Downloaded 15 times
Uploaded byPritish Chandra Patra
Romiplostim other indications.pptx
Romiplostim is a thrombopoietin receptor agonist that can be used to treat thrombocytopenia. It works by binding to and activating the thrombopoietin receptor on megakaryocyte precursors, which stimulates multiple cell signaling pathways and increases platelet production. Studies have shown romiplostim to be effective at improving platelet counts in conditions like immune thrombocytopenia, aplastic anemia, chemotherapy-induced thrombocytopenia, hematopoietic syndrome of acute radiation syndrome, liver disease, and as pre-procedure treatment for thrombocytopenia. Romiplostim has a versatile role in treating thrombocytopenia from various causes.
In this document
Powered by AI
Dr. Pritish Chandra Patra discusses the management of thrombocytopenia using Romiplostim.
A study shows normal platelet count ranges from 150,000-450,000/microL with mean values higher in females (266,000) than males (237,000).
Thrombocytopenia is defined as a count below 150,000/microL, classified into mild (100K-150K), moderate (50K-99K), and severe (<50K) with risks of bleeding.
Causes include decreased production, ineffective production, increased destruction and consumption, platelet sequestration, and combinations of these mechanisms.
TPO is produced in the liver, kidney, striated muscle, and bone marrow, regulating megakaryocyte proliferation and platelet production.
Overview of the development of TPO receptor agonists.
Romiplostim is a peptibody that activates TPO receptors in the bone marrow, similar to natural TPO.
Approved uses of Eltrombopag and Romiplostim in conditions like ITP and aplastic anemia.
64% of patients resumed chemotherapy after CIT with Romiplostim, supporting its effectiveness over 6 months.
Initial and maximum Romiplostim doses for CIT are outlined, noting increased risk of venous thromboembolism.
Romiplostim enhances recovery from HS-ARS via multiple mechanisms, with a recommended dose of 10 mcg/kg.
Romiplostim improves platelet counts in chronic liver disease and is used in various liver disease scenarios.
Romiplostim effectively increases platelet counts for surgical procedures across various pathologies.
Common causes of thrombocytopenia in ICU include sepsis, DIC, drug effects, and others.
In sepsis, thrombocytopenia is attributed to high consumption rates despite heightened platelet production.
Platelet recovery post-septic shock occurs on average several days after vasopressor discontinuation, median 2 days.
Considerations for TPO-RA administration, monitoring needs, and caution advised when discontinuing Romiplostim.
TPO is vital in platelet production; Romiplostim increases counts, reducing transfusions and bleeding risks.
Various applications of TPO-RA include treating ITP, aplastic anemia, liver disease, and chemotherapy-induced thrombocytopenia.
Presentation wraps up with a summary of Romiplostim's clinical significance and applications.
Discussion of the mechanisms of action for Romiplostim vs Eltrombopag.
Evaluating platelet indices such as MPV and P-LCR, utilizing automated analyzers.
Updates on Romiplostim's approval for use in Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS).
More Related Content
Similar to Romiplostim other indications.pptx
More from Pritish Chandra Patra
Romiplostim other indications.pptx
- 1. Management of other thrombocytopenia withRomiplostim Dr. Pritish Chandra Patra Associate Professor Dept. of Clinical Hematology IMS & SUM Hospital, Bhubaneswar
- 2. A normal plateletcount • A study from the USA involving over 12,000 adults in the National Health and Nutrition Examination Survey (NHANES) database found the following: • Platelet count • Range from: 150,000 - 450,000/microL • Slightly higher mean values in females (266,000/microL) than males (237,000/microL) • Slightly higher in younger people than older people
- 3. What is alow platelet count? • Thrombocytopenia- defined as a platelet count below the lower limit of normal: <150,000/microL • Degrees of thrombocytopenia- further subdivided into • Mild (100,000 - 150,000/microL) • Moderate (50,000 - 99,000/microL) • Severe (<50,000/microL) • Numbers Vs underlying disease (eg, in ITP, platelet count <30,000/microL - severe thrombocytopenia) • Clinical significance- Severe thrombocytopenia (platelet count <30,000 - 50,000/microL) • greater risk of bleeding- intracranial • implies a greater likelihood for needing treatment
- 4. Thrombocytopenia: basic mechanisms Decreased platelet production(IBMFS, AA, Leukemia, CIT) Ineffective platelet production (MDS, Megaloblastic anemia) Increased platelet destruction (ITP, HLH) Increased platelet consumption (MAHA- DIC, TTP, HUS) Platelet sequestration (Hypersplenism) Combination of multiple above mechanisms
- 5. Thrombopoietin (TPO) • Producedin • Liver- parenchymal cells & sinusoidal endothelial cells • Kidney- proximal convoluted tubule cells • Striated muscle • Bone marrow stromal cells • TPO is bound to the surface of platelets and megakaryocytes by the MPL receptor. • TPO regulates the differentiation of megakaryocytes and platelets. • Inside the platelets it gets destroyed, while inside the megakaryocytes it gives the signal of their maturation and consecutively more platelet production. Kaushansky K (May 2006). "Lineage-specific hematopoietic growth factors". The New England Journal of Medicine. 354 (19): 2034–45. Bussel JB et al. A Review of Romiplostim Mechanism of Action and Clinical Applicability. Drug Des Devel Ther. 2021 May 26;15:2243-2268.
- 6. Generations of TPO-RA DavidJ. Kuter. New Thrombopoietic Growth Factors. Clinical Lymphoma & Myeloma, Vol. 9, Suppl. 3, S347-S356, 2009
- 7. TPO-RA: Romiplostim VsEltrombopag • Romiplostim: • A peptibody comprising four TPO-R binding domains with high affinity for the TPO-R (MPL) and one carrier Fc domain. • Binds to and activates the TPO-R on megakaryocyte precursors in bone marrow. • Binds in the same manner as endogenous TPO and can displace TPO from its receptor. • Romiplostim activates many of the same pathways as TPO, leading to sustained improvement of platelet counts with continued treatment. • Different TPO-RAs activate the TPO-R in different ways • Romiplostim activates the extracellular domain of the TPO-R • Eltrombopag activates the transmembrane portion of the TPO-R
- 8. TPO-RA: Romiplostim VsEltrombopag
- 9. Approved indications • Eltrombopag:by US FDA & EMA • Chronic-ITP • Hep-C associated TCP • SAA • Romiplostim: • ITP • HS-ARS • although not approved for use in aplastic anemia by US FDA & EMA, it similarly stimulates the proliferation of residual stem and progenitor cells in patients with aplastic anemia (approval has been received for refractory aplastic anemia in Japan and Korea).
- 10.
- 11. Chemotherapy Induced Thrombocytopenia(CIT) (p < .001)
- 12. • 64% (n= 28) resumed the same chemotherapy regimen that had led to CIT • 36% (n = 16) resumed a different chemotherapy regimen • 58% (11/19) resumed full-dose or increased dose chemotherapy who had reduction in chemotherapy dose before enrollment • Only 6.8% (n = 3) experienced chemotherapy dose reduction or dose delay as a result of recurrent CIT within the specified time period • 64% (28/44) patients who resumed chemotherapy continued taking romiplostim for more than 6 months, and • 27% (12/44) continued for more than 1 year. • The longest exposure to romiplostim was 34 months. Soff GA et al. J Clin Oncol. 2019 Nov 1;37(31):2892-2898. Secondary end points:
- 16. • Dose: • Beginningat 2-4 mcg/kg, increased by 1-2 mcg/kg per week to target platelet count 100,000-150,000/mcL • Maximum dose: 10 mcg/kg weekly • TPO-RAs for CIT may increase the risk of venous thromboembolism (VTE) in patients with cancer. Therefore, caution is warranted. Chemotherapy Induced Thrombocytopenia (CIT)
- 18. Hematopoietic Syndrome ofAcute Radiation Syndrome (HS-ARS) • Romiplostim- reduces lethality and pancytopenia by multiple mechanisms • stimulation of splenic progenitor cells • induction of pulmonary megakaryocytopoiesis • prevention of bone marrow cell death • modulation of DNA repair • production of cytokines • Romiplostim has also been examined in combination with g-CSF and rEPO in irradiated mice, which led to 100% survival at day 30. • Recommended dose: 10 mcg/kg administered once as a subcutaneous injection. Administer the dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Bussel JB et al. A Review of Romiplostim Mechanism of Action and Clinical Applicability. Drug Des Devel Ther. 2021 May 26;15:2243-2268.
- 19. Chronic liver disease •CLD, especially cirrhosis- often have thrombocytopenia • In advanced CLD • TPO declines as a result of splenomegaly and hepatic damage such that the liver cannot make even normal amounts of TPO. • accelerated platelet destruction and reduced platelet production • Avatrombopag and lusutrombopag, have been approved specifically to increase the platelet count in patients with thrombocytopenia and liver disease undergoing a procedure. • Eltrombopag is approved to treat thrombocytopenia in patients with hepatitis C with liver disease to allow for the initiation and maintenance of interferon-based therapy. • Romiplostim case reports have shown to improve platelet counts in a patient with • hepatocellular carcinoma • hepatitis C
- 20. Peri-surgical • Romiplostim hasbeen used successfully to increase platelet counts in patients with thrombocytopenia caused by different underlying pathologic conditions in association with various surgical procedures. • The underlying causes of thrombocytopenia included ITP, chronic liver disease, hematologic malignancy, and drug-related and hereditary causes. • Retrospective data indicate that romiplostim can also improve platelet counts to levels conducive for performing various surgeries, including major cardiac, orthopedic, gastrointestinal, and neurologic surgeries. • Romiplostim >>> Eltrombopag
- 22.
- 23. Romiplostim reverts thethrombocytopenia in Dengue Hemorrhagic Fever Margarita S. Rodriguez-Mejorada et al; Refractory Thrombocytopenia Associated with Dengue Hemorrhagic Fever Responds to Romiplostim. Blood 2010; 116 (21): 4668.
- 24.
- 25. Common causes of thrombocytopeniain ICU patients: • Sepsis • Disseminated intravascular coagulation • Consumption (eg, major trauma, cardiopulmonary bypass) • Dilution (with massive transfusion) • Myelosuppressive chemotherapy • Mechanical circulatory support devices (eg, intra-aortic balloon pump) Less common but important causes of thrombocytopenia that should not be missed: • Heparin-induced thrombocytopenia • Hemophagocytic syndrome Uncommon causes of thrombocytopenia that develop during ICU admission: • Drug-induced thrombocytopenia (other than heparin or cytotoxic chemotherapy) • Leukemia, myelodysplasia, aplastic anemia, etc, unless abnormalities were already present before ICU admission • Thrombotic thrombocytopenic purpura • Immune/idiopathic thrombocytopenia • Post-transfusion purpura Causes of thrombocytopenia in the ICU Zarychanski R, et al. ASH Education Program Book. 2017 Dec 8;2017(1):660-6.
- 26. • Firstly, itwas assumed that the only mechanism of thrombocytopenia in sepsis was the decreased production of platelets • Lately it was found in studies that • Reticulated platelet percentage (RP%) and thrombopoietin (TPO); both markers were increased in septic patients. • Significant endotoxemia in sepsis increases pro-inflammatory markers such as TNF-α, IL-1, IL-6, and IL-8, which are known for being thrombopoietic, meaning that it can increase platelet production • Thus in patients with sepsis the thrombopoiesis rate is high, but the platelet consumption surpasses platelet production Proposed mechanism of thrombocytopenia in sepsis Gonzalez DA, et al. Cureus. 2022 May 27;14(5).
- 27. Time course ofthrombocytopenia in septic shock • Septic shock: • In patients with septic shock who develop thrombocytopenia, despite signs of clinical improvement, on average, platelet recovery is not anticipated until several days after vasopressor independence. • The median time from discontinuation of vasopressors to recovery of platelet counts above 100 x 109/L is 2 days (IQR, 0-4) • Mean platelet count in patients with septic shock who developed thrombocytopenia after ICU admission. • Time axis is anchored to the day that vasopressors were discontinued (day 0). Only data for survivors are included Menard CE, et al. Intensive Care Med Exp. 2016; 4(Suppl 1):A586
- 29. Practical issues • Routeof administration needs to be considered when choosing a TPO-RA. • More frequent hospital visits are required until platelet counts are stabilized. • Eltrombopag needs to be taken on an empty stomach (≥2 hours before or 4 hours after calcium- rich foods) and may not be suitable in patients with absorption problems, nausea, transaminitis, or irregular mealtimes. • Discontinuation of romiplostim should be done in a stepwise fashion, as abruptly stopping treatment can lead to rebound thrombocytopenia in patients who responded to treatment. • Platelet counts should be monitored at least weekly and for ≥2 weeks after discontinuation. • The dose of romiplostim should be increased 1 μg/kg/week if platelet counts decrease to <50 × 109/L or the patient exhibits symptoms.
- 30. Summary • Thrombopoietin isinvolved in multiple steps of platelet production, from the stem cell through development of mature megakaryocytes and possibly even platelet release. • Romiplostim, an TPO-RA acts by increasing platelet production and therefore increases platelet counts. • Increased platelet counts can reduce the need for platelet transfusions and decrease bleeding events in multiple conditions. • Romiplostim binds to and activates the TPO-R on megakaryocyte precursors, activating multiple cell-signaling pathways, leading to enhanced cell growth and cell viability, which results in increased platelet production. • Studies have also shown romiplostim to be effective in improving platelet counts in various preclinical and clinical settings, including CIT, aplastic anemia, animal models of acute radiation syndrome, and liver disease. • Although many indications have not been approved yet, these studies highlight the versatility of romiplostim in thrombocytopenic conditions other than ITP. In particular, in severe aplastic anemia, for which eltrombopag has been licensed as upfront treatment in combination with standard immunosuppressive therapy, a recent study showed similar efficacy of romiplostim.
- 31. Use of TPOReceptor Agonists • Immune thrombocytopenia (ITP) • Aplastic anemia • Hepatitis C related thrombocytopenia • Liver disease • Chemotherapy-induced thrombocytopenia (CIT) • Radiation protection (HS-ARS) • Pre-procedure thrombocytopenia • Inherited thrombocytopenia (MYH-9) • Stem cell transplant • AML induction/remission chemotherapy • Drug-induced thrombocytopenia • Myelodysplastic syndromes (MDS)
- 32.
- 33. MOA of TPO-RA:Romilostim Vs Eltrobopag
- 34. Other helpful plateletindices Platelet indices MPV PDW P-LCR IPF By automated hematology analyzers Large platelet
- 35. Romy Approved by DCGIin HS-ARS Romiplostim Approved by US-FDA in HS-ARS