Antithrombotic anticoagulants Updated resume for treatment

2. Marwa Mahmoud Khalifa
Faculty Of Medicine
Alexandria University
ANTITHROMBOTIC
AGENTS

3. Antithrombotic agents
Heparins
Direct
thrombin
inhibitors
Vitamin K
antagonists
Non vitamin K
oral
anticoagulants

4. HEPARINS
FondaparinuxLMWH ( dalteprin, enoxaprin
&tinzaparin)
Unfractionated heparin
Synthetic pentasaccharideManufactured by
enzymatically or controlled
depolymerization
Naturally occurring GAGs
extracted from porcine
intestine.
MW 3000-5000MW 15,000
SCSCIVI/ SC
T ½ 17 hT ½ 3-5 hT ½ 45-60 min
No monitoringMonitored APTT
According to typeBolus 80 IU/kg/h
Then 18 IU/kg/h
Protamine but less effectiveAntidote : protamine
No HITSE : same but less commonSE : hyperkalemia, HIT&
osteoprosis

5. HEPARINS
•Mechanism of action
Specific pentasaccharide sequence binds with
high affinity to antithrombin, produces
conformational changes that releases reactive
centre loop potentiating its activity
Inhibition FXa

6. HEPARINS
•Danaparoid
Hepainoid
Used with HIT
Indirectly inhibit FXa, thrombin
No effect on PT / APTT

7. Direct thrombin inhibitors
ArgatrobanBivalirudin
Metabolized by liver (cytochrome P450)Metabolized 80% proteolysis
20% by kidney
T ½ 50 minT ½ 25 min
Indication : HIT , renal impairmentIndication : ACS undergoing PCI
Continuous IVIContinuous IVI
Monitored by APTTMonitored by APTT

8. Vitamin K antagonists
• Vit K is needed for post translational modification of vit K
dependent factors (II, VII, IX, X, protein C & S)
• Vit K antagonists : warfain, acenocoumarol, phenindione, fluindione
& phenprocoumon.
• Affected by diet
• Many drug drug interactions
• Monitored by INR.
• Target INR for DVT, PE, stroke prevention in AF (2-3)
• Higher target for mechanical heart valves
• Take days to be effective, heparin is given initially.
• SE : skin necrosis, purple toe syndrome, rash hair loss and hepatitis
• Teratogenic

9. Vitamin K antagonists
If anticoagulant has to be stopped for surgery or invasive procedure
1. should be stopped 5 days before
2. BRIDGING therapy with short acting anticoagulant (LMWH)
3. Can be resumed the evening of surgery or next day
Emergency anticoagulation reversal
A. major bleeding
1. 25-50 U/kg four factor prothrombin complex concentrate
2. 5 mg IV vit K
B. Non major bleeding : 1-3 mg IV vit K
C. INR >8 , no bleeding : 1-5 mg oral vit K

10. • Bridging therapy :
1. Last episode VTE within previous 3 months
2. AF with previous stroke / TIA / multiple risk factors
3. Mitral MHV / non bileaflet aortic MHV/ bileaflet aortic MHV with
other risk factors

11. Warfarin dosing algorithm
Day 4Day 3Days 1 & 2
Dose ( mg)INRDose ( mg)INRGive 5 mg each day if
baseline INR <1.3
10<1.610<1.5
71.6-1.751.5-2
61.8-1.932.1-2.5
52-2.312.6-3
42.4-2.70>3
32.8-3
23.1-3.5
13.6-4
0>4

12. Non vit K antagonist oral anticoagulants
• Predictable dose resposes
• No need for routine monitoring
• No food interactions
• Limited drug interactions
• Fixed dose
• Rapid onset & short T ½
• Not ass with HIT
• Kidney excreted with variable degrees

13. EdoxabanApixabanRivaroxabanDabigatran
Inhibit FXaInhibit FXaInhibit FXaInhibit IIaTarget
9-11h10-14h7-13h12-17 hT1/2
60 mg od5 mg bd20 mg od150 mg bdDose AF
60 mg od10 mg bd for 7 d
then 5 mg bd
15 mg bd for 3 w
then 20 mg od
150 mg bdDose VTE
YesNoNoYesLMWH for
initial
treatment
35%25%33%80%Renal
excretion
LowHighHighlowProtein
binding

14. Time of stopping NOACs before elective surgery
Minor surgeryMajor surgery
2448Dabigatran
2448Rivaroxaban
2448Apixaban
2448Edoxaban

15. Management of bleeding with NOACS
1. The anticoagulant activity should be determined by most
appropriate lab assay ( calibrated anti Xa , dilute plasma thrombin
time )
2. Bleeding not severe : stop drug and detemine cause of bleeding
3. Severe bleeeding :
• Mechanical compression
• Surgical haemostasis
• Correction of additional coagulopathy
• FFP doesn’t reverse the effect