AM REPORT

The Budd Chiari Syndrome and Polycythemia Vera

Ryan Sanford

12.8.2009

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

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

So then, what are the causes?

FIRST THINK– Hypercoagulable– Polycythemia vera– Other myeloproliferative

diseases– Multiple causes in one

person

often see + JAK2 mutation

Centrilobular necrosis, dilated sinusoids filled with RBCs

Normal liverNormal R

hepatic vein

No R hepatic v. Rich collaterals

‘Spiders web’

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

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

Characteristic Findings on Venography and CT

1. Caudate Hypertrophy and IVC Compression

2. Mottled parenchyma / lack of perfusion

3. Retroperitoneal Varices

A Brief Ascites Review

Don’t forget the total protein

•>2.5: cardiac causes, Budd-Chiari

•<2.5: portal hypertension/cirrhosis

Treatment: longterm/indefinate anticoagulation and. . .

A moment on polycythemias

Suggested by . . .

Hgb > 16.5 [F] or 18.5 [M] g/dL Hct > 48 [F] or 52 [M] % Increased RBC count, less usefulThe 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

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

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

Polycythemia Vera

A chronic myeloproliferative disorder like CML, ET, myelofibrosis

Untreated survival 6-18 months 2/2 thrombosis, malignant transformation

Treated survival > 10 years

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

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

What is JAK2?

A cytoplasmic tyrosine kinase critical for intracellular signaling from the receptors for erythropoeitin, thrombopoeitin, IL-3, GM-CSF

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

Acquired??? Yes, not inherited

Why would polycythemia be a thrombophilic state?

Treatment

Phlebotomy to HCT < 42 [F] and 45 [M] % Consider

– Hydroxyurea– Low dose aspirin– IFN-alpha– Radioactive P32

Allopurinol for gout

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

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