Venous Thromboembolism Pharmacotherapy

1. Lesson 6
Venous Thromboembolism
Tsegaye Melaku (BPharm, MSc)
[Assistant Professor of Clinical Pharmacy]
tsegayemlk@yahoo.com or tsegaye.melaku@ju.edu.et +251913765609January, 2020
Pharmacotherapy of Cardiovascular Disorders
1

2.  Session Tips
2
 VTE and pregnancy
 Optimal management of anticoagulation
therapy
 VTE in patients with cancer
 HIT
 Treatment of VTE (DVT & PE)
 Diagnosis of VTE
 Prevention of VTE in surgical
and medical patients

3.  The process of blood clot formation at the site of vessel injury.
 Phases:
I. Initiation and formation of the platelet plug.
– Adhesion: deposition of platelets on the subendothelial matrix
– Activation: release of ADP, TxAs, other chemicals.
– Aggregation : platelet-platelet cohesion
– Secretion: release of platelet granule proteins
– Procoagulant activity: enhancement of thrombin generation
3

4. II. Propagation of the clotting process by the coagulation cascade
III. Termination of clotting by antithrombotic control mechanisms
– It is balanced by fibrinolytic system
IV. Removal of the clot by fibrinolysis
4

5. 5
 Coagulation system is divided into two pathways
– Extrinsic Pathway:
– Begins after trauma to vascular wall & surrounding tissue.
– Intrinsic Pathway:
– Begins in blood itself

6. 6
Activewithoutproteolyticmodification

7. 7
Fibrin degradation productsFibrinogen Fibrin-clot
PlasminPlasminogen
T-PA
FXIIa
HMWK
Kallikrein
Urokinase
Streptokinase
Clotting Cascade

8.  Prothrombin time (PT)
– Test of Extrinsic pathway
– Measure Vitamin K dependent factor activity (factor II, VII,
IX and X)
– Normal value: 12-14 seconds
 International normalize ratio (INR)
– Standardized PT reporting
– Normal value 0.8-1.2 seconds
– Most sensitive to alteration in factor VII levels.
– Prolonged decrease of normal factor VII activity.
8

9.  Activated Partial Prothrombin(APTT)
– Test for intrinsic common pathway
– Depends activity of all coagulation factor (except VII, XIII)
– Normal value: 25-35 seconds
– Prolonged only if coagulation factor reduced to <30% of
normal
9

10.  Thrombosis: the formation or presence of a blood clot within a blood
vessel ~Merriam-Webster’s Medical Dictionary
 Embolism: obstruction or occlusion of a vessel by a transported clot or
vegetation, a mass of bacteria, or other material ~ Stedman’s Medical
Dictionary
10

11.  Arterial thrombosis
– Occurs in the setting of high flow & high shear stress,
– Platelets play a prominent role in the initiation and growth of
the thrombus.
– AF & mural thrombus in the left ventricle following a MI
 Venous thrombosis
– Form in a low-flow, low-shear stress environment.
– Usually forms initially in the valve pockets of deep veins,
– Consists mainly of fibrin and red cells with few platelets.
11

12.  VTE : common and serious blood clotting condition
– Potentially fatal disorder/significant health problem in aging
society
– Blood clots in the veins
– Serious medical condition that can cause disability& even
death
– Preventable and can be treated
12

13.  Most frequently occurs in patients
– Sustain multiple trauma
– Undergo major surgery
– Immobile for a lengthy period of time
– Hypercoagulable disorder
13

14. 14
VTE
Deep-vein thrombosis (DVT)
Pulmonary embolism (PE)
• Death can occur within minutes after the onset of symptoms,
• Before effective treatment can be given.

15.  DVT: blood clot that typically forms in the deep veins of the leg.
 DVT can develop into a PE
– Life-threatening condition that occurs when the clot breaks
free and becomes lodged in the arteries of the lung.
15

16.  Often clinically silent,
– First manifestation may be sudden death
– Significant complication
 Post-thrombotic syndrome
 Chronic thromboembolic pulmonary hypertension (CTPH)]
16

17. 17

18.  Prevalence
18
Recurrence in 10 years

19.  One of the three major CV causes of death, along with MI and stroke.
 Unknown true incidence in the general population
– Due to >50%, have clinically silent disease
 ≈350,000 to 900,000 people develop VTE/yr in US
 >100,000 death/yr
 Leading cause of hospital associated premature death and disability
(DALY) world wide
ISTH Steering Committee for World Thrombosis Day. Thrombosis: a major contributor to global disease
burden.J Thromb Haemost 2014; 12: doi: 10.111/jth.12698
19

20.  Incidence rate of symptomatic VTE 100 per 100,000/yr.
 Incidence of VTE  >50% in the absence of effective
prophylaxis.
 Incidence of VTE high
– Prior Hx VTE
– Metastatic cancer
– MI, stroke, and spinal cord injury
– Disorders of hypercoagulability
20

21. MedicalSurgical
52% at risk for VTE (50% receive ACCP recommended prophylaxis)
64% at risk for VTE
59% receive ACCP
recommended prophylaxis
42% at risk for VTE
40% receive ACCP
recommended prophylaxis
32 countries; 358 sites, from 68,183 Patients
First patient enrolled August 2, 2006;Last patient enrolled January 4, 2007
21

22. 22
 Acquired
 Hereditary
Inherited thrombophilia
Factor V Leiden mutation
Prothrombin gene mutation
Protein S deficiency
Protein C deficiency
Antithrombin (AT) deficiency
Rare disorders Dysfibrinogenemia
Acquired disorders
Malignancy, central venous catheter
Surgery, especially orthopedic
Trauma, Pregnancy, Oral contraceptives
Hormone replacement therapy
Tamoxifen, Thalidomide, Lenalidomide
Immobilization, Congestive failure
Anti-phospholipid antibody syndrome
Myeloproliferative disorders
• Polycythemia vera
• Essential thrombocythemia
Paroxysmal nocturnal hemoglobinuria
IBD, Nephrotic syndrome

23. 23
 FAMILY HISTORY of blood clots or an inherited condition that Increases
clotting risk.
 HOSPITALIZATION for any reason increases the risk of developing a VTE.
 DECREASED BLOOD FLOW often caused by inactivity: confinement to
bed, limited movement, prolonged travel, paralysis, or stroke.
 INJURY TO A VEIN often caused by: fracture, surgery, or severe muscle injury

24. 24
 INCREASED ESTROGEN often caused by: birth control pills, hormone replacement
therapy, or pregnancy.
 CHRONIC MEDICAL CONDITIONS such as: cancer, lung disease, kidney
disease, inflammatory bowel disease, or obesity.
 AGE: anyone can get a clot, but the risk increases with age

25. 25

26. 26
RudolphVirchow
1821-1902

27.  A disruption of this system of checks and balances
– Thrombogenic and antithrombotic stimuli
27

28.  Stasis of blood (immobility, varicose veins, tumor, obesity, pregnancy, AF,
LV dysfunction, low HR/BP)
– Favors thrombogenesis
» ↓clearance of activated clotting factors from sites of
thrombus formation.
– Valves in the deep veins of the legs & contraction of the calf
and thigh muscles  Facilitate the flow of blood back to
the heart and lungs.
– Reduced venous blood flow
28

29.  Hypercoagulability
– Hereditary deficiencies, gene mutations, and acquired
diseases.
– Activated protein C resistance (most common)
• 90 % results from a mutation on factor V.
• aka factor V Leiden
– Prothrombin G20210A mutation(4%)
– ↑concentrations (VIII, IX, & XI or fibrinogen)
29

30.  Acquired cause:
– Malignancy, anti-phospholipid antibodies(SLE and IBD), estrogen use
– Infection and sepsis, dehydration
– Tumor cells
– Secrete a number of procoagulant substances
– Suppressed levels of protein C, protein S, & antithrombin
– Barrier for host immunity(mechanisms)
– Angiogenesis, metastasize
30

31. 31
 Estrogen-containing contraception
 Estrogen replacement therapy
 SERMs
 Estrogens
– ↑Serum clotting factor concentrations
– ↑Induce activated protein C resistance.
– During pregnancy & immediate postpartum period
Venous thrombosis

32.  All risk factors for VTE influence at least one of these 3 mechanisms
(Virchow's triad).
 Obstruction of venous outflow by thrombi
32
Embolization into the pulmonary circulation
Inflammation of the tissues surrounding it
Inflammation of the vein wall

33.  Dislodgement of blood clot
– Lower Extremities (65%-90%)
– Pelvic venous system
– Renal venous system
– Upper Extremity
– Right Heart
33

34. 34

35. 35
† Thrombus: majority in the lower extremities
† Once formed, may either
– Remain asymptomatic,
– Spontaneously lyse,
– Obstruct the venous circulation,
– Propagate into more proximal veins,
– Embolize, or combination of these

36. 36
 Post-thrombotic syndrome*, CTPH, recurrent VTE(long-term)
 Unilateral leg pain & swelling(frequent)
 Leg warmth
 Dilated superficial vein ‘’palpable cord’’
 Calf tenderness
 Pain on the back of the knee on dorsiflexion (Homan’s sign)

37.  Cough, Chest pain, Chest tightness
 SOB, hypoxia, diaphoresis, cyanosis
 Palpitation, tachypnea, tachycardia
 Hemoptysis, distended neck
 Dizziness, light headedness,
 Circulatory shock
 Confused with MI
37
Massive case

38.  History
– Dyspnea (73%)
– Pleuritic Chest pain (66%)
– Cough (37%)
– Hemoptysis (13%)
 With a large PE:
– Syncope
– Hypotension
38

39. 39

40. 40

41. 41

42. 42

43. S.No Criteria Point
1. Active cancer (Rx within <6 months or palliative care) (1)
2. Calf swelling (3 cm difference) (1)
3. Collateral superficial veins (1)
4. Paralysis, paresis, or recent immobilization LE (1)
5. Pitting edema confined to involved leg (1)
6. Bedridden within 3 days/surgery w/anesthesia <3mths (1)
7. Swollen leg (1)
8. Alternate dx more likely (RA. Infective cellulitis,
Superficial thrombophlebitis)
(-2)
43
Probability: Low (≤0 pts) Intermediate (1-2 pts) High (≥3 pts)

44.  Degradation product of fibrin blood clots
– 96-100%(sensitivity)
– Normal: <500 ng/mL (most studies)
 Low Well’s Score + normal D-Dimer:
– Low clinical risk of VTE
– 0.5% of patients develop DVT in 3 months
– Can defer further testing
 Risk of DVT in moderate-high risk Well’s score + normal D-Dimer?
– Moderate risk : 3.5%
– High risk: 21%
44

45.  Gold standard for DVT
 Invasive procedure
 Expensive
 Need administration of radio opaque dye to foot vein.
 Cause anaphylaxis/ nephrotoxicity due to dye
 Primarily a research tool
45

46.  Duplex scan of LE
– Compressibility of the vein
– Doppler flow within the vein
 Asymptomatic patient with proximal LE DVT
– Sensitivity: 47-62%
 Symptomatic patient with proximal LE DVT
– Sensitivity: 89-96%
– Specificity: 94-99%
 Symptomatic patient with distal LE DVT
– Sensitivity: 73-93%
46

47. 47
S.No Criteria Point
1. Clinical signs & symptoms of DVT? (Calf tenderness, swelling
>3cm, erythema, pitting edema affected leg only)
+3
2. PE is #1 Diagnosis, or Equally Likely/ No other suspected cause
for SOB/Dyspnea
+3
3. Heart Rate > 100 +1.5
4. Immobilization at least 3 days, or Surgery in the Previous 4 wks +1.5
5. Previous, objectively diagnosed PE or DVT? +1.5
6. Hemoptysis +1
7. Malignancy w/Rx within 6 mo, or palliative? +1
Probability of PE ≤2: Low ; 2 to 6: Moderate ;>6: High

48. 48

49.  Physical Exam
– Fever: T <102 ºF
– Tachypnea (70%)
– Rales, S4, Hypoxia
– Tachycardia (30%)
– “Massive PE”
 SBP <90 or a drop in
baseline SBP by ≥ 40mmHg
 Acute right HF
– Elevated JVP
– Right-sided S3
49
 Labs
– Arterial Blood Gas (ABG)
– Beta Natriuretic Peptide (BNP)
– Cardiac Enzymes: Troponin
– D-Dimer
 Diagnostic Studies
– EKG
 Imaging
– CXR
– Ultrasound
– V/Q Scan
– Angiography

50.  Pulmonary Angiogram
– Gold Standard
– Not easily accessible
– Radiologist dependent
– Sensitivity (83%)
– Specificity (96%): if negative, very
low likelihood that patient has P.E.
50
 Echocardiogram
– ↓Right Ventricle Size
– ↓Right Ventricular Function
– Tricuspid Regurgitation
– Rarely: RV thrombus

51.  Points are assigned as follows:
– 1 for each year of age
– 10 for male sex
– 20 for HR>110 beats/min
– 10 for heart failure
– 30 for malignancy
51
– 10 for chronic lung disease
– 30 for SBP<100
– 20 for RR>30
– 20 for Temperature <36°C/96.8°F
– 60 for AMS
– 20 for PaO2<90%

52. – 30 day mortality increases with each class
– Class V has a 25 fold higher risk of post-discharge death than Class I.
52
PESI Score Class Risk 30 day mortality Risk
0-65 I 0.0-1.6% Very low
66-85 II 1.7-3.5% Low
86-105 III 3.2-7.1% Intermediate
106-125 IV 4.0-11.4% High
≥125 V 10-24.5% Very high

53. 53

54. 54

55. – Short-term (i.e., few days to 6 months)
– Prevent propagation or local extension of the clot,
embolization, & death.
– Restore patency of the occluded vessel  recanalise vessel.
– Preservation of the function of venous valves.
– Long-term (i.e., >6 months after the first event)
– Prevent complications
55
 Prevent short & long-term complications of the disease

56.  UFH
 LMWH
– Dalteparin (Fragmin)
– Enoxaparin (Lovenox)
– Tinzaparin (Innohep)
 Anti-factor Xa inhibitors
– Fondaparinux
– Idraparinux
– Rivaroxaban
– Abipxaban
56
 Direct thrombin inhibitors
– Argatroban
– Bivalirudin
– Desirudin
– Lepirudin
– Dabigatran
 VKA
– Warfarin (Coumadin)
 Thrombolytics
– Streptokinase
– Urokinase
– Alteplase

57.  Initially: a rapid-acting anticoagulant(In the absence of contraindications)
– UFH, LMWH or fondaparinux
 Overlapped with warfarin for at least 5 days and until the patient’s INR is
greater than 2.
57

58.  Pregnant:
– LMWH
– Monitor anti-factor Xa levels q 4 weeks (4 hrs after dose)
– Goal: 0.6 – 1.0 IU/ml (bid) or 1-2 IU/ml for q day dosing
– Heparin bridge
– Stop LMWH 2 weeks before delivery.
– Start UFH with goal aPTT 1.5-2.3 X normal
– Hold for delivery with restart 6 hrs after vaginal delivery or
12 hrs after C-section.
– Coumadin in the post-partum period
– Three to Six months
– Need to cover at least six weeks post-partum
– Ok for breast-feeding.
58

59.  Obesity:
– Enoxaparin – Drop dose by 25% for patients >144 kg
– Dalteparin – Drop dose by 25% for patients > 190 kg
 General population:
– Enoxaparin:1 mg/kg every 12 hours or 1.5 mg/kg every 24 hours
– Dalteparin:100 units/kg every 12 hrs or 200 units/kg every 24 hrs
– Tinzaparin 175 units/kg every 24 hrs
59

60.  Chronic Kidney Disease:
– No consensus guidelines exist for choice of anticoagulation in patients
with GFR < 30 ml/min
– Bleeding risk and recurrent VTE risk are higher in such patients.
– If using LMWH, consider monitoring anti-factor Xa levels.
60

61.  Malignancy:
– LMWH favored over Coumadin for longterm therapy
– CLOT Trial (Randomized trial, n=672)
– Recurrent DVT 8% (dalteparin) vs 16% (warfarin)
– No difference in major bleeding, death
– Dosing: Dalteparin 200 IU/kg q day x 1 month, then 150 IU/kg q
day x 5 months.
– Max dose: 18,000 IU/day
– No monitoring required.
61

62.  UFH:
– For patients who are unstable, or
– For those who have an adverse prognosis,
– Easy "on/off” control of anticoagulation in the event that
thrombolysis or embolectomy is required
 LMWH :
– For stable patients with a good prognosis in whom advanced
therapy is not being considered.
62

63.  Fondaparinux:
– Selective inhibitor of factor Xa
– 7.5 mg SubQ QD
– For stable patients with a good prognosis;
– To treat stable patients with suspected or proven HIT(off-label)
 Argatroban:
– RF /HIT/suspected HIT
 Lepirudin/ bivalirudin:
– Liver disease/HIT/suspected HIT
63

64.  Meta-analyses have shown:
– Lower recurrence DVT (2.7% vs 7.0%)
– Lower incidence major bleeding (0.9% vs 3.2%)
– Lower death rate at 3 months (OR 0.71 (0.53-0.94))
 More predictable anticoagulation dose response;
 Improved SC bioavailability;
 Dose-independent clearance; Longer biologic half-life;
 Lower incidence of thrombocytopenia;
 Less need for routine laboratory monitoring.
(All favoring LMWH)
64Am J Med 1996 Mar;100(3):269-77; Ann Intern Med 1999 May 18;130(10):800-9

65. 65

66. 66

67. – Proteolytic enzymes (dissolve, or lyse, the fibrin clot)
– Their role in VTE controversial ! !
– Restore venous patency more quickly than anticoagulant;
– ↑bleeding risk
– Decrease short-term pain and swelling
– Prevent destruction of the venous valves
– Long-term benefits from the routine use ??
67

68.  Candidates for thrombolytic therapy
– Massive ilio-femoral DVT who are at risk of limb gangrene.
– Acute massive embolism who are hemodynamically unstable
[SBP<90 mm Hg] and at low risk for bleeding.
– Hemodynamically stable patients with right ventricular dysfunction ?
68

69.  Streptokinase
– 250,000 units IV over 30 mins followed by continuous IV infusion of
100,000 units/hr for 24 hrs (PE) or 24 to 72 hrs (DVT)
 Urokinase
– 4,400 IU/kg IV over 10 mins followed by 4,400 IU/kg/hr for 12 to 24
hrs (PE)
69

70.  Alteplase
– 100 mg by IV infusion over 2 hrs(PE)
 The aPTT should be measured after the completion of thrombolytic
therapy.
 Note: UFH should not be used during thrombolytic therapy.
– If the aPTT <2.5X control, a UFH infusion should be started.
70

71.  Remove a massive obstructive thrombus in a patient with significant
iliofemoral venous thrombosis.
 If the patient is either;
– Not a candidate for or has not responded to thrombolysis.
71

72.  Refer to DVT guidelines, with addition of:
– UFH is considered equal option to LMWH.
– Heparin dosing should be adjusted to achieve aPTT 1.5-2.5 x the
upper limit of normal.
– Thrombolytics: if hemodynamic instability.
– Indications: persistent hypotension, severe hypoxemia, large
perfusion defects, right ventricular dysfunction, free floating
right ventricular thrombus.
– Embolectomy
– IVC Filter
72

73. 73

74. 74

75. 75

76. 76

77.  Bleeding
– If severe, use protamine (1 mg per 100 units LWMH or Heparin)
slow IV infusion over 10 minutes
– If the LMWH dose was given in the previous 8 to 12 hours, the
protamine dose is 0.5 mg per 100 anti-factor Xa units.
– Protamine sulfate is not recommended if the LMWH was given
more than 12 hours earlier.
77

78.  HIT
 Respiratory collapse
– Case reports in 2008
– Hypotension / allergic reactions / deaths
– Epidemiologically linked to UFH use (mainly at dialysis centers)
78

79.  HIT is a profoundly hypercoagulable state
 It is an iatrogenic disorder usually mediated by IgG antibodies that
bind PF4-heparin complexes
– These antibodies cause a hypercoagulable state by activating
platelets and procoagulant microparticles.
 One-third to one-half of patients with HIT develop venous, arterial, or
microvascular thrombosis
 UFH associated with 10-fold increase in risk of HIT compared with
LMWH
79

80. High probability: 6-8 points
Intermediate probability: 4-
5 points
Low probability: ≤ 3 points
Lo J Thromb Haemost 2006;ASH 2009 Clinical Guide
– Clinical Probability Model
80

81.  Uncommon complication
 Occurs 4-10 days after heparin started.
 An immune-mediated reaction to heparins.
 2-3% with UFH ; <1% with LMWH.
 Treatment
– Stop Heparin
– Start**lepirudin /Argatroban
**(direct thrombin inhibitor)
– 0.1 to 0.4 mg/kg bolus followed by
0.1 to 0.15 mg/kg per hour infusion
81
 Diagnosis
– Thrombocytopenia (50%
↓platelet from baseline).
– Suspected if thromboembolic
event (e.g., DVT, PE, stroke,
MI, limb artery occlusion)
during or soon after
receiving UFH
– Skin necrosis can occur
– HIT assay.
**Because these drugs have no structural similarity to heparin, they do not cross-react with heparin-induced
antibodies.

82. Anticoagulant Dosing Clearance & Monitoring
Argatroban
(direct thrombin inhibitor)
IV
Bolus: None
Infusion: STANDARD (2 mcg/kg/min), REDUCED
DOSE for liver dysfunction, CHF, post-cardiac
surgery (0.5-1.2 mcg/kg/min)
• Hepatobiliary clearance
• Adjusted to aPTT 1.5-
3.0 times baseline
Bivalirudin
(direct thrombin inhibitor)
IV
Bolus: None
Infusion: STANDARD (0.15 mg/kg/hr); consider
REDUCED DOSE for renal or liver dysfunction
• Enzymatic clearance
• Adjusted to aPTT 1.5-
2.5 times baseline
Danaparoid
(indirect Xa inhibitor)
IV
Bolus: Weight-based (1500-3750 units)
Infusion: INITIAL ACCELERATED (400 units/hr x 4
hr, then 300 units/hr x 4 hr), then MAINTENANCE
(150-200 units/hr)
• Renal clearance
• Adjusted to anti-Xa
activity 0.5-0.8 units/mL
Fondaparinux
(indirect Xa inhibitor)
SC
< 50 kg  5 kg daily
50-100 kg  7.5 mg daily
> 100 kg  10 mg daily
• Renal clearance
• No monitoring
Rivaroxaban
(direct Xa inhibitor)
PO
HITT: 15 mg BIDx 3 weeks, then 20 mg QD
Isolated HIT: 15 mg twice daily until platelet count
recovery (≥ 150)
• Renal clearance
• No monitoring
82

83. Clinical Context Implications for Anticoagulant Selection
Critical illness
Increased bleeding risk
Possible urgent procedures
Argatroban or Bivalirudin (shorter duration of effect)
• If moderate or severe hepatic dysfunction (Childs-Pugh B
or C), may be advisable to avoid argatroban or use a
reduced dose
Life- or limb-threatening
VTE (massive PE or venous
limb gangrene)
Parenteral non-heparin anticoagulant preferred
(Argatroban, Bivalirudin, Danaparoid, Fondaparinux)
• Few such patients treated with DOACs
Clinically stable patients at
average bleeding risk
Fondaparinux or DOACs reasonable
• Most published DOAC experience with Rivaroxaban
83

84.  Absolute contraindications to
warfarin
– Active bleeding,
– Hemorrhagic tendencies,
– Pregnancy,
– Hx of warfarin-induced
skin necrosis.
 With great caution
– Hx of GI bleeding,
– Recent neuro-surgery,
– Alcoholic liver disease,
– Renal failure
84
 Contraindications to heparin
– Hypersensitivity to the drug,
– Active bleeding, hemophilia,
– Severe liver disease with ↑ PT,
– Severe thrombocytopenia,
– Malignant hypertension,
– Inability monitor treatment.

85. Critically Ill Patient
Patients suffering from
immediately life-
threatening illness
requiring admission to
intensive care unit
Acutely Ill
Medical Patient
Patients
hospitalized for
medical illness
Chronically Ill
Medical Patient
Those with medical
conditions who may be
cared for in long-term
care facilities
Long-distance
Traveler
Those traveling by
air for ≥ 4 hours
85

86.  At the time of hospital admission, all patients should be evaluated for
their risk of VTE,
 Strategies to prevent VTE appropriate for each patient’s level of risk
should be routinely employed.
 Optimal duration for VTE prophylaxis following surgery is not well
established.
 Prophylaxis should be continued throughout the period of risk.
86

87. 87

88. 88

89.  Ambulation
– Increases venous blood flow.
– Promotes the flow of natural antithrombotic factors into the lower
extremities.
 Graduated compression stockings (GCS)
– ↓incidence ~ 60% following general surgery/neurosurgery/stroke.
– Relatively inexpensive and safe.
– In low- to moderate-risk patients when pharmacologic interventions
are contraindicated.
– But, some patients are unable to wear because of the size or shape
of their legs.
89

90. 90

91.  Intermittent pneumatic compression (IPC) devices
– Increase the velocity of blood flow in the lower extremities.
– ↓risk >60% following general surgery/neurosurgery/orthopedic
surgery.
– More expensive > GCS
 Inferior vena cava (IVC) filters
– Aka Greenfield filters,
– Provide short-term protection against PE in very-high-risk patients.
91

92. 92

93. 93
Especially in case of PE

94.  Efficacy & safety
– Clinical signs and symptoms
– Laboratory tests and investigations
94

95.  A 75-year-old female patient is status post hip replacement eight days
ago. She is still unable to ambulate well. Her nurses have noticed that
she has had a drop in her platelet count. She is short of breath and has
inspiratory chest pain.
 Allergies: Penicillin (rash)
 Medications: Aspirin 81 mg chewable tablet (OTC) 1 po daily; calcium
citrate 600 mg tablet (OTC) 1 po BID; simvastatin 40 mg tablet 1 po at
bedtime; enalapril 10 mg tablet 1 po daily; prednisone 5 mg tablet 1
po daily, enoxaparin 30 mg/0.3 mL SubQ injection given q 12 hrs
95

96.  Physical Exam/Other Studies:
– Wt: 182 lb Ht: 63 in T: 98.6°F BP: 128/78 sitting HR: 77 RR :18
– TC: 178 LDL: 95 HDL: 55 TG: 140 SCr: 0.9 INR: 2.1
– PLT: 120 × 103 (Post-op Day 2: 227 × 103)
– Physical exam reveals clear lungs with no wheezes or crackles.
– CT angiography is consistent with pulmonary embolism.
– HIPA assay and heparin-PF4 ELISA assay are positive.
– The hospitalist on duty diagnoses her with heparin-induced
thrombocytopenia (HIT).
Q: What options are available to manage her HIT?
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97.  A 75-year-old female patient with a history of temporal neuralgia,
hypertension, dyslipidemia, and osteopenia develops avascular necrosis
of her left hip and is scheduled for hip replacement surgery.
 Allergies: Penicillin (rash)
 Medications: Aspirin 81 mg chewable tablet (OTC) 1 po daily; calcium
citrate 600 mg tablet (OTC) 1 po twice daily; simvastatin 40 mg tablet 1
po at bedtime; enalapril 10 mg tablet 1 po daily; prednisone 5 mg
tablet 1 po daily
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98.  Physical Exam/Other Studies:
– Wt: 182 lb Ht: 63 in T: 98.6°F BP: 128/78 sitting HR: 77 RR: 18
– TC: 178 LDL: 95 HDL: 55 TG: 140 SCr: 0.9
– All other labs were within normal limits.
– On the day after her surgery, her surgeon would like to begin venous
thromboembolism (VTE) prophylaxis with a low molecular weight
heparin (LMWH). Which of the following would be considered an
appropriate agent you will recommend as pharmacist ?
A. Fondaparinux
B. Argatroban
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C. Enoxaparin
D. Bivalirudin

99.  A 25-year-old woman presents to the emergency room with complaints
of shortness of breath and dyspnea. She is experiencing chest tightness
and pain with inspiration. Her symptoms began earlier in the day and
have gradually worsened, and she is now experiencing dizziness and
lightheadedness.
 Allergies: NKDA
 Medications: Combined oral contraceptive tablets 1 po daily
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100.  Physical Exam/Other Studies:
– Wt:122lb Ht: 66 in T: 98.6°F BP: 110/78 sitting HR: 77 RR: 18 SCr: 0.9
– Chest x-ray shows nonspecific infiltrates in the right lobe of the lungs.
– CT angiography & D-dimer results are consistent with pulmonary
embolism. She is diagnosed with a pulmonary embolism.
– Which of the following would be an appropriate treatment for
pulmonary embolism (PE)?
A. Unfractionated heparin
B. Argatroban
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C. Aspirin
D. Clopidogrel

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