Splenectomy for haematologic disorders

Indications for splenectomy in general

• Symptomatic splenomegaly
  • Abdo pain
  • Early satiety
  • Weight loss
  • Abdo distension
• Cytopaenia
• Unexplained splenomegaly - consider splenectomy

Relevant disorders

Autoimmune and idiopathic disorders

Immune thrombocytopaenia (ITP) - previously known as idiopathic thrombocytopaenic purpura

• • • Most common haematological indication for resection
    • Pathophysiology: Platelet destruction secondary to platelet autoantibodies. Production of IgG directed towards platelet glycoproteins increases destruction by reticuloendothelial system of spleen.
    • Diagnosis: Thrombocytopaenia <100, despite normal bone marrow and the absence of other causes of thrombocytopaenia that could be responsible.
      • Diagnosis of exclusion - consider HIV, SLE, APS, HCV, lymphoproliferative disorders, drugs (cocaine, gold, certain antibiotics, antihypertensives, anti-inflammatories, heparin, quinidine, abciximab), H. pylori infection
      • Primary ITP when there is no clear aetiology. Newly-diagnosed if <3 months, persistent if 3-12 months, and chronic >12 months.
      • Secondary ITP with a known cause.
    • Presentation: Usually asymptomatic until platelets <30. 'platelet-type bleeding' is bruising, purpura, petechiae, bleeding from oral mucosa, epistaxis, menorrhagia, and GIT bleeding seen rarely. Intra-cerebral haemorrhage occurs in 1%.
      • Does not present with splenomegaly, just hypersplenism
    • Treatment
      • Observation initially, especially in children, or if platelets >30 in adults
      • First-line: Corticosteroids (1-2mg/kg prednisolone daily for 2-4 weeks followed by taper) if persistent thrombocytopaenia despite observation or platelets <30. 25% will have a complete response.
      • Second-line: rituximab and thrombopoietin receptor antagonists.
      • Platelets only given with severe haemorrhage.
      • Splenectomy
        • Indications:
          • Low platelets <10 after 6-8 weeks of steroid therapy
          • Require toxic doses of steroids to achieve remission
          • Thrombocytopaenia refractory to medical treatment
          • Pregnant women in second trimester, with platelets <10 if asymptomatic or <30 if symptomatic, after medical treatment
        • NOT necessary when:
          • Platelets >50
          • ITP >6 months
          • No bleeding symptoms
          • Not engaged in high-risk activities
        • Consider IVIg in preparation for OT. 1g/kg per day for two days. Usually increases platelet count within 3 days, and increases efficacy of platelet transfusion.
        • If platelets are required, give them after splenic artery has been ligated ideally
        • Splenectomy can generally be performed safely with minimal bleeding risk even in patients with platelets <10
        • Outcomes
          • 75-85% permanent cure
          • Platelets normally improve within 10 days - likely to be durable if platelets >150 by day 3 or >500 by day 10
        • Relapse
          • Evaluate for missed accessory spleen - can use radionuclide imaging
          • Remove it, if safe to do so

Thrombotic thrombocytopaenic purpura (TTP)

• • • Deficiency of ADAMS13 protein leads to increased platelet aggregation and subsequent microvascular thrombosis
    • Often precipitated by factors (chemotherapy agents, quinine, cyclosporine, clopidogrel, ticlopidine, haematopoietic stem cell transplantation, or pregnancy)
    • Clinically: microangiopathic haemolytic anaemia, severe thrombocytopaenia, fever, neurologic complications, renal failure
    • Initial treatment with plasmapheresis
    • Splenectomy reserved for refractory thrombocytopaenia or frequent relapses

Autoimmune haemolytic anaemia

• • • Autoantibodies are formed and directed against RBC antigens
    • Warm
      • Initially treated with corticosteroids
      • Splenectomy indications
        • Fail to achieve remission in 3 weeks of steroids
        • Hb levels cannot be maintained with low-dose steroids
      • 50% of patients will still require low-dose steroids to maintain Hb concentrations after splenectomy
    • Cold
      • Haemolysis occurs at low temperatures
      • Usually caused by an infectious process such as EBV
      • Steroids not usually effective
      • Splenectomy is NOT indicated - RBCs are destroyed in the liver

Congenital disorders of the blood

Hereditary spherocytosis

• • • Pathophysiology: defect in RBC membrane. Usually autosomal dominant. Results in small, spherical RBCs that can't deform to fit through capillaries.
    • Most common congenital anaemia
    • Presentation
      • Most commonly a moderate haemolytic anaemia, and sometimes with jaundice, folate deficiency, and splenomegaly
      • Severe - anaemia, jaundice, splenomegaly, cholelithiasis with pigmented gallstones
      • Spherocytes on blood smear, other signs of haemolysis
    • Splenectomy is curative for almost all patients, but note that it doesn't fix the underlying problem
      • Indicated if growth retardation, skeletal changes, symptomatic haemolytic disease, anaemia-induced organ dysfunction, leg ulcers, development of extramedullary haematopoietic tumours
      • Controversial whether patients with mild disease should have splenectomy
    • Preoperative USS should be performed, and cholecystectomy should be performed at same time as splenectomy if they have gallstones
    • Delay surgery until after age 5 to prevent overwhelming post-splenectomy infection

Hereditary elliptocytosis

• • • Rare disorder resulting from mutation of RBC membrane skeleton proteins
    • Wide variety of clinical presentations
    • Can lead to severe haemolysis
    • Splenectomy indicated for those with symptomatic anaemia and is curative

Hereditary pyropoikilocytosis

• • • Subtype of hereditary elliptocytosis
    • Usually seen as anaemia and jaundice in newborns
    • Splenectomy is curative

Hereditary stomacytosis and xerocytosis

• • • Rare haemolytic anaemias
    • In severe cases, consider splenectomy, need strong indication as complications common

Thalassaemia

• • • Autosomal dominant inherited haematologic disorders caused by a defect in synthesis in one or more of the haemoglobin chains, with subsequent RBC destruction
    • Heterozygous (thalassaemia minor) forms are usually asymptomatic, with microcytosis and mild anaemia
    • Homozygous is much more severe - asymptomatic until 6 months old because of fetal haemoglobin, then become severely unwell
      • Treatment is periodic lifelong blood transfusions and iron chelation therapy
      • Splenectomy for increased blood transfusion requirements in setting of hypersplenism - some say >180-200ml/kg/year of pRBC should be threshold for splenectomy
      • Massive splenomegaly is rare, but can be treated with splenectomy if interfering with quality of life
      • 25-60% reduction in transfusion requirements can be expected after splenectomy
      • Delay until after age 5
    • Can get acute splenic sequestration crisis in beta-thalassaemia - severe anaemia, splenomegaly and an acute bone marrow response. Same as below with sickle cell anaemia. Splenectomy to prevent repeat attack.

Sickle cell anaemia

• • • Pathophysiology: Autosomal recessive haemoglobinopathy via point mutation in beta globin gene - RBCs have propensity to deform when exposed to low oxygen tension
    • Splenectomy rarely indicated because of auto-infarction of the spleen - vasoocclusion and progressive infarction. Generally leads to atrophied spleen by adulthood.
    • Indications
      • Splenic abscess - generally as a complication of infarction. Fever, abdominal pain, tender splenomegaly. May require urgent splenectomy after stabilisation.
      • Acute splenic sequestration - massive splenomegaly, acute exacerbation of anaemia, hypovolaemia. Initially treated by restoration of volume and RBC mass, but recurrence is common. Splenectomy can prevent further episodes.
      • Developmental delay due to metabolic effects of disease

Pyruvate kinase deficiency

• • • Defect in glycolytic pathway causes ATP deficiency. RBCs are less deformable and often destroyed in the spleen, leading to splenomegaly.
    • Tends to cause chronic haemolysis
    • Mild to severe anaemia accompanied by splenomegaly
    • Splenectomy if severe haemolytic anaemia, or patients that require significant numbers of transfusions. Delay until after age 5.

G6PD deficiency

• • • Typically seen in African, Middle-Eastern or Mediterranean ancestry
    • Damage to red cell macromolecules by toxic oxygen products
    • Tends to cause episodic haemolysis
    • Haemolysis precipitated by acute infections, oxidant drugs, and fava beans
    • Splenectomy is rarely, if ever, indicated

Neoplasms and myeloproliferative disorders

Hodgkin's lymphoma

• • • See separate topic under haematology
    • Malignant neoplasm of lymphoreticular cell origin that usually affects young adults 10-30yo
    • Primary treatment is CTX +/- radiation
    • Historically, splenectomy was performed as part of a staging laparotomy that included lymph node sampling and liver biopsy - this is rarely done today as CT and PET are better
    • Splenectomy can sometimes be useful in those who develop thrombocytopaenia or symptoms related to splenomegaly

NHL

• • • See separate topic under haematology
    • Most common type of lymphoma - diverse group of diseases
    • Most common primary splenic neoplasms with 60-80% having splenic involvement
      • Especially splenic marginal zone lymphoma - B cell lymphoma in older patients - splenectomy is diagnostic and therapeutic
    • Indications for splenectomy
      • Symptoms related to massive splenomegaly
      • Cytopaenias resulting from splenic sequestration
      • Requested by haematologists to obtain tissue for diagnosis or to guide therapy

Hairy cell leukaemia

• • • See separate topic under haematology
    • Rare
    • Fatigue, LUQ pain, fever, infection, coagulopathy
    • Commonly occurs in 5th decade
    • Splenomegaly, pancytopaenia, neoplastic peripheral mononuclear cells, BM infiltration
    • Splenectomy was historically important standard treatment, but now replaced by biologics
    • Splenectomy now reserved for cases of incomplete response to first-line therapy, persistent splenomegaly in absence of BM involvement, atraumatic splenic rupture, and severe bleeding from thrombocytopaenia

Chronic lymphocytic leukaemia (CLL)

• • • See separate topic under haematology
    • B-cell leukaemia in which there is progressive accumulation of functionally incompetent lymphocytes
    • Splenic infiltration is common, can lead to severe splenomegaly and substantial cytopaenias through hypersplenism
    • Splenectomy can be indicated to relieve symptoms, or to relieve secondary ITP and AIHA

Chronic myelogenous leukaemia (CML)

• • • See separate topic under haematology
    • Disorder of abnormal proliferation and accumulation of granulocytes
    • Characteristic Philadelphia chromosome
    • Splenomegaly in 40%
    • Acute blastic crisis can develop - severe splenomegaly and hypersplenism, leading to severe anaemia, bleeding complications and infection
    • Splenectomy indicated for palliation of severe symptoms of splenomegaly/hypersplenism

Primary myelofibrosis

• • • Chronic malignant haematologic disorder that results in hyperplasia of abnormal myeloid precursor cells leading to marrow fibrosis and extramedullary haematopoiesis in liver and spleen
    • Splenectomy indicated in haemolysis requiring significant transfusions, thrombocytopaenia, symptomatic splenomegaly, recurrent splenic infarctions, hypercatabolic symptoms, and portal hypertension with refractory ascites and variceal haemorrhage
    • Post-operative platelet-lowering agents can reduce thrombotic complications

Miscellaneous disorders

Amyloidosis

• • • Extracellular deposition of insoluble fibrillar proteins in tissues and organs
    • Hepatosplenomegaly can occur in 25%, with severe splenomegaly in 10%, and they can develop functional splenic insufficiency
    • Splenectomy indicated for signs and symptoms of splenomegaly, but does not alter ultimate course of disease
    • Splenectomy may improve factor X levels which can drop if liver not functioning properly
    • Pre-operative administration of factor VIIa is important

Gaucher's disease

• • • Glycolipid storage disease - deposition of glococerebroside in reticuloendothelial system
    • Leads to severe organomegaly, pulmonary infiltrates, BM infiltration
    • Anaemia, thrombocytopaenia, osteopaenia, bone pain, osteonecrosis, massive hepatosplenomegaly
    • Splenectomy indicated for severe and symptomatic splenomegaly and refractory cytopaenia - does not alter disease progression but removes chance of splenic rupture and can improve thrombocytopaenia
    • Partial splenectomy advocated in some children to preserve some splenic function
    • Splenectomy can actually increase risk of bone disease and lung/kidney function, so careful patient selection is essential

Felty's syndrome

• • • RA, otherwise unexplained neutropaenia, and splenomegaly
    • Treat with MTX or disease-modifying anti-rheumatic drugs
    • GCSF may be useful pre-op
    • Splenectomy indicated when medical treatment has failed, as evidenced by recurrent infections or severe neutropaenia. Results in 80% haematologic response rate.

Sarcoidosis

• • • Non-caseating granulomatous disase
    • 90% primary lung involvement, but can affect any organ
    • Splenic involvement is mostly as part of multi-organ disease - occurs in 10% or so
    • Treat with steroids, MTX
    • Indications for splenectomy - symptomatic splenomegaly, intractable pain, exclusion of neoplastic process, hypersplenism
    • Splenectomy does not alter disease course but can help with treatment of refractory hypercalcaemia

Idiopathic splenomegaly

• • • Diagnostic and therapeutic
    • About half of these patients have lymphoma

Pre-op considerations

• Assess size with CT/USS
• Look at anatomic relationships, vascular anatomy, presence of accessory spleens, perisplenic lymphadenopathy, inflammation
• Splenic artery embolisation can be helpful to reduce risk of blood loss, especially with Jehovah's witnesses (may cause severe pain and ischaemic complications)
• Stress dose steroids
• Give platelets only after ligating splenic artery
• Cameron's says can do it safely even platelets <20
• Post-op vaccinations (give pre-op in elective setting)
• Moderate splenomegaly: 11-20cm in greatest diameter
• Massive splenomegaly: >20cm
• Laparoscopic splenectomy should be possible even in massive splenomegaly (generally limited by size of retrieval device) - Cameron's says can do it up 25cm
• Examine abdomen for splenunculi - most commonly gastrosplenic ligament and greater omentum