A case of thrombophilia complicated with Budd Chiari syndrome

1. Thrombus Everywhere
Usama Ragab Youssif (Msc.)
Assistant Lecturer of Medicine
(20, June, 2016)

2. Personal History
• 23-year old female, H.G.S, from Mashtool Al-
Souq, Single, 5th year student, no special
habits of medical importance.

3. Chief Complaint
• Generalized body swelling and diffuse
abdominal pain of 8 months duration

4. History of present illness
• Condition started 2 years ago with acute onset
of abdominal pain, that was diffuse, not
radiating, increase and decrease in intensity on
its own pace, it was associated with distension,
absolute constipation, projectile vomiting. She
was then admitted to hospital with a diagnosis
of intestinal obstruction that was managed
initially by conservative means with no surgical
interference. The obstruction was relieved and
she was discharged later on.

5. History of present illness (cont.)
• Few months later, she started to develops
intermittent attacks of diffuse abdominal
pain, not radiating, not related to meals,
increase with movement and coughing,
relieved with holding breath.
• She sought medical advice, and was told that
she suffer from FMF and received medical
treatment in the form of colchicine 0.5 mg
t.d.s

6. History of present illness (cont.)
• 8 months later, she noticed that symptoms
not improved, start to develop lower limb
edema up to knee, abdominal distension, so
she sought medical advice again, diagnosis
was revised. PAUS was done reveled ascites,
hepatomeglay, average spleen.

7. History of present illness (cont.)
• A sample from ascites was sent for analysis
and reveled exudative reaction.
Patient
295 cell/μLTotal cell count
81% LymphocytesDiffrential count
NegativeAdenosinedeaminase

8. History of present illness (cont.)
• Tuberculin intradermal test was done, proved
to be negative.

9. History of present illness (cont.)
• Other Lab was done reveled normocytic
normochromic anemia, thrombocytopenia,
hypoalbuminemia, normal renal function.
• During this time, she started to experience
hair fall, photosensitivity, joint pain, mouth
ulcers.
• ESR was ordered was 80 mm/1st h
• ANA and Anti DNA were ordered and were
both positive

10. ????????
• At this point, shall we offer her a reasonable
diagnosis: Is it lupus or not?
A- Yes
B- No

12. History of present illness (cont.)
• She was diagnosed as lupus, received medical
treatment in the form of steroids,
azathioprine. At the same time, urine
collection for protien quantification was
done, didn’t revel significant proteinuria that
could explain her symptoms (generalized
edema)

13. History of present illness (cont.)
• Work up was done searching for the cause of
anasarca, Echocardiography was arranged to
her, reveled: mitral valve prolapse, normal
left ventricular size and functions.

14. History of present illness (cont.)
• ANA and Anti DNA was repeated thrice, and
were negative titre. Anti Smith Ab and anti
Ro were ordered, proved to be negative.
NormalPatientTest
82-193 mg/dL72 mg/dLC3
10-40 mg/dL12 mg/dLC4
Up to 200 ng/dL993 ng/mLSerum Ferritn
Up to 5 mg/dL35.94 mg/dLCRP

15. History of present illness (cont.)
• The condition progress, abdominal pain
increased in intensity, ascites become tense,
lower limb edema, become associated with
visible veins on both lower limbs.
• PAUS was repeated, reveled hepatomegaly,
splenomegaly, marked ascites.

16. History of present illness (cont.)
• Doppler study of hepatic veins and IVC was
ordered and reveled, hepatic veins and IVC
thrombosis (Suggestg Budd Chiari Syndrome)
• Triphasic CT of abdomen and pelvis reveled
thrombosis of hepatic veins, IVC, bilateral
common iliac, external iliac, and common
femoral viens.

17. History of present illness (cont.)
• Thrombophilia was suspected, they start to
search for it;
NormalPatient
72-160 %93.6 %Protein C
+veLupus anticoagulant

18. ????????
• Are these enough data to diagnose APS:
A- Yes
B- No

20. Past History
• Drugs: -ve
• Operation: -ve
• Diseases: -ve

21. Family history
• Her sister was diagnosed with lupus 5 years
ago on steroids and azathioprine.
• No +ve consanguinity.

22. Examination
• Patient is mentally stable.
• Vital Signs:
• Blood Pressure: 130/80
• Pulse: 100, regular, equal on both sided, of average
volume
• Temperature: 37.0ᵒc
• Respiratory rate: 14
• Decubitus: slight orthopnea
• HEENT: normal

23. Examination (cont.)
• Extremities:
• Upper limbs: no clubbing, no pigmentations, no pallor,
normal muscles and nerves.
• Lower limbs: bilateral lower limb edema up to knees, no
pigmentation, visible veins on both lower limbs
• Back: no pigmentation, no swelling, no spine deformities.

24. Examination (cont.)
Abdomenal examination
Inspection: distended abdomen with full flanks
bilaterally, visible viens, wide subcostal angle, everted
umbilicus, stria rubra, normal hair distribution, no
pigmentation, no hernial orifices.
Palpation: no rigidity, no tenderness, organomegally
cannot be detected.
Percussion: fluid thrill.
Auscultation: normal intestinal sound, no bruit or
venous hum.

25. Examination (cont.)
Cardiac examination: Normal
Chest examination: there is decrease air entry bilater
ally, normal vesicular breathing, no additional sound.
Neurological examination: Normal

26. Salient features
23 years, 5th year college student, normotensive, nondiabetic,
nonsmoker, presented with continuous dull aching pain in upper
abdomen which is not associated with food intake. There is no
radiation of pain. She also noticed distension of her abdomen
which is gradually increasing. There is no fever, cough, chest pain,
hematemesis or melena. Her bowel habit is normal. There is no
past history of jaundice. There is no history of intravenous drug
abuse OCP use or blood transfusion. There is no history of similar
illness in her family.

27. Investigations
ControlPatient
4-117.7WBCs
11.5 – 15.510.3 NC/NCHB
150-450160Platelets
1.49INR
35-4544.3PTT
0.5 – 1.2mg/dL0.55 mg/dLCreatinine
6 – 20 mg/dL14.9 mg/dLBUN
135 – 145 mmol/L128 mmol/LNa
3.5 – 5.5 mmol/L2.82 mmol/LK
8.5 – 10mg/dL8.16 (9.4) mg/dLCa
2.7 – 4.5 mg/dL2.14 mg/dLPh
2.46/4.71 g/dLAlbumin/TP
Up to 33 U/L11.7/27 U/LALT/AST
Up to 1.1 mg/dL0.82/1.21 mg/dLBilirubin

28. Investigations (cont.)
20 mm/1st hESR
No proteinuria
Pus cells: 5 – 7/HPF
RBCs: 1 – 2/HPF
No casts.
Urinaysis
Non reactiveHepatitis
B and
Hepatitis
C virus

29. Consultation
Vascular surgery consultGastroenterology consult
1. No surgical
interference.
2. Commence
antiplatelets
1. Tapping
2. Upper GI endoscopy:
reveled no OV, PHG GII
3. Commence diuretics,
anticoagulant if not
started

30. Treatment
1. Corticosteroids and AZA (AZA was withheld and steroids is
withdrwan)
2. LMWH + warfarin.
3. ASA
4. Diuretics
5. Antihypertensive.
6. Blood glucose and BP monitoring.
7. Daily weighing the patient.

31. Look for the differential
A case of venous thrombosis
Rudolf Virchow

32. Look for the differential
A case of thrombophilia
AcquiredHereditary
Advanced age
Immobilization
Inflammation
Pregnancy
Oral contraception use
Obesity
Diabetes
Hormone replacement therapy
Cancer (especially adenocarcinoma)
Lupus anticoagulant
Sickle cell anemia and other hemolytic
anemias (especially PNH).
Factor V Leiden
Prothrombin 20210A
Protein C deficiency
Protein S deficiency
Antithrombin deficiency

33. Look for the differential
Prevalence of Acquired or Hereditary Hypercoagulable Disorders and
Risks of Venous Thrombosis
Relative Risk
of Recurrent
VTE (%)
Relative Risk
of VTE (%)
Prevalence in
General
Population
(%)
Condition
1.34.33 – 7Factor V
Leiden
1.41.91 – 3Prothrombin
20210A
2.511.30.02 – 0.05Protein C
deficiency
2.532.40.01 – 1Protein S
deficiency
2.517.50.02 – 0.04Antithrombin
deficiency

34. Antiphospholipid antibody syndrome
Look for the differential
Primary or secondary
Currently, however, the preferred terminology is APS with or without
associated rheumatic disease.

35. Antiphospholipid antibody syndrome (cont.)
Look for the differential

36. Look for the differential
Budd Chiari Syndrome
Goel RM et al.Postgrad Med J. 2015 Dec. 91 (1082):692-7.

37. Prevalence of Thrombotic Risk Factors in Series
of Routinely Investigated BCS patients
DeLeve, L. D., et al. Hepatology (2009), 49(5), 1729-1764.

38. Look for the differential
Prothrombotic workup newly diagnosed Budd-Chiari patient
Martens, P., & Nevens, F. (2015). Budd-Chiari syndrome. United European gastroenterology journal, 2050640615582293.
TestsHistory
•JAK2 mutation, if negative a bone marrow biopsy is
necessary
•Activated protein C resistance and if present a
diagnostic test for Factor V Leiden.
•Levels of protein C, protein S and antithrombin*
•Molecular test for prothrombin G20210A.
•Flow cytometry for CD55 and CD99
•Lupus anticoagulant, anti-b2-glycoprotein and
anticardiolipin* antibodies
•Homocysteine* levels
- (Testing based on indication, e.g. colonoscopy in
Crohn’s disease, ACE testing in sarcoı ¨dosis.)
•Oral contraceptive use
•Personal history of thrombosis
•Family history of thrombosis
•Signs and symptoms of
associated diseases

39. Look for the differential
Hepatic vein thrombosis
Marudanayagam R, Shanmugam V, Gunson B, et al. Aetiology and outcome of acute liver failure. HPB (Oxford). 2009. 11(5):429-
34.
PresentationSubtypes
Characterized by rapid development of abdominal
pain, ascites, hepatomegaly, jaundice, and renal
failure.
Acute and subacute forms
Most common presentation; patients present with
progressive ascites; jaundice is absent;
approximately 50% of patients also have renal
impairment
Chronic form
Uncommon presentation; fulminant or
subfulminant hepatic failure is present, along with
ascites, tender hepatomegaly, jaundice, and renal
failure.
Fulminant form

40. What about?
1. TIPSS as a mean of portal decompression
(standard TIPS versus transcaval TIPS).
2. Beta Blockers: primary prophylaxis against
variceal bleeding.
3. Anticoagulant duration.

44. An alarmingly high rate of heparininduced
thrombocytopenia (HIT) has been reported with
unfractionated heparin in BCS as compared to other
indications (12.3%, compared with 2.7%,
respectively)???
Martens, P., & Nevens, F. (2015). Budd-Chiari syndrome. United European gastroenterology journal, 2050640615582293.
Take care