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.

THANK YOU