Here's how readers responded to a You Make the Call question about management of a patient with recurrent coronary artery closure.
Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.
A protein S activity test is not useful for this 71-year-old patient, nor is any other thrombophilia test, because anticoagulant deficiency is not associated with arterial events at this age. I suggest checking for suboptimal antiplatelet drug effect, although these tests are not well standardized in all labs.
Ravi Sarode, MD
Dallas, TX
Yes, I would use warfarin.
Suresh B. Katakkar, MD, ScD
Tucson, AZ
There is no role for warfarin because there are better options available that are not a >70-year-old cumbersome and outdated medication. Bury the drug already!
Matthew Taub, MD
Pembroke Pines, FL
I suspect this is not a hematology problem; it is a vascular problem. However, given that the questioner has tried antiplatelet agents, and given the seriousness of the clinical problem, I agree with adding a direct oral anticoagulant (DOAC) or warfarin to the antiplatelet agent.
Satvir Singh, MD
Snellville, GA
My advice is to learn more about hypercoagulability in this patient. It’s common to see low values of proteins C and S in patients with active thrombosis, so this it is not necessary a genetic problem. This patient might have undetected thrombophilia. I would also test liver function. Depending on the results, I would probably recommend aspirin plus cilostazol, and maybe apixaban or enoxaparin closer to the time of the CABG. Warfarin is not recommended in surgical procedures, and its management is difficult with other drugs.
Olga López OdrÃa, MD
Lima, Peru
Yes, there is a role for warfarin, with adequate antiplatelet therapy and transition (bridging) due to questionable protein C and S levels.
Shelby D. Rifkin, MD
Evanston, IL
I would not recommend warfarin for a patient with a modestly decreased protein S level.
David M. Baer, MD
Oakland, CA
I see no role for warfarin treatment. It is very unlikely that the borderline low/low normal value of protein S has a relevant pathogenetic role in these recurring coronary artery occlusions. I would suggest introducing a double antiplatelet therapy.
Bernhard Lämmle, MD
Mainz, Germany
There is no role for warfarin.
Ruth Fife-Crepage, CNS
Cleveland, OH
The mild deficiency of protein S in this patient is of no clinical consequence. However, the addition of warfarin may significantly reduce protein S activity, thus further increasing the patient's presumptive hypercoagulability. If anticoagulation is indicated, options would include low-molecular-weight heparins or DOACs.
Solomon I. Hamburg MD, PhD
Los Angeles, CA
There may be a role for adding anticoagulation in this patient. Several antiplatelet drugs may be useful to reduce the risk of occlusion of a grafted artery. However, because the question is being raised by an oncologist, perhaps the patient has cancer. If so, to avoid the interference of warfarin with any chemotherapy, I would recommend anticoagulation with a DOAC rather than warfarin plus aspirin or any other antiplatelet agent, because DOACs have proven to be efficient in preventing venous thromboembolism (VTE) in cancer patients and do not require laboratory monitoring.
Giuseppe Avvisati, MD, PhD
Rome, Italy
I would recommend starting enoxaparin to avoid problems of warfarin (e.g., drug interaction, lots of blood tests needed to monitor, narrow safety margin). These issues are relevant in such an elderly patient on multiple drugs.
Mohamed Salem, MD
Washington, DC
There is no role for warfarin.
Michael Elliott Pidcock, MBBS
Canberra, Australia
I would recommend using antiplatelet agents. If anticoagulation ends up being recommended, I would consider rivaroxaban or apixaban rather than full-dose warfarin.
Victoria Giffi, MD
Hagerstown, MD
There may be a role for a DOAC, but not for warfarin.
Antoine Sayegh, MD
Roseville, CA
Protein S deficiency is unlikely in this patient. In addition to this being a higher-than-expected value for true protein S deficiency, protein S activity levels are generally measured via a clot-based assay, which can be affected by multiple factors (e.g., acute illness, recent thrombosis, additional prothrombotic conditions). If I were concerned about protein S deficiency, I would want to know the total and, in particular, free protein S levels. If these tests were suggestive of protein S deficiency, genetic testing could be done.
That being said, protein S deficiency is only weakly associated with arterial thrombosis, and I would not pursue further protein S workup if no other clinical sequelae (e.g., history of unexplained VTE, strong family history of the same) are present. If it has not already been done by a cardiologist, it would be reasonable to rule out pathological conditions more closely linked to arterial thrombosis, especially antiphospholipid antibody syndrome. JAK2 testing may be considered, as a JAK2+ myeloproliferative neoplasm can be a rare cause of coronary vessel thrombosis.
A not-infrequent cause of stent thrombosis is platelet hyperreactivity or resistance to antiplatelet therapy, specifically anti P2Y12 therapy. Since three antiplatelet agents have not worked for this patient, and there is not reliable data on how to act upon the presence of increased in vitro platelet activity, I would not perform this testing at this time.
However, I would confirm adherence. Platelet aggregation studies that show absent aggregation after addition of arachidonic acid confirms aspirin consumption. This test is considered a reliable indicator of adherence, since true aspirin resistance is very rare. If the patient is adherent to medication and if additional risk factors are controlled for (e.g., hypertension, dyslipidemia, diabetes), then anticoagulation with warfarin is not unreasonable, although bleeding risk should be weighed in this decision and discussed with the patient. Rivaroxaban combined with antiplatelet therapy for secondary prevention after stent placement has been shown to be effective in reducing thrombotic complications, but it is impossible to say whether that effect would carry over here.
Perrin Jhaveri, MD
Palo Alto, CA
This patient would not be a candidate for warfarin without use of some other anticoagulant also, as the protein S level will decrease further. If the protein S level is already low, this could contribute to a hypercoagulable state. Options for anticoagulation would be adding an anti-factor Xa agent or dual antiplatelet therapy.
Andrew Shearer, MBBS
Cairns, Australia
The patient's variable level of protein S activity is unexplained, but it seems that he is closer to a hypercoagulable state, given his repeated stent and graft occlusion. I think it would be wise to add an anticoagulant to single antiplatelet therapy, but his risk of bleeding should be assessed. Warfarin is difficult to manage in the elderly population, so a DOAC might be a better choice.
Abdelrahman Soliman, MD, MSc
Ismailia, Egypt