scholarly journals Factor V Leiden Does Not Affect Bleeding in Aprotinin Recipients after Cardiopulmonary Bypass

2007 ◽  
Vol 106 (4) ◽  
pp. 681-686 ◽  
Author(s):  
Johannes Boehm ◽  
Joachim Burkhard Grammer ◽  
Fabian Lehnert ◽  
Wulf Dietrich ◽  
Stefan Wagenpfeil ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Blood Loss ◽  
Factor V Leiden ◽  
Postoperative Blood Loss ◽  
Factor V ◽  
Thromboembolic Complications ◽  
Antiplatelet Treatment ◽  
Factor V Leiden Mutation ◽  
Increased Risk

Background Carriers of the factor V Leiden mutation (FVL) are resistant to activated protein C proteolysis. Therefore, they are at increased risk of thromboembolic events. Aprotinin is an unspecific proteinase inhibitor frequently used during cardiac surgery procedures to reduce bleeding. However, aprotinin may cause thromboembolic complications after cardiopulmonary bypass (CPB). The primary endpoint of this study was the amount of blood loss after CPB in aprotinin recipients, and secondary endpoints were thromboembolic complications. Methods A total of 1,447 consecutive patients who underwent cardiac surgery with CPB were prospectively enrolled. All patients were screened for FVL by a fluorescence-based polymerase chain reaction method. Linear and logistic regression analyses were performed to assess associations of FVL on bleeding and thromboembolic complications. Results One hundred seven individuals (7.4%) were heterozygous FVL carriers. No difference was found between FVL carriers and noncarriers regarding age, sex, CPB, type of operation, EuroSCORE, antiplatelet treatment, and reoperation. FVL was not significantly associated with postoperative blood loss, whereas a significant influence was found for female sex (P < 0.0001), duration of CPB (P < 0.0001), reoperation (P = 0.001), and preoperative antiplatelet treatment (P < 0.002). Multiple linear regression analysis for total blood loss had an observed power of at least 99%. FVL carriers faced the same risk for postoperative transfusion (P = 0.391), reoperation (P = 0.675), myocardial infarction (P = 0.44), stroke (P = 0.701), and 30-day mortality (P = 0.4) as did noncarriers. Conclusions These data suggest that FVL carriers do not have reduced blood loss compared with noncarriers. Furthermore, the combination of aprotinin and FVL does not enhance the risk for thromboembolic complications.

Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽  
2015 ◽  
Vol 44 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Lea Weingarz ◽  
Marc Schindewolf ◽  
Jan Schwonberg ◽  
Carola Hecking ◽  
Zsuzsanna Wolf ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Cox Proportional Hazards ◽  
First Episode ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Younger Patients ◽  
Risk Of Recurrence ◽  
G20210a Mutation ◽  
Increased Risk ◽  
The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

Factor V Leiden and the risk of stillbirth in a German population

2003 ◽  
Vol 90 (09) ◽  
pp. 429-433 ◽  
Author(s):  
Rita Grimm ◽  
Daniel Robinson ◽  
Constanze Robinson ◽  
Thomas Kohlmann ◽  
Gudrun Schuster ◽  
...  
Keyword(s):  
Population Sample ◽  
Factor V Leiden ◽  
Population Based ◽  
German Population ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Number Of Children ◽  
North East ◽  
Increased Risk ◽  
Affected Woman

SummaryAn association between the factor V Leiden variant and an increased risk of pregnancy loss has been reported. Most previous studies were performed with clinically recruited patients and controls. This approach may cause selection bias. The present analysis was performed with the aim to investigate the association between the factor V Leiden mutation and the risk of stillbirth in a population-based sample.The Study of Health in Pomerania (SHIP) is a survey that was carried out in North East Germany. A random sample from the population aged 20 to 79 years was taken. The total SHIP population comprised 4,310 participants. The presence of the factor V Leiden variant was determined by PCR and Mnl I digestion. The presence of the factor V Leiden variant was neither associated with the number of pregnancies nor with the number of children per women. Data from 1,768 females who had at least one pregnancy with known outcome was available for the present analysis. Seventy-three women (4.1%) reported at least one stillbirth. Women with and without the factor V Leiden mutation did not differ with respect to the number of women with at least one stillbirth (OR for factor V Leiden variant 1.57; 95%-CI 0.76 – 3.25). Furthermore, the number of women with two or more stillbirths, the number of stillbirths per affected woman and the number of stillbirths per number of pregnancies per woman was similar between both genotype groups.In conclusion, there is no association between the factor V Leiden mutation and the risk of stillbirth in a representative population sample.

Factor V Leiden (G1691A) and Prothrombin Gene G20210A Mutations as Potential Risk Factors for Venous Thromboembolism after Total Hip or Total Knee Replacement Surgery

2002 ◽  
Vol 87 (04) ◽  
pp. 580-585 ◽  
Author(s):  
G. Larson ◽  
T. L. Lindahl ◽  
C. Andersson ◽  
L. Frison ◽  
D. Gustafsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Composite Endpoint ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
Symptomatic Pulmonary Embolism ◽  
Increased Risk ◽  
Prothrombin Gene

SummaryPatients (n = 1600) from 12 European countries, scheduled for elective orthopaedic hip or knee surgery, were screened for Factor V Leiden and prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations, respectively. All patients underwent prophylactic treatment with one of four doses of melagatran and ximelagatran or dalteparin, starting pre-operatively. Bilateral ascending venography was performed on study day 8-11. The patients were subsequently treated according to local routines and followed for 4-6 weeks postoperatively. The composite endpoint of screened deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE) during prophylaxis did not differ significantly between patients with or without these mutations. Symptomatic venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was significantly over-represented among patients with the prothrombin gene G20210A mutation (p = 0.0002). A tendency towards increased risk of VTE was found with the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over-represented in both the Factor V Leiden and prothrombin gene G20210A mutated patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the patients with these genetic risk factors will not suffer a VTE event, a general pre-operative genotyping is, in our opinion, of questionable value.

A Case Illustrating That Cancer Tips the Scale of Thrombosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4128-4128
Author(s):  
Emma C. Scott ◽  
Jeffrey Cohn ◽  
Stephen Heitner
Keyword(s):  
Tumor Cells ◽  
Ductal Carcinoma ◽  
Metastatic Cancer ◽  
Factor V Leiden ◽  
Cysteine Proteases ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Patients With Cancer ◽  
Increased Risk ◽  
Prothrombin Mutation

Abstract Background: There are many causes of thrombosis in cancer, including cancer itself, the release of TNF, IL-1 &IL-6 causing endothelial damage, the interaction between tumor cells and macrophages activates platelets, factors X11 &X. Cysteine proteases &tissue factor, in the tumor cells have pro-coagulant activity (Bick, R. New Engl J of Med. Volume 349. July 2003). Chemotherapy, hormonal therapy and indwelling central venous catheters also increase the risk of thrombosis. There is a RR of 4.1 for patients with cancer who did not have chemotherapy and 6.5 for patients with cancer who had chemotherapy (Heit et al. Arch Intern Med. 2000; 160: 809–815). Factor V Leiden mutation causes partial resistance to the inactivating effects of activated protein C. 5% of the population carries this mutation and it is present in 20% of patients with a 1st venous thrombotic episode. The risk of venous thrombosis is 3–8 fold. The prothrombin mutation is less common and the relative risk of thrombosis is about 2.0. In a large case control study it was found that carriers of the Factor V Leiden or the prothrombin mutation who also had cancer had an approximately 12–17 times increased risk of thrombosis; compared to an overall 7 times risk in patients with malignancy alone (Blom et al. JAMA. Feb 9, 2005. Vol 293, No 6). Case history: A 54 year old caucasion female was diagnosed with stage 1 infiltrating ductal carcinoma after palpating a lump in her left breast. The tumor was 1.6 cm, ER negative, PR negative and HER-2 negative. Lumpectomy and axillary node dissection revealed no residual carcinoma in the breast and no involvement of eleven lymph nodes. She completed 4 cycles of Cytoxan and Adriamycin successfully and was to start radiation therapy. 1 week after completing chemotherapy she had a focal seizure with tonicclonic movements of her right arm and no loss of consciousness. An MRI showed cortical infarcts, which were originally thought to be metastatic hemorrhages, in the left parietal and frontal areas and right parietal area. A follow up MRI showed considerable improvement of the cortical lesions, with no evidence of any metastatic cancer. Subsequently, she developed bilateral DVTs for which an IVC filter was placed as it was felt that she was not a candidate for anticoagulation given her recent CNS hemorrhage. She was also found to have bilateral pulmonary emboli on CT scan of the chest. Two other underlying disorders predisposing to thrombosis were found- Factor V Leiden mutation and the prothrombin gene mutation. Further imaging confirmed a thrombotic etiology for her CNS event, and coumadin was started. Conclusion: This case demonstrates the magnitude of the effect of cancer on thrombosis. This patient had 2 prothrombotic mutations, was a smoker, who had been on the OCP for 10 years prior to menopause, yet had no thrombotic episodes until she developed cancer. Also of interest is that the thrombotic episodes occurred shortly after completion of chemotherapy- another prothrombotic factor.

A Reduced Sensitivity for Activated Protein C in the Absence of Factor V Leiden Increases the Risk of Venous Thrombosis

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1271-1276 ◽  
Author(s):  
Marieke C.H. de Visser ◽  
Frits R. Rosendaal ◽  
Rogier M. Bertina
Keyword(s):  
Risk Factor ◽  
Confidence Interval ◽  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Apc Resistance ◽  
Increased Risk

Abstract Activated protein C (APC) resistance caused by the factor V Leiden mutation is associated with an increased risk of venous thrombosis. We investigated whether a reduced response to APC, not due to the factor V point mutation, is also a risk factor for venous thrombosis. For this analysis, we used the Leiden Thrombophilia Study (LETS), a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched controls. All carriers of the factor V Leiden mutation were excluded. A dose-response relationship was observed between the sensitivity for APC and the risk of thrombosis: the lower the normalized APC sensitivity ratio, the higher the associated risk. The risk for the lowest quartile of normalized APC-SR (&lt;0.92), which included 16.5% of the healthy controls, compared with the highest quartile (normalized APC-SR &gt; 1.05) was greater than fourfold increased (OR = 4.4; 95% confidence interval, 2.9 to 6.6). We adjusted for VIII:C levels, which appeared to affect our APC resistance test. The adjusted (age, sex, FVIII:C) odds ratio for the lowest quartile was 2.5 (95% confidence interval, 1.5 to 4.2). So, after adjustment for factor VIII levels, a reduced response to APC remained a risk factor. Our results show that a reduced sensitivity for APC, not caused by the factor V Leiden mutation, is a risk factor for venous thrombosis.

Preliminary pharmacogenetic evaluation of toxicity data in the prospective multicentre EORTC trial 40015 in metastatic colorectal cancer (CRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3072-3072
Author(s):  
D. Aust ◽  
C. Kohne ◽  
E. Goekkurt ◽  
J. De Greve ◽  
J. Hartmann ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Factor V Leiden ◽  
Phase Iii ◽  
Normal Colonic Mucosa ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Increased Risk ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Peripheral Leukocytes

3072 Background: EORTC phase III study 40015 was initiated in 2003 to compare capecitabine (C) + irinotecan (CPT-11) vs 5FU/LV/irinotecan ± celecoxib in 1st line treatment of mCRC. The study was suspended after enrollment of 85 pts due to 8 fatal events not related to disease progression, 4 of which included thrombo-embolic events. Purpose: To test whether genetic polymorphisms involved in metabolism of the drugs are related to the increased toxicity observed in the study. Methods: 71 pts signed informed consent for genetic analyses and material was available for 58 pts. DNA was extracted from normal colonic mucosa or peripheral leukocytes. Polymorphisms were determined using PCR-based RFLP and direct sequencing. Genotypes known to be associated with increased toxicity (diarrhea, mucositis, leucopenia) were classified as unfavorable. Results: Unfavorable genotypes were distributed equally between C+CPT-11 and LV/5FU+CPT-11 arms. Baseline characteristics and treatment duration were similar in the pts with or without unfavorable genotypes. Unfavorable genotypes of thymidylate synthase (TS-5; TS-3) and UDP-glucuronosyltransferase 1A1 (UGT1A1) were associated with increased grade 3/4 toxicity. 18/35 (51%) pts with unfavorable UGT1A1 genotype experienced toxicity grade 3/4 compared to 3/23 (13%) pts with favorable genotype. 16/36 pts (44%) with unfavorable TS-5 genotype showed toxicity grade 3/4 compared to 5/22 (23%) pts with favorable genotype. Toxicity grade 3/4 was observed in 18/41 (44%) pts with unfavorable TS-3 genotype and 3/17 (18%) pts with favorable genotype. Increasing grade 3/4 toxicity rates were observed in the pts expressing 0/1 (2/16 [13%]), 2 (7/24 [29%]) or 3 (12/16 [75%]) unfavorable genotype(s) (p=0.0001). Among the 4 pts who died of a thrombo-embolic event, only one has been analysed at this stage and showed a Factor (V) Leiden mutation linked to 10-fold increased risk for thrombo-embolic events. Analyses are ongoing and complete data will be available for presentation. Conclusion: Our data suggest an association between polymorphisms of TS and UGT1A1 and toxicity. No differences of pharmacogenetic patterns were observed that could explain the increased rate of fatal events in the C/CPT-11 arm. [Table: see text]

Abstract 200: Hypercoagulabilty Panel Testing in Neonates Undergoing Cardiac Surgery

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Sirisha Emani ◽  
David Zurakowski ◽  
Christopher Baird ◽  
Frank Pigula ◽  
Trenor Cameron ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Thrombin Generation ◽  
Factor V Leiden ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Coagulation Factors ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
C Protein ◽  
Cardiolipin Antibodies

Thrombosis is a crucial contributor of morbidity and mortality in neonates undergoing cardiac surgery. Although there is published data on several factors of the hemastatic system, there is no data correlating factor expression and/or function with thrombosis in neonates. We tested the hypothesis that hypercoagulability markers are predictive of thrombosis in neonates undergoing cardiac surgery. Sixty neonates undergoing cardiac surgery were tested for thrombin generation assay; coagulation factors; antithrombin III, protein C, protein S, and factor VIII; fibrinolytic inhibitors; thrombin-activatable fibrinolytic inhibitor, plasminogen activator inhibitor; and presence of cardiolipin antibodies by immunoassays. Factor V Leiden mutation was also tested in a few patients utilizing single nucleotide polymorphism assays. In this pilot study, thrombosis occurred in 15% of the neonates undergoing cardiac surgery. Significant risk factors associated with thrombosis were pre-mature birth, use of cardio pulmonary bypass, and single ventricle physiology. Hypercoagulability factors associated with thrombosis determined by univarent analysis were elevated thrombin generation, enhanced expression of thrombin-activatable fibrinolytic inhibitor and plasminogen activator inhibitor as well as presence of cardiolipin antibodies and factor V Leiden mutation. No correlation was observed between thrombosis and expression of coagulation factors antithrombin III, protein C, protein S, and factor VIII. Multivarient analysis has proven to show thrombin generation, thrombin-activatable fibrinolytic inhibitor, and presence of cardiolipin antibodies as multivariable predictors of thrombosis. These significant hypercoagulability markers are independent predictors of thrombosis. Thus thrombosis predictability can help in post-operative management and care for neonates undergoing cardiac surgery by regulating pro- and/or anti-coagulation therapy.

Oral Contraceptive-Associated Thromboembolism. A Retrospective Analysis of Thrombophilic Work-out and Long Term Follow up in 57 Cases

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5348-5348
Author(s):  
Emmanouil Papadakis ◽  
Smaragda Efremidou ◽  
Haris Kartsios ◽  
Margarita Mpraimi ◽  
Kiriaki Kokoviadou ◽  
...  
Keyword(s):  
Family History ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Apc Resistance ◽  
Increased Risk ◽  
Fv Leiden

Abstract Introduction: The increased risk of venous thrombosis in women taking oral contraceptives (OCs) has been recognized since the early 1960s. Coexistence of hereditary risk factors appears to have an additive effect. Women under OCs that carry the factor V Leiden mutation have a 35-fold increased risk of thromboembolic events compared to women without the mutation who are not on OCs. Evaluation of family and personal history is the mainstay of prophylaxis prior to OC administration, but often family thrombophilia or thromboembolic (TE) events are not reported prior to OCs prescription. Patients-Methods: Fifty-seven women with a median age of 28 (21–48) years, which suffered OC-associated TE, were studied. The median period of OC therapy prior to TE event was 2 months (0.5–60). Fifty-five of them experienced VTE while 2 suffered stroke. Leg thrombosis was the most common clinical finding [37/55 (67,2%) patients] Apart from personal and family history, Thrombophilia investigation included measurement of : serum Homocysteine, Antithrombin, Protein C and S, Lipoprotein (a), Activated Protein C (APC) resistance, antiphospholipid antibodies and lupus anticoagulant. In addition the presence of FV Leiden, FII 20210 GA mutations and MTHFR 677 CT polymorphism were determined. Results: A high prevalence of the factor V Leiden mutation was detected in the study group; 50% had APC-resistance test positive, 26 (45%) patients were found to be heterozygous and 3 (5,2%) homozygous for the FV Leiden mutation. Lp(a) elevation was observed in 19,3% and Homocysteine elevation in 15,8% of patients. In 9 women (15,8%) both family history and thrombophilic profile were negative. Serious VTE events (2 abdominal and 6 CNS thromboses) were observed only in the Leiden subgroup. During the follow up period ranging from months to 18 years, 3 women (6,25%) experienced a miscarriage and 14 suffered additional VTE events (25%) and they are currently on permanent anticoagulation. Conclusions : Universal thrombophilia screening of women prior to prescription of OCs is not advisable as it does not appear to be cost effective. However, screening certain subgroups, such as women with a known personal or family history, may be of great value. If a full thrombophilic profile can’t be performed, a mere activated protein C resistance test, that reflects the presence of the factor V Leiden mutation, may provide an easy and cheap way of identifying and consulting properly women at higher risk for VTE prior to OC use. Women with OC-associated VTE and thrombophilia carry a substantial recurrence risk that persists for years.

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