Hematologic Paraneoplastic Syndromes in Small Animals

Anemia is common in cancer patients. Anemia can result from the cancer itself (eg, bone marrow/leukemic involvement of lymphoma), from chronic disease, from immune-mediated RBC destruction, from hemorrhage in the tumor, or from cumulative bone marrow suppression secondary to long-term chemotherapy. Anemia occurs most commonly as a paraneoplastic syndrome in patients with lymphoma, leukemia, hemangiosarcoma, disseminated mast cell tumor, and histiocytic sarcoma; however, any patient with cancer can develop anemia.

Anemia can be regenerative or nonregenerativeat diagnosis, and the nature of the anemia can change over the course of the disease.

Treatment of anemia ranges from proactive monitoring if the anemia is mild, to aggressive hemodynamic support in the face of acute hemorrhage.

Anemia secondary to chemotherapy and anemia of chronic disease are typically mild. Immune-mediated anemia, anemia due to hemorrhage or tumor involvement within the bone marrow, and anemia due to cumulative myelosuppression are typically moderate to severe.

Depending on the severity of the anemia, clinical signs can include pale or icteric mucous membranes (see anemia image), tachycardia, tachypnea, weakness or collapse, anorexia, arrhythmia or heart murmur, palpable organomegaly, hematochezia, hematemesis, hematuria, or epistaxis. 

Paraneoplastic anemia, cat

Image

Courtesy of Dr. Brooke Britton.

Diagnostic testing, including blood smear, Coombs test, bone marrow aspiration, and feline retroviral testing can be helpful for further characterizing anemias.

If and until the underlying cancer can be successfully treated, anemia is treated typically with supportive care; transfusion with blood products might be warranted.

The most common malignancies associated with thrombocytopenia include hematologic cancers (eg, lymphoma, leukemia, myeloma), mammary adenocarcinoma, nasal adenocarcinoma, mast cell tumor, hemangiosarcoma, fibrosarcoma, and histiocytic sarcoma (1). 

Thrombocytopenia in cancer patients can be due to decreased platelet production, increased destruction or consumption or platelets, sequestration of platelets, or loss of platelets via hemorrhage. Rarely, cytotoxic myelosuppression can also occur with chronic antitumor therapy.

Patients with paraneoplastic thrombocytopenia can exhibit bruising and bleeding from and around tumors, petechiae or ecchymoses (usually at platelet counts < 50,000 platelets/mcL [see thrombocytopenia image]), or spontaneous bleeding (usually at platelet counts < 25,000 platelets/mcL). 

Thrombocytopenia, cat

Image

Courtesy of Dr. Brooke Britton.

Exercise intolerance and mentation abnormalities might be evident in patients with clinically significant bleeding due to thrombocytopenia. Patients with marked thrombocytopenia should be handled with care, minimizing blood draws and avoiding jugular sampling and intramuscular injections. NSAID medications should also be discontinued.

Transfusions of platelet-rich or whole blood products may be considered in severe cases of thrombocytopenia; however, the benefits of transfusion are short-lived (days) if the underlying cancer is not adequately addressed.

In select cases, vincristine and/or steroids may be considered in the short term if a secondary immune-mediated thrombocytopenia is suspected; however, treatment of the underlying cancer is the most effective means of more durably addressing paraneoplastic thrombocytopenia.

The goal of therapy in cases of thrombocytopenic cancer is to restore the platelet count to the threshold of a nonclinical state. However, thrombocytopenia might never fully resolve, particularly in the face of hematologic malignancies with marrow involvement or with an immune-mediated component secondary to the cancer.

Hyperglobulinemia commonly occurs with multiple myeloma and myeloma-related disorders, plasma cell tumors, and lymphoma/leukemia, whereby tumor cells produce an overabundance of a single type or component of immunoglobulin (M component). The typical result is a monoclonal gammopathy, which can be confirmed via serum protein electrophoresis (2). 

M components interfere with coagulation by coating platelets and inhibiting aggregation, potentially leading to hyperviscosity syndrome, in which "sludging" of blood in small vessels, ineffective oxygen and nutrient delivery to tissues, and coagulation abnormalities can occur (2). 

The extent of hyperglobulinemia can be mild to severe. Severely affected patients might develop interstitial nephritis and signs of renal failure, mentation changes, seizures, retinal hemorrhage or detachment, blindness, heart enlargement or failure, or bleeding diathesis.

Diagnostic testing, including serum protein electrophoresis and/or urine testing for Bence- Jones proteins (excretion of free immunoglobulin light chain detected in the urine), is useful to further characterize hyperglobulinemia and support an underlying neoplastic process.

Treatment of paraneoplastic hyperglobulinemia centers around treatment of the patient’s cancer. For patients with hyperviscosity syndrome, however, plasmapheresis may be considered for more immediate relief.

• Bailey DB. Paraneoplastic syndromes. In: Vail DM, Thamm DH, Lipták JM, eds. Withrow & MacEwen's Small Animal Clinical Oncology. 6th ed. Elsevier; 2020:98-100.

• Childress MO. Hematologic abnormalities in the small animal cancer patient. Vet Clin North Am Small Anim Pract. 2012;42(1):123-155. doi:10.1016/j.cvsm.2011.09.009

• Also see pet owner content regarding peripheral nerve disorders in dogs and cats.

1. Chisholm-Chait A. Mechanisms of thrombocytopenia in dogs with cancer. Compend Contin Educ Pract Vet. 2000;22(11):1006-1017.

2. MacEwen GE, Hurvitz A. Diagnosis and management of monoclonal gammopathies. Vet Clin North Am. 1977;7(1):119-132. doi:10.1016/s0091-0279(77)50010-x