1. SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA
DUE TO TIGECYCLINE ADMINISTRATION. CASE REPORT AND LITERATURE REVIEW
1 N. Sabanis, 2 E. Paschou, 3 E. Gavriilaki, 4 A. Pavlis, 3 A. Kalaitzoglou, 1 S. Vasileiou
1 Department of Nephrology, General Hospital of Pella, Edessa, Greece 2 Department of General Practice & Family Medicine, General Hospital of Pella, Edessa, Greece 3 Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece 4 Department of Internal Medicine, General Hospital of Pella, Edessa, Greece

2. IL 6 INFLAMMATION IL 1, TNF Liver fibrinogen
SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA DUE TO TIGECYCLINE ADMINISTRATION.
IL 6
INFLAMMATION
microRNA ?
Liver
IL 1, TNF
fibrinogen
ESRD  chronic subclinical Inflammation  higher fibrinogen levels
normal levels of fibrinogen = hypofibrinogenemia
(close to the lower limits)

3. REDUCED FIBRINOGEN LEVELS Hypodysfibrinogenemia Abnormal fibrinolysis
SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA DUE TO TIGECYCLINE ADMINISTRATION.
REDUCED FIBRINOGEN LEVELS
acute
Afibrinogenemia
Dysfibrinogenemia
Hypodysfibrinogenemia
Hepatic dysfunction
Severe malnutrition
DIC
Abnormal fibrinolysis
Large volume
blood transfusion
Drugs
Valproic acid
Synthetic ACTH
Prednisolone
L-asparginase
Allopurinol
Tigecycline

4. trauma infection after hip replacement surgery
SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA DUE TO TIGECYCLINE ADMINISTRATION.
74-year-old female (Medical History: ESRD undergoing periodic haemodialysis)
trauma infection after hip replacement surgery
WBC 13,7 G/l, CRP 13,8 mg/dl
trauma tissue cultures: multidrug-resistant A. baumannii
Treatment:
antibiotic monotherapy with tigecycline
loading dose of 100mg following by 50mg every 12 hours

5. abdominal u/s & CT: normal
SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA DUE TO TIGECYCLINE ADMINISTRATION.
abdominal pain
nausea
headache
ecchymosis
thormbocytopenia
coagulation disorders
hypofibrinogenemia
increase of dir. billirubin
abdominal u/s: normal
LMWH interruption
FFP transfusions
Reduced
CRP
Levels
PRCL (-)
abdominal u/s & CT: normal
Day
PLT
(X103/μL) PT
(sec)
aPTT
INR
FIBRINOGEN (mg/dl)
AST (IU/L)
ALT
(IU/L)
TBILL
(mg/dL)
CRP 1
172
13,6
25,6
1,21
499 9 6
0,399
13,8 5 94
24,7
24,2
1,37
434
0,397
9,6 10 90
>2min 64
6,33
297 12 13
2,221
8,4 15 76
21,3
58,5
1,92
199 31 25
3,122
5,7 19 50
18,8 57
1,71 42 47
8,335
3,2 21 53
15,1 39
1,35
152 68
4,342
2,9 22 70
13,9
41,4
1,24
188
113 78
3,94
2,7 24
14,4
37,1
1,29
313 75
3,14 29
187
27,8
475
108
1,645
1,9 33
186
12,9
36,6
1,15
498 20 44
1,524
0,75
Tigecycline
Interruption
Blood & Urine
Cultures negative

6. poor pos bioavailability IV administration Hepatic Metabolism
SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA DUE TO TIGECYCLINE ADMINISTRATION.
Tigecycline (GAR-936) : tetracycline
active against gram (+) and (-) microbes, anaerobic organisms
TARGET: protein synthesis
blocking entry of amino-acyl transfer RNA molecules into the A site of the 30s ribosomal subunit
complicated skin and skin structure infections
complicated intra-abdominal infections
community-acquired bacterial pneumonia.
Pharmacokinetics
ADVERSE EVENTS
discoloring dentition teratogenicity ,
hypofibrinogenemia
increase of ALP, T Bill, PT, INR,
thrombocytopenia, pancreatitis
nausea, vomiting, diarrhea
abdominal pain,
headache
increased SGPT
poor pos bioavailability
IV administration
Hepatic Metabolism
No dosage adjustment in patients with ESRD undergoing haemodialysis

7. Proposed Mechanisms Of Action
SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA DUE TO TIGECYCLINE ADMINISTRATION.
Tigecycline Induced Hypofibrinogenemia - cases
advanced liver cirrhosis
ESRD + prolonged tigecycline therapy
GREECE: series of 145 IUC patients on tigecycline decribe that high dosages of the drug lead to hypofibrinogenemia due to coagulation disturbances (Routsi et al, 2014)
Proposed Mechanisms Of Action
antibiotics
Reduced enteric
micro-flora
Coagulation disorders
Vit K