ITP and Splenic Lymphoma Edward Chin, MD March 19, 2004

U/S 2/25/04

CT 2/27/04

Liver-spleen Scan 3/1/04

Operative Findings Exploratory laparoscopy Normal-sized spleen, no obvious mass No accessory spleens Splenectomy performed; 1 pool plt given Extraction via enlarged trocar site JP left

Postop Course Plt count = 96K several hrs postop Clear liquids on POD#1, advanced Plt = 156 on POD#2 JP d/cd on POD#3 Awaiting NH placement

Pathology Spleen = 132 g. Atypical histiocytic infiltrates with hemophagocytosis, consistent with involvement by true histiocytic lymphoma/histiocytic sarcoma

ITP Acquired disorder, classically affecting young women Insidious vs. acute onset (bleeding) History of antecedent infection in pediatric cases (84%) Cross-reactivity b/w anti-viral Abs and plt antigens?

Thrombocytopenia 3 mechanisms: –decreased marrow production –increased splenic sequestration –accelerated destruction of plts Normal spleen: 30% of total plts within Splenectomy thrombocytosis (by 30%)

Manifestations –Petechiae/purpura, easy bruising –Epistaxis, gingival bleeding, menorrhagia –GI bleeding, gross hematuria rare –Intracranial hemorrhage even rarer Mucocutaneous bleeding:

Differential Diagnosis Gestational thrombocytopenia/ecclampsia Drug-induced thrombocytopenia –Heparin, quinidine, quinine, sulfonamides, gold Viral illness –HIV, mononucleosis, hepatitis Hypersplenism 2 nd liver disease SLE Myelodysplasia Congenital t-penias –Von Willebrand Disease 2B –Wiskott-Aldrich Syndrome –Alport Syndrome –Fanconi Syndrome –TAR Syndrome –TTP-HUS Chronic DIC

Diagnosis Isolated thrombocytopenia (plt < 50K) with otherwise normal blood counts, including peripheral smear exam By exclusion no clinically apparent associated conditions accounting for thrombocytopenia

Clinical Testing Peripheral smear Bone marrow aspiration/biopsy –For patients > 60, r/o MDS Antiplatelet Ab testing unnecessary

Treatment Natural history: –80-90% complete remission in peds pts –9% in adults Goal = establish safe plt count to prevent major bleeding (> 10K) Medical therapy 50% success in adults –Prednisone 1 mg/kg/day vs. dexamethasone Taper over 4-6 weeks if + response –IVIgG for acute bleeding episodes –anti-D (Win-Rho)

Surgery Reserved for medical failures Rationale splenectomy removes: 1)The major source of anti-plt Ab production 2)The major site of platelet destruction Does it work? –Complete remission of ITP ~50-65%

Lap vs. Open for ITP Dutch retropective study of 50 pts with ITP ( ) who LS Compared vs. 31 pts of OS ( ) Surg Endosc Feb 2;17(12)

Results OutcomeOpen (n=31)Lap (n=50)p OR time103 min159 < EBL725 cc615 ccNS LOS8.9 days5.5 days< Complications26%14%< Mortality00 - Surg Endosc Feb 2;17(12)

Remission LapOpenp Complete (plt > 120K) 64%64.5%NS Partial (plt K) 22%25.8%NS Failure (plt < 50K) 14%9.7%NS Median f/u = 40.7 and 84.9 months for Lap, Open Surg Endosc Feb 2;17(12)

Complications Surg Endosc Feb 2;17(12) Open (n=31) Lap (n=50) Wound infection42 Hemorrhage21 Dehiscence10 Pneumonia11 PE01 Pancreatic fistula02

Surgical Failure 20-35% long-term Immunosuppressive agents: –Azathiprine, cylophosphamide, vincristine/vinblastine, danazol How to screen: Steroid-responders (but steroid-dependent) are most likely to benefit from splenectomy 70% nl plts after 1 week

OPSI Literature review from studies, 19,680 patients, median f/u 6.8 yrs Risk of OPSI 3.2%, mortality 1.4% Mortality varies inversely with age; greatest risk in pediatric population (1.7 vs. 1.3%, p < 0.001) J Infection 2001; 43:

Vaccination Guidelines All post-splenectomy patients require pneumovax Recommend vaccination vs. hemophilus influenza, meningococcus Annual influenza vaccination Optimal timing of vaccination unclear and practices vary widely (immediate vs. delayed)

Data Prospective study of optimal timing of pneumovax after traumatic splenectomy 59 patients 3 groups (1, 7, 14 day) Antibody concentration and functional antibody response measured prevaccination, and 4 weeks post No difference in IgG concentration, but higher antibody activity in 14 d group Later study compared 14 vs 28 d; no effect J Trauma 1998; 44:

Further Guidelines Need for immediate medical attention for any infectious symptoms (cough, fever) Lifelong penicillin prophylaxis Daily penicillin for patients < 2 yrs Re-vaccination with pneumovax q5 yrs Clin Med 2002; 2(5):

Splenic Tumors Benign –Solid (hemangioma, lymphangioma, hemangioendothelioma, hamartoma –Cystic (parasitic, non-parasitic) Malignant –Lymphoproliferative (NHL, HL, CLL, HCL) –Myeloproliferative (CML, PV, essential thrombocythemia, myelofibrosis) –Vascular (hemangiosarcoma, lymphangiosarcoma) –Metastatic (breast, lung, melanoma) –Sarcomas (fibrosarcoma, leiomyosarcoma, Kaposi)

Primary Splenic Lymphoma Rare (but splenic involvement common) Subset of non-Hodgkins Lymphoma Disease confined spleen, hilar LN Splenomegaly** Subtypes: –B cell (MZL) –T cell (hepatosplenic gamma/delta) Treatment splenectomy (vs. chemo/XRT) Indolent Course