6. 3 שנים טרם הדימום
אישפוז עקב כאבי בטן ב LUQומותן שמאלי
החמרה בטרומבוציטופניה ובהמוליזה
CT SCANבטן
7.
8. לסיכום
Bleeding from gastric varices
Past history
Splenic and portal vein thrombosis
Coombs negative hemolytic anemia
Thrombocytopenia
Acute inferior wall MI
Aplastic anemia
11. Paroxysmal nocturnal
hemoglobinuria (PNH)
Prevalence 1 per 106
Men and women are affected equally
Average age at time of diagnosis 42 years
Diagnosis delayed on average by 3 years
13. Diagnosis
Flow cytometry - method of choice
Highly sensitive and specific
Best method for assessing clone size
Not affected by blood transfusions / lysis
Ham test, Sucrose lysis test
15. Thrombosis in PNH
40%-50% of patients
Leading cause of mortality
Usually involve the venous system
Arterial thrombosis is also increased
Related to the clone size
17. GI involvement in PNH
Recurrent bouts of abdominal pain
Cholelithiasis – bilirubin stones
Dysphagia
Secondary sclerosing cholangitis
18. Tendency to Bleed Thrombophilia
• Thrombopenia • Portal vein thrombosis
• Bleeding varices • Portal hypertension
To anticoagulate or not to anticoagulate?
19.
20. Treatment of thrombosis
Primary prophylactic anticoagulation –
never proven to prevent thrombosis
Acute thrombosis
Indication for heparin
Sometimes thrombolytic therapy
(in acute Budd-Chiari syndrome)
Williams Hematology, 8th Marshall A. Lichtman 2008
21. Treatment of thrombosis
Thrombocytopenia complicates treatment
Relative contraindication
Transfusions of platelets to a safe range
Patients with thrombosis should be
anticoagulated indefinitely
Williams Hematology, 8th Marshall A. Lichtman 2008
22. Historical management of
PNH – supportive treatment
Red cell transfusions
Iron supplementation
Folic acid supplementation
Steroids - limited efficacy, high toxicity
Bone marrow transplantation
23. Prognosis
Survival 50% at 15 years after diagnosis
15% - pancytopenia - aplastic anemia
1% - 5 % develop AML
Myelodysplastic syndrome
24.
25. SOLIRIS (eculizumab) Humanized
First in Class Anti - C5 Antibody
Human Framework Regions
C
H1
Hinge
CL
Complementarity Determining Regions
(murine origin)
CH2
Human IgG4 Heavy Chain
Human IgG2 Heavy Chain
Constant Regions 2 and 3
Constant Region 1 and Hinge
CH3
26. Lectin Pathway Classical Pathway Alternative Pathway
Carbohydrate Structures On -Antibodies Bound To Antigen -Microbial Membranes
Pathogens / Damaged Host Cells -Immune Complexes -Bacterial LPS
MBL, MASP-1, MASP-2 C1q, C1r, C1s C3
C4 + C2 C4 + C2 Factor B + D
C3 convertases
C4b2a, C3bBb
C3 C3a -Weak Anaphylatoxin
-Immune Complex And
Apoptotic Body Clearance C3b
-Microbial Opsonization
C5 convertases
C4b2a3b, C3bBb3b
-Potent Anaphylatoxin
Target of Eculizumab C5a -Leukocyte
C5 X Chemotaxis
C6,C7,C8,C9 -Cell Activation
C5b-9
-Cell Activation
-Cell Lysis
27. Eculizumab
Highly effective in reducing hemolysis
Decreases or eliminates need for
blood transfusions
Improves fatigue and quality of life
Reduces the risk of thrombosis
28. Reduction in thrombotic events
Principal Investigator: There were fewer thrombotic
events with eculizumab treatment than during the
Thrombotic events (n)
same period prior to treatment
Pre-eculizumab treatment Eculizumab treatment
1
Hillmen P et al. Blood 2007; 110: 4123-4128; 2Brodsky RA et al. Blood 2008; 111: 1840-1847;
29. בחזרה לחולה...
לאחר הדימום לא חודש הטיפול בקומדין
תרומבוציטופניה סביב -0002, 0 ללא דימומים
מתן דם כל 6-5 שבועות בגלל המוליזה
ב- 0102 הותחל טיפול ב - Eculizumab
מספר שבועות לאחר מכן, ירידת , LDHהפחתה
בעירויי דם ושיפור משמעותי באיכות החיים
30. לסיכום
חולה עם יל"ד פורטלי על רקע PNH
דילמה של טיפול בנוגדי קרישה בחולה עם
דימום, טרומבופיליה ותרומבוציטופניה
טיפול חדש ב- Eculizumabויתרונותיו
