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Manajemen Perioperatif Penderita dengan Immune ... Catharina Suharti... Manajemen Perioperatif Penderita dengan Immune Thrombocytopenia (ITP): Pendekatan Berbasis Bukti Catharina Suharti

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  • Manajemen Perioperatif Penderita dengan Immune Thrombocytopenia

    (ITP): Pendekatan Berbasis Bukti Catharina Suharti

    Surabaya, 6 Oktober, 2019

  • Immune Thrombocytopenia (ITP)

     ITP is an autoimmune disease in which antiplatelet antibodies accelerate the destruction of platelets.

     In addition, platelet production can be impaired because the platelet antibodies can also damage megakaryocytes.

     Although the thrombocytopenia of ITP can be severe, signs of bleeding are usually only minor.

     Additional modifiers: comorbidities, age, activities, medications may affect the risk of significant bleeding

    Neunert CA. Hematology 2013

  • Immune Thrombocytopenia (ITP)

    Phases of the disease:  Newly diagnosed ITP: within 3 months of diagnosis  Persistent ITP: 3-12 months from diagnosis  Chronic ITP: >12 months

    Diagnosis 12 months3 months

    Newly diagnosed ITP

    Persistent ITP Chronic ITP Rodeghiero F, et al. Blood 2009; 113: 2386–93

  • Immune Thrombocytopenia (ITP)

    Definitions

    Primary ITP:  Isolated thrombocytopenia, platelet count is repeatedly

  • Diagnosis of ITP

     There is no specific test to rule in or rule out ITP

     A diagnosis of exclusion: when history, PE, CBC and peripheral blood smear do not suggest an alternative etiology of thrombocytopenia

     The detection of isolated thrombocytopenia in the presence of otherwise normal leukocyte and erythrocyte parameters is usually sufficient for an initial diagnosis.

     A blood smears must always be examined

    Matzdorff A, et al. Immune Thrombocytopenia. Current Diagnostics and Therapy: recommendations of a joint working group of DGHO, OGHO, SGH, GPOH and DGTI. Oncol Res Treat 2018;41 suppl5:1-30. PE, physical examination; CBC, complete blood count

  • Clinical Diagnosis of ITP

    Medical history: • Review of systems: lupus • medication • bleeding history • family history

    Physical examination: • bleeding manifestation: extent,

    area, bleeding scores • splenomegaly (not consistent ITP) • Splenomegaly (not consistent ITP) • Hepatomegaly (not consistent ITP)

    The extent of any further diagnostic workup depends on the severity and course of the disease

    ISTH, 2016

  • Investigations in Persistent ITP

    Infections:

     HepatitisB

     Hepatitis C

     HIV

     CMV

     H. Pylory

    ISTH, 2016

  • Controversial Investigations in

    Persistent ITP

     Testing for platelet autoantibodies is not recommended (not sensitive or specific enough to direct treatment)

     Bone marrow examination: recommended only in thosewith abnormal features (signs and symptoms of systemic disease, CBC abnormalities), those >60 years, poor response to standard therapy, pre-splenectomy)

    Matzdorff A, et al. Immune Thrombocytopenia. Current Diagnostics and Therapy: recommendations of a joint working group of DGHO, OGHO, SGH, GPOH and DGTI. Oncol Res Treat 2018;41 suppl5:1-30

  • Pathophysiology of ITP

    The following pathomechanisms play a role in ITP:

    1. Platelet autoantibodies • Antibody-coated platelets bind to Fc receptors on macrophages in

    liver and spleen and subsequently degraded • Damaged platelets bind to Ashwell-Morell receptors in the liver and

    are subsequently degraded • Autoantibodies damage platelet directly • Autoantibodies interfere with platelet function

    Matzdorff A, et al. Immune Thrombocytopenia. Current Diagnostics and Therapy: recommendations of a joint working group of DGHO, OGHO, SGH, GPOH and DGTI. Oncol Res Treat 2018;41 suppl5:1-30

  • Pathophysiology of ITP

    The following pathomechanisms play a role in ITP:

    2. T lymphocytes • Reduced number of regulatory T lymphocytes (Tregs) lead to

    immunodysregulation • T lymphocytes directly damage platelet

    3. Impaired thrombopoiesis • Autoantibodies damage megakaryocytes • Relative deficiency of thrombopoietin • Impaired thrombopoietin production

    Matzdorff A, et al. Immune Thrombocytopenia. Current Diagnostics and Therapy: recommendations of a joint working group of DGHO, OGHO, SGH, GPOH and DGTI. Oncol Res Treat 2018;41 suppl5:1-30

  • Treatment ITP

  • Grading the severity of bleeding

     The severity bleeding in adults should be graded according to WHO bleeding scale or the National Cancer Institute Common Terminology Criteriafor Advanced Events (NCI-CTCAE)

    Matzdorff A, et al. Immune Thrombocytopenia. Current Diagnostics and Therapy: recommendations of a joint working group of DGHO, OGHO, SGH, GPOH and DGTI. Oncol Res Treat 2018;41 suppl5:1-30

  • Bleeding grades according WHO and NCI-CTCAE

    Bleeding grade Definition

    0 • No sign of bleeding

    I • Petechiae • Small hematoma, echymoses (1 h duration, or tamponade necessary) • Retinal bleeding without visual impairment • Vaginal bleeding (independent of menstruation, more than 2 bandages/d

    necessary) • Melena, hematemesis, hemoptysis, hematuria, hematochezia • Bleeding from puncture sites • Bleeding in muscle and joints

    Matzdorff A, et al. Immune Thrombocytopenia. Current Diagnostics and Therapy: recommendations of a joint working group of DGHO, OGHO, SGH, GPOH and DGTI. Oncol Res Treat 2018;41 suppl5:1-30

  • Bleeding grades according WHO and NCI-CTCAE

    Bleeding grade Definition

    III Transfusion

    required

    • Epistaxis • Bleeding from mucous membrane (mouth, nose) • Vaginal bleeding • Melena, hematemesis, hemoptysis, hematuria, hematochezia • Bleeding from puncture sites • Bleeding in muscle and joints

    IV Life threatening,

    potentially permanent functional

    impairment

    • Retinal bleeding with visual impairment • CNS bleeding • Hemorrhage in other organs with functional impairment (joints, muscles,

    kidneys, lung, etc) • Fatal bleeding (NCI-CTCAE grade V)

    Matzdorff A, et al. Immune Thrombocytopenia. Current Diagnostics and Therapy: recommendations of a joint working group of DGHO, OGHO, SGH, GPOH and DGTI. Oncol Res Treat 2018;41 suppl5:1-30

  • Indications for initiation of treatment: newly

    diagnosed ITP

    Platelet threshold: no evidence based

     Platelet

  • Treatment

    Before initiating treatment consideration must be given to:

     Patient related factors: age, PS, comorbidities, life style (sedentary vs active), and patient wishes

     Disease related factors: platelet count, previous major bleeding

     Additional risk factors for bleeding: the use of antiplatelet and anticoagulant agents, uremia, poorly controlled hypertension, aneurysm, fever, chronic liver disease, history of peptic ulcer

     Treatment related factors: contraindications and side-effects from particular treatment modalities

     The need of medical intervention that may cause bleeding

    Janssen A, et al, 2013; Matzdorff A, et al. 2018

  • Safe platelet count for medical interventions in

    patient with platelet production problem

    Dentistry ≥10-20.000/µL

    Extractions (simple) ≥30.000/µL

    Extractions (complex, molar) ≥50.000/µL

    Lumbar puncture ≥50.000/µL

    GI endoscopy with biopsy ≥20.000/µL

    Bronchoscopy ≥20.000/µL (≥50.000/µL if also biopsy)

    Organ biopsy ≥50.000/µL (< for bone marrow biopsy)

    Minor surgery ≥50.000/µL

    Major and neuro surgery ≥80.000/µL

    Epidural anesthesia ≥80.000/µL

    Janssen A, et al, 2013

  • Neuraxial analgesia and anesthesia

     Neuraxial analgesia and anesthesia is the standard of care for management of the labouring parturient and cesarian delivery

     Thrombocytopenia is considered a relative or even absolute contraindication in neuraxial techniques due to potential risk of epidural hematoma

     There is no consensus on the acceptable platelet count required to safely perform neuraxial techniques

    Lee LO, et al. Anesthesiology 2017; 126: 1053-64.

  • Neuraxial analgesia and anesthesia

    The multicentre perioperative outcomes group database and a systematic literature review were combined to estimate the relationship between platelet count and the risk of epidural hematoma requiring surgical decompression after neuraxial

    techniques:

    The upper bound for 95% CI for epidural hematoma risk (n=573)

    Platelet count/mm3 Epidural hematoma(%)

    0-49.000 11

    50.000-69.000 3

    70.000-100.000 0.2

    Lee LO, et al. Anesthesiology 2017; 126: 1053-64.

  • Frequently used drugs and dosages for ITP

    Corticosteroids

    Predniso(lo)n 1-2mg/kg/d/p.o. or i.v. for 1-2 weeks After response, weekly dose reductions in 10mg steps until a dose of 0.5mg/kg/d is reached, then dose reduction by 5mg/week Response: Initial rates 70%-80%; 1wk; 10%-30% have durable remission

    Methylprednisolone 125-1.000mg i.v. for 1-5 days (followed by prednisone 1mg/kg/d p.o. and subsequent dose reduction as above

    Dexamethasone 40mg p.0. dailyx4d, 4-6 cycles every 14-28 d

    Matzdorff A, et al. Immune Thrombocytopenia. Current Diagnostics and Therapy: recommendations of a joint working group of DGHO, OGHO, SGH, GPOH and DGTI. Oncol