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( 81t:D$Tw42dd35//0011   g M %p ` (L.4x$x̙33  (p ` | 81 (   (U 81D   ([h 81tD$  [h42dd3 5//0011 (.4x$x̙33  (g M  81  a  (uz w 81$  uz w1%5Idiopathic Thrombocytopenic Purpura: </,/%/,/// /)/00 40U8? -a/40U8 KaJ40U8 Ka40U8? -X0H0%40T8 -a(11%1 T  (R= 81|$  R=$5Diagnosis and Management</,// X0H040T8? -a(1116g M %p ` (, 1 ("egikmoqsuwy$([\{TABCDEFGHIJKRSTUXfhjlnprtvxz񁌁!%),.:;?]}T 4  @@``@T 4 T 4D k0@P T 4 @` T 4D k@` T 4D k0` T 4 k0@P T 4 k0@ T 4D @` TL <"ArialL <Times New RomanĘF1XL <Times New RomanĘF1XL <Times New RomanĘF1XL <Times New RomanĘF1XL <"Lucida Sans UnicodeF1XL <"Lucida Sans UnicodeF1XL <"Lucida Sans UnicodeF1XL <"Lucida Sans UnicodeF1XL <StarSymbol UnicodeF1X L <Wingdings UnicodeF1X $* <<,,<,,<,T4 -aT -aT -aT -aT -a<< <<U4? -aU KaU? -aU KaU? -a<<  <  < 4dddddddddd  .4x$x̙33  (p ` | 81 (   (U 81D   ([h 81tD$  [h42dd3 5//0011 (..4x$x̙33  (g M  81 Y S   (k> X 81{$  k> X#5Differential Diagnosis:</,//,X0H040T8 -a(111   (k  81>  $  k  42U Ka3:5Falsely Low platelet counts: In vitro platelet clumping caused by EDTA-dependent agglutinins or giant platelets abnormal blood smear Common causes of Thrombocytopenia: Pregnancy Gestational thrombocytopenia, Pre-Eclampsia Drug-induced thrombocytopenia Heparin, Quinidine, Quinine, Sulfoamides, Gold Viral Infections HIV, Infectious Mononucleosis, Hepatitis Hypersplenism due to chronic liver disease palpable spleen tip; Chronic liver disease portal HTN pooling of platelets in splenic sinusoids + decreased production of thrombopoietin thrombocytopenia ///a40U8 Ka)40U8? -a(11P16 g M % p ` (.4x/S////"// //,///////////%//+//,//  // T// //0040U8? -aj40U8 Ka#40U8? -a840U8 KaO40U8 Ka<40U8 Ka40U8 Ka(11:16g M %p ` (.4x$x̙33  (p ` | 81 (   (U 81D   ([h 81tD$  [h42dd3 5//0011 (D.4x$x̙33  (g M  81     (k> X 81 $  k> X 5Differential Diagnosis (contd):///,/,/,X0H0 40T8 -a(11 1   (k  81^.$D  k 5Other causes of Thrombocytopenia that mimic ITP: Myelodysplasia Acquired pure megakaryocytic aplasia Congenital thrombocytopenias von Willibrand disease type 2B, Wiskott-Aldrich syndrome, Alport syndrome, May-Hegglin anomaly, Fanconi syndrome, Bernard-Soulier syndrome, Thrombocytopenia-absent radius (TAR) syndrome Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome Chronic disseminated intravascular coagulation//0/$x̙33  (p ` | 81 (   (U 81D    ///$//////l/00140U8? -a40U8 Ka%40U8 Ka40U8 Ka>40U8 Ka.40U8 Ka(1116g M %p ` (.4x$x̙33  (p ` | 81 (   (U 81D   ([h 81tD$  [h42dd3 5//0011 (V.4x$x̙33  (g M  81 ] O   (k> X 81w$  k> X5Diagnostic Testing:</,//,X0H040T8 -a(111   (k  81F  $  k  "5No GOLD STANDARD test to establish a diagnosis of ITP Hx, PE, CBC, coagulation profile and examination of Blood smear HIV-associated Thrombocytopenia, Myelodysplasia, Acquired pure Megakaryocytic aplasia, TTP-HUS, DIC or ITP DIC: Increased PT, PTT, bleeding time, TT, Fibrin split products and D-dimer Decreased fibrinogen level and platelets Peripheral smear with schistocytes from damaged RBCs TTP-HUS: Hemolytic anemia Thrombocytopenia Acute Renal Failure Fever Fluctuating, transient neurologic signs (mental status changes hemiplegia)//5([h 81tD$D  [h42dd3 5//0011//@// k////G//(//4////////////?//  /p0`0640U8? -a40U8? -a40U8 KaH40U8? -a)40U8? -a540U8? -a 40U8 Ka40U8? -a40U8? -a40U8? -a40U8? -aL40U8? -a(11"16Rg M %p ` (.4x$x̙33  (p ` | 81 (   (U 81D   ([h 81tD$  [h42dd3 5//0011 (m[.4x$x̙33  (g M  81 &    (k> X 81$  k> Xw5Dx Testing (contd)///,/,/,X0H040T8 -a(111 _   (k  81  $D  k / 5Anti-platelet Antibody studies Not recommended due to the frequency of false negative and false positive results HIV testing HIV-associated thrombocytopenia Bone Marrow Aspiration with Biopsy (usually pts > 60 y/o) Acquired pure megakaryocytic aplasia megakaryocytes are absent in the bone marrow Myelodysplastic syndrome dysplastic marrow cells with blasts HIV-associated thrombocytopenia Decrease in megakaryocytes in the marrow while other hematologic elements may be normal ITP overall bone marrow cellularity is normal, with normal erythropoiesis and myelopoiesis Megakaryocytes are present in normal to increased numbers in some pts a shift toward younger megakaryocytes with lesser degrees of nuclear polyploidy and less evidence of platelet production may be noted. /// (_.4x$x̙33  (g M  81  G   (k> X 81/Q// // //://%// -//// $// // X//// W//://  /00 40U8? -aR40U8 Ka.40U8? -a;40U8? -aT40U8 Ka?40U8 Kaz40U8 Ka]40U8 Ka40U8? -a(1116 g M %p ` (.4x$x̙33  (p ` | 81 (   (U 81D   ([h 81tD$  [h42dd3 5//0011 (.4x$x̙33  (g M  81  G   (k> X 81o$  k> X 5Management:</,/ /,X0H0 40T8 -a(11 1 ]  (k  81$  k -5HIV-associated Thrombocytopenia Thrombocytopenia occurs in 30 to 60% of all HIV patients Risk is increased with decreasing CD4 Primary problem: Immune-mediated destruction of platelets via antiplatelet antibodies secondary to molecular mimicry between the HIV 120 antigen and the platelet GpIIb/IIIa receptor Infections and fevers can decrease the life span of platelets in HIV patients, contributing to the thrombocytopenia// / /s/o$< < k> X 5Conclusion:</,/ /,X0H0 40T8 -a(11 1   (k  8x0h0 40U8? -a940U8 Ka'40U8 Ka40U8 Kas40U8? -a(1116g M %p ` (.4x$x̙33  (p ` | 81 (   (U 81D   ([h 81tD$  [h42dd3 5//0011 (.4x$x̙33  (g M  81  G   (k> X 81o$  k> X 5Management:</,/ /,X0H0 40T8 -a(11 1   (k  81$D  k V42U? -a35Increased risk of bleeding with Plt <10,000-20,000 Treatment indicated for Plt < 30,000 or < 50,000 if coagulopathy or bleeding disorder present Treatment Options: Anti-retroviral therapy: Zidovudine (AZT) 600 mg/day Effective in 40% to 60% of HIV-associated Thrombocytopenia //2//^//1$= < k Yu5Plt > 30,000 Observe Plt < 30,000 w/ minor bleeding Glucocorticoid Plt < 10,000 w/ major bleeding Glucocorticoid, IVIG, platelet transfusion Failure of above treatment & plts < 20,000 Splenectomy Failure of Splenectomy & plts < 10,000 & significant bleeding steroids, vincristine, cy////G/00340U8? -a^40U8 Ka40U8? -a+40U8 Ka 40U8? -a;40U8? -a(1116 g M % p ` (.4x$x̙33  (p ` | 81 (   (U 81D    ([h 81tD$D  [h42dd3 5//0011 (.4x$x̙33  (g M  81  G   (k> X 81o$  k> X 5Management:</,/ /,X0H0 40T8 -a(11 1 ?  (k  81g$  k C5Specific treatment for ITP: Prednisone: 80-90% response rate (initial dose 1 mg/kg/day or 60-100 mg/d) Unclear whether long-term use may increase risk of HIV progression or fulminant Kaposi's sarcoma in men co-infected with HHV8 Intravenous gammaglobulin (IVIG): 1000 mg/kg x 2 days Response with significant increase (>100,000) in PLT counts within 24-48 hrs but not sustained Expensive reserve for acute bleeding or urgent need for invasive surgical procedure Anti-rhesus D (RhD) immunoglobulin has also been used with success; is easily administered and costs less than IVGGL/<///K//~/clophosphamide, cyclosporine, mycophenolate mofetil, danazol, azathioprine, IVIG// // (// /// W// K///4//^//T/s/0040U8 KaL40U8? -a40U8 Ka640U8? -a_40U8 KaT40U8 Kas40U8? -a(11C16 g M % p ` (.4x$x̙33  (p ` | 81 (   (U 81D    ([h 81tD$  [h42dd3 5//0011 (.4x$x̙33  (g M  81     (k> X 81tD$  k> X42T -a3,5//0011   (k  81$D  k |P5Splenectomy: Long-term response in approximately 60% of pts Increased risk of infection with encapsulated bacteria after splenectomy Other treatment modalities, such as dapsone, interferon, vincristine, danazol, low-dose splenic irradiation have shown limited success in ITP. Active bleeding: Packed RBCs and PLT transfusion plus IVGG// //.//I//Idiopathic Thrombocytopenic Purpura: Diagnosis and Management Differential Diagnosis: Falsely Low platelet counts: In vitro platelet clumping caused by EDTA-dependent agglutinins or giant platelets abnormal blood smear Common causes of Thrombocytopenia: Pregnancy Gestational thrombocytopenia, Pre-Eclampsia Drug-induced thrombocytopenia Heparin, Quinidine, Quinine, Sulfoamides, Gold Viral Infections HIV, Infectious Mononucleosis, Hepatitis Hypersplenism due to chronic liver disease palpable spleen tip; Chronic liver disease portal HTN pooling of platelets in splenic sinusoids + decreased production of thrombopoietin thrombocytopenia Differential Diagnosis (contd): Other causes of Thrombocytopenia that mimic ITP: Myelodysplasia Acquired pure megakaryocytic aplasia Congenital thrombocytopenias von Willibrand disease type 2B, Wiskott-Aldrich syndrome, Alport syndrome, May-Hegglin anomaly, Fanconi syndrome, Bernard-Soulier syndrome, Thrombocytopenia-absent radius (TAR) syndrome Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome Chronic disseminated intravascular coagulation Diagnostic Testing: No GOLD STANDARD test to establish a diagnosis of ITP Hx, PE, CBC, coagulation profile and examination of Blood smear HIV-associated Thrombocytopenia, Myelodysplasia, Acquired pure Megakaryocytic aplasia, TTP-HUS, DIC or ITP DIC: Increased PT, PTT, bleeding time, TT, Fibrin split products and D-dimer Decreased fibrinogen level and platelets Peripheral smear with schistocytes from damaged RBCs TTP-HUS: Hemolytic anemia Thrombocytopenia Acute Renal Failure Fever Fluctuating, transient neurologic signs (mental status changes hemiplegia) Dx Testing (contd) Anti-platelet Antibody studies Not recommended due to the frequency of false negative and false positive results HIV testing HIV-associated thrombocytopenia Bone Marrow Aspiration with Biopsy (usually pts > 60 y/o) Acquired pure megakaryocytic aplasia megakaryocytes are absent in the bone marrow Myelodysplastic syndrome dysplastic marrow cells with blasts HIV-associated thrombocytopenia Decrease in megakaryocytes in the marrow while other hematologic elements may be normal ITP overall bone marrow cellularity is normal, with normal erythropoiesis and myelopoiesis Megakaryocytes are present in normal to increased numbers in some pts a shift toward younger megakaryocytes with lesser degrees of nuclear polyploidy and less evidence of platelet production may be noted. Management: HIV-associated Thrombocytopenia Thrombocytopenia occurs in 30 to 60% of all HIV patients Risk is increased with decreasing CD4 Primary problem: Immune-mediated destruction of platelets via antiplatelet antibodies secondary to molecular mimicry between the HIV 120 antigen and the platelet GpIIb/IIIa receptor Infections and fevers can decrease the life span of platelets in HIV patients, contributing to the thrombocytopenia Management: Increased risk of bleeding with Plt <10,000-20,000 Treatment indicated for Plt < 30,000 or < 50,000 if coagulopathy or bleeding disorder present Treatment Options: Anti-retroviral therapy: Zidovudine (AZT) 600 mg/day Effective in 40% to 60% of HIV-associated Thrombocytopenia Management: Specific treatment for ITP: Prednisone: 80-90% response rate (initial dose 1 mg/kg/day or 60-100 mg/d) Unclear whether long-term use may increase risk of HIV progression or fulminant Kaposi's sarcoma in men co-infected with HHV8 Intravenous gammaglobulin (IVIG): 1000 mg/kg x 2 days Response with significant increase (>100,000) in PLT counts within 24-48 hrs but not sustained Expensive reserve for acute bleeding or urgent need for invasive surgical procedure Anti-rhesus D (RhD) immunoglobulin has also been used with success; is easily administered and costs less than IVGG Splenectomy: Long-term response in approximately 60% of pts Increased risk of infection with encapsulated bacteria after splenectomy Other treatment modalities, such as dapsone, interferon, vincristine, danazol, low-dose splenic irradiation have shown limited success in ITP. Active bleeding: Packed RBCs and PLT transfusion plus IVGG Conclusion: Plt > 30,000 Observe Plt < 30,000 w/ minor bleeding Glucocorticoid Plt < 10,000 w/ major bleeding Glucocorticoid, IVIG, platelet transfusion Failure of above treatment & plts < 20,000 Splenectomy Failure of Splenectomy & plts < 10,000 & significant bleeding steroids, vincristine, cyclophosphamide, cyclosporine, mycophenolate mofetil, danazol, azathioprine, IVIG References: Clinical Challenge - Thrombocytopenia i/ j/x0h040U8? -a040U8? -aL40U8? -a940U8? -a40U8? -a(11u16 g M % p ` (.4x$x̙33  (p ` | 81 (   (U 81D    ([h 81tD$ 8 [h42dd3 5//0011 (.4x$x̙33  (g M  81  G   (k> X 81o$ < k> X 5References:</,/ /,X0H0 40T8 -a(11 1 ;  (k  81c$? < k  5Clinical Challenge - Thrombocytopenia in a Woman With AIDS. AIDS Reader 8(2):43-44, 1998. 1998 Cliggott Publishing, Division of SCP Communications George, JN, Woolf, SH. Idiopathic thrombocytopenic purpura: A practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996; 88:3 Cines, DB, Blanchette, VS. Immune thrombocytopenic purpura. New England Journal of Medicine. 2002; 346:995. Olsson, B, Andersson, PO, Jernas, M. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003; 9:1123. Sandler, SG, Schexneider, K. Immune Thrombocytopenic Purpura. Emedicine. May 30, 2006. http://www.emedicine.com/med/topic1151.htmL/</:/ !/ / S/ ~/ 0/ n a Woman With AIDS. AIDS Reader 8(2):43-44, 1998. 1998 Cliggott Publishing, Division of SCP Communications George, JN, Woolf, SH. Idiopathic thrombocytopenic purpura: A practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996; 88:3 Cines, DB, Blanchette, VS. Immune thrombocytopenic purpura. New England Journal of Medicine. 2002; 346:995. Olsson, B, Andersson, PO, Jernas, M. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003; 9:1123. Sandler, SG, Schexneider, K. Immune Thrombocytopenic Purpura. Emedicine. May 30, 2006. http://www.emedicine.com/med/topic1151.htm / Z/ ]/ 5/ / / */ x0h040U8? -a40U8? -ao40U8? -a40U8? -a40U8? -a(1116} Y g M 71$7̙33$7$7ff3333f$7333MMM$7f$7f$73 ( .4x$x̙33  (g M  81 u _  (k> X 81$< < k> X/#5Click to edit the title text format</,/#/,X0H0#40T8 -a(11#1   (k  81N$X\k 5Click to edit the outline text format Second Outline Level Third Outline Level Fourth Outline Level Fifth Outline Level Sixth Outline Level Seventh Outline Level Eighth Outline Level Ninth Outline Level//&/ ///f/00&40U8? -a40U8 Ka40U8? -a40U8 Ka40U8? -a40U8? -a40U8? -a40U8? -a40U8? -a(111'p ` f0(.4x$x̙33  (p `  81 (   (U 81D   ([h 81tD$D$ $ [h42dd3 5//0011x p ` _0(.4x$x33  (p `  81 4  =   (p 81:e$% $  5*</,// X0H0408dd(111 =  (E  81:e$' $ U  5*</,// X0H0408dd(111 =  (p" _  81:#e$( #( ? 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Chronic liver disease portal HTN pooling of platelets in splenic sinusoids + decreased production of thrombopoietin thrombocytopenia Xj#i"7N%+- T; @`H < 0?rs ? ̙33"j0  @(  @J @  ppb?Title 1   @Differential Diagnosis (cont d):!!!  @  (i?,Content Placeholder 2,  *TOther causes of Thrombocytopenia that mimic ITP: Myelodysplasia Acquired pure megakaryocytic aplasia Congenital thrombocytopenias  von Willibrand disease type 2B, Wiskott-Aldrich syndrome, Alport syndrome, May-Hegglin anomaly, Fanconi syndrome, Bernard-Soulier syndrome, Thrombocytopenia-absent radius (TAR) syndrome Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome Chronic disseminated intravascular coagulation1z0$l @`H @ 0?rs ? ̙33"! 0 DQ(  D D  pt?Title 1   YDiagnostic Testing:  D  P?,Content Placeholder 2=  DNo GOLD STANDARD test to establish a diagnosis of ITP Hx, PE, CBC, coagulation profile and examination of Blood smear HIV-associated Thrombocytopenia, Myelodysplasia, Acquired pure Megakaryocytic aplasia, TTP-HUS, DIC or ITP DIC: Increased PT, PTT, bleeding time, TT, Fibrin split products and D-dimer Decreased fibrinogen level and platelets Peripheral smear with schistocytes from damaged RBCs TTP-HUS: Hemolytic anemia Thrombocytopenia Acute Renal Failure Fever Fluctuating, transient neurologic signs (mental status changes hemiplegia) 5@kG(4                ?       #  `H D 0?rs ? ̙33" 0   HD (  H0 H  p4?Title 1  I l&Dx Testing (cont d)  H  .I?,Content Placeholder 2, I &Anti-platelet Antibody studies Not recommended due to the frequency of false negative and false positive results HIV testing  HIV-associated thrombocytopenia Bone Marrow Aspiration with Biopsy (usually pts > 60 y/o) Acquired pure megakaryocytic aplasia megakaryocytes are absent in the bone marrow Myelodysplastic syndrome dysplastic marrow cells with blasts HIV-associated thrombocytopenia Decrease in megakaryocytes in the marrow while other hematologic elements may be normal ITP overall bone marrow cellularity is normal, with normal erythropoiesis and myelopoiesis Megakaryocytes are present in normal to increased numbers in some pts a shift toward younger megakaryocytes with lesser degrees of nuclear polyploidy and less evidence of platelet production may be noted. RijQ-:%-$ XW:       `H H 0?rs ? ̙33":0 0Lj(  L L  pt>I?Title 1  I Q Management:     L  @@I?,Content Placeholder 2, I /HIV-associated Thrombocytopenia Thrombocytopenia occurs in 30 to 60% of all HIV patients Risk is increased with decreasing CD4 Primary problem: Immune-mediated destruction of platelets via antiplatelet antibodies secondary to molecular mimicry between the HIV 120 antigen and the platelet GpIIb/IIIa receptor Infections and fevers can decrease the life span of platelets in HIV patients, contributing to the thrombocytopenia@ t t  `H L 0?rs ? ̙33"0 @PK(  P P  pnI?Title 1  I Q Management:     P  \jI?,Content Placeholder 2, I Increased risk of bleeding with Plt <10,000-20,000 Treatment indicated for Plt < 30,000 or < 50,000 if coagulopathy or bleeding disorder present Treatment Options: Anti-retroviral therapy: Zidovudine (AZT) 600 mg/day Effective in 40% to 60% of HIV-associated Thrombocytopenia 3^+G2^G   `H P 0?rs ? ̙33"h0 PT(  T T  pI?Title 1  I Q Management:    C T  I?,Content Placeholder 2m I ]CSpecific treatment for ITP: Prednisone: 80-90% response rate (initial dose 1 mg/kg/day or 60-100 mg/d) Unclear whether long-term use may increase risk of HIV progression or fulminant Kaposi's sarcoma in men co-infected with HHV8 Intravenous gammaglobulin (IVIG): 1000 mg/kg x 2 days Response with significant increase (>100,000) in PLT counts within 24-48 hrs but not sustained Expensive reserve for acute bleeding or urgent need for invasive surgical procedure Anti-rhesus D (RhD) immunoglobulin has also been used with success; is easily administered and costs less than IVGGL6tK~4^   T tD H T 0?rs ? ̙33"D0 `Xt(  X X  pDI?Title 1  I > 2 X  I?,Content Placeholder 2, I LPSplenectomy: Long-term response in approximately 60% of pts Increased risk of infection with encapsulated bacteria after splenectomy Other treatment modalities, such as dapsone, interferon, vincristine, danazol, low-dose splenic irradiation have shown limited success in ITP. Active bleeding: Packed RBCs and PLT transfusion plus IVGG y* .I )$Q  H X 0?rs ? ̙33"o 0 p\(  \ \  pI?Title 1  I Q Conclusion:    J \  I?,Content Placeholder 2, I dPlt > 30,000 Observe Plt < 30,000 w/ minor bleeding Glucocorticoid Plt < 10,000 w/ major bleeding Glucocorticoid, IVIG, platelet transfusion Failure of above treatment & plts < 20,000 Splenectomy Failure of Splenectomy & plts < 10,000 & significant bleeding steroids, vincristine, cyclophosphamide, cyclosporine, mycophenolate mofetil, danazol, azathioprine, IVIG,v hv  @`H \ 0?rs ? ̙33" 0 NF`(  ` `  pI?Title 1  I Q References:     `  XI?,Content Placeholder 2, I Clinical Challenge - Thrombocytopenia in a Woman With AIDS. AIDS Reader 8(2):43-44, 1998. 1998 Cliggott Publishing, Division of SCP Communications George, JN, Woolf, SH. Idiopathic thrombocytopenic purpura: A practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996; 88:3 Cines, DB, Blanchette, VS. Immune thrombocytopenic purpura. New England Journal of Medicine. 2002; 346:995. Olsson, B, Andersson, PO, Jernas, M. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003; 9:1123. Sandler, SG, Schexneider, K. Immune Thrombocytopenic Purpura. Emedicine. May 30, 2006. http://www.emedicine.com/med/topic1151.htm: u ~ 0  Z ] 5   +   @`H ` 0?rs ? ̙33"0 h (  hX h C 4z7    h S 4 92   " H h 0vn ? ̙3380___PPT10.W3k0 l (  lX l C 4z7    l S <4 92   " H l 0vn ? ̙3380___PPT10.W3k0 p  (  pX p C 4z7    p S  Ǒ4 92   " H p 0vn ? ̙3380___PPT10.W3k0 t (  tX t C 4z7    t S ̑4 92   " H t 0vn ? ̙3380___PPT10.W3k0 x (  xX x C 4z7    x S ґ4 92   " H x 0vn ? ̙3380___PPT10.W3k0 | (  |X | C 4z7    | S