Autoimmune thrombocytopenic purpura=الفرفرية بنقص الصفيحات المناعي الذاتي |
Autoimmune thrombocytopenic purpura
Idiopathic thrombocytopenic purpura (ITP), also known as primary immune thrombocytopenic purpura and autoimmune thrombocytopenic purpura, is defined as isolated thrombocytopenia with normal bone marrow and the absence of other causes of thrombocytopenia. The 2 distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults. ITP is a decrease in the number of circulating platelets in the absence of toxic exposure or a disease associated with a low platelet count. PathophysiologyITP is primarily a disease of increased peripheral platelet destruction, with most patients having antibodies to specific platelet membrane glycoproteins. Relative marrow failure may contribute to this condition, since studies show that most patients have either normal or diminished platelet production. Acute ITP often follows an acute infection and has a spontaneous resolution within 2 months. Chronic ITP persists longer than 6 months without a specific cause. Frequency
The incidence of ITP in adults is approximately 66 cases per 1,000,000 per year. An average estimate of the incidence in children is 50 cases per 1,000,000 per year. New cases of chronic refractory ITP comprise approximately 10 cases per 1,000,000 per year. According to studies in Denmark and England, childhood ITP occurs in approximately 10-40 cases per 1,000,000 per year. A study in Kuwait reported a higher incidence of 125 cases per 1,000,000 per year.
Physical
Evaluate the type and the severity of bleeding and try to exclude other causes of bleeding. Seek evidence of liver disease, thrombosis, autoimmune diseases (eg, nephritis, cutaneous vasculitis, arthritis), and infection, particularly HIV. Common physical findings include the following:
Causes
TreatmentPrehospital Care
Emergency Department Care
Consultations
Medication
Glucocorticoids and IVIg are the mainstays of medical therapy. Indications for use, dosage, and route of administration are based on the patient's clinical condition, the absolute platelet count, and the degree of symptoms. Consultation with a hematologist may be needed prior to starting therapy. Children who have platelet counts >30,000/mm3 and are asymptomatic or have only minor purpura do not require routine treatment. Children who have platelet counts <20,000/mm3 and significant mucous membrane bleeding and those who have platelet counts <10,000/mm3 and minor purpura should receive specific treatment. Adults with platelet counts >50,000/mm3 do not require treatment. Treatment is indicated for adults with counts <50,000/mm3 with significant mucous membrane bleeding. Treatment also is indicated for those adults with risk factors for bleeding (eg, hypertension, peptic ulcer disease, vigorous lifestyle) and in patients with a platelet count <20,000-30,000/mm3. IV anti-(Rh)D, also known as IV Rh immune globulin (IG), was not recommended by the 1996 American Society of Hematology practice guidelines. However, recent studies using higher dosages of IV RhIG in acute ITP in children and adults show platelet count increases at 24 hours faster than medicating with steroids and at 72 hours similar to IVIg. Although generally less toxic than IV steroids, IV RhIG is more expensive than IV steroids. Studies in children with chronic ITP show that escalating or elevated doses of IV RhIG have comparable responses to those of high-dose IVIg therapy in children. This therapy is not appropriate for patients who have undergone splenectomy. Acute intravascular hemolysis after infusing IV RhIG has been reported, with an estimated incidence of 1 in 1115 patients. Steroid use and immunosuppressives and splenectomy may be undesirable because of their associated complications. For long-term steroid use, this includes osteoporosis, glaucoma, cataracts, loss of muscle mass, and an increased risk of infection. For immunosuppressive therapy and splenectomy, risks include worsening immunosuppression and infection or sepsis. Studies of the use of multiagent therapies in refractory patients are ongoing. Some small studies have shown limited success. According to one study1 , using a combination of weekly vincristine, weekly methylprednisolone, both until platelet counts reached 50,000/mm3, and cyclosporine orally twice daily until the platelet count is normal for 3-6 months seems promising, though larger prospective studies are needed. Other therapies, such as cyclophosphamide, danazol, dapsone, interferon alfa, azathioprine, vinca alkaloids, accessory splenectomy, and splenic radiation have been studied. Many case series discussing these treatments are too small to show sufficient evidence of a clinically significant reduction in bleeding or mortality rate; however, they serve as additional therapeutic measures in ITP refractory-to-primary therapy (eg, glucocorticoids, IVIg immunoglobulin, splenectomy). Newer studies on rituximab suggest that this agent is an effective treatment option in splenectomized refractory or relapsed ITP patients.2,3 GlucocorticoidsThese agents are used to treat idiopathic and acquired autoimmune disorders. They have been shown to increase platelet count in ITP. Prednisone (Deltasone, Orasone, Sterapred)Useful in treating inflammatory and allergic reactions; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. DOC for all adult patients with platelet counts <50,000/mm3. Asymptomatic patients with platelet counts >20,000/mm3, or patients with counts 30,000-50,000/mm3 with only minor purpura, may not need therapy; withholding medical therapy may be appropriate for asymptomatic patients, regardless of count.
Adult1-2 mg/kg/d PO Pediatric4-8 mg/kg/d PO for severe, life-threatening bleeding with platelet counts <50,000/mm3, or for all patients with platelet counts <30,000/mm3
Estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals PrecautionsMay cause severe infections, hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, and growth suppression; abrupt discontinuation may cause adrenal crisis Methylprednisolone (Solu-Medrol, Depo-Medrol)Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased permeability. Used as alternative glucocorticoid of choice for all patients with severe, life-threatening bleeding or children with platelet counts <30,000/mm3. Careful observation without medical treatment may be appropriate in some asymptomatic children.
AdultLoading dose: 125-250 mg IV PediatricLoading dose: 2 mg/kg IV
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking concurrent diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PrecautionsHyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications Blood productsAdministration of IVIg may temporarily increase platelet counts in some children and adults with ITP. Consider IVIg if the situation requires a rapid, temporary rise in platelet count. Intravenous immune globulin (IVIg)DOC for severe, life-threatening bleeding or for children with platelet counts <20,000/mm3 with minor purpura; can be used alone or in addition to glucocorticoid therapy.
Adult1-2 g/kg IV administered over 1-5 d Pediatric1 g/kg once
None reported
Documented hypersensitivity; IgA deficiency and anti-IgE/IgG antibodies
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PrecautionsCheck serum IgA before IVIg (use IgA-depleted product, eg, Gammagard S/D); may increase serum viscosity and thromboembolic events; may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion) Thrombopoietic AgentThese agents directly stimulates bone marrow platelet production.6 Eltrombopag (Promacta)Oral thrombopoietin (TPO) receptor agonist. Interacts with transmembrane domain of human TPO receptor and induces megakaryocyte proliferation and differentiation from bone marrow progenitor cells. Indicated for thrombocytopenia associated with chronic idiopathic thrombocytopenic purpura in patients experiencing inadequate response to corticosteroids, immunoglobulins, or splenectomy. Not for use to normalize platelet counts but used when clinical condition increases bleeding risk.
Adult50 mg PO qd 1 h ac or 2 h pc PediatricNot established
CYP1A2, CYP2C8, UGT1A1, and UGT1A3 substrate; OATP1B1 inhibitor; UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15 inhibitor
None known
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PrecautionsMay cause hepatic impairment, monitor ALT, AST, and bilirubin, and discontinue if levels increase; may cause bone marrow fibrosis because of reticulin fiber deposition; excessive dose may increase platelet counts and produce thrombotic/thromboembolic complications (discontinue if platelet count >400 X 109/L after 2 wk at lowest dose); may increase risk for hematological malignancies; monitor CBC count weekly during dose adjustment, monthly following stable dose, and at least 4 wk after discontinuation Romiplostim (Nplate)An Fc-peptide fusion protein (peptibody) that increases platelet production through binding and activation of the thrombopoietin (TPO) receptor, a mechanism similar to endogenous TPO. Indicated for chronic immune (idiopathic) thrombocytopenic purpura in patients who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Adult1 mcg/kg (actual body weight) SC initially; adjust in increments of 1 mcg/kg SC qwk to achieve platelet count of 50 X 109/L or greater (median dose in clinical trials was 2 mcg/kg); not to exceed 10 mcg/kg/wk Pediatric<18 years: Not established
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