Bleeding Beast

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Hemorrhaging Hound
"Magnum"

Signalment:	11 year old Female (spayed), German Shepherd dog
Chief Complaint:	2 month duration of episodic red-tinged fluid around the nose and mouth. Has progressed over last 24 hours to occasional drops of blood from the left nares.
History:	Mostly inside dog; when outside, in a fenced yard; no other pets; not receiving any medication; no known trauma or toxin exposure. Over the last month the dog has had a mild decrease in activity. No change in food consumption, urination or defecation had been noted.
Physical examination:	Active, alert, well groomed dog in good body condition. A small drop of red fluid was present in the left nares. No oral lesions or evidence of bleeding at other locations found; normal color and consistency of feces (obtained on rectal examination). A fundoscopic examination was not done.

Clinicopathologic evaluation:

CBC

SERUM BIOCHEMISTRY PROFILE

TEST

RESULTS

Reference Range

TEST

RESULTS

Reference Range

WBC K/uL

RBC M/uL

Hb g/dl

HCT %

MCV fml

MCH pg

MCHC %

RDW

Platelets K/uL

Eos/uL

Bands/uL

Polys/uL

Lymph/uL

Monos/uL

Retics %

6.2
4.06
9.4
27.6
68
23
33.9
15.9
188
104
0
4628
1260
208
2.0

6.0-17.0
5.50-8.50
12.0-18.0
37.0-55.0
60-77
19.0-25.0
32.0-36.0
13.2-16.0
200-500
0-1250
0-300
3600-11500
1000-4800
150-1350

Glucose mg/dl

BUN mg/dl

Creatinine mg/dl

Sodium meq/l

Potassium meq/l

Na/K Ratio

Chloride meq/l

Carbon Dioxide meq/l

Calcium mg/dl

Phosphorus mg/dl

Total protein g/dl

Albumin g/dl

Globulin g/dl

Bilirubin mg/dl

ALP u/L

ALT u/L

Gamma gt U/L

Cholesterol mg/dl

94
21
1.5
146
4.8
30
111
20
12.2
5.5
11.1
1.4
9.7
0.1
60
63
4
214

65-130
6-29
0.6-1.6
140-158
4.0-5.7
27-40
100-115
18-26
8.0-12.0
3.0-7.0
5.4-7.6
2.3-4.0
2.7-4.4
0.0-0.5
10-84
5-65
2-10
150-275

Blood Smear
	The slide on the left is Magnum's. Notice how much bluer the smear is compared to a more normal smear on the right. The bluish coloration is a result of the hyperglobulinemia.

Urinalysis
Specific gravity	1.022
pH	7.0	RBC	0-4
Protein	negative	Glucose	Negative
WBC	0-2	Ketones	Negative

QUESTION

What problems can we identify from the history and physical examination?

QUESTION

What are your rule-outs and diagnostic plan for each problem?

COMMENTS	In Magnum’s case, although the epistaxis appeared to be unilateral, it was unknown if the hemorrhage always was associated only with the left nares. A bleeding problem could not be ruled-out. With coagulopathies, often the bleeding occurs from multiple sites, but hemorrhage in one location also may be associated with a platelet or coagulation problem.
	Marked hyperglobulinemia, regardless of the underlying etiology, may inhibit platelet function (by coating the platelets and inhibit their adhesive function) and result in the animal having a bleeding tendency.

QUESTION

What is a buccal mucosal bleeding time test and when is it indicated?

ASSESSMENT

With the detection of hyperglobulinemia, the localized bleeding (epistaxis) may be associated with a systemic problem. To further characterize the hyperglobulinemia, a serum protein electrophoresis was performed.

	Protein Electrophoresis

	NORMAL ELECTROPHORETOGRAM
	MONOCLONAL vs POLYCLONAL
MAGNUM		Dog with chronic pododermatitis

MONOCLONAL	The narrow spike of globulin (compared to the albumin spike is indicative of a monoclonal gammopathy. Monoclonal gammopathies have been found in dogs with plasma cell tumors, lymphoid neoplasia, ehrlichiosis, and leishmaniasis.
POLYCLONAL	The broad based spike (compare to albumin spike) is indicative of a polyclonal gammopathy, most commonly associated with chronic antigenic stimulation.

COMMENT

Although Magnum has never traveled outside of Washington, Ehrlichia canis should remain on the rule-out list for a monoclonal gammopathy. E. canis is uncommon in Washington, but the disease has been diagnosed in dogs which have never left the state.

QUESTION

What is your diagnostic and therapeutic plan for the monoclonal gammopathy?

COMMENT

With a monoclonal gammopathy, no history of travel out of Washington, and no serologic evidence of E. canis exposure, investigation for confirmation of multiple myeloma or lymphosarcoma should be initiated. A bone marrow aspirate for cytologic evaluation was performed.

BONE MARROW

COMMENT

With a monoclonal gammopathy and greater than 30% plasma cells in the bone marrow aspirate (in the absence of ehrlichiosis), adequate criteria for a diagnosis of a malignant plasma cell neoplasm is present. Because dogs with multiple lytic bone lesions, light chain proteinuria, or hypercalcemia may have a worse prognosis, survey skeletal radiographs and immunoelectrophoresis of the urine should be considered. In Magnum's case, the owner elected not to pursue any additional diagnostic tests. The dog was started on a chemotherapy protocol of melphalan and prednisone.

SUMMARY

A dog was presented with a history compatible with epistaxis. Once epistaxis was confirmed a bleeding tendency had to be differentiated from a primary nasal problem (neoplasia, foreign body, and fungal rhinitis were major rule-outs).

PROBLEMS IDENTIFIED	Red Fluid from Nares
	Thrombocytopenia
	Mild, not adequately regenerative anemia
	Hyperproteinemia due to hyperglobulinemia

Return to case discussion

PROBLEM	RULE-OUTS		Initial Diagnostic Plan
Anemia	Chronic Disease		Recheck CBC in 4 days to see if there is regenerative response If persistent epistaxis, PCV and total protein should be rechecked periodically.
	Acute Hemorrhage
	Bone Marrow Dysfunction

PROBLEM	RULE-OUTS	Specific Rule-outs	Initial Diagnostic Plan

Red Fluid from Nares	Epistaxis	Bleeding Problem	Thrombocytopenia Thrombocytopathia Coagulopathy Viscidities Hypertension	Cytological examination of the Fluid Complete oral examination PT/PTT Buccal mucosal bleeding time Measure Blood Pressure
		Primary Nasal Disease	Nasal mass Oral cavity disease (tooth root, oral mass, O-N fistula)) Foreign body Trauma Erosive inflammation
		Pharyngeal/ Pulmonary Disease	Numerous
	Oral cavity hemorrhage	Blood on tongue, transferred to nares (after licking)	Oral, pharyngeal, pulmonary problems

Hyperglobulinemia		Polyclonal	Chronic antigenic stimulation (infectious, noninfectious inflammation, neoplasia)	Serum protein electrophoresis (SPE) will differentiate monoclonal vs polyclonal. Depending on other medical problems and degree of hyperglobulinemia, SPE may or may not be necessary.
		Monoclonal	Most common causes of monoclonal gammopathies in dogs: Lymphoma, Myeloma, Ehrlichiosis

Thrombocytopenia	Rule-Outs (General)	Rule-outs (Few Specific Examples)	Diagnostic Evaluation May Include:
	Decreased Production	Drug/toxin	Recheck platelet count Assessment of coagulation (PT, PTT, FDPs, Fibrinogen)*** Fecal Ova Evaluation Rickettsial Titers Fungal Titers Abdominal Imaging (Radiographs, Ultrasonographic evaluation Cytologic Evaluation of a Bone Marrow Aspirate
		Bone Marrow infiltration
		Viral
		Histoplasmosis
		Immune Mediated Destruction
	Increased Utilization	Hemorrhage
		DIC
		Vasculitis, Rickettsial
	Peripheral Destruction	Immune-mediated thrombocytopenia (primary or secondary to an underlying disease)
	Sequestration	Splenomegaly
	Sequestration	Splenic Torsion
	Artifact	Traumatic Phlebotomy
	Artifact	Delayed Sample Evaluation

***Initial diagnostic plan for the mild thrombocytopenia in this dog.

Return to case discussion

Buccal Mucosal Bleeding Time

(BMBT)

Test Description

The test is performed by making a standard incision (using a retractable blade device, SimplateR), on the maxillary buccal mucosa. The time is measured from the time of incision, until a clot is formed. The area just ventral to the incision is blotted every 5 sec in order to detect the first sign of clotting.

Indications

The primary indication is to assess platelet function. When the thrombocytopenia is severe enough that it may result in spontaneous hemorrhage, (<40,000/ul), a BMBT will not be able to distinguish between a platelet functional problem and a problem of inadequate platelet numbers.

Return to case discussion

Diagnostic Plan for Magnum's Monoclonal Gammopathy
Erhlichia canis titer	If titer negative:	Optional Tests
	Cytologic evaluation of multiple lymph node aspirates	Survey radiographs of appendicular skeleton (may consider waiting until know if lymphoma or myeloma)
	Cytologic evaluation of a Bone marrow aspirate	IgG, IgM, IgA quantitation (radial immunodiffusion)
	Survey abdominal and thoracic radiographs (include dorsal spinus processes of vertebrae)	Measurement of relative plasma viscosity
	Cytologic evaluation of a splenic or hepatic aspirate if organomegaly or abnormal echogenicity present.	Urine immunoelectrophoresis

Therapeutic Plan	While awaiting the results of the Ehrlichia titer, (48 hours), the Magnum was begun on a regimen of doxycyline.