Spleen : Haematological

DEFINITION
Discusses splenectomy for haematological disorders.
Generally a symptomatic procedure; rarely leads to a cure.
Notes: a normal spleen is 11cm. Moderate splenomegaly is 11cm-20cm. Massive is >20cm
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EPIDEMIOLOGY

Not addressed.

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AETIOLOGY

Classification of Possible Indications for Splenectomy

Autoimmune / idiopathic
- idiopathic thrombocytopaenic purpura (ITP)
- thrombotic thrombocytopaenic purpura (TTP)
- idiopathic autoimmune haemolytic anaemia
- felty syndrome
- sarcoidosis

Genetic deficiencies
- Thalassemia
- Sickle cell anaemia
- Gaucher disease
- Pyruvate kinase deficiency
- G6PD deficiency
- Amyloidosis

Red blood cell disorders
- Hereditary spherocytosis
- Hereditary elliptocytosis
- Hereditary pyropoikilocytosis
- Hereditary stomatocytosis
- Hereditary xerocytosis

White blood cell disorders
- Hodgkin lymphoma
- Non-Hodgkin lymphoma
- Chronic lymphocytic leukaemia
- Chronic myelogeneous leukaemia
- Hairy cell leukaemia

Bone marrow disorders
- Primary myelofibrosis
- Myeloproliferative disorders


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BIOLOGICAL BEHAVIOUR
Brief Biology of More Common Indications

Autoimmune / idiopathic


Idiopathic thrombocytopaenic purpura (ITP)
Spleen produces an IgG that binds to platelets
--> Platelets are then cleared by phagocytes, mainly in spleen and liver.
--> Thrombocytopaenia, petechiae, purpura, ecchymosis, mucosal bleeding, risk of intracranial haemorrhage if platelets <20
--> F:M 3:1, but also children (us. self-limiting).
Spleen is of normal size.
Megakaryocytes on marrow biopsy.
Can be secondary to HIV, SLE, antiphospholipid antibody syndrome, hep C, lymphoproliferative disorders
- or drugs (cocaine, gold, antibiotics, heparin, qunidine, abciximab, anti-inflammatories).
Physicians will treat when platelets 20-30 thousand / mm3 or <50 with significant symptoms
- high-dose prednisone (4 mg/kg/day) and IV immunoglobulin Rx are cornerstones to therapy
- response rate is high but relapse common.
Splenectomy indication:
Failure of medical therapy (6-8 wk after steroids)
Persistent ITP >1yr
Severe thrombocytopaenia.
--> Response within a week; 75-85% permenant.

Thrombotic thrombocytopaenic purpura (TTP)
Rare. Endothelium-triggered platelet deposition in arterioles and capillaries.
--> micro-vascular thrombotic episodes.
- microangiopathic haemolytic anaemia, severe thrombocytopaenia, fever,
- organ failure: renal, cardiac failure and dysrhythmia.
- headache, mental state changes, seizures, coma,
May follow clopidogrel usage
Blood film shows schistocytes, nucleated red blood cells and basophilic stippling.
Physicians will treat with daily plasmaphoresis and FFP transfusions.  High dose steroids can limit recurrences.
--> high response rate.
- not platelets as risk deterioration of pathology
Splenectomy indication:
Frequent relapses.
--> Response rate only <50%

Autoimmune Haemolytic Anaemia (AIHA)
Autoantibodies formed and directed against RBC antigens.
--> anaemia, RBC sequestration
Idiopathic or related to infection, SLE, leukaemia
Can be warm or cold
- warm: IgG auto-antibodies optimally act at body temp; blood smear and direct antiglobulin test will show
- cold: less common 25%; autoantibodieas act at 5o; post-infection eg EBV, or in lymphoproliferative disorders; must avoid cold or get acute haemolytic crises.
Physicians treat with"
- warm: steroids (1-2mg/kg/day) with good response in 60%;
- cold: plasmaphoresis, alkylating agents, not steroids
Splenectomy indication:
Warm AIHA only.
- never cold as spleen not the problem there.
No remission in 3 weeks
Hb conc not maintained by steroids.
--> Most improve within 2 weeks; 50% will need ongoing steroids.

Felty Syndrome
Rheumatoid arthritis, neutropaenia, splenomegaly.
85% have HLA-DR4 antigen.
Severe or chronic infections due to neutropeania; counts <0.5x10^9
Rx methotrexate, DMARDS, G-CSF
Splenomegaly is variable
Splenectomy indication
Failure of medical therapy: recurrent infections or severe neutropaenia
80% haematological response rate

Sarcoidosis
Noncaseating granulomatous disease
Splenic involvement usually part of systemic disease
- 40% of sarcoid pts have splenomegaly; 3% massive.
- true splenic involvement with sarcoid only 10-15%
Treatment is with steroids or methotrexate
Splenectomy indication:
Symptoms from splenomegaly; sequestration, pain, ?tumours
Splenectomy does not alter course
- but can improve refractory hypercalcaemia

Red Blood Cell Disorders

1. Hereditary spherocytosis
AD inherited most common RBC disorder; fragile cells, get lodged in splenic pulp and destroyed
Range from asymptomatic, mild jaundice to jaundice, splenomegaly and pigment stones
- 50% develop stones after 5y
Splenectomy
Most common indication in anaemia; also cholecystectomy if gallstones.
Is curative in almost all patients.
Usually delayed til >5y old to limit OPSI
Controversy as to operating on pts wiht milder forms of disease
- some studies advocate partial splenectomy.

2. Hereditary elliptocytosis
Similar story but less common; biconcave ellipocytes
Less severe clinical course but less severe as more deformable cells in most forms.
May need splenectomy for severe haemolysis and it is curative.

3. Hereditary pyropoikilocytosis
AD disease of red cell membrane defects.
Usually presents young with severe jaundice / anaemia
Splenectomy is curative

4. Hereditary stomatocytosis and xerocytosis
Rare disorders, variable course; range from symptomatic to mild anaemia.
Increased cation permeability, leading to high cell volume.
Splenectomy may improve anaemia but does not fully correct haemolysis.
- anyway most are mild and don't need it.

Genetic syndromes

1. Thalassemia
AD disorders, of Hb chains.
Most common genetic disorder in the world.
Beta more common.
Heterozygous form (minor) usually asymptomatic but with microcytosis and mild anaemia.
Major is much more severe
- severe haemolytic anaemia as babies and complications of that.
Periodic lifelong blood transfusions and iron chelation.
High transfusion requirement may necessitate splenectomy to maintain cells.
- usually delayed until 4-5y old to limit OPSI
Marrow transplantation considered but most major pts die in <30y due to cardiac sequelae.

2. Sickle cell anaemia
AR haemoglobinopathy.
HgS propensity to deform and sickle-shpaes when in low-O2 tension.
Cause stasis and vasoocclusion in microvasculature
--> tissue ischaemia, severe pain and chronic organ damage; sickle cell crises.
Homozygotes autosplenectomy from multiple infarcts at young age.
Thus splenectomy rarely indicated; except splenic abscess.

3. Gaucher disease
Glycolipid stoage disease with deposition of glucocerebrosdie in reticuloendothelial system.
May get massive hepatosplenomegaly and splenectomy indicated with refractory cytopaenia.

4. Pyruvate kinase deficiency
Most common genetic defect causing hemolytic anaemia; AR disease
Results in ATP deficiency
- rbcs poorly deformable; destroyed
Hemolysis is exacerbated by acute infections and pregnancy.

5. Amyloidosis
Exceallular deposition if insoluble proteins; hepatosplenomegaly in 25%, severe splenomegaly in 10%
Splenectomy if functionally indicated.

White blood cell disorders

1. Hodgkin lymphoma
Lymphoreticular cell neoplasm, young adults in 2nd-3rd decades
Historically splenectomy was done for staging, now rarely needed unless thrombotypenia

2. Non-Hodgkin lymphoma
Most common lymphoma; diverse group with prognosis based on histologic type and features.
Splenic involvement in ~70%
Splenectomy if anemia, massive spleen and cytopaenia / sequestration.
Some types more likely to involve spleen;
- splenic marginal zone lymphoma = indolent B-cell neoplasm in older pts;
- first line Rx is splenectomy, leads to partial remission in many pts and complete remission in some.

3. Chronic lymphocytic leukaemia
B cell leukaemia, progressive accumulation of functionally incompetent lymphocytes.
Oder pts; splenic infiltration is common and can be severe splenomegaly and cytopaenia
Splenectomy can relieve symptoms and cytopaenia
- considered if refractory to medical therapies.

4. Chronic myelogeneous leukaemia
CML = abnormal proliferation and accumulation of granulocytes.
95% have the classic Philadelphia chromosome; reciprocal translocations.
Diagnosis during chronic phase (asymptomatic), often get splenomegaly
Can accelerate with fevers, increased WCC abnd splenomegaly.
Imatinib

5. Hairy cell leukaemia
Rare; B cells with proections
Indolent disease presents with splenomegaly, pancytopenia (hypersplenism)
Splenectomy used to be required routinely; chemotherapy improvements mean it is now rarely needed.
- note occasionally these WBC tumours can rupture, bleed spontaenously though

Bone marrow disorders

1. Primary myelofibrosis
Chronic malignant hematological disorder (abnormal myeloid precursors)
- leads to medullary fibrosis and extramedullary haematopoiesis
Splenomegaly can be massive with sequestration (and portal htn from venous thrombosis).
Splenectomy if thrombocytosis, hemolysis requiring transfusions, pain, infarctions, htn with ascietes.
High morbidity and mortality and highly selective.

2. Myeloproliferative disorders
Collection of disorders of abnormal  proliferation of erythroid, megakaryocytic or granulcytic myeeloid cells.
- beginning in marrow then extramedullary.
Splenomegaly can be massive
Splectomy can provide useful palliative treatment.

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MANIFESTATIONS

As above


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INVESTIGATIONS

As above
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MANAGEMENT

Pre-Op Considerations


1. Imaging is crucial for planning (ie CT)
- Anatomic location, relationships, size, etc.

2. Preop splenic artery embolization can be considered in portal htn
- can make lap surgery more manageable.

3. If platelet transfusion is reqd peri-operatively (platelets <10) or bleeding
--> hold transfusion until splenic artery ligated.

4. Preop antibiotics 50min prior to incision should cover flora.

5. Oro / nasogastric to decrease gastric distension
- better visualisation of short gastrics.

6. If steroids are needed, stress-doses given with a rapid taper post-op.

7. Vaccinate pre-op in elective cases 2 weeks prior to splenectomy
- H influenzae B, polyvalent pneumococcus, Meningococcus
- if emergency, vaccinate post-op

Operative Considerations

1. Either midline laparotomy or L subcostal.
- better midline if massive.

2. Ligate hilum
- either first or after mobilizing the spleen from splenophrenic, splenorenal and splenocolic attachements.
- consider prioritising if need for platelets, massive, malignancy, or dense adhesions.
--> enter lesser sac and identify vessels at hilum, gaining control and avoiding tail of the pancreas.

3. Hilar vessels taken individually
- 'prevents AV fistula' but that is probably extremely rare
- suture ligatures or linear stapling device (in massive spleens = useful)

4. Spleogastric ligament divided and short gastric vessels identified and suture ligated or clipped.
- EndoGIA for hilar vessels and ligasure for short gastrics in lap splenectomy.

5. Once removed, carefully inspect for accessory splenic tissue
- 10-30%; common locations should be checked
- ie, anywhere along the splenic vessles: gastrosplenic ligament, spenorenal ligament, retroperitoneally, in mesentery, omentum and occasionally in gonads or path of descent.
- (spleen forms near uorgenital ridge from which gonads develop; gonads may pull some splenic tissue down with them.
Patients with accessory spleens will lack old cells (howell-jolley bodies, heinz bodies, target cells, may require reexploration).
 
Post-Operative Considerations

Monitor for haemorrhage, atelectasis, infection.
Know that pts will usually have an increase in leukocytes post-op; physiologic.
Infections complications include suphrenic abscess and OPSI.
Give vacc's 2w post op if did not get pre-op
- if compliance a concern then give prior to d/c
- if immunocompromised, wait 3m
Other complications include pneumonia, thyrombocytosis, pleural effusions, pancreatitis, pancreatic fistula, injury to adjcent organs.
- higher risk in haematological / immunosuprression.
Thrombocytosis can occure immediately post-op but peaks up to 3weeks.
- antiplatelets only indicated for complications or when platelet counts hit 1 million.
- portal or mesenteric vein thrombosis is serious, reported in up to 14%, some studies reporting a higher rate in lap spleens.
--> higher risk in myeloproliferative disorders, hemolytic anemias, long splenic vein stumps, post-op thrombocytosis, hypercoagulable states and splenomegaly.
--> if treated quickly with systemic anticoagulation, then recannulation rates can be >90%.

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REFERENCES
Cameron 10th