Leiden Mutation Research Articles

Factor V Leiden mutation and acquired activated protein C resistance in Indian women with recurrent fetal loss

Objectives: To study the prevalence and association of factor V Leiden (FVL) mutation and acquired APC resistance (APCR) in women with recurrent fetal loss (RFL). Patients and Methods: Fifty women with two or more RFLs and 50 age-matched controls with no history of fetal loss and at least one live birth were included in the study. Complete blood counts and screening tests for coagulation (PT, APTT), APCR, and FVL (PCR) were done in all women. Results: Age of the patients ranged from 20–42 years with a mean ± SD of 27.4 ± 4.8 years. Prolonged PT and APTT were observed in 2% and 8% cases, respectively. None of the controls had prolonged PT/APTT. APCR was observed in 8% cases and 2% controls. The prevalence of APCR was higher in women with first-trimester fetal loss (24.2%) as compared to women with the second trimester (13.3%) fetal loss. FVL was not observed in any of the cases or controls. Conclusion: This study indicates that FVL mutation is not associated with RFL in the Indian population while APCR is observed in Indian women with RFL.

CONTRIBUTION OF THE G1691A ALLELE CARRYING OF THE COAGULATION FACTOR V GENE TO THE DEVELOPMENT OF THROMBOSES IN RADIATION-EXPOSED PATIENTS WITH REACTIVE CHANGES IN PERIPHERAL BLOOD.

to determine the influence of the G1691A allele of the proaccelerin gene carrying to the thrombosis development, taking into account the vascular type of their occurrence, the presence of RFs in individuals with RCPB (reactive leukocytosis and thrombocytosis, and secondary erythrocytosis), as well as with and without radiation anamnesis. In general, it was analyzed the results of clinical and molecular-genetic data of 152 patientswith RCPB, 19 patients had radiation anamnesis, 133 - did not have. The thrombotic complications were detected in5 (26.31 %) of radiation-exposer patients and 25 (18.79 %) patients without radiation anamneses. The carrying ofthe G1691A allele proaccelerin gene (APG) (Leiden mutation (LM)) was detected using the allele-specific polymerasechain reaction. The LM was found in 5.9 % (9 carriers) of the general cohort (GC) of RPBC patients. There were no differencein the LM frequency between the groups of patients with and without radiation anamnesis (р = 0.312). In the groupof radiation-exposer patients (р = 0.017), as well as in the group without its (р = 0.031), venous thromboses only weremore frequently in the LM carriers. In the presence of a radiation anamnesis, G1691A APG carriers with RFs have thehigher frequency (р = 0.008) and the probability of the occurrence (relative risk [RR] = 25.00; CI 95 %: 1.56-399.68)of venous thrombosis. In the group without radiation anamnesis, the frequency of venues thrombosis in the LMcarriers is higher in the younger age subgroup (р = 0.001), without RFs (p = 0.044) and without RFs under 60 years(р = 0.023). The risk of venous thrombosis in the G1691A APG carriers of the group without radiation anamnesis is5.78 (95 % CI: 1.58-21.13). In LM carriers without radiation anamnesis and RFs, as well as under the 60 years of age,the probability of venous thrombosis was 6.85 (95 % CI: 1.86-25.22) and 19.40 (95 % CI: 4.64-81.09), respectively,and in the absence of both criteria - 9.57 (95 % CI: 2.49-36.73). In patients with and without radiation anamnesis, the risk of venues thrombosis are observed moreoften in carriers of LM. The carrying of the G1691A APG in patients with RPBC and without RA increased the risk ofvenues thrombosis development in subjects without FRs and below 60 years of age. In the radiation-exposure group,the frequency and the risk of venues thrombosis in the G1691A APG carriers was higher in the subgroup with RFs. It isprobably due to the peculiarity of the samples, or prothrombogenic interaction between LM and radiation-associated endothelial damage.

Pregnancy-related thrombosis risk in patients with protein C deficiency and comparison with pregnant women with heterozygous factor V Leiden mutation.

: The risk of pregnancy-related venous thromboembolism is high in patients with inherited thrombophilia. The aim of this study was to compare the risk of pregnancy related-venous thromboembolism of women with protein C (PC) deficiency to patients with heterozygous factor V Leiden mutation. 145 consecutive pregnant women with confirmed PC deficiency or heterozygous factor V Leiden mutation were prospectively enrolled in the study. Lyon venous thromboembolism-risk score was used to individually tailor antithrombotic prophylaxis. The use of a validated clinical score presents the advantage to have a homogenous management of the venous thromboembolism risk in patients having similar risk factors. 53 pregnancies with PC deficiency were compared with 190 pregnancies in heterozygous factor V Leiden mutation carriers. 50% of the patients with PC deficiency and 64% of the heterozygous factor V Leiden mutation carriers were asymptomatic. According to the Lyon-venous thromboembolism risk score, 50% of patients with PC deficiency and 51% of heterozygous factor V Leiden carriers did not received any antepartum heparin prophylaxis. 34 and 37% of patients respectively received heparin prophylaxis during the third trimester only. No venous thromboembolism was observed in patients with PC deficiency and one postpartum venous thromboembolism occurred in a patient with heterozygous factor V Leiden. In the absence of randomized controlled clinical studies, we report here a large prospective series of pregnant women with PC deficiency. In our cohort, no difference of outcome, in terms of venous thromboembolism, was observed between pregnant women with PC deficiency and those with heterozygous factor V Leiden. Based on our results, low-molecular-weight heparin prophylaxis should not be mandatory in all pregnant women with PC deficiency. Similar prophylaxis strategies may be applied to women with factor V Leiden mutation or PC deficiency.

Iliocaval stent reconstruction following inferior vena cava filter associated chronic thrombotic occlusion in a patient with factor v leiden mutation – a case report and review of literature

Iliocaval stent reconstruction following inferior vena cava filter associated chronic thrombotic occlusion in a patient with factor v leiden mutation – a case report and review of literature

A study of hyperhomocysteinemia in cerebral venous sinus thrombosis.

Background & objectives:Vegetarianism may result in low vitamin B12 and acquired hyperhomocysteinemia leading to thrombotic conditions such as cerebral venous sinus thrombosis (CVST). The clinico-radiological presentation and outcome of patients with hyperhomocysteinemia may be different from those without, but there is a paucity of information. This study was undertaken to find out the relationship of homocysteine (Hcy) with vitamin B12, folic acid and methyltetrahydrofolate reductase (MTHFR) mutation in the patients with CVST, and compare clinico-radiological severity and outcome of patients with and without hyperhomocysteinemia.Methods:Ninety-six CVST patients in whom Hcy level was measured, were included, and their risk factors and neurological, magnetic resonance (MR) imaging and MR venography findings were noted. They were evaluated for prothrombotic conditions including Hcy, vitamin B12, folic acid and MTHFR 677C→T mutation. Three month outcome was categorized as death, poor and good.Results:Seventy three per cent patients had risk factors; hyperhomocysteinemia in 52.1 per cent, protein S deficiency in 47.8 per cent, protein C deficiency in 19.4 per cent, MTHFR 677C→T mutation in 30.7 per cent, antinuclear antibody 11 per cent, and Factor V Leiden mutation in two per cent each. Thirty two per cent patients with hyperhomocysteinemia had no other thrombotic cause, and 22 per cent of them had either vitamin B12 and or folic acid deficiency only. The patients with hyperhomocysteinemia more frequently had vitamin B12 deficiency (70 vs. 13%), MTHFR 677C→T mutation (47.5 vs. 9.1%) and superior sagittal sinus thrombosis (78 vs. 56.5%) than normal Hcy group. The clinico-radiological severity and outcome were similar.Interpretation & conclusions:Hyperhomocysteinemia was an important correctable risk factor of CVST in patients from northern India, and majority of them had either low vitamin B12 level or MTHFR mutation.

Arm Swelling From Subclavian Vein Thrombosis: Factor V Leiden Mutation

Factor V Leiden is a genetic condition that can decrease natural anticoagulant effect in response to activated protein C, increasing thromboembolic risk. We report a 17-year-old man, homozygous for the Factor V Leiden mutation, with sudden onset arm stiffness, pain and swelling caused by a deep vein thrombosis in the subclavian vein. Pediatricians should consider thromboembolic diseases in cases of spontaneous acute limb discomfort and discoloration with no obvious cause. Int J Clin Pediatr. 2020;9(1):1-3 doi: https://doi.org/10.14740/ijcp343

Rare emergency in children: Priapism and stepwise treatment approach.

Priapism is a rare condition in children and the treatment algorithm is controversial in this age group. Herein, we report eight cases with low-flow priapism and our stepwise treatment approach in light of literature. We present a simple stepwise treatment for low-flow priapism including five steps. Step 1: Cold compress and analgesia while evaluation the priapism and its etiology. Step 2: Corporal aspiration and adrenaline infusion in the ward. Step 3: Modified Winter shunt in the same place. Step 4: Ketamine application and caudal block in the operating room. Step 5: Sapheno-cavernous (Grayhack) shunt. Eight cases with low-flow priapism were reviewed retrospectively. Symptoms, duration of tumescence, the interventions, and step that provide detumescence were recorded. The mean age of patients was 8.5 years (1-17 y). The median time of the priapism before admission was 15 h (4-165 h). The etiological factors were sickle cell disease, hemodialysis due to chronic renal failure, and factor V Leiden mutation in three patients. Detumescence was achieved in one patient at Step 2, in two patients at Steps 3, 4, and 5, respectively. Rigidity of cavernous body was observed in one patient in long-term follow-up. Low-flow priapism is a urological emergency that may cause erectile dysfunction. Treatment options should be selected according to a protocol that prevents time loss and avoids more invasive treatment in unnecessary situations. Our algorithm with simple nature and its steps from less invasive to more invasive procedures may be an alternative for the treatment of low-flow priapism.

Duboka venska tromboza i rekurentna plućna embolija kod pacijenta sa trombofiličnim mutacijama i generalizovanom psorijazom - prikaz slučaja

Abstract: Introduction: Genetic risk factors that increase venous thromboembolism risk are disorders in the synthesis or activity of coagulation factors. Factor V Leiden, prothrombin (20210-A), antithrombin deficiency, protein C and protein S deficiency, and hyperhomocysteinemia are the most common venous thromboembolism-related gene mutations. When genetic factors are combined with non-provoking risk factors (obesity, psoriasis, smoking and previous venous thromboembolism) the result is increased venous thromboembolism risk for each factor individually. Previous venous thromboembolism is one of the strongest risk factors, even in patients actively treated with anticoagulants. Patients are more likely to have recurrent venous thromboembolism with longer duration. Psoriasis is a complex immune-mediated disease, associated with cardiovascular risk, hypercoagulability markers and elevated homocysteine. Lots of observational reports suggest increased incidence of venous thromboembolic events in patient with psoriasis. Case presentation: We present patient with inherited thrombophilia and chronic diffuse plaque psoriasis complicated with deep venous thrombosis and pulmonary embolism. DNA analysis indicates the presence of homozygosis for Factor V Leiden mutation as well as heterozygosis for Factor XIII V34L, PAI-1 5G/4G and MTHFR A1298C polymorphism. Dermatological anamnesis is positive for plaque psoriasis since 12 years ago. Conclusion: The presentation of this case indicates an association between venous thromboembolism and chronic psoriasis. All patients with recurrent thromboembolism, hereditary thrombophilia, and moderate to severe psoriasis should be considered to be at higher risk for venous thromboembolism and appropriately treated.

Maternal Factor V Leiden Mutation in Pre-eclampsia: A Case-Control South Eastern Indian Tertiary Care Hospital Based Study

Maternal Factor V Leiden Mutation in Pre-eclampsia: A Case-Control South Eastern Indian Tertiary Care Hospital Based Study

Venous Cerebral Infarction Caused by Intake of Hormonal Contraceptives in Adolescents with Congenital Thrombophilia

In recent years, an increase in dysmenorrhea among adolescents has been observed worldwide. Oral contraceptives are used in gynaecological practice to correct this condition. However, the prescription of drugs belonging to this group often misses the risk of developing vascular complications, such as cerebral venous thrombosis and cerebral venous infarction. Due to the growing percentage of patients with congenital genetic mutations, it is relevant and reasonable to consider the risk factors and clinical signs of venous infarction in adolescents. First, it is necessary to exclude congenital thrombophilia, factor V Leiden and prothrombin G20210A gene mutations, and deficiency of proteins C, S and antithrombin. Of particular notice are the young patients and adolescents with complaints of a first-time, intense, poorly treatable headache (or headache in anamnesis), changes in the eye fundus (edematous, hyperemic optic disks; dilated, plethoric veins in the fundus of the eye). In such cases, a thorough medical history is extremely important, including, in particular, detection of an infectious process, traumatic brain injury, venous thrombosis of any localization; the use of drugs (especially hormonal ones) that can provoke the development of a hypercoagulable state; and investigation of the family history. These measures will help to prevent development of a cerebral venous circulation disorder (venous infarction).

Breast reconstruction using Deep Inferior Epigastric Perforator (DIEP) flap in a patient with heterozygous Factor V Leiden: a case report

Factor V Leiden (FVLeiden) mutation is the commonest type of inherited thrombophilia. Free tissue transfer is very rarely used in such patients due to concerns about microvascular thrombosis and flap failure. Even when rarely offered, the peri-operative antithrombotic regimen for such cases is widely varied and based of personal experiences and preference. These regimens usually include multiple pharmacologic agents but their real benefit is based merely on anecdotal evidence. On the other hand, the potential complications of such drugs are well established in literature. Deep Inferior Epigastric Perforator (DIEP) flap is the most widely used autologous breast reconstruction technique. Here, we report a case of successful free DIEP flap breast reconstruction in a lady with heterozygous FVLeiden mutation. We have described our approach to this patient, including the simple single drug anticoagulation regimen used as advised by the hematologists for venous thromboembolism (VTE) prophylaxis. We have compared our approach to that of others who have reported similar cases before. Our report shows that it is feasible to offer successful free tissue breast reconstruction to these patients by following meticulous surgical technique without the need of additional systemic antithrombotic agents over and above the simple regimen indicated for general VTE prophylaxis.

Recurrent Stroke In 34 Year-Old, Unusual Presentation of Non-Bacterial Endocarditis

Factor V Leiden (FVL) and prothrombin G20210A (PGM) mutations are the most frequent genetic risk factors involved in deep venous thrombosis in Caucasians. Being heterozygous for both seems to increase the risk of venous events but it is not well established if the association increases the risk of arterial thrombosis or other thrombotic events. We present a case of recurrent stroke caused by non-bacterial thrombotic endocarditis (NBTE) in a 34-year-old Caucasian man heterozygous for both FVL and PGM. His diagnosis of NBTE was confirmed with pathology in the absence of other causes of NBTE.

The relationship of a Prothrombin G20210A mutation or a factor V Leiden mutation and on-aspirin platelet (re-)activity.

The interplay between platelets and pro-thrombotic factors may have been under-investigated in the identification of aspirin users at high risk for cardiovascular event reoccurrences. There is growing evidence that a Prothrombin G20210A (FII) or a Factor V Leiden (FVL) mutation might increase platelet activity. Subsequently, this study assessed on-aspirin platelet (re-)activity in non-pregnant participants with a FII - or a FVL mutation in comparison with non-pregnant data derived from controls. This study was conducted with data derived from the follow-up FRUIT-RCT. This is a unique cohort namely, participants without a history of cardiovascular disease or thrombotic events, but who are a carrier of a pro-thrombotic mutation. All participants were instructed to ingest aspirin once daily for 10days. Platelet (re-)activity was measured by the PFA Closure Time (PFA-CT), the VerifyNow (VN-ARU), and serum Thromboxane B2 (sTxB2) levels. In total, eight participants with a FII-, 15 with a FVL mutation, and 21 controls were included. The FII mutation carriers demonstrated significantly higher on-aspirin platelet (re)-activity (PFA-CT, -92sec.; VN-ARU, +37 ARU) vs. controls. The FVL carriers demonstrated similar on-aspirin platelet (re-)activity vs. controls. The sTxB 2 levels were similar in either of the carrier groups vs. controls. We feel these data are suggestive of increased on-aspirin platelet (re-)activity, as measured by the PFA-200 and the VerifyNow, in non-pregnant carriers of a FII-mutation, but not in carriers of FVL-mutation. Interestingly, this increased on-aspirin platelet (re-)activity is present in spite of low sTxB2 levels.

Hyperbaric oxygen treatment results in a group of Turkish central retinal artery occlusion patients with a combined presence of thrombophilic mutations

Central retinal artery occlusion (CRAO) is a rare ocular-ischemic syndrome causing irreversible blindness. Its pathophysiology has not been clarified, and no targeted therapies are available yet. Hyperbaric oxygen (HBO2) therapy is already an approved therapy for CRAO and has been shown to improve the visual acuity of CRAO patients safely. However, further clinical data are required to classify HBO2 therapy as a type-I general agreement for CRAO. Eleven patients with non-arteritic CRAO were enrolled. Patient demographics, medical history, detailed eye examinations, HBO2 therapy results, pre-/post HBO2 therapy visual acuity measurements and genotypes for common thrombophilic mutations (Factor V G1691A Leiden, Factor II G20210A, MTHFR A1298C, MTHFR C677T, and PAI-1-675 4G/5G) were obtained. Six patients (54%) responded to HBO2 therapy compared to five non-responders (46%). Patients admitted before 12 hours responded well to HBO2 therapy. No systemic diseases nor advanced age were statistically correlated to CRAO. A combination of mutations rather than single mutations for each patient could be seen as responsible for CRAO. No Factor V G1691A Leiden mutations and only one FII G20210A mutation were observed. Eight patients (72%) had MTHFR 677T allele, five patients (45%) had MTHFR 1298C allele, and 10 patients (91%) had the PAI-1-675 4G allele. Not a single mutation but a combination of mutations and other unknown factors probably lead to CRAO, and if intervention is timely, HBO2 therapy offers improvement in visual acuity safely.

Portal Vein Aneurysm Complicated by Thrombosis

The current study described a case of portal vein aneurysm at the confluence of the superior mesenteric and splenic veins, complicated by thrombosis in a patient with no liver pathology but with Factor V Leiden mutation.

Clinical Features of Visual Disturbances in Leiden Thrombophilia

The hereditary thrombophilias is a well-recognized important risk factor for a systemic and local thromboembolic events development. The case of Leiden thrombophilia family inheritance concomitant by the visual disturbances development are shown in this аrticle. Most commonly in hereditary thrombophilias, venous thrombembolias occur, arterial occlusions which have been reported in the recent literature only as individual clinical cases occur more rarely. In the European population hereditary thrombophilias are associated with a prothrombotic mutation in the coagulation factor V gene (Leiden factor) in a greater degree; herewith the risk of thrombotic complications is increasing significantly in homozygous polymorphism forms. Presence of combined mutations in several clotting factors also leads to risk of thrombembolias increase. Consequence of the Leiden mutation is a V activator resistance to the resolving action of the activated protein C which is a natural endogenous anticoagulant protein. Resistance development leads to a deceleration of V factor inactivation and to increasing of the thrombin amount. In the work presented here, development of the consistent bilateral occlusion of the central retinal artery (CRA) in a middle-aged patient with a heterozygous form of Leiden thrombophilia is the subject of interest. Along with the hereditary hemostatic system abnormality, the patient also had cardiovascular risk factors (hypertensive disease, atherosclerosis) which had a potentiating effect on the occlusion development. Taking into account the autosomal dominant nature of the Leiden mutation inheritance, the patient’s only daughter was examined; brief episodes of amaurosis fugax against the background of headaches similar to migraine were detected due to ophthalmological abnormalities. For verification of the Leiden thrombophilia diagnosis, both patients underwent molecular genetic diagnostics. Currently there are no large prospective studies showing the optimal and economically viable approach for identification of thrombophilia genetic polymorphisms in patients with retinal vascular occlusions in daily clinical experience. Possible additional risk factors for thrombembolias development, prevention services for manifest and recurrent vascular occlusions in patients with hereditary blood coagulation system abnormalities and their relatives are discussed in this article.

Prevalence of prothrombotic factors in patients with Budd-Chiari syndrome or non-cirrhotic nonmalignant portal vein thrombosis: A hospital-based observational study.

Comprehensive investigations on the prothrombotic factors of splanchnic vein thrombosis (SVT), including Budd-Chiari syndrome (BCS) and non-cirrhotic nonmalignant portal vein thrombosis (PVT), in Eastern patients are scarce. Between March 2012 and July 2017, 812 consecutive patients, including 418 BCS and 394 non-cirrhotic nonmalignant PVT patients, were admitted to Xijing Hospital (a Chinese tertiary academic hospital) and screened for prothrombotic factors. Odds ratios (ORs), 95% confidence intervals (CIs), and P-trends were calculated by using conditional logistic regression. The prevalence of myeloproliferative neoplasms (MPNs) was only 6.3% among BCS patients but 28.3% among PVT patients. Notably, the presence of MPNs was associated with a higher risk of hepatic vein-type BCS (OR 9.9, 95% CI 3.6-26.7, P-trend <0.001) and extensive thrombosis in PVT (OR 4.1, 95% CI 1.9-8.9, P-trend <0.001). Calreticulin mutations existed in 2.7% of SVT patients. Furthermore, the prevalence of antiphospholipid antibody syndrome and protein C, protein S, or antithrombin deficiency in BCS patients was 7.3% and 22.5%, respectively, similar to that in patients with PVT (7.4% and 25.7%). In addition, factor V Leiden mutation, prothrombin G20210A mutation, and paroxysmal nocturnal hemoglobinuria were identified in <1% of both BCS and PVT patients. There is a significant positive association between MPNs and hepatic vein-type BCS or non-cirrhotic nonmalignant PVT with extensive thrombosis. Additionally, calreticulin mutations should be tested in JAK2V617F -negative SVT patients in China. However, screening for factor V Leiden mutation, prothrombin G20210A mutation, and paroxysmal nocturnal hemoglobinuria may be unnecessary.

Clinical Implications of Different Risk Factor Profiles in Patients with Mesenteric Venous Thrombosis and Systemic Venous Thromboembolism – A Population-Based Study

It is unknown whether the risk factor profile for mesenteric venous thrombosis (MVT) is different from systemic venous thromboembolism (VTE). The aim of the present population-based study was to compare acquired and inherited risk factors in MVT versus VTE. Identification of all MVT patients at Skane University Hospital between 2000 and 2015 was performed in patient records and AuriculA (Swedish anticoagulation registry). VTE patients were retrieved from the Malmo Thrombophilia Study (MATS), including 1465 consecutive unselected VTE patients between 1998 and 2008. Patients with MVT (n = 120) were younger (p < 0.001), had higher glomerular filtration rate (p < 0.001), lower smoking rate (p < 0.001), and had less often undergone recent surgery (p = 0.025). The prevalence of solid cancer (19.2% in MVT versus 12.1% in VTE; p = 0.026) and intra-abdominal cancer (16.7% versus 2.3%; p < 0.001) were higher in MVT. The prevalence of factor V Leiden mutation without presence of cancer was lower in MVT compared to VTE (26.6% versus 38.9%; p = 0.031). Thirty-day mortality was higher in the MVT group (9.2% versus 0.6%; p < 0.001), but did not differ at long-term follow-up according to Kaplan–Meier analysis (p = 0.73). Patients with MVT have a higher prevalence of cancer and lower prevalence of factor V Leiden mutation than those with systemic VTE. Intra-abdominal cancer should be excluded in MVT patients, and the high prevalence of factor V Leiden mutation in patients without cancer in both groups suggests that screening for thrombophilia in patients without cancer should be considered in this population for both groups.

Thrombectomy and Thrombolysis by Catheter Through Right Gastroepiploic Vein of Acute Superior Mesenteric Venous Thrombosis with Peritoneal Signs

Thrombectomy and Thrombolysis by Catheter Through Right Gastroepiploic Vein of Acute Superior Mesenteric Venous Thrombosis with Peritoneal Signs

Peripheral Malignant Nerve Sheath Tumour: At the Heart of the Matter

A 51-year-old woman presented with a 2-month history of shortness of breath, generalized malaise, headache, and night sweats. Although there were no cardiovascular risk factors, the patient had a history of Factor V Leiden mutation and previous pulmonary embolus treated with anticoagulation. Transthoracic echocardiography confirmed normal biventricular systolic function with multiple echodense masses attached to the apical walls of the left ventricle (LV) (Fig. 1A; and Video 1 , view video online).