Search Results (17)

Background and Objectives: Congenital thrombophilias are biologically plausible contributors to chronic thromboembolic pulmonary hypertension (CTEPH), yet their frequency and clinical impact remain uncertain. We undertook a systematic review to (i) estimate the pooled prevalence of specific hereditary defects among adults with CTEPH, (ii) characterise associated demographic and haemodynamic phenotypes, and (iii) summarise peri-operative and survival outcomes after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in genetically defined subgroups. Methods: A protocol compliant with PRISMA-2020 was registered prospectively on the Open Science Framework (OSF). PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to 1 June 2025 using validated, PRESS-reviewed strings combining CTEPH and thrombophilia terms. Observational cohorts, case–control studies and trials reporting laboratory-confirmed congenital thrombophilias in adults with right-heart-catheter-defined CTEPH were eligible. Results: Eight studies encompassing 677 unique CTEPH patients met the inclusion criteria. Among the 400 individuals screened for deficiencies of the natural anticoagulant pathways, 56 possessed a defect: protein S deficiency 5.3% (21/400; 95% CI 3.3–8.0), protein C deficiency 4.3% (17/400; 2.5–6.8), and antithrombin deficiency 1.5% (6/400; 0.6–3.3). In 520 genotyped patients, factor V Leiden and prothrombin G20210A were infrequent (1.3% and 1.0%, respectively) and confined to European/North American cohorts. Baseline haemodynamics were uniformly severe (mean mPAP 46.7 mm Hg; pulmonary vascular resistance ≈ 9 WU). Definitive reperfusion therapy was common (PEA 63%; BPA 18%), reducing mPAP to 20.5 mm Hg and yielding a weighted one-year survival of 96.2%. No study demonstrated a thrombophilia-specific effect on surgical candidacy or early survival. Conclusions: Approximately one in seven patients with CTEPH harbours a congenital thrombophilia, most often protein S or protein C deficiency, whereas classic venous-thrombo-embolism mutations are rare and ethnically restricted. Current evidence indicates that genetic status does not materially influence haemodynamic severity, uptake of PEA/BPA, or short-term survival, supporting guideline recommendations for universal referral to specialist reperfusion centres. Future multicentre registries integrating systematic genotyping and long-term outcome capture are needed to clarify genotype-specific prognostic and therapeutic implications. Full article

Background: Inherited thrombophilia is increasingly recognized as a contributing factor to placental vascular pathology and adverse pregnancy outcomes. While the clinical implications are well-established, fewer studies have systematically explored the histopathological changes associated with specific genetic mutations in thrombophilic pregnancies. Materials and Methods: This retrospective observational study included two cohorts of placental samples collected between September 2020 and September 2024 at a tertiary maternity hospital. Group 1 included women diagnosed with hereditary thrombophilia, and Group 2 served as controls without known maternal pathology. Placentas were examined macroscopically and histologically, with pathologists blinded to group allocation. Histological lesions were classified according to the Amsterdam Consensus and quantified using a composite score (0–5) based on five key vascular features. Results: Placental lesions associated with maternal vascular malperfusion—including infarctions, intervillous thrombosis, stromal fibrosis, villous stasis, and acute atherosis—were significantly more frequent in the thrombophilia group (p < 0.05 for most lesions). A combination of well-established thrombophilic mutations (Factor V Leiden, Prothrombin G20210A) and other genetic polymorphisms with uncertain clinical relevance (MTHFR C677T, PAI-1 4G/4G) showed moderate-to-strong correlations with histopathological markers of placental vascular injury. A composite histological score ≥3 was significantly associated with thrombophilia (p < 0.001). Umbilical cord abnormalities, particularly altered coiling and hypertwisting, were also more prevalent in thrombophilic cases. Conclusions: Thrombophilia is associated with distinct and quantifiable placental vascular lesions, even in pregnancies without overt clinical complications. The use of a histological scoring system may aid in the retrospective identification of thrombophilia-related placental pathology and support the integration of genetic and histologic data in perinatal risk assessment. Full article

A 16-year-old patient, while an infant, incurred right-sided hemiparesis and had difficulty breast feeding. She was later diagnosed with a neonatal stroke and her genetic testing showed a missense mutation in her PROS1 (Protein S) gene. Both her grandfather and father, but not her mother, had hereditary Protein S (PS) deficiency. The patient was not prescribed any mediation due to her young age but was frequently checked by her physician. The patient’s plasma was first collected at the age of 13, and the isolated plasma from the patient and her father were analyzed by aPTT, thrombin generation, and enzyme-linked immunosorbent assays. These analyses showed low PS activity and clotting time associated with the missense mutation in the PROS1 gene. During the COVID-19 pandemic, the patient received her first Pfizer vaccination dose in 2021, followed by a booster dose in 2022. The plasma samples were collected 8 weeks post-immunization, after which her clotting parameters had improved for up to 6 months following vaccination. The patient’s plasma showed a significant reduction in thrombin generation and an improved aPTT clotting time. Mass spectrometry analysis revealed that her antithrombin-III level was significantly higher post-vaccination, and both thrombin and FXII levels were significantly lowered compared with her father. To our knowledge, this is the first report to document that COVID-19 vaccination can lower the risk of thrombosis in a patient with inherited thrombophilia. Although the effect was observed on a single mutation, it would be interesting to investigate the effect of COVID-19 vaccinations on other thrombophilia. Full article

(1) Background: The three factors within the Virchow triad play the leading role in the development of deep vein thrombosis (DVT) during pregnancy. (2) Methods: This research approaches the various risk factors associated with DVT and its most representative complications, pulmonary thromboembolism and cerebral venous thrombosis, in pregnant and postpartum women across a 15-year period (2007–2021). (3) Results: A total of 201 out of 287 patients with DVT had associated risk factors, while 86 did not present with any. Out of the 201 patients with risk factors, 47 developed pulmonary thromboembolism, while 12 experienced cerebral thrombosis. The statistical analysis of risk factors involved in DVT revealed high significance for obesity (OR 3.676; CI 2.484–5.439), gestational diabetes (OR 3.394; CI 2.101–5.483), hypertension (OR 2.325; CI 1.591–3.397), preeclampsia (OR 4.753; CI 2.342–9.645), thrombophilia (OR 12.138; CI 8.973–16.417), and varicose veins (OR 9.678; CI 7.321–12.793); for pulmonary thromboembolism, there was high significance for obesity (OR 7.867; CI 4.297–14.401), hypertension (OR 2.605; CI 1.246–5.446), preeclampsia (OR 7.483; CI 2.346–23.872), thrombophilia (OR 11.035; CI 5.910–20.602), and varicose veins (OR 6.837; CI 3.665–12.757); and for cerebral thromboembolism (CTE), the risk factors identified were obesity (OR 6.755; CI 1.954–23.347), hypertension (OR 1.167; CI 0.155–8.770), preeclampsia (OR 9.655; CI 1.283–72.672), and thrombophilia (OR 33.275; CI 12.884–85.939). (4) Conclusions: Obesity was the only significant factor found to influence DVT, pulmonary embolism and CTE risks, and hereditary thrombophilia was the main factor influencing the risk for pulmonary thromboembolism and CTE. Systemic lupus erythematosus and gestational diabetes revealed conflicting results that require further investigation. Full article

Background: FV Leiden is an autosomal dominant disease, representing one of the most prevalent genetic causes for hereditary thrombophilia manifested by venous thromboembolism. Methods: We report a case of a 30-year-old patient who was admitted for enrollment in phase II cardiac rehabilitation. The cardiovascular disease onset was five years ago when the patient was diagnosed with superficial vein thrombosis, for which anticoagulant treatment was recommended. However, he discontinued the prescribed treatment independently, which resulted in the development of deep vein thrombosis. A screening for risk factors associated with venous thromboembolism was conducted, leading to the identification of a heterozygous mutation of factor V Leiden. Later, the patient was hospitalized for acute coronary syndrome necessitating stent implantation. Following this procedure, the patient started a cardiac rehabilitation program, where the patient received multidisciplinary counseling. Conclusions: At the end of the cardiac rehab, significant improvements were observed in clinical and hemodynamic parameters. Consequently, the patient was advised to continue rehabilitation treatment in the outpatient setting. Also, for patients with suboptimal maintenance of the therapeutic range of INR, the use of apixaban might be considered. Furthermore, the utilization of a reduced dosage of apixaban has demonstrated its effectiveness in preventing further venous thromboembolism. Full article

Factor V (FV) Leiden and prothrombin G20210A are the most common hereditary thrombophilias. While their role in venous thromboembolism is well known, there are still uncertainties regarding their relationship with arterial thrombotic events, especially coronary ones. Our research, based on an in-depth analysis of the available literature, provides up-to-date information on the relationship between FV Leiden and prothrombin G20210A and acute myocardial infarction. FV Leiden and prothrombin G20210A screening should be implemented only in select cases, such as acute coronary syndrome in young individuals and/or in the absence of traditional cardiovascular risk factors and/or in the absence of significant coronary artery stenosis at angiography. Their identification should be followed by the implementation of optimal control of modifiable traditional cardiovascular risk factors to reduce the risk of recurrent events and genotyping and genetic counseling of all family members of affected cases for proper prophylaxis. An extended dual antiplatelet therapy (DAPT) may be considered, given the lower risk of bleeding under DAPT conferred by FV Leiden. Full article

Thrombosis is an extremely dangerous complication in elderly patients with COVID-19. Since the first months of the pandemic, anticoagulants have been mandatory in treatment protocols for patients with COVID-19, unless there are serious contraindications. We set out to discover if genetic thrombophilia factors continue to play a triggering role in the occurrence of thrombosis in patients with COVID-19 with prophylactic or therapeutic anticoagulants. We considered the following genetic markers as risk factors for thrombophilia: G1691A in the FV gene, C677T and A1298C in the MTHFR gene, G20210A and C494T in the FII gene, and (−675) 4G/5G in the PAI-I gene. In a cohort of 176 patients, we did not obtain a reliable result indicating a higher risk of thrombotic complications when taking therapeutic doses of anticoagulants in carriers of genetic markers for thrombophilia except the C494T mutation in the FII gene. However, there was still a pronounced tendency to a higher incidence of thrombosis in patients with markers of hereditary thrombophilia, such as FV G1691A and FII G20210A mutations. The presence of the C494T (Thr165Met) allele in the FII gene in this group of patients showed a statistically significant effect of the mutation on the risk of thrombotic complications despite anticoagulant therapy. Full article

Thrombophilia, also called hypercoagulability or prothrombotic condition, usually reflects a certain imbalance that occurs either in the coagulation cascade or in the anticoagulation/fibrinolytic system. A similar imbalance may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thrombotic complications are associated with multiorgan failure and increased mortality. In this context, activation of coagulation and thrombocytopenia appeared as prognostic markers in COVID-19. Our work provides a structured and updated analysis of inherited thrombophilia and its involvement in COVID-19, emphasizing the importance of diagnosing and initiating thromboprophylaxis. Since the state of hypercoagulation is directly correlated with COVID-19, we consider that studies on the genetic profiles of proteins involved in thrombophilia in patients who have had COVID-19 and thrombotic events are of great importance, both in treating and in preventing deaths due to COVID-19. Full article

Inflammatory bowel diseases (IBD) are systemic conditions characterized by multiple intestinal and extra-intestinal manifestations related to the associated chronic inflammatory state. Among their diverse extra-intestinal complications, venous thromboembolism (VTE) remains one of the most under recognized causes of morbidity and mortality in these patients, highlighting the need for a better understanding of the underlying mechanism of hypercoagulability, in addition to the role of acquired and inherited risk factors that further increase the risk of thrombosis with its impact on patients’ outcomes. We hereby present a review of the data regarding thrombosis in the setting of IBD, elucidating the possible role for screening in this high-risk category of patients and specifically in areas where inherited thrombophilia is expected to be highly prevalent, reporting two patients with IBD, one who developed a cerebrovascular event and another one who had recurrent VTE events; nevertheless, both of them had inherited thrombophilic mutations. The identification of specific genetic abnormalities in those patients reintroduces the controversy related to the need to screen a specific category of patients with IBD for hereditary thrombophilia, especially in regions characterized by a higher prevalence of such thrombophilic alterations. Full article

Cerebral venous thrombosis accounts for 0.5–1% of all cerebrovascular events and is one type of stroke that affects the veins and cerebral sinuses. Females are more affected than males, as they may have risk factors, such as pregnancy, first period after pregnancy, treatment with oral contraceptives treatment with hormonal replacement, or hereditary thrombophilia. This neurological pathology may endanger a patient’s life. However, it must be suspected in its acute phase, when it presents with variable clinical characteristics, so that special treatment can be initiated to achieve a favorable outcome with partial or complete functional recovery. The case study describes the data and the treatment of two patients with confirmed cerebral venous thrombosis with various localizations and associated risk factors, who were admitted to the neurology department of the Sf. Apostol Andrei Emergency Hospital in Constanta. The first patient was 40 years old and affected by sigmoid sinus and right lateral sinus thrombosis, inferior sagittal sinus, and right sinus thrombosis, associated with right temporal subacute cortical and subcortical hemorrhage, which appeared following a voluntary abortion. The second case was a patient aged 25 who was affected by left parietal cortical vein thrombosis, associated with ipsilateral superior parietal subcortical venous infarction, which appeared following labor. The data are strictly observational and offer a perspective on clinical manifestations and clinical and paraclinical investigations, including the treatment of young patients who had been diagnosed with cerebral venous thrombosis and admitted to the neurology department. Full article

Osteonecrosis of the jaws (ONJ) usually has a clear etiology. Local infection or trauma, radiotherapy and drugs that disrupt the vascular supply or bone turnover in the jaws are its major contributors. The thrombotic occlusion of the bone’s venous outflow that occurs in individuals with hereditary thrombophilia and/or hypofibrinolysis has a less known impact on jaw health and healing capability. Our research provides the most comprehensive, up-to-date and systematized information on the prevalence and significance of hereditary thrombophilia and/or hypofibrinolysis states in ONJ. We found that hereditary prothrombotic abnormalities are common in patients with ONJ refractory to conventional medical and dental treatments. Thrombophilia traits usually coexist with hypofibrinolysis traits. We also found that frequently acquired prothrombotic abnormalities coexist with hereditary ones and enhance their negative effect on the bone. Therefore, we recommend a personalized therapeutic approach that addresses, in particular, the modifiable risk factors of ONJ. Patients will have clear benefits, as they will be relieved of persistent pain and repeated dental procedures. Full article

Osteonecrosis of the femoral head (ONFH) is a debilitating disease with major social and economic impacts. It frequently affects relatively young adults and has a predilection for rapid progression to femoral head collapse and end-stage hip arthritis. If not diagnosed and treated properly in the early stages, ONFH has devastating consequences and leads to mandatory total hip arthroplasty. The pathophysiology of non-traumatic ONFH is very complex and not fully understood. While multiple risk factors have been associated with secondary ONFH, there are still many cases in which a clear etiology cannot be established. Recognition of the prothrombotic state as part of the etiopathogeny of primary ONFH provides an opportunity for early medical intervention, with implications for both prophylaxis and therapy aimed at slowing or stopping the progression of the disease. Hereditary thrombophilia and hypofibrinolysis are associated with thrombotic occlusion of bone vessels. Anticoagulant treatment can change the natural course of the disease and improve patients’ quality of life. The present work focused on highlighting the association between hereditary thrombophilia/hypofibrinolysis states and ONFH, emphasizing the importance of identifying this condition. We have also provided strong arguments to support the efficiency and safety of anticoagulant treatment in the early stages of the disease, encouraging etiological diagnosis and prompt therapeutic intervention. In the era of direct oral anticoagulants, new therapeutic options have become available, enabling better long-term compliance. Full article

Background. Some studies with inconclusive results have reported a link between sarcoidosis and an increased risk of pulmonary embolism (PE). This study aimed at assessing a possible correlation between potential risk factors and PE in sarcoidosis patients. Methods. A total of 256 sarcoidosis patients (84 males and 172 females; mean age at diagnosis 49 ± 13) were enrolled after giving written informed consent. Clinical evaluations, laboratory and radiology tests were performed to evaluate the presence of pulmonary embolism. Results. Fifteen sarcoidosis patients with PE (4 males and 11 females; mean age at diagnosis 50 ± 11), diagnosed by lung scintigraphy and 241 sarcoidosis patients without PE (80 males and 161 females; mean age at diagnosis 47 ± 13), were observed. There was a statistically significant increase of the presence of antiphospholipid antibodies in the sarcoidosis group with pulmonary embolism. There was no statistically significant difference between the two groups as to smoking habit, obesity or hereditary thrombophilia frequency (p > 0.05, respectively). Conclusions. This study demonstrates a significant correlation between the presence of antiphospholipid antibody positivity and the pulmonary embolism events in our sarcoidosis patients. Furthermore, we propose screening for these antibodies and monitoring, aimed at timely treatment. Full article

Rheumatic diseases (RD) and hereditary thrombophilias (HT) can be associated with high-risk pregnancies. This study describes obstetric outcomes after receiving medical care at a multidisciplinary consultation (MC) and compares adverse neonatal outcomes (ANOs) before and after medical care at an MC. This study is a retrospective observational study among pregnant women with RD and HT treated at an MC of a university hospital (southern Spain) from 2012 to 2018. Absolute risk reduction (ARR) and number needed to treat (NNT) were calculated. A total of 198 pregnancies were registered in 143 women (112 with RD, 31 with HT), with 191 (96.5%) pregnancies without ANOs and seven (3.5%) pregnancies with some ANOs (five miscarriages and two foetal deaths). Results previous to the MC showed 60.8% of women had more than one miscarriage, with 4.2% experiencing foetal death. MC reduced the ANO rate by AAR = 60.1% (95%CI: 51.6−68.7%). The NNT to avoid one miscarriage was 1.74 (95%CI: 1.5–2.1) and to avoid one foetal death NNT = 35.75 (95CI%: 15.2–90.9). A total of 84.8% of newborns and 93.2% of women did not experience any complication. As a conclusion, the follow-up of RD or HT pregnant women in the MC drastically reduced the risk of ANOs in this population with a previous high risk. Full article

Background and objectives: Abdominal wall endometriosis, also known as scar endometriosis, is a rare condition that is becoming increasingly common. The recent rise in incidence is attributed primarily to the surge of cesarean births, figures that could be influenced in a positive manner considering the improvements brought towards the ultrasound diagnostic methods that have been made in recent years. Materials and Methods: Here we report the cases of two Caucasian women of 38- (G2P2) and 36-years old (G1P1), both subjected to an ultrasound examination due to a specific symptomatic panel reported during anamnesis. Independently of the current status, in the first patient, there were no reported symptom-specific associations with endometriosis, but she had a known history of mild hereditary thrombophilia; the second woman suffered from two conditions positively associated with endometriosis. Results: In both cases, abnormal structures were revealed, with the diagnostic(s) of endometriosis being histologically confirmed based on a set of features observed during the investigation. Conclusions: This paper aims to highlight the importance of reducing cesarean births and to consider the diagnosis of scar endometriosis in women with a history of obstetric or gynaecological surgeries who present with cyclic, recurrent abdominal pain. Full article