Deep Venous Thrombosis

(DVT) & Anticoagulation

in Orthopaedics
By
Ihab El-Desouky (M.D.)
Ass. Prof. Orthopaedics & Traumatology
Pelvis and Joints Reconstruction Unit
Kasr Al-Ainy School of Medicine
Cairo University
2017
 DVT & Anticoagulation in Orthopedics

Why : Prophylaxis against Deep Venous thrombosis

To avoid fatal Pulmonary Embolism (PE)

Without prophylaxis:--- Deep venous thrombosis (DVT)

Historic fatal PE
1- 2%
Current fatal PE
0.1-0.2%
 DVT & Anticoagulation in Orthopedics

Pathogenesis for Deep Venous Thrombosis (DVT)

Rudolf Virchow Germany (1821-1902): HIS triad

All these---- activation of coagulation mechanism +

formation of blood clot+ propagation of the clot.
 DVT & Anticoagulation in Orthopedics

Thrombotic Stimuli During Total Hip and Knee

Arthroplasty:
Venous Stasis: Tourniquet placement + immobility during
the postoperative period
Tissue Injury: Manipulation during preparation of the
femoral prosthesis releases tissue thrombo-plastin
and other thrombogenic molecules
Hypercoagulability: Thrombogenic stimuli + reduction in
antithrombin III and fibrinolysins due to blood loss by
bleeding.
DVT & Anticoagulation in Orthopedics

Risk Factors:
Primary Hypercoagulopathies
(inherited)
Gene Mutation
Factor V Leiden Mutation
Antithrombin III Deficiency
Protein C Deficiency
Protein S Deficiency
Activated Protein C Resistance
 DVT & Anticoagulation in Orthopedics
Secondary factors (acquired)
Malignancy
Elevated Hormone Conditions
Hormone Replacement .Oral Contraceptive therapy &Late Pregnancy
Elevated Antiphospholipid Antibody Conditions
Lupus
History Of Thromboembolism
Major surgery with tourniquet
Obesity
Aging
CHF
Varicose Veins
Smoking
General Anesthetics (Vs. Epidural And Spinal)
Immobilization
DVT & Anticoagulation in Orthopedics
Diagnosis: PE
DVT Symptoms:
Leg swelling/erythema Dyspnoea
Leg pain Tachypnea
Superficial venous Tachycardia
congestion Pleuritic chest
Homans sign? pain
-ECG:
-Blood gases: PO2
DVT & Anticoagulation in Orthopedics
DVT: Imaging PE: Imaging
venography is gold Chest X-ray
standard (direct imaging) Nuclear medicine
Non-invasive ventilation-perfusion scan
Venous Duplex Ultrasound (V/Q)
is 96% sensitive, 98% Pulmonary angiography
specific
is gold standard
Helical chest CT
plethysmography is 75% widely considered first line
sensitive, 90% specific imaging modality
CT is 90% sensitive, 95%
specific
 DVT & Anticoagulation in Orthopedics
DVT: management PE: management
Prophylaxis: ANTI-COAGULATION ICU admission:
Treatment: O2
In-bedding for 10 days continuous IV heparin
LMWH /12 h (5 ds with 3 days infusion followed by
overlap) followed by long warfarin therapy
term Warfarin ( 3 months ) continuous IV heparin
infusion (7-10 days )+warfarin
therapy typically given for 3
Vena cava filter placement months
indications Thrombolytics; streptokinase
when anticoagulation is in specific cases
contraindicated (hypotensive )
Pulmonary embolectomy
Recurrent DVT despite
adequate anticoagulation
 Anticoagulation in Orthopedics
Clot formation:
(Intrinsic pathway by damage of B.V. endothelium ).
( Extrinsic pathway by tissue traumathrombo-plastin)

+ protein C &S
(Extrinsic pathway)

Antithrombin III (AT) : is a small protein by liver inactivates several factors

thrombin (IIa) + IXa+ Xa
 Anticoagulation in Orthopedics
How to prevent DVT:
1- Lower hypercoagulability: by anticoagulant & blood
loss.

2-Minimize tissue injury: shorter operation time & bone

and soft tissue manipulation.

3-Prevent stasis: mechanical measures &mobilization of

the limb and patient.
 Anticoagulation in Orthopedics
Anticoagulation (AC)methods:
1-Mechanical (non-pharmacological) measures:
- Graduated Compression (elastic) Stockings (GCS).
- Intermittent Pneumatic Compression (IPC) devices.
- Venous Foot Pumps (VFP) + combined (IPC+VFP)

Action:IPC venous stasis- blood flow velocity+ circulating fibrinolysins.

Advantage: no monitoring, no bleeding risk, tolerated.
Disadvantage: patient dependant + not effective alone
Not in ischemia or neuropathy

Stratification: ( which Risk Group?)

Combined in high and highest risk groups.
Alone in high risk of bleeding (AC over-dose, hepatic, haemophilia)
 Anticoagulation in Orthopedics
2-Pharmacological anticoagulants: (affect coagulation factors)
The evolution of anticoagulant therapy
Parenteral Oral
-Heparins -VKA
(UFH, LMWH)
-Thrombin -Thrombin
inhibitors inhibitors
(Hirudin, (Dabigatran)
Bivalirudin)
- Factor Xa -Factor Xa
inhibitor inhibitors
Fondaparinux (Rivaroxaban,
Apixaban,
Edoxaban)

UFH: unfractionated heparin; LMWH: low molecular weight heparin; VKA: vitamin K
antagonists
 Anticoagulation in Orthopedics(Parenteral)
1-Heparin: (father of parenteral AC)
History: 1916;McLean , USA,
started discovery from canine liver.
April 1937 (Unfractionated Heparin) UFH: 1st
safe injection in human.
Late 1980s: Low Molecular Weight heparin
(LMWH) derived from heparin.
Action: activates AT III
inhibits thrombin and Xa (equally).
(flooding of anticoagulation--- requires monitoring)

LMWH: short chains---mainly Xa+ thrombin

 Anticoagulation in Orthopedics(Parenteral)
Advantages: UFH : anticoagulant & antithrombotic DVT by 60-75%
Disadvantages: of UFH
1- Bleeding with increased dose ( not suitable for high risk )

2-Heparin Induced Thrombocytopenia (HIT): 2-4% , antibody induced--- Thrombosis

(gangrene) and DIC. !!!! (HIT& Thrombosis)-ttt Hirudin analogue. (no platelet)

3- OSteoporosis: & spontaneous fracture (prolonged use, vertebrae, pregnant).

4- Monitoring & dose adjustment.
Route of administration: 5000 U /S.C (I.V.)/ 8 hours.

Monitoring: APTT N= 25-35 sec warning levels above 75 sec

Antidote: Bleeding: protamine sulphate (Protam): 1mg for 100 units slow IV /10 min
HIT&T: Bivalirudin (Angiomax)
Stratification: moderate risk group only (higher dose for high risk---complications)
Not recommended by AAOS
 Anticoagulation in Orthopedics(Parenteral)
2-Low Molecular Weight Heparin (LMWH):
Family : Enoxaprin (Clexane), Nadroparin (Fraxiparine)
By depolymerization of UFH --- reduce chain length .
Advantages:
-Specific inhibition of AT III on Xa mainly (+ thrombin less ).
-No prolonged APTT- no monitoring
-Better bio-avaibility and t -- can given once.
-Renal & liver metabolism.
But: retroperitoneal hematoma + surgical site haemorrhage (1.7%)
(If given too early after operation before 1st clot)
Antidote: protamine sulphate or factor VII (r-VIIa)
Route of administration: Enoxaparin 40 mg/ once S.C. ( start 12-24h post-
operative
Stratification: moderate, high & highest risk groups with dose
adjustment (according to B.W.)

Duration: up to 35 days.
 Anticoagulation in Orthopedics(Parenteral)
3-Fondaparinux : (Arixtra 2.5 & 7.5mg) ( Year: 2002)
synthetic penta-saccharide similar to LMWH.
Inhibits AT III for Xa selectively.
(indirect Xa Inhibitior)
So:
-More powerful than enoxaparine.
-Longer t ( up to 20 h)- once daily -No monitoring
BUT:
- Episodes of Major bleeding (2.7% vs 1.7%)+ no antidote ( ?? R
FVIIa)
-Renal metabolism only: so creatinine clearance (CrCl) should be >
30 ml/min.
Route of administration: 2.5 mg once S.C.
Stratification: high and highest- risk groups. Duration: 35 d.
 Anticoagulation in Orthopedics(Parenteral)
4-Direct Thrombin Inhibitors:
1-Hirudin: extract of blood-sucking leeches(Hirudo medicinalis)
-Binds to thrombin directly --- inactivation.

-Recombinant hirudin (Thrombexx)

for S.C injection:15mg/ 12h/ max 12 d
-Renal excretion (not in renal ptn) + hypersensitivity.
-Bleeding episodes- no antidote.
No specific risk stratification by AAOS or ACCP.
2-Bivalirudin: (Angiomax) synthetic analogue
-with shorter half-life, less renal metabolism,
-and low immunogenicity
-IV for treating HIT+T
 Anticoagulation in Orthopedics(Oral)
1-Warfarin: (the father of oral AC):
History: Great Depression in USA 1929:
Farmers fed cattle & sheep by
mouldy sweet clover hay bleeding and death.(sweet clover
disease)
In 1933 : research started in Wisconsin University, USA.
In late 1940s: was promoted as rodenticide
but research continued
In 1955 :USA president Eisenhower suffered MI ----
given Warfarin---started commercial promotion.
Action: Vitamin K- Antagonist (VKA) :
Inhibits Vit K reduction no formation of Vit K
dependant factors (II, VII, IX & X + protein C&S.)
 Anticoagulation in Orthopedics (Oral)
1-Warfarin: (the father of oral AC):
Disadvantages : Slow action -Multiple interactions & Side effects.
-3 days to reach target ( target INR= 2.5)
-Numerous drug interaction strict monitoring ( about 800 drugs
including aspirin, diuretics, rifampicin , ------).
-Food interactions: e.g.: food rich in Vit K ( spinach) + alcohol.
-Genetic variation : (two types); so affect response.
- Side effects: Haemorrhage ( 3-5 %) and Many others.

However: reduces total DVT by 60-70% and Oral.

 Anticoagulation in Orthopedics (Oral)
1-Warfarin: (the father of oral AC):
Monitoring: Prothrombin time (PT) + International Normalized Ratio --
INR=(PT patient/PT normal)ISI ratio(without unit) to allow comparison
from lab. to another
-N= 0.8-1.2 Target= 2-3 (2.5)
Antidote: Vit. K : IV slow action (3 days for reversal),
Fresh Frozen Plasma: immediate action
Route of administration: oral 5 mg night before surgery---3 days---
INR--- adjust dose 2-10 mg once oral
Stratification: highest risk groups.( dose adjustment and many
interactions)
Duration: up to 35 d.
 Anticoagulation in Orthopedics (Oral)
2- NOVEL ORAL Anti-Coagulants : (NOACs):
No frequent monitoring- less inter and intra-patient variability.
1- Direct Thrombin inhibitor: Dabigatran (Pradaxa) (year 2010)
Action: inhibit thrombin action directly (IIa).
T : 16 h.
Metabolism: 80 % renal ( +liver) so not in Renal ptn
Efficacy: similar to enoxaparin.
Disadvantage: GIT upsets, bleeding (similar to enoxaparin 1.7%) and
Not in renal patient ( not if CrCl < 30ml/min .
Monitoring: no
Antidote: Idarucizumab (Praxbind)(2015)
Route of Administration: Oral : dose (110mg) 4h post-operative
then 220mg (two cap) once daily ( lower dose if CrCl 30 -60ml/min).
 Anticoagulation in Orthopedics
Risk Stratification: high and highest risk groups
Duration: up to 35 days ( TKR --- 2 weeks)
(THR--- 5 weeks)
 Anticoagulation in Orthopedics (Oral)
2- Direct factor Xa inhibitors:
1-Rivaroxaban (Year 2011)(Xarelto , Andorivaban, Vaxato)

2-Apixaban (Year 2012) (Eliquis)

Mechanism: direct Xa inhibitor
Metabolism: Rivaroxaban 1/3 by renal
Apixaban by renal
Disadvantage: bleeding ( Rivaroxaban similar to enoxaparin, Apixaban less).
Antidote :no current antidote (Prothrombin Complex Concentrates (PCCs),
trilas
 Anticoagulation in Orthopedics (Oral)
Route of administration: Oral Rivaroxaban 10 mg / once. 8 h post-
operative.
Apixaban: 2.5 mg / twice . 12 h post-operative
Risk Stratification: High and highest risk groups.
Duration: up to 35 days ( TKeeR --- 2 weeks) (THipR--- 5 weeks)
The evolution of anticoagulant therapy.
Year Anticoagulant drug
1940s Unfractionated heparin
1950s Warfarin
1980s Low molecular weight heparins
1990s Parenteral thrombin inh(Hirudin)
2002 Fondaparinux
2010 Dabigatran
2011 Rivaroxaban
2012 Apixaban
2014 Edoxaban
 Anticoagulation in Orthopedics

When to start Anticoagulation:

Wait till primary haemostasis (surgical site) developed
then start AC;
 Anticoagulation in Orthopedics
Risk Stratifications:
-Inclusion of the patient in a specific risk group that identifies the AC method and for
how long.
-Guidelines of AAOS (American academy of Orthopaedic surgeons) 2008 & ACCP
(American College of Chest Physicians) 2012.
-Scoring system:
 Anticoagulation in Orthopedics
Risk Stratifications:
Risk Factor Score 0-1 2 3-4 5+
DVT Incidence 2% 10-20% 20-40% 40-80%
RISK LEVEL LOW MODERATE HIGH HIGHEST
 Anticoagulation in Orthopedics
DVT prophylaxis according Risk Stratifications: (AAOS)
Low Risk: (e.g.: knee arthroscopy)
No, early ambulation,
only if other risk (previous DVT) LMWH .
Moderate Risk( e.g. distal LL fractures as tibia).
No, early ambulation,
only if other risk (as previous DVT) LMWH & IPC.
High Risk( major trauma e.g. long bone femur, multiple trauma &
spine).
LMWH 12 h after operation ( 40 mg once daily) &IPC.
Other ACs as highest risk group (no VKA).
Bleeding risk: IPC & VFoot Pump then switch to LMWH
 Anticoagulation in Orthopedics
DVT prophylaxis according Risk Stratifications:
4-Highest risk: (THR, TKR, HFS, Pelvic fracture, spine fracture with
paralysis)
1-LMWH: 40mg once, 12 h post-operative. S.C. OR
2-Fondaparinux: 2.5mg once 8h post-operative.(not in renal) S.C.
OR
3-VKA (warfarin): adjusted- dose, pre-operatively , 2-10 mg once
oral target INR 2.5. OR
4-Direct oral Thrombin Inhibitor: Dabigatran: dose (110) 4 h post-
operative then 220 once oral ( not in renal). OR
5-Direct oral Xa inhibitors: Rivaroxaban: 10mg once / 8 h post-
operative OR Apixaban: 2.5mg twice/ 12 h post-
operative.
IPC / GSC can be used.
 Anticoagulation in Orthopedics
Duration of DVT prophylaxis:
THR: 35 days (5 weeks) TKR 14 days (2 weeks)
Rest of groups : 14 d
If trauma patients + delayed surgery : start pre-operative
anticoagulation stop night of surgery continue 12 h post-op.)
Inferior Vena Caval Filter.
-Not recommended as
primary DVT prophylaxis.
-In complex fractures (pelvis) to prevent PE if:
1-Contraindication to AC OR
2-Emergency situations that needs surgery with possible DVT presence.
- Retrievable (removable) filters then continue AC.
Anti-platelets: (e.g. Aspirin):
Not recommended alone by AAOS for thrombo-prophylaxis.
 Take Home Message
-Anticoagulation prophylaxis after orthopaedic surgery is of
utmost importance to prevent Fatal PE.

-Historic Fatal PE was 1-2 % and current PE is 0.1-0.2 %.

-Evolution of AC therapy is a continuous process to take

more benefits with less complications and a wide range.

-Appropriate drug, timing and duration of AC should be

considered for each case according to the Risk Stratification.

-LMWHs are appropriate for All risk groups while antiplatelet and
UFH are Not recommended.
Thank you.