Comprehensive evaluation of genetic and acquired thrombophilia markers for an individualized prediction of clinical thrombosis in patients with lymphoma and multiple myeloma.

Patients diagnosed with lymphoma or multiple myeloma are at elevated risk of venous thromboembolism (VTE). Optimum risk stratification and effective thromboprophylaxis can only be achieved through the development of a multiple-specific risk score that successfully captures all aspects of the heterogeneous prothrombotic environment existing in these patients. Our aim was to identify risk factors for thrombosis and suggest an improved tool combining clinical data, thrombo-inflammatory biomarkers and genetic (Thrombo inCode® test) variables for predicting thrombotic risk in patients with lymphoma and multiple myeloma. A prospective longitudinal study was conducted on newly-diagnosed lymphoma and multiple myeloma patients who presented at our institution between February 2020 and January 2021. The study included 47 patients with lymphoma and 16 patients with multiple myeloma. We performed a follow-up of 1 year or until September 2021. The incidence of venous thrombosis and associated risk factors were analysed, including the genetic Thrombo inCode® test. Khorana and ThroLy scores for lymphoma patients and IMPEDE VTE score for myeloma patients were calculated. At a median follow-up of 9.1 months, VTE incidence was 9.5% (6/63), with 4 and 2 patients with lymphoma and myeloma who developed the events, respectively. Univariate analysis showed that the incidence of thrombosis was significantly higher in patients with ECOG ≥ 2 and prior immobility. Median factor VIII levels were significantly higher in patients with thrombosis (with increased values in all of them). Moreover, there was a trend in genetic variant rs5985 (factor XIII) as a protective factor, and a trend to higher thrombotic risk in patients with factor V Leiden, rs2232698 variant (serpinA10), low total protein S activity, elevated D-dimer, aggressive lymphoma and treatment with dexamethasone. The results of our study demonstrate promise for the potential use of widely accessible markers to increase precision in risk prediction for VTE in patients with lymphoma and multiple myeloma, particularly ECOG ≥ 2, immobility and higher factor VIII levels, as well as lymphoma aggressiveness, treatment with dexamethasone and the haemostatic biomarkers D-dimer and total protein S activity. Additionally, genetic variants factor V Leiden, serpinA10 rs2232698 and factor XIII-A Val34Leu warrant further investigation for use in the research setting.

Venous thrombosis risk factors in pregnant women.

Venous thromboembolism (VTE) is the third most common cause of death on Earth after myocardial infarctions and strokes, according to the World Health Organization (WHO). Pregnancy is a unique condition of woman, when enormous changes occur in functioning of the most important systems of homeostasis in a relatively short time. These are physiological hypercoagulation, slowing of blood flow, increase in circulating blood volume, etc. However, while being physiological, these changes increase the risks of venous thromboembolism by almost 6 times. In some cases, there appears an imbalance or dissociation between the functioning of natural antithrombotic systems and the activation of coagulation as a consequence of genetically or acquired determined causes (genetic thrombophilia, antiphospholipid syndrome, comorbidities, obstetric complications and other exogenous and endogenous factors). Accordingly, identification of risk factors, their systematization, and determination of VTE risks in pregnancy and puerperium is one of the most important tasks of clinical medicine. Various recommendations have appeared for practitioners during the last 10-15 years on the basis of the risk factors analysis in order to prevent VTE in pregnant women more effectively. Nevertheless, none of these recommendations can yet take into account all risk factors, although convenient scoring systems have emerged for risk assessment and clear recommendations on anti-thrombotic prophylaxis regimens in risk groups in recent years. This article will review historical understanding of thrombosis in pregnant women, progress in understanding VTE risk factors in pregnant women, and available reserves in identifying new risk factors during pregnancy and puerperium in order to stratify risks more efficiently.

In vitro diagnostics for the medical dermatologist. Part II: Hypercoagulability tests.

The skin often provides initial clues of hypercoagulability with features such as livedo reticularis, livedo racemosa, retiform purpura, necrosis, and ulcerations. Because these cutaneous manifestations are nonspecific, laboratory testing is often needed to evaluate for underlying causes of hypercoagulability. Importantly, these disorders are reported to be the most common mimicker, resulting in an erroneous diagnosis of pyoderma gangrenosum. Understanding inherent properties of, and indications for, available tests is necessary for appropriate ordering and interpretation of results. Additionally, ordering of these tests in an indiscriminate manner may lead to inaccurate results, complicating the interpretation and approach to management. This second article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of hypercoagulability and vasculopathic disease as it pertains to dermatologic disease.

Thrombophilia screening revisited: an issue of personalized medicine.

Clinical thrombophilia is the consequence of multiple gene and/or environment interactions. Thrombophilia screening requires a targeted patient with specific indication, in which a finding would have implications. Carrying out a thrombophilia examination in the physician's practice is often a cause of uncertainty and concern. The concerns begin in choosing the right patient to be examined, are associated with the time of investigation, with the choice of analysis, the test-material and with the correct interpretation of the results. Difficulties, which can influence the results, can occur with both organization and blood sampling. As common for any analysis, pre-analytical, analytical and post-analytical factors should be considered, as well as the possibility of false positive or false negative results. Finally, recommendation of correct therapeutic and prophylactic measures for the patient and his relatives is an additional focus. In this article we want to provide-on the basis of the evidence and personal experience-the theory of thrombophilia-investigation, the indications for testing, as well as practical recommendations for treatment options.

Venous thrombosis risk factors in pregnant women.

OBJECTIVES: Assess all risk factors of venous thromboembolism (VTE) in pregnancy and puerperium. METHODS: Different guidelines for VTE prevention have been analyzed. RESULTS: Various recommendations have appeared for practitioners during the last 10-15 years on the basis of the risk factors analysis in order to prevent VTE in pregnant women more effectively. Nevertheless, none of these recommendations can yet take into account all risk factors, although convenient scoring systems have emerged for risk assessment and clear recommendations on anti-thrombotic prophylaxis regimens in risk groups in recent years. CONCLUSIONS: VTE is the third most common cause of death on Earth after myocardial infarctions and strokes, according to the World Health Organization. Pregnancy is a unique condition of woman, when enormous changes occur in functioning of the most important systems of homeostasis in a relatively short time. These are physiological hypercoagulation, slowing of blood flow, increase in circulating blood volume, etc. However, while being physiological, these changes increase the risks of venous thromboembolism by almost six times. In some cases, there appears an imbalance or dissociation between the functioning of natural antithrombotic systems and the activation of coagulation as a consequence of genetically or acquired determined causes (genetic thrombophilia, antiphospholipid syndrome, comorbidities, obstetric complications and other exogenous and endogenous factors). Accordingly, identification of risk factors, their systematization, and determination of VTE risks in pregnancy and puerperium is one of the most important tasks of clinical medicine. This article will review historical understanding of thrombosis in pregnant women, progress in understanding VTE risk factors in pregnant women, and available reserves in identifying new risk factors during pregnancy and puerperium in order to stratify risks more efficiently.

Inherited and acquired thrombophilia in Indian women experiencing unexplained recurrent pregnancy loss.

The most frequently hypothesized cause of unexplained recurrent pregnancy loss (RPL) refers to a defective maternal haemostatic response leading to uteroplacental thrombosis. Approximately 20% women suffering from pregnancy loss (PL) are associated with autoimmune disorders and more than 50% remain idiopathic after common traditional investigations. The present study aims to investigate the prevalence of different genetic and acquired thrombophilia markers in a large series of Indian women with RPL. Such studies will help analyze the markers which pose maximum risk and help in the appropriate treatment in subsequent pregnancies. The study comprised of 587 women with no apparent etiological causes of RPL and 115 healthy women controls. p values were calculated with two tailed Fisher's exact test; statistical significance was assumed at p<0.05, 95% confidence interval. Relative risks were also calculated. Among genetic thrombophilia, the risk of PL was highest with protein S deficiency (16%, p=0.006) followed by plasminogen activator inhibitor-1 4G/4G (23%, p=0.007) polymorphism. Among acquired markers, the risk of PL was the highest in women with anti-cardiolipin antibodies (24%, p=0.0001), followed by anti-annexin V antibodies (23%, p=0.0009) and lupus anticoagulants (8%, p=0.02). Thrombophilia, inherited and acquired, is an important contributing factor in unexplained RPL and should be screened in the order of its prevalence.

Study of the frequency of occurrence of genetic and acquired thrombophilia in infertile women prior IVF.

This study of infertile women prior in vitro fertilization (IVF) is focused at the genetic and acquired thrombophilia before the IVF program, the identification of the frequency of occurrence of thrombophilia in them, the impact of thrombophilia of the offensive, the course and outcome of pregnancies, to improve the quality of cycles in terms of a pregnancy and childbirth. Forty-five women with infertility were examined. Thirty-two (71%) were identified thrombophilia: genetic thrombophilia in 32 cases (100%), among them a combination of several forms of genetic thrombophilia - 21 (63%) of them, other forms of thrombophilia (genetic and acquired) - in 5 of them (16%). In IVF 23 (72%) women became pregnant. In 87% of pregnancies ended in spontaneous birth, in 13% of cases of preterm birth.

Pediatric antiphospholipid syndrome: is it the same as an adult?

IMPORTANCE: Antiphospholipid syndrome in neonates and children is a rare, but in some cases life-threatening condition with arterial and/or venous thrombosis and/or non-thrombotic neurological, skin, ophthalmological and other manifestations. OBSERVATIONS: This review highlights the available information about the features of pediatric APS, including the rare catastrophic form, the differences between pediatric and adult APS, and the role of genetic thrombophilia in APS manifestation. CONCLUSIONS AND RELEVANCE: The clinical manifestations and treatment options for APS in children may differ from those in adults, and prescribing therapy can be challenging due to the unique clinical and morphological characteristics of the pediatric patient. Pediatric APS may be a predictor of the development of certain autoimmune diseases and classic manifestations of APS in adulthood, therefore, a revision of the existing criteria for the diagnosis and treatment of APS in children is necessary.

Diagnosis and Management of Cerebral Venous Thrombosis Due to Polycythemia Vera and Genetic Thrombophilia: Case Report and Literature Review.

(1) Background: Cerebral venous and dural sinus thrombosis (CVT) rarely appears in the adult population. It is difficult to diagnosis because of its variable clinical presentation and the overlapping signal intensities of thrombosis and venous flow on conventional MR images and MR venograms. (2) Case presentation: A 41-year-old male patient presented with an acute isolated intracranial hypertension syndrome. The diagnosis of acute thrombosis of the left lateral sinus (both transverse and sigmoid portions), the torcular Herophili, and the bulb of the left internal jugular vein was established by neuroimaging data from head-computed tomography, magnetic resonance imaging (including Contrast-enhanced 3D T1-MPRAGE sequence), and magnetic resonance venography (2D-TOF MR venography). We detected different risk factors (polycythemia vera-PV with JAK2 V617F mutation and inherited low-risk thrombophilia). He was successfully treated with low-molecular-weight heparin, followed by oral anticoagulation. (3) Conclusions: In the case of our patient, polycythemia vera represented a predisposing risk factor for CVT, and the identification of JAK2 V617F mutation was mandatory for the etiology of the disease. Contrast-enhanced 3D T1-MPRAGE sequence proved superior to 2D-TOF MR venography and to conventional SE MR imaging in the diagnosis of acute intracranial dural sinus thrombosis.

Thrombophilia Screening: Universal, Selected, or Neither?

The utility of thrombophilia testing in clinical practice is still a matter of debate because studies have not shown a benefit in the reduction of recurrent venous thromboembolism (VTE) risk in patients with thrombosis, despite the clearly higher VTE risk for first thrombosis. Screening for thrombophilia is indicated in selected patients. Particularly in selected young patients, especially women of childbearing age, the knowledge of the genetic thrombophilic defect may help in specific situations to decrease the risk of VTE events. Avoidance of modifiable risk factors and/or prophylactic thromboembolic procedures may be evaluated in selected patients. A comprehensive workup including personal and familial history, clinical examination, and laboratory test results including hereditary thrombophilia remains helpful in assessing the cumulative risk and the management of this group of selected patients.

Ischaemic stroke provoked by sexual intercourse.

The association between long term risk factors and stroke has been well established, but very little is known about factors that may precipitate acute stroke. We describe two young women presenting with ischaemic stroke triggered by sexual intercourse. Patient 1 presented with a cardioembolic stroke probably secondary to the interaction between a patent foramen ovale and thrombophilic abnormalities; Patient 2, presenting with orgasmic headache, had a cryptogenic striatocapsular infarct. Sexual intercourse should be considered as an unusual, but possible, trigger of cerebral ischaemia, especially in young patients presenting with cryptogenic stroke.