1 / 31

Autoimmune Thrombocytopenia (Idiopathic Thrombocytopenia Purpura, ITP)

Autoimmune Thrombocytopenia (Idiopathic Thrombocytopenia Purpura, ITP). Autoimmune Thrombocytopenia. Acquired disorder Platelet autoantibodies destroy host and transfused platelets More frequently detected with routine testing using automated cell counters

wolfe
Télécharger la présentation

Autoimmune Thrombocytopenia (Idiopathic Thrombocytopenia Purpura, ITP)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Autoimmune Thrombocytopenia(Idiopathic Thrombocytopenia Purpura, ITP)

  2. Autoimmune Thrombocytopenia • Acquired disorder • Platelet autoantibodies destroy host and transfused platelets • More frequently detected with routine testing using automated cell counters • Important to recognize a subgroup of mild, asymptomatic patients who require no treatment

  3. Autoimmune Thrombocytopenia Age and Sex Distribution Data redrawn from Beutler, E, Lichtman, MA, Coller, BS, et al, Williams Hematology, 5th ed. McGraw-Hill, New York, 1995

  4. Autoimmune ThrombocytopeniaRelationship of Bleeding to Platelet Count 1 = minimal bleeding after trauma 2 = spontaneous, self limited 3 = spontaneous, needing Rx 4 = severe, life-threatening Data from Lacy, JV, Penner, JA, Semin Thromb Haemost 1977;3:160

  5. Autoimmune ThrombocytopeniaBleeding Manifestations • None in some patients • Petechiae and ecchymoses > menorrhagia>GI >> intracranial bleeding • Risk of intracranial hemorrhage <1% • Risks may be greater in elderly due to comorbidity • Oral bleeding and widespread skin bleeding (“wet purpura”): generally, an indicator of increased risk of serious bleeding

  6. Autoimmune ThrombocytopeniaDiagnosis • A diagnosis of exclusion • No clinically apparent associated conditions that may cause thrombocytopenia • Isolated thrombocytopenia, with otherwise normal blood counts, including examination of peripheral smear

  7. I.T.P.: Megathrombocytes Normal Platelet Number & Size

  8. Pseudothrombocytopenia

  9. Autoimmune ThrombocytopeniaDiagnosis • No implicated drugs • especially heparin, quinine, quinidine, sulfonamides, b-lactams, fludarabine • No splenomegaly • No evidence of sepsis • Normal coagulation tests • No RBC microangiopathy

  10. Autoimmune ThrombocytopeniaDiagnosis • Usually idiopathic, but may be secondary to: HIV-1, CLL/NHL, other autoimmune diseases • Further testing: • HIV-1 in patients with risk factors • Bone marrow with karyotype in older patients to exclude myelodysplasia • Thyroid function testing to exclude infrequent coincidence of autoimmune thyroid disease

  11. Historical Background • 1951: Harrington, et al showed an “antiplatelet factor” in plasma caused ITP. • 1965: Shulman, et al identified a 7S IgG anti-platelet aby in pts’ plasma. • 1975: Dixon, et al first measured platelet associated IgG on plts. • 1987 Macmillan, et al in US and Kiefel, et al in Germany described new assays for platelet associated autoabys. Harrington, et al., J Lab Clin Med 38:1, 1951

  12. Immunopathogenesis of ITP IgG or IgA autoabys B cell-derived plasma cell GPIa/IIa Fc-mediated R.E. Cell Clearance GPIV, V GPIIb/IIIa GPIb/IX IFNg Platelet IL-10 IL-2 CD4 auto- reactive T cells gd Tcells

  13. Natural History of ITP • Stasi, et al (Am J Med 1995; 98:436) • 208 adults with ITP followed for median of 92 months: • 42% had pltc > 50,000 and were not treated • Spontaneous remission rate: 9% • At last follow-up in 95 treated pts, 43 in CR, 52 still being treated • 5 deaths attributable to thrombocytopenia

  14. Autoimmune Thrombocytopenia General Treatment Philosophy • Treatment should be restricted to pts with moderate (20-40K/mL) or severe (<20K/mL) thrombocytopenia. • Goal is to achieve a safe platelet count. • Treatment should be limited in duration once a response is obtained.

  15. Initial Treatment of ITPGlucocorticoids • Prednisone, 1 mg/kg/d • Response expected by 2 weeks. • Duration of therapy determined by platelet count response. Taper slowly (4-6 wks) • Complete response in 40%. • Most responders have recurrence with tapering. • Sustained response for 6 months in only 20%. • Other therapies will be needed in most

  16. Initial Treatment of ITPInitial Treatment with High Dose Dexametasone Cheng, Y, Wong, R.S.M., Soo, O.Y., et al. NEJM 2003; 349:831-835. • 157consecutive patients • 125 eligible with initial pltc mean of 12,200/mL given dexamethasone, 40 mg/d x 4 days • Good initial response (pltc increase of at least 30,000/mL) in 106/125 (85%) with mean pltc increase by at least 20,000/mL by day 3 and mean pltc increase to 101,400 ± 53,200/mLby 7 days after treatment • 53 (50%) had sustained response • 53 (50%) had relapse within 6 mos., most within first 3 mos. • Pltc < 90,000/mL on day 10 associated with high relapse risk. • Treatment well tolerated.

  17. Steroid-Refractory ITP Splenectomy • Traditionally considered second-line treatment for adults with ITP who fail steroids. • Opinions vary as to timing of splenectomy. • Approximately 50-65% will achieve a normal platelet count which is sustained. • CRs are achieved by week 2. • Only consistent predictor of response is age. • Response to steroids, IVIG, anti-D are all inconsistent predictors of response.

  18. Cumulative Response to Splenectomy Age < 40 Age < 40 Age > 40 Fabris, F, et al, Br J Haematol 2001;112:637

  19. Steroid Refractory ITPMorbidity from Splenectomy • Greatest morbidity in the obese, elderly and those with comorbidities. • Morbidity as high as 26% in one series of 78 splenectomized ITP pts. • Morbidity less with laparoscopic approach. • Sooner ability to eat liquid diet • Less pain • Quicker discharge • Operative time no shorter • Mortality from sepsis = 0.73 per 1000 pt.yrs.

  20. Other Initial Treatments IVIG • Especially useful for bleeding emergencies in pts with “acute” ITP to transiently increase platelet count. • Godeau, B, et al Br J Haematol 1999;107:716 randomized, prospective, multicenter (n = 36) • 0.5 or 1.0 g/kg on day 1, up to 2g/kg by day 4 if needed • Increase in platelet count >80,000: 6% and 28% on day 2; 24% and 67% on day 4; overall response to 2 g/kg by day 7: 78% • Transient, reversible side effects: hypertension, chills, emesis, hypotension; rarely, renal failure

  21. Other Initial Treatments Anti-(Rh)D • Effective only in Rh-positive patients. • Not expected to induce long-term CR • Dose: 50-75 mg/kg I.V. • Response rate in one series* was 70% with responses lasting >21 days in 50%. • Mild hemolytic anemia occurs. If RBC transfusion needed, use Rh neg. cells. Scaradavou, A, et. al. Blood 1997;89;2689

  22. Other Initial TreatmentsNovel Approaches • Evaluate for and treat H. pylori infection: Gasbarrini, et al* • High rate of H. pylori infection among their ITP pts • 8 of 11 who had eradication of infection had significant increase in pltc at 2 and 4 months; 6 of 8 had disappearance of autoantibody (p<0.003) • Others** have been unable to duplicate results • Splenic irradiation and splenic embolization * Gasbarrini, A., et al, Lancet 1998; 352:878 (Sept.) ** Jarque, I., et al, Br J Haematol 2001; 115:1002-1003

  23. Chronic Refractory ITP • ITP has persisted for > than 3 months • Failure to respond to first line therapy and splenectomy • Platelet count <30,000/mL • Best treatment uncertain

  24. Chronic Refractory ITPMultiple Therapeutic Approaches • High dose dexamethasone • Cytoxan, vincristine, prednisone (CVP) • Azathioprine • Danazol • Vinblastine • Interferon a • Cyclosporin • Accessory splenectomy • Rituximab (chimeric anti CD-20) • Mycophenolate mofetil • High dose cyclophosphamide/autologous PSCT

  25. Chronic Refractory ITPChimeric Anti-CD20 • Four reported series in literature as of 8/03 • Stasi, et al* • 25 pts with refractory primary ITP • Resistant to 2-5 regimens, 8 splenectomized • Complete response (pltc>100K) in 5 • Partial response (pltc 50-100K) in 3 • Minor response (pltc <50K, but stable) in 3 • Overall response = 52% • 7 with sustained responses (>6 months) • 2 relapses remitted with retreatment *Stasi, R, et al, Blood 2001;98:952

  26. Chronic Refractory ITPLong-term Outcomes • 183 patients (158 adults, 25 children)* • 47 refractory to splenectomy prospectively followed for median of 7.5 yrs • 12 with moderate thrombocytopenia, untreated • 35 treated with median of 2 salvage treatments • 36 (77%) reached durable pltcs >100K • 9 with no treatment • 27 with low dose steroids or azathioprine • In 6, pltc. remained at 35-100K • 5 remained severely thrombocytopenic • 3 adults and 1 child died of bleeding Bourgeois, E, et al. Br J Haematol 2003;1079-1088

  27. Chronic Refractory ITP(Modified from George, JN, et al NEJM 1994;331:1207)

  28. I.T.P. “Let the treatment fit the patient.” --James N. George, M.D. (NEJM 2003; 349:903-905

More Related