Lower Limb Deep Venous Thrombosis After Posterior Spinal Fusion as an Initial Manifestation of Factor V Leiden Mutation in a Pediatric Patient: A Case Report.

Deep venous thrombosis (DVT) is a serious condition in which a blood clot forms in a deep vein, usually of the lower extremity. In pediatric orthopedic surgery, the incidence of thrombotic events is rare. This is a case presentation of a 12-year-old female patient without previous events or a family history of thrombotic events who underwent a posterior spinal fusion due to severe adolescent idiopathic scoliosis. The patient developed a DVT due to an underlying Factor V Leiden mutation. The purpose of this case report is to create awareness, facilitate the diagnosis and management, and aid in future interventions and clinical outcomes.

Triple whammy in a patient with portal vein thrombosis.

Infection with SARS-CoV-2 has been shown to predispose to thromboembolic events. The risk of such thromboses further increases in those with underlying inherited or acquired prothrombotic states. The authors present a 30-year-old lady who developed acute abdominal pain, three days after recovery from a mild COVID-19 infection. She was also using oral contraceptive pills. Laboratory investigations revealed elevated inflammatory markers, and a contrast-enhanced abdominal CT scan demonstrated portal vein thrombosis (PVT). Due to the unusual site of thrombosis, a thrombophilia screen was performed, which detected a heterozygous Factor V Leiden mutation (FVL). Thus, her PVT was attributed three simultaneous risk factors, namely COVID-19 infection, OCP use and FVL mutation. She was initiated on anti-coagulation, with which she improved significantly. In patients presenting with thromboses at uncommon sites, investigation for evidence of recent Covid-19 infection and screening for inherited and acquired thrombophilia should be considered, while discontinuing any offending medications.

Successful microvascular surgery in patients with thrombophilia in head and neck surgery: a case series.

BACKGROUND: In this case series, a perioperative anticoagulation protocol for microvascular head and neck surgery in patients with thrombophilia is presented. Microvascular free-flap surgery is a standard procedure in head and neck surgery with high success rates. Nevertheless, flap loss-which is most often caused by thrombosis-can occur and has far-reaching consequences, such as functional impairment, prolonged hospitalization, and increased costs. The risk of flap loss owing to thrombosis is significantly increased in patients with thrombophilia. Therefore, perioperative anticoagulation is mandatory. To date, no perioperative anticoagulation protocol exists for these high-risk patients. CASE PRESENTATION: We present three exemplary male Caucasian patients aged 53-57 years with free flap loss owing to an underlying, hidden thrombophilia. CONCLUSION: We present a modified anticoagulation protocol for microvascular surgery in these high-risk patients, enabling successful microsurgical reconstruction.

Prevention of thromboembolic events after radical prostatectomy in patients with hereditary thrombophilia due to a factor V Leiden mutation by multidisciplinary coagulation management.

Objective: To examine the perioperative impact of factor V Leiden mutation on thromboembolic events' risk in radical prostatectomy (RP) patients. With an incidence of about 5%, factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia. The increased risk of thromboembolic events is three- to seven-fold in heterozygous and to 80-fold in homozygous patients. Methods: Within our prospectively collected database, we analysed 33 006 prostate cancer patients treated with RP between December 2001 and December 2020. Of those, patients with factor V Leiden mutation were identified. All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation. Thromboembolic complications (deep vein thrombosis and pulmonary embolism) were assessed during hospital stay, as well as according to patient reported outcomes within the first 3 months after RP. Results: Overall, 85 (0.3%) patients with known factor V Leiden mutation were identified. Median age was 65 (interquartile range: 61-68) years. There was at least one thrombosis in 53 (62.4%) patients and 31 (36.5%) patients had at least one embolic event in their medical history before RP. Within all 85 patients with factor V Leiden mutation, we experienced no thromboembolic complications within the first 3 months after surgery. Conclusion: In our cohort of patients with factor V Leiden mutation, no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept. This may reassure patients with this hereditary condition who are counselled for RP.

Determination of vWF, ADAMTS-13 and Thrombospondin-1 in Venous Thromboembolism and Relating Them to the Presence of Factor V Leiden Mutation.

Thrombophilia in venous thromboembolism (VTE) is multifactorial. Von Willebrand factor (vWF) plays a major role in primary hemostasis. While elevated vWF levels are well documented in VTE, findings related to its cleaving protease (ADAMTS-13) are contradicting. The aim of this study was to determine vWF, ADAMTS-13, and the multifactorial Thrombospondin-1 (TSP-1) protein levels in patients after 3-6 months following an unprovoked VTE episode. We also explored a possible association with factor V Leiden (FVL) mutation. vWF, ADAMTS-13 and TSP-1 were analyzed using ELISA kits in 60 VTE patients and 60 controls. Patients had higher levels of vWF antigen (P = .021), vWF collagen-binding activity (P = .008), and TSP-1 protein (P < .001) compared to controls. ADAMTS-13 antigen was lower in patients (P = .046) compared to controls but ADAMTS-13 activity was comparable between the two groups (P = .172). TSP-1 showed positive correlation with vWF antigen (rho = 0.303, P = .021) and negative correlation with ADAMTS-13 activity (rho = -0.244, P = .033) and ADAMTS-13 activity/vWF antigen ratio (rho = -0.348, P = .007). A significant association was found between the presence of FVL mutation and VTE (odds ratio (OR): 9.672 (95% confidence interval (CI) 2.074-45.091- P = .004), but no association was found between the mutation and the studied proteins (P > .05). There appears to be an imbalance between vWF and ADAMTS-13 in VTE patients even after 3-6 months following the onset of VTE. We report that the odds of developing VTE in carriers of FVL mutation are 9.672 times those without the mutation, but the presence of this mutation is not associated with the studied proteins.

The Combined Heterozygosity of Factor V Leiden and G20210A Prothrombin Gene Mutation in a Patient With Venous Thromboembolism.

Venous thromboembolism (VTE) is a chronic illness that includes pulmonary embolism (PE) and deep vein thrombosis (DVT), and many risk factors are associated. Anticoagulation therapy remains the cornerstone of venous thromboembolism management, and the duration of anticoagulation depends on the risk of venous thromboembolism. We report a case of a female with a combined heterozygosity of factor V Leiden and G20210A prothrombin gene mutation.

Cocaine Abuse as an Immunological Trigger in a Case Diagnosed with Eales Disease.

Background: Eales disease is a clinical syndrome affecting the mid-peripheral retina with an idiopathic occlusive vasculitis and possible subsequent retinal neovascularization. The disease can develop into visually threatening complications. Case Presentation: We report the case of a 40-year-old Caucasian male with a history of cocaine abuse who presented with blurred vision in the left eye (LE). Fundus examination showed vitreous hemorrhages, peripheral sheathing of venous blood vessels, areas of retinal neovascularization in the LE, and peripheral occlusive phlebitis in the right eye. The full serologic panel was negative except for the heterozygous mutation of factor V Leiden. Clinical and biochemical parameters suggested a diagnosis of Eales disease. Therapy with dexamethasone, 1 mg per kg per day, tapered down slowly over 4 months, and peripheral laser photocoagulation allowed a regression of clinical signs and symptoms. Conclusion: This case shows an uncommon presentation of Eales disease associated with cocaine abuse. Both cocaine abuse and a thrombophilic pattern, as cofactors, might have sensitized the retinal microcirculation on the pathogenetic route to this retinal pathology. Furthermore, in view of this hypothesis, a thorough ocular and general medical history investigating drug abuse and coagulation disorders is recommended for ophthalmologists in such cases.

Post-COVID myocarditis simulating acute coronary syndrome: Case report.

Acute myocarditis corresponds to an acute inflammation of the myocardium whose origin is most often viral. Several viruses can be incriminated to note the parvovirus B19, the virus herpes of the group 6 and to a lesser degree the virus of the hepatitis C (VHC). Since 2019 and with the discovery of SARS COV2 some cases of myocarditis associated with COVID have been noted, this last association is rare and is present in only 5% of cases. The diagnosis of myocarditis is sometimes difficult and can lead to confusion with acute coronary syndrome, especially in cases of ST-segment elevation on the EKG, hence the interest of magnetic resonance imaging, which has made it possible in recent years to reduce the rate of unnecessary coronary angiography, especially in the case of young subjects with no cardiovascular risk factors. Here, we report the case of a 33-year-old patient with no cardiovascular risk factors and no medical or surgical antecedents who was admitted to the emergency department for the management of acute chest pain, the patient had initially undergone an electrocardiogram which showed an ST-segment elevation in the inferior territory and in the low lateral territory with a mirror image in the high lateral territory. In view of the typical character of the pain and based on the electrical data, it was decided to carry out a coronary angiography which came back without any particularity. As part of the etiological work-up, an MRI scan was performed, which showed an appearance compatible with viral myocarditis. This case shows diagnostic difficulties and management of this disease.

Tranexamic acid is safe and effective in patients with heterozygous factor V Leiden mutation during total joint arthroplasty.

INTRODUCTION: Patients with an inherent hypercoagulable state are at a higher risk of venous thromboembolism (VTE) following total joint arthroplasty (TJA). Further administration of tranexamic acid (TXA) during TJA may increase the risk of VTE in these high-risk patients. There is no study that specifically analyzes the safety and efficacy of TXA during TJA in patients with factor V Leiden (FVL) mutation; therefore, the purpose of this study was to evaluate the safety and efficacy of TXA use on the risk of VTE and bleeding in patients carrying FVL mutation. MATERIALS AND METHODS: A total of 42 patients with FVL mutation (22 hips, 20 knees) and 40 control patients (20 hips, 20 knees) who underwent TJA were retrospectively reviewed. All patients received 1 g TXA intravenously 15 min before the skin incision and 2 g of TXA was administered locally at the surgical site as a periarticular injection. Pharmacological thromboprophylaxis (low-molecular-weight heparin) was administered to all patients. Estimated blood loss and in-hospital thromboembolic complications were compared between the groups. RESULTS: In both total knee arthroplasty (TKA) and total hip arthroplasty (THA) patients, there was no significant difference in the amount of estimated blood loss among the groups (p = 0.980, and p = 0963, respectively). None of the patients in the THA group received a blood transfusion. The transfusion rate was similar in the TKA group (p = 0.756, one patient in each group). No VTE, myocardial infarction, or any other complications related to TXA use were observed in any of the patients. CONCLUSIONS: The combined local and systemic administration of TXA could be safely used in patients with heterozygous FVL mutation receiving pharmacological thromboprophylaxis during TJA without increasing the risk of VTE.

Homozygous factor V leiden mutation: Rare etiology of pulmonary embolism.

Introduction and importance: Venous thromboembolic disease (VTE), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), is a major public health problem with high morbidity and mortality. The main risk factors for VTE are surgery, active cancer, immobilization, trauma or fracture, pregnancy and estrogen therapy. Genetic risk factors are also present and are dominated by the factor V Leiden mutation, which is present in 20% of VTE and in 2-5% of the general population with an annual incidence of 0.1% (Margaglione and Grandone, 2011; Ridker et al., 1995) [4,5]. This mutation can be heterozygous or homozygous, which is rarer. In this context, we report the case of a 37-year-old patient with no medical or surgical history and no notable risk factors who was admitted to the emergency room for the management of acute dyspnea at rest in connection with a bilateral proximal pulmonary embolism originating from a homozygous factor V Leiden mutation.Despite the efforts of the World Health organization, pulmonary embolism remains a major cause of morbidity and mortality in our days, and the etiological assessment is performed in a very few cases, which makes the management standardized and not specific. That is why it is important to make an etiological assessment in a systematic way especially in young subjects for an optimal management and to avoid recurrences. Case presentation: Here, we report a rare case of a 37-year-old patient, who was admitted for the management of resting dyspnea related to bilateral proximal pulmonary embolism, in whom the etiological work-up was in favor of a homozygous factor V Leiden mutation. This case shows diagnostic difficulties and management of this rare disease.

A Peculiar Case of Recurrent Coronary Artery Thrombosis.

Coronary artery thrombosis is a phenomenon physicians have studied throughout the years. The different risk factors that play a role in the formation of an atherosclerotic plaque leading to coronary artery blockage are vast and can affect the patient significantly if not examined and diagnosed carefully. The objective of this case report is to highlight this unusual occurrence of repeated coronary artery thrombosis. A 54-year-old Caucasian female presented to the emergency department with a one-day history of sharp chest pain in the substernal area that radiated between her shoulder blades and left arm. Despite being on dual antiplatelet therapy, an electrocardiogram (ECG) showed an inferior ST-elevation myocardial infarction (STEMI). Her medical history was extensive with factor V Leiden deficiency, hyperhomocysteinemia, recurrent deep vein thrombosis (DVT), and a family history of myocardial infarction. The patient was taken to the cardiac catheterization lab based on these characteristics. The patient was diagnosed with a 100% thrombosis in the distal right coronary artery (RCA), which was stented nine months before this current presentation. The patient had been compliant with all her medications from her previous stent placement. A new drug-eluting stent (DES) was inserted, and the patient was placed on prasugrel and apixaban. This was a very interesting topic for a case report due to the time frame of repeat thrombosis in a coronary artery with a DES and the patient's underlying hypercoagulable state. There are few cases of same vessel restenosis post-DES placement. Our case highlights the need for further research into the prevalence of genetic risk factors in coronary artery thrombosis and the need to investigate the efficacy of different anticoagulation therapies in patients with factor V Leiden thrombophilia.

Current Knowledge on Factor V Leiden Mutation as a Risk Factor for Recurrent Venous Thromboembolism: A Systematic Review and Meta-Analysis.

Background: Thrombophilia screening is widely done in clinical practice, and it is claimed that the extent of venous thromboembolism (VTE) recurrence risk in patients with common defects is still not fully understood. Aim: We aimed to summarize data of all observational studies prospectively assessing the association of heterozygous factor V Leiden (FVL) mutation and recurrent VTE in patients with VTE, and to calculate pooled relative risks (RR), overall and in various subgroups. Methods: We searched MEDLINE and EMBASE databases for cohort studies prospectively assessing VTE recurrence in patients with and without FVL mutation (PROSPERO: CRD42021182800). Data were extracted on cohort and study-level. The methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). RR were calculated overall and in subgroups using a random-effects model. Results: From 31 cohorts, 24 studies were finally included summarizing 13,571 patients. Heterozygous FVL mutation was identified in 2,840 individuals (21%). The methodological quality was estimated to be high in 20 studies (83%). The overall RR was 1.46 (95% CI: 1.31, 1.64), consistent across subgroups. Conclusions: Pooling all high-quality epidemiological data, the risk of recurrent VTE was increased by 46% in patients with heterozygous FVL mutation. Against the background of established risk factors, the FVL mutation plays only a marginal role in the risk assessment for recurrent VTE.

Heterozygous factor V Leiden mutation manifesting with combined central retinal vein occlusion, cilioretinal artery occlusion, branch retinal artery occlusion, and anterior ischaemic optic neuropathy: a case report.

BACKGROUND: Our purpose was to describe a patient who developed combined central retinal vein occlusion (CRVO), cilioretinal artery occlusion, branch retinal artery occlusion (BRAO), and anterior ischaemic optic neuropathy (AION) followed by CRVO in the second eye because of the heterozygous factor V Leiden (FVL) mutation. CASE PRESENTATION: A 39-year-old female with a history of recurrent pregnancy losses presented with acute blurred vision in the right eye (RE), with visual acuity limited to counting fingers. She was diagnosed with combined impending CRVO, cilioretinal artery occlusion, BRAO, and AION. The results of thrombophilia testing, not including the FVL mutation, were negative. Retinal atrophy with vascular attenuation and optic disc pallor developed after resolution of acute retinal findings. Nine months after initial presentation, the patient developed an impending CRVO in the left eye (LE), with a secondary progression to a complete CRVO causing a decrease in best corrected visual acuity (BCVA) to 20/40. The patient was determined to be heterozygous for the FVL mutation. She subsequently was treated with acenocoumarol. At the last follow-up visit, the BCVA was 20/400 in the RE and 20/20 in the LE, and there was a complete resolution of the acute CRVO findings in the LE. CONCLUSION: Our case shows that the heterozygous FVL mutation may manifest with combined retinal vascular occlusion involving multiple sites in both eyes. Early recognition of such an inherited thrombophilic disorder is important because it implies the need for long-term anticoagulative therapy to reduce the patient's risk of recurrent, sight-threatening and life-threatening thrombotic events.

Factor V Leiden G1691A and Prothrombin Gene G20210A Mutations on Pregnancy Outcome.

Factor V Leiden (FVL) G1619A mutation and prothrombin gene (PTG) G20210A are the most common inherited thrombophilias. They have been associated with various obstetric complications such as venous thromboembolism, recurrent pregnancy loss, preeclampsia, abruptio placentae, and small for gestational age fetus. The prevalence of these two mutations is 3-15% in Caucasians and is assumed to be far less common in other ethnic populations. However, there have been several controversies regarding advising routine screening of these thrombophilias because of a widely variable strength of association between different ethnic groups, as well as contradictory conclusions by different studies in regards to the association. In this study, the literature was analyzed thoroughly for the effect of FVL G1619A and PTG G20210A mutations on various obstetric outcomes. A review of multiple case-control and prospective studies suggests that despite the availability of robust data on this subject the results remain inconclusive and insubstantial. Further superior quality research, preferably prospective studies, is warranted to conclusively establish this relationship and to enable practitioners to follow a definitive protocol in the screening of various populations for these mutations to achieve an improved pregnancy outcome.

Arterial Thrombosis Associated with Factor V Leiden Mutation in a Child with Nephrotic Syndrome.

Thromboembolism remains a common complication of nephrotic syndrome (NS) in adults and a less common complication in children. Venous thrombosis is well recognized, but arterial thrombosis occurs less frequently and is seen primarily in children. We report a case of arterial thrombosis associated with factor V Leiden (FVL) mutation in a young girl with NS. Screening for inherited thrombophilias such as FVL mutation may be beneficial for NS patients with thromboembolic vascular events not explained by conventional risk factors.

Three-factorial Genetic Thrombophilia with Recurrent Thrombotic Events in a Saudi Patient: A Case Report.

Thrombophilia is caused by several genetic and acquired factors. Existence of more than one genetic factor may increase the risk of developing recurrent thrombotic events. Here, we present a case of a 48-year-old male with a known history of deep venous thrombosis and a known mutation in factor V Leiden combined with mild protein S deficiency, who presented with a painful swelling in the left leg. Moreover, the patient had a history of diabetes, dyslipidemia and obesity. Prothrombin time and platelet count were within the normal range. The international normalized ratio and activated partial thromboplastin time were 3.21 and 36.7 s, respectively. The Doppler study showed a thrombus in the saphenous vein, and complementary genetic screening investigations revealed heterozygous mutation for prothrombin (G20210A). A diagnosis of multifactorial genetic thrombophilia was established. The patient was treated with warfarin, which resulted in significant improvement in the follow-ups, and at the time of reporting this case, there were no clinical or biological signs of thrombosis. The presence of multiple hereditary and acquired thrombophilic factors is a rare clinical presentation that requires close monitoring, for which a lifelong anticoagulation therapy should be discussed based on the clinical response of the patient.

Choked Vein: Unusual Etiology of Extensive Deep Vein Thrombosis.

Deep venous thrombosis (DVT) is a commonly encountered diagnosis in clinical practice with a variety of established risk factors. Inferior vena cava atresia (IVCA) is a rare vascular anomaly, but an established risk factor, associated with DVT, found in approximately 5% of cases of unprovoked lower extremity DVT in young adults. Patients who develop DVT are at high risk of long-term complications, including DVT recurrence and post-thrombotic syndrome. Thirty percent of inferior vena cava (IVC) anomalies are associated with hypercoagulable conditions in the younger population, Therefore, a hypercoagulable workup is beneficial in this population. We report a rare case of a 31-year-old male who presented with an extensive DVT of bilateral lower extremities secondary to IVC atresia. The treatment of choice for IVC atresia associated with extensive DVT is catheter-directed thrombolysis (CDT), endovascular IVC reconstruction with nitinol stent, and long-term anticoagulation.

Comparative analysis of "APTT vs RVVT" based activated protein C resistance assay in the diagnosis of Factor V Leiden mutation.

BACKGROUND: Thrombophilia is a hypercoagulable state characterized by increased venous thrombosis. The most common cause of heritable thrombophilia is Factor V Leiden (FVR506Q) homozygous state, with a relative risk of 10-80 times as compared to normal individuals and Lupus anticoagulant is the most common cause of acquired thrombophilia. The main objective of this study is to compare the sensitivity of activated partial thromboplastin time (APTT) vs dilute Russell viper venom test (DRVVT) based APCR assays with predilution in Factor V-deficient plasma for diagnosis of Factor V Leiden mutation. MATERIALS AND METHODS: The coagulometer used for APCR test was Sysmex CS-5100. APTT reagent used is Pathrombin SL supplied by Siemens. All data were expressed as mean ± SD. Statistical analysis was done using unpaired students t-test and a P value <0.05 was considered as statistical significance. RESULTS: A total of 300 cases of APCR (200 cases of Factor V Leiden mutation was confirmed by PCR and 100 acquired) were studied. The sensitivity of screening APTT-based APCR for detection of Factor V Leiden mutation is 67% and for the noncarrier state, it is 62%. The sensitivity of modified APTT and DRVVT with predilution in FV-deficient plasma for detection of Factor V Leiden mutation is 82% and 84%, respectively and for acquired causes, it is 48% and 86%, respectively. CONCLUSION: Screening APTT test has increased in activated protein C resistance (APCR) due to Factor V Leiden mutation as well as acquired causes such as patients on direct-acting oral anticoagulants, warfarin, lupus anticoagulants, and oral contraceptive pills which are independent risk factors of venous thrombosis. Modified DRVVT with predilution in FV-deficient plasma is more sensitive than screening and modified APTT-based APCR test in the diagnosis of Factor V Leiden mutation and the former test can distinguish homozygous and heterozygous states from normal individuals.

Factor V Leiden Mutation Frequency and Geographical Distribution in Turkish Population.

BACKGROUND AND OBJECTIVE: Thrombophilia is a term used to define the conditions creating a tendency toward thrombosis. Factor V Leiden (FVL) is the most frequently observed genetic risk factor, and its frequency varies among societies and ethnicities. In this study, our aim is to identify the frequency of FVL mutation in patients with thrombosis, the frequency of FVL mutation for each thrombosis disease, whether there is any difference in the geographical distribution of FVL mutation in the Turkish population, correlation with age and gender, and correlation with arterial and venous thrombosis. METHODS: This is an observational case-control and retrospective study. Cases with the FVL mutation examination with clinical provisional diagnosis of arterial and/or venous thrombosis delivered and with the thrombosis proven by radiological visualization methods and laboratory examinations have been planned to be considered and assessed as cases with thrombosis. RESULTS: A total of 67 patients with thrombosis and 22 patients without thrombosis have been included within the study. Twenty-six of the cases with thrombosis were from the Black Sea region, 21 were from Eastern Anatolia, 12 were from Central Anatolia, 5 were from Marmara, and 3 were from Southeastern Anatolia. Eleven of the cases without thrombosis were from the Black Sea region, 1 was from Eastern Anatolia, 5 were from Central Anatolia, 2 were from Marmara, 1 was from Southeastern Anatolia, and 2 were from the Aegean region. The significance was resulted from the identification of thrombosis prevalence rate as significantly high in the Eastern Anatolian region. DISCUSSION: FVL mutation frequency is quite common in our country, and there are significant differences particularly in terms of regional distribution. Furthermore, FVL mutation is solely not the risk factor for thrombosis, and other coexisting genetic and acquired risk factors are substantial causes for the development of thrombosis.

Anticoagulation Therapy in a Patient With Heterozygous Factor V Leiden and Coexisting Homozygous Prothrombin Gene Mutations.

Coexistent heterozygous factor V Leiden and homozygous prothrombin G20210A gene mutations is a rare and potentially life-threatening occurrence. This inherited thrombophilia often presents as non-specific venous thromboemboli and can mimic a variety of emergent medical conditions. The pathophysiology of the disease has been well documented; however, long-term treatment efficacy remains poorly understood. We report the case of a 25-year-old male presenting with acute chest pain. A comprehensive workup revealed bilateral pulmonary emboli arising in part from concomitant heterozygous factor V Leiden and homozygous prothrombin G20210A gene mutations. Immediate and continuous treatment with anticoagulants enoxaparin and apixaban significantly reduced the patient's symptoms and D-dimer within one week. This case provides insight into an effective treatment regimen for this rare and inherited thrombophilia.