Budd Chiari Syndrome

Budd-Chiari syndrome is a group of disorders characterised by hepatic venous outflow obstruction.  The obstruction may occur anywhere from the hepatic venules to the right atrium.

As a result of this obstruction there is increased hepatic sinusoidal pressure, leading to:

• portal hypertension
• liver congestion
• decreased liver perfusion

For clinical disease to occur, 2 veins must be blocked. Clinical symptoms/signs include:

• RUQ pain
• ascites
• hepatomegaly

Causes of Budd-Chiari syndrome:

• 25% - no cause identified
• 75% -
• myeloproliferative disorders - commonest single cause, around 20% of cases
• antiphospholipid syndrome
• deficiencies of proteins C,S or antithrombin III
• factor V Leiden mutation
• oral contraceptive use
• pregnancy
• paroxysmal noctural haemoglobinuria
• metastatic invasion of hepatic vein/IVC

Investigation

• doppler ultrasound - assessment of hepatic venous flow - sensitivity/specificity >85% - first line
• MR - second line
• CT

Management

• medical
• anticoagulant therapy
• manage ascites - spironolactone
• surgical
• portosystemic shunt - typically a transjugular intrahepatic portosystemic shunt (TIPS)
• liver transplant

References
Aydinil, M. and Bayraktar, Y. Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. World J Gastroenterol. 2007; 13(19): 2693-6.
Cura, M., Haskal, Z. and Lopera, J. Diagnostic and interventional radiology for Budd-Chiari syndrome. Radiographics. 2009; 29(3): 669-681.

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Minimal change disease

Minimal change disease is the commonest cause of nephrotic syndrome in children and accounts for 15% of cases of primary nephrotic syndrome in adults. 

It is usually idiopathic but it can occasionally be secondary to: 

• Neoplasia – notable Hodgkins and non-Hodgkins lymphoma 
• Drugs – including NSAIDS, lithium, rifampicin, gold and tamoxifen 
• Infections – including TB, syphilis, HIV and mycoplasma 
• Atopic reactions 

It is believed to be T cell mediated. 

It is known as minimal change disease because under the light microscope no change is seen but with an electron microscope you can see effacement of the podocyte processes. 

Treatment 

• Oral corticosteroids - around 70% of patients respond to steroids
• Second line: Cyclophosphamide, cyclosporine, tacrolimus 

Prognosis: 

• Around a third make a complete recovery 
• A third have one relapse 
• A third have more than one relapse 

Complications are essentially the same as those of nephrotic syndrome: 

• Thrombosis 
• Infection
• Acute renal failure 

References

Cunnard, R. and Kelly, C. T cells and minimal change disease. J Am Soc Nephrol. 2002; 13(5): 1409-1411.  

Glassock, R. Seconary minimal change disease. Nephrol Dial Transplant. 2003; 18 Suppl 6: vi52-58.   

Waldman, M. et al. Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol. 2007; 2(3): 445-453.

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Wegener’s granulomatosis

Wegener’s granulomatosis is a small and medium vessel necrotizing granulomatous vasculitis which predominantly affects the upper airways, lungs and kidneys but can affect any organ system. 

Possible features include:

• Respiratory symptoms – 90%
• Cough 
• Pleuritis 
• Haemoptysis 
• Rhinorrhoea 
• Epistaxis 
• Sinusitis 
• Subglottic stenosis -20% 
• Saddle-shaped nose 
• Perforation of the nasal septum 
• Glomerulonephritis – develops in 80% at some point

Investigations: 

• Biopsy 
• Necrotising granulomatous vasculitis with neutrophilic infiltrates
• CXR 
• Bilateral nodular infiltrates 
• Alveolar haemorrhage 
• ANCA
• c-ANCA – positive in 90%
• p-ANCA – positive in 10% 

Treatment: steroids and cyclophosphamide, with co-trimoxazole to decrease opportunitistic infections 

5 year survival with treatment is around 76% 

Small print gem: Long-term treatment with cyclophosphamide is associated with increased risk of bladder cancer and myelodysplasia 

References

Langford, C. and Hoffman, G. Wegener’s granulomatosis Thorax. 1999; 54(7): 629-637. 

Lapraik, C. et al. BSR and BHPR guidelines for the management of adults with ANCA positive vasculitis. Rheumatology (Oxford). 2007; 46(10): 1615-1616. 

Paddock, M., Lynch, C. and Paska, L. Wegener’s granulomatosis in primary care. JRSM Short Rep. 2010. 1(7): 59.

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Thrombocytosis

Thrombocytosis is a raised number of platelets, usually defined as ≥ 450 x 10^9 

Thrombocytosis may be divided into : 

• Spurious 
• Caused by non-platelet structures in the blood which are counted as platelets by modern automated counters 
• Examples include 
• Cryoglobulin crystals 
• Microspherocytes (eg from severe burns) 
• Schistocytes 
• Pappenheimer bodies 
• Bacteria

• Primary thrombocytosis 
• Increase in platelets caused by alterations targeting the haematopoietic cells 
• Causes are
• Essential thrombocytheameia 
• Megakaryocyte proliferation 
• Not meeting WHO criteria for CML, PV, PMF or MDS
• Presence of JAK 2 or other clonal marker and no evidence of reactive thrombocytosis
• Increases risk of both thrombosis and bleeding 
• Treatment: 
• High risk patients (aged >60 OR platelet count >1500 OR disease-related thrombotis/haemorrhage) 
• Hydroxycarbamide plus aspirin 
• ? interferon alpha in young patients
• Other patients 
• Aspirin only
• Polycythaemia Vera
• Myelofibrosis 
• Chronic myeloid leukaemia

• Secondary/reactive thrombocytosis 
• Reactive to 
• Infection 
• Inflammation 
• Post-operative/trauma 
• Iron deficiency 
• Hyposplenism
• Haemorrhage 
• Malignancy 
• Drugs 
• Corticosteroids 
• Adrenaline 
• Rarely causes complications 
• Treat underlying cause 

Small print gem: extremely high platelet levels (>1500 x 10^9) result in more causes of bleeding than thrombosis 

References

Bleeker, J. and Hogan, W. Thrombocytosis: diagnostic evaluation, thrombotic risk stratification, and risk-based management strategies. Thrombosis. 2011; 2011: 536062. 

Harrison, C. et al. Guideline for investigation and management of adults and children presenting with a thrombocytosis. Bjh guideline. Available at http://www.bcshguidelines.com/4_HAEMATOLOGY_GUIDELINES.html?dtype=Haemato-oncology&dstatus=Current&dsdorder=&dstorder=&dmax=10&dsearch=thrombocytosis#gl 

Skoda, R. Thrombocytosis. Hematology Am Soc Hematol Educ Program. 2009: 159-167.

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