Archive for the ‘anti platelet drug’ Category


A 52-year-old diabetic woman who had undergone recent PCI with a DES developed a febrile illness which was diagnosed as Dengue fever. She has been taking DAPT (Dual antiplatelet) meticulously to maintain her stent. Now, her platelet count has dropped from 1.5 and subsequently to 1 lakh. She is asking now, whether to stop DAPT or not? What is the risk of stent occlusion if she stops? 

The D³ cube syndrome 

Infectious diseases rarely bother a cardiologist (maybe a few IE,  myocarditis, etc). Now, a unique situation is emerging.

*Dengue affects 50-100 million people worldwide every year and one billion are at risk. CAD affects 5 % of the population that amounts to  350 million. As we fight CAD, 2 million coronary stents are implanted annually and at least one-third of them may be on DAPT at any time.

When a  global population is at risk of an infection that targets human platelets and another chunk of the same population in whom platelets are targeted with drugs, what is the Incident risk of overlap between these two groups


If you look at these two maps, I think we will not hesitate to call both Dengue and DES a global epidemic affecting the platelet function. The top one depicts the world stent market and the bottom Dengue prone countries


Mechanism of thrombocytopenia in dengue

The mechanism of thrombocytopenia in dengue is not clear. Both production at the marrow level and destruction in the periphery is attributed. The antibody-mediated NS (nonstructural protein) is the original antigenic sin  (Click to know more)

Chiao-Hsuan Chao PLoS Pathog. 2019 Apr; 15(4): e1007625. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497319/

Meanwhile, DAPT paralyzes the platelet by blocking  P2Y12 and COX. It is obvious Dengue virus amplifies the antiplatelet action and increases the bleeding risk at any point during the illness.M

Risky period

Bleeding periods is highly unpredictable. The late recovery phase seems to be critical for hemorrhagic risk.it can go up to  2 to 3 weeks or even a month. (When we don’t have data, only experience becomes data. )

How to manage Antiplatelet agents in post PCI patients with dengue? 

While we have guidelines to stop DAPT during the need for emergency surgeries, the same can not be adopted in Dengue.(Curiously, we can stop DAPT without much fear, after all, dengue antigenic responses take up the role of antiplatelet agent )

Presario from Brasil proposed a practical suggestion.Pesaro AE  (Dengue: cardiac manifestations and implications in antithrombotic treatment. Arq Bras Cardiol. 2007 Aug;89(2):e12-5)


Switching to other drugs like eptifibatide or NSAIDs is not an option. 

Post dengue prolonged platelet dysfunction

Though the platelet count returns to normal soon after recovery, long-term platelet defects are also reported. This has implications in resumption of DAPT. Surprisingly, dengue recovery phase thrombocytosis also happens for some unknown reason. Ref: Rebound thrombocytosis causing MI following dengue fever? (Roy A, et al  Indian Heart J. 2007 Jan-Feb;59(1):94)

Final message

When both Dengue &  post PCI epidemics are trying to match in numbers, I guess D³ syndrome (Dengue-DES-DAPT)  would soon become a significant clinical issue. 

Now going back to the title question, Should I stop DAPT or not? 

  • Never easy to answer this question. It is a fine balance between the risk of bleeding vs the risk of stent thrombosis.No amount of algorithm and guideline may clarify it.
  • On any given day, the risk of bleeding in vital spots is more dangerous than thrombus.
  • It is wise to withhold antiplatelet drugs in all febrile illnesses when the platelet count is actively falling below 1 lakh. It may not be quixotic thinking to expect dengue viremia to help the DES with its DAPT equivalent action ! in the intervening period.


1. Ehelepola NDB, Athurupana Bowatte , Dissanayake  Continuation of Dual Antiplatelet Therapy in a Patient with a Coronary Artery Stent with Dengue Hemorrhagic Fever: A Clinical Conundrum.The American Journal of Tropical Medicine and Hygiene, 01 Jan 2020, 102(1):17-19  

2.Wishnu Aditya et all Proceedings of Singapore Healthcare 2019


Further queries

What about Heparin, Oral anticoagulation (OAC), usage in suspected Dengue?

Go back to basics. Heparin and OAC don’t affect platelet function. It is 100 % safe to continue.

Really? do you think so? No, coagulation physiology is not that simple. Thrombin and antithrombin interactions happen right on the platelet surface. Any antithrombin drugs do have some antiplatelet action as well. Extreme caution is required again. Withhold them unless absolutely indicated.


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Anti-platelet drugs find a place virtually in every prescription written by a cardiologist for CAD.No doubt, it sits right on top among the highest prescribed medication in the world. They are used in all forms of CAD/ ACS. It becomes  mandatory in  post PCI as a stent maintenance protocol. 

Cardiologists (at least me) are exhausted with so many studies with these drugs. When we thought we are relaxing for a while, the current issue of circulation release a big meta-analysis with 50,000 patient data.It tries to draw fresh battle lines between the three friendly  P2Y12 inhibitors.


  • The findings, from the meta-analysis, directly confront the famed study ISAR React 5 (NEJM 2019)which apparently crowned Ticagrelor the superiority cap over prasugrel  
  • It says Ticagrelor is as good as Prasugrel in any ACS patients. 
  • I guess this meta-analysis is meant to remove the huge faith cardiologists show towards Prasugrel (Still as on date, Prasu is probably  best for stent thrombosis prevention in complex PCIs)
  • While the humbled and knocked out clopidogrel still manages to woo, with its low bleeding risk and cost .(Comorbid patients) 
  • As expected Aspirin, is not even in the fighting ring, just chucked out by the referee for being too smart and threatening the famed heavyweights.(THEMIS brings Ticagrelor even for primary prevention 2020 FDA approved)

What should you believe in? 

This meta-analysis or the ISAR React 5? Don’t believe either,  Then what shall I do? Maybe, go with your Intuition. (Considering the fact, P2Y12 receptors are more attracted to unidentified wall street ligands, than Adenosine diphosphates)

Final message 

Let us hope true breakthroughs happen in antiplatelet drugs so that we no longer need to see these boring  fights between the same old drugs.



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Caution : Non-Academic stuff

Anti hypertensives, lipid-lowering drugs along with antiplatelet drugs always find a proud place in most cardiac prescriptions. The toxic rivalry between various drugs and their creators is a well-known secret. However, the current fight among the antiplatelet agents is reaching comical proportions. The punches and reverse punchs on and off the podium is there for everybody to see.

It all started with clopidogrel two decades ago which was crowned after conquering then-popular Ticlopidine. It was followed by Prasugrel and Ticagrelor. Ticagrelor seems to taste its own medicine from Prasugrel, which brought back memories of the same knock out punches both of them gave to clopidogrel in the past. I guess the ISAR bruised Ticagrelor is just taking a time out, expected to REACT with fresh vigor in the next bout vs Prasugrel.

While these financial heavyweights struggle to keep the bull run, in the multi-billion-dollar stent maintenance market . Aspirin, the aged warrior is enjoying the theatrics silently. While Aspirin is repeatedly shown ( shown literally means shown: Mind you, It is not a synonym for a proven fact ) that it is inferior in stented patients.For stable CAD Aspirin still in the very much in the reckoning. Let the Twilight shine soon. Don’t get a shock of your life, if Aspirin regains the championship one day.


Final message

Let us hope the fight gets over till another Grelor  crash lands from nowhere. Meanwhile, we shall strive hard as professional physicians to increase the per-capita antiplatelet drug consumption in  every acute and chronic coronary syndrome (with or without PCI). This will help keep Homosapien’s coronary artery eternally patent.


For pure Academics  (Conclusions in science is a misnomer . . . )




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DAPT -Dual anti-platelet therapy has become  a standard in many clinical situations of CAD.There has been significant confusion about ,Indications, best combination, duration of DAPT, withholding of DAPT, conversion to MAPT (mono) etc.The  JACC september 2016 issue  brings much needed clarity  on this issue.

Link to key summary from NEJM journal watch.


Full text guideline

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