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Immune Thrombocytopenia PowerPoint Presentation

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Description : Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia.

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Published on : Sep 27, 2022 | Views : 1935 | Downloads : 16

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Mohammad Amin Sabahi ` Immune Thrombocytopenia 2
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CONTENTS ITP Definition and Causes of Immune Thrombocytopenia The pathophysiology of ITP Diagnosis Treatment 3
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A 72-year-old woman who is receiving apixaban for atrial fibrillation but otherwise does not have a clinically significant medical history presents to the hospital with lower gastrointestinal bleeding. On admission, her hemoglobin level is 8.5 g per deciliter, platelet count 2000 per cubic millimeter, and white-cell count 5300 per cubic millimeter. She receives a transfusion of packed red cells and platelets that results in an increase in the hemoglobin level and a decrease in bleeding, but only a transient increase in the platelet count. The examination is unremarkable. A peripheral-blood smear shows no abnormalities other than thrombocytopenia. How should this case be managed? 4
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Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia. Patients may be asymptomatic at presentation or they may present with mild mucocutaneous to life-threatening bleeding , only 5% of patients present with severe bleeding, patients with ITP often report fatigue and impaired health-related quality of life The risk of VTE is twice as high among patients with ITP as among persons in the general population; (problematic) ITP may be a primary condition or it may be caused by other diseases. Overall, the incidence of ITP ranges from 2 to 4 cases per 100,000 person-years, with two peaks: one between 20 and 30 years of age with a slight female predominance and a larger one after 60 years of age with equal sex distribution. Although some patients have one episode of ITP followed by an immediate remission, chronic ITP develops in up to 70% of adults with this condition. Both spontaneous and treatment-induced remission can occur many years after diagnosis Definition 5
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The pathophysiology of ITP complex & incompletely understood . antibody-coated platelets are prematurely destroyed in the spleen, liver, or both through interaction with Fcγ receptors. complement-mediated desialylation-induced inhibit megakaryocyte function. antiplatelet antibodies are not detected in up to 50% of patients(alternative mechanisms) Abnormalities in T cells CD8 cells are also involved. 8
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ITP is defined as a platelet count below 100K per cubic millimeter in patients in whom other causes of thrombocytopenia have been ruled out.* Examination of the peripheral-blood smear in a patient with ITP shows reduced numbers of platelets with no other abnormalities (e.g., schistocytes and dysplastic changes); although some patients have large platelets, this is not a pathognomonic feature . There is NO diagnostic test for ITP; antiplatelet antibodies are detected in only 50 to 60% of patients with ITP and measurement of such antibodies is not recommended. Bone marrow examination is not diagnostic in patients with ITP Diagnosis 10
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The goals of treatment are: to stop active bleeding reduce the risk of future bleeding. Specific measures include : withdrawal of anticoagulant and antiplatelet agents platelet transfusions glucocorticoids intravenous immune globulin (IVIG) Platelet transfusions can help to limit bleeding.* IVIG raises the platelet count within 1 to 4 days in 80% of patients, but effects last only 1 to 2 weeks. IVIG is indicated in patients with active serious bleeding and in those with very low platelets (<10,000) Concomitant use of glucocorticoids with IVIG => more sustained response than that with IVIG alone. In life-threatening situations Antifibrinolytic treatment (tranexamic acid) can help to stop bleeding, particularly from mucous membranes, and menorrhagia can be treated with hormonal therapy. Treatment of Active Bleeding 12
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if asymptomatic or have only mild mucocutaneous bleeding => the decision to treat should be guided by the risk of future bleeding and patient preferences. However, predicting the risk of future bleeding among patients with ITP is challenging. A platelet count of less than 20,000 to 30,000 per cubic millimeter is frequently used as a criterion for treatment. increase in the 1-year risk of bleeding requiring hospitalization of 2.5 times (25,000 and 50,000) and 7 times (below 25,000 ). Risk factors that influence bleeding include : older age (e.g., >65 years) history of bleeding concomitant use of anticoagulants and platelet inhibitors the presence of coexisting conditions such as renal impairment and the risk of trauma from daily activities. patients who are receiving anticoagulants or antiplatelet agents => above 50,000 . Treatment to Prevent Future Bleeding 13
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the standard initial therapy for patients with ITP. Two commonly used regimens are : pulsed high-dose dexamethasone more prolonged course of oral prednisolone . overall responses at 6 months does not differ significantly. Adverse events such as : weight gain and cushingoid appearance => prednisolone. neuropsychiatric effects => dexamethasone. 60 to 80% of patients with ITP have an initial response to glucocorticoids only 30 to 50% of adults have a sustained response after glucocorticoids are discontinued. In some studies, continued use has been associated with a higher incidence of long-term remission (adverse effects). Glucocorticoids 14
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for patients who do not have an initial response to glucocorticoids who have recurrent decreases in platelet counts after glucocorticoids are discontinued thrombopoietin-receptor agonists & immunomodulators In the absence of randomized trials directly comparing these therapies or of biomarkers to guide the choice of medication, treatment decisions are based on other factors including : the availability of medications adverse effects the required speed of response and patient or physician preference. Among the available options, thrombopoietin-receptor agonists, rituximab, and fostamatinib have undergone the most rigorous study . Other Medical Therapies 15
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Eltrombopag and romiplostim FDA approved for patients with ITP that is refractory to other treatment and with disease lasting more than 6 months (Eltrombopag) or 12 months (romiplostim). 70 to 95% of patients had an increased platelet count with initial treatment 40 to 60% had durable response with ongoing treatment. TPO-Receptor Agonists 16
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Eltrombopag is administered as a daily tablet (with dietary restrictions), whereas romiplostim is administered in weekly subcutaneous injections. if one agent is ineffective, switching to the other results in a platelet response in up to 50% of patients. An initial response to thrombopoietin-receptor agonists usually occurs within 1 to 2 weeks. Once a response is achieved, ongoing treatment is ordinarily required to maintain effect. However, 10 to 30% of patients can discontinue treatment after receiving thrombopoietin- receptor agonists for many months or years, and the disease remains in remission, although late relapses may occur. TPO-Receptor Agonists 17
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In early studies, concerns were raised regarding adverse effects of these agents on bone marrow: moderately increased bone marrow reticulin fibrosis (10% and reversible on discontinuation) . increased risk of venous thromboembolism. (6% median follow-up of 2 years) . predominantly in patients with other coexisting conditions and risk factors. Eltrombopag => elevated liver aminotransferase levels (reversible) Avatrombopag, another oral thrombopoietin receptor agonist (which, unlike eltrombopag, can be administered without dietary restrictions), was approved by the FDA in June 2019 for the treatment of adults with chronic ITP. TPO-Receptor Agonists 18
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Rituximab is the most widely used immunomodulator in patients with ITP, not approved by the FDA. response in 60% of patients, with a complete response in 40% of patients. significantly higher incidence of complete response at 6 months with rituximab than with glucocorticoids or placebo. A response to rituximab is typically observed within 1 to 8 weeks . young women (<50 years of age) with a short duration of disease (<2 years) were reported to have a higher incidence of response and more durable responses than other patients. The main advantage of rituximab is sustained platelet responses that last more than 2 years in 50% of patients who have a response. Although ITP eventually relapses in most patients, most of those in whom the disease relapses have a response to retreatment with rituximab. An increase in minor infections. However, major complications such as progressive multifocal leukoencephalopathy are exceedingly rare. Immunomodulators 19
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Fostamatinib, an oral spleen tyrosine kinase (Syk) inhibitor, approved by the FDA in 2018 for patients with ITP in whom one previous therapy has failed. stable response was achieved in 18% .* A response * was achieved in 43% . The mean time to response was 15 days. Diarrhea, hypertension, transaminitis, and nausea were common adverse effects Other immunomodulatory agents such as mycophenolate mofetil, azathioprine, dapsone, and danazol are also used in patients with ITP. studies that suggest that 30 to 60% of patients have a response. Immunomodulators 20
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the most effective therapy for ITP long-lasting remissions in 60 to 70% of patients. consideration of splenectomy is usually limited to patients who do not have a response cannot receive standard medical therapies because of side effects at least a year has passed since diagnosis (to allow for remission to occur) due to , the potential complications of splenectomy, and the inability to predict which patients will have a response, The frequency of splenectomy has decreased substantially during the past two decade. Splenectomy 21
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Short-term risks : operative and postoperative complications, venous thromboembolism and sepsis. Laparoscopic splenectomy is associated with lower postoperative mortality and morbidity and a shorter recovery time than open splenectomy. immediate risk of venous thromboembolism can be reduced by thromboprophylaxis* risk of infection with encapsulated bacteria and require repeated vaccinations*. higher risk of both early and late sepsis vascular complications, such as CAD, stroke, and chronic thromboembolic pulmonary HTN. Splenectomy is generally not performed in : frail elderly patients because of increased surgical complications. Secondary ITP owing to a lower incidence of response and more adverse events Splenectomy 22
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A 72-year-old woman who is receiving apixaban for atrial fibrillation but otherwise does not have a clinically significant medical history presents to the hospital with lower gastrointestinal bleeding. On admission, her hemoglobin level is 8.5 g per deciliter, platelet count 2000 per cubic millimeter, and white-cell count 5300 per cubic millimeter. She receives a transfusion of packed red cells and platelets that results in an increase in the hemoglobin level and a decrease in bleeding, but only a transient increase in the platelet count. The examination is unremarkable. A peripheral-blood smear shows no abnormalities other than thrombocytopenia. How should this case be managed? 23
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THANK YOU 24