Case 6 SLOs

Describe the most common and dangerous complication of deep venous thrombosis.
Most common and dangerous complication of DVT: Pulmonary embolism where part of the blood clot breaks off and travels
to the lung. Approximately 95% of PE arise from DVT. PE may lodge in the bifurcation (saddle embolus) or large pulmonary
artery branches.
Endothelial injury is most important cause of thrombus formation.
Thrombusisalwaysfoundattachedtoavesselwall
List the risk factors for pulmonary embolism.
Postoperative states (stasis of blood), trauma, oral contraceptives (increased synthesis of coagulation factors, decreased
synthesis of antithrombin III), CHF, prolonged stasis (disrupts laminar flow brining platelets in contact with the endothelium,
prevents dilution of activated clotting factor, retards inflow of inhibitors of clotting fators).
>4 PE is likely on the Wells Score
Describe the clinical spectrum of symptoms seen in pulmonary embolism.
Common signs/symptoms: Shortness of breath (most common and becomes worse with exertion), Chest pain (may feel like
having a heart attack. Pain may become worse when you breathe deeply (pleurisy), cough, eat, bend, stoop and wont go
away until you rest, and Cough (produce bloody/blood-streaked sputum). Additionally, leg pain or swelling usually in the
calf, clammy or discolored skin, excessive sweating, rapid/irregular heartbeat, lightheadedness or dizziness.
Explain the wide range of effects of pulmonary embolism (pathophysiologic), from no symptoms altogether, to immediate
death, or hemorrhagic infarct of the lung, or pulmonary hemorrhage, or pulmonary hypertension and cor-pulmonale.
Large emboli-sudden cause of death (5% of cases). Obstruction of >60% of pulmonary circulation required to cause sudden
death and it is known as Cor pulmonale (right heart failure)
Medium emboli-may or may not cause infarction of lung. Generally no infarction because there is dual blood supply, but
infarction present with compromised cardiac function (i.e. decreased cardiac output). Pathology: Hemorrhagic wedge shape
infarct or coagulation necrosis.
Small emboli-usually asymptomatic and may cause transient dyspnea/tachypnea. No infarction (due to dual lung blood
supply) and generally resolved on its own.
Explain the basis and rationale of the d-Dimer test.
This test is used to rule out a blood clot or stroke. D-dimer protein fragment is made when you have blood clot. Blood clots
generally begin to slowly break down by the presence of plasmin after they are formed, and this process releases D-dimer
into the blood. D-dimer is made of fibrin. High levels of D-dimer mainly used to diagnose DIC, DVT, PE, cancer, or sickle
cell anemia.
Explain the mechanism of action and therapeutic benefit of low molecular weight heparin, vitamin K antagonists, and
unfractionated heparin in PE.
Low molecular weight heparin
o Mechanism of action: activates antithrombin 3 blocking thrombin from acting on fibrinogenfibrin conversion and
ultimately preventing clot formation.
o Therapeutic benefit: Many patients now use this instead of unfractionated heparin in PE for DVT.
Vitamin K antagonists
o Mechanism of action: blocks the hepatic synthesis of coagulation factors II, VII, IX, and X, as well as protein C and
protein S involved in coagulation cascade. Vitamin K epoxide reductase is an enzyme the reduces vitamin K after it
has been oxidized in the carboxylation of glutamic acid residues in blood coagulation enzymes.
o Therapeutic benefit: Coumarin/Warfarin is the most common Vit. K antagonist and is considered an anticoagulant.
Unfractionated heparin in PE
o Mechanism of action: activates antithrombin 3 blocking thrombin from acting on fibrinogenfibrin conversion and
ultimately preventing clot formation.
o Therapeutic benefit: short acting (doesnt cause excess/unwanted bleeding) heparin, given to pregnant women that
need it and administered via IV.

Outline typical EKG findings in patients with PE.

Outline typical EKG findings in patients with PE.

Reviewaboutthediagnostictechniquesincommonuse,suchasXrayandCTscans,EKG,sputumexamination,
bronchoscopyandlungbiopsy.
TwolevelPEwellsscoreestimatesclinicalprobabilityofpulmonaryembolisminPE:Traditional(>6ishigh,26is
moderate,and<2islow).Alternative:>4PEislikelyandshouldconsiderdiagnosticimaging<4PEisunlikelyandconsider
DdimertoruleoutPE.

Xray/CTscanshighcontrastanalysisthatcanallowforimprovedimagingofpulmonaryvasculatureandbeabletodetect
segmentalandsubsegmentalemboli.CTPAcandetectwithmoreaccuracybylookingatthepulmonaryvesselsinparticular
forcontrastwhereanymassfillingdefectappearsdarker.
EKGseeabove
Sputumexamination maypresentwithhemoptysis,whichistheexpectorationofbloodorbloodtingedsputumfromthe
lungs
BronchoscopyandLungBiopsyhelplookforhemorrhagesorblockages
ListanddiscussprophylaxisandtherapeuticapproachesforDVTandP.E.
I. Lifestyle modifications
A. Avoid obesity and inactivity
i. Nutrition without excess calories
ii. Exercise
1. Daily aerobic such as walking
2. Anaerobic activity useful for muscle toning
a. Heavy weightlifting may traumatize muscles
b. Anaerobic does not substitute for aerobic
B. Avoid dehydration
i. Drink water
ii. Minimize alcohol consumption
C. Avoid cigarette smoking
i. Quit smoking
1. Willpower is best
2. Nicotine patch, gum, nasal spray
3. Bupropion (Wellbutrin [GlaxoSmithKline])

D. Maintain normal blood pressure

i. Note some guidelines define normal as <120/80 mm Hg rather than <140/90
mm Hg
ii. If lifestyle changes do not reduce blood pressure, use medication
II. Mechanical measures
A. Vascular compression stockings
i. 10 to 18 mm Hg if immobilized or in bed; otherwise, use higher compression
levels
ii. 20 to 30 mm Hg below-knee stockings if no varicose veins, swelling, or skin
pigmentation changes
iii. 30 to 40 mm Hg below-knee stockings if leg exam has evidence of prior
venous disease
B. Intermittent pneumatic compression boots
i. Ideal for immobilized patients, either in hospital, skilled nursing facility, or at
home
ii. Device is better tolerated when combined with 10- to 18-mm Hg vascular
compression stockings
iii. Some devices have cooling buttons to enhance comfort
III. Pharmacological measures
A. Injectable medications
i. Low-molecular-weight heparin
1. Enoxaparin 40 mg daily
2. Dalteparin 5000 Units daily
ii. Unfractionated heparin 5000 Units every 8 hours
iii. Fondaparinux 2.5 mg daily
B. Oral medication
i. Warfarin
C. Baby aspirin 81 mg daily
i. Provides more protection against heart attack and stroke than against DVT
ii. DVT prevention effect is weak
IV. Combined mechanical and pharmacological measures
Definethrombophilia.Explaintheriskfactors,mechanismofinheritance,andcommonmutationsunderlyingthedisease.
Thrombophiliahypercoagulablestatesoragroupofinheritedoracquiredconditionsthatcauseariskforthrombosis.Theseinclude
deficienciesthathaveeitheradeficiencyinphysiologicantithromboticfactororanincreasedlevelofprothromboticfactor.
Riskfactors:venousthrombosisinpatientslessthan40yearsold,recurrentvenousthrombosisorthrombophlebitis,venous
thrombosisinunusualsite,arterialthrombosisinpatientlessthan30yearsold,strongfamilyhistoryofvenousthrombosis,recurrent
fetalloss,skinnecrosisinpatientreceivingwarfarin,purpurafulminans
Mechanismofinheritance:Riskofdevelopinganabnormalclotinabloodvesseldependsonwhetherapersoninheritsoneortwo
copiesoftheF2genemutationthatcausesprothrombinthrombophilia.Inthegeneralpopulation,theriskofdevelopinganabnormal
bloodclotinabout1in1000peopleperyear.OnecopyofF2genemutationistherisk2to3in1,000.Peoplewhoinherittwocopies
ofthemutation,onefromeachparent,mayhaveariskashighas20in1,000.Canbethoughtofdominantinheritanceandvariable
expression.
5mostcommonhereditaryformsofthrombophilia:

FactorVLeiden(FVL)mutatedformoffactor5cannotbecleaveandthusinactivatedbyproteinsCandproteinsSbecause
itlacksthecleavagesite.


AntithrombinIIIdeficiencythrombinisnormallyproducedbytheendothelialcellstohelpcleavefibrinogenfibrinthatis
neededforclotformation.DeficiencyinantithrombinIIIwillleadtounregulatedproteaseactivityandfibrinformationand
wontallowproperinhibitionofthrombinandactivatedcoagulationfactors.

ProteinCdeficiencyleadstounregulatedfibringenerationbecauseofimpairedinactivationoffactorsVIIIaandVa,two
essentialcofactorsinthecoagulationcascade

ProteinSdeficiencyproteinSistheprincipalcofactorofactivatedproteinC(APC),anditsdeficiencymimicsthatofprotein
CincausinglossofregulationoffibringenerationbyimpairedinactivationoffactorsVIIIaandVa.

Prothrombingenemutationincreasedexpressionofprothrombin,whichwillthenbeconvertedtothrombin,andhigherlevel
ofthrombinwillleadtohigherlevelsoffibrinandclotting.Prothrombincleavedintothrombinviafactor10aandCa 2+.
IRAT
Endothelialcellinjuryistheprincipalmechanismfortheproductionofthrombosisinatheroscleroticcoronaryarteries
Clinicalpathologytellsusthatwithregardstopulmonaryemboli,theyareclinicallysilent.70%ofpulmonaryemboliseenare
clinicallysilent.
ApplicationQuestions
OralcontraceptivesandpregnancycausedecreasedsynthesisofantithrobinIIIandincreasedsynthesisofcoagulationfactors.
IfanindividualhasadiagnosisofaPEandyouhaveaplantoadministerthrombolytictherapy,theclinicalfeaturesthatdefine
treatmentdecisionisclinicalevidenceofhypotension/shock.Therehastobeevidenceofhemodynamiccollapsebeforeyouprogress
tothromobolytictherapybecauseitisgenerallynotthefirstlinetreatment
Ultimately,decisiontousefibrinolytictherapydependsonthecliniciansassessmentof1)Pulmonaryembolismseverity,2)
Prognosis,and3)Riskofbleeding.
1) SeveritysystemicthrombolysisislifesavingandconsideredstandardtherapyinpatientswithmassivePEand
cardiogenicshock.ThrombolysisrapidlyreversessevereRVdysfunctionbydissolutionthatotherwisemightleadto
chronicpulmonaryhypertension.Thrombolysismayalsodissolvemuchofthesourceoftheresidualthrombusinthe
deepveins,therebyminimizinglikelihoodofrecurrentPE.
2) PrognosisThrombolytictherapyshouldonlybeusedinpatientswhoare1)hemodynamicallyunstable,2)mayalsobe
consideredinpatientswithsubmassivePE,
3) RiskofbleedingnotrecommendedforroutinetreatmentofPEbecausetherecanbeseriouscomplications,including
majorhemorrhage.