Primary Thrombophilia Research Articles

Primary thrombophilia in Mexico XVIII: Increased rate of thrombosis in persons with the sticky platelet syndrome in the COVID-19 era.

Primary thrombophilia in Mexico XVIII: Increased rate of thrombosis in persons with the sticky platelet syndrome in the COVID-19 era.

Epidural venous plexus enlargement secondary to left iliac vein occlusion: case report

We present a 34-year-old male case, with a history of primary thrombophilia under treatment with rivaroxaban, deep vein thrombosis of the left leg and extremities plus pulmonary thromboembolism 10 years ago. He reported digestive symptoms and chronic low back pain with left leg edema. Phlebography diagnoses occlusion of the left iliac vein with dilated veins of more than 3 cm on the left peri-vertebral side. Angioplasty plus stent placement is performed, the collateral venous network and the patient's symptoms disappear.

Multisystem inflammatory syndrome complicated by pulmonary embolism in a child

Purpose - to present a clinical case of a particular complication of post-COVID multisystem inflammatory syndrome (MIS) - pulmonary embolism (PE) which developed due to primary hereditary thrombophilia in a child for better understanding of the MIS evolution and prognosis in children (MIS-C). Case report. In an 11-year-old boy who previously had no hemorrhagic manifestations, the first symptoms of the disease occurred in the form of fever and a hemorrhagic rash on the lower extremities. Later, he developed signs of respiratory failure, his condition worsened, and bilateral community-acquired viral pneumonia caused by COVID-19 was diagnosed. The child presented with post-COVID MIS manifested as PE, which caused further genetic examinations for hereditary thrombophilia. Primary thrombophilia was detected (F2 gene - prothrombin (20210 G>A) D68.5). Concomitant hereditary pathology was probably the reason for a severe course of the infection and the development of a complication in the form of PE requiring intensive and long-term anticoagulant therapy. Conclusions. In case of PE detection, especially in young patients, examinations to confirm or rule out hereditary or acquired thrombophilia are required, that defines recurrent venous thromboembolism prevention programs. This clinical case report is a contribution to the study on the issues of MIS-C, defining links between pulmonary complications (transient or persistent) and serious sequelae in the future. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Cerebral infarction and in-hospital mortality for patients admitted to hospital with intracardiac thrombus: insights from the National Inpatient Sample.

The factors associated with cerebral infarction and mortality in patients hospitalized with intracardiac thrombus are unknown. A retrospective cohort study was undertaken of nationally representative hospital admissions in the National Inpatient Sample with a diagnosis of intracardiac thrombus between 2016 to 2019. Multiple logistic regressions were used to define factors associated with cerebral infarction and in-hospital mortality. There were a total of 175,370 admissions for patients with intracardiac thrombus and 10.1% patients had cerebral infarction (n = 17,675). Intracardiac thrombus represented 4.4% of primary diagnosis for admissions while circulatory conditions (65.4%), infection (5.9%), gastrointestinal conditions (4.4%), respiratory conditions (4.4%) and cancer (2.2%) were the other prevalent primary diagnoses. All-cause mortality was higher for patients with cerebral infarction (8.5% vs 4.8%). The five factors most associated with cerebral infarction were nephrotic syndrome (OR 2.67 95%CI 1.05-6.78), other thrombophilia (OR 2.12 95%CI 1.52-2.95), primary thrombophilia (OR 1.99 95%CI 1.52-2.53), previous stroke (OR 1.61 95%CI 1.47-1.75) and hypertension (OR 1.41 95%CI 1.27-1.56). The strongest independent predictors of death were heparin induced thrombocytopenia (OR 2.45 95%CI 150-4.00), acute venous thromboembolism (OR 2.03 95%CI 1.78-2.33, p < 0.001) acute myocardial infarction (OR 1.95 95%CI 1.72-2.22), arterial thrombosis (OR 1.75 95%CI 1.39-2.20) and cancer (OR 1.57 95%CI 1.36-1.81). Patients with intracardiac thrombus are at risk of cerebral infarction and in-hospital mortality. Nephrotic syndrome, thrombophilia, previous stroke, hypertension, and heparin induced thrombocytopenia were associated with cerebral infarction, while acute venous thromboembolism, acute myocardial infarction, and cancer were predictors of mortality.

Iliofemoral thrombosis in a patient with recurrent nephrotic syndrome

Nephrotic syndrome is one of the most common glomerulopathies in children, accompanied by a high risk of thrombosis due to hypoalbuminemia, hypovolemia, hyperlipidemia, hyperfibrinogenemia, and antithrombin III deficiency. The article describes a clinical case of iliofemoral thrombosis in a 16-year-old boy with recurrent nephrotic syndrome and primary thrombophilia (heterozygote F5 — Leiden mutation) was diagnosed. The presented clinical observation indicates the multifactorial origin of thrombotic complications in nephrotic syndrome, caused by a combination of an imbalance between the proand anticoagulant components of the blood coagulation system and individual risk factors (severity of proteinuria, hypoalbuminemia, comorbidity, hereditary thrombophilia), and therefore further study is needed to determine the tactics of prevention and treatment.

Primary Thrombophilia XVII: A Narrative Review of Sticky Platelet Syndrome in México.

Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined with other coagulopathies, contributes significantly to the morbidity and mortality of patients with primary thrombophilia. It is easily treatable with antiplatelet drugs; however, the methods for diagnosis are not readily available in all clinical laboratories and the disorder is often overlooked by most clinicians. Herein, we present the results of more than 20 years of Mexican experience with the study of SPS in a Mestizo population.

Features of hereditary thrombosis (analysis of clinical cases in newborns)

Background. Dysfunctions of hemostasis include conditions occurring both with hemorrhagic syndrome and in the form of thrombosis, the number of which is growing due to the intensification of the therapy. The relevance of the topic is determined by the prevalence of these pathological conditions in newborns, the peculiarities of the hemostasis system in the neonatal period, as well as the difficulties of diagnosis and interpretation of laboratory parameters.&#x0D; Aim. Studying the features of clinical manifestations and genetic markers in newborns with clinical thrombosis on the background of primary thrombophilia.&#x0D; Materials and methods. A retrospective continuous analysis of the case histories of newborn children with thrombophilia who were hospitalized at the Krasnoyarsk Regional Clinical Center for Maternity and Childhood Protection in the period from January 2014 to January 2020 was carried out.&#x0D; Results. The debut of thrombosis in newborns is represented mainly by venous thrombosis of various localizations. Genetic mutations were identified in these patients, which are mainly associated with the work of the folate and methionine cycles (MTHFR: g.677CT, MTHFR: g.1298AC, MTRR: g.66AG and MTR: g.2756AG). A complicated course was noted in the presence in the genome of the combinations MTHFR: g.677CT, MTR: g.2756AG and MTRR: g.66AG and/or homozygous carriage of MTHFR: g.677CT, MTHFR: g.1298AC. The main trigger was peripheral vascular catheterization.&#x0D; Conclusion. A decrease in the levels of natural anticoagulants in newborns with some physiological features of hemostasis deserves close attention of neonatologists and clinicians, requires an integral assessment of the hemostasis system and additional examinations, including the analysis of genetic changes not only in the hemostasis system, but also in folate and methionine cycles.

Immunological mechanisms in multiple spontaneous cervical artery dissection: An illustrative case and review of the literature

Dissection of the cervical arteries is the leading cause of stroke in young adults, yet the etiology and pathogenesis of this event remain unclear. However, a growing number of data in the literature support the potential implications of immunological mechanisms in the pathogenesis. Several large patient groups and multicentre cohorts have reported significant associations with recent infections and elevated inflammatory markers. There are also several case reports and case series suggesting an association with various autoimmune disorders and viral infections. Some case reports have also detailed cervical artery dissections linked to the use of biological therapies for other pathologies. In the present case, a 38-year-old female patient with triple spontaneous cervical artery dissection presented multiple potential trigger factors as recent infection, autoimmune thyroid disease, primary thrombophilia and hyperhomocysteinemia. This report sought first presents this case, and then reviews the existing relevant literature data regarding the potential immunological mechanisms implicated in the pathogenesis of cervical artery dissection.

Gender Differences in Risk Factor Profile and Clinical Characteristics in 89 Consecutive Cases of Cerebral Venous Thrombosis.

Gender has been shown to be an important variable in cerebral venous thrombosis (CVT) risk and significantly influences its clinical manifestations and outcome. The aim of our study was to investigate the gender-specific risk factor profile and clinical picture of this rare cerebrovascular disorder. Materials and methods: We retrospectively reviewed the medical records of 89 consecutive cases of CVT at a tertiary neurology clinic in Târgu Mures, Romania, between June 2009 and January 2021 to analyze the gender-related differences in etiology, clinical presentation, and outcome. Results: Women comprised 62.5% of the cohort. Females were significantly younger than males (37.3 years versus 48.8 years, respectively, p = 0.001), and the main risk factors were hormone related in 37.9% of the cases, followed by primary thrombophilia (34.4%), smoking (25.8%), obesity (17.2%), infections (17.2%), mechanical factors (17.2%), cancer (8.6%), systemic autoimmune disorders (8.6%), and hematological disorders (8.6%). In male patients, the main risk factors were smoking (41.9%), primary thrombophilia (29%), infections (22.6%), heavy alcohol consumption (16.1%), and venous thromboembolism in the medical history (12.9%). Frequency of headache was higher in females than in males (75.9% versus 67.7%), whereas frequency of coma (6.5% in males versus 1.7% in females) and dizziness (19.4% in males versus 10.3% in females) was higher in males. CVT onset was acute in 41.4% of females and 38.7% of males. The Rankin score at discharge was significantly lower in females compared with males (0.6 versus 1.6), reflecting a more favorable short-term outcome. Mortality was 6.4% in males and 1.7% in females. Conclusions: CVT is a multifactorial disorder that has a broad spectrum of risk factors with important gender-related differences in clinical manifestation and prognosis. Female patients, especially those with hormone-related risk factors, have a more favorable outcome than male patients.

Postpartum Cerebral Venous Thrombosis—A Single-Center Experience

Background: Cerebral venous thrombosis (CVT) is a rare variant of stroke in the general population, but an important subtype among pregnancy- and puerperium-related cases. Studies describing its risk factors and clinical characteristics are limited. The aim of our study is to disclose these aspects and compare with cases unrelated to pregnancy and puerperium. Materials and Methods: We performed a retrospective analysis including 88 consecutive cases from a tertiary neurology clinic with a diagnosis of CVT. Ten of the 88 cases (11.3%) appeared during the postpartum period. Results: The mean age of the puerperal CVT cases was 26.5 years. The main pregnancy-related risk factors besides puerperium were cesarean delivery (5/10), preeclampsia (2/10), and stillbirth (1/10). General risk factors for thrombosis, i.e., infection, smoking, and primary hypercoagulability, were identified in 50% of cases. Onset was in the first 3 weeks after delivery, with a mean value of 9.6 ± 5.6 days. Headache was present in 90% of postpartum CVT cases and in 76.1% of non-postpartum female cases. Seizures were more frequent in the postpartum group (60% vs. 34.8%). Onset was acute (<48 h) in 50% of postpartum cases and in 30.4% of the non-postpartum female group. The Rankin score at discharge was significantly lower in the postpartum group (0.22 vs. 0.7, p = 0.02), suggesting a more favorable short-term outcome. Conclusions: The early postpartum period represents an important risk for the development of CVT. Cesarean delivery and preeclampsia, besides general risk factors such as infection, smoking, and primary thrombophilia, contribute to enhanced risk. Puerperium-related CVT presents a more favorable outcome compared with CVT with other etiologies.

Primary Thrombophilia XVI: A Look at the Genotype of the Sticky Platelet Syndrome Phenotype.

The sticky platelet syndrome (SPS) was described by Mammen in 1983. Since then, scientists in several countries have identified the condition and published cases or series of patients, thus enabling the description of the prevalence of the inherited condition, its salient clinical features, and the treatment of the disease. The diagnosis of the SPS phenotype requires fresh blood samples and special equipment which is not available in all coagulation laboratories. In the era of molecular biology, up to now it has not been possible to define a clear association of the SPS phenotype with a specific molecular marker. Some molecular changes which have been described in platelet proteins in some persons with the phenotype of the SPS are here discussed. Nowadays, the SPS phenotype may be considered as a risk factor for thrombosis and most cases of the SPS developing vaso-occlussive episodes are the result of its coexistence with other thrombosis-prone conditions, some of the inherited and some of them acquired, thus leading to the concept of multifactorial thrombophilia. Ignoring all these evidence-based concepts is inappropriate, same as stating that the SPS is a nonentity simply because not all laboratories are endowed with adequate equipment to support the diagnosis.

A Nationwide Analysis of Budd–Chiari Syndrome in the United States

The Budd-Chiari Syndrome (BCS) is a rare disorder characterized by hepatic venous outflow obstruction. The primary objectives of our study were to assess temporal trends in the prevalence of BCS among hospitalized patients in the United States using the National Inpatient Sample (NIS) database and to evaluate demographics, risk factors, and common presentation of BCS. Data were extracted from the NIS to identify patients >18 years of age using all listed diagnosis of BCS from 1998 to 2017 and analyzed. Between 1998 and 2017, we identified a total of 8435 hospitalizations related to BCS. Over the 19-year period, the hospitalization rate for BCS increased consistently from 4.96 per 1,000,000 US population in 1998 to 10.44 per 1,000,000 in 2017, with an annual percentage change increase of 4.41% (95% confidence interval [CI]: 4.23%-4.59%, P < 0.0001). The most common risk factor (7.75%) was myeloproliferative disorder (essential thrombocythemia, polycythemia vera, myelofibrosis, chronic myeloid leukemia) followed (7.32%) by a hypercoagulable state (primary thrombophilia, protein C deficiency, factor V Leiden mutation, antiphospholipid antibody syndrome or prothrombin gene mutation) and paroxysmal nocturnal hemoglobinuria (1.63%). Cirrhosis was present in 18.7%, Portal vein thrombosis in 7.9%, and inferior vena cava thrombosis in 6.4%. The most common manifestations of BCS were ascites (29.9%) or acute kidney injury (18.8%) followed by hepatic encephalopathy (9.6%) and acute liver failure (5.6%). This large population-based study from the United States showed increasing hospitalizations related to BCS. Common presentation was ascites and acute kidney injury.

Primary thrombophilia XV: antithrombotic treatment of sticky platelet syndrome worldwide

Background: Sticky platelet syndrome (SPS) is a common but under-recognized cause of thrombosis. Treatment with antiplatelet drugs results in a low re-thrombosis rate. The aim of this study is to analyze the treatment of persons with SPS in different parts of the world. Methods: Data from 43 publications describing 1,494 patients with SPS worldwide were analyzed. Data concerning treatment was available in 16 of these papers, and involving 332 patients. Results: Three hundred thirty two patients were treated with antiplatelet drugs; 303 were given solely aspirin and 29 received combinations with aspirin (heparin or coumadin), whereas two persons did not receive aspirin. The re-thrombosis rate for patients given antiplatelet drugs was 5/332 (1.5%) and only 3 patients died. Conclusions: Most patients with SPS are treated with antiplatelet drugs worldwide, the re-thrombosis rate is very low. Physicians worldwide are aware of the fact that the best treatment for persons with the SPS is the use of antiplatelet drugs.

P022: Primary thrombophilia increases the risk of pregnancy complications (gestational diabetes and pregnancy-induced hypertension): experience of a medical center

P022: Primary thrombophilia increases the risk of pregnancy complications (gestational diabetes and pregnancy-induced hypertension): experience of a medical center

Primary Thrombophilia in Mexico XIII: Localization of the Thrombotic Events in Mexican Mestizos With the Sticky Platelet Syndrome.

The sticky platelet syndrome (SPS) is a common cause of both arterial and venous thrombosis, being a dominant autosomal disease with qualitative platelet alterations and familial occurrence. It is characterized by platelet hyperreactivity with increased platelet aggregability in response to low concentrations of platelet agonists: epinephrine, adenosine diphosphate, or both. The clinical manifestations involve venous or arterial thrombosis, recurrent pregnancy loss, and fetal growth retardation. To analyze the localization of the thrombotic episodes in a cohort of Mexican mestizo patients with SPS. Between 1992 and 2016, 86 Mexican mestizo patients with SPS as the single thrombophilic condition were prospectively identified; all of them had a history of thrombosis. There were 15 males and 71 females. The thrombotic episodes were arterial in 26 cases and venous in 60 (70%). Arterial thrombosis was mainly pulmonary thromboembolism, whereas venous thromboses were identified most frequently in the lower limbs. Mexican mestizo population with SPS is mainly female; the type I of the condition is the most frequent; both arterial and venous thrombosis can occur, and they are mainly pulmonary embolism and lower limbs venous thrombosis, respectively.

Challenges of Anticoagulation Therapy in Pregnancy.

Thrombotic complications in pregnancy represent a major cause of morbidity and mortality. Pregnancy is a primary hypercoagulable state due to enhanced production of clotting factors, a decrease in protein S activity, and inhibition of fibrinolysis. These physiologic changes will yield a collective rate of venous thromboembolism (VTE) of about 1-2 in 1000 pregnancies for the general obstetric population, which represents a five- to tenfold increased risk in pregnancy compared to age-matched non-pregnant peers. A select group of women, however, will carry a significantly higher rate of thrombosis due to primary thrombophilia, either inherited or acquired. This introduces a population of women who may benefit from prophylactic anticoagulation, either antepartum or postpartum. The coagulation changes that occur in preparation for the hemostatic challenges of delivery endure for several weeks postpartum. In fact, daily risk for pulmonary embolism (PE) is the highest postpartum. Use of anticoagulation in pregnancy introduces particular risk at the time of delivery, where bleeding and clotting risk collide. Altered metabolism rates of anticoagulants in pregnant women often necessitate closer monitoring than is required outside of pregnancy in order to ensure efficacy and safety. Heparin products are the mainstay of treating VTE in pregnancy, chiefly because they do not cross the placenta. In women with mechanical heart valves, the ideal anticoagulation regimen remains controversial as heparin use has shown inferior outcomes for preventing thromboembolic complications compared to warfarin, but warfarin carries risk for fetal embryopathy. Other populations where a heparin alternative is necessary include women with a history of heparin-associated thrombocytopenia (HIT) or other heparin intolerance. Further challenging the management of anticoagulation in pregnancy is the dearth of randomized clinical trials. The evidence governing treatment recommendations is largely based on expert guidelines, observational studies, or extrapolation from non-pregnant cohorts. A careful critique of a woman's history, as well as the available data, is essential for optimal management of anticoagulation in pregnancy. Such decisions should involve a multidisciplinary team involving obstetrics, hematology, cardiology, and anesthesia.

Primary thrombophilia in México XII: Miscarriages are more frequent in persons with the Sticky Platelet Syndrome (SPS)

Objective:Sticky platelet syndrome (SPS) is an inherited condition that leads to arterial and venous thrombosis. There is scant information about the association between SPS and obstetric complications. This study aimed to assess the relationship between SPS and fetal loss at a single institution.Materials and Methods:The obstetric histories of all consecutive female patients prospectively studied in a 324-month period at a single institution with a history of thrombosis and a clinical marker of primary thrombophilia were reviewed.Results:Between 1989 and 2016, 268 consecutive patients with a clinical marker of primary thrombophilia and a history of arterial or venous thrombosis were studied; of these, 108 were female patients. Within this subset of thrombophilic females, 77 (71%) had been pregnant at some point. Twenty-eight of these 77 patients (37%) had had a spontaneous abortion and 24 of those (86%) were found to have SPS. On the other hand, in a subset of 73 female patients with SPS who had been pregnant, 32% had miscarriages. These figures are significantly higher than the prevalence of spontaneous abortions in the general Mexican population of pregnant women, which is 12%-13% (chi-square: 7.47; p=0.0063). Accordingly, the relative risk of having a miscarriage is 2.66 times higher in female patients with SPS than in the general population (p=0.0014).Conclusion:In Mexico, female patients with SPS experience significantly more spontaneous abortions than the general population. Since the treatment of SPS is simple and effective and could in turn prevent adverse obstetric outcomes, its investigation in women treated for obstetric complications may be useful and deserves further research.

Primary Thrombophilia in México XI: Activated Protein C Resistance Phenotypes are Multifactorial.

Activated protein C resistance (aPCR) phenotypes represent around 20% of the laboratory findings in Mexican Mestizos having suffered thrombosis and displaying clinical markers of thrombophilia. In a single institution for a 276-month period, 96 Mexican mestizos with a history of thrombosis and clinical markers of a primary thrombophilic state were prospectively studied to identify a thrombophilic condition. An abnormal aPCR phenotype was identified in 18 individuals. Evaluation of those with an abnormal aPCR phenotype, identified that 44% had factor V Leiden mutation, 22% increased levels of factor VIII, 16% anti-phospholipid antibodies and 6% a lupus anticoagulant. In the remaining 22%, the use of direct oral anticoagulants (DOACs) in the past period of 12-24h was recorded. We found significant associations between abnormal aPCR phenotype and the factor V Leiden mutation (p=0022), between abnormal aPCR phenotype and the use of DOACs (p=0.006) and between antiphospholipid antibodies and lupus anticoagulant (p<0.0001). These data are consonant with those observed in other populations and further identify that consideration be given to identifying whether individuals are being treated with the novel DOACs when conducting laboratory studies oriented to identify the etiology of thrombosis.

Primary Thrombophilia in Mexico XII: Miscarriages Are More Frequent in Persons with the Sticky Platelet Syndrome (SPS)

Background: The sticky platelet syndrome (SPS) is an inherited condition which leads into arterial and venous thrombosis. There is scant information about the association between the SPS and obstetric complications.Objective: To assess the relationship of the SPS and fetal loss in a single institution.Material and methods: The obstetric history of all the consecutive female patients prospectively studied along a 324 month period, in a single institution with a history of thrombosis and a clinical marker of primary thrombophilia was reviewed.Results: Between 1989 and 2016, 268 consecutive patients with a clinical marker of primary thrombophilia and a history of arterial or venous thrombosis were studied; of these, 108 were female patients. Within this subset, 77 (71%) had been pregnant at some moment. Twenty eight of these 77 patients (37%) had had an abortion and 24 out of these (86%) were found to have the SPS. On the other hand, in a subset of 73 female patients with the SPS who had been pregnant, 32% had miscarriages (14 had one abortion, 5 two abortions and 4 three or more abortions). These figures are significantly higher than the prevalence of abortions in the Mexican general population of pregnant women, which is 12-13% (chi square = 7.47; p = 0.0063). Accordingly, the relative risk of having a miscarriage is 2.66 times higher in female patients with the SPS than in the general population (p = 0.0014 ).Conclusion: In México, female patients with the SPS experience significantly more miscarriages than the general population. Since the treatment of the SPS is simple and effective and could in turn prevent adverse obstetric outcomes, its investigation in women studied because obstetric complications may be useful and deserves further research. DisclosuresNo relevant conflicts of interest to declare.

Primary thrombophilia in Mexico: a single tertiary referral hospital experience.

Thrombophilia is a complex hypercoagulable state that increases the risk of thrombosis. Most reports in medical literature of the Mexican population with this disease lack statistical validity. Therefore, the aim of this study is to describe the prevalence of primary thrombophilia in a tertiary referral hospital in Mexico. This is a study of patients referred to our hospital because of a hypercoagulable state and who later on were diagnosed with primary thrombophilia. The thrombophilia workup included methylenetetrahydrofolate reductase (MTHFR) C677T, antiphospholipid antibodies, protein C, protein S, antithrombin, factor VIII, factor V Leiden, prothrombin mutation G20210A, activated protein C resistance, JAK2 V617F and homocysteine. Ninety-five individuals were tested. The MTHFR C677T polymorphism was the most frequent anomaly in 84.1% of the tested individuals. There was a relatively low prevalence of factor V Leiden (5.2%) and anticoagulant protein deficiency (8.3%). The MTHFR C677T polymorphism has a very high prevalence compared with the low prevalence of anticoagulant protein deficiency and factor V Leiden mutation in Mexicans.