scholarly journals IS ACROMEGALY A HYPERCOAGULABLE CONDITION? CASE REPORTS AND REVIEW OF THE LITERATURE

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Khalid Al Dahmani ◽  
Churn-Ern Yip ◽  
David Anderson ◽  
Karen Burch ◽  
David B Clarke ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Medical Therapy ◽  
Case Reports ◽  
Factor V Leiden ◽  
Acute Chest Pain ◽  
Protein S ◽  
Cardiovascular Complications ◽  
Factor V ◽  
Axillary Vein ◽  
Increased Risk

Introduction: Cardiovascular complications are a major cause of morbidity and mortality in patients with uncontrolled acromegaly. However, there are no published reports of an increased risk of venous thromboembolism (VTE) in such patients. We report three patients with uncontrolled acromegaly who presented with VTE. Clinical Cases: A 52-year-old male with uncontrolled acromegaly despite transsphenoidal (TSP) surgery and medical therapy presented in 2012 with acute chest pain and shortness of breath that was later con rmed as secondary to pulmonary embolism. A 44-year-old male immigrant, previously treated for acromegaly with radiation therapy alone, in 1992, in his native country, was referred to our centre in 2006 for acromegaly which remained uncontrolled despite medical therapy until 2009 when he achieved remission through TSP surgery. He had several episodes of VTE between 2008 and 2010. A 69-year-old male with uncontrolled acromegaly for 28 years despite two surgical resections and radiation therapy in 1986 and 1992, as well as continuous medical therapy, presented with VTE of the right axillary vein and bilateral pulmonary emboli in 2011. A thrombophilia screen in case 1 showed mild protein S de ciency, case 2 was homozygous for factor V Leiden (FVL) mutation and case 3 was heterozygous for FVL. Extensive investigations revealed no evidence of malignancy and echocardiography showed preserved ejection fraction in all three patients. Conclusion: Patients with uncontrolled acromegaly may be at increased risk of VTE. However, larger studies are required to further assess this association and determine the underlying cause. Key words: Acromegaly, pituitary tumours, thromboembolism 

Co-inheritance of the 20210A Allele of the Prothrombin Gene Increases the Risk of Thrombosis in Subjects with Familial Thrombophilia

1997 ◽  
Vol 78 (06) ◽  
pp. 1426-1429 ◽  
Author(s):  
M Makris ◽  
F E Preston ◽  
N J Beauchamp ◽  
P C Cooper ◽  
M E Daly ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Protein C Deficiency ◽  
Antithrombin Deficiency ◽  
Control Subjects ◽  
Increased Risk ◽  
Venous Thromboembolic

SummaryThe presence of the 20210A allele of the prothrombin (PT) gene has recently been shown to be a risk factor for venous thromboembolism. This is probably mediated through increased plasma prothrombin levels. The aim of this study was to compare the prevalence of the prothrombin 20210A allele in control subjects and in subjects with recognised thrombophilia and to establish whether the additional inheritance of the PT 20210A allele is associated with an increased risk of venous thromboembolism. 101 subjects with a history of venous thromboembolism and diagnosed as having either factor V Leiden (R506Q) or heritable deficiencies of protein C, protein S or antithrombin were studied. The prevalence of the PT 20210A allele in this group was compared with the results obtained for 150 control subjects. In addition, the relationships were examined between genetic status and the number of documented thromboembolic episodes, and between plasma prothrombin levels and possession of the PT 20210A allele. 8 (7.9%) of the 101 patients were also heterozygous for the PT 20210A allele. This compares with 0.7% in the control subjects (p = 0.005). After exclusion of patients on warfarin, the mean plasma prothrombin of 113 subjects without 20210A was 1.09 U/ml, as compared with 1.32 U/ml in 8 with the allele (p = 0.0002). Among the 101 patients with either factor V Leiden, protein S deficiency, protein C deficiency or antithrombin deficiency, the age adjusted mean (SD) number of venous thromboembolic episodes at diagnosis was 3.7 (1.5) in those with the PT 20210A allele, as compared with 1.9 (1.1) in those without (p = 0.0001). We have demonstrated that the prevalence of the PT 20210A allele is significantly greater in subjects with venous thrombosis and characterised heritable thrombophilia than in normal control subjects and that the additional inheritance of PT 20210A is associated with an increased risk of venous thromboembolism. We have also confirmed that plasma prothrombin levels are significantly greater in subjects possessing the PT 20210A compared with those who do not.

Coinheritance of the HR2 Haplotype in the Factor V Gene Confers an Increased Risk of Venous Thromboembolism to Carriers of Factor V R506Q (Factor V Leiden)

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3062-3066 ◽  
Author(s):  
E.M. Faioni ◽  
F. Franchi ◽  
P. Bucciarelli ◽  
M. Margaglione ◽  
V. De Stefano ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Family Members ◽  
Factor V Leiden ◽  
Protein S ◽  
Fold Increase ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Multicenter Cohort Study ◽  
Vein Thrombosis ◽  
Increased Risk

With the aim of establishing whether the HR2 haplotype in factor V affects the risk of venous thromboembolism, a retrospective multicenter cohort study was performed in 810 family members identified through 174 probands who suffered from at least 1 episode of deep vein thrombosis and/or pulmonary embolism and had an inherited defect associated with thrombophilia (antithrombin, protein C, or protein S deficiency; factor V R506Q or prothrombin G20210A). Fifty-eight percent (468/810) of the family members had an inherited defect and 10% (47/468) were symptomatic. The HR2 haplotype was found in association with factor V R506Q more frequently in family members with venous thromboembolism (18%) than in those without (8%). Double heterozygosity for factor V R506Q and HR2 conferred a 3- to 4-fold increase in the relative risk of venous thromboembolism compared with factor V R506Q alone. The median age at first event was lower when the 2 defects were associated (46v 52 years). No increase in risk of venous thromboembolism could be demonstrated when the HR2 haplotype was associated with inherited thrombophilic defects other than factor V R506Q. Because both factor V R506Q and the HR2 haplotype are very frequent, the effect of their coinheritance on the risk of venous thromboembolism might represent a clinically relevant issue, and screening for HR2 in carriers of factor V R506Q should be considered.

Danger of false negative (exclusion) or false positive (diagnosis) for ‘congenital thrombophilia’ in the age of anticoagulants

2019 ◽  
Vol 57 (6) ◽  
pp. 873-882 ◽  
Author(s):  
Emmanuel J. Favaloro
Keyword(s):  
False Positive ◽  
Ex Vivo ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
False Negative ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Increased Risk

Abstract Background Most guidelines and experts recommend against performance of thrombophilia testing in general, and specifically against testing patients on pharmacological anticoagulants, due to substantially increased risk of false positive identification. For example, vitamin K antagonist (VKA) therapy affects protein C (PC) and protein S (PS), as well as some clotting assays (e.g. as used to investigate activated PC resistance [APCR]). Although heparin may also affect clotting assays, most commercial methods contain neutralisers to make them ‘insensitive’ to therapeutic levels. Direct oral anticoagulants (DOACs) also affect a wide variety of thrombophilia assays, although most reported data has employed artificial in vitro spiked samples. Methods In the current report, data from our facility for the past 2.5 years has been assessed for all ‘congenital thrombophilia’ related tests, as evaluated against patient anticoagulant status. We processed 10,571 ‘thrombophilia’ related test requests, including antithrombin (AT; n=3470), PC (n=3569), PS (n=3585), APCR (n=2359), factor V Leiden (FVL; n=2659), and prothrombin gene mutation (PGM; n=2103). Results As expected, VKA therapy affected PC and PS, and despite manufacturer claims, also APCR. Most assays, as suggested by manufacturers, were largely resistant to heparin therapy. DOACs’ use was associated with falsely low APCR ratios (i.e. FVL-like effect) and somewhat unexpectedly, anti-Xa agents apixaban and rivaroxaban were also associated with lower AT and higher PS values. Conclusions It is concluded that ex-vivo data appears to confirm the potential for both false positive and false negative ‘thrombophilia’ events in patients on anticoagulant (including DOAC) treatment.

scholarly journals Review of Management and Outcomes in Women with Thrombophilia Risk during Pregnancy at a Single Institution

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Alhossain A. Khalafallah ◽  
Abdul-Rauf O. Ibraheem ◽  
Qiong Yue Teo ◽  
Abdul-Majeed AlBarzan ◽  
Ramanathan Parameswaran ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Anticoagulation Therapy ◽  
Factor V Leiden ◽  
Protein S ◽  
Obstetric Complications ◽  
Obstetric Outcomes ◽  
Control Group ◽  
Factor V ◽  
Protein C Deficiency ◽  
Increased Risk

Pregnancy is a hypercoagulable state associated with an increased risk of venous thromboembolic disease (VTE). We retrospectively studied 38 Caucasian pregnant women with thrombophilia risk and compared their obstetric outcomes with a matched cohort without known thrombophilia risk during the period between January 2007 and December 2010. There were (2) cases with factor V Leiden, (6) prothrombin gene mutation, (1) antithrombin III deficiency, (2) protein C deficiency, (3) protein S deficiency, (10) MTHFR mutation, (7) anti-cardiolipin antibodies, and (1) lupus anticoagulant. Patients without thrombophilia who presented with recurrent unprovoked VTE were considered as high risk (6 cases). Most patients received anticoagulation (34/38) with aspirin only (6), enoxaparin (27), and warfarin (1). Twenty-six out of thirty-eight pregnant women (68.4%) with an increased risk of thrombophilia experienced one or more obstetric complications defined as hypertension, preeclampsia, placenta abruptio, VTE, and oligohydramnios, compared with 15 out of 40 (37.5%) pregnant women in the control group (OR 3.6; 95% CI 1.42, 9.21, P<0.001). The incidence of obstetric complications was significantly higher in the thrombophilia group compared to the controls. However, these complications were the lowest among patients who received full-dose anticoagulation. Our study suggests that strict application of anticoagulation therapy for thrombophilia of pregnancy is associated with an improved pregnancy outcome. The study was registered in the Australian and New Zealand Clinical Trials Registry under ACTRN12612001094864.

Inherited Thrombophilia and First Venous Thromboembolism during Pregnancy and Puerperium

2002 ◽  
Vol 87 (05) ◽  
pp. 791-795 ◽  
Author(s):  
Valerio De Stefano ◽  
Emanuela Taioli ◽  
Katia Paciaroni ◽  
Elena Rossi ◽  
Mannucci Pier ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Protein S ◽  
First Episode ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Prothrombin Mutation ◽  
Heterozygous Carriers

SummaryVenous thromboembolism is a rare but threatening complication of pregnancy. Little conclusive information is available on the actual risk of venous thromboembolism during pregnancy or puerperium in women with inherited thrombophilia, particularly in carriers of factor V Leiden and of the G20210A prothrombin gene mutation. To determine the pregnancy-related and puerperium-related risk of venous thromboembolism in women with inherited thrombophilia, we performed a case-control study on 119 women who had a first episode of deep vein thrombosis and/or pulmonary embolism during pregnancy or puerperium and 232 healthy women who had at least one pregnancy without thrombosis. Inherited thrombophilia was diagnosed in 47 patients (39.5%) and 15 controls (6.5%). The relative risk of venous thromboembolism was 10.6 (95% CI, 5.6-20.4) for heterozygous carriers of factor V Leiden, 2.9 (95% CI, 1.0-8.6) for heterozygous carriers of the prothrombin mutation and 13.1 (95% CI, 5.0-34.2) for those with antithrombin, protein C or protein S deficiency taken together. Sixty-eight of the 119 women (57%) had thrombosis after delivery, confirming the puerperium as a particularly high-risk period. When women were divided into two groups of those with antenatal or postnatal thrombosis, the relative risks associated with each type of inherited thrombophilia were of similar magnitude. In conclusion, women with inherited thrombophilia have an increased risk of venous thromboembolism during pregnancy. Among thrombophilic abnormalities, the prothrombin mutation was the weakest risk factor. Thrombosis occurred more frequently in puerperium than in pregnancy, whether or not thrombophilia was diagnosed.

Risk Factors in Venous Thromboembolism

2001 ◽  
Vol 86 (07) ◽  
pp. 395-403 ◽  
Author(s):  
Ida Martinelli
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Nucleotide Substitutions ◽  
Inherited Thrombophilia ◽  
G20210a Mutation ◽  
Increased Risk

SummaryVenous thromboembolism is a serious disorder because of its potential complications, such as pulmonary embolism and the post-thrombotic syndrome. Inherited determinants of venous thromboembolism are only in part known, but in the past decades considerable progress has been made in the understanding of risk factors for the disease and their clinical impact. In particular, the development of molecular biology techniques and the increasing interest in their application, allowed an identification of two causes of inherited thrombophilia, i.e., factor V Leiden and the prothrombin G20210A mutation. Their recent discovery provided a new approach for improving the knowledge of inherited thrombophilia. In contrast to deficiencies of the naturally occurring anticoagulant proteins antithrombin, protein C and protein S, these two mutations cannot be considered true genetic defects, since they are nucleotide substitutions resulting in a more efficient coagulation process. Since they are rather common in the general populations of Caucasian descent and are associated with a moderate increased risk of venous thromboembolism, the effect of the interaction between inherited and environmental risk factors for venous thromboembolism has become an even greater field of interest. Prevention of first events and recurrences of venous thromboembolism can be optimized only through a knowledge of the main risk factors, their effect, and their interaction with environmental factors.

Distribution of Hypercoagulation Laboratory Diagnoses among Patients with History of Thromboembolic Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3952-3952
Author(s):  
Murray M. Bern ◽  
Nancy McCarthy ◽  
Jamie Bonner
Keyword(s):  
Protein C ◽  
Elective Surgery ◽  
Factor V Leiden ◽  
Protein S ◽  
Thromboembolic Disease ◽  
Factor V ◽  
Plasminogen Activator Inhibitor 1 ◽  
Total N ◽  
Increased Risk ◽  
Pai 1

Abstract This abstract demonstrates the distribution of hypercoagulation diagnosis among patients with histories of thromboembolic disease (TED) among a group of patients detected at surgery prescreening clinic or through other referral sources. The consulting hematologists determined which laboratory tests were ordered; thus not all patients had all tests. This abstract describes the results of those clinical consultations. For this study the hospital’s computer logs were probed for patients having had measurements of protein C and factor V Leiden from 11/7/01until 8/1/07. The laboratory records of identified patients were searched for additional hypercoagulation laboratory parameters. A total of 383 patients have been identified, among whom abnormal diagnostic results were found for 231. Genomic assays were performed often for the commonly found defects (i.e., factor V Leiden and prothrombin 20210) and selectively for other situations, such 4G/5G for patients with elevated plasminogen activator inhibitor 1 (PAI-1) and unresolved venous thrombus, or methylene tetrahydrofolate (MTH) reductace for unexplained elevation of homocysteine. The table demonstrate the distribution of these laboratory diagnoses. The risk of having TED associated with these results will be stratified to emphasize the increased risk associated with the more severe abnormalities of protein C, protein S, ATIII, PAI-1, and homocysteine. These results demonstrate that laboratory explanations for TED may be found in a large proportion of patients with TED, which thereafter can be used to design prophylactic programs for at risk patients upon entry to hospital, especially elective surgery. Hypercoagulation Parameters Patients Protein C* (&lt;60%) Protein S* (&lt;60%) AT III (&lt;80%) Homocysteine (&gt;12 um/L) Lupus anticoagulant Anti-phospholipid syndrome** * excludes patients taking warfarin; includes functional and antigen assays. ** combines anticardiolipin; anti-beta2, glycoprotein1; and anti-phosphotidyl -serine, -ethanolamine and -choline antibodies. total n 350 358 244 252 166 234 abnormal n (%) 7(2) 64(18) 29 (12) 89(35) 18 (11) 41 (18) PAI-1 (&gt;42) ng/ml) APC Resistance (&lt;2.1) VIII:c & VIII:vW (&gt;180%) Factor V Leiden Prothrombin 20210 MTH Folate Reductace 4G/5G 36 75 61 225 219 10 9 22 (61) 10 (13) 11 (18) 37 (16) 16 (7) 8 (80) 8 (90)

scholarly journals Prophylactic Anticoagulation With Intermediate-Dose Certoparin in Vascular-Risk Pregnancies—The PACER-VARP Registry

2021 ◽  
Vol 27 ◽  
pp. 107602962110165
Author(s):  
Martin Grünewald ◽  
Esther Häge ◽  
Stephanie Lehnert ◽  
Christiane Maier ◽  
Alexandra Schimke ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Vascular Risk ◽  
Vascular Events ◽  
Factor V Leiden Mutation ◽  
Increased Risk ◽  
Prophylactic Anticoagulation ◽  
Intermediate Dose

The management of pregnant women at increased risk of thromboembolic/other vascular events is still a matter of debate. In a single-center, retrospective, observational trial, we analyzed the safety and efficacy of prophylactic anticoagulation with certoparin in pregnant women at intermediate- or high-risk by EThIG criteria of thromboembolic/other vascular events. Subcutaneous certoparin 8,000 IU once daily was administered immediately after pregnancy confirmation and continued for 6 weeks postpartum. We investigated 74 pregnancies (49 women; mean age 31.8 years; weight 77.3 kg). Most prevalent risk factors were factor V Leiden mutation (40.5%), thrombogenic factor II mutation (12.2%) and protein S deficiency (8.1%). In 76 control pregnancies prior to registry inclusion/without anticoagulation there were 14 cases [18.4%] of venous thromboembolism (between week 7 gestation and week 8 postpartum); 63.2% pregnancies resulted in abortion (median week 8.6 gestation). With certoparin anticoagulation, thromboembolism was 1.4%, exclusively non-major bleeding was 4.1% and abortion was 10.8%. One case of pre-eclampsia necessitating obstetric intervention occurred. Prophylactic anticoagulation with intermediate-dose certoparin throughout pregnancies at increased venous vascular risk was safe and effective.

Coinheritance of the HR2 Haplotype in the Factor V Gene Confers an Increased Risk of Venous Thromboembolism to Carriers of Factor V R506Q (Factor V Leiden)

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3062-3066 ◽  
Author(s):  
E.M. Faioni ◽  
F. Franchi ◽  
P. Bucciarelli ◽  
M. Margaglione ◽  
V. De Stefano ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Family Members ◽  
Factor V Leiden ◽  
Protein S ◽  
Fold Increase ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Multicenter Cohort Study ◽  
Vein Thrombosis ◽  
Increased Risk

Abstract With the aim of establishing whether the HR2 haplotype in factor V affects the risk of venous thromboembolism, a retrospective multicenter cohort study was performed in 810 family members identified through 174 probands who suffered from at least 1 episode of deep vein thrombosis and/or pulmonary embolism and had an inherited defect associated with thrombophilia (antithrombin, protein C, or protein S deficiency; factor V R506Q or prothrombin G20210A). Fifty-eight percent (468/810) of the family members had an inherited defect and 10% (47/468) were symptomatic. The HR2 haplotype was found in association with factor V R506Q more frequently in family members with venous thromboembolism (18%) than in those without (8%). Double heterozygosity for factor V R506Q and HR2 conferred a 3- to 4-fold increase in the relative risk of venous thromboembolism compared with factor V R506Q alone. The median age at first event was lower when the 2 defects were associated (46v 52 years). No increase in risk of venous thromboembolism could be demonstrated when the HR2 haplotype was associated with inherited thrombophilic defects other than factor V R506Q. Because both factor V R506Q and the HR2 haplotype are very frequent, the effect of their coinheritance on the risk of venous thromboembolism might represent a clinically relevant issue, and screening for HR2 in carriers of factor V R506Q should be considered.

Activated Protein C Resistance, the Factor V Leiden Mutation, and a Laboratory Testing Algorithm

2002 ◽  
Vol 126 (5) ◽  
pp. 577-582 ◽  
Author(s):  
Elizabeth M. Van Cott ◽  
Britt L. Soderberg ◽  
Michael Laposata
Keyword(s):  
Laboratory Testing ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Increased Risk ◽  
Testing Algorithm

Abstract Objectives.—To present the current understanding of factor V Leiden and activated protein C resistance, and to propose a laboratory testing algorithm. Data Sources.—Publications on MEDLINE with the terms factor V Leiden or activated protein C resistance through mid 2001, as well as publications in the authors' files, were screened for inclusion in this report. Study Selection.—Original studies that report a novel finding on testing or clinical features of activated protein C resistance or factor V Leiden are included. Data Extraction.—The novel or key findings from the selected studies are analyzed. Data Synthesis.—Protein C and protein S are the integral components of an anticoagulation pathway that limits fibrinogen conversion to fibrin through the degradation of factors Va and VIIIa. When factor Va is resistant to degradation by activated protein C, this anticoagulation pathway does not operate properly, and patients have an increased risk for thrombosis. This report describes the protein C/protein S pathway, the significance of activated protein C resistance and the factor V Leiden mutation, and the clinical testing used to detect activated protein C resistance and the factor V Leiden mutation. A proposed laboratory testing algorithm is also provided. Conclusions.—Factor V Leiden is a risk factor for venous thrombosis and it is particularly common in white populations. A laboratory testing algorithm is proposed.

Sign in / Sign up

Export Citation Format

Share Document