Hereditary Thrombophilia Research Articles

The effect of hereditary thrombophilia on recurrent pregnancy loss: a retrospective cohort study

ObjectiveThrombophilia screening has been performed in patients with conditions such as previous fetal death, (fetal growth restriction) FGR, preeclampsia, (hemolysis. elevated liver enzyme, low platelet count) HELLP Syndrome, previous abruptio placentae, previous thrombosis in pregnancy, and abnormal placental histology. The actual role of hereditary thrombophilia in recurrent pregnancy loss (RPL) is still debated. This study was intended to determine the incidence of specific gene defects for hereditary thrombophilia and to ascertain their impact on RPL in central Anatolia in Turkey.MethodsThis retrospective cohort study was performed between January 2012 and December 2022. All pregnant women with a complete hereditary screening profile were included. The investigated gene polymorphisms were methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, Factor V Leiden G1691A, and Factor II prothrombin G20210A. Cases of pregnant women at least two or more consecutive pregnancy losses before 22 weeks of gestation were defined as RPL. The rates of genetic screening and their association with RPL were analyzed.ResultsRPL was identified in 224 (27.58%) of the 812 pregnant women with complete genetic screening. Although there was no difference in terms of age, body mass index, numbers of ectopic pregnancies, molar pregnancies, or dilatation & curettage (p > 0.05), gravity (2.0 [2.0–3.0] vs. 4.0 [3.0–5.0]), parity (1.0 [1.0–2.0] vs. 1.0 [0–1.0]), live birth (1.0 [1.0–2.0] vs. 1.0 [0–1.0]), anembryonic pregnancy (0 [0–0] vs. 0 [0–0]), miscarriage (0 [0–1.0] vs. 3.0 [2.0–3.0]), and stillbirth (0 [0–0] vs. 0 [0–0]) numbers differed significantly between the groups (p < 0.05). While no significant differences were determined in MTHFR A1298C, Factor V Leiden, factor II prothrombin G20210A, or homocysteine levels (p > 0.05), the homozygous MTHFR C677T positivity rates differed significantly (6.3% in the non-RPL group vs. 11.6% in the RPL group, p = 0.027) .ConclusionThe homozygous MTHFR C677T polymorphisms was found to be more frequent in women with RPL. Further studies with larger cohorts are needed to confirm our results.

Value of Functional Protein S Activity Assays for Detection of Type II Protein S Deficiency

Abstract Background Protein S deficiency is a hereditary thrombophilia which occurs in three forms: Type I (quantitative), type II (qualitative) and type III (qualitative due to a gain of function). Literature suggests that of these, type II is the rarest and most difficult to diagnose. Type II protein S deficiency is only detectable by assaying protein S activity with a functional, clot-based test. However, this test is susceptible to interference and has a lower specificity when compared to antigen assays used to detect free and total protein S levels. Subsequently, the Choosing Wisely Guidelines released by the ABIM Foundation recommends against using protein S activity assays entirely. Instead, they suggest using only free protein S antigen assays. Although the rationale is to avoid false positive results from the protein S activity assay, it ultimately may result in a failure to detect type II protein S deficiency. Objective This study, performed at a tertiary medical center in the Midwestern region of the United States, aims to determine the proportion of false positives in functional assays as well as the percent of true type II protein S deficiency cases within this testing population. Methods All cases with abnormal protein S function within the institution were evaluated from July 2018 through July 2023 and classified as acquired or hereditary deficiencies. Cases were classified as acquired if there was evidence of liver disease, vitamin K deficiency, ongoing thrombosis, consumption, disseminated intravascular coagulopathy, or pregnancy. Possible hereditary deficiency cases were classified as type I, type II and type III: Type I if all assays were low, type III if both active and free protein S assays were low with normal total protein S, and type II if only protein S activity was low. The cutoff defined for normal total and free protein S levels was greater than 70% activity, and the low protein S activity cutoff was defined as less than 50%. Patients with low protein S activity but normal immunologic protein S and an elevated factor VIII were considered falsely low values. Chart review will be performed for remaining cases with low protein S activity to rule out confounders such as vitamin K deficiency, warfarin use, acute phase reaction, or pregnancy. Results From a total of 8805 panels performed to assess for possible thrombophilia, 1580 (18%) were found to have decreased protein S activity. Of these cases, 599 (38%) were considered falsely decreased due to elevated factor VIII levels. 322 cases (3.7%) were considered possible hereditary deficiencies: 217 type III (2.5%), 27 type II (0.3%), and 80 type I (0.9%). Discussion Our data indicates the prevalence of subtypes may be differently distributed than previously believed, which may call for current guidelines to be reevaluated.

Migraine in antiphospholipid syndrome and hereditary thrombophilia: pregnancy-related clinical and diagnostic features and therapeutic issues

Introduction. Migraine is one of the most common primary headaches and a risk factor for cardiovascular and cerebrovascular diseases. Antiphospholipid syndrome (APS) and hereditary thrombophilia (HT) causing pathological pregnancy are highly associated with migraine. Timely migraine recognition related to APS and HT facilitates earlier initiation of thrombophilia pathogenetic therapy and prevention of potential complications.Aim: to analyze the literature data on migraine clinical and diagnostic features in APS and HT as well as pregnancy-related therapeutic issues.Materials and Methods. A search for scientific literature was conducted in electronic databases including PubMed, Google Scholar, eLibrary from 2004 until May 2024. The search methodological basis included the presence of the following keywords and their combinations in Russian and English: "migraine", "antiphospholipid syndrome", "thrombophilia", "migraine and pregnancy", "migraine and thrombophilia", "migraine and cardiovascular diseases". As a result, a total of 184 publications were identified. Next, 62 articles were included in the review.Results. At the current stage, neurologists have no means to diagnose migraine in APS and HT based on headache-intrinsic characteristics. Pregnancy increases a risk of thrombotic complications. A migraine observed in patient's history should be crucial while assessing pregnancy-related obstetric risk. While diagnosing migraine, neurologists need to examine patient obstetric history. The data on most effective and safe therapy for pregnancy-related migraine attacks remain scarce.Conclusion. The frequent association between APS and HT with migraine, the lack of clear migraine clinical features in thrombophilia, patients’ reproductive age, and the high risk of thrombotic complications necessitate collaboration between neurologists and obstetricians-gynecologists for timely diagnostics and management of such patients. The impact of various types of antithrombotic therapy on migraine course requires further clarification. It is promising to conduct studies able to determine of whether migraine attack prevention can avoid adverse pregnancy outcomes in women with former migraine.

Functional outcome predictors and recanalization in cerebral venous thrombosis: A single-center cross-sectional study

Abstract OBJECTIVES: Cerebral venous thrombosis (CVT) is a rare type of stroke. Functional outcome (FOC) in CVT can be affected by different factors, and recanalization is an important determinant. This study aimed to identify the FOC predictors including recanalization in patients with CVT. METHODS: This retrospective study reviewed electronic charts of patients with CVT admitted to the King Fahd Hospital of the University, a teaching and referral hospital between January 2012 and March 2023. Demographic and other clinicoradiological characteristics were noted. Factors affecting FOC were investigated using the Chi-square test, odds ratios (ORs), and 95% confidence interval (CI). RESULTS: Out of 64 patients, 78% achieved good FOC. Age was significantly higher in patients having poor FOC as compared to those having good FOC (P ≤ 0.001). Women had more likelihood to be functionally independent as compared to men (OR = 1.35, 95% CI = 1.01–1.80, P = 0.02). Altered consciousness (OR = 2.94, 95% CI = 1.23–6.99, P = 0.01), venous hemorrhagic infarction (OR = 3.26, 95% CI = 1.36–7.82, P = 0.008), and nonrecanalization (OR = 1.44, 95% CI = 0.97–2.14, P = 0.02) were significantly associated with poor FOC. Hereditary thrombophilia (OR = 0.60, 95% CI = 0.31–1.12, P = 0.03) and infections (OR = 0.59, 95% CI = 0.31–1.12, P = 0.01) were associated with less likelihood of good FOC. Age ≥50 years (P = 0.01) and illness of more than 1-month duration (P = 0.01) were associated with nonrecanalization. CONCLUSION: Older age, male sex, presence of venous hemorrhagic infarction, and nonrecanalization can predict poor FOC in CVT. The recanalization process can be affected by late presentation, and the plausible reason could be a delay in therapeutic anticoagulation. Further prospective and multicenter studies are needed to determine the predictors of FOC and to understand the process of recanalization in CVT.

Hereditary thrombophilia as a possible risk factor for severe disease in COVID-19: a case series.

The risk factors that modulate one's susceptibility for severe COVID-19 have been well documented. Despite this, hypercoagulability remains an often overlooked risk factor for severe disease for COVID-19. Because COVID-19 infection is a risk factor for hypercoagulability, a reasonable presumption/hypothesis is that patients with hereditary thrombophilia would be at a higher risk of thrombotic complications associated with COVID-19 infection. This case report details two cases where previously unknown hereditary thrombophilias likely contributed to the mortality of COVID-19 patients. The first COVID-19 patient's cause of death was pulmonary thromboemboli from deep vein thrombosis due to heterozygous MTHFR C667T and heterozygous PAI-1 4G/5G mutations. The second COVID-19 patient's cause of death was an acute myocardial infarct due to a coronary artery thrombosis in the setting of heterozygous MTHFR A1298C and homozygous PAI-1 4G/5G mutations. In each case, COVID-19 infection was also considered contributory to death. The occurrence of these fatal thrombotic events in COVID-19 patients with hereditary thrombophilias raises questions as to whether this combination of thrombotic risk factors for hypercoagulability may have placed patients at a significant enough risk to experience these fatal thrombotic complications. Thus, while not sufficient alone to prove that SARS-CoV-2 patients with hereditary thrombophilias are at increased risk for thrombotic complications, these two cases indicate that further investigation is warranted into elucidating the relationship between thrombotic risk factors as it may identify an additional high-risk medical condition for COVID-19 and have important diagnostic and therapeutic ramifications.

Clinical characteristics and thrombophilia associated gene variants in Egyptians with unprovoked venous thromboembolism: three centers experience.

Thrombophilias are characterized by excessive venous and arterial thrombosis at regular or unusual sites. It may result from inherited, acquired, or a combination. Hereditary thrombophilia (HT) is detected in 30-40% of patients with thromboembolism. Venous/arterial thrombosis is considered a multifactorial disorder, some patients may have more than one risk factor which may be transient or permanent. Assess the clinical characteristics of patients with unprovoked thromboembolic events and the role of inherited thrombophilia as a causative or additive risk factor. 210 consecutive adult patients with unprovoked thromboembolic events were reviewed in hematology units at three tertiary Egyptian centers between September 2022 and September 2023. The diagnosis of thromboembolic events was confirmed by clinical and radiological findings. Laboratory screening for thrombophilia-associated. Among our patients, 53(25.2%) patients presented with isolated DVT, followed by portal vein thrombosis, 32(15.2%) had a pulmonary embolism, and sagittal sinus thrombosis was developed in 23(10.9%) patients. Younger people who experience spontaneous thromboembolism run the chance of having hereditary thrombophilia; the more mutations discovered, the higher the risk of thrombosis; the lower leg and deep vein thrombosis were the most common sites. Lastly, MTHFR C677T was the most common polymorphism in Egyptians, detected in almost half of the cases.

Venous thromboembolism risk in adults with hereditary thrombophilia: a systematic review and meta-analysis.

This systematic review and meta-analysis assesses venous thromboembolism (VTE) risk in adults with hereditary thrombophilia, including Factor V Leiden (FVL) mutation, prothrombin G20210A (FII) mutation, compound heterozygosity, protein C (PC), protein S (PS), and antithrombin (AT) deficiency. Eligibility criteria included studies suitable for quantitative synthesis with extractable information on VTE risk in adults (> 15 years). There were no restrictions on VTE type, location, or occurrence. Two authors reviewed all studies and extracted data from 107 publications, encompassing 107,130 individuals (21,560 experiencing VTE). We used a random effects model and calculated odds ratios (ORs) with 95% confidence intervals (CIs). The highest risk was associated with homozygous FVL (OR 5.58, 95% CI 4.61-6.74), homozygous FII (OR 5.16, 95% CI 3.12-8.52), and compound heterozygosity (OR 4.64, 95% CI 2.25-9.58). In contrast, VTE risk was lowest for FVL heterozygosity (OR 2.97, 95% CI 2.41-3.67) and FII heterozygosity (OR 2.21, 95% CI 1.70-2.87), whereas PC (OR 3.23, 95% CI 2.05-5.08), PS (OR 3.01, 95% CI 2.26-4.02), and AT deficiency (OR 4.01, 95% CI 2.50-6.44) demonstrated an intermediate VTE risk. These results highlight an increased risk of venous thromboembolism in adults with hereditary thrombophilia. However, the risk for patients with PC, PS, and AT deficiency appears to be lower than previously stated, likely due to varying thrombogeneity of the underlying genetic mutations. Further research addressing this aspect of VTE risk in hereditary thrombophilia is imperative to improve patient management. TRIAL REGISTRATION: PROSPERO registration number CRD42022376757.

Thrombophilia as a reason for the development of ischemic stroke at young age. Features of the clinic and diagnosis

Introduction. Thrombophilia is a common cause of neurological complications.Aim. to present a clinical observation of the development of ischemic stroke in a patient with hereditary thrombophilia.Main findings. A case is presented of a man, aged 30, who developed an ischemic stroke in the basin of the left medial artery. A diagnostic study revealed that the development of the ischemic stroke was facilitated by thrombophilia caused by a combination of polymorphic variants of the fibrinogen genes (G-455A(G-467A)) and methylenetetrahydrofolate reductase (C677T). Thus, hereditary thrombophilia was a risk factor for the development of ischemic stroke in the patient at a young age. Therefore, in the absence of traditional risk factors for the development of ischemic stroke, a genetic analysis for thrombophilia is necessary.

Hereditary Thrombophilia: A Case of Subacute Pulmonary Embolism in a 68-Year-Old Female with a Mutation in the PROC Gene.

Hereditary Thrombophilia: A Case of Subacute Pulmonary Embolism in a 68-Year-Old Female with a Mutation in the PROC Gene.

The Burden of Deep Vein Thrombosis and Risk Factors in Pregnancy and Postpartum-Mirroring Our Region's Particularities.

(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.

The embodied experience of genetic inheritance in hereditary thrombophilia.

Our study focuses on exploring the embodied experiences of genetic inheritance within and between bodies. Drawing on insights from studies on embodied experiences and family risk we examine how interviewees perceive their vulnerability, negotiate family narratives, genetic inheritance, and the transmission of genetic knowledge within families. To answer these questions, we conducted an interpretative phenomenological analysis, based on 10 in-depth interviews with patients with thrombophilia diagnosis and venous thromboembolic disease, in Hungary. Three Experiential Themes were identified: The body as a repository of risk (1), Family heritage (2), and The borderline of thrombophilia-liminality (3). Our study has found that patients living with thrombophilia interpret their bodies as repositories of genetic risk. It seems that an important aspect of adapting to thrombophilia is the creation of genetically vulnerable identities. Alongside the new identity(ies), living with risk can induce newly discovered forms of familial responsibility, within the common identification experience of family history and succession. Based on our research, we see that individuals living with thrombophilia experience the liminality of borderlands. In some cases, however, the space between health and illness represents a dynamic permeability for people with thrombophilia, which can be triggered by medical uncertainty in addition to individual experiences and life events.

LACTOFERRIN IN THE TREATMENT OF INTERSTITIAL CYSTITIS: A RETROSPECTIVE PILOT STUDY.

Interstitial cystitis (IC), defined as a painful bladder syndrome (PBS), is a chronic condition that manifests itself as a suprapubic pain associated with an enhancing of frequency/urgency of urination, and for which there is no cure. Here, we present a retrospective pilot study on women affected from IC/PBS and treated with bovine lactoferrin (bLf). A total of 31 women, affected (20) or unaffected (11) from hereditary thrombophilia (HT), presented the median of 6 episodes of IC/PBS during the 6 months before the study. Treatment consisted of 17 weeks of orally administered Valpalf® capsules, containing bLf plus sodium bicarbonate and citrate. Out of 31 patients, only 3 women had one episode of IC/PBS during the follow-up period, while no episode was observed in 28 women. In the HT group, a significant decrease in both serum IL-6 and D-dimers was found after Valpalf® treatment. Moreover, in Valpalf®-treated women, cystoscopy revealed a global improvement in the appearance of the bladder, especially in term of inflammation/irritation and presence of Hunner ulcers. Even if our results must be corroborated by randomized double-blinded controlled trials on a larger number of patients, our observations indicate that bLf treatment is efficient in relieving IC/PBS symptoms, without side effects.

P-432 The association of early pregnancy loss and thrombophilia

Abstract Study question Is there a correlation between thrombophilia and the occurrence of pregnancy loss? Summary answer No statistically significant association is observed between thrombophilia and the live births. What is known already The understanding of recurrent pregnancy loss is a subject of controversy, encompassing both its causes and potential treatments and there is currently no consensus regarding the criteria for examining patients experiencing pregnancy loss, the specific tests to be conducted, or the appropriate treatment approaches. The connection between hereditary thrombophilia and pregnancy loss remains unclear. Study design, size, duration Within the timeframe of 01/12/2020 to 01/06/2022, pregnancy loss clinic of a tertiary university hospital received a total of 296 patients who had experienced at least one pregnancy loss. Following examination, these patients were encouraged to return to clinic if they became pregnant again. Among them, 192 patients did become pregnant and sought further care. These patients received treatment based on pregnancy loss clinic’s management algorithm, and their subsequent pregnancies were closely monitored. Participants/materials, setting, methods This prospective study involved 192 patients who, after undergoing examination, experienced subsequent pregnancies. These patients were categorized into two groups based on their obstetric outcomes: live birth and pregnancy loss. The primary focus of the study was to compare hereditary and acquired thrombophilia between these two groups. Additionally, secondary outcomes included a comparison of obstetric history, genetics, uterine anomalies, and results from biochemical and hormonal examinations between the two groups. Main results and the role of chance 150 of 192 patients achieved live birth (78.13%). The prevalence of hereditary thrombophilia mutations showed no significant differences between the two groups. Specifically, in the pregnancy loss group, the FV Leiden mutation rate was 12.5%, compared to 13.7% in the live birth group (p = 0.836). The Prothrombin gene mutation was observed in 7.5% of the pregnancy loss group and 7.25% of the live birth group (p = 1.000). Additionally, the PAI 4G/5G polymorphism was present in 60% of the pregnancy loss group and 52% of the live birth group (p = 0.347), the MTHFR/C677T polymorphism was detected in 62.5% of the pregnancy loss group and 56.5% of the live birth group (p = 0.500), and the MTHFR/1298C polymorphism was identified in 62.5% of the pregnancy loss group and 60.1% of the live birth group (p = 0.788). While antithrombin III levels were comparable between the two groups (p = 0.53), a noteworthy decline in antithrombin III levels was observed with an increasing history of losses: 110.2 for one loss, 106.0 for two losses, and 100.2 for three or more losses (p = 0.033). The homocysteine level was found to be 10.85 μM (range: 6.60-24.80 μM) in the pregnancy loss group and 9.40 μM (range: 4.90-37.00 μM) in the live birth group (p = 0.023). Limitations, reasons for caution A limitation of our study is its single-center nature. Additionally, we did not include a healthy control group with no history of pregnancy loss, preventing a direct comparison between the pregnancy loss group and a group unaffected by such experiences. Wider implications of the findings Our study provides valuable insights into questioning the live birth expectations of women who have experienced pregnancy loss and underscores the significance of thrombophilia in the context of pregnancy loss. Trial registration number not applicable

Heterozygous Prothrombin Mutation-Associated Thrombophilia.

Venous thromboembolism (VTE) is predisposed by thrombotic mutations in patients with hereditary thrombophilia. Although prothrombin deficiencies caused by homozygous or compound heterozygous mutations are associated with bleeding diathesis, rare cases have shown a correlation between heterozygous prothrombin mutations and thrombosis. We surveyed genetic variants involved in thrombosis and hemostasis in 347 patients with unprovoked VTE or having a positive family history of thrombosis. For patients identified with heterozygous prothrombin mutations, we conducted family investigations and performed a thrombin generation test (TGT) to elucidate the thrombotic risk. Novel mutants were expressed and subjected to functional assays to clarify the underlying thrombotic mechanisms. Heterozygous prothrombin mutations were identified in 3.5% of patients (12/347), including three novel mutations Phe382Ser, Phe382Leu, and Asp597Tyr found in one patient each, as well as previously reported Arg541Trp mutation in four patients and Arg596Gln mutation in five patients. A total of 42 mutation carriers were identified within the 12 pedigrees, among whom 64.3% (27/42) had experienced thrombotic events. TGT results demonstrated hypercoagulability for carriers of the five mutations, with Arg596Gln showing the highest thrombin generation potential followed by Arg541Trp. The Phe382-associated mutations severely impaired thrombomodulin-binding ability of thrombin, resulting in obviously reduced protein C (PC) activation. The Asp597Tyr mutation exhibited a mild reduction in both inactivation by antithrombin and PC activation reactions. The presence of heterozygous prothrombin mutations represents a potential genetic predisposition for VTE. All thrombosis-associated mutations potentiate coagulation activity by either conferring antithrombin resistance and/or impairing PC pathway activity.

Recurrent Pulmonary Embolism at High Altitude in a Mountaineer with Hereditary Thrombophilia.

Szymczak, Robert K., Magdalena Sawicka, and Małgorzata Jelitto. Recurrent pulmonary embolism at high altitude in a mountaineer with hereditary thrombophilia. High Alt Med Biol. 00:000-000, 2024.-It is speculated that high-altitude travel is an independent risk factor for thrombosis. Mountaineering-specific factors, such as hypoxia, cold, and immobilization, may interact with patient-specific risk factors and contribute to thrombus formation. We present the case of a mountaineer with hereditary thrombophilia who experienced recurrent pulmonary embolism during high-altitude expeditions.

The risk profiles of pregnancy-related cerebral venous thrombosis: a retrospective study in a comprehensive hospital

ObjectivesTo investigate the risk factors and underlying causes of pregnancy-related cerebral venous thrombosis (PCVT).MethodsA retrospective cohort of 16 patients diagnosed with CVT during pregnancy and postpartum (within six weeks after delivery) in a comprehensive hospital in China between 2009 and 2022 were carefully reviewed, focusing on demographic, clinical, and etiological characteristics, especially underlying causes. We matched 16 PCVT patients with 64 pregnant and puerperal women without PCVT to explore risk factors and clinical susceptibility to PCVT.ResultsPCVT occurred commonly during the first trimester (43.75%) and the puerperium (37.5%). The frequency of anemia, thrombocytosis and thrombocytopenia during pregnancy, dehydration, and pre-pregnancy anemia was significantly higher in women with PCVT than in those without PCVT (P < 0.05). Among the 16 patients, five were diagnosed with antiphospholipid syndrome and one was diagnosed with systemic lupus erythematosus. Three patients had distinct protein S deficiency and one had protein C deficiency. Whole Exome Sequencing (WES) was performed for five patients and revealed likely pathogenic mutations associated with CVT, including heterozygous PROC c.1218G > A (p. Met406Ile), heterozygous PROS1 c.301C > T (p. Arg101Cys), composite heterozygous mutation in the F8 gene (c.144-1259C > T; c.6724G > A (p. Val2242Met)) and homozygous MTHFR c.677C > T (p. Ala222Val).ConclusionsThe occurrence of anemia, thrombocytopenia and thrombocytosis during pregnancy, dehydration and pre-pregnancy anemia suggested a greater susceptibility to PCVT. For confirmed PCVT patients, autoimmune diseases, hereditary thrombophilia, and hematological disorders were common causes. Screening for potential etiologies should be paid more attention, as it has implications for treatment and long-term management.

Thrombophilia testing for whom, why and when – a review of current practices

Thromboembolic conditions have accounted for 1 in 4 deaths worldwide in 2010. Thrombosis, which is the common pathogenesis of myocardial infarction, ischaemic stroke, and venous thromboembolism (VTE), is the leading cause of death (1/5 deaths in 1990). Hospital-acquired VTE accounts for approximately 60 percent of all VTEs annually. Others include cancer-associated thrombosis and gender associated risks. In addition to the disease burden, it also causes a significant economic burden world-wide. Multiple diagnostic tests and treatment, prolonged hospital stay and follow-up care, including management of recurrent VTE can be extremely costly. Therefore, it is important to focus on VTE prevention so that health care systems can save money, improve outcomes and save lives. In this background, it is important to have a clear direction as to when, how and whom to test for thrombophilia. Testing for thrombophilias is often performed without a clear understanding of the clinical implications of such results. Guidelines vary in the appropriate use of thrombophilia testing. In this review, these variations in thrombophilia testing and the implications mentioned in the recent guidelines and other articles are discussed. The review of such guidelines, guidance statements, review articles conclude that screening for hereditary thrombophilia has very limited advantage in the management of patients with thrombosis. Screening for antiphospholipid syndrome (APLS) is more important given its high rate of recurrence in both venous and arterial thrombosis. Screening for underlying haematological conditions such as myeloproliferative neoplasms (MPN) and paroxysmal nocturnal haemoglobinuria (PNH) is also considered important.

Spontaneous coronary artery dissection in a young woman with signs of connective tissue dysplasia and hereditary thrombophilia: clinical case

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a disease that develops unrelated to intracoronary intervention, atherosclerosis, aortic dissection, or mechanical trauma and causes a false lumen (intramural hematoma) in the wall of the coronary artery (CA) with impaired blood flow in it and myocardial ischemia in the affected region of the CA. SCAD most often develops in young and middle-aged adults (aged ≤50 years); among women, it becomes the culprit in 24%–35% of cases of acute myocardial infarction (MI). SCAD is a risk factor for MI, and incorrect interpretation of the angiographic picture and intravascular imaging methods can lead to incorrect tactics of patient behavior.&#x0D; CLINICAL CASE DESCRIPTION: This article presents a clinical case of SCAD leading to the development of MI in a young woman with concomitant connective tissue dysplasia and hereditary thrombophilia. The angiographic disease course resembled focal atherosclerosis, and in the course of invasive management, complications had arisen, confirming the probable genesis of coronary artery obstruction.&#x0D; CONCLUSION: SCAD is a complex disease, with a sudden onset and an ambiguous prognosis. In most cases, SCAD develops in young women in the absence of cardiovascular factors. It is difficult to diagnose because its signs and symptoms are similar to more common diseases, mainly MI. SCAD can masquerade as focal stenosis on an angiogram, mimicking an atherosclerotic plaque. The «gold standard» for diagnosing SCAD is optical coherence tomography (OCT). OCT enables the visualization of the state of all coronary artery walls and elucidates the pathogenetic mechanisms of MI. If performing OCT is impossible after diagnostic coronary angiography in young patients in suspected cases, the likelihood of DST and SCAD risk must be assessed to avoid errors in choosing treatments. The technical accessibility of intracoronary imaging methods reduces the frequency of diagnostic and, consequently, treatment errors.

Review Article: Early Recurrent Pregnancy Loss

Recurrent pregnancy loss, which affects 2%–5% of individuals, is just a significant concern for women's health. Uterine malformations, antiphospholipid syndrome, metabolic or endocrine diseases, as well as chromosomal abnormalities are among the often reported established reasons. Alternative aetiologies, like chronic uterine infections, hereditary thrombophilias, luteal stage insufficiency, or excessive male DNA disintegration rates, have been put forward yet remain regarded as debatable. The results for individuals who experience recurrent miscarriage had increased throughout time because to evidence-based therapies including surgical repair of chromosomal abnormalities, aspirin as well as anticoagulation in anticardiolipin disorder. About 50% of the instances, though, are still unsolved, so they are managed effectively with estrogen augmentation, anticoagulation, and/or immunostimulatory therapies. Regardless of the reason, couples who experience recurrent fetal death have a favourable long-term outlook and also the majority ultimately has a safe live delivery. Several miscarriages, though, may have a major psychological impact just on afflicted people, and numerous attempts are now being undertaken to enhance therapies or shorten the time it takes to conceive successfully. With an emphasis on inexplicable repeated fetal loss as well as the current usage of empiric therapies, this article reviews the recognised or contentious aetiologies as well as the suggested therapeutic approaches. As well, it covers the present use of pre - implantation genetic screening inside the treatment of repeated miscarriages.

Immunological Risk Factors in Recurrent Pregnancy Loss in Patients With Hereditary Thrombophilia.

Recurrent pregnancy loss (RPL) is a complicated reproductive disorder with underlying genetic and immunological causes. RPL may be influenced by hereditary thrombophilia, a class of blood clotting-related genetic abnormalities, via the vascular and immune systems. This study examines the immunological characteristics that hereditary thrombophilia patients have in common with RPL. A prospective cohort study included 300 patients split into two groups: a control group without hereditary thrombophilia and a group with the condition. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ)levels were measured, along with demographic specifics, antiphospholipid antibodies, natural killer (NK) cell counts, and other cytokines. Group differences were found using statistical analysis. Antiphospholipid antibodies were significantly more common in the thrombophilia group (42% testing positive, p=0.001) compared to the control group (12% testing positive), despite demographic factors being similar between groups (p=0.372 and p=0.093).When body mass index (BMI) was taken into account, the studyfound a statistically significant difference (p=0.046), with the thrombophilia group having a higher mean BMI (26.3 kg/m2, standard deviation (SD): 2.8) than the control group (24.7 kg/m2, SD: 3.1). IL-6(14.8 pg/mL, SD: 3.2, p=0.029) were higher than the control group (12.4 pg/mL,SD: 2.1), and TNF-α levels were higher in the thrombophilia group (10.5 pg/mL, SD: 2.0, p=0.012) compared to the control group (8.9 pg/mL,SD: 1.5), but NK cell counts did not differ significantly (p=0.213). This study emphasizes the role of elevated pro-inflammatory cytokines (IL-6 and TNF-α) and antiphospholipid antibodies in RPL among people with hereditary thrombophilia. In this population, early detection and immunomodulatory interventions may improve pregnancy outcomes. To fully comprehend these mechanisms and create customized treatments, collaborative research is required.