Amaurosis Fugax Caused by Heritable Thrombophilia-Hypofibrinolysis in Cases Without Carotid Atherosclerosis

Glueck, Charles J.; Golnik, Karl C.; Wang, Ping

doi:10.1177/1076029606298735

Cited by 6 publications

(7 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our report, as well as earlier studies,16,27–29 has established thrombophilia as a common pathoetiologic cause of RVO. In this study, in agreement with previously published studies,27,34,47–51 we found significant enrichment in hyperhomocysteinemia in our 132 CVRO cases (15% versus 2% in controls; P = 0.0008).…”

Section: Discussionsupporting

confidence: 89%

“…Most studies associating estrogen–progestin oral contraceptives with CRVO or CRAO are case reports of only one to three cases 18,21–23. Most reports of CRVO or CRAO associated with estrogens or estrogen agonists8–14,18–21 have not assessed interactions between pharmacologic thrombophilia conferred by estrogens or estrogen agonists and the inherited and acquired thrombophilia15,16,24–35 known to be causally associated with RVO.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thrombophilia and retinal vascular occlusion

Glueck¹,

Hutchins²,

Jurantee³

et al. 2012

OPTH

View full text Add to dashboard Cite

PurposeThe purpose of this research was to assess associations of thrombophilia with central retinal vein occlusion (CRVO), central retinal artery occlusion (CRAO), and amaurosis fugax (AF); to evaluate outcomes of normalizing high homocysteine; and to study CRVO, CRAO, and AF developing in estrogens/estrogen agonists in women subsequently shown to have thrombophilia.MethodsMeasures of thrombophilia–hypofibrinolysis were obtained in 132 CRVO cases, 15 CRAO cases, and 17 AF cases. Cases were compared to 105 healthy control subjects who did not differ by race or sex and were free of any ophthalmologic disorders. All cardiovascular disease (CVD) risk factors were compared to healthy general populations.Main outcome measuresThe main outcome measure of this study was thrombophilia.ResultsCRVO cases were more likely than controls to have high homocysteine (odds ratio [OR] 8.64, 95% confidence intervals [CI]: 1.96–38), high anticardiolipin immunoglobulin M (IgM; OR 6.26, 95% CI: 1.4–28.2), and high Factor VIII (OR 2.47, 95% CI: 1.31–7.9). CRAO-AF cases were more likely than controls to have high homocysteine (OR 14, 95% CI: 2.7–71.6) or the lupus anticoagulant (OR 4.1, 95% CI: 1.3–13.2). In four of 77 women with CRVO (two found to have high homocysteine, two with inherited high Factor XI), CRVO occurred after starting estrogen–progestins, estrogen–testosterone, or estrogen agonists. In one of eight women with CRAO found to have high anticardiolipin antibody IgG, CRAO occurred after starting conjugated estrogens, and AF occurred after starting conjugated estrogens in one of eleven women with AF (inherited protein S deficiency). Therapy for medians of 21 months (CRVO) and 6 months (CRAO-AF) was 5 mg folic acid, 100 mg B6, and 2000 mcg/day B12 normalized homocysteine in 13 of 16 (81%) CRVO cases and all five CRAO-AF cases with pretreatment hyperhomocysteinemia. The CRVO cases had an excess of hypertension; CRAO-AF cases had an excess of type 2 diabetes and hypertension.ConclusionTreatable thrombophilia, hyperhomocysteinemia in particular, is more common in RVO cases than in normal controls. RVO occurs after estrogens or estrogen agonists were administered in women subsequently shown to have thrombophilia.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Thrombophilia and retinal vascular occlusion

Glueck¹,

Hutchins²,

Jurantee³

et al. 2012

OPTH

View full text Add to dashboard Cite

show abstract

“…21 Subsequently, in 19 patients with amaurosis fugax associated with heritable thrombophilia-hypofibrinolysis without ipsilateral atherosclerotic carotid plaque, we examined the hypothesis that case-specific thromboprophylaxis would prevent subsequent amaurosis fugax episodes. 24 We reported that within 1 month of starting thromboprophylaxis patients became asymptomatic and have remained asymptomatic for 1 or more years on therapy. 24 Our previous studies of 12 patients with NAION 17 revealed that patients with NAION were more likely than controls to demonstrate thrombophilic homozygosity for the C677T MTHFR mutation, 50% versus 11%, P = .0009.…”

Section: Original Articlesmentioning

confidence: 99%

Ocular Vascular Thrombotic Events: A Diagnostic Window to Familial Thrombophilia (Compound Factor V Leiden and Prothrombin Gene Heterozygosity) and Thrombosis

Glueck

Wang

2007

Clin Appl Thromb Hemost

Self Cite

View full text Add to dashboard Cite

In a 12-member, 3-generation kindred with conjoint inheritance of G1691A factor V Leiden (FVL) and G20210A prothrombin gene (PTG) mutations, identified through a proband with amaurosis fugax and his father with nonarteritic ischemic optic neuropathy (NAION), the authors' hypothesis was that ocular thrombosis was a diagnostic window to familial thrombophilia-thrombosis. The authors used polymerase chain reaction (PCR) measures for thrombophilia (FVL, PTG, C677T-A1298C methylenetetrahydrofolate reductase [MTHFR], platelet glycoprotein PLA1A2) and hypofibrinolysis (plasminogen activator inhibitor-1 4G4G). The 39-year-old white male proband, with amaurosis fugax and transient ischemic attacks (TIA), was found to be a compound heterozygote for FVL and PTG mutations. His symptoms resolved only after coumadin. His 44-year-old brother (deep venous thrombosis [DVT]) and 46-year-old sister (DVT, pulmonary embolus [PE]) were compound FVL-PTG gene heterozygotes. Of 4 asymptomatic children born to these 3 siblings, 2 were FVL heterozygotes and 2 PTG heterozygotes. The proband's 69-year-old father, with NAION and ischemic stroke, had PTG heterozygosity, familial high factor VIII, and compound MTHFR C677T-A1298C mutation with homocysteinemia. The proband's 61-year-old aunt had PTG heterozygosity, recurrent DVT, and mesenteric artery thrombosis. The proband's 67-year-old mother, free of thrombotic events, was a FVL heterozygote, had high factor VIII, and PAI-1 4G4G homozygosity. In this extended kindred, ocular thrombotic events (amaurosis fugax, NAION) were associated with variegated thrombotic events, including TIA, ischemic stroke, DVT, PE, and mesenteric artery thrombosis, and opened a diagnostic window to family screening and treatment for complex thrombophilias, which had previously been undiagnosed.

show abstract

“…The patient, a 70-year-old non-smoking Caucasian male, was referred to our center because of non-cardiogenic recurrent amaurosis fugax, and transient ischemic attacks (TIAs) and ischemic strokes in the presence of normal carotid and coronary artery imaging, and in the absence of atrial fibrillation. He was found to be heterozygous for the G20210A prothrombin gene mutation, which is known to be associated with retinal artery thrombotic occlusion, amaurosis fugax, [5,6] and ischemic stroke, [7,8] as well as, more commonly, venous thrombosis. [9][10][11][12][13] Due to increased frequency of amaurosis fugax episodes and ischemic stroke-TIAs, [14] he was initially anticoagulated with enoxaparin (1 mg/kg/twice per day), with a sharp reduction in the frequency of amaurosis fugax attacks, and non-recurrence of TIAs and ischemic strokes.…”

Section: Case Reportmentioning

confidence: 99%

Bilateral upper extremity severe ecchymosis in a patient on alirocumab, rivaroxaban, and clopidogrel therapy

Shah

Glueck

Jetty

2016

CRIM

View full text Add to dashboard Cite

The PCSK9 inhibitors, alirocumab and evolocumab, are a new class of powerful LDL cholesterol lowering agents which allow previously unattainable lowering of LDL cholesterol (LDLC). Once past the necessarily restrictive confines of placebo-controlled clinical trials, in current medical practice, some patients with concomitant thromboembolism and arterial disease may also be taking potent anticoagulants and/or anti-platelet agents in addition to PCSK9 inhibitors. There are currently no reports on drug interactions and no warnings when alirocumab or evolocumab are used in conjunction with anticoagulants and/or anti-platelet therapy. Here, we present a case of patient with exceptional LDLC lowering (LDLC < 4 mg/dl) on alirocumab 150 mg/ml every 2 weeks and concomitant anti-platelet (clopidogrel 75 mg/day) and anti-coagulation therapy (rivaroxaban 10 mg/day) because of recurrent non-cardiogenic amaurosis fugax, and transient ischemic attacks, and ischemic stroke associated with heterozygosity for the G20210A prothrombin gene mutation. On this regimen, the patient developed gradually spreading intensive skin ecchymosis and bleeding on both arms. This resolved after stopping alirocumab, clopidogrel, and rivaroxaban, and did not reappear when clopidogrel and rivaroxaban were restarted without alirocumab.

show abstract

Amaurosis Fugax Caused by Heritable Thrombophilia-Hypofibrinolysis in Cases Without Carotid Atherosclerosis

Cited by 6 publications

References 22 publications

Thrombophilia and retinal vascular occlusion

Thrombophilia and retinal vascular occlusion

Ocular Vascular Thrombotic Events: A Diagnostic Window to Familial Thrombophilia (Compound Factor V Leiden and Prothrombin Gene Heterozygosity) and Thrombosis

Bilateral upper extremity severe ecchymosis in a patient on alirocumab, rivaroxaban, and clopidogrel therapy

Contact Info

Product

Resources

About