warfarin and Activated-Protein-C-Resistance

Venous thrombosis is a cause of considerable morbidity and is often responsible for chronic venous disorders that frequently lead to visits to dermatologists and others involved in wound healing. Over the past several years, many new causes of thrombophilia have been identified and have dramatically altered the approach to patients presenting with thrombosis. Newly described abnormalities associated with thrombophilia include the syndrome of activated protein C resistance, the prothrombin 20210A mutation, hyperhomocysteinemia, and elevated levels of coagulation factors VIII and XI. Clinicians can now frequently determine causes of thromboses that have previously been deemed idiopathic.

Topics: Activated Protein C Resistance; Anticoagulants; Blood Coagulation Disorders; Contraceptives, Oral; Factor V; Female; Humans; Hyperhomocysteinemia; Mutation; Pregnancy; Pregnancy Complications, Cardiovascular; Prothrombin; Recurrence; Risk Factors; Warfarin

Venous thromboembolism (VTE) is a major complication of myeloma therapy recently observed with the increasing use of up-front thalidomide and dexamethasone (thal-dex). The pathogenesis of thal-induced VTE is not well recognized, and the role of prothrombotic factors, especially of thrombophilic abnormalities, is not yet determined.. Two hundred and sixty-six patients with newly diagnosed multiple myeloma (MM) were primarily treated with thal-dex in preparation for subsequent high-dose therapy and autologous stem-cell transplantation. Out of these 266 patients, 190 were evaluated for thrombophilic alterations at baseline, and 125 of them were also re-assessed after thal-dex therapy.. The presence of genetic thrombophilic polymorphisms among patients with MM was superimposable to that of normal controls and was associated with a twofold increase in the relative risk of VTE. aAPCR and elevated factor VIII levels were frequent, albeit transient, alterations and were not associated with a significant increase in the risk of VTE. Two hundred and forty-six patients received a thromboprophylaxis with fixed low-dose warfarin (1.25 mg/day) during thal-dex therapy. Of these patients (or 10.6%), 26 had symptomatic VTE events. Their patients-years rate of VTE (35.5%) was significantly lower in comparison with the 86.2% rate recorded among the first 19 patients who initially entered the study and did not receive any kind of thromboprophylaxis (P = 0.043).. On the basis of these data, a baseline thrombophilic work up is not recommended in patients with receiving up-front thal-dex. For these patients, fixed low-dose warfarin may be a valuable prophylaxis against VTE.

Topics: Activated Protein C Resistance; Adult; Aged; Anticoagulants; Case-Control Studies; Dexamethasone; Factor V; Factor VIII; Female; Humans; Male; Middle Aged; Multiple Myeloma; Prothrombin; Risk Factors; Thalidomide; Thrombophilia; Thrombosis; Venous Thromboembolism; Warfarin

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.

Topics: Activated Protein C Resistance; Administration, Oral; Anticoagulants; Antithrombins; Blood Coagulation Tests; Factor V; False Negative Reactions; False Positive Reactions; Humans; Protein C; Protein S; Thrombophilia; Warfarin

To study the incidence, clinical risk factors and outcome of thrombotic events in pediatric age group of 1 mo-12 y.. This prospective observational study was conducted in a tertiary care institute from September 2015 through October 2017. Forty nine children with thrombosis from 1 mo-12 y were enrolled.. Out of 49 cases, 30 (61.2%) were due to venous thromboembolism (VTE) and 19 (38.8%) were of arterial thromboembolism (ATE). The cumulative average annual incidence for VTEs was found to be 38.2 (n = 30) and for ATEs it was found to be 24.2 (n = 19) per 10,000 hospital admissions over 2 y of study period. With total of 19 (38.7%), catheters were the leading cause of thrombosis followed by infection numbering to 10 cases (20.4%). Total 42.8% cases (n = 21) achieved complete resolution. Partial resolution was noted in 53.2% of cases (n = 26) and no resolution in 4% cases (n = 2). Total seven (14.3%) deaths were recorded during the study period.. The present study showed that thrombosis is an emerging problem in tertiary care setting adding to both mortality and morbidity in children. Central venous catheters followed by infection were the leading cause of thrombosis in this study.

Topics: Activated Protein C Resistance; Anticoagulants; Antithrombin III; Child; Child, Preschool; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Incidence; Infant; Male; Prospective Studies; Risk Factors; Thrombosis; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

Antiphospholipid antibodies may interfere with the anticoagulant activity of activated protein C (APC) to induce acquired APC resistance (APCr).. To investigate the frequency and characteristics of APCr by using recombinant human APC (rhAPC) and endogenous protein C activation in antiphospholipid syndrome (APS).. APCr was assessed in APS and non-APS venous thromboembolism (VTE) patients on warfarin and normal controls with rhAPC or Protac by thrombin generation. IgG anti-protein C and anti-protein S antibodies and avidity were assessed by ELISA.. APS patients showed greater resistance to both rhAPC and Protac than non-APS patients and normal controls (median normalized endogenous thrombin potential inhibition): APS patients with rhAPC, 81.3% (95% confidence interval [CI] 75.2-88.3%; non-APS patients with rhAPC, 97.7% (95% CI 93.6-101.8%; APS patients with Protac, 66.0% (95% CI 59.5-72.6%); and non-APS patients with Protac, 80.7 (95% CI 74.2-87.2%). APS patients also had a higher frequency and higher levels of anti-protein C antibodies, with 60% (15/25) high-avidity antibodies. High-avidity anti-protein C antibodies were associated with greater APCr and with a severe thrombotic phenotype (defined as the development of recurrent VTE while patients were receiving therapeutic anticoagulation or both venous and arterial thrombosis). Twelve of 15 (80%) patients with high-avidity anti-protein C antibodies were classified as APS category I.. Thrombotic APS patients showed greater APCr to both rhAPC and activation of endogenous protein C by Protac. High-avidity anti-protein C antibodies, associated with greater APCr, may provide a marker for a severe thrombotic phenotype in APS. However, in patients with category I APS, it remains to be established whether anti-protein C or anti-β2 -glycoprotein I antibodies are responsible for APCr.

Topics: Activated Protein C Resistance; Adult; Aged; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Biomarkers; Blood Coagulation Tests; Case-Control Studies; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Fibrinolytic Agents; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Peptides; Phenotype; Protein C; Recombinant Proteins; Severity of Illness Index; Venous Thromboembolism; Warfarin

Activated protein C resistance assays can detect factor V Leiden with high accuracy, depending on the method used. Factor Xa inhibitors such as rivaroxaban and direct thrombin inhibitors including dabigatran, argatroban, and bivalirudin can cause falsely normal results. Lupus anticoagulants can cause incorrect results in most current assays. Assays that include dilution into factor V-deficient plasma are needed to avoid interference from factor deficiencies or elevations, which can arise from a wide variety of conditions such as warfarin, liver dysfunction, or pregnancy. The pros and cons of the currently available assays are discussed.

Topics: Activated Protein C Resistance; Adult; Antithrombins; Arginine; Benzimidazoles; beta-Alanine; Biological Assay; Blood Coagulation Tests; Child; Dabigatran; Factor V; Factor Xa; False Positive Reactions; Female; Hirudins; Humans; Lupus Coagulation Inhibitor; Morpholines; Peptide Fragments; Pipecolic Acids; Pregnancy; Protein C; Recombinant Proteins; Rivaroxaban; Sulfonamides; Thiophenes; Warfarin

Mesenteric venous thrombosis (MVT) is a rare but life threatening form of bowel ischemia. It is implicated in 6%-9% of all cases of acute mesenteric ischemia. The proportion of patients with primary (or idiopathic) MVT varies from 0% to 49%, with a decrease in frequency secondary to more recent availability of newer investigations for hypercoagulability. The presence of factor V Leiden (FVL) and prothrombin G20210A mutations (PGM) have been well documented in these cases. However, there have been scarce case reports describing MVT in heterozygotes of both these mutations occurring simultaneously and its implications on long term management. Our case describes acute MVT in a previously asymptomatic young patient with no prior history of venous thromboembolism. The patient was found to be heterozygous for FVL and PGM and treated with lifelong anticoagulation with warfarin (goal international normalized ratio: 2-3) and avoidance of hormonal contraceptives.

Topics: Activated Protein C Resistance; Anticoagulants; Blood Coagulation; DNA Mutational Analysis; Factor V; Female; Genetic Predisposition to Disease; Heterozygote; Humans; International Normalized Ratio; Ischemia; Mesenteric Ischemia; Mesenteric Vascular Occlusion; Mesenteric Veins; Mutation; Phenotype; Phlebography; Prothrombin; Tomography, X-Ray Computed; Vascular Diseases; Venous Thrombosis; Warfarin; Young Adult

We present a case report of a young man with spontaneous deep venous thrombosis. He tested positive for heterozygote factor V Leiden mutation and was treated with warfarin. However, he turned out to be resistant to warfarin, and another venous thrombosis occurred during the insufficient treatment. The antithrombotic treatment was then successfully replaced by phenprocoumon. This case report emphasizes the importance of critically evaluating the efficacy of a treatment and substitute if proven insufficient.

Topics: Activated Protein C Resistance; Adult; Anticoagulants; Humans; Male; Metabolism, Inborn Errors; Thrombophilia; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) is a disease with a high prevalence in elderly people, affecting > 5% of the population > 65 years of age. Cancer patients have a 4.3-fold higher incidence of thrombotic complications, due to multiple risk factors that are not always related to the disease. Among hematologic malignancies, multiple myeloma (MM) confers a high risk of developing such complications, with a VTE rate of nearly 10%. Multiple factors are involved in MM-related VTE, such as increased blood viscosity, high levels of immunoglobulin, procoagulant activity of monoclonal protein, and inflammatory cytokines. Since the introduction of the immunomodulatory derivatives (IMiDs) thalidomide and lenalidomide in the therapeutic armamentarium of MM, VTE has emerged as one of the leading complications, in particular in patients with newly diagnosed MM. In this setting, IMiDs-based treatments are associated with rates of VTE reaching values up to 14 to 26%, particularly when dexamethasone or chemotherapy are added. The optimal prophylaxis for patients receiving these antiangiogenetic agents is still a matter of debate. Due to the lack of prospective randomized clinical trials, different studies have used various anticoagulant prophylaxes, including fixed low-dose warfarin (1 mg or 1.25 mg), therapeutic doses of warfarin (international normalized ratio between 2.0 and 3.0), low molecular weight heparin, or low-dose aspirin. As yet, no study has clearly demonstrated a significant superiority of one prophylactic regimen in comparison with the others. Further investigation and more randomized clinical trials are needed to define the best thromboprophylaxis.

Topics: Activated Protein C Resistance; Aged; Anticoagulants; Aspirin; Boronic Acids; Bortezomib; Dexamethasone; Humans; Immunologic Factors; International Normalized Ratio; Lenalidomide; Multiple Myeloma; Proteasome Inhibitors; Pyrazines; Risk Factors; Thalidomide; Thrombosis; Venous Thromboembolism; Warfarin

A 45-year-old man with heterozygous Factor V Leiden presented with his third cerebrovascular accident despite being on warfarin at a therapeutic international normalized ratio. Subsequent investigation revealed a second genetic diagnosis of Fabry disease. He then had an acute myocardial infarction whilst on aspirin and warfarin.

Topics: Activated Protein C Resistance; alpha-Galactosidase; Aspirin; Atorvastatin; Coronary Stenosis; Defibrillators, Implantable; Drug Therapy, Combination; Enzyme Replacement Therapy; Fabry Disease; Factor V; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Metoprolol; Middle Aged; Perindopril; Pyrroles; Quality of Life; Recurrence; Sequence Deletion; Stents; Stroke; Stroke Rehabilitation; Thrombophilia; Warfarin

Reported here is a 22-year-old professional wrestler who was diagnosed to have Paget-Schroetter syndrome after Greco-Roman wrestling. On substantial neuromuscular examination and laboratory testing, he was found to have also thoracic outlet syndrome and heterozygous mutations for factor V Leiden and methyltetrahydrofolate reductase genes. To the best knowledge of the authors, the concomitance of these pathologies is discussed for the first time in the literature.

Topics: Activated Protein C Resistance; Anticoagulants; Aspirin; Enoxaparin; Factor V; Heterozygote; Humans; Magnetic Resonance Angiography; Male; Methylenetetrahydrofolate Reductase (NADPH2); Occupational Diseases; Subclavian Vein; Thoracic Outlet Syndrome; Thrombophilia; Upper Extremity Deep Vein Thrombosis; Warfarin; Wrestling; Young Adult

Topics: Activated Protein C Resistance; Adult; Androgens; Anticoagulants; Causality; Erectile Dysfunction; Factor V; Gynecomastia; Humans; Hypogonadism; International Normalized Ratio; Klinefelter Syndrome; Male; Medication Adherence; Pulmonary Embolism; Testis; Testosterone; Ultrasonography; Venous Thrombosis; Warfarin

Several studies suggest that antiphospholipid antibodies interfere with the activity of activated protein C (APC). This acquired form of APC resistance has been proposed as a possible pathogenic mechanism underlying hypercoagulability associated with the antiphospholipid syndrome (APS).. We wanted to investigate the inhibitory effect of recombinant APC (rAPC) on ex vivo thrombin generation in plasma and the modification of this effect by the presence of lupus anticoagulants (LA).. We analyzed plasmas from 81 patients with LA (52 patients fulfilling the criteria for the APS) and 91 controls. Percent inhibition of the endogenous thrombin potential (ETP) as a parameter of APC sensitivity was determined in plasmas using a thrombin generation-based APC resistance test probed with rAPC. All results were normalized using pooled normal plasma (PNP) as a reference.. Normalized percent inhibition of ETP by APC was lower in patients with LA [61.4%, 95% confidence interval (CI) 45.8-74.5%] compared to controls (107.8%, 95% CI: 107.1-109.3%). In patients with LA and APS, median inhibition was lower than in patients with LA without APS (44.6%, 95% CI: 30.1-55.7% vs. 78.8%, 95% CI: 73.9-95.8%). This difference also persisted when patients on warfarin therapy were excluded from the APS subgroup.. APC resistance can be demonstrated with a thrombin generation-based test in a majority of patients with the LA laboratory phenotype. A history of thrombotic events in patients with LA is associated with a stronger resistance to the anticoagulant effect of APC.

Topics: Activated Protein C Resistance; Adult; Antiphospholipid Syndrome; Blood Coagulation Tests; Case-Control Studies; Female; Humans; Lupus Coagulation Inhibitor; Male; Middle Aged; Protein C; Recombinant Proteins; Thrombin; Thrombophilia; Thrombosis; Warfarin

Topics: Activated Protein C Resistance; Anticoagulants; Factor V; Fluorescein Angiography; Heparin; Humans; Point Mutation; Protein S Deficiency; Retinal Vein Occlusion; Warfarin

Polycythemia Vera (PV) and Essential Thrombocythemia (ET) are chronic myeloproliferative disorders complicated by a high incidence of thrombotic complications. Extensive coagulation studies failed to demonstrate a consistent pattern of abnormalities associated with thrombosis. Recently, a poor anticoagulant response to activated protein C (APC), due to a mutation of factor V (FV Leiden), has been identified as the most frequent hereditary disorder associated with venous thrombophilia. We investigated in 304 patients with PV and ET whether the presence of FV Leiden could be a risk factor for thrombosis. FV Leiden was found in 14/304 patients (4.6%) and was associated with venous thromboembolism (VTE) occurred before and at diagnosis (5/27,16%, with a significant difference of prevalence in comparison of that observed in asymptomatic patients, 9/263, 3%, p = 0.003). Carriership of FV Leiden was associated with VTE relapse, with a prevalence of 3.6% in asymptomatic patients, 6.9% in patients with a single episode of VTE and 18.1% in patients with recurrent VTE. The prevalence of FV Leiden in patients with and without arterial thrombosis was similar (5/79, 6% and 9/211, 4%, respectively, p = 0.337). This study indicates that the prevalence of the FV Leiden mutation in patients with PV and ET is comparable with that observed in the general population. FV Leiden mutation is a risk factor for VTE before and at time of diagnosis and for VTE recurrences. Screening for FV Leiden may be considered to identify PV and ET patients at higher risk of recurrences.

Topics: Activated Protein C Resistance; Anticoagulants; Austria; Cardiovascular Diseases; Cohort Studies; Comorbidity; Factor V; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Male; Middle Aged; Polycythemia Vera; Prevalence; Recurrence; Risk Factors; Thrombocythemia, Essential; Thrombophilia; Venous Thrombosis; Warfarin

To report nonarteric anterior ischemic optic neuropathy (NAION) as an ocular manifestation in a woman with combined primary antiphospholipid syndrome and Factor V Leiden (FVL) mutation.. Case report of a middle-aged woman with hematological investigations confirming the diagnosis of both primary antiphospholipid syndrome and Factor V Leiden mutation, who presented with visual disturbance in her left eye.. NAION was noted in her left eye. The patient was promptly treated with low molecular weight heparin, followed by warfarin, which resulted in the reversal of the ischemic optic neuropathy.. Primary antiphospholipid syndrome and coexisting Factor V Leiden mutation should be considered in the differential diagnosis of NAION. Prompt treatment with anticoagulants can result in the reversal of the ischemic process.

Topics: Activated Protein C Resistance; Anticoagulants; Antiphospholipid Syndrome; Arteritis; Enzyme-Linked Immunosorbent Assay; Factor V; Female; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Optic Neuropathy, Ischemic; Point Mutation; Polymerase Chain Reaction; Warfarin

To determine the prevalence of endogenous and exogenous risk factors for venous thrombosis in patients with upper limb deep vein thrombosis (DVT), and to evaluate the risk of clinically detectable pulmonary embolus, recurrent DVT, and postphlebitic symptoms in these patients.. A combined prospective and retrospective descriptive analysis of a cohort of patients with upper limb DVT compared with age- and sex-matched patients with lower limb DVT.. Internal medicine departments, and hematology and vascular surgery outpatient clinics at a tertiary-care university hospital.. Consecutive patients with "spontaneous" upper limb DVT diagnosed between 1989 and 1997 were studied. Twenty age- and sex-matched patients with lower limb DVT admitted to the hospital via the emergency department served as control patients.. Eighteen patients with upper limb DVT were studied. An endogenous risk factor (thrombophilia) was present in 11 of 18 patients vs 8 of 20 control patients (p = not significant). In the upper limb group, nine patients had activated protein C resistance, four patients had anticardiolipin antibodies, and two patients had both forms of thrombophilia. Furthermore, 14 of the upper limb DVT patients were found to have an exogenous risk factor for thrombosis compared with 7 of the patients with lower limb DVT (p = 0.01), and 66.6% of patients with upper limb DVT had both an exogenous and an endogenous risk factor for thrombosis vs 15% of patients with lower limb DVT (p < 0.002). No clinically detectable pulmonary emboli occurred among the upper limb DVT patients. Three patients have minor postphlebitic symptoms. Two patients experienced recurrent DVT.. In the majority of patients with upper limb DVT that we studied in this relatively small study, exogenous (environmental) or endogenous risk factors for venous thrombosis, or a combination of both, were found. Furthermore, in our patients, these thromboses had a low propensity to cause clinically significant pulmonary embolus and did not cause significant postphlebitic symptoms. Finally, we suggest that anticoagulant therapy for these thromboses may be adequate and that thrombolytic agents and surgical intervention are not routinely indicated.

Topics: Activated Protein C Resistance; Adult; Aged; Antithrombin III Deficiency; Drug Therapy, Combination; Enoxaparin; Female; Fibrinolytic Agents; Humans; Leg; Male; Middle Aged; Phlebography; Pregnancy; Prospective Studies; Protein S Deficiency; Recurrence; Retrospective Studies; Risk Factors; Streptokinase; Thrombolytic Therapy; Thrombophilia; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin

To investigate a case of a young woman with both primary antiphospholipid syndrome and factor V Leiden mutation who developed multiple retinal arteriolar occlusions.. Case report of a 25-year-old woman with history and laboratory tests confirming the diagnosis of both primary antiphospholipid syndrome and factor V Leiden mutation who presented with blurred vision in both eyes.. Multiple retinal arteriolar occlusions were observed in both of her eyes. The patient was treated first with heparin and then with warfarin.. Primary antiphospholipid syndrome and factor V Leiden mutation, as well as other forms of thrombophilia, should be considered in the differential diagnosis of unexplained retinal vascular occlusions. The coexistence of several thrombophilic disorders may carry a particularly high risk for thrombotic manifestations.

Topics: Activated Protein C Resistance; Adult; Antiphospholipid Syndrome; Arterioles; Factor V; Female; Fluorescein Angiography; Heparin; Humans; Point Mutation; Retinal Artery Occlusion; Warfarin

Topics: Abdominal Muscles; Activated Protein C Resistance; Anticoagulants; Dyspnea; Ecchymosis; Factor V; Hemothorax; Humans; Male; Middle Aged; Point Mutation; Venous Thrombosis; Warfarin

Clotting-based activated protein C (APC) assays have limitations when testing patients on oral anticoagulant (OA) therapy or with a lupus anticoagulant (LA). Predilution in factor V (FV)-deficient plasma and testing with phospholipid-rich Russell Viper venom (RVV)-based methods have been shown to be the most suitable methods when testing these patient groups, respectively. We evaluated a modified RVV based clotting test (Gradileiden V test; Gradipore, Sydney, Australia) in a large patient cohort and determined its sensitivity to the FV Leiden mutation. We also examined whether normal plasma can be used to dilute plasma from warfarinized patients without compromising sensitivity to the FV Leiden mutation. A total of 1,956 plasmas were studied including congenital protein C (five plasmas), and protein S deficiency (five plasmas), LA (29 plasmas), FV Leiden heterozygote (102 plasmas), and homozygote (five plasmas), warfarin (54 plasmas), standard heparin therapy (37 plasmas) and normal healthy controls (21 plasmas). Molecular analysis was performed on all samples. The effect of FV Leiden concentration on the APC ratio was examined by determining the APC resistance of a homozygous plasma serially diluted in six sources of normal plasma (NP). The relationship was non-linear and dependent on the initial APC ratio of the chosen source of NP. APC resistance was demonstrated in the varying sources of NP in dilutions of 1/4 (25% FV Leiden) to 1/32 (3% FV Leiden). A 1/2 dilution in pooled NP is recommended for patients on OA therapy because the test remains sensitive at levels of 25% FV Leiden and this is the dilution routinely used for other applications in a coagulation laboratory. The effect of a LA on the APC ratio was similarly studied by determining the APC resistance of a homozygous plasma serially diluted in two sources of LA-positive plasma. This relationship was also non-linear and dependent on the initial APC ratio of the LA-positive plasma. APC resistance was demonstrated in dilutions of 1/16 (6% FV Leiden) to 1/64 (1.5% FV Leiden) demonstrating the sensitivity of the test to APC resistance in the presence of a LA. Our results show the modified RVV-based test clearly predicts the presence of factor V Leiden in a large cohort of patients. The method offers advantages when testing patients with a LA and patients receiving warfarin providing a 1/2 predilution step in pooled NP is performed. Pooled NP does not affect the sensitivity of the test to the mutati

Topics: Activated Protein C Resistance; Anticoagulants; Factor V; Heparin; Heterozygote; Homozygote; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Mutation; Protein C; Protein S Deficiency; Warfarin

A method for detecting activated protein C (APC)-resistant factor V, especially factor V Leiden, is described, which uses reagents containing two unfractionated snake venoms. The procedure can be used for testing plasma samples from patients receiving oral anticoagulant therapy, heparin therapy and patients with lupus anticoagulant, and does not require the use of factor-V-deficient plasma. The sample plasma is first incubated with dilute venom from Agkistrodon contortrix contortrix (Southern Copperhead) which activates the endogenous protein C and then a dilute Russell's viper venom time test is performed. In individuals with APC-resistant factor V, especially factor V Leiden, a marginal prolongation of dilute Russell's viper venom time was noted [1.14 +/- 0.14 s (n = 16)]. Non-carriers were easily discriminated in each patient group, with a prolongation of 2.69 +/- 0.30 s for normal blood donors (n = 127), 2.61 +/- 0.38 s for patients taking oral anticoagulants (n = 102), 2.41 +/- 0.45 s for patients taking heparin (n = 96), and 2.38 +/- 0.41 s for patients with lupus anticoagulant (n = 22). Patients taking oral anticoagulants with moderate prolongation (between 1.5- and 2.0-fold) may have low levels of functional protein C and this might additionally indicate a subgroup of such patients at higher than normal thrombotic risk.

Topics: Activated Protein C Resistance; Agkistrodon; Animals; Blood Coagulation; Crotalid Venoms; Factor V; Heparin; Heterozygote; Homozygote; Humans; Kinetics; Lupus Coagulation Inhibitor; Point Mutation; Protein C; Protein S; Warfarin

Resistance to activated protein C, caused by a single point mutation in the factor V gene (Arg506Gln or FV Leiden), is the most prevalent single risk factor associated with venous thromboembolic disease. The aim of this study was to investigate the effectiveness of standard oral anticoagulant therapy (OAT) in patients with the Arg506Gln mutation compared with a matched control group. The study compared selected variables in 27 patients carrying the Arg506Gln mutation with 27 sex- and age-matched controls in steady state oral anticoagulant treatment (OAT). The study showed that similar doses of vitamin K antagonists in carriers and noncarriers suppress and generate a uniform distribution of coagulation markers in steady state OAT. Thus, it seems that OAT with standard treatment doses is just as effective in patients with the Arg506Gln mutation as in comparable controls without the mutation.

Topics: Activated Protein C Resistance; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Arginine; Case-Control Studies; Factor V; Female; Glycine; Humans; Immunoenzyme Techniques; Linear Models; Male; Middle Aged; Phenprocoumon; Point Mutation; Polymerase Chain Reaction; Statistics, Nonparametric; Warfarin