Case presentation:Case presentation:

Dr. Mohammad Shaikhani.Dr. Mohammad Shaikhani.Dr. Mohammad Omer Mohammad.Dr. Mohammad Omer Mohammad.

Sulaimanyah University.Sulaimanyah University.College of Medicine.College of Medicine.

Department of Medicine.Department of Medicine.

SH.K, SH.K, 20 years old, Studen from Darbandixan,Sulaimanyiah, Iraq. 20 years old, Studen from Darbandixan,Sulaimanyiah, Iraq.

Date of admission: 9.9.08Date of admission: 9.9.08

CC: abdominal distention for the last 2 weeksCC: abdominal distention for the last 2 weeks

H.P.I: a female with abdominal distention and H.P.I: a female with abdominal distention and yellow discoloration of skin and sclera yellow discoloration of skin and sclera associated with pain during voiding and associated with pain during voiding and frequency with lower pelvic pain. There were frequency with lower pelvic pain. There were no fever no rigor.no fever no rigor.

P.M.H: not significantP.M.H: not significant

D.H: on HRT for irregular cycles. There is no D.H: on HRT for irregular cycles. There is no Hx of blood transfusion, tattooing or drug Hx of blood transfusion, tattooing or drug injection injection ““ addiction addiction””

Review of systems:Review of systems:Resp: SOB, no cough no sputumResp: SOB, no cough no sputumCVS: no palpitation, no leg edema.CVS: no palpitation, no leg edema.GIT: decr. Appetite, nausea, constipation.GIT: decr. Appetite, nausea, constipation.

O/E: conscious oriented young ladyO/E: conscious oriented young ladyTing of jaundice, no cyanosisTing of jaundice, no cyanosis……mild pallormild pallorChest: clear, N.V.BChest: clear, N.V.BPrecordium: NDR, no added soundsPrecordium: NDR, no added soundsAbdomen: soft, hepatospleenomegally Abdomen: soft, hepatospleenomegally Ascitis with +ve shifting dullness and trans thrill Ascitis with +ve shifting dullness and trans thrill Neurology: intactNeurology: intactVita signs Vita signs ……

Ix:Ix:

LFT: Bilirubin 0.9 , 0.7LFT: Bilirubin 0.9 , 0.7

Alk. Phosphatase: 87 , 69Alk. Phosphatase: 87 , 69

S. GOT: 8S. GOT: 8 , 26, 26 S.GPT: 5 , 25 S.GPT: 5 , 25

T.S.P: 7.6 , 7.7T.S.P: 7.6 , 7.7

PT: 21.7 sec , INR: 2.4 - 19.5 INR: 2.0PT: 21.7 sec , INR: 2.4 - 19.5 INR: 2.0

PCV: 42 , 37PCV: 42 , 37

CBP: Hb: 13.2 – MCV: 39.8 – MCH: 22.0 – MCHC: CBP: Hb: 13.2 – MCV: 39.8 – MCH: 22.0 – MCHC: 33.3 – WBC: 4200 , 8700 – 80% N 17% L – PLT: 33.3 – WBC: 4200 , 8700 – 80% N 17% L – PLT: 586.000586.000

Bl. Film: RBC: normochromic normocytic Bl. Film: RBC: normochromic normocytic screeninig for infection & infl. Disorders. WBC: screeninig for infection & infl. Disorders. WBC: Neutrophilia, Lymphopenia. Platelet: Markedly Neutrophilia, Lymphopenia. Platelet: Markedly increased.increased.

ESR: 11 ,14ESR: 11 ,14

GUEGUE……

U/S: mild liver enlargement, coarse texture no U/S: mild liver enlargement, coarse texture no focal lesion, mod-severe large spleen mod. focal lesion, mod-severe large spleen mod. Amount of ascitis.Amount of ascitis.

Ascetic fluid aspiration: Ascetic fluid aspiration:

WBC = lymphocytosisWBC = lymphocytosis

Ptn= 4.5,4.8Ptn= 4.5,4.8

Sugar= 100Sugar= 100

AFB: negativeAFB: negative

Cytology= LC, no malignant cellsCytology= LC, no malignant cells

ANA and AMC Ab Ads DNA Ab A LKMANA and AMC Ab Ads DNA Ab A LKM…… - -VEVE

ANTILIVER KIDNEY MICROSOME= -VEANTILIVER KIDNEY MICROSOME= -VE

Viral marker= -ve (twice)Viral marker= -ve (twice)

OGD= esophagitis, gastritisOGD= esophagitis, gastritis

Peritoneal biopsy: no granuloma, no malig.Peritoneal biopsy: no granuloma, no malig.

S. Copper: 150Mg Ceruloplasmin: 36.3mgS. Copper: 150Mg Ceruloplasmin: 36.3mg

RBS: 126 , RFT: Bl U: 11 , S Creat: 0.5RBS: 126 , RFT: Bl U: 11 , S Creat: 0.5

SGPT: 13 , SGOT: 18 , PT: 20.6 , INR: 2.1SGPT: 13 , SGOT: 18 , PT: 20.6 , INR: 2.1

Ascitic Fluid: Lymphocytosis: 70% , Pr: 5.2 Ascitic Fluid: Lymphocytosis: 70% , Pr: 5.2 Sug: 120 , no AFBSug: 120 , no AFB

CBP: Hb: 12.7 – MCV: 65.9 - MCH: 21.9 – CBP: Hb: 12.7 – MCV: 65.9 - MCH: 21.9 – MCHC: 33.3 – WBC: 13600 – PLT:813.000MCHC: 33.3 – WBC: 13600 – PLT:813.000

Bl. Film: RBC: hypochromic microcytic Bl. Film: RBC: hypochromic microcytic anisopoikilocytosis elliptocytosis. WBC:mild anisopoikilocytosis elliptocytosis. WBC:mild Neutrophilia. Platelet: Markedly increased with Neutrophilia. Platelet: Markedly increased with anisothrombia many Giant cells seen.anisothrombia many Giant cells seen.

S Pr. Elec: S Pr. Elec:

AlB: normal 58.20AlB: normal 58.20

Alpha 1: low 0.07Alpha 1: low 0.07

Alpha 2: low 3.65Alpha 2: low 3.65

Beta: low 6.62Beta: low 6.62

Gama: high 31.46Gama: high 31.46

Total: 8.20 gm/dlTotal: 8.20 gm/dl

A/G : 1.39A/G : 1.39

Doppler study:Doppler study:

11stst: prominent caudate lobe, mild coarse liver : prominent caudate lobe, mild coarse liver texture, nr hepatic flowtexture, nr hepatic flow

22ndnd: hepatomegaly, prominent caudate, no : hepatomegaly, prominent caudate, no focal mass, acute thrombosis of portal and focal mass, acute thrombosis of portal and splenic vein.splenic vein. Huge splenomegaly and Huge splenomegaly and moderate abdominal Ascitis.moderate abdominal Ascitis.

Last PT: 24.7 INR: 3Last PT: 24.7 INR: 3

Final diagnosis:Final diagnosis:

Portal vein/splenic vein thrombosis due to Portal vein/splenic vein thrombosis due to hypercoagulable state from ?essential hypercoagulable state from ?essential throbocythemia potentate by oral contraceptive throbocythemia potentate by oral contraceptive use.use.

OTHER CASE REPORTS FROM INTERNET & OTHER CASE REPORTS FROM INTERNET & LITERETURE:LITERETURE:

Case 2Case 252 year old man with a history of PNH originally diagnosed in 1978 (at 52 year old man with a history of PNH originally diagnosed in 1978 (at age 28) when he presented with dark urine and was noted to have age 28) when he presented with dark urine and was noted to have moderate hemolytic anemiamoderate hemolytic anemia

Treated initially at that time with prednisone and blood transfusions. Treated initially at that time with prednisone and blood transfusions. Had a relatively mild course with infrequent episodes of hematuria and Had a relatively mild course with infrequent episodes of hematuria and very few blood transfusionsvery few blood transfusions

Did not see a hematologist for over 20 yearsDid not see a hematologist for over 20 years

Case PresentationCase PresentationPresented in April 2002 with abdominal pain and distension and was Presented in April 2002 with abdominal pain and distension and was noted to be jaundicednoted to be jaundiced

Hepatitis workup was negative but an MRI of the abdomen revealed Hepatitis workup was negative but an MRI of the abdomen revealed hepatic vein thrombosis (Budd-Chiari syndrome)hepatic vein thrombosis (Budd-Chiari syndrome)

Underwent a transjugular liver biopsy on 4/23/02 which revealed Underwent a transjugular liver biopsy on 4/23/02 which revealed extensive fibrosis, no cirrhosis, sinusoidal dilatation and central vein extensive fibrosis, no cirrhosis, sinusoidal dilatation and central vein fibrosis consistent with Budd-Chiari syndromefibrosis consistent with Budd-Chiari syndrome

Despite anticoagulation and numerous paracenteses, refractory ascites Despite anticoagulation and numerous paracenteses, refractory ascites was present and he underwent a TIPS procedure in 7/02was present and he underwent a TIPS procedure in 7/02

Case PresentationCase PresentationPatient subsequently developed hepatic encephalopathy, requiring Patient subsequently developed hepatic encephalopathy, requiring multiple hospital admissions over 2 months following TIPS placementmultiple hospital admissions over 2 months following TIPS placement

Ultrasounds confirmed patency of shuntUltrasounds confirmed patency of shunt

Referred to Dr Bessler in 9/02. Evaluation revealed a jaundiced, mildly Referred to Dr Bessler in 9/02. Evaluation revealed a jaundiced, mildly encephalopathic man with normal abdomenencephalopathic man with normal abdomen

CBC revealed Hgb 11.9 with MCV 97.2, plt cnt 90,000, ANC 2,700, CBC revealed Hgb 11.9 with MCV 97.2, plt cnt 90,000, ANC 2,700, INR 1.7, creatinine 0.8, and bilirubin 6INR 1.7, creatinine 0.8, and bilirubin 6

Case PresentationCase Presentation

Flow Cytometry:Flow Cytometry:erthrocytes: 17% CD59 deficienterthrocytes: 17% CD59 deficient

granulocytes: 99.8% CD59/CD24 deficientgranulocytes: 99.8% CD59/CD24 deficient

monocytes: 82% CD59 deficientmonocytes: 82% CD59 deficient

lymphocytes: 24% CD59 deficientlymphocytes: 24% CD59 deficient

Anticoagulation increased, folic acid started, and Anticoagulation increased, folic acid started, and referred for consideration of hematopoietic stem cell referred for consideration of hematopoietic stem cell transplantationtransplantation

Case: 3

Case:4

Case: 5,6

Case: 1

More cases

Vascular diseases of the liver; Budd-Vascular diseases of the liver; Budd-chiari/portal vein thrombosis& other chiari/portal vein thrombosis& other

veno-occlusive disorders:veno-occlusive disorders:Conditions in which radiologists & Conditions in which radiologists &

interventional radiologists can interventional radiologists can contribute much.contribute much.

Prepared by:Prepared by:

Dr.Mohammad Shaikhani.Dr.Mohammad Shaikhani.

Mshaikhani_@hotmail.comMshaikhani_@hotmail.com

DefinitionDefinition

Heterogeneous group of disorders characterized Heterogeneous group of disorders characterized by hepatic venous outflow obstruction at the level by hepatic venous outflow obstruction at the level of the hepatic venules, the large hepatic veins, the of the hepatic venules, the large hepatic veins, the IVC, or the right atriumIVC, or the right atrium

PathogenesisPathogenesis Obstruction of the hepatic venous outflow tract Increased hepatic sinusoidal pressure /portal

hypertension. Portal venous perfusion of the liver is decreased, which

may result in portal venous thrombosis. The ensuing venous stasis and congestion lead to hypoxic

damage to adjacent hepatic parenchymal cells& the ischemic injury to the sinusoidal lining cells results in the release of free radicals& oxidative injury to the hepatocytes ensues with hepatocyte necrosis in the centrilobular regions, progressive centrilobular fibrosis, nodular regenerative hyperplasia, ultimately, cirrhosis

If the hepatic sinusoidal pressure is reduced by the creation of a portosystemic shunt or by the development of a portal venous collateral system, liver function improves.

BCS:Blood disorders

Major causes of vascular liver diseases. Atypical myeloproliferative diseases most

commonly implicated. Frequent combination of several causes. Permanent anticoagulation is generally

recommended once prophylaxis for portal hypertensive bleeding has been instituted.

Clinical ManifestationsClinical Manifestations Depends on the extent &rapidity of the Depends on the extent &rapidity of the

hepatic-vein occlusion & whether a venous hepatic-vein occlusion & whether a venous collateral circulation has developed to collateral circulation has developed to decompress the sinusoids.decompress the sinusoids.

Four TypesFour TypesFulminantFulminantAcuteAcuteSubacuteSubacuteChronicChronic

Clinical PresentationClinical Presentation FulminantFulminant

hepatic encephalopathy within eight weeks of development of hepatic encephalopathy within eight weeks of development of jaundice; uncommonjaundice; uncommon

AcuteAcute

symptoms of short duration, intractable ascites, hepatic symptoms of short duration, intractable ascites, hepatic necrosis with the formation of venous collaterals; usually necrosis with the formation of venous collaterals; usually thrombosis of all major hepatic veinsthrombosis of all major hepatic veins

Clinical PresentationClinical Presentation

SubacuteSubacute

most common; more insidious onsetmost common; more insidious onset

ascites& hepatic necrosis may be minimal; 1/3 ascites& hepatic necrosis may be minimal; 1/3 of patients with thrombosis of all major of patients with thrombosis of all major hepatic veinshepatic veins

Chronic Chronic

manifest as cirrhosismanifest as cirrhosis

Clinical PresentationClinical Presentation

Abdominal pain, hepatomegaly and ascites are Abdominal pain, hepatomegaly and ascites are present in almost all patients with Budd-Chiari present in almost all patients with Budd-Chiari syndromesyndrome

Nausea, vomiting and mild jaundice is more Nausea, vomiting and mild jaundice is more frequent in fulminant and acute formsfrequent in fulminant and acute forms

Splenomegaly and esophagogastric varices Splenomegaly and esophagogastric varices may be present in the chronic formmay be present in the chronic form

DiagnosisDiagnosis Serum AST / ALT may be >*5 ULN in the fulminant &acute forms,

whereas increases are smaller in the subacute form. Serum alkaline phosphatase /bilirubin also increase to a varying

extent, along with a decrease in serum albumin. The serum–ascitic fluid albumin gradient is high, with the total

protein level in the ascitic fluid usually > 2.5 g per deciliter, similar to ascites of cardiac disease.

Doppler ultrasonography of the liver, with a sensitivity/pecificity of 85 percent or more, is the technique of choice for initial investigation when suspected.

Necrotic areas of the liver are better seen, on contrast-enhanced CT, which may be recommended to delineate the venous anatomy & the configuration of the liver when a TIPS is being considered.

MRI with VIBE sequence is better for visualizing the whole length of the inferior vena cava & may permit differentiation of the acute form from the subacute & chronic forms.

In some patients, echoc may be needed to rule out tricuspid regurgitation, constrictive pericarditis, or a right atrial myxoma.

DiagnosisDiagnosis Confirmed by a “spiderweb” pattern on hepatic venography& the

confirmation is necessary, even with a negative result on ultrasonographic exam, when there is a strong clinical suspicion.

The inferior vena cava may have a thrombus or may be compressed by an enlarged caudate lobe.

Measurement of the portacaval venous pressure gradient (the portal-vein pressure minus the infrahepatic vena caval pressure) may be useful in determining the likelihood that portacaval shunting will be successful.

If possible, a transjugular liver biopsy of both the right and left lobes should be carried out at the time of the angiographic investigation to confirm the diagnosis and to help guide therapy, though the appropriateness of biopsy has not yet been established.

DiagnosisDiagnosis

Management Management

Medical Medical

Sodium restrictionSodium restriction

FurosemideFurosemide

SpironolactoneSpironolactone

ParacentesisParacentesis

Heparin /Warfarin INR 2.0-2.5Heparin /Warfarin INR 2.0-2.5

ManagementManagement

ManagementManagement

ManagementManagement

Local FactorsLocal Factors ThrombophiliaThrombophiliaInflammatoryInflammatory SurgicalSurgical InheritedInherited AcquiredAcquired

SepsisSepsis Liver Liver TransplantTransplant FVLFVL MalignancyMalignancy

PancreatitisPancreatitis SplenectomySplenectomyProthrombin Prothrombin

Mutation Mutation 20210G/A20210G/A

APL syndromeAPL syndrome

DiverticulitisDiverticulitis ColectomyColectomy Anti-Anti-thrombin IIIthrombin III Anti-cardiolipinAnti-cardiolipin

AppendicitisAppendicitisUmbilical Umbilical

Vein Vein CathetersCatheters

Protein C/S Protein C/S deficiencydeficiency

Elevated Elevated HomocysteineHomocysteine

Peptic Ulcer DzPeptic Ulcer Dz Portocaval Portocaval ShuntShunt OCPsOCPs

Blunt TraumaBlunt Trauma PregnancyPregnancy

IBDIBD

Etiologies of PVTEtiologies of PVTCirrhosis is most common - 10-30%

10-50% 40-60%

Etiologies of PVTEtiologies of PVT

PVT without liver PVT without liver disease is raredisease is rare Cirrhotics with PVT Cirrhotics with PVT

11%-27%11%-27% General PopulationGeneral Population

unknownunknown

Non-cirrhotic PVTNon-cirrhotic PVT Local FactorsLocal Factors

10-50%10-50% ThrombophiliaThrombophilia

40-60%40-60%

Local FactorsLocal Factors ThrombophiliaThrombophilia

InflammatoryInflammatory SurgicalSurgical InheritedInherited AcquiredAcquired

CirrhosisCirrhosis Liver Liver TransplantTransplant FVLFVL MalignancyMalignancy

SepsisSepsis SplenectomySplenectomy Prothrombin Prothrombin MutationMutation

APL APL syndromesyndrome

PancreatitisPancreatitis ColectomyColectomy Anti-Anti-thrombin IIIthrombin III

Anti-Anti-cardiolipincardiolipin

DiverticulitisDiverticulitisUmbilical Umbilical

Vein Vein CathetersCatheters

Protein C/S Protein C/S deficiencydeficiency

Elevated Elevated HomocysteineHomocysteine

AppendicitisAppendicitis Portocaval Portocaval ShuntShunt OCPsOCPs

PUDPUD PregnancyPregnancy

Blunt TraumaBlunt Trauma

IBDIBD

Consequences of PVTConsequences of PVT

Pain, nausea and vomiting, anorexiaPain, nausea and vomiting, anorexia

Bowel IschemiaBowel Ischemia From venous congestionFrom venous congestion

Hypersplenism traits: thrombocytopeniaHypersplenism traits: thrombocytopenia

Bleeding Esophageal VaricesBleeding Esophageal Varices Manifests in 30% of casesManifests in 30% of cases Lower morbidity and less rebleeding in non-Lower morbidity and less rebleeding in non-

cirrhotics*cirrhotics*

Consequences of PVTConsequences of PVT

Pain, nausea and vomiting, anorexiaPain, nausea and vomiting, anorexia

Bowel IschemiaBowel Ischemia From venous congestionFrom venous congestion

Hypersplenism traits: thrombocytopeniaHypersplenism traits: thrombocytopenia

Bleeding Esophageal Varices – 30% of casesBleeding Esophageal Varices – 30% of cases Lower frequency of rebleeding in non-cirrhotics (Condat)Lower frequency of rebleeding in non-cirrhotics (Condat) Vleggaar (1998) - Endoscopic VBL highly successfulVleggaar (1998) - Endoscopic VBL highly successful

95% 5 year survival rate95% 5 year survival rate No mortality related to recurrent bleedingNo mortality related to recurrent bleeding

Treatment of PVT and the Treatment of PVT and the Prothrombin mutationProthrombin mutation

Unclear and nonspecific in literatureUnclear and nonspecific in literature

In cirrhosis - traditional portal HTN treatment aloneIn cirrhosis - traditional portal HTN treatment alone Debate of anticoagulation use in non-cirrhotic PVTDebate of anticoagulation use in non-cirrhotic PVT - Condat and Sheen – 78-90% show resolution or- Condat and Sheen – 78-90% show resolution or recanalization of the thrombusrecanalization of the thrombus

Vague Recommendations with AnticoagulationVague Recommendations with Anticoagulation

Does the Prothrombin mutation warrant prophylactic Does the Prothrombin mutation warrant prophylactic anticoagulation?anticoagulation?

Other References:Other References:

www.uptodate.comwww.uptodate.com K.V. Narayanan Menon, M.D., Vijay Shah, M.D., and Patrick S.

Kamath, M.D. The Budd-Chiari Syndrome. N Engl J Med 2004;350:578-85.

Cheryl J. Davis, MD, internet case presentation & review: Cheryl J. Davis, MD, internet case presentation & review: November 27, 2007.November 27, 2007.

Portal Vein Thrombosis, An Unexpected Finding in a 28 Portal Vein Thrombosis, An Unexpected Finding in a 28 year old male with Abdominal Pain, internet case year old male with Abdominal Pain, internet case presentation & review; Jason Ferguson, DO CPT, MC, USA; presentation & review; Jason Ferguson, DO CPT, MC, USA; Tripler Army Medical Center; Honolulu, HawaiiTripler Army Medical Center; Honolulu, Hawaii