Download MDS in STEMI by Mary Antoniette Tan and Ana

Mortality & morbidity
conference
Ana Mae Quintal-Quetua, M.D.
Mary Antoniette Tan, M.D.
Case Objectives
 To present a case of a patient with
Myelodysplastic Syndrome who had multiple
medical problems, and developed acute STelevation myocardial infarction
 To discuss the management and treatment
options for a patient with MDS who had STEMI
 Hematologic- overview of AA and MDS
 Cardiac
Patient Data
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M.L.
61 years old
Female
Known HPN, on Diltiazem
Known asthmatic
Non-diabetic
Obese class II
Patient Data
 March 2009, 2nd week - consult at MMC for
pancytopenia; BMA done
Bone Marrow cytology report (Mar-17-09)
 60-70% marrow hypercellularity with erythroid
hyperplasia and mild dyserythropoiesis
 Diagnostic comment: correlation with cytogenetic
studies for chromosomal haploinsufficiency is
recommended
 Started on Prednisone; platelet counts improve with
increased doses
Patient Data
 March 2009, 4th week- sought 2nd opinion at
SLMC; 2nd BMA done
Bone Marrow cytology report (Apr-03-09)
 5-10% marrow hypocellularity with pancytopenia
with relative lymphocytosis; marrow space
occupied mainly by fibroadipose tissue
 Cellular smears with dyserythropoiesis and
dysgranulopoiesis
Conclusion: Thrombocytopenia secondary to Severe
Aplastic Anemia , cannot rule out low-grade Hypoplastic
Myelodysplastic Syndrome
Patient Data
 April 5- 9, 2009 - admitted at MMC for ATG
administration (with Solumedrol) and was started
on Cyclosporine 300mg OD; discharged stable
 April 2009, 4th week - Prednisone dose was
increased up to 100mg OD
 Steroid-induced hyperglycemia, on Humulin R 80-2 and Humulin N 28-0-10
History of Present Illness
 3 days PTA, (+) productive cough, throat
irritation and hoarseness but (-) fever, DOB,
chest pain, bleeding
 12 hours PTA, (+) blood-tinged sputum
 May 6, 2009 - admitted for blood transfusion
due to decreased platelet count (PC 10,000)
Physical Examination on Admission
General
Survey
Conscious, coherent, ambulatory, not in respiratory distress
Vital Signs
BP = 110/70
BMI = 31kg/m2
HEENT
Anicteric sclerae, pale palpebral conjunctivae, (+) TPC with whitish
plaques on pharyngeal mucosa, (-) CLAD
HR = 78 bpm
RR = 20 cpm
Temp = 37.0C
Chest/ Lungs Clear breath sounds, symmetric chest expansion, no rales or
wheezes
CVS
Adynamic precordium, normal rate, regular rhythm, distinct S1 and
S2, no murmurs
Abdomen
Flabby, soft, normoactive bowel sounds, (-) masses or tenderness,
no splenomegaly
Extremities
Full and equal pulses, no pedal edema, no cyanosis, no clubbing
Admitting Impression
 Severe Aplastic Anemia vs Hypoplastic
Myelodysplastic Syndrome
 Upper Respiratory Tract Infection vs
Community Acquired Pneumonia
 Laryngitis, Oral Candidiasis
COURSE IN THE WARDS
PROBLEM-BASED
1. Pancytopenia
BM biopsy (May-29-09, MMC)
 10-20% hypocellularity with panhypoplasia,
dyserythropoiesis, left- shift granulocytic
maturation focal collagen fibrosis, Inc Iron
stores
 CONCLUSION: presence of significant
dysplasia favors a diagnosis of Hypocellular
Myelodysplatic Syndrome
MYELODYSPLASTIC
SYNDROME
APLASTIC ANEMIA
 Ineffective
 Marrow failure secondary
hematopoiesis due to
abnormal differentiation
and maturation, leading
to bone marrow failure
 Peripheral cytopenia,
dysfunctional blood
elements
 Possibility of leukemic
conversion
to inability to produce
blood cell components
 Maybe immune- mediated
(T- cells) or due to direct
bone marrow injury (drugs,
chemicals)
 Pancytopenia, Bone
marrow hypocellularity
MYELODYSPLASTIC
SYNDROME
 Bone marrow maybe
hypercellular, hypocellular
or normal
 Cytogenetic abnormality
involving chromosome 5,
7, 11, 12 and 20 deletions,
and/or trisomy 8
 Recurrent chromosome
deletions Loss of tumor
suppressor genes are
involved in the
pathogenic process
APLASTIC ANEMIA
 Bone marrow consists
primarily of fatty space
and stromal cells
 Evolution of AA to MDS/
AML is marked with
increased proliferative
activity +/- development of
cytogenetic abnormalities
 9% risk of developing to
AML
Differentiating AA from Hypoplastic MDS:
Diagnosis dictates management and prognosis
 A hypocellular bone marrow is seen in 20%
of MDS , which maybe confused with AA
 Hypoplastic MDS- cytopenia, marrow
dysplasia and marrow hypocellularity
 Incidence of 7.7% among a large series of
MDS patients evaluated
 Increase in mast cells and lymphoid cells
 Cytogenetic studies: changes in chromosome
7, especially monosomy 7
 3/5 cases transforming from AA to H- MDS
showed monosomy 7
 Monosomy 7 found in Hypoplastic MDS
indicates a poor prognosis, with patients
progressing to refractory cytopenia, with 80%
risk of evolving into Acute Myeloid Leukemia
 Trisomy 8- immune pathophysiology; often
responds clinically to immunosuppressive Tx
International Prognostic
Scoring System
Treatment Algorithm
Treatment
MYELODYSPLASTIC
 Poor response to
cytotoxic chemotherapy
 Stem Cell
Transplantation offers
cure, 50% survival rate at
3 yrs
 Demthylating agentsPyrimidine analogues
(Azacitidine, Decitabine)
 Lenalidomide,
Cyclosporine, ATG, GCSF
APLASTIC ANEMIA
 Immunosuppression:
Combination of
Cyclosporine & AntiThymocyte Globulin
 Stem Cell
Transplantation
 Supportive - transfusion
1. Pancytopenia
ISSUES
 Hemoglobin: 6.3 – 12.4 g/dl
 WBC: 410 – 5,100
 Platelet count: 2,000 – 160,000
 Persistent pancytopenia despite multiple
blood transfusion and repeated GCSF admin.
 Risk for severe infection, hemodynamic
instability and bleeding
1. Pancytopenia
MANAGEMENT
 Multiple transfusion of blood products
 ATG
 Cyclosporine
 Repeated GCSF administration
 Steroid administration
 Erythropoietin, thrombopoietin
 Vitamin K and tranexamic acid
administration
Effect of Multiple Blood
Transfusion
 Supportive therapy: PLT transfusion
 However, repeated PLT transfusion may fail
to show the desired increment in PLT counts
 PLT refractoriness develop in 30-70%; maybe
due to the underlying condition (fever, sepsis,
drugs) or it may be due to alloimmunization
 Patients with transfusion failure due to HLAantibodies may be given HLA- matched PLT
components
1. Pancytopenia
ETIOLOGY
 Thrombocytopenia secondary to Severe
Hypoplastic Myelodysplastic Syndrome
 Platelet refractoriness secondary to
multiple blood transfusion
 Unresolving Sepsis secondary to
Pneumonia in the Immunocompromised
2. Pneumonia and Fungal Laryngitis
in the Immunocompromised
ISSUES
 Severe infection; sepsis
 Unresolving lung infiltrates and persistent
pleural effusion
 Persistent wheezing/bronchospasm sec. to
hyperreactive airways
2. Pneumonia and Fungal Laryngitis
in the Immunocompromised
MANAGEMENT
 Sputum cultures, blood cultures
 Chest radiographs, chest UTZ, chest CT scan
 Attempted thoracentesis/chest pigtail insertion
 Use of broad-spectrum antibiotics, antifungals,
antivirals
 Inhaled and systemic bronchodilators and
mucolytics; steroid administration
CT scan of the chest, plain
(May 31, 2009)
 Pneumonia, left lower lobe
 Soft tissue density in the LUL and pulmonary
nodular opacities in the right lung may still be
related to the infectious process
 Subcentimeter granuloma, RLL
 Minimal pleural effusion, left
 Calcified lymph nodes, right paratracheal and
right hilar regions. These were already noted in
the study of April 4, 2009.
3. Respiratory Failure
CAUSES
 Severe infection (laryngeal candidiasis and
unesolving pneumonia) and sepsis in the
immunocompromised
 Pulmonary congestion sec.to hypervolemia,
hypoalbuminemia
 Persistent wheezing/bronchospasm sec. to
hyperreactive airways
 Anemia
 Airway and intrathoracic bleeding
 Empyema/pyothorax considered
3. Respiratory Failure
MANAGEMENT
 Alternating BIPAP and in-line neb.
 Endotracheal intubation and subsequent
tracheostomy
 Inhaled and systemic bronchodilators in
increased doses
 Inhaled and systemic mucolytics
4. Hypoalbuminemia
CAUSES
 Nutritional
 Hepatic failure
ISSUES
 Third spacing: congestion, effusion and edema
MANAGEMENT
 Repeated IV infusions of 25% human albumin
5.
Hyperglycemia
CAUSES
 Steroid-induced
 Stress-induced
ISSUES
 Risk for uncontrolled infection,
cardiovascular/coronary events
MANAGEMENT
 CBG monitoring and insulin administration
6. Renal Failure
CAUSES
 Sepsis
 Decreased renal perfusion sec. to anemia
(shunting of blood away from the kidney
for protection of O2 delivery to vital
organs)
 Drugs (Cyclosporine, Amphotericin,
antibiotics)
6. Renal Failure
ISSUES
 Hypervolemia (increased BP and CVP 1419 cmH2O, edema) due to multiple
transfusions, steroid admin.
 On the 22nd HD, (+) oliguria with rising
serum crea 2.0 from 0.9 mg/dl (est. crea
clearance 21 ml/min from 47 ml/min)
6. Renal Failure
MANAGEMENT
 Dose adjustments of antibiotics and other
medications
 12-hour urine collection
 Diuresis (Furosemide, Spironolactone,
Bumetanide)
 Subsequent hemodialysis
7. Abdominal Distension
CAUSES
 Septic ileus
 Ileus sec.to metabolic derangement
 Pseudomembranous colitis considered
ISSUES
 Increasing abdominal girth with intermittent
episodes of voluminous watery stools
7. Abdominal Distension
MANAGEMENT
 NPO
 Plain film of the abdomen
 CT scan of the abdomen
 Prokinetics, laxatives, enemas
 Vancomycin per orem
 Rectal tube insertion
 Total parenteral nutrition
CT scan of the abdomen, plain
(May 31, 2009)
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Ileus
Few descending colon diverticula
Distended gall bladder
Atrophic pancreas
Possible right renal cortical cyst
Subcentimeter appendicolith vs. inspissated
barium with no associated inflammatory
changes
 The rest is normal
8.
Metabolic Encephalopathy
CAUSES
 Sepsis
 Electrolyte derangements
 Hypovolemia episodes during
hemodialysis
 Hepatic failure
8.
Metabolic Encephalopathy
MANAGEMENT
 Referral to Neurology service on the 27th HD
 Cranial MRI and MRA of intracranial vessels
requested
 EEG showed encephalopathy probably sec. to
hypovolemia (hypotension episodes during
dialysis)
 Correction of electrolyte abnormalities;
manage sepsis
9. Elevated Blood Pressure
(130-200/70-100 mmHg)
CAUSES
 Volume overload sec. to multiple blood
transfusion, steroid use
 Increased cardiac output sec. to tachycardia
 Catecholamine release (stress-induced)
9. Elevated Blood Pressure
(130-200/70-100 mmHg)
MANAGEMENT
 Ca-channel blockers (Amlodipine,
Nicardipine, Verapamil)
 Clonidine
 Diuresis
10. Tachycardia with PACs
and PVCs (100 – 180 bpm)
CAUSES
 Sepsis/stress-induced
 Anemia
 Metabolic derangements (i.e. electrolyte
imbalance)
 Bronchodilators in increased doses
10. Tachycardia with PACs
and PVCs (100 – 180 bpm)
MANAGEMENT
 2D-echocardiogram with CFDS
 Electrolyte correction
 Beta-blockers (Metoprolol, Nebivolol)
 Digoxin stat doses
 Verapamil
 Amiodarone
 Ivabradine
 Trimetazidine
2D-echocardiogram with CFDS
(baseline)
 May 15, 2009 - Normal LV dimension with
NWMC, EF 75%; calcified non- coronary cusp
of aortic valve without restriction of motion.
Calcified aortic walls; normal MV, TV, PV;
minimal pericardial effusion; color flow
Doppler= MR, mild; TR, mild; mild pulmonary
hypertension as evidenced by pulmonary
acceleration time of 100 msec; Doppler
evidence of impaired LV relaxation.
On the 35th hospital day…
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Tracheostomy done
O2 desaturation noted ~ 90%
HR much controlled: 78 bpm
BP 104/55 mmHg
12-lead ECG post-trache showed: new Twave inversions at V1 – V3, ST-elevations
at II and AVF
Cardiac Enzymes
 May 13: TCPK 60, CKMB 1.5, Trop I 0.08
 June 10: TCPK 47, CKMB 7, Trop T 0.51
 June 11: TCPK 29, CKMB 2.9, Trop I 0.37
 May 13: serum BNP 4,071
2D-echocardiogram with CFDS
(repeat)
 June 11, 2009 - concentric LVH with NWMC,
EF 55%; color flow Doppler = MR, mild;
Doppler evidence of LV diastolic dysfunction
(E/A velocity ratio and isovolumic relaxation
time); mild pulmonary hypertension by
pulmonary acceleration time 108 msec;
compared with previous study done may 15,
increase in LV wall thickness; no note of
pericardial effusion.
On the 41st hospital day…
 While on hemodialysis, ST-segment
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elevations were noted on cardiac monitor,
and patient had 3 episodes of HR 30s – 40s (5
– 10 secs)
BP = 100-130/60-80 mmHg
Awake, responsive
(-) chest pain
12-lead ECG showed….
11. STEMI
ISSUES
 Risk factors: age, atherosclerosis, anemia,
obesity, HPN, hyperglycemia,
dyslipidemia, hemodialysis, multiple blood
transfusion (blood viscosity? increased
platelet aggregation? endothelial
damage?), heparin-induced
thrombocytopenia (?)
11. STEMI
MANAGEMENT
 Nitroglycerin drip
 Nicorandil 5mg/tab 1 tablet BID
 Coronary angiogram
 Options: anti-platelet and anti-coagulation
(?), PTCA (?)
Coronary Angiogram
 Results:
Left ventriculogram – intentionally omitted due to
elevated LV EDP 31mmHg
Coro angio – L main coronary artery normally
patent; LAD normal; L circumflex has slow flow with
abrupt cut off distally which indicates an
endovascular thrombus; RCA is dominant and
normal.
 Assessment: Coronary thrombus involving L
circumflex artery
 Recommedation: Consider Cilostazol at low dose
50mg BID
How Was The Patient Managed?
 Post- coronary angiography recommendations:
Interventional Cardiology - low-dose Cilostazol
50 mg BID
Cardiology – Enoxaparin 40mg SC OD
 Hematology service, however, did not agree
 Due to persistent pancytopenia, Interventional
Cardiology entertained the possibility of HIT,
and suggested discontinuation of Heparin and
use of Bilvalirudin and Aspirin 325 mg OD
Heparin- Induced Thrombocytopenia?
 HIT is a pro-thrombotic, immune- mediated adverse
reaction to heparin therapy;
 It should be suspected whenever the PLT falls at
least 50% and/ or thrombosis occurs between day 4
and 14 following initiation of heparin
 Based on results reported by Warkentin et al. and a
meta- analysis of 15 studies, it appears that HIT
type II occurs in 1-3% of all patients receiving UFH &
in only 0.3- 0.8% receiving LMWH
Heparin-InducedThrombocytopenia?
 When heparin is administered in the presence of
platelet factor 4 (PF4), an immune complex can form
and result in the production of anti-PF4/ Heparin
antibody (HIT antibody)
 This complex initially causes PLT aggregation,
followed by a decrease in the PLT count (due to
consumption and elimination from the circulation) &
the development of thrombosis.
 Paradoxical thrombosis in the presence of
thrombocytopenia is a hallmark of HIT
Heparin- Induced Thrombocytopenia?
 Diagnostic tests include C-Serotonin Release Assay,
Platelet aggregation test, Heparin- induced platelet
aggregation test, ELISA
 Treatment is prompt discontinuation of heparin
and use of an anti-thrombin agent (ie, Argatroban,
Bivalirudin) to prevent thrombotic complications
 Associated thrombotic events frequently noted are
Deep Vein Thrombosis, Pulmonary
Thromboembolism, Mesenteric Arterial Thrombosis
Bivalirudin
 Newer direct thrombin inhibitor; binds to the
substrate- binding site of thrombin, with high
affinity
 Has a rapid, dose- dependent anticoagulation, with
half- life 25 minutes
 Eliminated by the kidneys
 As with all direct thrombin inhibitors, it has no
structural similarities to heparin and has no crossreactivity with HIT antibodies
Patient Outcome
 Hematology service did not agree on the
diagnosis of HIT; however agreed on the use
of Aspirin 325 mg OD (only 1 dose was given)
 3rd day post MI and post angiogram,
persistent pancytopenia and hemodynamic
instability
 Ventricular fibrillation
 After 4o minutes of CPR, patient expired
IS IT POSSIBLE TO DO
PERCUTANEOUS
CORONARY
INTERVENTIONS
IN PATIENTS WITH
MYELODYSPLASTIC
SYNDROME?
Myelodysplastic Syndrome &
Myocardial Infarction
 The association of CAD and thrombocytopenia due
to MDS is rare, and published data on the
management of obstructive lesions through PCI is
limited
 This presents a challenge to interventional
cardiology, because PCI requires preventing both
intracoronary thrombosis with antiplatelet agents,
and bleeding after the procedure
 61/ M, known case of MDS, hypertensive,
presented with pressure- like chest pain,
 Dx: Unstable Angina; submitted to coronary
angiography and stenting
 Platelet count was 40,000;
 prophylactic, 10 unit platelet transfusion 2 days
prior to coronary angiography
 80% stenosis of the RCA and 30% in the LAD
 After a 6- day Clopidogrel 75 mg OD regimen, and
2 hrs after another 10 unit PLT transfusion, stenting
DES of the RCA lesion was done
 6F catheter, femoral approach; introducer was
removed 4 hrs after the procedure
 100 IU/ kg Heparin during the procedure
 Local compression for 20 minutes; no bleeding nor
hematoma was observed after the removal of
introducers
 Discharged with Clopidogrel 75 mg OD to complete 30
days of continuous use.
 Platelet count remained stable at 40,000 on Clopidogrel
 6 months later, TMST showed ST depression in the
inferior leads; repeat coronary angiography showed a
70% in-stent stenosis; He refused another PCI
 20 months after stenting, patient remained
asymptomatic, maintained on the same medication
(Clopidogrel 75 OD, propranolol 40 mg BID, Simvastatin
20 mg OD)
 His last platelet count was 104,000
 In spite of the low PLT, this patient evolved with
progressively unstable angina, suggesting that regardless
of the small number, platelet function remained normal,
thereby justifying the use of anti- platelet agents
 Clopidogrel alone was the treatment of choice in this
study, since it is better tolerated than Ticlodipine
 This case report suggest that PCI in patients with
thrombocytopenia is a safe procedure, provided that
prophylactic platelet transfusion is done, although
restenosis may occur
Management Dilemmas
Is it possible to do stent placement?
•Bare- Metal Stent vs Drug- Eluting
Stent?
If patient tolerates stent
implantation, is it possible to
maintain her on an anti- thrombotic
regimen?
•Single or Dual Anti- PLT therapy?
•ASA vs Clopidogrel vs Cilostazol?
• Dose and duration?
STENTS
 Stents are used in the management of ACS and its
use has improved the outcomes of percutaneous
coronary revascularization
 The metallic surface of the bare-metal stent (BMS)
can stimulate thrombosis before it becomes entirely
covered with endothelial tissues
 Disadvantage: subsequent development of an instent restenosis due to significant loss of lumen
STENTS
 Drug – eluting stents (DES) are believed to inhibit restenosis by inhibition of cytokine- mediated and GF-
mediated proliferation of lymphocytes and smooth
muscle cells
 DES indicated for high- risk patients (diabetics, long
lesions, small vessels, presence of a thrombus)
 DES and dual anti- PLT therapy with ASA and
Clopidogrel reduce stent re-thrombosis rates to <2%
 However the consequences for patients with potential
bleeding conditions are potentially life- threatening
Drug- Eluting stents vs Bare metal stents: Off- label indications, A Propensity- score Matched Outcome Study
Stent Thrombosis
 Catastrophic, mortality rate of 20-45%
 Most commonly, about 1% occurs in the first
month after stent implantation ( subacute ) and
about 0.19% occur after a few months to a few
years ( late )
 BMS are associated with higher incidence of
stent thrombosis compared to DES
 Timing of thrombosis appears to be delayed in
DES (higher early stent thrombosis with BMS,
and late thrombosis with DES)
Drug- Eluting stents vs Bare metal stents: Off- label indications, A Propensity- score Matched Outcome Study
BMS or DES ?
 DES is indicated in
high- risk patients:
diabetic, small vessel,
long lesion, presence of
a thrombus (off- label)
BMS - Shorter duration of
anti- platelet therapy
(minimum of 2 weeks to
1 month for those at risk
of bleeding) thereby
minimizing the risk of
bleeding
• However, BMS are prone
to early stent thrombosis
Aggressive: PCI
 BMS has a shorter duration of anti- platelet therapy
(minimum of 2 weeks to 1 month for those at risk of
bleeding)
 for post- BMS stent, Clopidogrel 75 mg OD for at least 1
month (ideally up to 1 year if not at risk for bleeding;
then it should be given for a minimum of 2 weeks if at
risk)
 a lower dose of 75- 162 mg of ASA is reasonable (during
the initial period after stent placement) in patients at risk
of bleeding
 Cilostazol has similar anti- PLT affects with less serious
side effects;
Use of
ANTI- PLATELET
AGENTS
in
Hematologic Patients
Literature reports on ITP patients who underwent
PTCA/ PCI, with use of anti-PLT:
 62/M with PLT 3,000, underwent LAD stenting,
tolerated 4wks of ASA and 2wks of Clopidogrel;
no bleeding (Caputo, et al.)
 68/F with PLT 22,000, underwent LAD stenting,
maintained on Ticlodipine, no bleeding (Kikuchi
et al.)
 54/M with PLT 8,000, underwent BMS stenting,
given Enoxaparin; discontinued due to epistaxis
(Marques et al.)
 77/M with PLT 70,000, underwent PTCA, on ASA
and Clopidogrel; discontinued due to petechiae
Use of Anti- Platelet Agents
ASPIRIN
Irreversible inhibition of COX-1, which prevents formation of
PGH2, the precursor of thromboxane A2
Patients with thrombocytopenia from whatever cause
(PLT 50,000) are at extremely high- risk of excessive
bleeding. Therefore, Aspirin is harmful in these patients
and should not be administered (Class III
RECOMMENDATION)
 In those who underwent stent placement, a lower dose of
75- 162 mg of ASA is reasonable (during the initial period
after stent placement) in patients at risk of bleeding
The Society of Thoracic Surgeons Practice Guideline Series : ASA and other Anti- Platelet agents during operative coronary
revascularization, 2003
2007 Focused Update on STEMI Guideline
CLOPIDOGREL
Inhibits binding of PLT to ADP receptors
2007 STEMI guideline
• For STEMI patients not undergoing PCI (medical or
PTCA without stenting), treatment with Clopidogrel
75mg OD x 14 days
• Recommends all post- PCI stent patients receiving a
DES, Clopidogrel 75 mg OD for at least 12 months if
patient is not at high risk of bleeding; for post- BMS
stent, Clopidogrel 75 mg OD for at least 1 month
(ideally up to 1 year if not at risk for bleeding; then it
should be given for a minimum of 2 weeks if at risk)–
Level of evidence, B
• Premature discontinuation of Clopidogrel is
associated with a marked increase in risk of stent
thrombosis, & is the leading independent predictor
in multiple studies
• For every 100 patients treated with Clopidogrel +
ASA, 2 events of CV death, non- fatal MI, or stroke
will be prevented but 1 patient will suffer a major
bleed (ie, ICH)
1 Prevention of Premature Discontinuation of Dual anti- Platelet Therapy
2 AHA 2007 Focused Guideline on STEMI
3 CURE (Clopidogrel in Unstable angina to prevent Recurrent Event )Trial
Predictors of Thrombosis
CLINICAL
 Advanced Age
 Acute coronary Syndromes
 Diabetes
 Renal Failure
 Low ejection Fraction
Premature Discontinuation of Dual anti- PLT Therapy in
Patients with Stents (Journal of AHA, 2007)
CILOSTAZOLPhosphodiesterase III inhibitor; anti- proliferative effect
Cilostazol for RESTenosis (CREST) clinical trial in
post BMS
 Preliminary results suggested that Cilostazol
(phosphodiesterase III inhibitor) reduces
restenosis by nearly 40% over standard therapy
alone
 It has similar anti- PLT affects with less serious
side effects (esp bleeding) ; common SE
include thrombocytopenia and leukopenia/
agranulocytosis
CILOSTAZOL
In the study “Triple vs Dual Anti- platelet Therapy
After Coronary Stenting”, addition of Cilostazol
resulted in further reduction of PLT activation due
to additional suppression of P- selectin (a marker
of PLT activity)
 The rate of major bleeding was similar in both
groups
 However, patients with known bleeding disorders
and PLT< 150T were excluded in the study
 Recommended dose 100 mg BID, but may be
decreased to 50 BID if with concomittant use of
CYP450 inhibitors (ie, Diltiazem)
SINGLE ANTIPLATELET THERAPY
OR
DUAL ANTI- PLATELET
THERAPY
Current ACC/ AHA/ Society of Cardiovascular
Angiography & Interventions for prevention of
stent thrombosis post PCI
_________________________________________
At minimum, patients
should be treated with :
Clopidogrel 75 mg OD &
ASA 325 mg OD for
 1 month after BMS,
 3-6 months after DES,
and ideally up to 1 year if
they are not at risk for
bleeding
Dual Anti- PLT Therapy for Prevention of Ischemic
Cardiovascular Events & Stent Thrombosis
Use of a single antiplatelet regimen may
possibly reduce the
risk of bleeding
•Aspirin - 75- 162 mg is
reasonable (during the
initial period after stent
placement) in patients
at risk of bleeding
•Cilostazol has similar
anti- PLT affects with
less serious side effects;
Outcome
 Hematology service agreed on Aspirin
325 mg OD
 3rd day post angiogram, persistent
pancytopenia and hemodynamic
instability
 ventricular fibrillation
 After 45 minutes of CPR, patient
expired
Final Diagnoses
 Cardiopulmonary Arrest sec.to Ventricular





Fibrillation post STEMI, anterolateral wall
Myelodysplastic Syndrome
Sepsis sec.to Pneumonia and Laryngeal
Candidiasis in the Immunocompromised
Acute Renal Failure, multifactorial
Steroid-induced Hyperglycemia
Hypertensive Atherosclerotic Cardiovascular
Disease
 Arrhythmia is a serious complication of
STEMI
 Possibility of another infarction may have
precipitated the arrhythmia
 In retrospect, in an immunocompromised
patient with severe hematologic disorder
with a coronary artery thrombus, who was
septic, undergoing dialysis for acute renal
failure, with impending liver failure, would an
aggressive approach like PCI do more harm
than good?
CONCLUSION
 It is apparent that any medical or surgical
intervention has both systematic and random
effects, some of which are beneficial and some
are unintended negative consequences
 Therefore , the practice of medicine often
necessitates a probabilistic balancing of these
conflicting effects, and management should be
individualized, depending on the risk: benefit
ratio
Thank You
“….. The science of medicine becomes a structured
and organized way of using probability,
uncertainty, and facts in preventive medicine
and clinical care to best benefit the patient and
the community…”
-Jenicek, Foundations of Evidence- Based Medicine