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 Table of Contents  
Year : 2023  |  Volume : 9  |  Issue : 1  |  Page : 91-94

Subacute stent thromboses in marijuana user associated with isolated protein S deficiency: Thirteenth month of the famine

1 Department of Cardiology, Fellowship in Interventional Cardiology, ICPS, Paris, France; Department of Cardiology, Yashoda Hospital, Somajiguda, Hyderabad, Telangana, India
2 Department of Internal Medicine, Yashoda Hospital, Somajiguda, Hyderabad, Telangana, India

Date of Submission21-Aug-2022
Date of Decision02-Dec-2022
Date of Acceptance07-Mar-2023
Date of Web Publication04-May-2023

Correspondence Address:
Pankaj V Jariwala
Department of Cardiology, Yashoda Hospital, Somajiguda, Hyderabad - 500 082, Telangana

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcs.jpcs_52_22

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We present the case of a young professional male, marijuana user who experienced subacute stent thromboses following percutaneous coronary intervention. We identified that he also had a protein S deficiency when we investigated the medical causes of procoagulant conditions. The patient was subjected to a surgical revascularization and began direct oral anticoagulant combined with antiplatelet agents to prevent recurrent thrombotic events. There is no proven way of revascularization in these cases, and antithrombotic medications are ineffective in preventing recurrent ischemia episodes, necessitating more research to determine definitive therapeutic methods for these subsets of cases.

Keywords: Cannabis, case report, marijuana abuse, protein S deficiency, stent thrombosis

How to cite this article:
Jariwala PV, Gude D. Subacute stent thromboses in marijuana user associated with isolated protein S deficiency: Thirteenth month of the famine. J Pract Cardiovasc Sci 2023;9:91-4

How to cite this URL:
Jariwala PV, Gude D. Subacute stent thromboses in marijuana user associated with isolated protein S deficiency: Thirteenth month of the famine. J Pract Cardiovasc Sci [serial online] 2023 [cited 2023 Jun 8];9:91-4. Available from: https://www.j-pcs.org/text.asp?2023/9/1/91/375812

Learning Objectives

  • Deficiencies of protein S and/or C are prevalent causes of spontaneous thrombosis in diverse arterio-venous territories
  • It is unusual to find an association between protein S deficiency and subacute stent thrombosis in marijuana users
  • In younger patients with coronary thrombosis, a search for additional prothrombotic states should be conducted.

  Introduction Top

”Thirteenth month of famine (

-A Marathi Proverb”.

Cannabis sativa plants are the source of marijuana, which typically affects the nervous system. However, due to the rising global prevalence of marijuana use, it is crucial to understand the negative effects of marijuana on the cardiovascular system, especially the likelihood of myocardial infarction (MI), even though only a small number of marijuana-related MI cases have been observed [1],[2]. Delta 9-tetrahydrocannabinol (THC), the main psychoactive element in marijuana, interacts with the endocannabinoid cannabinoid system via two G-protein-coupled membrane receptors, cannabinoid receptor type 1 (CBR1) and CBR2. CBR1 is widely distributed throughout the nervous system and causes most cardiovascular effects via sympathetic nervous system activation.[3]

Cannabis use may increase the risk of coronary artery thrombosis.[2] Marijuana has indeed been proven to raise the threat of MI by approximately five times within 60 min of exposure, with a 1.5%–3% annual risk of adverse cardiac catastrophes.[4] Protein C and protein S deficiencies are infrequent causes of coronary artery thrombosis.[5] Physicians may have difficulties in achieving effective management. We present a case of subacute stent thromboses (SST) in a young marijuana user attributable to isolated protein S deficiency.

  Case Report Top

A 42-year-old man presented with complaints of retrosternal chest pain on exertion that had been present for 6 weeks. He admits to using marijuana as a recreational drug. There were no additional risk factors recorded, nor was there a personal or family history of any medical illness. The vital parameters, general examination, and cardiac examination were unremarkable. Laboratory and cardiac investigations, including an electrocardiogram and echocardiography, were all normal.

He underwent coronary angiography, which revealed a left dominant circulation along with significant stenosis of the mid-segment of the left anterior descending (LAD) artery and the distal segment of the left circumflex (LCx) artery extending to the inferior descending artery. In view of his young age, discrete lesions, and patient preference, he underwent percutaneous coronary intervention (PCI) with zotarolimus drug-eluting stents to the LAD (3.5 mm × 18 mm) and LCx (2.5 × 33) without any edge dissection and thrombolysis in myocardial infarction (TIMI) III flow [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. He was discharged without incident 2 days after the index procedure on dual antiplatelet therapy, which included aspirin and ticagrelor, as well as other guideline-directed medical therapy for the secondary prevention of coronary artery disease (CAD).
Figure 1: Coronary angiography of the left coronary artery demonstrated critical stenoses of the mid-segment of the left anterior descending artery and the distal segment of the left circumflex artery (solid arrows; Panels a and b). The percutaneous coronary intervention was executed on both stenoses utilizing drug-eluting stents with thrombolysis in myocardial infarction III flow with no residual dissection and satisfactory stent expansion (curved dashed lines; Panels c and d)

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The patient returned to the emergency room 2 days after the procedure with a new complaint of chest pain. There was ST-segment elevation of anterolateral leads, whereas the inferior leads had reciprocal ST-segment depression. He developed hypotension and repeated pulseless ventricular tachycardia that necessitated direct current cardioversion, so he was transferred to the Cath laboratory for coronary angiography. There were SST in both stents, as anticipated. Thromboaspiration was attempted several times, and postdilatation of the stents with noncompliant balloons at higher pressures was successful in establishing TIMI 2 flow in both arteries [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d.
Figure 2: Coronary angiography of the left coronary artery demonstrated thrombotic occlusion of both stents of the left anterior descending and circumflex arteries in caudal views with thrombolysis in myocardial infarction flow 0 (dashed arrows; Panels a and b). Percutaneous old balloon angioplasty using noncompliant balloons at high pressures and thrombo-aspiration could establish TIMI 2 flows in left anterior descending and circumflex arteries (curved dashed lines; Panels c and d). TIMI: Thrombolysis in myocardial infarction

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Despite the use of antiarrhythmic drugs and repeated electrical cardioversion, he continued to have chest discomfort, hypotension, and ventricular tachycardia. To stabilize the hemodynamic, a mechanical circulatory assist device in the form of an intra-aortic balloon pump was inserted. After stabilization, the Heart team decided on surgical revascularization to prevent the recurrence of symptoms caused by recurrent stent thrombosis in marijuana users. He underwent total arterial revascularization, and coronary artery bypass surgery, which included 4 arterial grafts to the LAD and LCx territories. He had an uneventful stay in the hospital and was discharged 1 week after the surgery.

Traces of THC was detected in urine toxicology. The verify now, P2Y12 platelet reactivity tests demonstrated that there was no ticagrelor resistance. Plasma protein S activity was low (34%; Normal range 77%–143%) discovered in his thrombophilia profile, but the rest of his procoagulant work-up such as protein C activity, prothrombin time, dilute Russell viper venom time, plasma antithrombin activity, plasma Homocysteine, Lupus anticoagulant, Serum immunoglobulin M (IgM) and IgG antiphospholipid antibodies, were unremarkable.

The antithrombotic regimen consisted of a combination of dual antiplatelet therapy in the form of aspirin 75 mg once daily, and clopidogrel 75 mg once daily as well as a direct oral anticoagulant in the form of rivaroxaban 20 mg once daily for initial 3-month. Following that, we adhered to the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial regimen of antithrombotic agents comprising single antiplatelet therapy, aspirin 150 mg plus rivaroxaban 2.5 mg twice daily. He is currently being actively monitored every 3 months, with cardiac evaluations such as echocardiography and stress testing, and there has been no resurgence of his symptoms in the past 2 years.

  Discussion Top

Unless additional cardiovascular risk factors are present, CAD is almost never the cause of acute coronary syndrome (ACS) in younger individuals. This is the case even when other risk factors are present. Even though nonatherosclerotic causes of ACS are rare, it is important to take them into consideration in young patients.[1] In our case, the stent thrombosis was caused by two nonatherosclerotic factors: marijuana use and a protein S deficiency. Because there is no case report in the literature about this rare triple association, we classified the clinical evidences into three categories.

Stent thrombosis and protein S deficiency

Protein C and S are important physiological anticoagulants. Protein S is a Vitamin K-dependent glycoprotein that is synthesized by hepatocytes and megakaryocytes and functions as a cofactor for protein C.[6] Their inadequacies cause hypercoagulability, which generally manifests as recurring venous thromboembolism. Spontaneous coronary artery occlusion has also been recorded as an arterial thrombotic episode. The probability of clinical presentation is higher before the age of 40 years.[5] Kurniawan and Pratanu reported an interesting triple association of SST, clopidogrel resistance, and protein S deficiency where the patient developed SST, 2 days later like in our case, and underwent a repeat procedure.[7]

Although case reports have connected protein C and S deficiency to arterial thrombosis and MI, larger investigations have been unable to substantiate this relation. Furthermore, the established significance of inflammation in affecting the ratio of measurable, unbound to bound protein S, as well as the likelihood that altering protein S levels in the setting of MI are indicative of the elevated inflammatory state instead of a causative of CAD.[6]

Stent thrombosis and marijuana use

The primary psychoactive molecule in marijuana, delta 9-THC, plays the role on the endocannabinoid system to induce numerous cardiovascular toxic effects and has been linked to several negative cardiovascular effects, including ACS, arrhythmias, and sudden cardiac death. Yoo et al. studied the prevalence and safety of marijuana use among PCI patients, and 3970 of 113,477 patients admitted to using it. Patients who used marijuana tended to be younger, more likely to smoke cigarettes, had a history of MI with ST-segment elevation, and have less risk factors for cardiovascular disease.[8] Wengrofsky et al. reported a case of a young male who had recurrent acute MI secondary to coronary thrombosis without any underlying significant coronary artery lesion.[4] Similar to our case, Kayapinar et al. described a case of ST-segment elevation MI and SST in a young marijuana user after PCI.[9] Myocardial ischemia and injury caused by the interaction of endothelial dysfunction and variable vasoconstriction and vasodilation, with characteristic coronary angiographic findings of sluggish coronary flow phenomenon.[10]

Marijuana usage and protein S deficiency

There is only a case reported to date in the literature in phase IV clinical observation of the United States food and drug administration.[11] Where the use of marijuana leads to acquired protein S deficiency or it aggravated congenital protein S deficiency is not clear. The interplay of various comorbidities observed in our case resulted in the development of SST as shown in [Figure 3].
Figure 3: Schematic representation of the mechanism of stent thrombosis in our case and its clinical presentation and management. PCI: Percutaneous coronary intervention, CABG: Coronary artery bypass surgery, APT: Antiplatelet therapy, OC: Oral anticoagulant

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Future directions

It is yet unknown which revascularization method is better for patients who have protein C and/or S deficiencies. In our situation, adding ticagrelor to the combination did not prevent SST. In these subsets of patients with a strong thrombotic tendency, there are limited case reports of surgical revascularization. However, the long-term viability of grafts is also debatable. Should a dual antiplatelet therapy combined with oral anticoagulation be used as a routine anti-thrombotic approach for these patients' secondary prevention of recurrent thrombotic events? Is it better to use Vitamin K antagonists or direct oral anticoagulants as anticoagulants? Although patients of protein S deficiency were not included in this trial, we used the antithrombotic technique and doses indicated in the COMPASS trial.[9] To answer all these questions, we will need more clinical data.

  Conclusion Top

So far, no reports of SST in marijuana users linked with isolated protein S deficiency have been published in peer-reviewed journals. The emergence of this link could be attributed to any of the interrelationships of etiological causes. In our situation, it is unclear if marijuana usage caused protein S deficiency or whether inherited protein S deficiency was exacerbated by marijuana use. However, SST should be viewed as a serious and potentially fatal complication in marijuana users, and proper therapeutic precautions must be undertaken.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Ethics clearance

No Institutional Ethical Committee (IEC) clearance required for the publication of the case reports unless patient identity is not revealed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Lawin D, Lawrenz T, Tego A, Stellbrink C. Cannabis-induced recurrent myocardial infarction in a 21-year-old man: A case report. Eur Heart J Case Rep 2020;4:1-5.  Back to cited text no. 1
Matta A, Elenizi K, Elbaz M, Roncalli J. Left main coronary artery thrombus after cannabis consumption: A case report. Eur Heart J Case Rep 2021;5:ytab179.  Back to cited text no. 2
Gelfand EV, Cannon CP. Rimonabant: A cannabinoid receptor type 1 blocker for management of multiple cardiometabolic risk factors. J Am Coll Cardiol 2006;47:1919-26.  Back to cited text no. 3
Wengrofsky P, Mubarak G, Shim A, Kariyanna PT, Buzidkowski A, Schwartz J, et al. Recurrent STEMI precipitated by marijuana use: Case report and literature review. Am J Med Case Rep 2018;6:163-8.  Back to cited text no. 4
Acar G, Dogan A, Altinbas A, Turker Y. Recurrent acute stent thrombosis associated with protein C and S deficiencies. Int J Cardiovasc Imaging 2006;22:333-7.  Back to cited text no. 5
Abdel-Latif A, Moliterno DJ. Editorial: Protein C and S deficiency as a risk factor for stent thrombosis – When a rare disorder can predispose to rare events. J Interv Cardiol 2010;23:565-8.  Back to cited text no. 6
Kurniawan MZ, Pratanu I. Sub-acute stent thrombosis and in-stent restenosis associated with antiplatelets clopidogrel resistance and protein s deficiency. Folia Med Indones 2015;51:214-20.  Back to cited text no. 7
Yoo SG, Seth M, Vaduganathan M, Ruwende C, Karve M, Shah I, et al. Marijuana use and in-hospital outcomes after percutaneous coronary intervention in Michigan, United States. JACC Cardiovasc Interv 2021;14:1757-67.  Back to cited text no. 8
Kayapinar O, Kaya A, Sayin GAAE, Koc E. ST segment elevation myocardial infarction and subacute stent thrombosis in a young marijuana user. Ann Cardiol Cardiovasc Med 2017;1:1006.  Back to cited text no. 9
Pacher P, Steffens S, Haskó G, Schindler TH, Kunos G. Cardiovascular effects of marijuana and synthetic cannabinoids: The good, the bad, and the ugly. Nat Rev Cardiol 2018;15:151-66.  Back to cited text no. 10
Marijuana and Protein s Deficiency, a Phase IV Clinical Study of FDA Data – eHealthMe n.d. Available from: https://www.ehealthme.com/ds/marijuana/protein-s-deficiency/. [Last accessed on 2021 Jun 09].  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3]


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