Idiopathic Thrombosis Research Articles

Thrombophilia Screening: Not So Straightforward.

Although inherited thrombophilias are lifelong risk factors for a first thrombotic episode, progression to thrombosis is multifactorial and not all individuals with inherited thrombophilia develop thrombosis in their lifetimes. Consequently, indiscriminate screening in patients with idiopathic thrombosis is not recommended, since presence of a thrombophilia does not necessarily predict recurrence or influence management, and testing should be selective. It follows that a decision to undertake laboratory detection of thrombophilia should be aligned with a concerted effort to identify any significant abnormalities, because it will inform patient management. Deficiencies of antithrombin and protein C are rare and usually determined using phenotypic assays assessing biological activities, whereas protein S deficiency (also rare) is commonly detected with antigenic assays for the free form of protein S since available activity assays are considered to lack specificity. In each case, no single phenotypic assay is capable of detecting every deficiency, because the various mutations express different molecular characteristics, rendering thrombophilia screening repertoires employing one assay per potential deficiency, of limited effectiveness. Activated protein C resistance (APCR) is more common than discrete deficiencies of antithrombin, protein C, and protein S and also often detected initially with phenotypic assays; however, some centres perform only genetic analysis for factor V Leiden, as this is responsible for most cases of hereditary APCR, accepting that acquired APCR and rare F5 mutations conferring APCR will go undetected if only factor V Leiden is evaluated. All phenotypic assays have interferences and limitations, which must be factored into decisions about if, and when, to test, and be given consideration in the laboratory during assay performance and interpretation. This review looks in detail at performance and limitations of routine phenotypic thrombophilia assays.

A rare stroke: Cerebral Venous-Sinus Thrombosis; A Case Series Analysis Presented to Emergency Department and Review of the Literature

ABSTRACT 
 Cerebral venous sinus thrombosis (CVST) is a rare but acute and life-threatening disease. In this study, we present a case series of 10 patients with CSVT diagnosed in the emergency department of a tertiary hospital. Demographic characteristics, CVST etiologies, diagnostic characteristics in their history, radiological signs and prognosis were recorded during their hospitalization. The median age of the patients was 32 years. Half of the patients were women. It was known that three patients had otitis media, and the other three patients had pregnancy, puerperium and hormonal contraceptives. One patient had chronic inflammatory disease and one patient had idiopathic thrombosis. All but one of the patients had headache. The diagnostic tool was magnetic resonance venography and all patients had transverse sinus occlusion. All patients received anticoagulant treatment in the neurology department, 9 patients were discharged with good recovery, 1 patient died. Emergency clinicians should be more careful, especially in young patients and patients with thrombotic risk factors. Hormonal contraceptives are a major preventable risk factor. However, pregnancy and the postpartum period are thrombotic risk factors on their own. Intracranial infections such as otitis media may spread and cause cerebral vein thrombosis. Magnetic resonance venography is the most successful diagnostic tool for SSVT.

A case of idiopathic intracardiac and pulmonary arterial thrombosis successfully treated with surgical thrombectomy

AbstractWe report an asymptomatic case of idiopathic multiple thromboses that progressively worsened despite dabigatran administration. An 81‐year‐old Japanese man was admitted for orbital apex syndrome. He had a history of sustained atrial fibrillation and was taking dabigatran. Dabigatran was temporarily changed to heparin in preparation for the biopsy. However, it was resumed after the biopsy had been taken. The patient was diagnosed with an asymptomatic recurrent cerebral infarction and thrombosis of the pulmonary artery and left atrium. Heparin‐induced thrombocytopenia was the suspected cause for idiopathic thrombosis, but the diagnosis was not confirmed serologically. Left atrial appendectomy and anticoagulant therapy with argatroban resulted in improvement. It is important to evaluate the D‐dimer levels and investigate the development of thrombi after heparin administration.

Eye-Neck Integrated Ultrasound in Idiopathic Intracranial Hypertension and Cerebral Venous Sinus Thrombosis.

Background: The clinical presentation of cerebral venous sinus thrombosis (CVST) overlaps with that of idiopathic intracranial hypertension (IIH), but no screening tool exists. We investigated the role of eye-neck integrated ultrasound in the diagnosis and differentiation of IIH and CVST.Methods: Twenty IIH patients, 30 CVST patients, and 40 healthy controls were retrospectively analyzed. The ultrasonographic optic nerve sheath diameter (ONSD) and hemodynamic characteristics of the internal jugular veins (IJVs) were recorded. The cerebrospinal fluid opening pressure was measured after ultrasonic examination.Results: The ONSD was significantly larger in IIH patients than in controls (4.71 ± 0.41 vs. 3.93 ± 0.24 mm, p < 0.001). The ONSD cut-off for IIH diagnosis was 4.25 mm (AUC = 0.978; 95% CI: 0.95–1.0, p < 0.001, sensitivity: 90%, specificity: 93%). In the CVST group, 22 (73.3%) patients had elevated intracranial pressure (ICP); the mean ONSD was significantly higher in patients with increased ICP than in those without (4.43 ± 0.33 vs. 3.95 ± 0.17 mm, p < 0.001). The mean blood flow volume (BFV) was significantly reduced in CVST patients (425.17 ± 349.83 mL/min) compared to that in controls (680.37 ± 233.03 mL/min, p < 0.001) and IIH patients (617.67 ± 282.96 mL/min, p = 0.008). The optimal BFV cut-off for predicting CVST was 527.28 mL/min (AUC = 0.804, 95% CI: 0.68–0.93, p < 0.001, sensitivity: 80%, specificity: 78%). The velocity of the unilateral IJVs-J3 segment decreased or remained constant during deep inspiration (abnormal respiratory modulate blood flow test, ARMT) in 32.5% of controls, with no bilateral ARMT. The prevalence of bilateral ARMT was 25% in IIH patients (χ2 = 12.9, p = 0.005) and 27% in CVST patients (χ2 = 17.6, p = 0.001).Conclusion: Eye-neck integrated ultrasound is an easily available bedside technique to assess ICP and hemodynamic characteristics of IJVs. ONSD measurement can identify patients with increased ICP, and reduced IJV BFV may aid the differentiation of CVST and IIH.

57-Year-Old Woman With Weakness and Word-Finding Difficulties

57-Year-Old Woman With Weakness and Word-Finding Difficulties

S1636 Idiopathic Mesenteric Venous Thrombosis in a Young Female

S1636 Idiopathic Mesenteric Venous Thrombosis in a Young Female

Central venous catheters are an important factor in paediatric thrombosis.

To establish the incidence and characteristics of paediatric thrombosis (PT) in a Canadian tertiary care centre during the era of low molecular weight heparin (LMWH). A retrospective observational case study of all patients <18years of age evaluated for arterial and venous thrombosis from May 2008 to July 2018 at McMaster Children's Hospital was conducted through the electronic medical record. The incidence of PT was 52.2 per 10000 hospital admissions (n=477/91462). Provoked thrombosis was more prevalent (88.9%, n=424/477) than unprovoked (2.9%, n=14/477) or idiopathic thrombosis (4%, n=19/477). Half of PT were in children <2years (51.2%, n=244/477). Central vascular catheterisation was a contributory factor in more than half of thrombotic events (56.2%, n=268/477), while trauma (1.1%, n=5/477), oral contraceptives (4%, n=19/477), infection (4%, n=19/477), surgery (6.9%, n=33/477) and malignancy (8.4%, n=40/477) were also risk factors. Arterial ischaemic stroke was diagnosed in 11.1% of cases (n=53/477), while pulmonary embolism was identified in 7.1% (n=34/477) and 1.7% of cases were fatal (n=8/477). LMWH was the first-line therapeutic of choice (47.8%, n=228/477), with 28.1% (n=134/477) requiring no intervention. These data reiterate the elevated thrombosis risk to which infants and children with central vascular access are exposed.

Characterization of Plasma-Derived Small Extracellular Vesicles Indicates Ongoing Endothelial and Platelet Activation in Patients with Thrombotic Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease, characterized by thrombosis, obstetric complications and the presence of antiphospholipid antibodies (aPL), which drive endothelial injury and thrombophilia. Extracellular vesicles (EVs) have been implicated in endothelial and thrombotic pathologies. Here, we characterized the quantity, cellular origin and the surface expression of biologically active molecules in small EVs (sEVs) isolated from the plasma of thrombotic APS patients (n = 14), aPL-negative patients with idiopathic thrombosis (aPL-neg IT, n = 5) and healthy blood donors (HBD, n = 7). Nanoparticle tracking analysis showed similar sEV sizes (110–170 nm) between the groups, with an increased quantity of sEVs in patients with APS and aPL-neg IT compared to HBD. MACSPlex analysis of 37 different sEV surface markers showed endothelial (CD31), platelet (CD41b and CD42a), leukocyte (CD45), CD8 lymphocyte and APC (HLA-ABC) cell-derived sEVs. Except for CD8, these molecules were comparably expressed in all study groups. sEVs from APS patients were specifically enriched in surface expression of CD62P, suggesting endothelial and platelet activation in APS. Additionally, APS patients exhibited increased CD133/1 expression compared to aPL-neg IT, suggesting endothelial damage in APS patients. These findings demonstrate enhanced shedding, and distinct biological properties of sEVs in thrombotic APS.

Sigmoid sinus thrombosis in an elderly client with chronic varicose vein in the leg: a case report

Dehydration and malignancies are known as the most frequent predisposing factors of cerebral venous sinus thrombosis in older adults despite the fact that 30% of them remain idiopathic cerebral venous thrombosis (CVT) cases with no clear etiology. Cases of left sigmoid sinus involvement were rarely reported. Herein, an elderly case of sigmoid sinus thrombosis with unilateral hearing loss with chronic varicose vein in the leg was reported. Sigmoid sinus thrombosis that affects hearing is one of the rare complications of otitis media. Whether or not a large chronic varicose vein in the leg can serve as a predisposing factor for CVT requires further studies. Successful management of anticoagulant therapy prevented serious complications in the patient.

Idiopathic Ovarian Vein Thrombosis: A Rare Case in Nonpregnant Woman

Ovarian vein thrombosis (OVT) is a rare cause of abdominal pain, is an entity most commonly diagnosed after pregnancy. It is also associated with gynecological malignancies, caesarean deliveries, abortions, hypercoagulability and pelvic inflammatory disease. Prompt diagnosis and treatment is warranted to avoid serious complications [1]. We report the rare case of idiopathic ovarian right vein thrombosis.

Neuroimaging findings in patients with idiopathic intracranial hypertension and cerebral venous thrombosis, and their association with clinical features

ABSTRACTObjective: To investigate the frequency of neuroimaging findings of intracranial hypertension in patients with idiopathic intracranial hypertension (IIH) and cerebral venous thrombosis (CVT). We also aimed to compare these findings in two patient groups and investigate the association of these findings with some clinical parameters.Methods: Patients with IIH and CVT admitted to the neurology, neuro-ophthalmology outpatient clinics, and emergency services between 2017 and 2019 were enrolled in this study. The presence of eight previously defined neuroimaging signs of intracranial hypertension were evaluated on MRIs. The values of total MRI scores were formed to use in the analyses investigating the association between neuroimaging findings and clinical parameters.Results: Twenty-three patients with proven IIH and seven patients with CVT with signs of intracranial hypertension were included in this study. Body mass index (BMI) values were higher in the IIH group than in the CVT group (31.0/25.9; p = 0.022). There were no differences in terms of gender distribution, age, ortotal MRI scores between the patient groups. The most common neuroimaging parameters found in the IIH group were the following: increased peri-optic cerebrospinal fluid (CSF) (n = 20) and optic nerve tortuosity (n = 12). There were no significant correlations between values of total MRI scores, lumbar puncture opening pressure, and BMI.Conclusion: Neuroimaging findings are useful tools with high diagnostic sensitivity in IIH. The most sensitive finding was increased peri-optic CSF. The utility of these neuroimaging correlates and their potential significance as solely diagnostic markers in IIH should be investigated in future large-scale studies.

Diagnosis and management of early-onset thrombophilia/thrombosis: a review

Evidence of the molecular epidemiology of thrombophilia is growing, and the clinical management of adult thromboembolism patients has recently made significant progress. On the other hand, there is little or no evidence concerning the genetic variation, treatment, and prophylaxis of thromboembolism development in the early life stage. The clinical presentation of early-onset thrombosis/thrombophilia, which mostly occurs in newborns and adolescents, differs from that in cases of adult-onset. Recurrent purpura fulminans and/or intracranial hemorrhage/infarction leads to dangerous lifelong complications. As in the setting of cancer genomic medicine, germline variants require determination for the individualized control of early-onset thrombophilia. The genetic predisposition to thrombosis varies among ethnicities. In the Japanese population, the protein S variant (PS-Tokushima, K196E) has attracted attention as the cause of a common and low-risk prothrombotic predisposition in adults, while protein C deficiency greatly impacts the onset of pediatric thrombosis. In 2020, 3 years after the registration of idiopathic thrombosis as a designated intractable disease, genetic tests have been promulgated for health insurance portability. Disease-specific therapy for early-onset thrombophilia is crucial. Here, we review the genetic heterogeneity, prophylaxis, and treatment strategy of the rare subgroups of severe heritable thrombosis conditions in Japan.

Surgical tactics of treatment in patients, suffering an acute arterial ischemia of the lower extremities on background of atherosclerotic arterial affection

Objective. To improve the diagnosis and to optimize a surgical tactics of treatment in patients, suffering an acute ischemia of the lower extremities, severe stage of the extremity ischemia, depending on the prognostic criteria for surgical treatment revealed.Materials and methods. There were examined 70 patients, suffering an acute arterial occlusion: men - 44 (63%), women - 26 (37%) ageing (65.2 ± 3.5) yrs old. The patients were distributed into three groups: the 1st - 32 (45.7%) patients with the arteries embolism revealed, the second - 5 (7.1%) patients with the lower extremities idiopathic arterial thrombosis, and the third - 33 (47.1%) patients with arterial thrombosis, which have developed on background of their atherosclerotic affection. In all the patients there were conducted a general clinical examination, ultrasonographic duplex scanning of the lower extremities arteries, spiral CT with contrasting. In 54 patients a degree of the skeletal muscles damage and a state of the acid-base balance were studied up.&#x0D; Results. In 88% patients a hemodynamically significant atherosclerotic occlusive-stenotic affection of the lower extremities arteries was revealed. The staged tactics of treatment was elaborated for patients, suffering an acute arterial occlusion and atherosclerotic affection of the lower extremities arteries. So on, after performance of thrombectomy the ultrasonographic duplex scanning of the lower extremities arteries is conducted with further application of various methods of revascularization, endovascular and the open-access shunting reconstructive operations on arteries of the lower extremities. Prognostic criteria, determining tactics of treatment in a patient with the extremity vitality preservation, were elaborated.&#x0D; Conclusion. There was established, that while the ischemia duration increase the possibility of the extremity blood flow restoration reduces. A correct tactics selection in patient is promoted due to determination of a rabdomyolisis markers.

Giant mass but small symptoms; huge thrombosis in the right atrium originating from the superior vena cava and protruding to the right ventricle: a case report

BackgroundThrombosis of the superior vena cava with propagation to the right heart chambers can be seen in the presence of chronic indwelling catheters. Moreover, the idiopathic right atrial thrombi may become entrapped in Chiari’s networks, and idiopathic thrombosis of the superior vena cava may occur rarely because of the underlying coagulation disorders or malignancies.Case presentationA 43-year-old Iranian (Persian) woman was admitted to our hospital with palpitation of 2 years’ duration and mild to moderate dyspnea of 10 days’ duration. Her past medical history, basic laboratory test results, and cardiac enzyme measurements were unremarkable. Imaging studies revealed a 1.4-cm × 7.4-cm multilobulated, hypermobile mass in the right atrium, extending into the right ventricle, that appeared to be emanating from the superior vena cava. Moreover, partial filling defects were visible in the distal parts of both right and left pulmonary arteries extending to their branches, suggesting massive pulmonary emboli. The patient’s huge mass and emboli were removed by surgery, and pathologic evaluations confirmed that all of the specimens were thrombosis. A number of mutations known as risk factors of thrombosis were detected during genetic evaluations. However, mild symptoms of the patient along with a huge mass in the right atrium, thrombosis in the superior vena cava, and massive thromboembolism remained unexplained.ConclusionHuge and dangerous thrombosis inside the heart and superior vena cava can evolve without expected considerable symptoms. Also, detecting the underlying causes of these thromboses sometimes is not feasible by only checking the prevalent known risk factors. Therefore, comprehensive evaluations should be carried out in these patients.

Incidence and features of thrombosis in children with inherited antithrombin deficiency.

Pediatric thromboembolism (≤18 years) is very rare (0.07-0.14/10,000/year) but may be more prevalent in children with severe thrombophilia (protein C, protein S or antithrombin deficiency). The aim of this study was to define the prevalence and clinical characteristics of pediatric thrombosis in subjects with inherited antithrombin deficiency. Our observational retrospective multicentric study from two countries recruited 968 patients of any age from 441 unrelated families with genetically, biochemically and functionally characterized antithrombin deficiency. Seventy-three subjects (7.5%) developed thrombosis before 19 years of age. Two high-risk periods for thrombosis were identified: adolescence (12-18 years, n=49) with thrombus localization (lower limb deep venous thrombosis or pulmonary embolism) and triggering factors common to adults (oral contraceptives, surgery or pregnancy); and the neonatal period (<30 days, n=15) with idiopathic thrombosis at unusual sites. The clinical evaluation of pediatric thrombosis in subjects with antithrombin deficiency revealed: i) a high prevalence of cerebral sinovenous thrombosis (n=13, 17.8%), mainly at young age (8 neonates and 4 children <6 years); ii) severe outcome with fatality in six cases (3 neonates, two of them homozygous for p.Leu131Phe). The majority of subjects (76.7%) carried quantitative type I deficiency. This retrospective analysis includes the largest cohort of subjects with inherited antithrombin deficiency so far and provides strong evidence for an increased risk of pediatric thrombosis associated with this thrombophilia (300-fold compared with the general population: 0.41%/year vs. 0.0014%/year, respectively). Our results support testing for antithrombin deficiency in children of affected families, particularly in case of type I deficiency.

Idiopathic Pulmonary Vein Thrombosis – A presentation of two case reports and review of the current literature

Idiopathic Pulmonary Vein Thrombosis – A presentation of two case reports and review of the current literature

Idiopathic thrombosis.

Idiopathic thrombosis involves a group of inherited thrombophilia predisposed to severe thrombosis of early onset and associated with an adverse outcome due to recurrence, and therefore, requires long-term anticoagulation therapy. The causative factors of a predisposition to thrombosis include immobility, dehydration, infection, surgery, injury, cancer, pregnancy, and estrogen use. The inherited deficiencies of antithrombin (AT), protein C (PC), and protein S (PS) are specified as "Specific Pediatric Chronic Diseases." However, medical expense assistance for patients terminates when they reach the age of 20 years. On April 1st 2017, "Idiopathic Thrombosis due to Inherited Thrombophilia," consisting of inherited AT, PC, and PS deficiencies, was specified as an "Intractable Disease," and aid for medical expenses became available. Accordingly, progress in the research and practice of idiopathic thrombosis is expected in future to improve the medical care system and to construct a database via clinical surveys.

Trombozla başvuran pediatrik hastaların risk faktörleri açısından retrospektif olarak değerlendirilmesi: tek merkez deneyimi

Purpose: Thrombosis in children is a multifactorial disorder associated with both genetic and acquired factors. Idiopathic thrombosis is a rare condition. This study aimed to examine the etiology and risk factors of thrombosis in pediatric patients followed at Baskent University Adana Teaching and Research Center, a reference hospital in the southern part of Turkey. Material and Methods: This study included a sample of 49 pediatric patients who were retrospectively evaluated. The patient records were examined retrospectively in terms of age at diagnosis with thrombosis, gender, family history of thrombosis, localization of thrombosis, underlying primary disease and presence of catheter, as well as indicators of genetic risk factors. Results: The number of children presenting to our clinic during the study period was 10358. The incidence of thrombosis was calculated as 49 cases in 10358 children. The median age of the patients was 5.1 years (ranging from 0 to 17.2 years), and there were 32 (65.3%) males. In the analysis of the genetic factors causing susceptibility to primary thrombosis, only a portion of the patients were studied for genetic mutations. Among these, 5 patients showed factor V Leiden mutation, 13 patients MTHFR 1298C mutation, and 18 patients MTHFR 677CT mutation. Seven patients were found have a combination of multiple mutations. When we investigated any possible correlation between high lipoprotein (a) levels and the distribution of mutations, we found that 7 patients with mutations had normal levels of high lipoprotein (a), while other 10 patients with mutations were found to have elevated levels of lipoprotein (a). Conclusion: We conclude and strongly emphasize that lipoprotein (a) elevation is one of the important genetic risk factors, which might prove a major risk indicator, as valuable as other mutation screening tests performed by molecular genetics

Abstract 330: Testicular Vein Thrombosis Etiology and Outcomes

Background: Testicular vein thrombosis (TVT) is not currently well-described in the literature. A better understanding of the natural history of TVT will allow for development of optimal management strategies for this little known entity. Methods: The goal of this project was to compare TVT with ovarian vein thrombosis (OVT) and lower extremity deep vein thrombosis (DVT). Patients with TVT, OVT, or DVT between 1995 and 2015 were identified and a chart review was performed. Results: A total of 39 patients with TVT occurring between 1995 and 2015 were identified and compared with 35 patients with OVT and 114 randomly chosen DVT patients. Mean duration of follow-up was 2.9 years (range 0-16.1). Patient demographics can be seen in table 1. Cancer-related (p-value=&lt;0.0001) and idiopathic thrombosis (p-value=0.01) rates were significantly different among the groups. Recurrence rates were similar between TVT and OVT (4.2 vs. 3 per 100 patient-years, p-value = 0.9) as well as TVT and DVT (4.2 vs 2.2 recurrences per 100 patient-years, p-value= 0.37). There were 25 deaths (22%) in DVT patients, 9 (26%) in OVT patients, and 12 (31%) in TVT patients (p-value= 0.541). There was one major bleeding event in both an OVT patient and a TVT patient. Conclusion: Etiology of TVT differs from that of OVT and DVT, specifically in cancer-related and idiopathic thrombosis rate. Our data supports a similar rate of recurrent venous thromboembolism and death in TVT as compared with DVT and OVT.

Detection of malignant neoplasms procoagulant activity

Aim. To determine possibilities of malignant neoplasms procoagulant activity detection by idiopathic thrombosis ultrasound imaging.Methods. 587 patients were examined. 347 patients with malignant neoplasms diagnosed in the outpatient clinic settings of the Tatarstan Regional Clinical Cancer Center (Kazan), were included in the main group. 240 patients, in which cancer pathology was excluded, were included in the control group. The groups were matched on age, sex and frequency of venous thromboembolic complications development risk factors not caused by malignant neoplasms. Both groups underwent clinical examination and ultrasound examination of the inferior vena cava, distal abdominal aorta, iliac arteries and veins, lower extremities arteries and veins.Results. Thrombosis clinical manifestations were detected in 12 patients, including 9 patients of the main group and 3 patients of the control group. In most cases of venous thrombosis in the main group (34 people, 79%) there were no clinical signs of thrombosis and it was detected only by ultrasound examination, which allowed to detect venous thrombus in 43 patients of the main group (12.4%) and in 5 patients of the control group (2.1%; t=3.2, p &lt;0.05).Conclusion. The inferior vena cava system venous thrombosis frequency in patients with malignant neoplasms was significantly higher than that in patients without cancer, which indicates malignant neoplasms high procoagulant activity; ultrasonography has high sensitivity in the idiopathic thrombosis detection in cancer patients, and it should be performed regardless of the presence or absence of venous thromboembolic complications clinical manifestations.