High factor XI, recurrent pregnancy loss, enoxaparin

Glueck, Charles J.; Pranikoff, Joel; Khan, Naveed Ali; Riaz, Kashif; Chavan, K. M.; Raj, P Varun; Umar, Muhammad; Wang, Ping

doi:10.1016/j.fertnstert.2009.12.084

Cited by 7 publications

(5 citation statements)

References 76 publications

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“…High factor VIII was more common in the 11 men (36%) than in normal male controls (2%) (P ¼ 0.005), and more common than in T-controls (4%) (P ¼ 0.023). The factor V Leiden mutation [17] and high factors VIII [18][19][20] and XI [17,21] are recognized familial thrombophilias associated with thrombotic events. The increased incidence of high factor VIII levels and the factor V Leiden mutation in men who took T and sustained DVT-pulmonary embolism-osteonecrosis points to a thrombosis-enhancing effect of exogenous T when given to men with previously undiagnosed thrombophilia-hypofibrinolysis, as in this and our other studies [1][2][3][4].…”

Section: Discussionmentioning

confidence: 99%

Testosterone, thrombophilia, thrombosis

Glueck¹,

Friedman²,

Hafeez³

et al. 2014

Blood Coagulation &Amp; Fibrinolysis

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We assessed previously undiagnosed thrombophilia-hypofibrinolysis in 11 testosterone (T)-taking men, five of whom developed deep venous thrombosis (DVT), four pulmonary embolism, one spinal cord infarction, and one osteonecrosis 3.5 months (median) after starting T gel (50-160 mg/day) or T intramuscular (50-250 mg/week). In the order of referral because of thrombosis after starting T, thrombophilia-hypofibrinolysis was studied in 11 men, and, separately, in two control groups without thrombosis - 44 healthy normal male controls and 39 healthy men taking T. Nine men had DVT or DVT-pulmonary embolism after 3.5 months (median) on T, one spinal cord infarction after 5 days on T, and one had osteonecrosis (knee and then hip osteonecrosis after 6 and 18 months on T). Four of the 11 men (36%) had high factor VIII (≥150%) vs. one of 42 (2%) controls (P = 0.005), and vs. one of 25 (4%) T-controls, (P = 0.023). Of the 11 men, two (18%) had factor V Leiden heterozygosity vs. none of 44 controls, (P = 0.04) and vs. none of 39 T-controls(P = 0.045). Of the 11 men, three had 4G4G plasminogen activator inhibitor-1 homozygosity, one prothrombin G20210A heterozygosity, one low protein S, and one high factor XI. When T was continued, second DVT-pulmonary embolism recurred in three of 11 men despite adequate anticoagulation. T interacts with thrombophilia-hypofibrinolysis leading to thrombosis. Men sustaining DVT-pulmonary embolism-osteonecrosis on T should be studied for thrombophilia. Continuation of T in thrombophilic men appears to be contraindicated because of recurrent thrombosis despite adequate anticoagulation. Before starting T, to prevent T-associated thrombosis, we recommend measures of factor V Leiden, factor VIII, and the prothrombin gene.

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Section: Discussionmentioning

confidence: 99%

Testosterone, thrombophilia, thrombosis

Glueck¹,

Friedman²,

Hafeez³

et al. 2014

Blood Coagulation &Amp; Fibrinolysis

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“…factor V Leiden heterozygosity and high factor VIII in 21% of our cases were much more common than in healthy Cincinnati controls, 2% of whom were factor V Leiden heterozygotes, 11 4.5% of whom had high factor VIII. 9 Factor V Leiden heterozygosity, 22 high factors VIII 23 and XI, 24 the lupus anticoagulant, 25 and low antithrombin III 26 are all associated with increased risk of DVT and PE. 27–29 Osteonecrosis is associated with the factor V Leiden mutation, high factors VIII and XI, and with the hypofibrinolytic 4G4G mutation of the PAI-1 gene.…”

Section: Discussionmentioning

confidence: 99%

Testosterone, Thrombophilia, and Thrombosis

Glueck

Richardson-Royer

Schultz

et al. 2013

Clin Appl Thromb Hemost

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We describe thrombosis, deep venous thrombosis (DVT) pulmonary embolism (PE; n = 9) and hip-knee osteonecrosis (n = 5) that developed after testosterone therapy (median 11 months) in 14 previously healthy patients (13 men and 1 woman; 13 Caucasian and 1 African American), with no antecedent thrombosis and previously undiagnosed thrombophilia-hypofibrinolysis. Of the 14 patients, 3 were found to be factor V Leiden heterozygotes, 3 had high factor VIII, 3 had plasminogen activator inhibitor 1 4G4G homozygosity, 2 had high factor XI, 2 had high homocysteine, 1 had low antithrombin III, 1 had the lupus anticoagulant, 1 had high anticardiolipin antibody Immunoglobulin G, and 1 had no clotting abnormalities. In 4 men with thrombophilia, DVT-PE recurred when testosterone was continued despite therapeutic international normalized ratio on warfarin. In 60 men on testosterone, 20 (33%) had high estradiol (E2 >42.6 pg/mL). When exogenous testosterone is aromatized to E2, and E2-induced thrombophilia is superimposed on thrombophilia-hypofibrinolysis, thrombosis occurs. The DVT-PE and osteonecrosis after starting testosterone are associated with previously undiagnosed thrombophilia-hypofibrinolysis. Thrombophilia should be ruled out before administration of exogenous testosterone.

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“…Em relação ao pequeno número de pacientes deste estudo, embora reconhecida como limitação, estudos semelhantes nesta área, com amostragem semelhante 15,[30][31][32][33][34] também demonstraram que a implementação de tratamento com base em HPBM em gestantes melhora o prognóstico perinatal. O tratamento instituído pode ter levado a efeito direto na minimização da disfunção placentária nas gestantes estudadas, como é apresentado pela literatura 2 .…”

Section: Discussionunclassified

Eficácia de intervenção com enoxaparina baseada em sistema de pontuação nos desfechos perinatais de gestantes com trombofilias

Figueiró-Filho¹,

Oliveira²,

Breda³

et al. 2012

Rev. Bras. Ginecol. Obstet.

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ResumoOBJETIVO: Avaliar se a intervenção com heparina de baixo peso molecular (HBPM) -enoxaparina sódica -foi eficaz na melhora dos desfechos perinatais de mulheres com trombofillias com base em sistema de pontuação. MÉTODOS: Estudo prospectivo, não randomizado, não controlado, realizado em um Ambulatório de Gestação de Alto Risco, durante o período de novembro de 2009 a novembro de 2011. Foram incluídas gestantes com diagnóstico e intervenção terapêutica para trombofilias adquiridas e/ou hereditárias na gestação atual. Os dados obstétricos e perinatais das gestantes anteriores à intervenção foram comparados com os desfechos subsequentes à intervenção, sendo analisados estatisticamente através do teste do χ 2 , com correção de Yates, considerando significativos quando p<0,05. A dosagem inicial de HBPM foi norteada por sistema de pontuação, baseado no histórico clínico e gestacional das pacientes, além de exames de rastreamento de trombofilias adquiridas e/ou hereditárias. RESULTADOS: Foram incluídas 84 mulheres grávidas com 175 gestações anteriores ao diagnóstico, das quais 20,0% resultaram em morte fetal ou perinatal, 40,0% resultaram em abortamento, 17,7% desenvolveram pré-eclâmpsia ou eclâmpsia, 10,3% foram partos a termo e 29,7% partos pré-termo. Nas 84 gestações após a intervenção, 6,0% resultaram em morte fetal ou perinatal, 1,2% em abortamento, 4,8% desenvolveram pré-eclâmpsia/eclâmpsia, 22,6% em parto prematuro e 70,2% parto a termo. Observou-se redução significativa na taxa de óbito fetal ou perinatal (p<0,05) e abortos (p<0,0001), e aumento significativo (p<0,05) no número de nascidos vivos após a intervenção. CONCLUSÃO: A intervenção baseada na enoxaparina utilizando um sistema de pontuação em gestantes com trombofilia mostrou-se eficaz na melhora do desfecho perinatal. Abstract PURPOSES:To assess whether an enoxaparin-based intervention using a score system was effective in improving perinatal outcome in women with thrombophilia. METHODS: Study Design: Prospective, not randomized, uncontrolled, performed at a Clinic of High-Risk Pregnancy from November 2009 to November 2011. We included women with a diagnosis and therapeutic intervention for thrombophilia acquired and/or inherited in the current pregnancy. The obstetric and perinatal outcomes of pregnant women before the intervention were compared with outcomes after the intervention, and statistically analyzed using the χ 2 test with Yates correction, considered significant when p<0.05. The initial dose of low-molecular-weight Heparin (LMWH) was guided by a scoring system based on the clinical and gestational history of the patients and screening tests for acquired and/or inherited thrombophilia. RESULTS: We included 84 pregnant women with 175 pregnancies before diagnosis, 20.0% of which resulted in fetal ou perinatal death, 40.0% resulted in abortion, 17.7% developed preeclampsia/eclampsia, 10.3% resulted in full-term births, and 29.7% in premature births. In the 84 pregnancies after intervention, 6.0% resulted in fetal ou perinatal death, 1.2% in ...

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High factor XI, recurrent pregnancy loss, enoxaparin

Cited by 7 publications

References 76 publications

Testosterone, thrombophilia, thrombosis

Testosterone, thrombophilia, thrombosis

Testosterone, Thrombophilia, and Thrombosis

Eficácia de intervenção com enoxaparina baseada em sistema de pontuação nos desfechos perinatais de gestantes com trombofilias

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