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Hematological Indications for Splenectomy

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      Hematological Indications
         for Splenectomy                                                           Advisory Board Member / Consultant:
                                                                                                     Bayer
                      Mark T. Reding, M.D.
               Assistant Professor, Department of Medicine                                       Novo Nordisk
         Division of Hematology, Oncology, and Transplantation
          Director, Center for Bleeding and Clotting Disorders                  (Activities related exclusively to hemophilia)
                          University of Minnesota
                             Minneapolis, MN
                                                                                 Off label use and/or investigational use will
                74th Annual University of Minnesota Surgery Course
                Advances in Hepatic, Biliary, and Pancreatic Surgery                          not be discussed
                                 Minneapolis, MN
                                 June 2 - 5, 2010




                     Lecture Outline                                                          The Spleen
                                                                                                      Galen (ca. 130 – 200 AD)
                                                                                                       •   “Organ of mystery”
         1. Functions of the Spleen                                                                    •   Function related to mood and
                                                                                                           good or ill humors

         2. Splenomegaly                                                                              18th century
                                                                                                       •   Relationship to immune and
                                                                                                           hematologic systems recognized
         3. Indications for Splenectomy                                                               Not necessary for life…
                                                                                                       •   Many functions redundant and
         4. Post Splenectomy Sepsis                                                                        can be assumed by organs

                                                                                  Yet, the spleen is an important part of many
                                                                                  disease processes, as well as normal function
                                                                                  of the immune and hematologic systems




                Anatomy of the Spleen
White Pulp
•   Sheath of lymphoid cells around arterial
                                                                White
                                                                Pulp
                                                                        Red
                                                                        Pulp   Normal Functions of the Spleen
    branches (PALS)
•   T cells, plasma cells, macrophages
•   B cell clusters appear in follicles along                                           1. Hematopoiesis
    PALS at arterial branches
•   Ag processing, Ab production, immune
                                                                                        2. Filtering
    regulation

Red Pulp                                                                                3. Immune defense
•   Vascular sinuses, cords of Billroth
    (phagocytes and reticular cells)
•   Phagocytosis
•   RBC processing
•   Hematopoiesis
•   Storage of platelets, leukocytes




                                                                                                                                            1
 Normal Functions of the Spleen                               Normal Functions of the Spleen
                       Hematopoiesis                                             Filtering
                                                          •   Removal of senescent and poorly deformable RBCs
 •   The spleen is a major site of hematopoiesis              that cannot tolerate the acidic, hypoxic, and
     during fetal life, primarily during the second           hypoglycemic environment within the spleen
     trimester                                            •   “Culling” function capitalized upon when splenectomy
                                                              used to treat hereditary spherocytosis
 •   At birth, this function of the spleen has            •    “Pitting” function removes particles from RBCs such
     become dormant, and the bone marrow is                   as nuclear remnants (Howell-Jolly bodies) and
     the primary hematopoietic organ                          insoluble globin proteins (Heinz bodies)
 •   Extramedullary hematopoiesis can result in
     splenomegaly, and may be seen in a variety
     of bone marrow diseases and chronic
     hemolytic anemias




 Normal Functions of the Spleen                                             Spleen Size
                    Immune defense
                                                      •   Normal size: average 150 gm, 13 cm long axis
 •   The spleen is the largest lymphoid organ
                                                      •   15% of children and 3% of young adults have
         25% of total lymphoid mass
                                                          palpable spleens without evidence of illness
         50% of total Ab producing B cells
                                                      •   Involutes with age; palpable spleen in an older
 •   Sinusoids clear bacteria from circulation,           adult is more likely to be associated with disease
     mononuclear phagocytes process foreign
     material, stimulating opsonizing antibody        •   Diagnostic criteria for many disease states have
     production by B lymphocytes                          been built on physical exam, not imaging – thus,
                                                          the clinical or diagnostic significance of a
 •   Particularly important in defense against            modestly enlarged spleen on scan that is not
     encapsulated microorganisms                                    (“scanomegaly”
                                                          palpable (“scanomegaly”) is uncertain




                    Splenomegaly                                 Indications for Splenectomy
Major causes of splenomegaly                                  • Should be performed for clinical indications,
       disease……………………
 Liver disease…………………… 33%
                                                               not for specific diagnoses
              malignancy………
 Hematologic malignancy……… 27%
 Infection…………………………. 23%
 Infection………………………….                                         • May be diagnostic, therapeutic, or both
 Congestion / inflammation…….. 8%
              inflammation……..
 Primary splenic disease……….. 4%
                  disease………..                                • May be curative, palliative, or ineffective
         unknown…………………
 Other / unknown………………… 5%
              O’Reilly, West J Med 1998; 169:88
                                                                            Immune cytopenias
Massive splenomegaly
                                                                         Hematologic malignancy
 CML
 Myelofibrosis                                                     RBC membrane / enzyme disorders
 Gaucher disease
 Lymphoma
                                                                                Thalassemia
 Parasitic infection                                                                 TTP
 Thalassemia




                                                                                                                     2
           Indications for Splenectomy                                                         Indications for Splenectomy
                  Immune cytopenias (ITP, AIHA)                                                              Hematologic Malignancy

                                                                                      Hodgkin’
                                                                                      Hodgkin’s Disease
            Indications                   Mechanism of action                           •    Staging laparotomy now much less common, due to improved
     •   Failure to respond to                 •   Remove source of                          imaging studies and increased use of chemotherapy
         medical therapy                           Ab production                        •    Necessary only in rare cases of early stage disease for which
     •   Inability to taper steroids           •   Remove primary                            the use of limited radiation alone considered, or when CT
                                                   site of platelet and                      guided biopsy not feasible
     •   Intractable steroid side
         effects                                   RBC destruction
                                                                                      Non-
                                                                                      Non-Hodgkin Lymphoma              Chronic Lymphocytic Leukemia
                                                                                        •    May be diagnostic          •   Consider for patients with refractory
           Effectiveness                                                                •    May be therapeutic
                                                                                                                            anemia or thrombocytopenia not
                                                                                                                            responsive to chemotherapy
                  •   ITP: 85% initial response, but 25% relapse
                                                                                        •    Not routinely
                      within 5 – 10 years
                                                                                             indicated
                                                                                                                        •   Consider for patients with immune
                                                                                                                            cytopenias not responsive to
                  •   AIHA: 50 – 60%
                                                                                                                            steroids




         Indications for Splenectomy                                                           Indications for Splenectomy
                      Hematologic Malignancy                                                          Other Hematologic Disorders

    Hairy cell leukemia                   Idiopathic myelofibrosis                          Hereditary spherocytosis, elliptocytosis
•    First effective treatment           •   Splenectomy indicated for                      Pyruvate kinase deficiency
                                             painful splenomegaly, recurrent                  •   Only appropriate for those severely affected
•    Normalization of CBC in
                                             infarctions, severe cytopenias
     40 – 70% even without
     bone marrow remission               •   High post op morbidity and                     Beta-
                                                                                            Beta-thalassemia
                                             mortality (10%) due to bleeding,                 •   Indicated if excessive transfusion requirements
•    5 year survival 70%
                                             infection, thrombosis
•    Little role for splenectomy
                                                                                                  lead to iron overload
                                         •   Progressive, rapid
     since the introduction of
                                             hepatomegaly and marked                          •   25 - 60% reduction in transfusions typical
     purine analogs
                                             thrombocytosis may occur
                                                                                            Thrombotic Thrombocytopenic Purpura
                                         •   Excellent palliation usually
                                             achieved in spite of risks                       •   Should be considered for those with primary
                                                                                                  refractory disease, or chronic relapsing TTP




            Post Splenectomy Sepsis                                                               Post Splenectomy Sepsis
      Overwhelming post splenectomy infection / sepsis
           is uncommon but has high mortality

     •   Incidence: 1 per 175 patient years in children,
         and 1 per 400 – 500 patient years in adults                                    •   PSS is classically caused by encapsulated bacteria:
     •   Highest incidence is in children who have                                          Streptococcus pneumoniae, Haemophilus influenzae,
         splenectomy during infancy, and in lymphoma                                        and Neisseria meningitidis
         patients receiving chemotherapy                                                •   In a review of 349 episodes of sepsis in asplenic
     •   Between 50 and 80% of severe infections and                                        patients, Streptococcus pneumoniae accounted for
         deaths occur within 3 years of splenectomy, but                                    57% of infections and 59% of deaths
         may also occur decades later
                                                                                        •   PSS may follow upper or lower respiratory symptoms,
     •   Estimated lifetime risk of ~ 5%                                                    but can also develop precipitously without any prior
                                                                                            symptoms
     Schwartz, JAMA 1982; 248:2279              Cullingford, Br J Surg 1991; 78:716
     Styrt, Am J Med 1990; 88:33N               Eber, Ann Hematol 1999; 78:524                                                  Holdsworth, Br J Surg 1991; 78:1031




                                                                                                                                                                      3
Prevention of Post Splenectomy Sepsis                                          Prevention of Post Splenectomy Sepsis
         Pneumococcal vaccine
         •   23-valent pneumococcal polysaccharide vaccine (PPSV23)
         •   Re-immunize once after 5 years                                       Timing of Vaccination
                                                                           •    Bacterial vaccines should be
         Haemophilus influenzae vaccine
                                                                                administered 14 days prior to
         •   Conjugated polysaccharide vaccine (Hib) given once                 elective splenectomy, or at
         •   Most adults already have immunity, kids routinely immunized
                                                                                least 14 days post-operatively
         Meningococcal vaccine                                             •    Post vaccination Ab titers do
         •   Meningococcal conjugate vaccine (MCV4) for ages 2 – 55             not differ, but opsonophagocytic
         •   Meningococcal polysaccharide vaccine (MPSV4) if > 55               function is diminished if
                                                                                vaccinated before POD 14
         Influenza vaccine
                                                                                      Shatz, J Trauma 1998; 44:760
         •   Yearly influenza vaccine recommended, as influenza is a
             risk factor for secondary bacterial infections that can be
             severe in asplenic patients




Prevention of Post Splenectomy Sepsis                                          Prevention of Post Splenectomy Sepsis
 Antibiotic Prophylaxis – Landmark Studies                                      Antibiotic Prophylaxis – Recommendations
Gaston, NEJM 1986; 314:1593
    Daily prophylaxis with penicillin in children with sickle             1.     Children should receive daily prophylaxis with oral
      cell disease reduced the incidence of pneumococcal                          penicillin or amoxicillin until age 5 or at least 3
      bacteremia by 85%                                                           years after splenectomy
Jugenburg, J Pediatr Surg 1999; 34:1064                                    2.     Highly immunocompromised individuals may be
    Daily antibiotic prophylaxis in asplenic children reduced                    considered for prophylaxis until age 18 or beyond
      the incidence of infection by 47% and decreased
      mortality by 88%                                                     3.     Routine prophylaxis not recommended in adults
                                                                                  due to the low incidence of PSS and concerns
However…                                                                          about antibiotic resistance
  These studies were done in an era of exquisite
                                                                           4.     Life long daily prophylaxis may be considered in
      pneumococcal sensitivity to penicillin
                                                                                  pediatric or adult survivors of pneumococcal PSS




Prevention of Post Splenectomy Sepsis
 Empiric antibiotic therapy for febrile illness

 Although controlled trials are lacking, aggressive
  management of a febrile illness with liberal use
  of empiric antibiotic therapy may be life saving

  1. Antibiotics should be readily available and taken at
     the first sign of any febrile illness
                amoxicillin – clavulanate
                cefuroxime axetil
                fluoroquinolone
  2. After taking the first dose of antibiotic, proceed to the
     nearest health care facility
  3. Empiric therapy should be continued for 7 – 10 days




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