PULMONARY EMBOLISM
Done by : Ali Al-Thubyani , Pharm D Candidate
Supervised by : Hend Metwali , Associate Clinical Pharmacist
Background Pulmonary embolism (PE), is a sudden blockage in
a lung artery. The blockage usually is caused by a blood clot that travels to the lung from a vein in the leg.
A clot that forms in one part of the body and travels in the bloodstream to another part of the body is called an embolus .
If a blood clot is large, or if there are many clots, PE can cause death
Background PE is a serious condition that can:
Damage part of your lung because of a lack of blood flow to your lung tissue. This damage may lead to pulmonary hypertension (increased pressure in the pulmonary arteries).
Cause low oxygen levels in your blood. Damage other organs in your body
because of a lack of oxygen
Etiology of PE
1) Stagnation of blood flow.
Stagnation of blood may be related to: Bed rest, paralysis, varicose veins,
surgery Reduced cardiac output, e.g. in heart
failure
Etiology of PE
2) Increasing the risk of hyper-coagulability
include: Surgery Pregnancy, estrogen administration Malignancy, myocardial infarction Several acquired or inherited disorders of
coagulation e.g, (antithrombin III, ptn C&Sdeficiency)
Etiology of PE
DVT : it is the most common cause of PE.
Deep vein clots are not like clots in veins close to the skin's surface. Those clots remain in place and do not cause PE.
Clinical presentation of PE
Symptoms :
Cough, chest pain/tightness, dyspnea, palpitation, hemoptysis.
Dizziness with large PE . Symptoms often confused with MI . Patients may die suddenly before TTT
can be initiated.
Clinical presentation of PE
Signs:
Tachypnea, tachycardia, diaphoresis, distended neck veins .
Cyanosis or hypotension if large PE . Cardiovascular collapse (shock, oliguria) .
Laboratory tests ↑ESR & leukocyte count
of PE Diagnosis
Diagnostic Test :
Pulmonary angiography (gold standard) difficult & expensive
Ultrasonography . CT . Ventilation-perfusion (V/Q) D-dimer test (good negative) help exclude
PE. Wells Criteria
Treatment of PE Treatment of PE involves the use of anticoagulants
and, in severe cases, thrombolytic drugs.
Warfarin should begin concurrently with UFH
or LMWH therapy. For patients with acute PE ,
heparin and warfarin therapy should be overlapped
for at least 4 to 5 days. The UFH or LMWH can then
be discontinued once the INR is within the desired
range for 2 days .
Warfarin Warfarin is the most widely used
coumarin because of potency, reliable
bioavailability and an intermediate half life
of elimination (36 h) .
It Inhibits vitamin K–dependent
clotting factors II, VII, IX, and X, ptn C&S.
Full antithrombotic effect achieved
8 to 15 days after initiation of
Therapy .
Indications of Warfarin
Duration of treatment Event 3 months for first events Venous thrombosis
Lifelong for recurrent attacks
3 months for first events Pulmonary Embolism
Life long for recurrent attacks
Life long Atrial Fibrillation
Life long Mechanical heart valve
Dosage And Resistance Begin warfarin on day 1 of heparin initiate at 5–10 mg/day.
In case of resistance to warfarin try to :
May increase warfarin dosage to 10-mg. Monitor INR and plasma concentrations of
Warfarin. Alternative: low-molecular-weight heparin
(LMWH).
Special Population
Specific patient populations may need starting dose of 5 mg/day or less.
Elderly Malnourished patients Debilitated patients Major surgery Heart failure Hepatic impairment
Adverse effects of warfarin
Bleeding . Epistaxis, hematuria, gastrointestinal
(GI) hemorrhage, bleeding gums .
Skin Necrosis . Extensive thrombosis of venules and capillaries
Caused by protein C or protein S deficiency If occurs, discontinue warfarin and initiate
heparin. Restart warfarin at low dose (e.g. 2 mg/dose) and
increase gradually over several weeks
Adverse effects of warfarin
Purple toe syndrome. It is rare but if it occurs discontinue warfarin , it
may takes several weeks to months till discoloration disappear .
Teratogenicity
If pregnant, Unfractionated heparin or
LMWH is safe to use. Breastfeeding: can use warfarin
because not excreted in breast milk
Monitoring Parameter
Signs and symptoms of bleeding:
a. Nose bleeds, bleeding gums, hematuria, unusual bruising, prolonged bleeding from cuts
b. Purple toes
International normalized ratio
Monitoring Parameter Usually, goal INR is 2.0–3.0 In patients with mechanical heart valve the targeted
INR is 2.5-3.5
Mildly elevated INR (3.5 to 5.0): reduce dose or
hold 1 or 2 doses. INR 5 to 9: hold warfarin ± low dose vitamin K.
Serious/life-threatening bleeding IV vitamin K fresh frozen plasma clotting factor concentrates recombinant factor VII
Bridge anticoagulation
Bridge anticoagulants is recommended
During invasive procedures .
Discontinue warfarin 5 days preoperatively and perform procedure when the INR has normalized.
Bridge anticoagulation
Start LMWH after 4 days preoperatively and hold it 24-hours before surgery .
Resume both warfarin and LMWH 12-24 hours after surgery .
NO need to change anticoagulation
therapy for dental procedures, cataract surgery, or dermatologic procedures
Heparin There are two forms of heparin : UFH and
LMWH (enoxparin , dalteparin and tinazaparin )
Advantages of LMWH over UFH: Predictable anticoagulation dose response. Improved subcutaneous bioavailability Longer biologic t½. Lower incidence of thrombocytopenia. Reduced need for laboratory monitoring.
Indications of LMWH Deep vein thrombosis treatment (with or
without PE ) Hip-replacement surgery (prophylaxis) Knee-replacement surgery (prophylaxis Abdominal surgery (prophylaxis)
Dose : 1 mg/kg SC /12 h or 1.5 mg/kg SC / 24 h of Enoxaparin
Adverse effects of LMWH :
Most common: bleeding Thrombocytopenia , avoid
with HIT history
If CrCl < 30 mL/min :
Reduce enoxaparin dose Or use UFH.
Dalteparin & tinzaparin less
accumulation in renal insufficiency which could be a good alternatives .
Monitoring Parameter
Monitoring by aPTT but not necessary due to predictable anticoagulant response with SC administration .
Monitor CBC . Monitor platelets count every 2-4 days
from day 4 to 14. Monitor Serum creatinine .
Factor Xa Inhibitors Fondaparinux
FDA-approved indications :• VTE prophylaxis following orthopedic
surgery• DVT/PE treatment
HIT in pregnancy
Dosage and monitoring VTE prevention: 2.5 mg SC once daily 6 to 8
hr after surgery• < 50 kg: not indicated
DVT or PE treatment: 7.5 mg SC once daily
◦ > 100 kg: 10 mg once daily
◦ < 50 kg: 5 mg daily
Monitor for bleeding : CBC and Kidney function test , if CrCl less than 30 discontinue .
Direct Thrombin Inhibitors
Four parenteral agents: Lepirudin, Desirudin, Bivalirudin, Argatroban
Oral agent : dabigatran .
Dose adjustment
Monitoring Indication Drug
↓ renalfunction
PTT HIT lepirudin
↓ renalfunction
PTT VTE prophylaxis in hip surgery
desirudin
↓ renalfunction
ACT and aPTT
unstable anginaundergoing PTCA
Bivalirudin
↓ liverfunction
ACT and aPTT
HIT Argatroban
Adverse effects of DTIs
serious hemorrhage minor bleeding no agents to reverse DTI activity Concurrent use of DTIs & thrombolytic
agents increases bleeding risk
Special population
Pregnancy :
Warfarin is contraindicated .
LMWH is more preferred than UFH.
Cancer patients : VTE is frequent complication of
Malignancy. LMWH has lower incidence of bleeding . warfarin often not used .
Heparin Induced Thrombocytopenia (HIT)
Serious adverse effect Severe thrombotic complications High morbidity & mortality ↑ incidence with UFH than LMWH Typically begins at days 4 to 14 but can
be delayed up to 20 days .
Heparin Induced Thrombocytopenia (HIT)
Diagnosis:
+ve heparin antibody drop in platelet count > 50% from
Baseline platelet activation & thrombin
generation
Heparin Induced Thrombocytopenia (HIT)
Treatment :
Once HIT is diagnosed: discontinue all sources of heparin DTIs: drug of choice for HIT + thrombosis Only lepirudin & argatroban are FDA approved both considered equally suitable for initial TTT administered IV infusion titrated based on aPTT .
Heparin Induced Thrombocytopenia (HIT)
For warfarin : initial rapid reduction of protein C ↑
risk of thrombosis in patients with HIT. can be used for long-term
anticoagulation.
Avoid heparin for at least 3 to 6 months.
Reference Joseph T. Dipiro , Robert L. Talbert & Gary C. Yee . (2008) Pharmacotherapy A pathophysiologic Approach . Seventh
Edition Adam C. et al .HIT Pocket Guide
(2009).American society of hematology.
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