Acute Coronary Syndrome (ACS) in Polycythemia Vera: A Case Report with Review of Literature

Polycythemia Vera (PV) is a chronic bone marrow disorder which causes hyper viscosity of blood thereby, increasing the risk of coronary thrombosis and acute myocardial infarction (MI). We report a 65-year-old male patient with history of PV presented with ST segment elevation hyper-acute anterior wall myocardial infarction (MI). His blood investigation report showed higher levels of hemoglobin (Hb) and hematocrit (Hct). This case illustrates the importance of recognizing PV as a major cause of thrombotic occlusion of coronary arteries and to prevent future ischaemic events by initiating suitable therapy.


INTRODUCTION
Myocardial infarction (MI) and heart failure (HF) are the most common cause of death in the world [1]. Traditional risk factors for MI are hypertension, diabetes, dyslipidemia, smoking and a family history of premature coronary heart disease (CHD) [1].
Polycythemia Vera (PV) is a rare type of blood cancer in which body produces too many red blood cells. If not treated, PV can lead to life-threatening complications [2][3][4]. This disorder is marked by increased bleeding and thrombotic occlusion of coronary arteries leading to morbidity and mortality in 40% to 60% of the patients [3].
Patients with a prior history of vascular thrombosis and who are in advanced age (≥ 60 years) are at a higher risk for complications [3,5]. The rate of incidence of PV is higher among men than women (~2.8 per 100,000 men and ~1.3 per 100,000 women) [6]. The overall incidence is 2.30/1,00,000 persons/year [7]. Cytoreductive treatment by phlebotomy or chemotherapy and antiplatelet therapy with low-dose aspirin have significantly reduced the number of thrombotic complications and substantially with improved survival [8].

CASE PRESENTATION
A 65 year old non-diabetic and non-hypertensive male presented to our hospital with severe retrosternal compressive chest pain radiating to left arm with sweating since the past one hour. On physical examination, his pulse rate and blood pressure (BP) was recorded as 96/min and 110/80 mmHg respectively. Patient is a non-smoker and without any history of drug use or a family history of coronary artery disease (CAD). On auscultation, there was no S3 gallop or any cardiac murmurs, but had bilateral basal crackles (rales) in the lung fields. The oxygen saturation was 92% on room air. However, patient was a known case of Polycythemia Vera (PV) (positive for JAK2 V617F mutation) diagnosed 2 years back. He was on hydroxyurea for one year, which was stopped due to recurrent infections and altered platelet counts. The patient underwent Phlebotomy six months back, there after he was asymptomatic.
We also determined the levels of lipids such as total cholesterol and LDL and found 146 mg/dl of 88 mg/dl respectively. Since, there is reduced life expectancy in PV patients, and also risk of transformation to myelofibrosis and acute myeloid leukemia, consultation with haematologist was necessary.
Early diagnosis and treatment of MI in PV is challenging and should be carefully managed using a multi -disciplinary approach. In this respect, meager information is available on the treatment of MI in PV patient's hence we can't expect answers to all the queries.  are prescribed [13], but it is uncertain which type of coronary reperfusion procedure is appropriate for treating MI in PV patients. The safety and efficacy of fibrinolytic therapy as the treatment of choice for acute STEMI in patients with PV is yet to be established. Effective fibrinolytic therapy may still be associated with residual coronary thrombus, which is more likely seen in PV patients who have high platelet counts [14].
Cytoreductive treatment with phlebotomy to achieve hematocrit of ≤45% is critical in optimizing the outcomes in patients with PV [5]. Phlebotomy and myelosuppression are the treatment options most often utilized, either alone or in combination. However, therapeutic phlebotomy to reduce hematocrit levels before primary angioplasty can lead to unnecessary delay and should not be pursued in an acute setting. Hyper-viscosity and platelet aggregation can increase the risk of stent thrombosis [15], making the patient vulnerable, due to post procedure drop in the levels of anticoagulation. Therefore, in our patient, it was decided to perform phlebotomy after the PTCA, to maintain the haematocrit level below 45%, and therapy with dual antiplatelet medication and Hydroxyurea. Long term hydroxyurea can also reduce the risk of PV transformation to post fibrotic myelofibrosis and acute myeloid leukemia.
Patients after a thrombotic episode with PV would be on both Aspirin and Hydroxyurea. The benefit of hydroxyurea is not only as a cytoreductive but has shown reduce risk of repeat thrombosis when given with aspirin alone. Willoughby et al. [7] reported that prophylactic aspirin use in patients with PV reduced the occurrence of major vascular events by 22% and nonfatal myocardial infarction by 30%. However, it has also shown that MI patients with PV exhibit recurrent stent thrombosis, despite appropriate anti-platelet therapy due to underlying hyper-viscosity [15]. This study further revealed addition of GPIIb/IIIa receptor blockers like Abciximab reduced the risk of acute and sub-acute thrombosis, but led to increased risk of bleeding. Hence, this treatment should be considered on case to case basis to reduce the risk of adverse events.
Friedrich et al. [16] have reported a rare case of splenic rupture following the use of GPIIb/IIIa antagonist for MI patients with PV. It has becomes imperative to use best possible anti-platelet agents to prevent post-PTCA stent thrombosis. Long term use of anticoagulation with vitamin-k antagonists or newer oral anticoagulants often lead to increased risk of major bleeding, especially in elderly population. Hence, current evidence supports using high potency anti-platelet medication (e.g. ticagrelol or prasugrel), aggressive therapeutic phlebotomy and cytoreductive therapy using hydroxyurea [17] or anagrelide [1] post PTCA [18]. Some of the studies dealing the association between ACS and PV are summarized (Table 1).

CONCLUSION
Our case illustrates the importance of recognizing PV as an important cause of coronary thrombosis and MI so as to initiate appropriate treatment strategies. It is also important to consider adequate use of myelosuppressive agents such as hydroxyurea or ruxolitinib in high risk patients to prevent future thrombotic events. The search for laboratory markers to detect functional defects in platelets or leukocytes to predict thrombotic events is awaited. New strategies for the management in MI patients with PV undoubtedly have become high priority research in future.