Thrombocytopenia

From Cat
File:Thrombo01.jpg
Feline blood smear. The small anucleated discoid-shaped cells with purple granules are normal cat platelets. Wright's stained; 100 x objective.
File:Thrombo02.jpg
Feline blood smear. There is a large macroplatelet present in the left center of the field. These can be seen in thrombocytopenic animals with active thrombopoiesis. Macroplatelets are also common in cats that do not have thrombocytopenia. Wright's stained; 100 x objective
File:Thrombo03.jpg
Feline blood smear. There is a large platelet clump present on the feathered edge of the blood smear. When evaluating an animal for thrombocytopenia it is important to make sure that there is not a false decrease in platelets due to multiple clumps of platelets in the sample. Due to the difficulty in obtaining blood from cats, it is not uncommon to get samples with many platelet clumps. Wright's stained; 50 x objective.

Thrombocytopenia, a reduction in circulating thrombocytes (<300,000 platelets per microlitre), is a rare primary blood disorder of cats.

Its opposite disorder, thrombocytosis also occurs in cats.

Thrombocytopenia causes reduced blood clotting and results in increased bleeding tendencies. Thrombocytopenia is commonly caused by a decreased production of thrombocytes, but can also be induced by increased consumption or increased sequestration of platelets. Decreased production is more often caused by diseases affecting the bone marrow. It is usually found secondary to some other disease process, such as retrovirus infections (FeLV, FIV), immune-mediated thrombocytopenia, cytotoxic drugs aplastic anemia, lymphoma, leukemia, myelodysplasia, myelofibrosis and marrow histoplasmosis[1].

Causes

Causes of thrombocytopenia in cats include:

- viruses - Panleukopenia, FIP, FeLV, FIV, FCV
- protozoans Mycoplasma haemofelis, M. haemominutum, Ehrlichia risticii, Anaplasma phagocytophilum, Babesia felis, Cytauxzoon felis, Histoplasma spp
  • cancer - lymphoma, haemangiosarcoma, usually with hypercalcemia and elevated liver enzymes, especially ALT
  • chronic renal disease - through reduced production of erythropoietin by the renal cortex (peritubular fibroblast cells)
  • inflammatory triggers - chronic inflammation caused by trauma, fat necrosis/steatitis, pancreatitis, hepatitis, pneumonitis
  • heart diseases - cardiomyopathy, hyperthyroidism and 2ry cardiomyopathy
  • drug toxicity - aspirin, propylthiouracil, methimazole, griseofulvin, albendazole, chloramphenicol, cytotoxic drugs (doxorubicin, carboplatin, azathioprine, etc.)
  • Primary immune-mediated thrombocytopenia (Evans syndrome) - rare[3]

Clinical signs

Primary immune-mediated thrombocytopenia is difficult to diagnose, because spontaneous bleeding is rare in cats. Usual early symptoms may include lethargy, inappetence, occasional vomiting and dehydration, petechiation, epistaxis, melena and haematuria. These non-specific signs may lead to occasional blood in faeces or vomiting blood. Splenomegaly may be present due to hyperplasia, extramedullary haematopoiesis or neoplasia.

Diagnosis

In cats, decreased platelet counts are a common laboratory finding. However, this is often a so-called pseudo-thrombocytopenia (incorrect low platelet values) which can occur with automated counting of platelets. It is related to the tendency for feline platelets to aggregate and the size of some of the platelets that in this species can be similar to the size of red blood cells. Therefore, manual counting (e.g., using Thrombo Plus®-tubes, Sarstedt and a Neubauer counting chamber) or slide evaluation must always be done to confirm whether the thrombocytopenia is real or artifactual. For blood sampling it is advisable to collect the initial 1-2 ml of blood for clinical chemistry. The following blood is then collected in K-EDTA tubes for haematological evaluation. The EDTA- tubes should be carefully checked for small blood clots and the counting of thrombocytes should be completed within 30 minutes, if possible. Studies have shown that estimation of platelet numbers on stained blood smears is reliable over a wide range of platelet counts in cats. Each platelet per oil immersion field represents a circulating platelet count of approximately 20,000/µl. Obvious platelet clumps in the blood smear, however, prevent accurate determination of the platelet number per oil immersion field.

A reduced production, increased destruction or increased utilization of platelets, sequestration in the spleen, or a combination of these pathomechanisms can cause thrombocytopenia.

Clinical studies evaluating the causes for thrombocytopenia in cats are infrequently found in the literature.

The main causes of thrombocytopenia in cats are viral infections. The mechanisms associated with thrombocytopenia during a viral infection may be multifactorial and vary with the agent. Virus induced thrombocytopenia may be caused by inhabiting precursor cells, thus reducing megakaryocytopoiesis, direct platelet damage or lysis by the virus itself, removal of platelets by the mononuclear phagocytic system, or by disseminated intravascular coagulation (DIC). Immune-mediated destruction of the platelets can be a contributing factor.

Inflammatory diseases are another important cause for decreased platelet counts in cats. In inflammatory disease states interactions of platelets with altered or damaged endothelial surfaces cause extensive platelet activation, clumping, and removal of platelets by the mononuclear phagocytic system. Platelet destruction in bacterial infections can occur as a result of platelet adherence or aggregation to activated monocytes or neutrophils. Exotoxins may directly damage platelets and contribute to thrombocytopenia. Immune-mediated destruction might contribute to thrombocytopenia in different infectious diseases.

In neoplastic disease there is a wide variety of pathomechanisms that may cause thrombocytopenia: Platelets may be sequestered in the spleen, liver, or the tumour as such; consumption of platelets may be increased (e.g., due to DIC); they may be destroyed by immune reactions, and production may be reduced due to bone marrow involvement.

In cats primary or secondary immune-mediated thrombocytopenia (ITP) have rarely been described or characterized. ITP occurs as a primary or idiopathic (pITP) and as a secondary (sITP) form. In sITP, infections, other immune-mediated diseases (e.g. Systemic lupus erythematosus), drugs, neoplasias, blood transfusions, or vaccination may trigger an increased production of antibodies which may adhere to or cross react with platelet receptors causing an increased destruction of platelets by the mononuclear phagocytic system. The diagnosis of a primary ITP in cats is based as in other species on the exclusion of underlying diseases, the presence of a mostly severe thrombocytopenia, the response to immunosuppressive therapy, and the presence of platelet-bound antibodies (PBA). For cats, little information is available on the application of direct or indirect methods to detect platelet-bound or anti-megakaryocytic antibodies to evaluate immunological factors in the pathogenesis of thrombocytopenia. Recently we have described flow cytometry for evaluation of PBA in cats.

Treatment

In cases of primary thrombocytopenia, treatment usually involves low-dose daily prednisolone, 2-4 mg/kg orally. Blood transfusion may be necessary to replace lost thrombocytes.

In secondary thrombocytopenia, treatment of the underlying cause is essential. Chlorambucil (Leukeran) 0.02 mg/kg IV,

cyclophosphamide 50mg/m2 orally on alternate days or cyclosporine 5mg/kg orally twice daily have been used successfully in cats.

References

  1. Mackin, A (2006) Platelet disorders. In August, JR (Ed) Consultations in feline internal medicine. Vol 5. Elsevier Saunders, Philadelphia. pp:575
  2. August, JR (2006) Consultations in feline internal medicine. Vol 5. Elsevier Saunders, Philadelphia, pp:582-583
  3. Jordan, HL et al (1993) Thrombocytopenia in cats: a retrospective study of 41 cases. J Vet Intern Med 7:261-265