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Consensus Statements > ACVIM consensus statement on the treatment of immune thrombocytopaenia in dogs and cats > Flashcards

ACVIM consensus statement on the treatment of immune thrombocytopaenia in dogs and cats Flashcards

1
Q

What is immune thrombocytopaenia?

A

It is an acquired immune-mediated disorder that can result in haemorrhage because of a failure of primary haemostasis.

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2
Q

Describe the pathogenesis of ITP.

A

Involves antiplatelet autoantibody formation that can results in platelet clearance and compliment mediated platelet destruction. Platelet destruction by cytotoxic T cells contributes to thrombocytopaenia development and can occur in the absence of detectable platelet-surface associated immunoglobulins. Platelet production may be inhibits by antibodies and T-cells that target megakaryocytes and through inappropriate thrombopoietin concentrations.

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3
Q

What are the broad treatment principles for primary ITP?

A

Typically involves immunosuppression using glucocorticoids and other immunosuppressive drugs. Adjunctive treatments also includes vincristine and human IV immunoglobulin or transfusion with blood products as needed.

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4
Q

What are the broad treatment principles for secondary ITP?

A

Aims to eliminate disease triggers and in some cases provide treatment for the associated immune-mediated disorders.

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5
Q

What is the treatment goal of dog and cats with ITP?

A

Platelet count of >100,000ul with no evidence of bleeding

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6
Q

Describe the algorithm for the initial treatment of ITP in dogs and cats.

A
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7
Q

Describe the algorithm for management of drug withdrawal, remission and relapse in dogs and cats.

A
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8
Q

Define no response to treatment.

A

A platelet count < 30,000/ul or ongoing bleeding at least 2 weeks after the initial treatment.

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9
Q

Define partial response to treatment.

A

A platelet count > 30,000/ul and <100,000/ul combined with >2-fold increase in platelet count from diagnosis.

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10
Q

Define complete response.

A

Platelet count >100,000 without bleeding.

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11
Q

Define full remission.

A

Platelet count >100,000/ul without bleeding in the absence of ongoing treatment.

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12
Q

In dogs with primary ITP is combined treatment with glucocorticoids and vincristine compared with use of glucocorticoids alone associated with different primary or secondary outcomes?

A

There is moderate evidence to suggest a single IV dose of vincristine in conjunction with glucocorticoids accelerate initial platelet count recovery and shortens hospitalisation times.

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13
Q

What is the recommended dose of vincristine?

A

0.02mg/kg IV once with a maximum dosage of 0.5mg/m2 for dogs >25kg

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14
Q

Which breeds should vincristine be used with caution?

A

Dog breed with a high incidence of MDR1 gene mutation including smooth and rough collies, shetland sheepdogs, aussie shephards and long-haired whippets.

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15
Q

What should be monitored following vincristine administration? Why?

A

Neutrophil counts as it can induced neutropaenia.

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16
Q

What is a good second line immunosuppressive drug for the treatment of pITP?

A

Cyclosporine

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17
Q

What is an important consideration when using vincristine if you are wanting to start cyclosporine?

A

Ideally commencement of cyclosporine should be delayed several days after vincristine to minimise the risk of drug induced neutropaeniA.

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18
Q

In cats with primary ITP is combined treatment with glucocorticoids and vincristine compared with use of glucocorticoids alone associated with different primary or secondary outcomes?

A

There is insufficient evidence to determine with certainty if vincristine affects outcomes in cats with pITP. It is not recommended until more evidence becomes available.

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19
Q

What is vincristine? and What is the mechanism of action on platelets?

A

Vincristine is a vinca alkaloid that results in an increase in circulating platelet count through several hypothesized mechanisms including:

  1. stimulation of thrombopoiesis
  2. acceleration of fragmen-tation of megakaryocytes
  3. impairment of the phagocytosis of platelets by macrophages
  4. interference with antiplatelet anti-body formation and binding.
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20
Q

Is there rationale to use vincristine alone without the use of glucocorticoids?

A

No. The only time when is should be considered in case where glucocorticoid administration must be delayed e.g. recent NSAID administration.

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21
Q

In dogs with primary ITP is treatment with combined glucocorticoids and hIVIg compared with use of glucocorticoids alone associated with different outcome?

A

There is strong evidence that a single IV hIVIg infusion dogs with presumed pITP, in conjunction with immunosuppressive dosages of glucocorticoids, accelerates initial platelet count recovery and shortens hospitalization time, com-pared with glucocorticoids alone.

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22
Q

What is the dose of hIVIg in dogs?

A

0.5-1g/kg IV over 6-12 hours no more than 3 days of treatment

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23
Q

In dogs, is hIVIg or vincristine preferred in emergency situation of ITP?

A

Vincristine.

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24
Q

In dogs, which situation if hIVIg indicated instead of vincristine?

A

In dogs with a high incidence of the MDR1 gene mutation?

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25
Q

In dogs, can you combine vincristine and hIVIg?

A

Yes it can be considered in dogs with life-threatening bleeding.

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26
Q

What are the potential complications of hIVIg administration?

A

Single administration appear relative safe as very few side effects are reported. However, a hypercoagulable state has been reported.

27
Q

In cats with primary ITP is treatment with combined glucocorticoids and hIVIg compared with use of glucocorticoids alone associated with different outcome?

A

There is weak evidence that hIVIG in combination with glucocorticoids may induced recovery of platelets compared to glucocorticoid s alone. It can be used as an emergency option in cats with clinically relevant bleeding or refractory pITP.

28
Q

What dose of HIVIg should be used in cats?

A

0.5-1.0g/kg IV given once over 6-12 hours

29
Q

In dogs, what should be useds as a first line treatment, vincristine or HIVIg? Why?

A

Vincristine.
Why?: Lower cost, ready avaliability and ease of administration.

30
Q

Is combined glucocorticoids and IVIg or combined glucocorticoids and vincristine associated with better outcomes?

A

Mostly equivocal. Studies have shown the median time to reach PLT>40,000 was 2.5 days with a range on 1-4 in the vinc group and 1-10 in the the HIVIg group.

31
Q

In cats, is hIVIg or vincristine preferred in emergency situation of pITP?

A

Limited data suggests HIVIg should be considered in preference to vincristine in cats.

32
Q

In dogs with pITP is combined glucocoritcoids with a second immunosuppressive medication compared to glucocorticoids alone associated with different outcomes?

A

Unknown.
Insufficient evidence.

33
Q

When should a second immunosuppressive medication be considered in cases of pITP in dogs?

A
  1. No response within 5-7 days of starting glucocorticoids
  2. Development of severe adverse effects to glucocorticoids
  3. Relapse during tapering of glucocorticoids after clinical remission
  4. Active, refractory haemorrhage, if initial control measures e.g. HIVIg and vinc are unsuccessful within 1-3 days of diagnosis.
  5. Severe haemorrhage requiring multiple transfusions

OR
Early used of a 2nd immunosuppressive medication may be considered:
- in dogs >25 kg to allow more rapid tapering of glucocorticoids doses.
- dogs were severe bleeding because of anticipated delayed onset of action of secondary drugs.

34
Q

What are the options for a secondary immunosuppressive drugs in dogs?

A
  1. Cyclosporine
  2. Azathiprine
  3. Leflunomide
  4. Mycophenolate mofetil
35
Q

In cats with pITP is combined glucocoritcoids with a second immunosuppressive medication compared to glucocorticoids alone associated with different outcomes?

A

Unknown.
Insufficient evidence.

36
Q

When should a second immunosuppressive medication be considered in cases of pITP in cats?

A
  1. No response within 5-7 days of starting glucocorticoids
  2. Development of severe adverse effects to glucocorticoids
  3. Relapse during tapering of glucocorticoids after clinical remission
  4. Active, refractory haemorrhage, if initial control measures e.g. HIVIg and vinc are unsuccessful within 1-3 days of diagnosis.
  5. Severe haemorrhage requiring multiple transfusions

OR

Early used of a 2nd immunosuppressive medication may be considered:
- Cats with severe bleeding because of anticipated delayed onset of action of secondary drugs.

37
Q

What are the options for a secondary immunosuppressive drugs in cats?

A
  1. Modified cyclosporine
  2. Chlorambucil
38
Q

Why should azathioprine not be used in cats?

A

Because they have an inability to metabolise it and there is a risk of fatal myelosuppression

39
Q

What is a common side effect of chlorambucil in cats?

A

Thrombocytopaenia when used chronically.

40
Q

In dogs and cats with pTIP what are the best predictors of disease severity?

A
  1. GI bleeding, specifically melena
  2. CNS or pulmonary haemorrhage
  3. Anaemia
  4. High BUN/urea
41
Q

Is there a difference between dex and pred in dogs and cats?

A

There is no evidence to suggest improvement in any outcome when dex is used compared to pred.

42
Q

Can HIVIg be used as sole treatment in dogs and cats?

A

Not recommended

43
Q

In dogs and cats with pITP are high doses of pred > 2mg/kg/day compared to more conservative doses 2mg/kg/day or 50-60mg/m2/day (dogs) associated with better outcomes?

A

No. High doses are not recommended in dogs. It is not recommended in cat either however other study have shown in cases of IMHA higher doses (3-4mg/kg/day) may be required and thus, could be considers in pITP.

44
Q

In dogs and cats with pITP is a maintenance treatment with glucocorticoids and a 2nd immunosuppressive drug superior to glucocorticoids alone to prevent relapse?

A

No, there is insufficient evidence ion dogs and no evidence in cats.

45
Q

What are the reported relapse rates in dog and cats? Why do relapses occur?

A

Ranges from 9 - 47% most occuring early in the disease course.

Potential triggers of relaspes can include:
1. Rapid tapering
2. Stopping immunosuppressive medications
3. New co-morbidity triggering an autoimmune response
4. Persistence of occult co-morbidity the escaped detection

46
Q

In dogs can cats experiencing relapses what tests or diagnostics should be performed?

A

Level of diagnostics should be guided by interval since diagnosis and recent changes in therapy
1. History including drug and travel exposures
2. CBC and blood smear
3. Serum biochemistry
4. UA
5. cytology, infectious disease testing or imaging can be considered

47
Q

How should dogs and cats with pITP that experience relapse be managed?

A
  1. Reconfirm the diagnosis as per consensus guidelines
  2. Assess for potential triggers
  3. If relapsed occurs whilst tapering increase the dose of immunosuppressive medications
  4. Depending on severity could used vinc or HIVIg (only if it hasnt be used previously)
  5. Life long immunosuppressive treatment at the lowest achievable dose may be necessary if recurrent relapses occurs despite careful, gradual tapering
48
Q

If there is a need for continuous immunosuppressive treatment or repeated relapses what could be considered?

A
  1. Romiplostim
    OR
  2. Splenectomy
49
Q

What is the role of immunosuppression in dogs and cats with secondary ITP?

A

Short term immunosuppression can be used in cases of severe life threatening in conjunction with the administration of specific treatment or when the perceived risk of life threatening haemorrhage is greater than the risk of immunosuppression.

50
Q

In dogs and cats with pITP is treatment with melatonin associated with different outcomes?

A

No.

51
Q

What is the thought behind use of melatonin for treatment pITP in dogs and cats?

A

Only been seen in an experimental setting but:
1. Enhancement of MHC II mediated antigen presentation
2. Increased natural killer cell numbers
3. Promotion of haematopoiesis
4. Increase or decreased production of pro-inflammatory cytokine and interleukin-10

52
Q

In dogs and cats with pITP, is treatment with TPO receptor agonists associated with better outcomes?

A

TPO agonist romiplostim may be associated with improved platelet counts in dogs with treatment-refractory ITP. It is considered a safe and effective option in dogs with refractory ITP. No reports of used of TPO agonists in cats.

53
Q

In dogs with pITP is treatment wiht splenectomy associated with improved outcomes?

A

In dogs it may lead to increase PLT counts in some animals refractory to medical treatment and is generally well tolerated. However, future relapses of thrombocytopaenia is common. long-term response rates are variable.

In cats there is insufficient evidence. In cats routine splenectomy is not recommended.

54
Q

In dogs and cats dose use of an anti-thrombotic improve outcomes in pITP?

A

In dogs and cats the use of antithrombotic drugs is generally not indicated unless there is pre-existing co-morbidities that may predispose to thrombosis.

55
Q

In dogs and cats is the used of sulcralfate or other GI protectants associated with less evidence of gastric erosion or ulceration or gI bleeding?

A

The use of gastro-protectants should only be considered in the presence of observed or suspected melena.

56
Q

Is there a rationale to employ pro-biotics in the treatment of dogs and cats with pITP?

A

Routine administration of pro-biotics is not recommend currently

57
Q

In dogs and cats, are vaccinations after ITP diagnosis associated with a higher rate of relapse?

A

There is very limited data regarding the association between vaccination and ITP relapse. Consider titre testing, risk of disease and environment (i.e. solely indoor cats vaccination may not be requried).
Administering only one vaccine per visit is recommended and only after immunosuppressive drugs are discontinued or limitied to anti-inflammatory dose 0.5mg/kg q24 only if glucocorticoid discontinuation is not anticipated. Measuring PLT count should be considered at 2 and 5 weeks post-vaccination.

58
Q

In dogs and cats with pITP, what supportive treatments should be provided beyond transfusion?

A
  1. Anxiolytics
  2. Restricted exercise
  3. Food should be soft e.g. canned or soaked
  4. No hard chew toys
  5. No SC or IM injections
  6. Anticoagulant or anti-platelet medications should be avoided
  7. If DIC has been ruled out anti-fibrinolytic medications can be considered
59
Q

How is DIC ruled out?

A

If PT and APTT normal you can consider DIC ruled out?

60
Q

In cases of thrombocytopaenia and organ samples or cystocentesis, how would you prepare a patient?

A
  1. Stop all anti-platelet or anti-coagulants
  2. Considers a TEG is hyperfibrinolytics can give TXA
  3. Consider PLT transfusion
61
Q

In dogs and cats with pITP how should pred be tapered?

A

Consensus is to reduced glucocorticoids doses by 25% every 2-4 weeks provided PLT count in stable. and confirmed immediately before each dose reduction.

62
Q

In dogs and cats with pITP how should 2nd immunosuppressive medications be tapered?

A

Unsure. Some clinicians discontinue glucocorticoids before tapering 2nd immunosuppressive drugs

63
Q

How should we monitor treatment during inpatient, outpatient and remission phases?

A
  1. Physical exam close attention paid to mucocutaenous petechiae, ecchymoses, retinal haemorrhage and melena and signs of secondary infection
  2. CBC
  3. Inpatient monitoring should consist on daily PE and PCV/TP and a CBC every 2-3 days until bleeding stops and the PLT count exceeds 40-50,000/UL
  4. On an outpatient basis PLT >40-50,000 and no signs of bleeding monitoing may be decreased idealy every 1-2 weeks for a month, then every 2-4 weeks until remission is achieved.
  5. A physical exam, CBC and blood smear should precede any large dose reduction and followed by a planned re-evaluation
  6. Monthly biochem to monitor for potential adverse drug effects
64
Q

Deck completed

A

Deck completed

Consensus Statements (2 decks)

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