Dvt.warda [compatibility mode]

‫ﷲ‬‫ﷲ‬‫ﷲ‬‫ﷲ‬‫ﷲ‬‫ﷲ‬‫ﷲ‬‫ﷲ‬
‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬
Osama Warda,MDOsama Warda,MD
‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬‫ا‬

Deep Vein Thrombosis ( DVT )Deep Vein Thrombosis ( DVT )
in Pregnancyin Pregnancy
(((((((( AN OVERVIEW OF THE LITERATURE )AN OVERVIEW OF THE LITERATURE )
ByBy
OSAMA M.WARDA, MDOSAMA M.WARDA, MDOSAMA M.WARDA, MDOSAMA M.WARDA, MDOSAMA M.WARDA, MDOSAMA M.WARDA, MDOSAMA M.WARDA, MDOSAMA M.WARDA, MD
Obstetrics and Gynecology Dept.Obstetrics and Gynecology Dept.
Faculty of MedicineFaculty of Medicine--Mansoura UniversityMansoura University

EpidemiologyEpidemiology
DVT of the lower limbs during pregnancy occurs inDVT of the lower limbs during pregnancy occurs in
00..1313 toto 00..6161 per thousand pregnancyper thousand pregnancy..
Despite its relatively low incidence, DVT may leadDespite its relatively low incidence, DVT may lead
to pulmonary embolism; the most common cause ofto pulmonary embolism; the most common cause of
maternal death in developed countries.maternal death in developed countries.
maternal death in developed countries.maternal death in developed countries.
DVT occurs with relatively equal frequency in allDVT occurs with relatively equal frequency in all
trimesterstrimesters.. However, in the past it was mostHowever, in the past it was most
common in the postcommon in the post--partum period due to medicalpartum period due to medical
practices as instrumental deliveries, prescription ofpractices as instrumental deliveries, prescription of
prolonged bed rest after delivery, and use ofprolonged bed rest after delivery, and use of
estrogens to stop lactationestrogens to stop lactation..

Risk Factors for DVT inRisk Factors for DVT in
PregnancyPregnancy
PregnancyPregnancyPregnancyPregnancy itselfitselfitselfitself; DVT is; DVT is 55 times more in pregnant than nontimes more in pregnant than non--
pregnant agepregnant age--matched female.matched female.
VVirchowirchow’’s triad:s triad: (( hypercoagulabilityhypercoagulability, stasis, and endothelial, stasis, and endothelial
VVirchowirchow’’s triad:s triad: (( hypercoagulabilityhypercoagulability, stasis, and endothelial, stasis, and endothelial
injury) operates during pregnancy and puerperium.injury) operates during pregnancy and puerperium.
11-- HYPERHYPER--COAGULABILITYCOAGULABILITY: Increased levels of clotting factors: Increased levels of clotting factors
(factor I,II,VII,IX, and X) .Decreased fibrinolysis and(factor I,II,VII,IX, and X) .Decreased fibrinolysis and
reduced levels of natural anticoagulants (e.g. proteinreduced levels of natural anticoagulants (e.g. protein-- S)S)
contribute to this state of hypercoagulability duringcontribute to this state of hypercoagulability during
pregnancy .pregnancy .

Risk factorsRisk factors (continued)(continued)
VVirchowirchow’’s triad:s triad: (( hypercoagulabilityhypercoagulability,, stasisstasis, and endothelial, and endothelial
injury) operates during pregnancy and puerperium.injury) operates during pregnancy and puerperium.
22-- STASISSTASIS: Venous stasis due to pressure of the: Venous stasis due to pressure of the
gravid uterus on the IVC and decreased venousgravid uterus on the IVC and decreased venous
gravid uterus on the IVC and decreased venousgravid uterus on the IVC and decreased venous
tone are further predisposing factors present in alltone are further predisposing factors present in all
pregnant women. At term, flow velocity of thepregnant women. At term, flow velocity of the
femoral vein slows to less thanfemoral vein slows to less than 11//33rdrd of the velocityof the velocity
in the first trimester, and subsequently in the postin the first trimester, and subsequently in the post--
partum period. Moreover, the vessel diameter ofpartum period. Moreover, the vessel diameter of
the deep leg vein increases during pregnancy.the deep leg vein increases during pregnancy.

Risk factorsRisk factors (continued)(continued)
VVirchowirchow’’s triad:s triad: (( hypercoagulabilityhypercoagulability, stasis, and, stasis, and endothelialendothelial
injuryinjury) operates during pregnancy and puerperium.) operates during pregnancy and puerperium.
33-- ENDOTHELIAL VASCULAR INJURY:ENDOTHELIAL VASCULAR INJURY: Although pregnancyAlthough pregnancy
33-- ENDOTHELIAL VASCULAR INJURY:ENDOTHELIAL VASCULAR INJURY: Although pregnancyAlthough pregnancy
itself is not associated with endothelial injury, theitself is not associated with endothelial injury, the
trauma of operative delivery may result vasculartrauma of operative delivery may result vascular
injury, leading to postinjury, leading to post--partum DVT.partum DVT.

Risk factorsRisk factors ((continued)continued)
OtherOther RiskRisk FactorsFactors include:include:
Increased parity (Increased parity (>> 44).).
Obesity .Obesity .
Obesity .Obesity .
Operative or difficult instrumental delivery.Operative or difficult instrumental delivery.
Prolonged immobility.Prolonged immobility.
Previous thromboPrevious thrombo--embolism or DVT.embolism or DVT.
Thrombophilias.Thrombophilias.

Pathogenesis:Pathogenesis:
Multiple risk factors are often presentMultiple risk factors are often present
in women who develop DVT duringin women who develop DVT during
pregnancy and these risk factors arepregnancy and these risk factors are
pregnancy and these risk factors arepregnancy and these risk factors are
cumulative.cumulative.
In addition, an occult thrombophiliaIn addition, an occult thrombophilia
such assuch as FactorFactor--VV-- Leiden mutationLeiden mutation
may become unmasked during anmay become unmasked during an
otherwise normal pregnancy.otherwise normal pregnancy.

PPathogenesis:athogenesis: (continued)(continued)
WWhich side is more prone during pregnancy for DVT ?hich side is more prone during pregnancy for DVT ?
During pregnancy venous thrombosis begins mostDuring pregnancy venous thrombosis begins most
frequentlyfrequently either in the calf veins or in the ilioeither in the calf veins or in the ilio--
femoral segmentfemoral segment of the deep venous system.of the deep venous system.
There is a striking propensity for theThere is a striking propensity for the leftleft legleg, with, with
8080% of DVT in pregnancy occurring on this side.% of DVT in pregnancy occurring on this side.
This may be due to the fact that the venousThis may be due to the fact that the venous
drainage of the left leg flows a more tortuousdrainage of the left leg flows a more tortuous
course through the pelvis, with the left commoncourse through the pelvis, with the left common
iliac vein traversed by the right common iliac artery.iliac vein traversed by the right common iliac artery.

DDiagnosis :iagnosis : Clinical picture;Clinical picture;
Clinical diagnosis of DVT and thromboembolism isClinical diagnosis of DVT and thromboembolism is notoriouslynotoriously
unreliable because:unreliable because:
The intensity of the classical symptoms of pain, tenderness,The intensity of the classical symptoms of pain, tenderness,
and swelling of the affected limb depends on the extent of theand swelling of the affected limb depends on the extent of the
vascular occlusion, existing collateral circulation, and thevascular occlusion, existing collateral circulation, and the
associated inflammatory response.associated inflammatory response.
vascular occlusion, existing collateral circulation, and thevascular occlusion, existing collateral circulation, and the
associated inflammatory response.associated inflammatory response.
The physiological changes of pregnancy further complicateThe physiological changes of pregnancy further complicate
interpretation of the patientinterpretation of the patient’’s history, physical findings, ands history, physical findings, and
test results.test results.
DVT in pregnancy may present atypically with diffuseDVT in pregnancy may present atypically with diffuse
abdominal pain.abdominal pain.
Dyspnea, a common symptom of DVT, is experienced inDyspnea, a common symptom of DVT, is experienced in 7575%%
of females during normal pregnancy.of females during normal pregnancy.

DDiagnosis :iagnosis : NonNon--invasive tests;invasive tests;
In the lateIn the late 19901990--ies, nonies, non--invasive diagnostic studiesinvasive diagnostic studies
such assuch as impedanceimpedance plethysmographyplethysmography,, realreal timetime BB
mode U/Smode U/S, and, and duplex doppler scanningduplex doppler scanning havehave
replaced venography asreplaced venography as the initial screening testthe initial screening test inin
replaced venography asreplaced venography as the initial screening testthe initial screening test inin
the diagnosis of DVT.the diagnosis of DVT.
These diagnostic tests have high sensitivity forThese diagnostic tests have high sensitivity for
detection of thrombosis in the iliodetection of thrombosis in the ilio--femoral veinsfemoral veins butbut
notnot in the distal deep veins of the lower limbs.in the distal deep veins of the lower limbs.

ImpedanceImpedance PPlethysmography :lethysmography :
Measures changes in electric resistanceMeasures changes in electric resistance
measured bymeasured by 22 electrodes wrapped aroundelectrodes wrapped around
the calf in relation to changes in venousthe calf in relation to changes in venousthe calf in relation to changes in venousthe calf in relation to changes in venous
volume.volume.
Serial normal studies areSerial normal studies are sufficient tosufficient to
withhold therapywithhold therapy in both nonin both non--pregnant andpregnant and
pregnant patientspregnant patients

Doppler ultrasonography:Doppler ultrasonography:
This technique has become the diagnostic test ofThis technique has become the diagnostic test of
choice in cases of suspectedchoice in cases of suspected proximal veinproximal vein
occlusion.occlusion.
occlusion.occlusion.
With expert sonographer, a correct diagnosis withWith expert sonographer, a correct diagnosis with
high sensitivity and specificity (high sensitivity and specificity (9191% and% and 9999%%
respectively) in evaluation of proximal veinrespectively) in evaluation of proximal vein
thrombosis is obtained.thrombosis is obtained.
Limitations includeLimitations include: less effectiveness in calf vein: less effectiveness in calf vein
thrombosis, and less sensitivity for diagnosis ofthrombosis, and less sensitivity for diagnosis of
asymptomatic thrombosis.asymptomatic thrombosis.

DDiagnosis ;iagnosis ; VV e n o g r a p h y:e n o g r a p h y:
What is the role?What is the role?
Venography remains the diagnostic standardVenography remains the diagnostic standard
for DVT in both pregnant and nonfor DVT in both pregnant and non--pregnantpregnant
patients.patients.
It has the advantage ofIt has the advantage of accuratelyaccurately
It has the advantage ofIt has the advantage of accuratelyaccurately
evaluating theevaluating the entireentire lower limb from thelower limb from the
calf veins to the common iliac vessels.calf veins to the common iliac vessels.
AlthoughAlthough invasiveinvasive, it is still more reliable, it is still more reliable
than the nonthan the non--invasive techniques ininvasive techniques in
differentiating betweendifferentiating between intraintra--luminalluminal defectsdefects
andand externalexternal venous compression.venous compression.

HHow safe is it?ow safe is it?
Potential side effects include:Potential side effects include:
1.1. Chemical phlebitis,Chemical phlebitis,
2.2. Leg swelling, leg painLeg swelling, leg pain
3.3. Skin necrosis due to dye extraSkin necrosis due to dye extra--vasationvasation
Procedure is invasive & associated withProcedure is invasive & associated with
risks of provoking thrombosis and contrastrisks of provoking thrombosis and contrast
reaction.reaction.
Procedure is relatively expensive & theProcedure is relatively expensive & the
results can be difficult to interpret.results can be difficult to interpret.

HHow safe is it? (contd.)ow safe is it? (contd.)
Estimated fetal radiation exposure isEstimated fetal radiation exposure is
negligible; approximatelynegligible; approximately 00..314314 rad for arad for a
unilateral procedure without abdominalunilateral procedure without abdominal
shielding.shielding.
shielding.shielding.
Limited venography, using an abdominalLimited venography, using an abdominal
shield, can reduce the estimated fetalshield, can reduce the estimated fetal
exposure to less thanexposure to less than 00..0505 rad.rad.

CONCLUSIONCONCLUSIONCONCLUSIONCONCLUSION
The role of venography in diagnosingThe role of venography in diagnosing
DVT in pregnancy remains unresolved.DVT in pregnancy remains unresolved.
Venography may be helpful when theVenography may be helpful when the
results of nonresults of non--invasive imaging studiesinvasive imaging studies
are equivocal OR serial scanning isare equivocal OR serial scanning is
impractical.impractical.

DDDDDDDD I A G N O S I SI A G N O S I SI A G N O S I SI A G N O S I SI A G N O S I SI A G N O S I SI A G N O S I SI A G N O S I S
Recent Advances:Recent Advances:
MAGNETICMAGNETIC RESONANCERESONANCE IMAGINGIMAGING::
MRI has been established to be reliable methodMRI has been established to be reliable method
for diagnosing pelvic and lower limb venousfor diagnosing pelvic and lower limb venous
thrombosis.thrombosis.
thrombosis.thrombosis.
Despite its cost it has the following advantages:Despite its cost it has the following advantages:
1.1. At least it is as accurate as venography forAt least it is as accurate as venography for
proximal thrombosis in the lower limb and evenproximal thrombosis in the lower limb and even
more sensitive for pelvic vein thrombosis.more sensitive for pelvic vein thrombosis.
2.2. Advantages in pregnancy; nonAdvantages in pregnancy; non--invasive, noinvasive, no
ionizing radiation, and excellent resolution of theionizing radiation, and excellent resolution of the
IVC and pelvic veins.IVC and pelvic veins.

Recent Advances:Recent Advances: (contd.,)(contd.,)
B L O O D T E S T SB L O O D T E S T S
Several tests are available that reflect the formation ofSeveral tests are available that reflect the formation of
intravascular fibrin. Results are invariablyintravascular fibrin. Results are invariably +ve when+ve when
thrombosis has occurred.thrombosis has occurred.
The most important tests are assays for fibrinopeptide A (FPA)The most important tests are assays for fibrinopeptide A (FPA)
and fibrin degradation products (FDP); Dand fibrin degradation products (FDP); D--dimers are the mostdimers are the most
sensitive.sensitive.
Elevations in DElevations in D--dimer levels are found even in uncomplicateddimer levels are found even in uncomplicated
pregnancy, in levels increasing during the course ofpregnancy, in levels increasing during the course of
pregnancy.pregnancy.
However, a finding of normal level of these, essentially rulesHowever, a finding of normal level of these, essentially rules
out DVT.out DVT.

Recent Advances:Recent Advances: (contd.,)(contd.,)
B L O O D T E S T SB L O O D T E S T S
DIAGNOSTIC WORK UP FOR CONGENITALTHROMBOPHILIASDIAGNOSTIC WORK UP FOR CONGENITALTHROMBOPHILIAS
Activated protein-C resistance due to factor V Leiden
mutation is the commonest thrombophilia. The defect is
rare in Africans, and Asians. So, diagnostic work-up for
rare in Africans, and Asians. So, diagnostic work-up for
thrombophilia is not indicated in all cases of DVT in
pregnancy, but only in selected cases with clinical indicators
of hypercoagulable state which include:
1. Family history of thrombosis, Recurrent thrombosis, or
idiopathic thrombosis
2. Thrombosis at unusual sites (e.g., axillary, cerebral,
mesenteric, portal, hepatic veins)
3. Skin necrosis after starting warfarin therapy

M A N A G E M E N TM A N A G E M E N TM A N A G E M E N TM A N A G E M E N TM A N A G E M E N TM A N A G E M E N TM A N A G E M E N TM A N A G E M E N T
The Aims of TreatmentThe Aims of Treatment
1.1. To prevent extension of the thrombusTo prevent extension of the thrombus
2.2. To restore venous patencyTo restore venous patency ----------»»preventprevent
postpost--phlebitic syndrome (chronic pain,phlebitic syndrome (chronic pain,
swelling, ulceration) due to venousswelling, ulceration) due to venous
swelling, ulceration) due to venousswelling, ulceration) due to venous
insufficiencyinsufficiency
3.3. The most important aim is to preventThe most important aim is to prevent
pulmonary embolism or its recurrencepulmonary embolism or its recurrence

IsIsIsIsIsIsIsIs bed rest absolutely necessary in all cases of acutebed rest absolutely necessary in all cases of acutebed rest absolutely necessary in all cases of acutebed rest absolutely necessary in all cases of acutebed rest absolutely necessary in all cases of acutebed rest absolutely necessary in all cases of acutebed rest absolutely necessary in all cases of acutebed rest absolutely necessary in all cases of acute
DVT?DVT?DVT?DVT?DVT?DVT?DVT?DVT?
Bed rest with elevation of the affected limb isBed rest with elevation of the affected limb is
invaluable initially because it promotes venousinvaluable initially because it promotes venous
return & decrease edema.return & decrease edema.
As soon as symptoms permit, the patient should beAs soon as symptoms permit, the patient should be
As soon as symptoms permit, the patient should beAs soon as symptoms permit, the patient should be
encouraged to ambulate, since bed rest itself mayencouraged to ambulate, since bed rest itself may
enhance venous stasis.enhance venous stasis.
There is no evidence that bed rest will preventThere is no evidence that bed rest will prevent
embolus detachment .embolus detachment .
Sitting with legs dependant is contraindicated.Sitting with legs dependant is contraindicated.

SSSSSSSShouldhouldhouldhouldhouldhouldhouldhould wwwwwwwweeeeeeee Advocate Elastic BandageAdvocate Elastic BandageAdvocate Elastic BandageAdvocate Elastic BandageAdvocate Elastic BandageAdvocate Elastic BandageAdvocate Elastic BandageAdvocate Elastic Bandage //////// Stocking?Stocking?Stocking?Stocking?Stocking?Stocking?Stocking?Stocking?
When correctly designed, elastic stockings increaseWhen correctly designed, elastic stockings increase
the velocity of venous return.the velocity of venous return.
The pressure gradient should decrease from ankleThe pressure gradient should decrease from ankle
to thigh without a constricting garter at the top.to thigh without a constricting garter at the top.
Elastic bandages once in vogue, are best avoidedElastic bandages once in vogue, are best avoided
because they are easily wrapped incorrectly withbecause they are easily wrapped incorrectly with
the greatest pressure ending up at the top, thusthe greatest pressure ending up at the top, thus
impeding venous return.impeding venous return.

Does DVT limited to theDoes DVT limited to theDoes DVT limited to theDoes DVT limited to theDoes DVT limited to theDoes DVT limited to theDoes DVT limited to theDoes DVT limited to the calfcalfcalfcalfcalfcalfcalfcalf require treatment?require treatment?require treatment?require treatment?require treatment?require treatment?require treatment?require treatment?
The need for treatment of thrombosis below theThe need for treatment of thrombosis below the
level of popliteal fossa remains disputable as risk oflevel of popliteal fossa remains disputable as risk of
pulmonary embolism in such cases is very low(pulmonary embolism in such cases is very low(11%).%).
However, because aboutHowever, because about 2020% of lower DVT% of lower DVT’’ss
However, because aboutHowever, because about 2020% of lower DVT% of lower DVT’’ss
extend proximally and anticoagulants can preventextend proximally and anticoagulants can prevent
this spread, many believe that treatment isthis spread, many believe that treatment is
required.required.
An alternative is frequent doppler flow studies toAn alternative is frequent doppler flow studies to
detect extension and then treat.detect extension and then treat.

MANAGEMENTMANAGEMENTMANAGEMENTMANAGEMENTMANAGEMENTMANAGEMENTMANAGEMENTMANAGEMENT
Anticoagulant TherapyAnticoagulant Therapy
How safe are the anticoagulants in pregnancyHow safe are the anticoagulants in pregnancy
FDA categoryFDA categoryAgentAgent
DDWarfarinWarfarin
CCUnfractionated heparinUnfractionated heparin
BBDalteparin sodium (LMWH)Dalteparin sodium (LMWH)
BBEnoxaparin sodium (LMWH)Enoxaparin sodium (LMWH)
CCStreptokinaseStreptokinase
BBUrokinaseUrokinase

Anticoagulant TherapyAnticoagulant Therapy (cont’d.)(cont’d.)(cont’d.)(cont’d.)(cont’d.)(cont’d.)(cont’d.)(cont’d.)
W A R F A R I NW A R F A R I N
It is the most widely used coumarin derivative forIt is the most widely used coumarin derivative for oraloral
anticoagulation. Its therapeutic efficacy lies in its ability toanticoagulation. Its therapeutic efficacy lies in its ability to
inhibit the action of vitamin K, which is a cofactor for theinhibit the action of vitamin K, which is a cofactor for the
synthesis ofsynthesis of 44 essential clotting factors in the liver (essential clotting factors in the liver (factor VII,factor VII,
IX, X, prothrombinIX, X, prothrombin).).
IX, X, prothrombinIX, X, prothrombin).).
DOSAGE: usual dose=DOSAGE: usual dose=1010--1515 mg daily until therapeuticmg daily until therapeutic
prolongation of PT is achieved (INR=prolongation of PT is achieved (INR=22--33). Heparin is). Heparin is
continued for thecontinued for the 11stst week of warfarin therapy as its action isweek of warfarin therapy as its action is
not immediate.not immediate.
MONITOURING: PT daily forMONITOURING: PT daily for 77 days, thendays, then 22/week for/week for 22w,thenw,then
weekly for several months depending on the response.weekly for several months depending on the response.

Avoid large loading dose as it may cause overAvoid large loading dose as it may cause over--coagulationcoagulation
due to excessive protein C inhibition.due to excessive protein C inhibition.
Warfarin use during pregnancy is limited as it crosses theWarfarin use during pregnancy is limited as it crosses the
placenta with the following fetal hazards:placenta with the following fetal hazards:
Risk of embryopathy(Risk of embryopathy(55%) if taken between%) if taken between 66thth andand 1212thth
1.1. Risk of embryopathy(Risk of embryopathy(55%) if taken between%) if taken between 66thth andand 1212thth
weeks of gestation. (nasal, epiphysealweeks of gestation. (nasal, epiphyseal--limb hypoplasia).limb hypoplasia).
2.2. If taken afterIf taken after 11stst trimester of pregnancy it may causetrimester of pregnancy it may cause
neurological & ophthalmic anomalies. Also can cause fetal&neurological & ophthalmic anomalies. Also can cause fetal&
neonatal hemorrhage, and placental abruptionneonatal hemorrhage, and placental abruption
It can cause major maternal hemorrhage & its action is notIt can cause major maternal hemorrhage & its action is not
as easily reversed as that of heparin.as easily reversed as that of heparin.

For its risks, Warfarin:For its risks, Warfarin:
Is absolutely contraIs absolutely contra--indicated during first trimester.indicated during first trimester.
Its use inIts use in 22ndnd && 33rdrd trimesters is controversial.trimesters is controversial.
If its use during pregnancy is specifically indicated;If its use during pregnancy is specifically indicated;
If its use during pregnancy is specifically indicated;If its use during pregnancy is specifically indicated;
it should replace heparin after theit should replace heparin after the 1212thth week, andweek, and
replaced by heparin after thereplaced by heparin after the 3636thth week or at theweek or at the
onset of labor.onset of labor.
If labor started while using it, parenteral vitamin KIf labor started while using it, parenteral vitamin K
and fresh frozen plasma can reverse its effect.and fresh frozen plasma can reverse its effect.

WHAT IS THE MOST COMMONLY USED ANTICOAGULANTWHAT IS THE MOST COMMONLY USED ANTICOAGULANTWHAT IS THE MOST COMMONLY USED ANTICOAGULANTWHAT IS THE MOST COMMONLY USED ANTICOAGULANTWHAT IS THE MOST COMMONLY USED ANTICOAGULANTWHAT IS THE MOST COMMONLY USED ANTICOAGULANTWHAT IS THE MOST COMMONLY USED ANTICOAGULANTWHAT IS THE MOST COMMONLY USED ANTICOAGULANT
DURING PREGNANCY?DURING PREGNANCY?DURING PREGNANCY?DURING PREGNANCY?DURING PREGNANCY?DURING PREGNANCY?DURING PREGNANCY?DURING PREGNANCY?
Unfractionated heparin(UFH):Unfractionated heparin(UFH):
Naturally occurring mucopolysaccharide.Naturally occurring mucopolysaccharide.
In plasma, it combines with antiIn plasma, it combines with anti--thrombin III tothrombin III to
become a potent inhibitor of thrombin& to increasebecome a potent inhibitor of thrombin& to increase
become a potent inhibitor of thrombin& to increasebecome a potent inhibitor of thrombin& to increase
the circulating levels of activated factor X inhibitor.the circulating levels of activated factor X inhibitor.
ANTIDOTE :ANTIDOTE :If necessary heparin effects can beIf necessary heparin effects can be
reversed rapidly withreversed rapidly with protamine sulfateprotamine sulfate in a dose ofin a dose of
11mg/mg/100100 units of administered heparin. No moreunits of administered heparin. No more
thanthan 5050mg should be given over anymg should be given over any 1010 min. periodmin. period
because itself can cause bleeding.because itself can cause bleeding.

WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?
Lack of adequate anticoagulation increase the riskLack of adequate anticoagulation increase the risk
of recurrence of thrombosis byof recurrence of thrombosis by 1111--1515 folds.folds.
Optimal anticoagulation is obtained with an APTT ofOptimal anticoagulation is obtained with an APTT of
6060--8080 sec (sec (11..55--22..55 times control).times control).
PrePre--treatment : CBC, Platelet count, PT, APTT,treatment : CBC, Platelet count, PT, APTT,
Urine analysis.Urine analysis.
Loading dose:Loading dose: 100100 u/kgu/kg with minimum ofwith minimum of 50005000 u.u.
following it, the initial infusion rate should befollowing it, the initial infusion rate should be 1515--
2525u/kg/hr.u/kg/hr.
APTT should be obtained after the loading dose andAPTT should be obtained after the loading dose and
appropriate adjustment should be made.appropriate adjustment should be made.

WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?WHAT ARE THE THERAPEUTIC DOSES OF HEPARIN?
MAINTENANCE DOSAGE: continuous IV infusion forMAINTENANCE DOSAGE: continuous IV infusion for 33--55
days for active thromboembolism or symptoms resolved &days for active thromboembolism or symptoms resolved &
there is no recurrence.there is no recurrence.
It is followed by adjusted dose regimen of heparin forIt is followed by adjusted dose regimen of heparin for 44
months followed by a prophylactic dose for the remainder ofmonths followed by a prophylactic dose for the remainder of
months followed by a prophylactic dose for the remainder ofmonths followed by a prophylactic dose for the remainder of
pregnancy andpregnancy and 66--1212 weeks postpartum.weeks postpartum.
Adjusted dose regimen:Adjusted dose regimen: S.C.S.C. heparin /heparin /1212hrs. Dose adjusted tohrs. Dose adjusted to
obtain APTT=obtain APTT=11..55--22..00 times control attimes control at 66hrs. Once a stablehrs. Once a stable
dose reached, middose reached, mid--interval APTT done weekly at the antenatalinterval APTT done weekly at the antenatal
visits.visits.
Heparin requirements should be anticipated to increase duringHeparin requirements should be anticipated to increase during
pregnancy until term.pregnancy until term.

SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?
If DVT occurredIf DVT occurred ≥≥ 33months before the EDD,months before the EDD,
anticoagulation during labor is NOT indicated.anticoagulation during labor is NOT indicated.
Patient instructed to discontinue therapy with onsetPatient instructed to discontinue therapy with onset
of labor. The morning dose should not be taken byof labor. The morning dose should not be taken by
of labor. The morning dose should not be taken byof labor. The morning dose should not be taken by
those who are planned for cesarean delivery.those who are planned for cesarean delivery.
Heparin is resumedHeparin is resumed 44--66 hours postpartum.hours postpartum.
Regional anesthesia is not contraindicated if APTTRegional anesthesia is not contraindicated if APTT
is normal and heparin not given in lastis normal and heparin not given in last 44--66hrs.hrs.

SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?SHOULD ANTICOAGULANT BE GIVEN DURING LABOR?
If heparin is required during labor, the dose shouldIf heparin is required during labor, the dose should
be adjusted to achieve an APTT ofbe adjusted to achieve an APTT of 11..55 times controltimes control
during labor and delivery.during labor and delivery.
Conduction anesthesia is contraindicated in theseConduction anesthesia is contraindicated in these
patients.patients.
With this dose the incidence of PPHge.is notWith this dose the incidence of PPHge.is not
increased in a normal labor, but the incidence ofincreased in a normal labor, but the incidence of
episiotomy hematoma is increased.episiotomy hematoma is increased.

WHAT ARE THE COMPLICATIONS OF HEPARIN THERAPY?WHAT ARE THE COMPLICATIONS OF HEPARIN THERAPY?WHAT ARE THE COMPLICATIONS OF HEPARIN THERAPY?WHAT ARE THE COMPLICATIONS OF HEPARIN THERAPY?WHAT ARE THE COMPLICATIONS OF HEPARIN THERAPY?WHAT ARE THE COMPLICATIONS OF HEPARIN THERAPY?WHAT ARE THE COMPLICATIONS OF HEPARIN THERAPY?WHAT ARE THE COMPLICATIONS OF HEPARIN THERAPY?
Heparin does not cross placenta, soHeparin does not cross placenta, so no fetal hazardsno fetal hazards. All. All
complications are maternal;complications are maternal;
1.1. BleedingBleeding: not significantly more in pregnant than non: not significantly more in pregnant than non
pregnant. SC heparin may cause persistent anticoagulationpregnant. SC heparin may cause persistent anticoagulation
after cessation of use, so it is recommended to convert toafter cessation of use, so it is recommended to convert to
IV heparinIV heparin 2424 hrs before elective induction of labor.hrs before elective induction of labor.
IV heparinIV heparin 2424 hrs before elective induction of labor.hrs before elective induction of labor.
2.2. Osteoporosis;Osteoporosis; reversible, more in pregnant than nonreversible, more in pregnant than non
pregnant (prolonged therapy, pregnancy & lactationpregnant (prolonged therapy, pregnancy & lactation
demineralization.demineralization.
3.3. ThrombocytopeniaThrombocytopenia;; 22 formsforms (a)(a) early benignearly benign, mild occurs, mild occurs
11--66 days of treatmentdays of treatment (b)(b) delayed severedelayed severe,, immuneimmune--
mediated, occursmediated, occurs 66--1010 days of treatment. Thedays of treatment. The 22ndnd form mayform may
be associated with paradoxical arterial and venousbe associated with paradoxical arterial and venous
thrombosis. Requires immediate heparin withdrawal.thrombosis. Requires immediate heparin withdrawal.

WHAT IS HEPARIN RESISTANCE?WHAT IS HEPARIN RESISTANCE?WHAT IS HEPARIN RESISTANCE?WHAT IS HEPARIN RESISTANCE?WHAT IS HEPARIN RESISTANCE?WHAT IS HEPARIN RESISTANCE?WHAT IS HEPARIN RESISTANCE?WHAT IS HEPARIN RESISTANCE?
Defined as the need for more thanDefined as the need for more than 2020,,000000 unitsunits
of heparin/day. Mainly occurs in patients withof heparin/day. Mainly occurs in patients with
large venous thrombolarge venous thrombo--emboli.emboli.
Mechanism of resistance:Mechanism of resistance:
1.1. Inherited or acquired decrease in AT III levels.Inherited or acquired decrease in AT III levels.
1.1. Inherited or acquired decrease in AT III levels.Inherited or acquired decrease in AT III levels.
2.2. Increased plasma levels of factor VIII.Increased plasma levels of factor VIII.
3.3. Increased plasma levels of heparin bindingIncreased plasma levels of heparin binding
proteins.proteins.
Monitoring here is not with APTT, but with antiMonitoring here is not with APTT, but with anti--
factor Xa assay.factor Xa assay.
Low molecular weight heparin should be usedLow molecular weight heparin should be usedLow molecular weight heparin should be usedLow molecular weight heparin should be usedLow molecular weight heparin should be usedLow molecular weight heparin should be usedLow molecular weight heparin should be usedLow molecular weight heparin should be used
alternatively as they have less protein binding.alternatively as they have less protein binding.alternatively as they have less protein binding.alternatively as they have less protein binding.alternatively as they have less protein binding.alternatively as they have less protein binding.alternatively as they have less protein binding.alternatively as they have less protein binding.

WHAT ARE LOW MOLECULAR WEIGHT HEPARINWHAT ARE LOW MOLECULAR WEIGHT HEPARINWHAT ARE LOW MOLECULAR WEIGHT HEPARINWHAT ARE LOW MOLECULAR WEIGHT HEPARINWHAT ARE LOW MOLECULAR WEIGHT HEPARINWHAT ARE LOW MOLECULAR WEIGHT HEPARINWHAT ARE LOW MOLECULAR WEIGHT HEPARINWHAT ARE LOW MOLECULAR WEIGHT HEPARINS (LMWH)S (LMWH)S (LMWH)S (LMWH)S (LMWH)S (LMWH)S (LMWH)S (LMWH)????????
Are fragments of conventional heparin produced byAre fragments of conventional heparin produced by
enzymatic or chemical breakdown.enzymatic or chemical breakdown.
Like heparin, they donLike heparin, they don’’t cross the placenta, aret cross the placenta, are
Like heparin, they donLike heparin, they don’’t cross the placenta, aret cross the placenta, are
nonnon--teratogenic, and not secreted in milk.teratogenic, and not secreted in milk.
By virtue of their shorter & lighter structures,By virtue of their shorter & lighter structures,
LMWHs produce predominantly antiLMWHs produce predominantly anti--thromboticthrombotic
effect through their inhibition of factor Xa with littleeffect through their inhibition of factor Xa with little
anticoagulant activity.anticoagulant activity.

ARE DIFFERENT LMWHs SIMILAR IN ACTION?ARE DIFFERENT LMWHs SIMILAR IN ACTION?ARE DIFFERENT LMWHs SIMILAR IN ACTION?ARE DIFFERENT LMWHs SIMILAR IN ACTION?ARE DIFFERENT LMWHs SIMILAR IN ACTION?ARE DIFFERENT LMWHs SIMILAR IN ACTION?ARE DIFFERENT LMWHs SIMILAR IN ACTION?ARE DIFFERENT LMWHs SIMILAR IN ACTION?
LMWs have a molecular weight betweenLMWs have a molecular weight between
44,,000000 toto 66,,000000. Various formulations differ. Various formulations differ
in mean MW, glucosaminoglycan content,in mean MW, glucosaminoglycan content,
and anticoagulant activity.and anticoagulant activity.
and anticoagulant activity.and anticoagulant activity.
Each LMWH has its own bioavailability,Each LMWH has its own bioavailability,
plasma clearance, and release of tissueplasma clearance, and release of tissue
factor inhibitor. So properties of a particularfactor inhibitor. So properties of a particular
LMWH are not applicable to another.LMWH are not applicable to another.

WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?
LMWHsLMWHsUFHUFHEffectEffect
33,,000000--99,,0000001515,,000000--3030,,000000Mean MWt. [dalton]Mean MWt. [dalton]
22--44::1111::11Anti Xa : Antithrombin ratioAnti Xa : Antithrombin ratio
22--44::1111::11Anti Xa : Antithrombin ratioAnti Xa : Antithrombin ratio
MinimalMinimalSignificantSignificantProtein bindingProtein binding
RareRareNot rareNot rareThrombocytopeniaThrombocytopenia
±±9090%%±±3030%%BioavailabilityBioavailability
scscSc or ivSc or ivRoute of administrationRoute of administration

WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?WHAT ARE THE ADVANTAGES OF LMWHs OVER UFH?
1.1. Less hemorrhagic complications.Less hemorrhagic complications.
2.2. Lower risk of heparin induced thrombocytopenia.Lower risk of heparin induced thrombocytopenia.
3.3. Less frequent dosages [increased bioavailability&Less frequent dosages [increased bioavailability&
longer half life].longer half life].
longer half life].longer half life].
4.4. No heparin induced osteoporosis.No heparin induced osteoporosis.
5.5. Anti Xa, activity is correlated with body weight,Anti Xa, activity is correlated with body weight,
this allows administration in fixed dose.this allows administration in fixed dose.
6.6. No need for lab. Monitoring for coagulation testsNo need for lab. Monitoring for coagulation tests
like PT and APTT.like PT and APTT.

CAN LMWHs BE USED FOR ACUTE TREATMENT OF D.V.T?CAN LMWHs BE USED FOR ACUTE TREATMENT OF D.V.T?CAN LMWHs BE USED FOR ACUTE TREATMENT OF D.V.T?CAN LMWHs BE USED FOR ACUTE TREATMENT OF D.V.T?CAN LMWHs BE USED FOR ACUTE TREATMENT OF D.V.T?CAN LMWHs BE USED FOR ACUTE TREATMENT OF D.V.T?CAN LMWHs BE USED FOR ACUTE TREATMENT OF D.V.T?CAN LMWHs BE USED FOR ACUTE TREATMENT OF D.V.T?
Until recently, the use of LMWHs in pregnancy wasUntil recently, the use of LMWHs in pregnancy was
limited to chronic phase of the disease &forlimited to chronic phase of the disease &for
prophylaxis.prophylaxis.
Intravenous unfractionated heparin is graduallyIntravenous unfractionated heparin is gradually
being replaced in modern practice by s.c. LMWs,being replaced in modern practice by s.c. LMWs,
being replaced in modern practice by s.c. LMWs,being replaced in modern practice by s.c. LMWs,
granting equal or even better efficacy;granting equal or even better efficacy; much easiermuch easier
dosing, a wider therapeutic window, fewer bleedingdosing, a wider therapeutic window, fewer bleeding
complications, and faster and more reliable resultscomplications, and faster and more reliable results..
Full anticoagulation dose of LMWHs:
ENOXAPARIN=ENOXAPARIN=11mg/kg SC bdmg/kg SC bd
DALTEPARIN=DALTEPARIN=100100 iu/kg SC bdiu/kg SC bd

DO ALL PATIENTS WITH DVT REQUIRE HOSPITALIZATION?DO ALL PATIENTS WITH DVT REQUIRE HOSPITALIZATION?DO ALL PATIENTS WITH DVT REQUIRE HOSPITALIZATION?DO ALL PATIENTS WITH DVT REQUIRE HOSPITALIZATION?DO ALL PATIENTS WITH DVT REQUIRE HOSPITALIZATION?DO ALL PATIENTS WITH DVT REQUIRE HOSPITALIZATION?DO ALL PATIENTS WITH DVT REQUIRE HOSPITALIZATION?DO ALL PATIENTS WITH DVT REQUIRE HOSPITALIZATION?
Advent of LMWHs for treatment of DVTAdvent of LMWHs for treatment of DVT
with advantages of sc once or twicewith advantages of sc once or twice
daily dosage without monitoring hasdaily dosage without monitoring has
daily dosage without monitoring hasdaily dosage without monitoring has
made it possible to treat patients in anmade it possible to treat patients in an
outpatient setting.outpatient setting. But pregnant stateBut pregnant state
is a contraindication for suchis a contraindication for such
treatment.treatment.

Thrombolytic TherapyThrombolytic Therapy
No controlled trials on the safety and efficacyNo controlled trials on the safety and efficacy
of thrombolytics in pregnant patients haveof thrombolytics in pregnant patients have
been done.been done.
Because of the risks of maternal hge. and fetalBecause of the risks of maternal hge. and fetal
loss, thrombolytic therapy should beloss, thrombolytic therapy should be
Because of the risks of maternal hge. and fetalBecause of the risks of maternal hge. and fetal
loss, thrombolytic therapy should beloss, thrombolytic therapy should be
reserved to the following:reserved to the following:
1.1. Massive PE with hemodynamic instability.Massive PE with hemodynamic instability.
2.2. The affected limb viability is in jeopardy,The affected limb viability is in jeopardy,
eg. Phlegmasia alba dolens & phlegmasiaeg. Phlegmasia alba dolens & phlegmasia
cerulae dolenscerulae dolens..

ThromboThrombo--prophylaxisprophylaxis
Risk of recurrent DVT in pregnancy is aboutRisk of recurrent DVT in pregnancy is about 44--
1515%.%.
Prophylaxis: (sc heparinProphylaxis: (sc heparin 77..500500::1010..000000 U/bd)U/bd)
1.1. H/O DVT + risk factor (eg, thrombophilia,H/O DVT + risk factor (eg, thrombophilia,
1.1. H/O DVT + risk factor (eg, thrombophilia,H/O DVT + risk factor (eg, thrombophilia,
APLAS): start inAPLAS): start in 11stst trimestertrimester-- toto-- 66 weeks postweeks post--
partum.partum.
2.2. Only H/O DVT:Only H/O DVT:
a) clinical surveillance followed by warfarina) clinical surveillance followed by warfarin
postpartum xpostpartum x 44--66 weeks.weeks.
b) UFH or LMWHs throughout pregnancy followedb) UFH or LMWHs throughout pregnancy followed
by warfarin/LMWHs xby warfarin/LMWHs x 44--66 wks.wks.

REFFERENCESREFFERENCES
Brandjes DP, Heijboer H, Buller HR, et al: Acenocoumarol and heparin comparedBrandjes DP, Heijboer H, Buller HR, et al: Acenocoumarol and heparin compared
with acenocoumarol alone in the initial treatment of proximalwith acenocoumarol alone in the initial treatment of proximal--veinvein
..[Medline][Medline]99--14851485):):2121((327327;;1919NovNov19921992thrombosis. N Engl J Medthrombosis. N Engl J Med
Feied CF: Pulmonary embolism. In: Rosen P, Barkin RM, eds. EmergencyFeied CF: Pulmonary embolism. In: Rosen P, Barkin RM, eds. Emergency
Medicine Principles and Practice. VolMedicine Principles and Practice. Vol 33.. 44th ed. St. Louis, Mo: Mosby;th ed. St. Louis, Mo: Mosby; 19981998::
ChapterChapter 111111..
Feied CF: Peripheral venous disease. In: Rosen P, Barkin RM, eds. EmergencyFeied CF: Peripheral venous disease. In: Rosen P, Barkin RM, eds. Emergency
Feied CF: Peripheral venous disease. In: Rosen P, Barkin RM, eds. EmergencyFeied CF: Peripheral venous disease. In: Rosen P, Barkin RM, eds. Emergency
Medicine Principles and Practice. VolMedicine Principles and Practice. Vol 33.. 44th ed. St. Louis, Mo: Mosby;th ed. St. Louis, Mo: Mosby; 19981998::
ChapterChapter 107107..
Feied CF: Deep Vein Thrombosis and Pulmonary Embolism. In: Rosen P, BarkinFeied CF: Deep Vein Thrombosis and Pulmonary Embolism. In: Rosen P, Barkin
RM eds. Emergency Medicine: Concepts and clinical practice .RM eds. Emergency Medicine: Concepts and clinical practice . 55th ed. St.th ed. St.
Louis, MO: Mosby;Louis, MO: Mosby; 20012001: Chapter: Chapter 8383..
Havig O: Deep vein thrombosis and pulmonary embolism. An autopsy study withHavig O: Deep vein thrombosis and pulmonary embolism. An autopsy study with
multiple regression analysis of possible risk factors. Acta Chir Scand Supplmultiple regression analysis of possible risk factors. Acta Chir Scand Suppl
..[Medline][Medline]120120--11::478478;;19771977
Konstantinides S, Geibel A, Olschewski M, et al: Association between thrombolyticKonstantinides S, Geibel A, Olschewski M, et al: Association between thrombolytic
treatment and the prognosis of hemodynamically stable patients with majortreatment and the prognosis of hemodynamically stable patients with major
pulmonary embolism: results of a multicenter registry. Circulationpulmonary embolism: results of a multicenter registry. Circulation 19971997 AugAug
..[Medline][Medline]88--882882):):33((9696;;55

Kucher N, Koo S, Quiroz R: Electronic alerts to prevent venousKucher N, Koo S, Quiroz R: Electronic alerts to prevent venous
thromboembolism among hospitalized patients. N Engl J Medthromboembolism among hospitalized patients. N Engl J Med 20052005
..[Medline][Medline]7777--969969):):1010((352352;;1010MarMar
Nakamura M, Nakanishi N, Yamada N: Effectiveness and safety of theNakamura M, Nakanishi N, Yamada N: Effectiveness and safety of the
thrombolytic therapy for acute pulmonary thromboembolism: resultsthrombolytic therapy for acute pulmonary thromboembolism: results
of a multicenter registry in the Japanese Society of Pulmonaryof a multicenter registry in the Japanese Society of Pulmonary
..[Medline][Medline]99--8383):):11((9999Mar;Mar;20052005Embolism Research. Int J CardiolEmbolism Research. Int J Cardiol
..[Medline][Medline]99--8383):):11((9999Mar;Mar;20052005Embolism Research. Int J CardiolEmbolism Research. Int J Cardiol
Tretbar LL: Venous Disorders of the Legs.Tretbar LL: Venous Disorders of the Legs. 11st ed. New York, NY:st ed. New York, NY:
SpringerSpringer--Verlag;Verlag; 19981998:: 11--138138..
Vossen CY, Conard J, Fontcuberta J: Risk of a first venous thromboticVossen CY, Conard J, Fontcuberta J: Risk of a first venous thrombotic
event in carriers of a familial thrombophilic defect. The Europeanevent in carriers of a familial thrombophilic defect. The European
Prospective Cohort on Thrombophilia (EPCOT). J Thromb HaemostProspective Cohort on Thrombophilia (EPCOT). J Thromb Haemost
..[Medline][Medline]6464--459459):):33((33Mar;Mar;20052005
Weiss RA, Feied CF, Weiss MA, eds: Vein Diagnosis & Treatment: AWeiss RA, Feied CF, Weiss MA, eds: Vein Diagnosis & Treatment: A
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11--304304..

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