Pulmonary EmbolismPulmonary Embolism

Learning OutcomesLearning OutcomesCausesCausesDiagnosisDiagnosisRisk FactorsRisk FactorsTreatmentTreatment

Blood flow to the lungsBlood flow to the lungs Venous system from Venous system from

upper and lower parts upper and lower parts of the body drains into of the body drains into the right atrium and the right atrium and then pumped into the then pumped into the right ventricleright ventricle

The right ventricle The right ventricle pumps blood to the pumps blood to the lungslungs

The Clot TravelsThe Clot Travels So if a clot occurs in any So if a clot occurs in any

vein it will eventually (if it vein it will eventually (if it breaks free) end up in the breaks free) end up in the right side of the heartright side of the heart

The heart then pumps it The heart then pumps it into the pulmonary into the pulmonary arteriesarteries

As the pulmonary artery As the pulmonary artery becomes smaller, the becomes smaller, the blood clot will become blood clot will become caught in the lungs. This caught in the lungs. This is a Pulmonary Embolismis a Pulmonary Embolism

Lung Blood FlowLung Blood Flow Typically there is Typically there is

more flow to the lower more flow to the lower area of the lungs, due area of the lungs, due to gravityto gravity

PEs can occur PEs can occur anywhere in the lung, anywhere in the lung, but more are seen in but more are seen in the lower portion than the lower portion than upper portionupper portion

No preference to No preference to which side it occurswhich side it occurs

Saddle EmbolusSaddle Embolus This is where a clot This is where a clot

occurs at the point of occurs at the point of the pulmonary artery the pulmonary artery branchingbranching

This can be fatal, due This can be fatal, due to the large amount of to the large amount of blood flow that is blood flow that is inhibitedinhibited

Incidence of PEIncidence of PE In the UK, PE occurs in 3-4 per 10 000 In the UK, PE occurs in 3-4 per 10 000

peoplepeople This could be possibly higher as this is This could be possibly higher as this is

only based on clinical dataonly based on clinical data Between 2005-2008 it was mentioned on Between 2005-2008 it was mentioned on

the death certificates of 12 - 13 000 peoplethe death certificates of 12 - 13 000 people It is thought that this figure could be as It is thought that this figure could be as

high as 60 000 per year in the UKhigh as 60 000 per year in the UK(NICE 2013)(NICE 2013)

DiagnosingDiagnosing A large number of A large number of

patients are patients are misdiagnosed and misdiagnosed and only found to have a only found to have a PE on autopsyPE on autopsy

We can test for them We can test for them but results can come but results can come back as negative (or back as negative (or inconclusive)inconclusive)

DiagnosingDiagnosing Most PEs come from Most PEs come from

Deep Venous Deep Venous Thrombosis (DVT)Thrombosis (DVT)

Most DVTs (75%) come Most DVTs (75%) come from the legs, from the legs,

20% of clots embolise 20% of clots embolise with higher incidence with higher incidence above the knee rather above the knee rather than belowthan below

The emboli travel via the The emboli travel via the Inferior Vena Cava (IVC), Inferior Vena Cava (IVC), to the heart, to the lungs to the heart, to the lungs PEPE

In the lungs the blood clot In the lungs the blood clot gets lodged in the gets lodged in the pulmonary artery, so pulmonary artery, so there is no more there is no more perfusion to that area of perfusion to that area of lung, thus ventilation lung, thus ventilation occurs without perfusion occurs without perfusion forming a dead spaceforming a dead space

The blood that should The blood that should have gone to that area is have gone to that area is then diverted to other then diverted to other areas of the lung, this areas of the lung, this causes a V/Q Mismatchcauses a V/Q Mismatch

Lung InfarctLung Infarct There is also an increase There is also an increase

in resistance to blood in resistance to blood flow, this can cause a flow, this can cause a cardiac arrest cardiac arrest

The lungs may infarct, but The lungs may infarct, but this is difficult due to the this is difficult due to the dual blood supply, from dual blood supply, from both the pulmonary artery both the pulmonary artery and also from the aorta, and also from the aorta, as it sends branches to as it sends branches to the lungthe lung

Risk FactorsRisk Factors Orthopaedic Procedure – THR, TKR, #sOrthopaedic Procedure – THR, TKR, #s

Lack of mobilisationLack of mobilisation No thrombo-prophylaxis – TEDS, Flowtrons, No thrombo-prophylaxis – TEDS, Flowtrons,

Dalteparin , Warfarin Dalteparin , Warfarin Abdo / Pelvic surgery - especially for CaAbdo / Pelvic surgery - especially for Ca ObesityObesity Women >30yrs on oral contraceptive who smokeWomen >30yrs on oral contraceptive who smoke Hyper-coaguable state – Protein C & S deficiencies, Hyper-coaguable state – Protein C & S deficiencies,

Factor V LeidenFactor V Leiden PregnancyPregnancy

SymptomsSymptoms May be normalMay be normal TachycardiaTachycardia AFAF Reduced chest movement Reduced chest movement

(due to pain)(due to pain) TachypnoeaTachypnoea Pleural rubPleural rub Haemoptysis (especially in Haemoptysis (especially in

lung infarction)lung infarction) Low grade feverLow grade fever Signs of DVTSigns of DVT PP22 Sound, Sound, Right Heart failure- Right Heart failure- CO, CO,

JVP, JVP, BP and Perfusion BP and Perfusion PressurePressure

DiagnosisDiagnosis ABG – ABG – pH / pH / pCO pCO22/ / pO pO22 (or lower normal range) (or lower normal range) Respiratory AlkalosisRespiratory Alkalosis pOpO22 due to V/Q Mismatch due to V/Q Mismatch pCOpCO22 due to tachypnoea (trying to make room for O due to tachypnoea (trying to make room for O2)2)

AAlveolar-arterial oxygen (A-a) gradient lveolar-arterial oxygen (A-a) gradient PPAAOO22 - P - PaaOO22 Alone they are not diagnostic of pulmonary embolism Alone they are not diagnostic of pulmonary embolism

(PE), but they may be useful in excluding the diagnosis (PE), but they may be useful in excluding the diagnosis of PE if their values fall within the normal range of PE if their values fall within the normal range

AAlveolar-arterial oxygen (A-a) lveolar-arterial oxygen (A-a) gradientgradient

PPAAOO22 - P - PaaOO2 2 should equal (Age (years) / 4) + 4should equal (Age (years) / 4) + 4 PPAAOO2 2 = [(F= [(FiiOO22) x (760 – 47)] – (P) x (760 – 47)] – (PaaCOCO22 / 0.8) / 0.8)

Barometric Pressure = 760mmHgBarometric Pressure = 760mmHg

Water Vapour Pressure = 47mmHgWater Vapour Pressure = 47mmHg

Respiratory Coefficient = 0.8Respiratory Coefficient = 0.8

UseUse PPaaOO2 2 andand PPaaCOCO22 in mmHg not KPa in mmHg not KPa

Eg 40 Yr old, Eg 40 Yr old, FFiiOO22 0.6 0.6 PPaaCOCO2 2 32.5 mmHg32.5 mmHg (4.27KPa)(4.27KPa)PPaaOO2 2 65 mmHg (8.55KPa)65 mmHg (8.55KPa)PPAAOO2 2 =(0.6 x 713) – 40.6 = 387.2=(0.6 x 713) – 40.6 = 387.2PPAAOO22 - P - PaaOO2 2 = 387.2 – 65 = 322.2= 387.2 – 65 = 322.2(40/4) = 10 (+4) = 14 (40/4) = 10 (+4) = 14 Therefore 322.2 > 14Therefore 322.2 > 14So if the A-a gradient > 14 it may be indicative of a PESo if the A-a gradient > 14 it may be indicative of a PE

Chest X-rayChest X-rayChest X ray – most common finding with a Chest X ray – most common finding with a

PE is a normal x-rayPE is a normal x-rayBut they are useful as X-rays help to rule But they are useful as X-rays help to rule

out pneumonia and pneumothorax as out pneumonia and pneumothorax as causes of dyspnoea etccauses of dyspnoea etc

Possible signs indicating a PE are as Possible signs indicating a PE are as followsfollows

Hamptons HumpHamptons Hump Not always seenNot always seen Wedged shaped Wedged shaped

pleural based lesionpleural based lesion PE in one area PE in one area

(Bottom arrow) and (Bottom arrow) and everywhere else is everywhere else is infarctinfarct

Causes pleurisy, Causes pleurisy, irritationirritation

Westermark SignWestermark Sign On this X-ray PE is in On this X-ray PE is in

Left lungLeft lung Increase in blood flow Increase in blood flow

to right side.to right side. Minimal blood flow Minimal blood flow

seen to Left lungseen to Left lung So the side that looks So the side that looks

clearer is the side clearer is the side with reduced blood with reduced blood flow, therefore the clotflow, therefore the clot

ECGECG SSIIQQIIIIIITTIIIIII Can be seen in any Can be seen in any

cor-pulmonale cor-pulmonale syndrome where syndrome where pulmonary artery pulmonary artery systolic pressure is systolic pressure is elevatedelevated

Eg Normal PQRST Eg Normal PQRST

ECGECG Lead Lead II Exaggerated S waveExaggerated S wave

Lead Lead IIIIII Exaggerated Q waveExaggerated Q wave T Wave inversionT Wave inversion

Not specific to PE, but Not specific to PE, but gets you to possibly gets you to possibly think of the diagnosisthink of the diagnosis

ECG – Precordial LeadsECG – Precordial Leads Peaked T wavesPeaked T waves V1-V4V1-V4 Makes you think about :-Makes you think about :-

Right Heart Strain, Right Heart Strain, PE, Cor-pulmonalePE, Cor-pulmonale

Tachycardia nearly Tachycardia nearly always seen in PE but always seen in PE but also most other problems also most other problems so non-specificso non-specific

D-dimerD-dimer By-product of fibrin By-product of fibrin

degradationdegradation As clot degraded by As clot degraded by

enzymes, Fibrin enzymes, Fibrin Degradation Products Degradation Products (FDP) are released, one (FDP) are released, one of these is the D-dimerof these is the D-dimer

Little clots in body release Little clots in body release D-dimers, therefore if test D-dimers, therefore if test +ve - do not know if it is +ve - do not know if it is from a PE, from a PE,

But test is so sensitive But test is so sensitive that if no D-dimer ( –ve) that if no D-dimer ( –ve) you can rule out PEyou can rule out PE

UltrasoundUltrasound Non-invasive Non-invasive Looks at lower limbsLooks at lower limbs Doppler USS looks at Doppler USS looks at

vein for flow and vein for flow and compressibilty to see compressibilty to see if clot presentif clot present

USS ResultsUSS Results If +ve for DVT and patient has If +ve for DVT and patient has

respiratory distress symptoms respiratory distress symptoms you can rule in a PE, since the you can rule in a PE, since the DVTs can embolise easily and DVTs can embolise easily and enter the lungs causing enter the lungs causing respiratory problemsrespiratory problems

If -ve for DVT, unsure whether If -ve for DVT, unsure whether there is a PE or not, as a clot there is a PE or not, as a clot from other part of body may from other part of body may have embolised the lung, or a have embolised the lung, or a whole DVT may have travelled whole DVT may have travelled to the lungto the lung

So a –ve result does not give a So a –ve result does not give a thorough answer, whilst a +ve thorough answer, whilst a +ve result may rule it inresult may rule it in

ECHOECHO Sometimes beneficialSometimes beneficial The right ventricle The right ventricle

pumps blood to lungs pumps blood to lungs If clot is present the If clot is present the

pressure at site of clot pressure at site of clot increases and so increases and so does the pressure in does the pressure in the right ventriclethe right ventricle

ECHOECHO The severity of this Pulmonary The severity of this Pulmonary

Artery Pressure (PAP) and the Artery Pressure (PAP) and the severity of the clot, is found by severity of the clot, is found by looking at the tricuspid valve looking at the tricuspid valve and noting how much regurge and noting how much regurge occurs (Tricuspid jet)occurs (Tricuspid jet)

If tricuspid jet is high then PAP If tricuspid jet is high then PAP differential between RA and differential between RA and RV is great and the clot burden RV is great and the clot burden is largeis large

All these tests may help in the All these tests may help in the possible diagnosis of a PE, but possible diagnosis of a PE, but are not definitive testsare not definitive tests

VQ ScanVQ Scan Nuclear medicine scanNuclear medicine scan Looks at perfusion and ventilationLooks at perfusion and ventilation In pneumonia for example, you would get In pneumonia for example, you would get

decreased perfusion and decreased ventilation decreased perfusion and decreased ventilation due to the purulent material present this is a due to the purulent material present this is a “Matched Deficit”“Matched Deficit”

In a PE there is decreased perfusion of the lung In a PE there is decreased perfusion of the lung in the area but ventilation remains the same this in the area but ventilation remains the same this is an “Unmatched Deficit”is an “Unmatched Deficit”

Does Not affect patient in renal failureDoes Not affect patient in renal failure Impaired view if patient has pneumonia etcImpaired view if patient has pneumonia etc

VQ ScanVQ Scan The patients ventilation is The patients ventilation is

assessed by them assessed by them breathing in Xenonbreathing in Xenon

For perfusion the patient For perfusion the patient is injected with Technigas is injected with Technigas (T(Tcc99mMAA)99mMAA)

Use Gamma Camera (a Use Gamma Camera (a glorified Geiger counter) glorified Geiger counter) to measure the nuclear to measure the nuclear materialmaterial

Probability of PEProbability of PE Normal - Full ventilation Normal - Full ventilation

and perfusion seenand perfusion seen Low Pobability for PE – Low Pobability for PE –

(<20%)(<20%) Intermediate probability Intermediate probability

for PE- for PE- V and V and P in P in same areasame area(Matched deficit) (20-(Matched deficit) (20-80%)80%)

High Probability for PE – High Probability for PE – Normal V and Normal V and P (Un-P (Un-Matched deficit) (>80%)Matched deficit) (>80%)

CTPACTPA Contrast injected into body, Contrast injected into body, CT Scan obtained as this is CT Scan obtained as this is

occurringoccurring Vessels viewed on end and Vessels viewed on end and

seen if they light up with seen if they light up with contrast.contrast.

If only partially light up with If only partially light up with contrast there may be a blood contrast there may be a blood clot present stopping flowclot present stopping flow

Do not use if in renal failure Do not use if in renal failure ((Creatanine) (could use Creatanine) (could use HCOHCO33 cover to stop cover to stop nephrotoxic effect of contrast)nephrotoxic effect of contrast)

Unlike VQ Scan if patient has Unlike VQ Scan if patient has a pneumonia it will not affect a pneumonia it will not affect resultsresults

CTPACTPA In 2006 ‘The Christopher Study’ showed that if In 2006 ‘The Christopher Study’ showed that if

you perform a CTPA that was negative for a you perform a CTPA that was negative for a blood clot with a –ve D-dimer result, it was blood clot with a –ve D-dimer result, it was shown to be safe to withhold anticoagulation, shown to be safe to withhold anticoagulation, this supports the reasoning that you should not this supports the reasoning that you should not do a repeat CT scan if first found to be –ve for a do a repeat CT scan if first found to be –ve for a clotclot

The CTPA is the test of choice for diagnosis of The CTPA is the test of choice for diagnosis of PE, if unable to perform this due to PE, if unable to perform this due to Creatanine, the next choice would be a VQ Creatanine, the next choice would be a VQ Scan. Scan.

BUT, these are not the ‘Gold Standard’BUT, these are not the ‘Gold Standard’

Gold StandardGold Standard Pulmonary Angiogram – Pulmonary Angiogram –

Most accurate test, but Most accurate test, but not always best for not always best for patient (most invasive)patient (most invasive)

Catheter inserted into Catheter inserted into right side of the heart, right side of the heart, dye is injected directly dye is injected directly into pulmonary artery, into pulmonary artery, observed under observed under fluoroscopyfluoroscopy

Dangerous, Dangerous, mortality rate, mortality rate,

especially in patients with especially in patients with PEPE

TreatmentTreatment AnticoagulationAnticoagulation Eg Warfarin / HeparinEg Warfarin / Heparin

-Blood thinning-Blood thinning-Prevent new clots-Prevent new clotsNon-thrombolytic Non-thrombolytic treatment treatment

ThrombolyticsThrombolytics-Dissolve Clot, -Dissolve Clot, -not solely used for -not solely used for PE treatmentPE treatment

DVT Treatment 3-6 monthsDVT Treatment 3-6 months PE Treatment 6-9 monthsPE Treatment 6-9 months

IVC FilterIVC Filter

If anticoagulation If anticoagulation treatment treatment contraindicated contraindicated IVC IVC FilterFilter

If clot travels it gets If clot travels it gets caught in IVC Filtercaught in IVC Filter

IVC FilterIVC Filter It is possible for blood clot to be caught and It is possible for blood clot to be caught and

develop in IVC filterdevelop in IVC filter Cochrane Collaboration recommends IVC forCochrane Collaboration recommends IVC for1.1. Recurrent PE despite use of anticoagulation, Recurrent PE despite use of anticoagulation,

or in absolute contra-indication to or in absolute contra-indication to anticoagulationanticoagulation

2.2. Proximal DVT with massive pulmonary Proximal DVT with massive pulmonary thrombosis – next one could kill patientthrombosis – next one could kill patient

3.3. Trauma Patient – needing operationTrauma Patient – needing operation

AnticoagulationAnticoagulation Ideally start Fast acting and slow acting anticoagulants, Ideally start Fast acting and slow acting anticoagulants,

when slow acting anticoagulants at desired level, stop when slow acting anticoagulants at desired level, stop fast actingfast acting

Fast acting -Heparin productsFast acting -Heparin productsHeparin (IV) orHeparin (IV) orLow Molecular Weight Heparin (S/C)Low Molecular Weight Heparin (S/C)

Slow acting – Vitamin K AntagonistsSlow acting – Vitamin K AntagonistsWarfarinWarfarin

Fast ActingFast Acting Heparin productsHeparin products

IV Heparin IV Heparin Aim for therapeutic APTTAim for therapeutic APTTCan be started Can be started immediatelyimmediatelyQuick Anticoagulation Quick Anticoagulation actionactionIf bleeding occurs can If bleeding occurs can stop it and reduced stop it and reduced effects occur within few effects occur within few hours as it has a short hours as it has a short half life (45-60min)half life (45-60min)

Heparin Induced Heparin Induced ThrombocytopaeniaThrombocytopaenia

Can cause highest incidence of HITCan cause highest incidence of HIT-Usually occurs 5-14 days after starting -Usually occurs 5-14 days after starting Heparin Heparin (even if discontinued) or sooner if previously had (even if discontinued) or sooner if previously had heparinheparin-Immune response to heparin-Immune response to heparin

-Antibodies combine with heparin and platelets -Antibodies combine with heparin and platelets causing causing platelet activation of microparticles platelet activation of microparticles which which initiate the initiate the formation of blood clots; the platelet formation of blood clots; the platelet count falls as a count falls as a result, So,result, So,-Platelet count drops by >50%-Platelet count drops by >50%-Get hyper-coaguable state, get more clotting -Get hyper-coaguable state, get more clotting even even though platelet count lowthough platelet count low-If this occurs change from heparin products-If this occurs change from heparin products

Fast ActingFast Acting Low Molecular Weight Heparin (SC)Low Molecular Weight Heparin (SC)

Eg clexane, dalteparin, fondaparinuxEg clexane, dalteparin, fondaparinuxGive twice per day dependent on Creatanine Clearance Give twice per day dependent on Creatanine Clearance

(CrCl) (CrCl) (20-29ml/min)(20-29ml/min)Or if CrCl ≥30ml/min give once a dayOr if CrCl ≥30ml/min give once a dayProblem is if given, anticoagulation is present for next 12 or Problem is if given, anticoagulation is present for next 12 or 24hrs (as half life is four times as long as heparin, about 4 24hrs (as half life is four times as long as heparin, about 4

hrs)hrs)Incidence of HIT is lower than IV HeparinIncidence of HIT is lower than IV HeparinEasy and quick to administerEasy and quick to administer

Also available is rivaroxaban, a fast acting oral medication, Also available is rivaroxaban, a fast acting oral medication, The The effects lasts 8 to 12 hours, but factor Xa activity does not return to effects lasts 8 to 12 hours, but factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible. normal within 24 hours so once-daily dosing is possible.

To work out CrClTo work out CrCl Takes into account Takes into account

Patients Age, Gender, Patients Age, Gender, Ideal Weight (Kg) Serum Ideal Weight (Kg) Serum Creatanine (Creatanine (μμmol/L) from mol/L) from last 24hrslast 24hrs

Use the equationUse the equation((140-Age) x (ideal weight) / ((140-Age) x (ideal weight) /

Cr) x1.23(male) = CrClCr) x1.23(male) = CrCl((140-Age) x (ideal weight) / ((140-Age) x (ideal weight) /

Cr) x1.04(female) = CrClCr) x1.04(female) = CrClUse STH treatment of Use STH treatment of

Thromboembolic Disease Thromboembolic Disease Dalteparin Prescription Dalteparin Prescription ChartChart

ExamplesExamplesEg Age 67 yrsEg Age 67 yrsGender - MaleGender - MaleIdeal Weight 85KgIdeal Weight 85KgCr 73 Cr 73 μμmol/Lmol/LEg (140-67 = 73) Eg (140-67 = 73) 73 x 85 = 6205 73 x 85 = 6205 6205/ 73 =85 6205/ 73 =85 85 x 1.23 = 104.ml/min85 x 1.23 = 104.ml/minSo, 18 000 iu Dalteparin once per day as CrCl > 30ml/minSo, 18 000 iu Dalteparin once per day as CrCl > 30ml/min

Age 85 yrsAge 85 yrsGender – FemaleGender – FemaleIdeal Weight 60KgIdeal Weight 60KgCr – 160 Cr – 160 μμmol/Lmol/L(140-85 = 55) (140-85 = 55) 55 x 60 = 3300 55 x 60 = 3300 3300 / 160 = 20.6 3300 / 160 = 20.6 20.6 x 1.04 = 20.6 x 1.04 =

21.24ml/min21.24ml/minSo, 5000iu Dalteparin am and 5000iu Dalteparin pm as CrCl 20-29ml/minSo, 5000iu Dalteparin am and 5000iu Dalteparin pm as CrCl 20-29ml/min

If patient weighed more than 100Kg split dose if CrCl If patient weighed more than 100Kg split dose if CrCl ≥30ml/min≥30ml/min

Slow ActingSlow Acting Slow – Vitamin K antagonistsSlow – Vitamin K antagonists

eg warfarin 5mg po odeg warfarin 5mg po odAffects factors 2, 7, 9, 10, C and SAffects factors 2, 7, 9, 10, C and SIf started on 10mg po od can get a drop in If started on 10mg po od can get a drop in protein C and S (shortest acting vitamin K protein C and S (shortest acting vitamin K dependent factors), which can cause a dependent factors), which can cause a

hyper-coaguable statehyper-coaguable stateTakes 2-3 days to reach desired level Takes 2-3 days to reach desired level

shown shown by INR of 2-3by INR of 2-3If any medication changes, check INR as If any medication changes, check INR as

can can be affectedbe affected

PreventionPrevention Bilateral Lower Extremity Bilateral Lower Extremity

Sequential Compression Sequential Compression DevicesDevices

TEDs and FlowtronsTEDs and FlowtronsWhen the legs are When the legs are

squeezed the veins release a squeezed the veins release a factor which thins the blood factor which thins the blood stopping clot formation, stopping clot formation, the rhythmic motion copies the rhythmic motion copies that of leg movementthat of leg movement

ThromboprophylaxisThromboprophylaxisDalteparinDalteparin

Genetic Blood TestsGenetic Blood Tests 25-50% of patients with VTE have an inherited disorder25-50% of patients with VTE have an inherited disorder There are genetic causes of metabolism which may be tested forThere are genetic causes of metabolism which may be tested for- Factor V Leiden – causes increased clotting as variant cannot be Factor V Leiden – causes increased clotting as variant cannot be

inactivated by Factor Protein C (5% of popinactivated by Factor Protein C (5% of popn n and 20% of pts with and 20% of pts with thrombus)thrombus)

- Factor Protein C Deficiency – results in normal cleaving of Factor Factor Protein C Deficiency – results in normal cleaving of Factor Va and Factor VIIIaVa and Factor VIIIa

- 20210 (prothrombin) Mutation – 2-3 times risk of clot formation20210 (prothrombin) Mutation – 2-3 times risk of clot formation- MTHMFR affects regulation of homocysteineMTHMFR affects regulation of homocysteine- Lupus anticoagulant- prothrombotic agent which can cause Lupus anticoagulant- prothrombotic agent which can cause

inappropriate clottinginappropriate clotting- Anti phospholipid antibody – confused autoimmune responseAnti phospholipid antibody – confused autoimmune response

If any of these are positive and patient has a clot then may need If any of these are positive and patient has a clot then may need treatment for longertreatment for longer

So, RememberSo, Remember