Immune-mediated thrombocytopaenia

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Immune-mediated thrombocytopaenia
Other namesImmune-mediated thrombocytopenia
Specialty Haematology
Symptoms Lethargy, anorexia, pyrexia, haemorrhage, bruising
Complications Platelet destruction
Usual onsetBetween >1 and 14 years
CausesUnderlying condition (secondary IMT only)
Risk factors Bitches, certain breeds, neuter status
Diagnostic method Platelet count measurement (both) and exclusion of underlying conditions (primary)
TreatmentImmunosuppression, steroids, blood transfusion, therapeutic plasma exchange
Medication Corticosteroids, azathioprine, prednisone
Prognosis 74-97% short term survival rate

Immune-mediated thrombocytopaenia (IMT) is a disease common in dogs and rare in cats. The disease is characterised by a low platelet count caused by destruction of the platelets from the immune system. IMT is the most common cause of thrombocytopaenia in dogs. [1]

Contents

Signs and symptoms

Common symptoms of IMT include lethargy, anorexia, pyrexia, haemorrhage, and bruising. [1] Destruction of platelets occurs when immunoglobins attach to the surface of the platelet, which causes macrophages to initiate phagocytosis. [2] IMT is differentiated from other forms of thrombocytopaenia by the immune-mediated component of the condition. [3]

Causes

Primary immune-mediated thrombocytopaenia

The immune system mistakenly destroying normal thrombocytes is pathognomonic of primary IMT. [4]

Secondary immune-mediated thrombocytopaenia

Secondary IMT may be the result of viruses, parasites, or bacteria; neoplasia; drug-induced aetiology; [5] blood transfusion; allergic and vaccine reaction [6] which disrupts the homeostasis of the immune system and results in immune-mediated platelet destruction. [7] [8] [9]

Risk factors

Bitches are twice as likely as male dogs to be affected. [10] Breeds with documented predispositions are: cocker spaniels, miniature and toy poodles, Old English sheepdogs, [10] golden retrievers, and German shepherd dogs. [1] Neutered dogs have a significantly increased risk of developing IMT. [11]

Age of onset

Age of onset has been reported in the literature as ranging from >1–14 years. The median age is reported to be between 4 and 8.1 years. [6] [10] [12]

Diagnosis

Dogs usually present with lethargy, asthaenia, anorexia, or mild pyrexia. Signs of platelet dysfunction such as petechiae or ecchymosis, epistaxis or rhinorrhagia and in severe cases with haematuria; gingival or ocular haemorrhages are used to identify and diagnose thrombocytopaenia. Up to half of dogs may present with splenomegaly. [2] [8] [1]

Patients can be screened to check for drugs and toxins that may cause haemostasis or secondary IMT. PCR serology tests may be performed to screen for diseases. [13] Serum chemistry, coagulation panels, and Coombs tests can be performed to rule out or diagnose comorbidities including: von Willebrand's disease, haemophilia A, disseminated intravascular coagulation, immune-mediated haemolytic anaemia, or renal failure. [3] [14]

Radiographic and ultrasonographic procedures can rule out splenic hemangiosarcoma, mast cell tumours, pancreatitis, infection, endocarditis, and other diseases with similar symptoms. [13] [14] A biopsy of bone marrow can identify platelet production problems. Biopsies of diseased tissue can identify neoplasia through cytological evaluation. [8] [13]

Differential diagnosis

Primary IMT is idiopathic and is diagnosed after exclusion of secondary IMT and other causes of thrombocytopaenia. [12] [10] Measure of platelet counts are used to diagnose thrombocytopaenia ( >30,0000-50,000/μL). [15] [16] Primary IMT makes up 5-15% of IMT cases. [17] [18] [19]

Treatment

Treatment varies based on whether or not it is primary or secondary IMT; however, all cases require immunosuppression. [1]

Immunosuppression

Immunosuppressive drugs are the most common treatment with corticosteroids being commonly used. [16] Vincristine and human intravenous immunogoblin have been shown to increase platelet count and improve recovery; however, none of these treatments have been shown to produce better long term survival than corticoseroid treatment. [18] [20] [5] Alternative immunosuppressants may be used in more severe cases such as: azathioprine, cyclophosphamide, leflunomide, danazol, mycophenolate, mofetil, and cyclosporine. [21] [8] Azathioprine is not recommended for cats due to susceptibility to myelosuppressive effects. [22] [23] In patients that do not respond well to immunosuppressive therapy or have constant relapse a splenectomy may be undertaken. Removal of the spleen removes the primary site of clearance of platelets and prevents production of autoantibodies. [1] Survival following splenectomy is unpredictable and lifelong care is often needed. [1] [8]

Blood transfusion

Blood transfusions are typically used in patients with secondary anaemia rather than isolated thrombocytopaenia as the platelets will likely be destroyed on transfusion. [8] Fluid therapy may be used to correct hypovolaemia and dehydration in cases without anaemia; however, this decreases platelet production. [15] [8]

Therapeutic plasma exchange

Therapeutic plasma exchange (TPE) is a novel treatment for immune-mediated diseases and little research has been done for the effectiveness of TPE and patients with IMT. [15] TPE requires removing the patient's plasma which contains antibodies and replacing it with fluids such as sodium chloride, frozen plasma, packed red blood cells, and hetastarch. [15] Kopecny et al. found this treatment to be effective in three out of four dogs with IMT who were unresponsive to other treatments. [15] Francey et al. found that dogs treated with TPE for IMT had similar prognosis to those treated differently; however, Francey et al. discussed its safety as a treatment and recommended further research. [24] [lower-alpha 1]

Steroids

Prednisone and prednisolone are steroids used to suppress immune response to restore platelet levels. [5] [8] [1] Side effects of these include adrenal atrophy, proteinuria and glomerular changes, weight loss, dermatitis, regurgitation, diarrhoea, gastroinestinal ulceration, hyperglycaemia, polyuria, polydipsia, decreased T4 levels, and other side effects. [21] [25] Patients generally start on a higher rate which is tapered off. [3] [25] Tapering is commenced once patients have gone two weeks with a normal platelet count. [8] [25]

Prognosis

Studies have identified short-term survival rates of 74–97% with a recurrence rate of 24–58%. Melaena and high blood urea nitrogen were associated with worse outcomes. Cummings and Rizzo identified a 60% survival rate in cases comorbid with melaena and high blood urea nitrogen. [5] [26] [10] [27] [28] A study following up on 45 dogs identified with IMT after 1 year found a mortality rate of 11.9%. 89.6% of dogs survived to discharge and 31% of those discharged relapsed, with an average of 78 days for dogs with multiple relapses and 149 days for dogs with only one relapse. The longest time between discharge and relapse was over 3 years. Seven dogs experienced relapse more than once and one dog relapsed five times before being euthanised. [16] In dogs with a platelet count below < 30,000 cells/μL there is an increased risk of spontaneous haemorrhage; [26] however, haemorrhage cannot be predicted in dogs with IMT. [29]

Notes

  1. ↑ This study used a different fluid to Kopecny et al.

Related Research Articles

<span class="mw-page-title-main">Platelet</span> Component of blood aiding in coagulation

Platelets or thrombocytes are a blood component whose function is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm derived from the megakaryocytes of the bone marrow or lung, which then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates, thrombocytes circulate as intact mononuclear cells.

<span class="mw-page-title-main">Immune thrombocytopenic purpura</span> Medical condition with rash and bleeding risk

Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is an autoimmune primary disorder of hemostasis characterized by a low platelet count in the absence of other causes. ITP often results in an increased risk of bleeding from mucosal surfaces or the skin. Depending on which age group is affected, ITP causes two distinct clinical syndromes: an acute form observed in children and a chronic form in adults. Acute ITP often follows a viral infection and is typically self-limited, while the more chronic form does not yet have a specific identified cause. Nevertheless, the pathogenesis of ITP is similar in both syndromes involving antibodies against various platelet surface antigens such as glycoproteins.

<span class="mw-page-title-main">Hemangiosarcoma</span> Cancer of blood vessel lining

Hemangiosarcoma is a rapidly growing, highly invasive variety of cancer that occurs almost exclusively in dogs, and only rarely in cats, horses, mice, or humans. It is a sarcoma arising from the lining of blood vessels; that is, blood-filled channels and spaces are commonly observed microscopically. A frequent cause of death is the rupturing of this tumor, causing the patient to rapidly bleed to death.

<span class="mw-page-title-main">Thrombotic thrombocytopenic purpura</span> Medical condition

Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that results in blood clots forming in small blood vessels throughout the body. This results in a low platelet count, low red blood cells due to their breakdown, and often kidney, heart, and brain dysfunction. Symptoms may include large bruises, fever, weakness, shortness of breath, confusion, and headache. Repeated episodes may occur.

<span class="mw-page-title-main">Thrombocytopenia</span> Abnormally low levels of platelets in the blood

In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients and a third of surgical patients.

<span class="mw-page-title-main">Wiskott–Aldrich syndrome</span> Medical condition

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John W. Semple is a Canadian Scientist formally at St. Michael's Hospital and a Professor of Pharmacology at the University of Toronto. He is currently a Professor of Transfusion Medicine at Lund University in Sweden. He was born in Windsor, Ontario in 1959 and received his PhD in Immunology at Queen's University at Kingston, Ontario. In 1991, Semple, along with John Freedman, discovered a T helper cell defect in patients with the bleeding disorder called immune thrombocytopenia (ITP). ITP is a condition of having a low platelet count (thrombocytopenia) and most causes appear to be related to antibodies and T cells against platelets. Very low platelet counts can lead to a bleeding diathesis and purpura. The T cell defect was initially shown to be an exaggerated interleukin-2 response when T cells were cultured with platelets in vitro. Subsequently, this cytokine abnormality was shown by others to be responsible for many of the autoimmune mechanisms causing the disorder.). The importance of understanding the T cell defects in ITP is that novel therapies aimed at these cells may significantly benefit patients with ITP.

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<span class="mw-page-title-main">Pancreatitis (veterinary)</span> Medical condition

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<span class="mw-page-title-main">Cushing's syndrome (veterinary)</span> Medical condition

Cushing's syndrome disease, also known as hyperadrenocorticism and spontaneous hypercortisolism, is a condition resulting from an endocrine disorder where too much adrenocorticotropic and cortisol hormones are produced, causing toxicity. It may arise in animals as well as in humans. Cushing's is an umbrella term for conditions caused by elevated cortisol and adrenocorticotropic hormone levels.

References

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