Identification of a Spontaneous Noncoding Mutation on Chromosome 18 Which Suppresses Thrombosis in Factor V Leiden Homozygous, TFPI Deficient Mice

Factor V Leiden (FVL) is an incompletely penetrant thrombosis susceptibility variant common in humans. This incomplete penetrance suggests there are modifiers of FVL (F5L) that alter the susceptibility to a thrombotic event. To identify modifiers, we performed a sensitized ethylnitrosourea (ENU) mutagenesis screen in mice to induce mutations suppressing the F5L/LTfpi+/- perinatal lethal thrombotic phenotype. Although we identified thrombosuppressor mutations in two of our 22 independent MF5L mouse lines thus far, the others are still unknown. Our mouse line MF5L16 has produced a large, highly penetrant (77.2%), multigenerational pedigree containing 136 viable F5L/LTfpi+/- mice. We performed the Prothrombin Time (PT) assay on plasma from a subset of these mice and observed a significantly longer PT in MF5L16F5L/LTfpi+/- mice compared to F5+/LTfpi+/- and Tfpi+/- control mice (q<0.01). The aim of our study was to identify the MF5L16 thrombosuppressor. First, we analyzed four mice by whole genome sequencing and identified a total of 44 candidate ENU mutations. Sanger re-sequencing analysis determined that 22 were false-positive calls. Seven arose in our F5L/L breeding colony and were introduced into MF5L16 by these mice. Three arose on the Tfpi- mouse background. The remaining 12 candidates could not be analyzed as they were in repetitive/low complexity regions. Due to the lack of ENU-induced mutations segregating in MF5L16, we next analyzed the seven mutations entering the pedigree from the F5L/L breeders in all 136 MF5L16 F5L/LTfpi+/- mice. We identified a significant association between a Chromosome 18 intergenic variant (Chr18 G to A, Chr18A) and F5L/LTfpi+/- mouse survival (p=0.0031). Two additional mutations within intronic regions on Chromosomes 9 and 13 were also significantly associated with survival when co-inherited with the Chromosome 18 mutation (p=0.000113). Importantly, no coding variants were linked to these variants. To re-create the suppression of the lethal F5L/LTfpi+/- phenotype, we bred a F5L/L Chr18A/A mouse onto the Tfpi- background to produce F5+/L Chr18+/ATfpi+/- mice. We then bred these F5+/L Chr18+/ATfpi+/- triple heterozygous mice to F5L/L Chr18A/ATfpi+/+ mice to observe the effects of Chr18A on F5L/LTfpi+/- mouse survival. The first litter of six mice from this cross yielded one F5L/LTfpi+/- mouse that was also heterozygous for Chr18 (F5L/LTfpi+/- Chr18+/A: expected ratio ~1:8). This suggests that the Chr18A variant suppresses F5L/LTfpi+/- lethal thrombosis and that noncoding genomic variants can act as potent thrombosuppressors. Our genetic analyses suggest that thrombosuppressor variants arose in our F5L mouse colony due to positive selective pressure for the best F5L breeders. In addition, the genomic interactions between the putative thrombosuppressor variants described here illuminate the complexities of thrombosis genomics and could provide insights into human thrombosis. Disclosures No relevant conflicts of interest to declare.

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APC-resistance as a possible predictor of recurrent thrombosis in women with Factor V Leiden

Journal of obstetrics and women s diseases ◽

10.17816/jowd67650-59 ◽

2018 ◽

Vol 67 (6) ◽

pp. 50-59 ◽

Cited By ~ 1

Author(s):

Maria G. Nikolayeva ◽

Andrey P. Momot ◽

Marina S. Zaynulina ◽

Ksenia A. Momot ◽

Natalia N. Yasafova

Keyword(s):

Thrombotic Event ◽

Activated Protein C ◽

Factor V Leiden ◽

Resistance Index ◽

Reproductive Age ◽

Control Group ◽

Factor V ◽

Recurrent Thrombosis ◽

Apc Resistance ◽

Venous Thromboembolic

Hypothesis/aims of study. The current analysis was undertaken to elucidate the role of Factor Va resistance to proteolytic cleavage by activated protein C in FVL(1691)GA female carriers in the development of acute and recurrent thromboses. Study design, materials and methods. A prospective clinical cohort study of 1100 women of reproductive age was conducted, with the course and outcomes of 2,707 pregnancies analyzed. Two cohorts were specified: the main group consisted of 500 patients with FV(1691)GA genotype, and the control group consisted of 600 patients with FVL(1691)GG genotype. Results. FVL(1691)GA genotype was significantly associated with the development of venous thromboembolic complications (VTEC) compared to FVL(1691)GG genotype (OR 9.3; p < 0.0001). Episodes of recurrent thrombosis during and outside of pregnancy were registered only in FVL(1691)GA patients (OR 5.7, p = 0.2). In all cases, at the time of the thrombotic event and during the period before the episode of acute or recurrent thrombosis, an APC resistance normalized ratio (NR) value was ≤ 0.49, with no episodes of VTEC registered with an APC resistance NR value ≥ 0.5. Conclusion. Venous thromboses occur under the condition of expressed APC resistance with underlying FVL(1691)GA carriage. The APC resistance index can serve as an objective biochemical marker to determine the feasibility of thromboprophylaxis within the framework of personalized medicine.

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High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance) [see comments]

Blood ◽

10.1182/blood.v85.6.1504.bloodjournal8561504 ◽

1995 ◽

Vol 85 (6) ◽

pp. 1504-1508 ◽

Cited By ~ 648

Author(s):

FR Rosendaal ◽

T Koster ◽

JP Vandenbroucke ◽

PH Reitsma

Keyword(s):

Venous Thrombosis ◽

Protein C ◽

Absolute Risk ◽

Thrombotic Event ◽

Activated Protein C ◽

Factor V Leiden ◽

Coagulation Factor ◽

Factor V ◽

Increased Risk ◽

The Absolute

Resistance to activated protein C (APC) is a common inherited risk factor for venous thrombosis, which is associated with a mutation in coagulation factor V (factor V Leiden). We investigated the risk of venous thrombosis in individuals homozygous for this abnormality. We determined the factor V Leiden genotype in 471 consecutive patients aged less than 70 years with a first objectively confirmed deep-vein thrombosis and in 474 healthy controls. We found 85 heterozygous and seven homozygous individuals among the cases with thrombosis and 14 heterozygous individuals among the control subjects. The expected number of homozygous individuals among the controls was calculated from Hardy-Weinberg equilibrium and estimated at 0.107 (allele frequency, 1.5%). Whereas the relative risk was increased sevenfold for heterozygous individuals, it was increased 80-fold for homozygous individuals. These patients experienced their thrombosis at a much younger age (31 v 44 years). The homozygous individuals were predominantly women, most likely due to the effect of oral contraceptives. Because of the increased risk of thrombosis with age, the absolute risk becomes most pronounced in older patients, both for heterozygous and homozygous individuals. For the homozygous individuals, the absolute risk may become several percentage points per year. This implies that most individuals homozygous for factor V Leiden will experience at least one thrombotic event in their lifetime.

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Genetic Modifiers of Thrombosis in Mice.

Blood ◽

10.1182/blood.v114.22.sci-44.sci-44 ◽

2009 ◽

Vol 114 (22) ◽

pp. SCI-44-SCI-44

Author(s):

David Ginsburg

Keyword(s):

Large Scale ◽

Genetic Factors ◽

Conflicts Of Interest ◽

Factor V Leiden ◽

Mouse Genetics ◽

Von Willebrand Disease ◽

Modifier Genes ◽

Factor V ◽

Genetic Modifiers ◽

Von Willebrand

Abstract Abstract SCI-44 The genetic factors responsible for the highly variable clinical course of inherited bleeding disorders including von Willebrand disease and hemophilia are largely unknown. Similar factors are also likely to contribute to the variability of common thrombotic disorders, including factor V Leiden. Studies by our lab over the past 10 years have used the power of mouse genetics to identify genes contributing to this variability (referred to as ‘modifier‘ genes). By performing genetic crosses between inbred strains of mice with elevated plasma levels of von Willebrand Factor (VWF) and other strains with low levels, we have mapped a total of 6 genetic factors contributing to the control of murine plasma VWF levels. Similar studies in ADAMTS13-deficient mice are in progress aimed at characterizing genes modifying susceptibility thrombotic thrombocytopenic purpura. We have also conducted large scale mutagenesis studies in the mouse in an effort to identify larger numbers of genes contributing to thrombosis risk in the setting of Factor V Leiden, and most recently are extending this approach to similar genetic screens in zebrafish. Finally, recent advances in human genetics are expanding the potential opportunities for directly identifying bleeding and thrombosis modifier genes in humans. Disclosures No relevant conflicts of interest to declare.

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The Phenotypic Expression of Homozygous and Compound Heterozygous Factor V R506Q (Factor V Leiden, FVL) and Factor II A20210G: Ten Years Experience At a Referral Center

Blood ◽

10.1182/blood.v118.21.5252.5252 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5252-5252

Author(s):

Hamid A B Al-Mondhiry ◽

Thomas P Nifong ◽

Mary Elaine Eyster

Keyword(s):

Recurrent Events ◽

Conflicts Of Interest ◽

Phenotypic Expression ◽

Factor V Leiden ◽

The Other ◽

Compound Heterozygous ◽

Factor V ◽

Degree Relative ◽

Referral Center ◽

Factor Ii

Abstract Abstract 5252 Heterozygous Factor V Leiden, the most common inherited thrombotic disorder with an estimated incidence of about 5% in Caucasian population, poses a moderate risk of first venous thromboembolic (VTE) event. The homozygous and compound heterozygous states are comparatively rare but are thought to be associated with high risk of recurrent VTE. This report describes ten years experience with homozygous and compound heterozygous FVL and Factor II A20210G at a major referral center in central Pennsylvania, USA. Between January 2000 and December 2010, 31 homozygous F VL patients, 2 homozygous FII A20210G, 10 compound heterozygous FVL and F II A20210G and 6 compound heterozygous F VL and protein C (PC), protein S (PS) or antithrombin (AT) deficiency were encountered. The reasons for referral were personal or family history of VTE or a first degree relative diagnosed with any of these conditions. Among these patients, 5 homozygous F VL, 1 compound heterozygous F VL and F II A20210G, and 1 compound heterozygous factor VL and PC deficiency remained free of VTE at age 17–64 years, even though they were exposed to prothrombotic conditions, e.g., surgery, hormones or pregnancy. Two compound heterozygous F VL and PS deficient patients suffered ischemic strokes, one at age 3 ½ years and the other at age 45 years, but no VTE. The other patients suffered lower extremity deep vein thrombosis and/or pulmonary embolism or visceral thrombosis. Most had recurrent events. Our experience highlights the serious thrombotic risks associated with homozygous and compound heterozygous F VL and F II A20210G status but also indicates that some patients remain thrombosis free despite exposure to additional prothrombotic conditions. However, because of referral bias this series of patients may not truly reflect the overall occurrence of VTE in patients with homozygous or compound heterozygous inherited thrombophilia. Disclosures: No relevant conflicts of interest to declare.

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Clinical and Molecular Profile Of Hereditary Antithrombin (AT) Deficiency: A Single Institution Cohort

Blood ◽

10.1182/blood.v122.21.2369.2369 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2369-2369

Author(s):

Ashish V Chintakuntlawar ◽

Jennifer Guenther ◽

Rajiv K Pruthi ◽

John A. Heit ◽

Mrinal M. Patnaik

Keyword(s):

Conflicts Of Interest ◽

Thrombotic Event ◽

Factor V Leiden ◽

Bleeding Complications ◽

Molecular Profile ◽

Cerebrovascular Event ◽

Factor V Leiden Mutation ◽

At Deficiency

Abstract Introduction Hereditary antithrombin (AT) deficiency is an autosomal dominant thrombophilia. It is classified into type 1 (quantitative) or type 2 (qualitative) deficiency based on the AT antigen and activity levels (Haemophilia 2008:14; 1229). The goal of this study was to correlate clinical phenotype with AT molecular defects. Methods After IRB approval, patients with a diagnosis of hereditary AT deficiency established at the Mayo Clinic, Rochester, were identified from the clinical database (1997-2012). AT activity was assayed by a chromogenic Factor Xa assay and AT antigen level was assayed by latex immunoassay. Peripheral blood leukocyte genomic DNA was extracted using standard methods. PCR-amplification and ABI BigDye Terminator cycle sequencing kit was performed for all SERPINC1 exons, intronic splicing regions and the 3’UTR. SERPINC1 sequence was analyzed using Mutation Surveyor software (SoftGenetics). Clinical data were obtained from patient interview and medical record review. An event was defined as an episode of venous thromboembolism (VTE), including deep vein thrombosis and/or pulmonary embolism; arterial thrombosis, including cerebrovascular event and/or myocardial infarction, and an obstetric event, including miscarriages and/or spontaneous abortions. Statistical analysis was performed with SAS 9.1.3 (SAS Institute Inc. Cary, NC). Results Of 30 patients with hereditary AT deficiency; sequence data was available on 22. Twenty-nine (97%) patients were white, and 19 (63%) were females. Six patients (20%) were smokers and 9 (30%) had a body mass index of >30. Based on the AT activity and antigen levels, 18 (81%) had type 1 AT deficiency, while the remainder had type 2. Eleven patients were heterozygous for six novel (all type 1) mutations. One patient was also a homozygous carrier for the Factor V Leiden mutation. The median age at first thrombotic event was 24.4 years (range, 16.2-70.7), and the median age at diagnosis of AT deficiency was 40.7 years (range, 17.8-76). Both, the median ages at first thrombotic event and at diagnosis were comparable in type 1 versus type 2 AT deficiency patients (P=0.52 and 0.97 respectively). Thirteen patients (43%) had unprovoked thrombotic events. Majority had VTE (n=21, 70%), which included one patient each with splanchnic venous thrombosis, and cerebral venous sinus thrombosis. At last follow up, twenty-one patients (70%) were on chronic anticoagulation [17 (81%) were on warfarin, 2 (9.5%) on enoxaparin and 2 (9.5%) were on rivaroxaban]. Median number of events was 1 (range 0-7). Four patients (19%) had bleeding complications from anticoagulation. Only one death was noted in the cohort and cause of death could not be determined. Conclusions Type 1 hereditary AT deficiency is the most clinically prevalent subtype in practice. Of the patients who developed thrombosis; clinical characteristics did not differ between type 1 and type 2 AT deficiency. We report 6 novel mutations in patients with hereditary AT deficiency. Disclosures: No relevant conflicts of interest to declare.

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Molecular Analysis of Factor V, Prothrombin and Methylenetetrahydrofolate Redutase in Thrombolic Patients

Blood ◽

10.1182/blood-2018-99-118777 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5050-5050

Author(s):

Aldair Sousa Paiva ◽

Hugo Diogenes De Oliveira Paiva ◽

Geraldo Barroso Cavalcanti ◽

Gioconda DR Leão ◽

Marcos Dias Leão ◽

...

Keyword(s):

Risk Factors ◽

Conflicts Of Interest ◽

Factor V Leiden ◽

Mthfr C677t ◽

Factor V ◽

Hereditary Risk ◽

Hemostatic System ◽

Pcr Rflp ◽

Prothrombin Gene ◽

Detection Of Mutations

Abstract Background: The study of thrombotic events requires knowledge of changes in the hemostatic system associated with multiple acquired and hereditary risk factors that suggest predisposition to thrombosis. The factor V or Leiden (G1621A), Prothrombin (G21210A) and Methylenetetrahydrofolate redutase-MTHFR (C677T) mutations are the major genetic risk factors for venous thrombosis. This study assessed the frequency of mutations of the Factor V (Leiden), Prothrombin and MTHFR in patients with thrombophilia from the DNA Center Laboratory, Natal - RN. Methods: The detection of mutations was made by PCR-RFLP followed by enzymatic restriction with HindIII (Leiden and Prothrombin) and HinfI (MTHFR). Results: From 69 selected patients, 52 (75.36%) were females and 35 (24.64%) were males. The frequency of genotypes for the Factor V were: 3 mutated homozygous (4.35%), 4 heterozygous (5.80%) and 62 normal homozygous (89.85%). Regarding the mutation in the Prothrombin gene it was observed in 65 normal homozygous patients (94.2%) and 4 (5.8%) heterozygous. The analysis of the mutation in the gene MTHFR showed 35 (50.7%) normal homozygous patients, 5 (7.2%) mutated homozygous patients and 29 heterozygotes patients (42.1%). Conclusions: Approximately 50% of patients tested had at least one type of genetic alteration combined. Based on data obtained it is indicated the investigation of three markers (Factor V, Prothrombin and MTHFR) thrombophilia-related, targeting the real impact of the molecular mutations in thrombosis and the conduct of treatment. Disclosures No relevant conflicts of interest to declare.

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Analysis of Ordering Practice of Thrombophilia Testing at a Single Large Teaching Hospital

Blood ◽

10.1182/blood.v116.21.3188.3188 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3188-3188

Author(s):

Judy Peih-Ying Tsai ◽

Evelyn O. Taiwo ◽

Natalie Cervantes ◽

Guadalupe Jasso ◽

Eugene P. Frenkel ◽

...

Keyword(s):

Teaching Hospital ◽

Protein C ◽

Conflicts Of Interest ◽

Thrombotic Event ◽

Young Patients ◽

Factor V Leiden ◽

Repeat Testing ◽

Large Teaching Hospital ◽

Thrombophilia Testing ◽

Abnormal Results

Abstract Abstract 3188 Background: Thrombophilia describes either an inherited or acquired predisposition to thrombosis. There are no well defined guidelines for thrombophilia testing. Thus, testing after a single episode of thrombosis in unselected patients has become a common yet often inappropriate practice. An ideal work-up includes: antithrombin (AT) activity, protein C (PC) activity, protein S (PS) activity and antigen (total and free), activated protein C resistance (APC-R), factor V Leiden (FVL) if the APC-R is abnormal, prothrombin gene mutation (PGM), factor VIII (FVIII) and antiphospholipid antibodies (aPL) (lupus anticoagulant, anti-cardiolipin, and anti-β2 glycoprotein I, IgG, M and A). Objective: The purpose of this retrospective observational study was to characterize the pattern of such thrombophilia testing at a single large teaching hospital. Methods: All laboratory requests for thrombophilia testing in October and November of 2009 were included in this retrospective evaluation. The tests included were PC, PS, AT, FVIII, FVL, PGM, homocysteine and aPL. Clinical information was extracted from electronic medical records and analyzed for indication and timing of testing, completeness of the tests, whether the tests were performed on anticoagulation, and whether an abnormal test result was repeated to confirm the diagnosis. Results: The study consisted of 100 consecutive patients (69 females, 68 less than 50 years of age). 70 patients had a known event prior to thrombophilia testing, 34 had an inappropriate indication [provoked thrombosis, 1–2 pregnancy losses, pre-eclampsia] (Table 1). 88% of the patients who were tested had an incomplete workup for the indication. Of the 70 patients who had an identifiable event prior to testing for thrombophilia, 41 patients were tested at the time of the event (<1 week) when natural anticoagulants could be consumed and results will not alter the management. Of all 100 patients, 30 were tested after anticoagulant therapy was initiated, which is known to affect results of several laboratory tests listed above; 8 of these patients had abnormal results and only 2 had repeat testing to confirm. 53% of all patients in the cohort tested positive; 20 of which underwent repeat testing, with half showing normalization (Table 2). Of the 36 patients tested for the appropriate indications [unprovoked thrombosis, or ≥3 pregnancy losses], only 3 had complete testing; 20 were tested at the time of the acute event, and 13 were tested on anticoagulant. Conclusions: Only 36% of patients had thrombophilia testing done for the appropriate thrombotic or obstetric indications. 10% had confirmed positive tests, while 33% had an abnormal result that remained unconfirmed. Thrombophilia testing at our center deviates markedly from what would be considered appropriate in terms of indication, completeness, timing from thrombotic event, testing off anticoagulation and necessity of repeat testing. Ideally testing should be performed on young patients with unprovoked events, off anticoagulation to allow factor levels to return to baseline, and repeated for all abnormal results. Building on these observations, this study aims to devise standards of practice to minimize cost and prevent misdiagnosis in thrombophilic patients. Disclosures: No relevant conflicts of interest to declare.

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Diagnostic ramifications of ocular vascular occlusion as a first thrombotic event associated with factor V Leiden and prothrombin gene heterozygosity

Clinical Ophthalmology ◽

10.2147/opth.s80714 ◽

2015 ◽

pp. 591 ◽

Cited By ~ 7

Author(s):

Samantha Schockman ◽

Charles J Glueck ◽

Robert K Hutchins ◽

Ping Wang ◽

Parth Shah ◽

...

Keyword(s):

Thrombotic Event ◽

Factor V Leiden ◽

Vascular Occlusion ◽

Factor V ◽

Prothrombin Gene

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Prevalence of Common Thrombophilia and Antiphospholipid Antibodies in Unexplained Infertility Women Undergoing in Vitro Fertilization (IVF)

Blood ◽

10.1182/blood.v120.21.628.628 ◽

2012 ◽

Vol 120 (21) ◽

pp. 628-628

Author(s):

Arie Steinvil ◽

Raanan Raz ◽

Shlomo A. Berliner ◽

David M Steinberg ◽

David Zeltser ◽

...

Keyword(s):

In Vitro Fertilization ◽

Success Rate ◽

Conflicts Of Interest ◽

Factor V Leiden ◽

Unexplained Infertility ◽

Factor V ◽

Vitro Fertilization ◽

History Of ◽

The Mean

Abstract Abstract 628 Assisted reproductive technology (ART) is extensively used as a tool for pregnancy achievement in subfertile couples. Congenital and acquired thrombophilia have been suggested by some investigators to play a role in abnormal embryos implantation and placentation. The objective of this study was to assess the role of common thrombophilia in women with unexplained infertility undergoing in vitro fertilization (IVF). We enrolled five hundred ninety-four women from a large healthcare maintenance organization going through IVF and who had a thrombophilia workup, and compared them for prevalence of thrombophilia to two reference groups consisting of 637 fertile women from previous work and 17,337 women members of the same healthcare organization with no history of venous thromboembolisms. The mean age of the women at the first cycle of IVF was 30.9 years (SD: ±4.1).The mean number of IVF cycles was 7.3 (SD: 5.0), and the mean fertility success rate per woman was 14.6% (SD: 19.0). None of the common thrombophilia tested was found to be significantly associated with the number of IVF cycles or with lower fertility success rate. Rather, women who had APCR and/or factor V Leiden and lupus anticoagulant had significantly higher live birth rates (12.25% and 12.64%, respectively) in comparison to women who were tested negative (8.98% and 9.7%, respectively). Thus, hypercoagulability is not associated with failure to achieve pregnancy. These data suggest that neither screening for thrombophilia nor anticoagulant treatment is indicated in cases with unexplained reproductive failure. Disclosures: No relevant conflicts of interest to declare.

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Incidence Of Symptomatic Venous Thromboembolism In Patients With Hemophilia Undergoing Joint Replacement Surgery: A Retrospective Study

Blood ◽

10.1182/blood.v122.21.2348.2348 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2348-2348

Author(s):

Juliana Perez Botero ◽

Daniel B Spoon ◽

Mrinal M Patnaik ◽

Robert T Trousdale ◽

Rajiv K Pruthi

Keyword(s):

Venous Thromboembolism ◽

High Risk ◽

Conflicts Of Interest ◽

Femoral Vein ◽

Factor V Leiden ◽

Factor V ◽

Compression Stockings ◽

Vte Prophylaxis ◽

Joint Replacement Surgery ◽

Pharmacologic Prophylaxis

Abstract Background Hip and knee arthroplasty (THA and TKA), in general, pose a high risk for venous thromboembolism (VTE), and pharmacologic VTE prophylaxis is often strongly recommended. In patients (pt) with hemophilia undergoing THA/TKA, given the underlying bleeding diathesis, the routine use of pharmacologic VTE prophylaxis is controversial. In this study, we report THA/TKA outcomes in pt with hemophilia in our institution. Methods Retrospective chart review of Mayo Comprehensive hemophilia center pt undergoing THA and TKA. Medical records were reviewed for objectively documented VTE for up to 3 months after surgery. Results 42 consecutive pt with hemophilia A (n=38) or B (n=4) underwent 71 operations: THA (n=32) and TKA (n=39) over a period of 39 years. All pt received compression stockings up to 6 weeks after surgery; 6/71 (8.4%) received sequential intermittent compression and 2/71 (2.8%) received postoperative low molecular weight heparin (LMWH). Symptomatic femoral vein DVT occurred in 1/42 pt (2%); (1/71, 1.4% of operations (1.4%)), 10 days after THA for traumatic hip fracture and after the LMWH was discontinued. The patient was subsequently found to be heterozygous for the factor V Leiden gene mutation. For up to 3 months after surgery, there were no additional cases of symptomatic DVT. There was no unexpected bleeding in the 2 patients receiving LMWH. Conclusion In this this study, routine use of compression stockings without the use of pharmacologic prophylaxis resulted in a low rate of symptomatic VTE in patients with hemophilia. This may be similar to the incidence in the general population receiving LMWH (Heit, JA et al Annals of Internal Medicine 2000) A limited sample size precludes definitive recommendations for practice. For appropriate high risk patients, limited use of pharmacologic prophylaxis may still be important. Disclosures: No relevant conflicts of interest to declare.

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