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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 9  |  Issue : 2  |  Page : 116-119

An interesting case of hyperhomocysteinemia presenting as acute myocardial infarction and cerebral venous thrombosis


Department of Medicine, MVJ Medical College and Research Hospital, Hoskote, Karnataka, India

Date of Submission14-Jan-2020
Date of Decision14-Jan-2020
Date of Acceptance07-Mar-2020
Date of Web Publication21-Apr-2021

Correspondence Address:
Dr. Shreyashi Ganguly
309, Sai Charita Green Oaks, Horamavu Main Road, Bengaluru - 560 043, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJIM.AJIM_1_20

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  Abstract 


When a young patient presents with ischemic stroke or recurrent venous thromboembolism of unknown aetiology or “young” myocardial infarction in the absence of traditional risk factors, a detailed thrombophilia workup becomes an imperative. In a setting of arterial and venous occlusive disorders hyperhomocysteinemia is an important risk factor in the absence of traditional contributory aetiologies. Here we present a case of 28-year-old man, never-smoker with no known comorbidities who initially presented to the hospital with acute, retrosternal chest pain, radiating to the left side. His ECG showed ST elevation in V1-V3 in the setting of raised cardiac enzymes, and 2d-echo demonstrating regional wall motion abnormality. He was diagnosed to have acute anteroseptal MI and thrombolysed with streptokinase. Subsequently, his coronary angiogram showed a non-occluded LAD. CT Angio with IVUS done at a staged interval revealed minimal luminal irregularities suggestive of MINOCA. 8 months later the patient presented with headeache, fever, and left focal seizure accompanied by signs of increased intracranial pressure. MRI brain with contrast-MR venogram showed complete thrombosis of superior sagittal sinus. Due to the previous history of MI, and present CVT the patient was subjected to detailed thrombophilic evaluation which was normal except the levels of vitamin B12 (126.9 pg/mL) was low his homocysteine level was abnormally elevated to a level of 38.23 μM/L. The patient was treated with heparin, anti-oedema measures and anti-epileptics followed by oral anticoagulant plus folate, vitamin B6, and vitamin B12. Young patients presenting with arterial or venous thrombosis without any risk factors for atherosclerosis and venous thrombosis which is recurrent, unexplained, or at unusual sites, need screening for thrombophilic states and hyperhomocysteinemia should be ruled out as it can lead to both arterial and venous disease.

Keywords: Cerebral vein thrombosis, hyperhomocysteinemia, myocardial infarction with nonocclusive coronary arteries, thrombophilia, Vitamin B12 deficiency


How to cite this article:
Avinash B L, Kamath V, Ganguly S. An interesting case of hyperhomocysteinemia presenting as acute myocardial infarction and cerebral venous thrombosis. APIK J Int Med 2021;9:116-9

How to cite this URL:
Avinash B L, Kamath V, Ganguly S. An interesting case of hyperhomocysteinemia presenting as acute myocardial infarction and cerebral venous thrombosis. APIK J Int Med [serial online] 2021 [cited 2021 Jun 12];9:116-9. Available from: https://www.ajim.in/text.asp?2021/9/2/116/314191




  Introduction Top


Stroke in young, recurrent cerebral vein thrombosis (CVT), and/or “young” myocardial infarction (MI) are all concepts that prompt a clinician to approach a case presenting as such with caution lest the easy comfort of a standard workup lull us in to disregarding the causes that are not initially obvious. However, going on a wild goose chase with a plethora of laboratory diagnostics leads to financial burden for a patient and often confounds more than elucidates. Here, we present an interesting case of a young man initially diagnosed with acute MI and subsequently CVT. Through the judicious use of imaging and diagnostic laboratory workup, he was found to have an elevated serum homocysteine (HCY) level associated with Vitamin B12 deficiency which left untreated can lead to these complications.


  Case Report Top


A 28-year-old man, never smoker, nonalcoholic, with no known comorbidities, presented to the hospital with the complaints of left-sided chest pain for 1 h. It was retrosternal, crushing type, radiating to the left upper limb, and it was associated with dyspnea and sweating. On examination, he was anxious and sweating. His vitals were stable.

Electrocardiogram (ECG) done showed ST segment elevation in V1–V3 leads, suggestive of anteroseptal MI [Figure 1]. Cardiac enzymes were checked and were found to be highly elevated (troponin I: 0.54 ng/ml [0–0.04 ng/ml], serum creatinine phosphokinase [CPK]: 434 IU/L [25–200 IU/L], and CPK-MB: 39 IU/L [0–25 IU/L]), suggesting an acute ischemic attack.
Figure 1: Electrocardiogram showing ST elevation in V1–V3

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Laboratory tests performed on admission revealed a hemoglobin level of 14.1 g/dL, normal (red blood cell [RBC]) indices, and normal RBC morphology. Liver function tests were normal. Lipid profile revealed serum cholesterol of 197 mg/dL, serum low-density lipoprotein-cholesterol of 151 mg/dL, and high-density lipoprotein of 17 mg/dL. Two-dimensional echo shows left ventricular (LV) segmental akinesia. Reduced LV function (ejection fraction 44%), trivial tricuspid regurgitation. No obvious clot.

Treatment was initiated with injection streptokinase 1.5 million IU. He improved clinically, and his subsequent ECG showed resolution of the ST segment elevation postthrombolysis [Figure 2]. Subsequently, the patient was put on tablet aspirin 150 mg once daily, tablet clopidogrel 75 mg once daily, tablet atorvastatin 20 mg once daily at night, tablet sorbitrate 5 mg sublingual sos. He was also started on low-molecular-weight heparin (injection enoxaparin 60 mg/0.6 mL) to improve the coronary artery blood flow. Coronary angiogram was done, and it showed a nonoccluded left anterior descending [Figure 3].
Figure 2: Postthrombolysis electrocardiogram showing normalization of ST elevation in V1–V3

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Figure 3: Coronary angiography showing nonoccluded left anterior descending. Computed tomography angiogram with intravascular ultrasound done at a staged interval revealed minimal luminal irregularities, suggestive of myocardial infarction with nonocclusive coronary arteries

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Eight months later, the patient presented with a history of headache, fever, and focal seizure of the left lower limb along with the signs of increased intracranial pressure for 2 days. On examination, he had papilledema but no signs of meningeal irritation. Rest of the central nervous system examination was normal. There were no signs of deep venous thrombosis.

Computed tomography of the brain done was normal. Magnetic resonance imaging of the brain with contrast-magnetic resonance venogram showed complete thrombosis of superior sagittal sinus [Figure 4].
Figure 4: Magnetic resonance imaging brain and magnetic resonance venogram showing superior sagittal thrombosis

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Due to the previous history of MI, and present CVT, the patient was subjected to detailed thrombophilic evaluation. There were no laboratory signs of inflammation (white blood cell: 5390/mm3, erythrocyte sedimentation rate: 12 mm/h, and C-reactive protein: within normal limits) and no anemia/polycythemia (Hgb: 14.5 g/dL). Immunological tests, including those for lupus anticoagulant and anticardiolipin antibodies, were negative.

General studies of the coagulation profiles disclosed no abnormalities: fibrinogen - 254.5 mg/dL (N: 200–400 mg/dL); fibrin degradation products - <10 μg/mL (N: <10 μg/mL); antithrombin-III - 85.8% (N: 80%–120%); D-dimer - 93 ng/dL (N: <500 ng/dL); protein C - 84%; and protein S - 264%. The levels of Vitamin B12 (126.9 pg/mL, N: 200–500 pg/mL) were low and folate (4.26 ng/mL, N: 3–17.0 ng/mL) were normal. However, total plasma HCY was abnormally elevated to a level of 38.23 μmol/L (4 and 15 μmol/L).

The patient was treated with heparin, antiedema measures, and antiepileptics followed by oral anticoagulant plus folate, Vitamin B6, and Vitamin B12.


  Discussion Top


When a young patient presents with ischemic stroke or recurrent venous thromboembolism of unknown etiology or “young” MI in the absence of traditional risk factors, a detailed thrombophilia workup becomes imperative.[1]

For investigation of patients suffering from thrombotic events, it is essential to differentiate provoked and unprovoked thrombosis through history and physical examination. Thrombotic events are observable under diverse conditions. Therefore, a broad differential diagnosis is essential including more frequent (immobilization and travel) and less frequent entities such as cardiac disease (atrial fibrillation, cardiomyopathy, mitral valve prolapse, and prosthetic valves), nonbacterial thrombotic endocarditis, and hematologic causes such as disseminated intravascular coagulopathy and heparin-induced thrombocytopenia.

Thrombophilia should be a differential diagnosis for vaso-occlusive events. Arterial thrombosis, such as osteonecrosis, ischemic stroke, and MI, can be related to thrombophilia. Celik et al. investigated a population of young patients suffering from MI. They concluded that the established cardiovascular risk factors but not thrombophilias contributed to MI in young patients.[2] Other studies suggest to include thrombophilia in the differential diagnosis of MI with nonocclusive coronary arteries (MINOCA).[3] Thrombophilias might also be associated with stroke in young people by venous thromboembolism through a patent foramen ovale.

Our patient satisfied the diagnostic definition of MINOCA and unprovoked CVT; therefore, thrombophilia workup for him became essential – showing hyperhomocysteinemia in the setting of Vitamin B12 deficiency.

HCY is a metabolic intermediary derived from the essential sulfur-containing amino acid, methionine. Hyperhomocysteinemia is defined as a medical condition characterized by an abnormally high level (>15 μmol/L) of HCY in the blood. It is classified as moderate (16–30 μmol/L), intermediate (31–100 μmol/L), and severe (>100 μmol/L) hyperhomocysteinemia.[4] Elevated plasma HCY levels can be caused by several factors, both acquired and hereditary. Acquired hyperhomocysteinemia can be caused by Vitamin B6, Vitamin B12, or folate deficiency; renal failure; hypothyroidism; rheumatoid arthritis; and certain drugs, such as methotrexate, niacin, anticonvulsant, theophylline, levodopa, thiazide, cyclosporin A, or phenytoin.[5]

Hereditary hyperhomocysteinemia is caused by polymorphisms in the MTHFR gene. The gene product is an enzyme necessary in HCY conversion pathways. Homozygous alterations of the MTHFR gene are present in 10%–13% of the population, whereas heterozygous alterations are found in 30%–40%.[1] Mild elevation in the HCY level is associated with the low levels of Vitamin B12 and enhances the formation of atherosclerotic plaque.[6]

Vitamin B12, folate, and Vitamin B6 are needed in the HCY remethylation pathway and transsulfuration pathway; they are called HCY-lowering vitamins. In patients with hyperhomocysteinemia, folic acid alone was shown to reduce HCY levels by 22% and Vitamin B12 by 11%. However, when both are administered together, they act synergistically and reduce the HCY levels by 38.5%.[6]

It is to be noted that, although vitamin supplementation can lead to marked decline in the levels of HCY, it does not translate into a clinical reduction in vascular events. The use of Vitamin B12 or folate as a therapeutic strategy in preventing future vascular events has still not been proven in randomized controlled trials.

Compared to diet, the effect of genetic factors in raising the HCY level seems to be modest. This has been shown in multiple studies done in the Asian-Indian population living in the Indian subcontinent and comparing them to those living in more affluent areas abroad (practice of multivitamin supplementation is common in these people unlike the subcontinental cohorts).[7] Therefore, the presence of a dietary deficiency of one or more of the vitamins involved in the metabolism of HCY superimposed on a background of MTHFR polymorphism seems to be responsible for the very high incidence of hyperhomocysteinemia.[4]

Hyperhomocysteinemia may be associated with thrombotic processes through several mechanisms, including increased platelet aggregation, increased activity of factor V, prothrombin activation, inhibition of protein C activation, and decreased tissue plasminogen activator binding to endothelial cells.[8]

Hyperhomocysteinemia is an independent risk factor for occlusive arterial vascular disease and venous thromboembolism. HCY levels above the 90th percentile of normal confirs a risk for coronary artery disease of 1.7, for cerebrovascular disease 2.5, for peripheral vascular disease 6.8, and venous thrombosis 2.955.[9]


  Conclusion Top


Hyperhomocysteinemia can be genetic, acquired, or a combination of both. In the classical form of the disease, there is deficiency of the enzyme cystathionine beta-synthase, which converts HCY to cystathionine in a reaction that uses Vitamin B12, Vitamin B6, and folic acid.

Our patient presented with atherosclerosis of both arterial in the form of MI and venous in the form of CVT without any risk factors. On further evaluation, thrombophilia workup showed hyperhomocysteinemia and low vitamin B12. The rest of the workup was normal. Hence, hyperhomocysteinemia was thought to be the cause of both arterial and venous thrombosis.

Young patients presenting with arterial or venous thrombosis without any risk factors for atherosclerosis and venous thrombosis, which is recurrent, unexplained, or at unusual sites, need screening for thrombophilic states, and hyperhomocysteinemia should be ruled out as it can lead to both arterial and venous diseases.

Declaration of patient consent

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

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Eldibany MM, Caprini JA. Hyperhomocysteinemia and thrombosis: An overview. Arch Pathol Lab Med 2007;131:872-84.  Back to cited text no. 1
    
2.
Celik M, Altintas A, Celik Y, Karabulut A, Ayyildiz O. Thrombophilia in young patients with acute myocardial infarction. Saudi Med J 2008;29:48-54.  Back to cited text no. 2
    
3.
Angeline T, Aruna RM, Ramadevi K, Mohan G, Jeyaraj N. Homocysteine status and acute myocardial infarction among Tamilians. Indian J Clin Biochem 2005;20:18-20.  Back to cited text no. 3
    
4.
Yajnik CS, Deshpande SS, Lubree HG, Naik SS, Bhat DS, Uradey BS, et al. Vitamin B12 deficiency and hyperhomocysteinemia in rural and urban Indians. J Assoc Physicians India 2006;54:775-82.  Back to cited text no. 4
    
5.
Wierzbicki AS. Homocysteine and cardiovascular disease: A review of the evidence. Diab Vasc Dis Res 2007;4:143-50.  Back to cited text no. 5
    
6.
Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM. Effect of homocysteine-lowering therapy with folic acid, Vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: The Swiss Heart study: A randomized controlled trial. JAMA 2002;288:973-9.  Back to cited text no. 6
    
7.
Chandalia M, Abate N, Cabo-Chan AV Jr., Devaraj S, Jialal I, Grundy SM. Hyperhomocysteinemia in Asian Indians living in the United States. J Clin Endocrinol Metab 2003;88:1089-95.  Back to cited text no. 7
    
8.
Mukherjee M, Joshi S, Bagadi S, Dalvi M, Rao A, Shetty KR. A low prevalence of the C677T mutation in the methylenetetrahydrofolate reductase gene in Asian Indians. Clin Genet 2002;61:155-9.  Back to cited text no. 8
    
9.
Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995;274:1049-57.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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