1. AM REPORT

2. The Budd Chiari Syndrome and Polycythemia Vera Ryan Sanford 12.8.2009

3. Budd Chiari [BC], Why a Syndrome? Any process that interrupts blood outflow from the liver: hepatic venous outflow obstruction Usually refers to obstruction in large hepatic veins or IVC NOT – right heart failure – pericardial disease – sinusoidal obstructive syndome [hepatic veno-occlusive disease] SOS is fibrotic, not thrombotic related to hematologic transplantation Categories: based on rapidity of onset and collateralization – Acute +/- fulminant: 20%, F>M, Severe RUQ pain, HSM, Rapid development of jaundice, ascites; AST/ALT > 5x ULN; ↑↑ bili; +/- encephalopathy – Sub-acute: 40%; variable presentation; typical is partial occlusion; asymptomatic to mildly symptomatic – Chronic: 40%; seen as cirrhosis

4. Signs and Symptoms Abdominal Pain Hepatomegaly Ascites N/V Jaundice, esp if acute Venous collateralization – varices, abdominal/flank collaterals LEE Absence of hepatojugular reflux Laboratory evidence of liver dysfunction

5. So then, what are the causes? FIRST THINK – Hypercoagulable – Polycythemia vera – Other myeloproliferative diseases – Multiple causes in one person often see + JAK2 mutation

6. Centrilobular necrosis, dilated sinusoids filled with RBCs Normal liver Normal R hepatic vein No R hepatic v. Rich collaterals ‘Spiders web’

7. How to diagose? Clinical context + imaging – Liver U/s + doppler: first choice – CT Abdomen Can see necrosis Venous anatomy Sequelae of liver disease – MRA Abdomen: as for CT; can help distinguish acuity Idiopathic? Check for JAK2 mutation for myeloproliferative disorder

8. Liver Ultrasound with Doppler Studies normal right hepatic vein doppler study showing normal expected biphasic waveform across hepatic vein no hepatic vein, no venous flow

9. Characteristic Findings on Venography and CT 1.Caudate Hypertrophy and IVC Compression 2.Mottled parenchyma / lack of perfusion 3.Retroperitoneal Varices

10. A Brief Ascites Review Don’t forget the total protein >2.5: cardiac causes, Budd-Chiari <2.5: portal hypertension/cirrhosis

11. Treatment: longterm/indefinate anticoagulation and...

12. A moment on polycythemias

13. Suggested by... Hgb > 16.5 [F] or 18.5 [M] g/dL Hct > 48 [F] or 52 [M] % Increased RBC count, less useful The above are all concentrations/fractions and depend on the denominator – plasma volume GOLD = RBC Mass study; a dilution technique by self-transfusing radioactive tagged RBCs

14. Terms Relative Polycythemia – Isolated decrease in plasma volume – aka Gaisböck’s syndrome, stress erythrocytosis Absolute Polycythemia – Primary: PV and other rarer causes; low erythropoietin – Secondary: a circulating factor [epo] stimulates RBC production Inappropriate secretion Appropriate secretion

15. Polycythemias that are not PV Inappropriate epo secretion: RCC/HCC Appropriate epo secretion: think hypoxemia – Chronic pulmonary disease – Cyanotic heart disease – OSA, obesity/hypoventilation – High altitude – Chronic carbon monoxide exposure – smoking – Hemoglobinopathies that increase oxygen affinity Miscellaneous: think cyclists – Anabolic steroids – Blood doping – Surreptitious use of ESA’s

16. Polycythemia Vera A chronic myeloproliferative disorder like CML, ET, myelofibrosis Untreated survival 6-18 months 2/2 thrombosis, malignant transformation Treated survival > 10 years

17. Signs and Symptoms HA, weakness, dizzy, diaphoretic, gout Amaurosis, scotomata, ocular migraine Pruritus: especially post bath/shower Erythromelalgia: burning pain in feet and hands w/ accompanying pallor/cyanosis/erythema w/ present pulses  microvascular thrombus Arterial and venous thrombosis, often unusual Splenomegaly, hepatomegaly, facial plethora

18. Other labs Often PLT > 400k or WBC > 12k Low epo level Endogenous erythroid colony formation in vitro BM Bx: hypercellular, iron absent Presence of a JAK2 mutation

19. What is JAK2? A cytoplasmic tyrosine kinase critical for intracellular signaling from the receptors for erythropoeitin, thrombopoeitin, IL-3, GM-CSF

20. JAK2 and PV >95% of all PV from JAK2 exon 14 mutation V617F [phenylalanine in place of valine] The remainder can have exon 12 mutation Leads to constitutively active JAK2 and dysregulated cellular signalling

21. Acquired??? Yes, not inherited

22. Why would polycythemia be a thrombophilic state?

23. Treatment Phlebotomy to HCT < 42 [F] and 45 [M] % Consider – Hydroxyurea – Low dose aspirin – IFN-alpha – Radioactive P32 Allopurinol for gout

24. References Campbell PJ, Green AR. “The myeloproliferative disorders”. N Engl J Med. 2006 Dec 7;355(23):2452-66. Janssen H. L.A., Garcia-Pagan J.-C., Valla D.-C., Cardenas A., Menon K.V. N., Shah V., Kamath P. S. The Budd-Chiari Syndrome. N Engl J Med 2004; 350:1906-1908, Apr 29, 2004 Up To Date Online