Few data are available with regard to the safety and tolerability of antiplatelet medications in patient with thrombocytopenia Risk stratification by thrombotic and bleeding risks should be performed.PCI and dengue management should consider the timing of coronary intervention and the severity of the dengue infection. Management based on expert opinion; this should be determined by the clinician on a case-by-case basis.

1. Dengue,
Thrombocytopenia &
Cardiovascular Diseases
Presenter
Dr. Safikun Nahar
Phase B resident (Cardiology)
NICVD
Moderator
Dr. Arifur Rahman Sajal
Junior Consultant (Cardiology)
NICVD

2. Background
• Dengue outbreak causes a alarming situation in Bangladesh
• Put cardiologist in a great challenge because of thrombocytopenia
• Currently there is no guideline or consensus regarding management
of these patient

5. Dengue
• Dengue is a disease caused by a virus of the Flavivirus genus
• Widely disseminated, occurring endemically or sometimes epidemically in
tropical regions
• Transmitted by mosquitoes of the Aedes genus, mainly Aedes aegypti
• Predominant in cities
• The virus is subdivided in 4 serotypes that do not provide cross-immunity.

6. Courses of dengue
• Most cases of dengue are self-limited
• The course of the disease is a nonspecific febrile state, general malaise
and weakness
• Patients may feel severe muscle pain and retro-orbital pain, with or
without skin rash
• Laboratory tests may reveal increased hepatic enzyme levels, leukopenia
and thrombocytopenia

7. Cardiac manifestations of dengue
• Atrioventricular conduction disorders :
 junctional rhythm
 atrioventricular block
 supraventricular arrhythmias
• Myocarditis
• Ventricular dysfunction
• Pericarditis
• Dengue-related shock syndrome

8. Causes of bleeding during dengue
• Thrombocytopenia
• Reductions of different coagulation factors: fibrinogen, factorV, factor VIII,
factor IX and factor X, besides antithrombin-2 and α2-antiplasmin.
Evidenced by prolongation in PT and APTT

9. Causes of thrombocytopenia in dengue
1. Hypocellular bone marrow
2. Hemophagocytosis: causes reduction of platelet count
3. Alterations in platelet function
 Platelet counts return to normal within 7 to 10 days after the
defervescence phase
Platelet function resumes its normal conditions 2 to 3 weeks after the
initial convalescence period

10. Thrombocytipenia in ACS
 Thrombocytopenia, defined as a platelet count of <150×10˄9/L
 Present in approximately 5% of ACS patients
 Incident thrombocytopenia can be expected in 13% of patients with
ACS
• older
• diabetes
• renal insufficiency
• heart failure
• prior cardiovascular disease.

11. Classification of thrombocytopenia
Classification Platelet count
Mild 150-100×10˄9/L
Moderate 100-50×10˄9/L
Severe ˂50×10˄9/L

12. Why thrombocytopenia causes coronary thrombosis?
• Platelets are larger
• More adhesive to the vascular surface
• Large platelets have a higher thrombotic potential
• Adenosine-5′-diphosphate, collagen, or epinephrine directly proportion to
the platelet volume
• PMP: in thrombocytopenia active PMPs may be thrombogenic at high
concentrations

13. Prognosis in thrombocytopenia
• Inpatient mortality and bleeding correlated directly with severity of
thrombocytopenia.
• Even mild thrombocytopenia associated with increased risks of
mortality.
• Every 10% decrease in platelet count was associated with increased
mortality and bleeding risk

14. Prognosis in thrombocytopenia (contd)
• Thrombocytopenia in ACS patients predicts significantly worse
outcomes.
• Approximately one in four patient who developed moderate/severe
thrombocytopenia did not survive the hospitalization

15. Drug choice during thrombocytopenia
• Clopidogrel offers a lower bleeding risk compared with ticagrelol or
prasugrel
• Gastrointestinal bleeding is less with clopidogrel
• Due to higher bleeding rates better to avoid prasugrel and ticagrelor
• Ticagrelor as monotherapy drug of interest due to reversible binding
• If platelet count <50×10˄9/L or in the setting of active bleeding, advised
to stop all antiplatelet therapy and avoidance of PCI

16. Drugs should avoided during thrombocytopenia
Medications associated with the development of thrombocytopenia
should be discontinued
• Unfractionated heparin
• Glycoprotein IIb/IIIa inhibitors
• Furosemide
• NSAIDs
• Penicillin based antibiotics

17. Strategies to minimize bleeding risk in patient with
significant thrombocytopenia
• Avoid non-steroidal anti-inflammatory drugs
• Avoid glycoprotein IIb/IIIa inhibitors
• Utilize a proton pump inhibitor unless contraindicated
• Aspirin should be used in low-dose form
• If a patient is already receiving a long-term anticoagulation agent, triple
therapy should be avoided

18. If a patient is undergoing percutaneous
coronary intervention
• Radial approach preferred to femoral approach
• Restrict dual antiplatelet therapy to 1month post-stent
• Second generation drug-eluting stent preferred to bare-metal
stent

20. Approach to ACS patients with thrombocytopenia.

21. approach to stable coronary artery disease
patients with thrombocytopenia.

22. Categorization of patient with thrombosis
High short term risk of thrombosis Low short term risk of thrombosis
Recent coronary angioplasty with stent
implantation
Coronary angioplasty with stent implantation
more than six months before.
Mechanical valvular prostheses, with
associated AF
Biological valvular prostheses.
Patients with AF and multiple thrombotic risk
factors
AF and no risk factors for thrombosis
Prior thromboembolism or more than one
mechanical valve.
Stable coronary artery disease.

23. Implications of antithrombotic agents in cardiac
patients with dengue
All patient with
dengue
should avoid using Aspirin for one week . In patients at high risk of
thrombosis treatment with antiplatelet agents may be maintained
provided platelet counts are regularly monitor
Dengue and at a
high short term risk
of thrombosis
replace warfarin with heparin as soon as the INR level is below the
therapeutic range. Reintroduce warfarin after one week.
antiplatelet interruption considered depending on number of
platelets.
Dengue and at low
short term risk of
thrombosis
interrupt the use of aspirin. Consider interrupting clopidogrel and
warfarin for one week.
Patients with dengue
hemorrhagic fever
interrupt immediately all antithrombotic agents.

24. Categorization of patient after PCI
The high thrombotic risk
• patients with recently implanted DES ⩽3months or BMS/angioplasty ⩽1 month,
• complex interventions (e.g. left main or bifurcation stenting)
• use of multiple stents (especially if small stents and/or
long stents)
The low thrombotic risk
• patients with implanted DES >3 months or BMS/angioplasty >1 month.
These criteria are not exhaustive and are based on expert opinion; this should be
determined by the clinician on a case-by-case basis.

25. Recommended antiplatelet management in post-PCI
patient with dengue infection.
When to stop antiplatelet therapy? When to restart antiplatelet
therapy?
Dengue + high thrombotic risk Stop both anti-platelets when
platelet<50k
Load both anti-platelets when
platelets upward trend and >50k.
Dengue + low thrombotic risk
Stop both anti-platelets when
platelet<70k
Restart both anti-platelets when
platelets upward trend and >50k
Dengue+ clinically significant
bleeding + high thrombotic risk
Stop both anti-platelets when
platelet<100k
Load both anti-platelets when
platelets upward trend and >70–
80k and no further bleeding
Dengue + clinically significant
bleeding + low thrombotic risk
Stop both anti-platelets when
platelet<100k
restart both platelets sequentially
when platelets upward trend and
>70–80k and no further bleeding.

26. Throbocytopenia with CABG
• One guideline is to avoid giving aspirin after CABG to patients who
have thrombocytopenia (defined as platelet count <50 ×109/L
• In patients with ITP, successful PCI and CABG with supportive platelet
transfusion have been reported.

27. Take home massage
• Few data are available with regard to the safety and tolerability of
antiplatelet medications in patient with thrombocytopenia
• Risk stratification by thrombotic and bleeding risks should be
performed

28. Take home massage(contd)
• PCI and dengue management should consider the timing of coronary
intervention and the severity of the dengue infection.
• Management based on expert opinion; this should be determined by
the clinician on a case-by-case basis.

29. THANK YOU