1 DEPARTMENT OF NEPHROLOGY, GENERAL HOSPITAL OF PELLA, EDESSA, GREECE2 DEPARTMENT OF GENERAL PRACTICE & FAMILY MEDICINE, GENERAL HOSPITAL OF PELLA, EDESSA,

GREECE3 MEDICAL SCHOOL, ARISTOTLE UNIVERSITY OF THESSALONIKI, THESSALONIKI, GREECE4 DEPARTMENT OF INTERNAL MEDICINE, GENERAL HOSPITAL OF PELLA, EDESSA, GREECE

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

SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA DUE TO TIGECYCLINE ADMINISTRATION.

IL 6

INFLAMMATION

IL 1, TNF fibrinogen

Liver

ESRD chronic subclinical Inflammation higher fibrinogen levels normal levels of fibrinogen = hypofibrinogenemia

(close to the lower limits)

microRNA ?

SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA DUE TO TIGECYCLINE ADMINISTRATION.

REDUCED FIBRINOGEN LEVELS

AfibrinogenemiaDysfibrinogenemia

Hypodysfibrinogenemia

Hepatic dysfunctionSevere malnutrition

DICAbnormal

fibrinolysisLarge volume

blood transfusionDrugs

Valproic acidSynthetic ACTH

PrednisoloneL-asparginase

AllopurinolTigecycline

acute

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

Day PLT(X103/μL)

PT(sec)

aPTT(sec) INR

FIBRINOGEN (mg/dl)

AST (IU/L)

ALT(IU/L)

TBILL(mg/dL)

CRP(mg/dL)

1 172 13,6 25,6 1,21 499 9 6 0,399 13,85 94 24,7 24,2 1,37 434 9 6 0,397 9,6

1090 >2min 64 6,33 297 12 13 2,221 8,4

15 76 21,3 58,5 1,92 199 31 25 3,122 5,719 50 18,8 57 1,71 42 47 31 8,335 3,2

21 53 15,1 39 1,35 152 68 50 4,342 2,922 70 13,9 41,4 1,24 188 113 78 3,94 2,724 90 14,4 37,1 1,29 313 90 75 3,14 2,929 187 13,9 27,8 1,24 475 50 108 1,645 1,933 186 12,9 36,6 1,15 498 20 44 1,524 0,75

SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA DUE TO TIGECYCLINE ADMINISTRATION.

TigecyclineInterruption

abdominal pain nausea headache

ecchymosisthormbocytopenia

coagulation disorders

hypofibrinogenemia

increase of billirubin

abdominal u/s: normal

LMWH interruption

FFP transfusions

abdominal u/s & CT: normal

ReducedCRPLevels

PRCL (-)

Blood & UrineCultures

negative

SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA DUE TO TIGECYCLINE ADMINISTRATION.

Tigecycline (GAR-936) : tetracycline active against gram (+) and (-) microbes, anaerobic organisms

TARGET: protein synthesisblocking 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 infectionscommunity-acquired bacterial pneumonia.

discoloring dentition teratogenicity ,

hypofibrinogenemia

increase of ALP, T Bill, PT, INR,thrombocytopenia, pancreatitis

nausea, vomiting, diarrheaabdominal pain,

headache increased SGPT

ADVERSE EVENTS

Pharmacokinetics

•poor pos bioavailability •IV administration •Hepatic Metabolism

No dosage adjustment in patients with ESRD

undergoing haemodialysis

SEVERE, LIFE-THREATENING HYPOFIBRINOGENEMIA DUE TO TIGECYCLINE ADMINISTRATION.

Tigecycline Induced Hypofibrinogenemia - cases1. advanced liver cirrhosis 2. ESRD + prolonged tigecycline therapy 3. 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)

antibiotics

Reduced enteric micro-flora

Coagulation disorders

Vit K

Proposed Mechanisms Of Action