Acute Pulmonary Embolism in the

Critical Care Unit: Is it different ?

Kenneth V. Leeper Jr. MD

Associate Professor of Medicine
Division of Pulmonary, Allergy and Critical Care Medicine
Emory School of Medicine
Atlanta, Georgia
Acute Pulmonary Embolism in the
Critical Care Unit: Is it different ?
ƒ Case Presentation
ƒ The incidence of VTE in MICU patients
ƒ Clinical Clues of VTE in MICU Patients
ƒ Treatment of VTE in Critically – Ill Patients
ƒ Impact of current prophylaxis on the
prevention of DVT in MICU patients
Acute Pulmonary Embolism in the
Critical Care Unit: Is it different ?
ƒ Case Presentation
ƒ The Risk Factor and Incidence of VTE in
MICU patients
ƒ Clinical Clues of VTE in MICU Patients
ƒ Impact of current prophylaxis on the
prevention of DVT in MICU patients
 VTE in the ICU – Case Study

ƒ 58-y-o AAM presented to the MICU with a

RML and RLL pneumonia
ƒ Patient required 100% non-rebreather to
maintain O2 saturation > 90%
ƒ PMH: History of right lower extremity DVT
after a long car drive 8 years PTA
ƒ No medications, no allergies
 VTE in the ICU – Case Study

ƒ Physical exam
ƒ Weight 112 kg, RR 36, BP 142/78 mm Hg,
T 38.7 °C, egophony right posterior chest,
2/6 SEM; rest of exam unremarkable
ƒ O2 sat 91% on 100% NRM
ƒ Labs: WBC 15,600 (84 PMNs, 10 bands)
ƒ CXR: RML/RLL pneumonia
ƒ Initial Rx: ceftriaxone / azithromycin
ƒ DVT prophylaxis: UFH 5,000 SC q 8 h
 VTE in the ICU – Case Study

ƒ MICU course
ƒ Patient required face mask ventilation with BiPAP for
48 hours then weaned to 50% Venturi mask
ƒ Day 4: persistent fever with episode of hypotension that
responded to fluid therapy
ƒ Day 5: persistent fever, WBC normalizing; LE Dopplers
obtained: right proximal LE DVT → Rx with weight-based
UFH
ƒ Evening of day 5: episode of hypotension requiring fluids
and brief vasopressor therapy → spiral CT scan of the
chest obtained
 VTE in the ICU – Case Study

ƒ Spiral CT scan of the chest – large bilateral

PE
ƒ Both troponin and BNP elevated
ƒ Cardiology fellow performed
echocardiogram: Severe RV enlargement
with RV wall motion abnormalities
ƒ Management options?
Acute Pulmonary Embolism in the
Critical Care Unit: Is it different ?
ƒ Case Presentation
ƒ The Risk Factor and Incidence of VTE in
MICU patients
ƒ Diagnosis of VTE in MICU Patients
ƒ Impact of current prophylaxis on the
prevention of DVT in MICU patients
 The Challenge of VTE in Critically Ill
Patients
ƒ Critically ill patients commonly develop DVT
ƒ Rate varies from 22 – 60% depending on
patient characteristics
ƒ Methods of prophylaxis are not universal
ƒ In high-risk groups more effective
prophylaxis regimens are needed
 Clinical Risk Factors for VTE in
Critically Ill Patients
Factors before ICU admission Additional factors acquired in ICU
ƒ Recent surgery ƒ Central venous lines
ƒ Trauma, burns ƒ Sepsis
ƒ Malignancy and treatment ƒ Pharmacologic interventions:
ƒ Sepsis sedation, paralysis
ƒ Immobilization / bed rest, ƒ Mechanical ventilation
stroke, spinal cord injury
ƒ Increasing age
ƒ Heart / respiratory failure An autopsy study revealed that 20%
ƒ Previous VTE of patients who died in the ICU
ƒ Pregnancy / puerperium had evidence of PE. Moser KM.
ƒ Estrogens JAMA 1981.
 Prevalence of of DVT
Among Patients in the MICU

ƒ Ultrasound in 100 patients admitted to MICU for

> 48 hours
ƒ Incidence of DVT – 33%
ƒ 61% received DVT prophylaxis
ƒ Patients with DVT – more likely to have a history
prior VTE
ƒ Hospital MR – 36% w/ DVT vs. 24% w/o DVT (P =
0.028)

Hirsch DR, et al. JAMA. 1995;274:335-7.

 VTE on Presentation to the ICU

ƒ Prospective study of 196 COPD patients

admitted to a respiratory ICU
ƒ Ultrasound on day of admission
ƒ 21/196 (11%) – had DVT, all above the knee
ƒ 18/21 – asymptomatic
ƒ No differences in age, ABG, FEV1, or dyspnea
ƒ Physical exam not helpful to detect DVT

Schonhofer B, Kohler D. Respiration. 1998;65:175-7.

VTE in Decompensated CHF patients
requiring CCU admission
ƒ 198 patients admitted with severe
decompensated CHF over 31 month period
ƒ 18/198 – acute PE / 8 of 18 (44.4%) DVT
ƒ Thromboprophylaxis: 12/18 (66.7%) vs
126/180 (70%) NS
ƒ Independent risk factors associates with PE
ƒ Cancer OR 26.9
ƒ RV abn OR 9.7
ƒ Prev. VTE OR 9.1
Darze ES.et.al. Chest 2005; 128;2576 - 2580
DVT in medical-surgical critically ill patients:
prevalence, incidence and risk factors. Cook D et.al.
Crit. Care Med. 2005 33:1565-71
ƒ Prospective cohort study closed university
affiliated ICU
ƒ Consecutive patients enrolled, excluded
trauma, orthopedic surgery, pregnancy and
life support withdrawn
ƒ Bilateral LE US within 48 hrs of admission
and twice weekly and if DVT was suspected
ƒ Thromboprophylaxis was protocol directed
and universal
DVT in medical-surgical critically ill patients:
prevalence, incidence and risk factors. Cook D et.al.
Crit. Care Med. 2005 33:1565-71
ƒ 261 patients with APII of 25.5
ƒ Prevalence of DVT on admission – 2.7%
ƒ Incidence over the ICU stay – 9.6%
ƒ Independent risk factors for DVT
ƒ Personal or FH of VTE – HR 4.0
ƒ ESRD – HR 3.7
Consequences of DVT
ƒ Platelet transfusions – HR 3.2
Longer ICU stay p=0.00
ƒ Vasopressor use – HR 2.8
Longer duration on MV
Longer hospitalization p
 Deep Vein Thrombosis
During Prolonged Mechanical
Ventilation Despite Prophylaxis
Ibrahim EH, Iregui M, Prentice D, Sherman G, Kollef M, Shannon W.

Critical Care Medicine. 2002;30:771-4.

Objective: Determine the prevalence of DVT among patients

requiring prolonged mechanical ventilation in the ICU
 DVT During Prolonged Mechanical
Ventilation Despite Prophylaxis

ƒ Measurements
ƒ Total of 110 patients requiring mechanical
ventilation for > 7 days were enrolled
ƒ Prophylaxis against DVT employed in 110
patients (100%)
ƒ 26 patients (23.6%) developed DVT

Ibrahim EH, et al. Crit Care Med. 2002;30:771-4.

 DVT During Prolonged Mechanical
Ventilation Despite Prophylaxis

20 Risk factors for DVT

ƒ Underlying malignancy
15 ƒ Renal failure
ƒ GI disturbances
Percent

10 ƒ Duration of CVP line

Clinical outcomes
5
ƒ PE – more common with
DVT (11.5 vs. 0.0%)
ƒ No difference in LOS or
0 mortality
1 2 3 4
Week DVT detected

Ibrahim EH, et al. Crit Care Med. 2002;30:771-4.

 DVT During Prolonged Mechanical
Ventilation Despite Prophylaxis
Incidence and Prevention

90 80.8
80 73.1
70
60
Percent

50
40
26.9
30
19.2
20
10
0
UE-DVT LE-DVT UFH SCD

Ibrahim EH, et al. Crit Care Med. 2002;30:771-4.

Prevalence of VTE in and LTAC Setting:
Preliminary Data. VTE – LTAC Study Group
ƒ Select LTAC ECLH: July 1 2006 – June 13,
2007
ƒ 50 admissions to the Emory Pulmonary
Service
ƒ 40/50 had screening US of the lower
extremities and upper extremities ( if
clinically indicated)
ƒ 6/40 (15%) - VTE events on screening US. 4
LE DVT and 2 UE DVTs
 Vasopressor Administration May Predispose ICU
Patients to DVT

Multivariable analysis identified vasopressor administration as an

independent risk factor (hazard ratio 2.8, 95% CI 1.1 - 7.2) for DVT

Days in ICU
Patients*

Vasopressors

DVT

*Patients (9 of
261) who
recevied
vasopressors
and developed
DVT

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90
Days in ICU

Cook D et al. Crit Care Med. 2005;22:1565- 1571.

VTE in Severe Sepsis: Incidence of VTE in Severe sepsis
treated with Drotrecogin alfa with or without prophylactic
heparin. Levy M. Abstract Chest 2006

ƒ Xpress study – large phase 3B 28 day mortality and

the relative incidence of VTE in patients treated with
drotrecogin alfa (DAA) with or without heparin
ƒ Dec 2002 – July 2005
ƒ Adult pts with high risk for severe sepsis
ƒ All pts received DAA
ƒ Study drugs: heparin 5000Usc q 12 hrs, enoxaparin 40mg
sc qd and placebo
ƒ Randomization: 1:1:2
ƒ Lower extremity US 4 and 6 days
VTE in Severe Sepsis: Incidence of VTE in Severe sepsis
treated with Drotrecogin alfa with or without prophylactic
heparin. Levy M. Abstract Chest 2006
ƒ 1935 patients were enrolled and received DAA and
one of the study drugs
ƒ 959 placebo
ƒ 976 Heparins ( 498 UFH/478 LMWH)
Incidence of VTE
ƒ Study period heparins placebo pvalue
ƒ 0-6 days 4.6% 5.1% 0.6
ƒ 0 – 28 days 5.7% 7.0% 0.26
ƒ Subgroups with highest incidence of VTE: previous
VTE, age > 75, recent surgery, pts on baseline
heparin randomized to placebo VTE incidence –
8.1%
Sources of Thrombi: Central Vein
Catheter-Related Thrombi in the ICU
ƒ Prospectively performed duplex scans just
before or within 24 hours after removing the
IJ or subclavian CVL in ICU patients
ƒ 208 lines studied
ƒ Mean duration was 9 ± 5 days
ƒ Catheter-related clot – 33% of patients

Timsit JF, et al. Chest. 1998:114;207-13.

 What is the embolic potential for UE-
DVT?

PE%
Sources of Thrombi:HIT
Diagnosis
ƒ Suspect if the platelet count drops below
150,000/mm3 while patient receiving UFH or
LMWH
ƒ Suspect if the platelet count drops 50% from
pre-heparin baseline levels
ƒ Suspect if new thrombosis while the patient
is receiving UFH or LMWH
ƒ Suspect if heparin resistance develops
ƒ Confirm with laboratory test (SRA, HIPA or
ELISA)
Incidence of HIT and VTE After Use of
UFH and LMWH
ƒ Literature review: Identify studies using UFH or
LMWH for thromboprophylaxis or treatment in which
new or recurrent VTE and serologically confirmed HIT
ƒ 10 studies
ƒ 386 of 6,219 heparin-treated patients had VTE
ƒ 32 of 386 VTE patients also had HIT
ƒ Among 32 cases of HIT in 386 VTE patients
ƒ 17 cases occurred in 129 IV UFH-treated patients (13.2%)
ƒ 14 cases occurred in 113 SC UFH-treated patients (12.4%)
ƒ 1 case occurred in 144 LMWH-treated patients (0.7%)
Levine RL, et al. Chest. 2006;130:681-7.
Acute Pulmonary Embolism in the
Critical Care Unit: Is it different ?
ƒ Case Presentation
ƒ The Risk Factor and Incidence of VTE in
MICU patients
ƒ Diagnosis of VTE in MICU Patients
ƒ Impact of current prophylaxis on the
prevention of DVT in MICU patients
Clinical Symptoms and Signs of VTE in
MICU Patients
ƒ Nonspecific
ƒ Persistent Fever
ƒ In MV patients, unexplained increase in
minute ventilation
ƒ ET CO2 measurement
ƒ In MV patients – Paradoxical hypercarbia
Neither baseline tests of molecular
hypercoagulability nor D-dimer levels predict DVT
in critically ill medical surgical patients
ƒ Predicting patients who are harboring
asymptomatic DVT or PE is a desirable
clinical goal
ƒ Prospective study of 197 patients in a med-
surg ICU
ƒ 6 commercial D-dimer test and markers of
hypercoagulabilty
ƒ Conclusion: None of the test patients at risk
for DVT
Crowther MA. Et.al intensive Care Med 2005;31: 48-55
 Which diagnostic tests for VTE
evaluation in the ICU patients?
ƒ Depends upon clinical stability and renal
function.
ƒ Suspect VTE
ƒ Clinically stable + normal renal function or
ESRD: Spiral CT scan of the chest and either
CTV or Doppler US the extremities
ƒ Clinically stable + ongoing renal insufficency: US
of the extremities and TTE/TEE
ƒ Clinically unstable – unable to move off the unit:
US of the extremities and TEE ( esp in the MV pt.)
Acute Pulmonary Embolism in the
Critical Care Unit: Is it different ?
ƒ Case Presentation
ƒ The Risk Factor and Incidence of VTE in
MICU patients
ƒ Diagnosis of VTE in MICU Patients
ƒ Impact of current prophylaxis on the
prevention of DVT in MICU patients
 ACCP Recommendations 2004
Critical Care Unit

ƒ Upon admission to a critical

care unit, all patients should
be assessed for their risk of
DVT/PE
ƒ Accordingly, most should receive
thromboprophylaxis (grade 1A)
ƒ Low-molecular-weight heparin (LMWH)
ƒ Low-dose unfractionated heparin (UFH)
(q 12 h or q 8 h)

ACCP=American College of Chest Physicians

Geerts WH et al. Chest. 2004;126(3 suppl):338S-400S.
 Initial Prophylaxis Considerations in
Critical Care Patients
High bleeding risk Usual bleeding risk
ƒ Mechanical ƒ Low-dose UFH
prophylaxis 5,000 U q 8 h
ƒ Delay prophylaxis until ƒ LMWH
high bleeding risk ƒ Combine AC and
resolves mechanical
ƒ Screen for proximal prophylaxis
DVT with DUS in high
risk patients

Geerts W, et al. J Crit Care. 2002;1:95-104

 Trials for VTE prophylaxis in the ICU

Study/Year Size, n Type of ICU Method of Control Active Tx Results

Patient Detection

Cade 119 General FUT for 14d Placebo UFH 5000 29 v. 13%
1982 ICU bid

Kapoor 791 Medical DUS on q 3 Placebo UFH 5000 31 v. 11%

1999abst ICU days bid

Fraisse 223 Ventilated Venograph Placebo Nadroparin 28 v. 15%

2000 COPD by day 21 65 U/kg SC
q day
Goldhaber 325 Medical DUS on UFH 5000 Enoxapar. 13 v. 16%
2000abst ICU day 3,7,10 bid 300 mg bid

Cook 129 Med-Surg CUS UFH 5000 Dalteparin NR v NR

ICU bid 5000 IU/d
 Do mechanical prophylaxis devices
reduce DVT incidence in ICU patients?
ƒ Stimulates endogenous fibrinolysis
production of plasminogen activator
ƒ More efficacious in moderate risk post-
operative patients
ƒ Robust data lacking efficacy in medical ICU
patients
INTERMITTENT PNEUMATIC COMPRESSION

Indication: contraindication
to anticoagulation

Evidence: limited

Compliance: poor

Cost: $56.00 per day

equipment rental

Bleeding risk: NONE

 Combination Strategy

ƒ Randomized trial of 2,551 consecutive

cardiac surgical patients. SCDs + LDUH –
62% reduction in post-surgical PE ( 1.5% vs
4%) *
ƒ Nonhemorrhagic Stroke – 40 fold reduction
risk of DVT**

•*Ramos R. et.al. Chest 1996

•**Kamran SL. Et.al. Neurology 1998
Role of Mechanical prophylaxis in preventing DVT
in high risk populations: Stannard JP. J Bone and
Joint Surgery 2006: 88; 261 -266
ƒ 224 patients with blunt trauma – prospective study
investigating VTE
ƒ Group A (97) – enoxaparin SQ BID starting 24 – 48
hrs after blunt trauma
ƒ Group B (103) – pulsatile foot pumps at time of
admission and delayed enoxaparin
ƒ Group A – 13 DVTs (13.4%) and 2 PEs (2.1%)
ƒ Group B – 9 DVTs ( 8.7%) no PEs
ƒ Group A – 11 large and occulsive clots (11.3%)
ƒ Group B – 3 large and occlussive clots (2.9%)
p=0.025
Prevention of VTE in the Obese MICU Patient
ƒ Anti-Xa levels with fixed dose LMWH regimens correlate
negatively with BMI in critically ill patients (Priglinger U
2003)
ƒ Standard prophylactic regimens are twice as likely to fail in
orthopedic patients with BMI >32
ƒ BMI > 32 VTE rate 32% vs 17% BMI <32 –Samama MM, 1995
ƒ Nonrandomized studies in bariatric surgery patients suggest
a decrease DVT rates with enoxaparin 40mg sq BID vs 30mg
BID – Scholten DJ. 2002
ƒ No data to guide adjustments in therapy
ƒ Options include:
ƒ Use standard dose
ƒ Empiric dose adjustments
ƒ Add mechanical measures
MICU Patient with Renal Insufficiency:
VTE Prevention
ƒ Delayed renal clearance of LMWHs and
Fondaparinux very problematic
ƒ Lack of outcomes based data
ƒ FDA approved enoxaparin 30 mg sq qd for
patients with CCL <30 ml/min based on
pharmacokinetic data alone
ƒ Additional options UFU and/or mechanical
devices.
 Elderly Patient in the MICU

ƒ Mahe et.al. monitored anti-Xa levels in 68

consecutive hospitalized elderly patients (mean age
82) receiving enoxaparin 40mg sq qd for
prophylaxis
ƒ Day 2 >50% had levels >0.5IU/ml ( optimal range)
ƒ Day 8 69.4 levels >0.5 IU/ml
ƒ BE CAREFUL: consider empiric reduction of
enoxaparin or use mechanical devices alone in
elderly with low body weight < 45 kg or marginal
creatinine clearane
 Patients with Prior HIT

ƒ Treatment of HIT is a thrombin inhibitor

bridge to warfarin therapy
ƒ Optimal future VTE prevention strategies are
lacking in this population
ƒ Avoid UFH and LMWH
ƒ DTIs are impractical for primary VTE prophylaxis
ƒ Fondaparinux – indirect anti-Xa inhibitor may be
a promising prophylaxis scheme
ƒ Fondaparinux does not bind platelet factor 4
ƒ No apparent in vitro cross reactivity to HIT antibiodies
 Prophylactic Anticoagulation With
Enoxaparin: Is the Subcutaneous Route
Appropriate in the Critically Ill?

Priglinger U, Delle Karth G, Geppert A, Joukhadar C, Graf S, Berger R,

Hülsmann M, Spitzauer S, Pabinger I, Heinz G

Critical Care Medicine. 2003. 31:1405-409

Objective: Determine anti-Xa activities in critically ill

patients and in noncritically ill patients receiving
prophylactic doses of subcutaneous enoxaparin
Prophylactic Anticoagulation With Enoxaparin:
Is the SC Route Appropriate in the Critically Ill?
1.0
F over time = 39, P = 0.001 ICU patients (n = 16)
F between groups = 23, P = 0.001 General ward (n = 13)
0.8
Anti-Xa activity (U/mL)

0.6

0.4

0.2

0
0 3 6 9 12
Time (hours)
Priglinger U, et al. Crit Care Med. 2003. 31:1405-409.
Prophylactic Anticoagulation With Enoxaparin:
Is the SC Route Appropriate in the Critically Ill?
1.0
F over time = 43.2, P = 0.001 ICU patients (n = 16)
F between groups = 1.5, P = 0.2 General ward (n = 13)
0.8
Anti-Xa activity (U/mL)

0.6

0.4

0.2

0
0 24 48 72 96 120
Time (hours)
Priglinger U, et al. Crit Care Med. 2003. 31:1405-409.
Prophylactic Anticoagulation With Enoxaparin:
Is the SC Route Appropriate in the Critically Ill?

ƒ Conclusion: Critically ill patients with normal

renal function demonstrated significantly
lower anti-Xa levels in response to a single
daily dose of subcutaneous enoxaparin when
compared with medical patients in the normal
ward.

Priglinger U, et al. Crit Care Med. 2003. 31:1405-409.

 THE EVALUATION OF VENOUS THROMBOEMBOLISM PROPHYLAXIS THERAPY IN A
MEDICAL INTENSIVE CARE UNIT VIA THERAPEUTIC DRUG MONITORING .H. Patel,
A. Velasquez, D. Shaz, K. Leeper, Pulmonary/Critical Care Medicine, Emory Healthcare,
Atlanta, GA;

Introduction : Patients in a medical intensive care unit (MICU) are often at

very high risk of developing a venous thromboembolism (VTE). Heparin
and low molecular weight heparins (LMWHs) are pharmacological agents
used for prevention of VTE.

Hypothesis: Current dosing guidelines for VTE prophylaxis may be

inadequate in MICU patients who often have altered pharmacokinetic and
pharmacodynamic profiles.

Methods : Patients in the MICU receiving VTE prophylaxis with heparin

or LMWH had anti-Xa levels monitored in this prospective, observational
study. Anti-Xa levels were drawn at least after 4 doses and 4 hours after
subcutaneous administration of medication.
THE EVALUATION OF VENOUS THROMBOEMBOLISM PROPHYLAXIS THERAPY IN
A MEDICAL INTENSIVE CARE UNIT VIA THERAPEUTIC DRUG MONITORING .H.
Patel, A. Velasquez, D. Shaz, K. Leeper, Pulmonary/Critical Care Medicine, Emory
Healthcare, Atlanta, GA;

ƒ Results : From March 2007 to August 2007, 50 patients had anti-Xa levels
monitored. Among the 50 patients, 12 patients (24%) acheived
appropriate anti-Xa levels compared to 38 patients (76%) who were non-
therapeutic. Among those in the appropriate range, 8 patients (67%) were
receiving LMWH. ICU length of stay and days on the ventilator were
longer in patients with non-therapeutic anti-Xa levels.

Conclusions : Current dosing guidelines of heparin for VTE prophylaxis

are inadequate in an MICU setting. Weight based dosing of heparin
should be considered in future patients. The LMWHs may have a better
predictability. Future studies should evaluate whether subtherapeutic
VTE prophylaxis correlates to a higher incidence of VTE compared to
therapeutic dosing.
 Strategies to Improve
Thromboprophylaxis
Comparison of strategies among 1,827 patients in 3 similar CCUs

No special compliance
intervention 38%

Education provided to
physicians 62%

Education and mandatory

computer order entry 97%

Levi et al. Chest. 1998;114(Suppl):392S.

 Summary
ƒ Critically ill patients are at high risk of VTE
ƒ Low rate of clinical diagnosis
ƒ Prevalence 10 – 60%
ƒ Predominant test: ultrasound
ƒ Prophylaxis
ƒ UFH 5000 U q 8 h
ƒ LMWH (enoxaparin 40 mg SC/d)
ƒ Dalteparin 5000 IU SC daily
ƒ Fondaparinux 2.5 mg SQ daily
ƒ Intermittent compression devices
ƒ Utilization of prophylaxis is inadequate AND or prophylactic
regimens may be inadequate
ƒ New sources of thrombi – HIT induced thrombosis
ƒ We can do better !!!
Treatment of VTE in the Critical Care
Patients

Kenneth V. Leeper Jr. MD

Associate Professor of Medicine
Division of Pulmonary, Allergy and Critical Care Medicine
Emory School of Medicine
Atlanta, Georgia
 Summary of Sixth American College of Chest Physicians
(ACCP) Guidelines for Antithrombotic Therapy in the Treatment
of Venous Thromboembolism

Recommendations Guidelines for Treatment

Grade 1A i.v. LMWH/UFH or adjusted-dose s.c. heparin
initially for at least 5 days
Overlap with oral anticoagulation for at least 4-5 days
Discontinue LMWH/UFH on day 5/6 if INR is
therapeutic for 2 consecutive days
Grade 2B LMWH preferred over UFH
Grade 1C Massive pulmonary embolism/severe iliofemoral
thrombosis: LMWH/UFH for approximately 10 days
Grade 1C+ LMWH: dose based on manufacturers’ instructions
UFH: adjust to correspond to a plasma heparin level
of 0.2-0.4 IU/mL (protamine sulfate) or 0.3-0.4
IU/mL (amidolytic anti-Xa assay)
.Turpie AGG et al. Sem Thromb & Hemost. 2002;28(Suppl 3):3-11.
56 y.o man with a history of alcoholism admitted to the MICU in
respiratory failure secondary to pneumonia. He is on no
vasopressors and renal function is normal and on heparin 5000 units
sq BID
ƒ On day 5 his WBC count is normal but
temperature is 38.6C
ƒ Differential Dx: 1.Slow resolution of the
pneumonia. 2. VAP. 3 Possible DVT
ƒ Evaulation: Mini BAL negative, LE dopplers
Positive for DVT right deep femoral
ƒ Treatment: No contraindications to heparin
therapy: Treat with UFU or LMWH
 Therapeutic peak anti-Xa levels with
LMWHs for the treatment of VTE
ƒ Enoxaparin 1mg/kg q 12 hrs 0.6-1.0IU/ml
ƒ Enoxaparin 1.5mg/kg qd 1.0 –1.5 IU/ml
ƒ Tinzaparin 175 IU/kg qd 0.85 – 1.0 IU/ml
ƒ Dalteparin 100IU/kg q 12 hrs 0.4 – 1.1 IU/ml
ƒ Dalteparin 200 IU/kg qd 1.0-2.0 IU/ml
ƒ Prophylaxis 0.1 – 0.6 IU/ml
Chromogenic anti-Xa level assay drawn 4 hours after the subq dose
This is a 62 y.o woman with diabetes and ESRD, admitted to the
MICU with MRSA bacteriemia. The patient is placed on SCDs for DVT
prophylaxis. On MICU day 4 she developes a sudden onset of
dyspnea ,hypoxemia and SPB of 98 mmHg .

ƒ Evaluation: Spiral CT scan of the chest – large right

main pulmonary embolism. LE dopplers – Right
popliteal DVT.
ƒ TEE – Moderate RV dilation with parodoxical septal
shift.
ƒ Management
ƒ Hypotension responded to fluid therapy
ƒ Pharmacologic management and other options
ƒ UFH infusion
ƒ UFH infusion and retrieveable filter
ƒ Thrombolysis
ƒ Pulmonary embolectomy
51 y.o man underwent coronary artery bypass surgery
complicated by a hemopericardium, requiring pericardial
window drainage.

ƒ Fifth post – op day prophylactic therapy with

enoxaparin was started.
ƒ 9th post-op day fever to 39C and hypotension
with BP 90/70, abdominal tenderness and
distention.
ƒ Admission platelet count – 182X109 cells/l
post-op day 3, now – 40 X109 cells cells/l
51 y.o man underwent coronary artery bypass surgery
complicated by a hemopericardium, requiring pericardial
window drainage
ƒ Differential Diagnosis: Sepsis with DIC
ƒ Management
ƒ Moved to the ICU
ƒ Antibiotics and fluids started
ƒ DIC profile negative
ƒ Serum cortisol ordered
ƒ Argatroban started
ƒ HIT – ELISA for heparin – induced PF 4 antibodies strongly positive
ƒ CTscan of abdomen – revealed bilateral adrenal necrosis
ƒ Serum cortisol < 1ug/ml
ƒ Patient improved – discharged on adrenal replacement and warfarin
51 y.o man underwent coronary artery bypass surgery
complicated by a hemopericardium, requiring pericardial
window drainage: Comment

ƒ If there is a moderate suspicion of HIT - treat with

DTI
ƒ Large amount of heparin during bypass was
sensitizing along with the LMWH.
ƒ When heparin was stopped greatest risk period for
new thromboembolic complications
ƒ Adrenal necrosis is a microthrombotic lesion with
secondary necrosis and hemorrhage
ƒ Diagnosis: HIT with acute adrenal crisis
Incidence of HIT and VTE After Use of
UFH and LMWH
ƒ Literature review: Identify studies using UFH or LMWH for
thromboprophylaxis or treatment in which new or recurrent
VTE and serologically confirmed HIT
ƒ 10 studies
ƒ 386 of 6,219 heparin-treated patients had VTE
ƒ 32 of 386 VTE patients also had HIT
ƒ Among 32 cases of HIT in 386 VTE patients
ƒ 17 cases occurred in 129 IV UFH-treated patients (13.2%)
ƒ 14 cases occurred in 113 SC UFH-treated patients (12.4%)
ƒ 1 case occurred in 144 LMWH-treated patients (0.7%)

Levine RL, et al. Chest. 2006;130:681-7.

Pretest Scoring System for HIT. Warkentenin
and Heddle. Curr Hematol Rep 2003
4Ts 2 Points 1 point 0 points
Thrombocytopenia Platelet count >50% Platelet count> 30- Platelet count < 30%
and platelet nadir 50%
>20 X109/L
Timing of platelet Clear onset between Consistent with Platelet count <4
count decrease days 5 -10 or platelet immunization but days without recent
dec with one day unclear history exposure
Thrombosis or other New thrombosis, Suspected None
sequelae skin necrosis, thrombosis not yet
systemic rx to post proven
IV UFU bolus
Other causes of No apparent Possible Definite
thrombocytopenia