacent structures including
muscle
Node
N0 No evidence
N1 Regional LN
involvement
N2 Distant LN
involvement
Metastasis
M0 No evidence of
metastasis
M1 Evidence of
distance
metastasis
14. Back to Megan…
Post Operatively:
Due to her loss of blood and thrombocytopenia she
required
fresh frozen plasma and Packed red cell transfusion
(post operative PCV 6%, Hg 2 g/dl) with good response
over the following 24h.
She was sent home on strict cage rest, pain medications,
antibiotics, and antiemetics. With a recheck in 10 days to
remove the sutures and talk about chemotherapy
treatment options.
15. Megan’s Treatment Plan
Pre Chemotherapy:
Heart Scan
Showed adequate contractility
Abdominal scan
Revealed a nodule on the left kidney that should be
monitored
Start Doxorubicin therapy.
One dose every 3 weeks, for 4-6 doses.
She received her first dose this week.
If protocol not tolerated, discussed switching to metronomic
chemotherapy.
17. References
Canine hemangiosarcoma: retrospective analysis of 104 cases.Brown
NO, Patnaik AK, MacEwen EG J Am Vet Med Assoc. 1985 Jan 1;
186(1):56-8.
Kahn, S. Anthony, et al. "Doxorubicin and deracoxib adjuvant therapy
for canine splenic hemangiosarcoma: A pilot study." The Canadian
Veterinary Journal 54.3 (2013): 237.
Sorenmo, K. U., Baez, J. L., Clifford, C. A., Mauldin, E., Overley, B.,
Skorupski, K., Bachman, R., Samluk, M. and Shofer, F. (2004), Efficacy
and Toxicity of a Dose-Intensified Doxorubicin Protocol in Canine
Hemangiosarcoma. Journal of Veterinary Internal Medicine, 18: 209–
213. doi: 10.1111/j.1939-1676.2004.tb00162.x
Thamm DH. Hemangiosarcoma. In: Withrow SW, Vail DM, editors. Small
Animal Clinical Oncology. 4th ed. St Louis, Missouri: Saunders/Elsevier;
2007. pp. 785–795.
Hinweis der Redaktion
- Presented as a emergency to the SAH for worsening lethargy- occurring over a course of several weeks, along with intermittent anemia that was dx by her regular vet.
- On clinical exam: the most significant clinical findings included slightly pale MM, and a fluid thrill that was noted on abdominal palpation. She also had an audible grade 1 heart murmur. No petechial haemorrhage or scleral haemorrhage was noted and her pulse quality was reasonable.
**Hx: Dog previously diagnosed with idiopathic epilepsy
-Further diagnostic investigation revealed…
-A large volume of free fluid in the abdomen, along with a small cavitated mass sitting adjacent to the spleen, and a larger mass arising in the caudal abdomen.
-Blood was obtained from Abdomenocentesis
-Hematology revealed a moderate anemia, neutrophilia, and marked thrombocytopenia, as well as a mildly prolonged Activated Partial Thromboplastin Time
-Thoracic radiographs were clear, and a cardiac scan revealed no obvious masses.
Additional info:
Abdominal US: to look for amount of fluid present, to look for masses, to assist in sampling.
Ddx for abdominal masses: Neoplasia, cysts, hematomas.
- Abdomenocentesis- PCV of abdominal fluid will be > than peripheral blood if active bleeding is occurring.
- Orthogonal thoracic radiographs to look for- metastasis (or if trauma possible- look for concurrent thoracic injury or diaphragmatic rupture)
Cardiac scan to look for HSA (most common sites- Spleen and commonly the RIGHT ATRIUM)
Hematology: Anemia- results of the abdominal bleed. Leukocytosis is often noted in associated with stress, trauma, or NEOPLASIA. The thrombocytopenia is likely due to PLT consumption.
Significance with haematology and coagulation tests and parameters***
At this point a diagnosis of hemoabdomen was made. Using the information gathered from our hx, clinical exam, diagnostic imaging and hematology- the most likley cause of the hemoabdomen is secondary to abdominal neoplasia, however there are several other possible causes of non traumatic hemoabdomen including:
Splenic hematoma
Splenic torsion
Coagulopathies. For example: rodenticide poisoning, hepatic disease and hemophilia
-In one study I found, up to 80% of intra-abdominal neoplasia in dogs was malignant, and of those 88% were hemangiosarcomas.
Other malignant tumors (of spleen, or abdomen): mesotheliomas, lymphosarcomas, various other sarcomas and possibly metastatic carcinomas
Additional information:
•neoplastic effusion can be differentiated from non-neoplastic as neoplastic effusions have:
•significantly lower glucose concentrations (72.6 mg/dL v 110.0 mg/dL)
•significantly higher lactate concentrations (3.81 mmol/L v 1.68 mmol/L)
-Megan was referred to Soft tissue service for an emergency exploratory lapartomy, where a small mass was found on falciform fat and removed. Another larger mass in the caudal abdomen was consistent with a large blood clot adherent to omentum and mesentery, the bladder and abdominal wall although not originating from any of these organs. The mass was dissected and removed without causing further haemorrhage.
-on histopath, the masses were found to be hemangiosarcomas, and the changes in the liver were mild and consistent with degeneration likely secondary to hypoxia.
-Before continuing on with Megan’s case, I’m now going to talk to you a bit more in depth about Hemangiosarcoma in dogs.
Additional Information:
***POST OP INFORMATION:
Due to Megan's loss of blood and thrombocytopenia she required a FFP (fresh frozen plasma) and PRCs (packed red cells) transfusion (post operative PCV 6%, Hg 2 g/dl) with good response over the following 24h (current PCV 23% with TS 52 g/dl). Her aPTT was very increased following surgery as well (170s). Her HR and BP have remained stable and within normal and she has been more mobile and alert although with no appetite.
**look up transfusion information
-Hemangiosarcomas are highly malignant tumors of endothelial cells (so of the linings of the body’s blood vessels). Sarcomas- arise from transformed cells of mesenchymal origin.
HSA occurs most frequently in dogs, and is often characterized by its:
High fatality rate
There is a strong breed association, suggesting there is likely an inherited or familial predisposition.
- There is also a higher reported incidence in male dogs.
References:
Thamm DH. Hemangiosarcoma. In: Withrow SW, Vail DM, editors. Small Animal Clinical Oncology. 4th ed. St Louis, Missouri: Saunders/Elsevier; 2007. pp. 785–795.
2. Canine hemangiosarcoma: retrospective analysis of 104 cases.Brown NO, Patnaik AK, MacEwen EG
J Am Vet Med Assoc. 1985 Jan 1; 186(1):56-8.
-The most common primary sites include :
-the spleen
-and the right atrium of the heart
-and less commonly- the skin or subcutaneous tissue.
Metastasis and local infiltration occur early in the disease progression. And the most common sites for metastasis include:
The lungs
The spleen
The kidneys and
The liver
Other less common sites of metastasis: brain (20%), intestines (20%), adrenal glands (20%), skeletal muscle (20%), visceral lymph nodes (15%), skin and subcutaneous tissue (15%), left ventricle (10%), and mesentery and omentum (10%)
Reference:
3. Cutaneous hemangiosarcoma in 25 dogs: a retrospective study.Ward H, Fox LE, Calderwood-Mays MB, Hammer AS, Couto CG
J Vet Intern Med. 1994 Sep-Oct; 8(5):345-8.
Common laboratory findings associated with HSA include:
regenerative anemia with morphological changes to the red blood cells that can be due to iron loss, or DIC and sluggish flow through abnormal vascular channels resulting in increased membrane fragility
Neutrophilia- due to stress or tumor rupture and necrosis
and a Thrombocytopenia.
Additional Information:
Thrombocytopenia can be associated with---
--Kasabach-Merritt syndrome is characterized by an enlarging vascular tumor, thrombocytopenia, anemia, prolonged PT and APTT, decreased FDP, and increased fibrin split products
- Thoracic radiographs- useful to check for metastatic spread to the lungs.
Abdominal Ultrasound- highly useful in finding the primary tumor, and also for evaluating the spleen and other abdominal organs for metastasis.
Echo- helps detect the presence of tumors, or structural abnormalities
ECG- can detect ventricular arrhythmias commonly associated with HSA. These can be due to hypoxia, anemia or hypovolemia
Additional information:
Thoracic Rads:
•false-negative results are high: 22% from splenic HSA and > 50% for right atrial HAS
US: •ultrasound-guided FNA or needle-core biopsy contraindicated due to risk of seeding and low diagnostic yield
-Doxorubicin is usually the chemotherpeutic of choice. It is often used in a single agent protocol, but occasionally is seen in combination protocols with Cyclophosphamide and Vincristine.
-Doxorubicin treatment can result in cardiotoxicity and the common side effects of chemotherapy in general can include: myelosuppression, and GI upset. So some dogs may not tolerate treatments well.
-Another option is Continuous Low-Dose Oral Chemotherapy
-One study I read showed similar mean survival times to conventional doxorubin single agent treatment, and this may be tolerated better by some dogs.
Additional Info:
complications of chemo: neutropenia (common), severe gastroenteritis, cardiotoxicity, hemorrhagic cystitis and sepsis
( for Adjuvant Therapy of Splenic Hemangiosarcoma in Dogs- alternating cycles of low dose cyclophosphamide, etoposide,and piroxicam was used as adjuvant therapy for dogs with stage II HAS- showing similar mean survival times to conventional doxorubicin single agent treatment.
Immunotherapy
•immunotherapy aims at altering host-tumor response
•mixed bacterial vaccination and liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTPE) have been investigated with mixed results Other Treatments
•angiogenesis inhibitors and gene therapy
-You will approach staging HSA like you approach any other cancer case- using the TNM system.
-Metastasis and local infiltration occur early in the disease progression, so often cases of HSA are not detected until later stages.
The prognosis for canine HSA is relatively poor.
Surgery mean survival time is based off of splenic HSA, and refers to total splenectomies
- It should be noted that dog’s with splenic HSA that have ruptured, have a poorer prognosis.
-Post operatively Megan received a FFP and PRC transfusion. Her PCV continued to increase, coagulation times reduced, and PLT count returned to normal after a few days.
-She was given another abdominal ultrasound where they found a degree of inflammation around the site of the larger mass and a suspicious area in the kidney, which they were concerned may represent spread of the tumour.
-after discussion with the owner, they were keen to proceed with Doxorubicin therapy every 3 weeks for 4-6 doses to optimize her survival prospects.
-before doxorubicin treatment started she received a heart scan (which showed her heart had adequate contractility to begin treatment). She will receive another heart scan after receiving 4 doses of Doxorubicin since it is associated with DCM.
Her abdominal US revealed a nodule on her left kidney that could potentially be an indication of tumor spread. This will be closely monitored.
She received her first dose of Doxorucin this week (with Chlorphenamine IV and Maropitant SC), and was sent home with cerenia tablets.
