UNASSIGNED: Inherited thrombophilia, mainly the Factor V Leiden (FVL) and Prothrombin mutation (PTM) are the most risk factors for venous thrombosis especially during pregnancy and was strongly associated with recurrent pregnancy loss (RPL), a devastating reproductive problem that affects more than 1% of couples who are trying to conceive. The frequencies also the correlation among these polymorphisms and RPL have been reported controversially in various populations.
UNASSIGNED: In this study we evaluated the presence inherited thrombophilia amongst 35 Tunisian women with more than 2 miscarriages, referred to our genetic counseling.
UNASSIGNED: DNA was extracted from peripheral blood samples and PCR-RFLP was performed for the molecular diagnosis of mutation.
UNASSIGNED: FVL and PTM were detected in 5.7 % and 2.9% respectively; in women with a particular history of early fetal loss and thrombotic events.
UNASSIGNED: This study emphasizes the importance of testing for FVL and FIIM in women with RPL; mainly in the context of thrombotic events. Multi-center collaboration is necessary to clarify the real impact of thrombotic molecular defects on the pregnancy outcome, to ascertain the effect of inherited thrombophilia on recurrent pregnancy loss and then to evaluate the appropriate therapeutic approach.

Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at determining the risk factors involved recognizes a group of \"traditional\" risk factors, but also more recent studies identified over 100 \"novel\" ones which may have a role in the disease. Among the latter is the thrombophilia profile of a patient, a pathology well-established for its involvement in venous thromboembolism, but with less studied implications in arterial thrombosis. This paper reviews the literature, explaining the pathophysiology of the thrombophilia causes associated most with coronary thrombosis events. Results of several studies on the subject, including a meta-analysis with over 60,000 subjects, determined the significant involvement of factor V Leiden, prothrombin G20210A mutation, plasminogen activator inhibitor-1 and antiphospholipid syndrome in the development of coronary artery disease. The mechanisms involved are currently at different stages of research, with some already established and used as therapeutic targets.

Prothrombin G20210A mutation occurs in only 2% to 3% of the population, but usually does not become apparent unless the individual exhibits another risk factor for clotting. A risk factor such as hyperglycemia in the setting of diabetes mellitus may accelerate this clotting process, even at a very young age. In this case report, we discuss a 15-year-old boy presenting with left calf swelling and pain, found to have extensive deep vein thrombosis in the setting of hyperglycemia and a newly discovered prothrombin G20210A mutation. Venous thromboembolism in the setting of type 2 diabetes mellitus has not been described in children.

Lumbar puncture (LP) is rarely complicated by cerebral vein thrombosis (CVT), especially if other risk factors coexist. We describe the case of a 28-year-old woman who developed CVT after corticosteroid treatment and LP performed for suspected multiple sclerosis. The day after LP, she developed intense headache and on Day 8 generalized tonic-clonic seizures. A brain computed tomography scan showed thrombosis of the superior sagittal sinus and cortical veins. Thrombophilia screening showed heterozygous G20210A prothrombin mutation. Anticoagulant therapy with low molecular weight heparin and then warfarin was administered until Day 16 after LP, when a brain magnetic resonance imaging showed a subdural hematoma. Warfarin was interrupted and dabigatran was started. The patient recovered completely, both from the initial thrombotic event and the hemorrhagic complication. This case highlights the importance to keep in mind CVT in the differential diagnosis of post-LP headache not responsive to standard therapy, and suggests that dabigatran can be considered an effective and safe treatment of CVT.

Background and Objectives: The diagnostic value of thrombophilia remains unknown in young patients with patent foramen ovale (PFO) and stroke. In this study we hypothesized that inherited thrombophilias that lead to venous thrombosis are more prevalent in patients with PFO. Materials and Methods: The study included patients of the tertiary center Vilnius University Hospital Santaros Klinikos who had a cryptogenic ischemic stroke between the ages of 18 and 50 between the years 2008 and 2021. Transient ischemic attacks were excluded. Contrast-enhanced transcranial Doppler ultrasound and extensive laboratory testing were performed. Results: The study included 161 cryptogenic stroke patients (mean age 39.2 ± 7.6 years; 54% female), and a right-to-left shunt was found in 112 (69.6%). The mean time between stroke and thrombophilia testing was 210 days (median 98 days). In total, 61 (39.8%) patients were diagnosed with thrombophilia. The most common finding was hyperhomocysteinemia (26.7%), 14.3% of which were genetically confirmed. Two patients (1.2%) were diagnosed with factor V Leiden mutation, three patients (1.9%) with prothrombin G20210A mutation, one patient (0.6%) had a protein C mutation and one patient (0.6%) had a protein S mutation. No antithrombin mutations were diagnosed in our study population. A total of 45.5% of patients with inherited thrombophilia had a right-to-left shunt, while 54.5% did not, p = 0.092. Personal thrombosis anamnesis was positive significantly more often in patients with antiphospholipid syndrome. Conclusions: The hypothesis of the study was rejected since inherited venous thrombophilia was not significantly more common in patients with PFO. Due to the rarity of thrombophilias in general, more research with a larger sample size is required to further verify our findings.

Inherited thrombophilia is an important cause of venous thrombosis. The Factor V Leiden (FVL) is the most commonly encountered mutation, followed by the prothrombin G20210A gene mutation (PTM). The typical venous thrombotic events (VTEs) associated with PTM mutations are deep vein thrombosis (DVT) and pulmonary embolisms (PE). The PTM is inherited in an autosomal dominant pattern with variable penetrance. While heterozygous PTM mutations are more frequent and well documented in the literature, rare cases of homozygous PTM mutations are also reported. In this report, we discuss a 56-year-old male with a past medical history of homozygous prothrombin gene mutation (G20210A) who presented with an unprovoked DVT of the right lower extremity involving both the proximal and distal veins associated with multiple bilateral PEs. This case is unique in terms of the homozygous PTM inheritance, the age at which the patient presented (usually presentation is earlier in life), and the fact that he had a recurrence of both DVT and PE simultaneously.

Congenital prothrombin deficiency is an extremely rare, autosomal recessive bleeding disorder with a prevalence of 1 in 2 million individuals. Here, we report a case of congenital prothrombin deficiency with two concurrent mutations in the prothrombin gene (F2), affecting the heavy B chain. The patient presented with a history of multiple bleeding events in his youth that are mostly trauma associated, with a family history of prothrombin deficiency. Laboratory analysis showed a prolonged activated partial thromboplastin time and a prothrombin activity level of 5%. Genetic analysis of the F2 gene identified two heterozygous variants; one is a previously reported pathogenic deletion (c.1814_1815del; p.His605Argfs*13), and the other is a novel missense variant (c.1147C>T; p.Arg383Trp). In silico analysis predicted that p.Arg383Trp is likely to be disease causing, as it affects one of the anion-binding exosites-I of the B chain. This case highlights the significance of molecular findings in confirming the diagnosis of patients with congenital prothrombin deficiency.

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 Skåne University Hospital between 2000 and 2015 was performed in patient records and AuriculA (Swedish anticoagulation registry). VTE patients were retrieved from the Malmö 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.

We sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (Ks) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2-6 hours (h) after and 20-25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (Ks -12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for Ks and CLT before rivaroxaban intake. At 2-6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (Ks +38 %, and +37 %, CLT -25 % and -25 %, CLT-TAFI -20 % and -24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (Ks -12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20-25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.

METHODS: A 53-year-old man, ethnicity unknown.
UNASSIGNED: Leg swelling and pain.
UNASSIGNED: The patient has a history of atrial fibrillation that had been treated with 3 separate cardiac ablations, most recently in the year 2014. According to the patient, the symptoms had begun the day after his most recent cardiac ablation on June 27, 2014. The catheter for the procedure was inserted via the right femoral vein. The patient had returned to work, where he sits for an average of 8 hours per day, but his pain became unbearable, so he went to the emergency department on July 3, 2014.
UNASSIGNED: In 2013, he was evaluated for a possible stroke. He reported consuming 1 to 2 alcoholic drinks per month, not using tobacco, and not being currently sexually active. He has no history of excessive bleeding or bruising.
UNASSIGNED: The patient underwent an operation for an unruptured aneurysm in 2011; ablation for atrial fibrillation in 2006, 2009, and 2014; gastric bypass in 2006; left knee arthroscopy in 2010; and rotator cuff repair in 2013.
UNASSIGNED: The patient\'s sister had died of a pulmonary embolism (age at time of death unknown). His father had died of a stroke at age 49 years. His mother, who is still living, has a history of intracranial aneurysms.
RESULTS: The patient was alert and oriented; he cooperated with medical staff. His vital signs were normal, and all body systems were functioning normally. A large ecchymosis extended from his groin to his knee.
RESULTS: See Tables 1-5.