Use of Anticoagulant

By. Mulugeta ( RII)

Moderator: Dr.Tadele Hailu, MD, Pediatrician

Consultant Hematologist and Oncologist
January 20, 2025
 Table of contents

Introduction
– Coagulation cascade
– Laboratory evaluation of hemostasis
• Thrombotic disorder of children
– Epidemiology
– Risk factor
– Clinical manifestation
– Diagnosis
• Anticoagulant agents
• Anticoagulant therapy in VTE
• Use of anticoagulant in PTE
• Use of anticoagulant in arterial ischemic stroke
• Use of anticoagulant in neonate
• Use of anticoagulant in cardiac patient
• Use of anticoagulant in special circumstances
 Hemostasis
• Hemostasis is the process of blood clotting in areas of
blood vessel injury
• The main components of the hemostatic process are
– Vessel wall

– Platelets

– Coagulation proteins

– Anticoagulant proteins

– Fibrinolytic system
 Laboratory Evaluation of Hemostasis
Prothrombin Time
• measures the activation of clotting by tissue factor
• PT has been standardized using the international
normalized ratio (INR ) so that values can be compared
from one laboratory or instrument to another
Partial Thromboplastin Time
• measures the initiation of clotting at the level of factor XII
through sequential steps to the final clot end point
• Normal ranges for PTT have much more interlaboratory
variability than those for PT
Nelson 21 edition
 Thrombotic Disorders in Children
Thrombophilia ;is an abnormality in blood coagulation that
increase the risk of thrombosis.
Inherited Thrombophilia (IT) ; refers to genetic risk factors that
predispose individuals to developing venous thromboembolism
(VTE).
Acquired Thrombophilia; refers to external factors that may
predispose individuals to developing VTE
 Epidemiology
Overall incidence of thrombosis in the general pediatric
population in US is quite low - 0.07/100,000.
The rate of VTE in hospitalized children is 60 per 10,000
admissions.The estimated annual incidence of VTEs is about
0.5 per 10,000 newborns.
However, the majority of VTEs within the first year of life are
associated with central venous access devices.
Pediatric VTE occurs in a bimodal distribution, most
commonly encountered < 1 year infants and 2nd peak is
during adolescents.
 Pathogenesis.
• Unlike in the adult population, VTEs in children are almost always
provoked.
• Risk factors that contribute to the development of a VTE are those that
disrupt 1 or more of the Virchow triad’s components:
• Blood flow stasis
• Endothelial injury, and/or
• Hypercoagulable state.
Virchow’s triad
Risk Factors for Thrombosis
 Arterial Thrombosis
Initially occurs under conditions of rapid blood flow and often is the
result of a process that damages the vessel wall.
The thrombus is composed of tightly coherent platelets that contain
small amounts of fibrin and few erythrocytes and leukocytes (white
thrombus).
The most serious consequence of arterial thrombosis is vascular
occlusion.
Arterial thrombotic events occur in a number of congenital and
acquired diseases.
 Venous Thrombosis
Develop under conditions of slow blood flow.
They may occur by way of activation of the coagulation system
with or without vascular damage.
Venous thrombi are composed of large amounts of fibrin
containing numerous erythrocytes, platelets, and leukocytes (red
thrombus).
The most serious consequence is embolization from a deep vein
thrombosis resulting in pulmonary embolism.
 Inherited Thrombophilias
• There are 2 main categories of inherited thrombophilias:
1. Genetic conditions associated with deficiencies of natural
anticoagulants (antithrombin, protein C, and protein S)
2. Gain-of-function mutations in procoagulant factors
(factor V leiden [FVL] and prothrombin G20210A mutation
Inherited thrombophilia should be suspected when the patient
has:
• Recurrent or life-threatening venous thromboembolism starting in
infancy/childhood,
• A family history of venous thrombosis before age 45 years;
• No apparent acquired risk factors for thrombosis .
• A history of multiple abortions, stillbirths, or both .
 Factor V Leiden (Activated Protein C Resistance)
• In Caucasians, it is the single most common inherited disorder
predisposing to thrombosis.
• It results from a single G to A point mutation at nucleotide 1691 within
the FV gene, arginine is replaced by glutamine at
position (R506Q), rendering activated FV relatively resistant to
inactivation by protein C.
• Approximately 95% of patients with activated protein C resistance test
positively for FV Leiden mutation
 The remaining 5% of cases are attributable to oral contraceptive usage,
presence of a LA, or other rare mutations in the FV gene.
 Has been associated with cerebral infarction and with venous thrombosis in
children.
 Both heterozygous and homozygous cases of FV Leiden mutation have
increased risk for either venous or arterial thrombosis throughout life but
usually are asymptomatic in youth unless associated with other acquired or
genetic prothrombotic conditios
 like CVC, trauma, surgery, cancer, pregnancy, COC, Deficient protine C
or homocysteinemia.
 2. Prothrombin(FII) G20210A Mutation

 The second most common inherited thrombotic defect.

 Due to the genetic defect at nucleotide position 20210 in the prothrombin
gene.
 abnormally high prothrombin levels and contributes to thrombotic risk
by promoting increased thrombin generation.
 individual with the defect usually presents with thrombotic episodes in
adulthood.

22/11/2024
 Protein C Deficiency
• PC deficiency is inherited in an autosomal-dominant manner.
• Is subdivided into two types;
• Type I PC deficiency: (low activity and low antigen level) is a
quantitative deficiency with decreased plasma concentration and
functional activity to approximately 50% of normal.
• Type II PC deficiency: (low activity and normal antigen level) is
less common and is characterized by a qualitative decrease in
functional activity, despite normal levels of PC antige
 Plasma levels of PC below 50% (normal range, 70 - 110%) are associated with the
risk of thrombotic complications.
 The clinical manifestation of heterozygous PC deficiency is primarily venous
thrombotic episodes during the 2nd decade of life or young adulthood.
 Heterozygous deficiency of PC is not a significant problem during the neonatal
period, but homozygous deficiency or compound heterozygous individuals with
protein C deficiency may cause a fatal thrombotic disorder.
 It may present with neonatal purpura fulminans, DIC, progressive
skin necrosis with microvascular thrombosis, and thrombosis of
the renal veins, mesenteric veins, and dural venous sinuses.
 One of the major causes of warfarin induced skin necrosis.
 Warfarin decreases PC more rapidly than FIX, FX, and FII
resulting in a hemostatic imbalance with resultant microvascular
thrombosis.
 Bridging with heparin when starting on warfarin until the desired
INR is attained
 Protein S Deficiency
• Is inherited as an autosomal-dominant manner.
• Is also a vitamin-K-dependent anticoagulant that circulates in the plasma
in two forms:
• Free active form (40%) and
• Inactive form bound to C4b-free binding protein (60%).
• PS functions as a cofactor to PC by enhancing its activity against factors
Va and VIIIa.
• Free PS levels (normal range, 44 -92%) correlate clinically with
thrombotic episodes.
 Anti-thrombin Deficiency
• Antithrombin is a serpin (serine protease inhibitor) and its primary
targets are thrombin, Factor XI, FXa and FIXa.
• It is a heterozygous disorder.
• Two major types of AT deficiency
• Type I AT deficiency (low activity and low antigen level) is a
quantitative defect caused by a mutation resulting in both decreased
synthesis and functional activity of AT.
• Type II AT deficiency is a qualitative defect characterized by
decreased AT activity and normal antigenic levels.
• Thrombotic complications of AT deficiency usually occur in the
2nd decade of life.
• In affected individuals AT levels are about 40 - 60% (normal
range, 80 -120%).
• The risk of developing thrombotic complications depends on the
particular subtype of AT deficiency and on other coexisting
inherited or acquired risk factors.
• In children with heterozygous AT deficiency the relative risk of
developing thrombotic episodes is increased 10-fold.
 Acquired Thrombophilia
Antiphospholipid antibody syndrome (APS)
Is an autoimmune disease that is a very rare condition in children.
Occurs in approximately 3% of patients before 15 years.Affect
both arterial and venous circulation. Cxzed by recurrent fetal loss,
& persistent circulating antiphospholipid antibodies (APLs), i.e.,
circulating lupus anticoagulant (LA), anticardiolipin antibodies
(aCLs) and anti-β2-glycoprotein-1 (anti-β2GP-1)
 Acquired Thrombophilia
• Antiphospholipid antibody syndrome (APS)
• Is an autoimmune disease that is a very rare condition in
children. Occurs in approximately 3% of patients before 15
years.
• Affect both arterial and venous circulation.
•Cxzed by recurrent fetal loss, & persistent circulating antiphospholipid
antibodies (APLs), i.e., circulating lupus anticoagulant (LA),
anticardiolipin antibodies (aCLs) and anti-β2-glycoprotein-1 (anti-β2GP-1)
• DVT, PE & Ischemic stroke are the principal manifestations, but any
vessel can be involved.
• APS can be either
– Primary, if it occurs in the absence of any underlying disease
[primary antiphospholipid syndrome (PAPS)]
– Secondary, when it occurs in association with another autoimmune
disorder, most commonly systemic lupus erythematosus (SLE) or
lupus-like disease
• Important candidate mechanisms for thrombosis are;
– Antibody-induced concentration of prothrombin on phospholipid
surfaces in vivo, resulting in enhanced thrombin generation
– Interference with the activated protein C anticoagulant pathway
– Increased monocyte and endothelial tissue factor expression.
– Increased platelet activation and inhibition of fibrinolysis by
antiphospholipid antibodies.
 CVC-related TE
Is associated with more than 90% of diagnosed VTEs in neonates
and more than 60% in older children.
Causes thrombosis by injuring the endothelial wall and disrupting
the blood flow.
When the catheter is used to deliver foreign substances, such as
total parenteral nutrition, chemotherapy, or antibiotics, further
damage and disruption occurs.
Studies have shown that more than half of upper extremity VTEs
in children and almost 80% in neonates are associated with a CVC.
 Catheter dysfunction or bloodstream infection may be the first signs of a
VTE.
 Asymptomatic right atrial thrombosis (RAT).
 Usually, signs of superior vena cava (SVC) obstruction like plethora,
swelling, and edema of head and neck and collateral vessels over chest and
neck are later findings.
 Edema of head and neck and collateral vessels over chest and neck are later
findings.
 Clinical Manifestation
Deep Vein Thrombosis;
Commonly present in the lower extremities, especially in the Iliac,
Femoral, &/Or Popliteal Veins.
 Presents with unilateral pain, swelling, and/or erythema of the
involved extremity.
Larger calf diameter in the affected leg compared with the
contralateral leg.
Homans' sign is unreliable for signaling the presence of DVT in
children.
 Deep Vein Thrombosis

• Upper extremity DVT

 manifests with unilateral swelling and discoloration of the arm
and hand & Swelling of the face if the thrombus extends into
the SVC.
 Effort-related upper extremity DVT (Paget-Schroetter
syndrome or venous thoracic outlet syndrome) is a rare condition
that typically affects young, healthy individuals, most
commonly males
 MRV, CT, or contrast venography
 Duplex ultrasound
the initial test for diagnosis
Noncompressibility of the vein with or without visible
intraluminal thrombus and absence of flow are the major
22/11/2024
criterion for the diagnosis
 Pulmonary Embolism

 Ssx include SOB, pleuritic chest pain, cough, hemoptysis, fever, tachypnea,
tachycardia, and/or, in the case of massive pulmonary embolism,
hypotension and right sided heart failure.
 often undiagnosed because young children are unable to describe their
symptoms accurately, and their respiratory deterioration may be masked by
other conditions
 CT Angiography (CTA) should be obtained in patients where PE is clinically
suspected

22/11/2024
 Cerebral Sinovenous Thrombosis

 Results from thrombosis of the superficial dural or deep venous sinus system
leading to impaired drainage wherein ischemia, infarction, or hemorrhage may
occur.
 Ssx of CSVT may be subtle and may develop over many hours or days
 Neonates with CSVT often present with seizures, whereas older children often
complain of headache, vomiting, seizures, visual changes, and/or focal
neurologic signs.
 risk factors may include concurrent sinusitis or mastoiditis, trauma, meningitis,
or dehydration.
 CT venography is sensitive to identify the thrombus
 MRI/MRV can identify associated non-hemorrhagic brain lesions.

22/11/2024
 Renal Vein Thrombosis

 Is the most common spontaneous VTE in neonates

 may present with triad of hematuria, abdominal mass, and thrombocytopenia.
 Approximately 25% of cases are bilateral.
 risks include PNA, shock, polycythemia, cCHD, maternal diabetes, and
sepsis, which result in reduced renal flow, hyperviscosity, hyperosmolality,
and hypercoagulability.
 Cxns include irreversible renal atrophy, HTN, and CKD.
 ultrasonography is the radiographic test of choice.

22/11/2024
 Portal Vein Thrombosis

 Often occurs during the neonatal period

 often asymptomatic, only manifesting in those patients who develop symptomatic
portal hypertension after the initial thrombotic event
 The most common risk factor associated with PVT is an umbilical venous
catheter
 Pancreaticoduodenal and peribilliary collaterals resulting in “cavernous
transformation” eventually develop around the obstructed veins  risk for variceal
bleeding
 spontaneous resolution is seen in 70-77% of patients.
 Neonates with acute occlusive PVT may warrant anticoagulation (6-12 weeks).
 Nonocclusive clots may be monitored by serial ultrasounds with annual screening
recommended for evolving portal hypertension for >5 years postdiagnosis.

22/11/2024
 Investigations
• Complete blood count
• Baseline Prothrombin time (PT) and aPTT & INR.
• Fibrinogen level
• Factor VIII activity level & D- dimer level
 Diagnosis
Lower extremity DVT;
 Compression ultrasonography is recommended for initial evaluation.
 If ultrasonography is normal and the clinical suspicion of DVT
remains high, the study can be repeated after a week.
 In children with suspected proximal extension of femoral DVT, MRV
is the appropriate diagnostic study.
 Upper extremity DVT
• Initial assessment - Ultrasonography; however, it is insensitive
for detection of central intrathoracic VTE.
MRV, CT, or contrast venography; we prefer MRV because it
does not expose the child to radiation.
 Pulmonary Embolism
 Arterial blood gas;
• hypoxemia, hypocapnia, and respiratory alkalosis
 Brain natriuretic peptide;prognostic role in PE.
 Troponin.
 ECG;nonspecific ST-segment and T-wave;S1Q3T3
 Atrial arrhythmias
 Right bundle branch block
 Inferior Q-waves
 Precordial T-wave inversion and ST-segment changes
 Chest radiography;Atelectasis or a pulmonary parenchymal
abnormality,Pleural effusion.
 V/Q scan;combinations of clinical and lung scan probability
 CT-pulmonary angiography (CTPA)
 gold standard
 A filling defect or abrupt cutoff of a small vessel
 Spiral (helical) CT.
 Anticoagulant therapy and Thrombolytics
to reduce the
The of
goal halt clot ex- prevent recur-
risk em-of anticoagulation
tension rence
bolism
 ANTICOAGULANT AGENTS

• Anticoagulant agent commonly used in children

include
• low molecular weight heparin (LMWH)
• Unfractionated heparin (UFH)
• direct oral anticoagulants
 Indications and duration of anticoagulant therapy in VTE
• Provoked VTE- develop due to identifiable underlying conditions
and risk factors
• In Provoked VTE with additional fulfillment of the following criteria

( low chance of recurrence)

– Patient has no prior history of VTE

– VTE is not severe or life threatening

– Provoking risk factor is transient

– Thrombus has resolved or is nonocclusive within six weeks

six weeks of anticoagulant therapy rather than the conventional three

month duration is suggested
 Cont..

• For those with persistent provoking risk factors and

those with severe or life-threatening VTE, at least three
months of anticoagulant therapy is suggested

• Unprovoked VTE - Therapeutic anticoagulation for 6 to

12 months
• Recurrent unprovoked VTE- VTE are treated indefinitely
 Initial and subsequent treatment in VTE
• Initial therapy (first 5 to 10 days) - administering

parenteral anticoagulant therapy for at least five days.

• For most patients, LMWH rather than UFH is suggested

• Subsequent treatment —

– Adolescent patients (age ≥12 years)- DOACs are suggested

– Children 2 to <12 years old- either a DOAC or LMWH is

suggested

– Infants and children <2 years old - LMWH is suggested

UpToDate 2023
Enoxaparin dose
 Transitioning from parenteral to oral therapy
• DOACs –
– when transitioning from LMWH, DOAC should be started at the time of or
up to two hours prior to the next scheduled LMWH dose.
– When transitioning from a continuous UFH infusion, the DOAC is started
at the time that the UFH infusion is discontinued

• VKA
– it can be started after one to two days of parenteral therapy.

– Treatment should overlap with UFH or LMWH until the international

normalized ratio (INR) is in the therapeutic range (ie, 2.0 to 3.0) on two
consecutive days.
 APPROACH TO VTE PROPHYLAXIS
• Primary prophylaxis — Indications for primary prophylaxis in children

without a prior episode of VTE are not well established.

• Hospitalized patients

– Mechanical prophylaxis – The use of mechanical methods for VTE risk

reduction and Early mobilization is encouraged this may be sufficient

prophylaxis in patients who are low risk ≤1 VTE risk factor

– Indications for pharmacologic thromboprophylaxis – There are no

established standards of practice regarding when to initiate

thromboprophylaxis in hospitalized children; decisions are individualized

 APPROACH TO VTE PROPHYLAXIS

• Secondary prevention — For patients with a prior episode of VTE if the

patient has either of the following:

– prior history of provoked VTE with ongoing or persistant VTE risk factor(s)

other than CVC

– Recurrent unprovoked VTE

• Recommended Choice –low molecular weight heparin (LMWH) is generally

the preferred agent since there is greater experience with this agent
• Duration – Thromboprophylaxis is continued only so long as important

clinically relevant risk factors persist.

• Patients with long-lasting VTE risk - warfarin is suggested because

greater experience and more data available regarding its use

Advantages and disadvantages of different anticoagulants for treatment of venous
thromboembolism in children and adolescents

UpToDate
 Advantages and disadvantages of different anticoagulants for
treatment of venous thromboembolism in children and adolescents
Special considerations
 Thrombolytics

• Directly promote fibrinolysis

• Tissue-type plasminogen activator is an activator of
fibrinolytics system
• In hemodynamically significant PE and extensive limb
threatening VTE
• potential reduction in the risk of post-thrombotic syndrome
 Contraindications to thrombolytics
• Active bleeding

• Inability to maintain the platelet count >75,000/ μL

• Preterm GA < 32 wks

• A major operation within 7 to 10 days,

• Seizures within 48 hours

• Central nervous system surgery/ischemia/trauma/hemorrhage

within 30 days,
• Uncontrolled HTN
 Other therapeutic agents
• plasma protein C concentrate –

– Severe congenital protein C deficiency

– purpura fulminans secondary to sepsis or meningococcemia

• Antithrombin- replacement

– congenital severe AT deficiency,

– prevention of L-asparaginase–associated VTE in ALL

– acute VTE undergoing heparinization in whom significant AT

deficiency ( heparin resistance)
 Adjunctive therapy

Vena cava filters

– Contraindication for anticoagulation exist
– Recurrent VTE
– Irreversible risk factor for coagulation
– Complications -caudal migration, filter fractures, or caval wall
perforation.
 Pulmonary thromboembolism
• Initial treatment with a parenteral anticoagulant (LMWH or UFH) for 5 to 10 days,

then ongoing anticoagulation with LMWH, a DOAC, or VKA

Duration of anticoagulant therapy

• For non severe PE associated with a transient risk factor - anticoagulation therapy

is continued for six weeks

• For PE that is severe and/or associated with a persistent risk factor -

anticoagulation therapy is continued for a minimum of three months

• For unprovoked PE, the duration of treatment is 6 to 12 months

• thrombolytic agent - should be individualized and considered only extensive and

hemodynamically compromising PE
 Anticoagulation in Arterial Ischemic Stroke ( AIS)

• Acute antithrombotic therapy use and regimens highly variable

worldwide
• Rarely employed in perinatal and neonatal AIS

• in Children Daily aspirin 1 - 5 mg/kg per doses is widely used for

3 months to 1 year
• Patients who experience recurrent AIS while on antiplatelet
therapy should be considered for therapeutic anticoagulation
• Thrombolytic approaches have been employed in isolated cases
 Hemostasis in new born and infant

• Qualitative and quantitative differences in procoagulant

coagulation inhibitors, fibrinolytic components, and platelet
associated factors proteins exist between neonates and
adults
• The overall rate of thrombin inhibition is lower in newborns
than adults
 Thrombotic disorder of the neonates
Homozygous Prothrombotic Disorders
• protein C deficiency less commonly protein S deficiency
• C/F- cerebral or ophthalmic damage in utero, purpura fulminans and rarely
large-vessel thrombosis
• Dx - clinical picture, protein S deficiency & parental heterozygosity
• Tx
– 10 to 20 mL/kg of FFP every 6 to 12 hours
– protein C concentrate 100 to 120 IU/kg then maintained of 45 to 60 IU/kg BID
– Long term management include oral anticoagulation therapy with warfarin
– INR is maintained between 2.5 and 3.5
 Thrombotic disorder of the neonates

• Acquired Prothrombotic Disorders

• Much common in newborns than any other age groups

• 80% of venous and 90% of arterial thrombosis are associated

with IV catheters
on
 PREVENTION OF CATHETER-ASSOCIATED THROMBOSIS
• Arterial catheters –

– use a low-dose heparin infusion to maintain patency of arterial catheters, including both

umbilical artery catheters and peripheral arterial catheters

– This typically consists of an infusion of NS containing UFH at a concentration of 0.25 to 1.0

units/mL at a rate of 0.5 to 1 mL per hour.

• Central venous catheters (CVCs) –

– Heparin flushes (either as a continuous low-dose infusion or intermittent flushes are

commonly used in the NICU

• Obstructed CVCs can be cleared with local instillation of tissue-type plasminogen

activator (tPA; 0.25 to 0.50 mg)

UpToDate 2023
 Thrombotic disorder of the neonates
Renal vein thrombosis
• commonest form of non–catheter-related thrombosis

• Unilateral RVT ( in absence of uremia and extension to IVC)

– supportive care with serial radiographic monitoring or

– heparin therapy with therapeutic doses for 6 weeks to 3 months

• Unilateral RVT extending to the inferior vena cava or bilateral RVT

– Heparin therapy with therapeutic doses for 6 weeks to 3 months

• Bilateral RVT and renal failure

– Thrombolytic therapy should be considered

 Anticoagulation Therapy in Newborns
Heparin
• limited strength of the recommendations

• May have higher relative risk of major bleeding comparing

with adults
• Used in thromboses that are extending or when organ or limb
viability is threatened
• Requirements of neonates are decreased compared to adult
 Anticoagulation Therapy in Newborns
• Average doses depending on gestational age
– bolus doses of 25 to 100 U/kg

– maintenance doses of 15 to 28 U/kg/hr,

• Adjustments
– heparin assays,

– with a target-level anti-Xa range of 0.35 to 0.70 U/mL

• In event of hemorrhage
– Discontinuation of heparin infusion
– Protamine sulfate with caution of anaphylactoid reactions
 Anticoagulation Therapy in Newborns

Low molecular wight heparin

• offers significant therapeutic advantages over unfractionated
heparin
• higher doses requirement in neonates compared with adults
• Doses -1.5-2 mg/kg SC BID, higher dose for the premature
neonates
• Monitoring - anti-Xa heparin assays (target 0.5 to 1 U/mL )
• In event of hemorrhage - Protamine sulfate
 Anticoagulation Therapy in Newborns

During treatment
– Avoid Intramuscular and arterial puncture
– Avoid use of antiplatelet medications

– platelet counts should be monitored periodically

– thrombocytopenic patients should be evaluated for heparin-induced

thrombocytopenia and treated with alternative therapies

• Duration of treatment- 10 to 14 days

• If there is subsequent extension of the thrombus in the absence of

anticoagulation therapy oral anticoagulants may be considered
 Anticoagulation Therapy in Newborns
Warfarin
• Should be avoided

• if used it should be with possible lowest effective dose

• Weekly or biweekly INR measurements and frequent dose

adjustments are required
• Doses are affected by diet, medications, and intercurrent
illnesses
 Antiplatelet and Thrombolytics in newborns

Antiplatelet Agents in Newborns

• Rarely used in newborns for antithrombotic therapy

• Aspirin may be used as adjuvant in thrombotic cerebrovascular events

Thrombolytic Therapy in Newborns

• Indicated in serious thrombotic complications

• Reduced response in neonates

• Plasminogen replacement can be considered if no response

Use of anticoagulant in cardiac diseases
Hypercoagulability state
(coagulation
abnormality,polycythemia,
iron deficiency anemia )

Altered blood follow Endothelial injury

(stasis and turbulent (Turbulent blood flow and
blood flow) inflammation )

Throm-
bosis
Common Thrombotic Complications in CHD Prevention and Treatment
1. Early Postoperative Thrombosis
• Prevention

– Recognize the potential triggers of thrombosis

– Minimize these risk factors whenever possible

– Recognize the signs of perioperative thrombosis and treat

– Always be suspicious of thrombi in high-risk patients

– Thromboprophylaxis is used in aortopulmonary shunt and single

ventricle palliation staged surgeries
Anticoagulation in prosthetic
valve

© 2020 by the American College of Cardiology Foundation and the American Heart Association, Inc.
Treatment of thrombosis and thromboembolism in prosthetic valve

© 2020 by the American College of Cardiology Foundation and the American Heart Association, Inc.
Cont..
Cont..
When the risk of bleeding is
Forlowinvasive Procedures
• Perform the procedure without interruption in anticoagulation

when the risk of thrombosis is low

• Stop the warfarin 48 to 72 hours before the procedure
• Restart the warfarin within 24 hours of the procedure without a heparin bridge

when the risk of both thrombosis and bleeding high

• Stop the warfarin typically 48 hours before the procedure
• Begin UFH when the INR is 2.0 or less and discontinue it 4 to 6 hours before the
procedure
• Restart heparin after the operation Restart heparin after the operation as soon as
the risk of bleeding is determined to be low
• Restart the warfarin and continue the heparin until the INR is 2 or the target INR is
reached
 Thrombolytic Therapy in Children and Adolescents with
Heart Disease

Indication
• a life- or limb-threatening thrombotic event

• intracardiac masses secondary to infective endocarditis.

• catheter-related intracardiac thrombi

 Special circumstance
• Active cancer some clinicians prefer LMWH for treatment of VTE

in pediatric patients with active cancer. However, a DOAC may be

a reasonable option for an older adolescent patient, based upon

indirect evidence from the adult trials.

• Nephrotic syndrome – There are limited data on the use of

DOACs in patients with nephrotic syndrome. Some clinicians

prefer LMWH or VKA when treating VTE in these patients.

.
 Cont..
• Heavy menstrual bleeding – In post menarchal females, there

is increased risk of heavy menstrual bleeding in patients

receiving DOACs compared with VKA; the risk appears to be

greatest with rivaroxaban

• APS – warfarin is generally the preferred agent in patients with

APS. An extended duration is often warranted.

• Heparin-induced thrombocytopenia (HIT) –a non-heparin

anticoagulant should be administered

 Reference
• Nelson 21st edition

• NATHAN_AND_OSKI’S_HEMATOLOGY 8th edition

• 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease

• Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease

Scientific Statement From the American Heart Association Circulation December 17, 2013
Vol 128, Issue 24
• Moss_Adams’_Heart_Disease_in_Infants,_Children,_and_Adolescens

• UpToDate 2023

• NATHAN_AND_OSKI’S_HEMATOLOGY
Thank you