JOURNAL AVAILABLE AT RADIOLOGYUPDATE.ORG Factors contributing to the hypercoagulable state. Clinical case of intracardiac thrombosis and massive pulmonary embolism Julius Vidikas1, Evelina Gudavičiūtė², Matas Kalinauskas² 1Lithuanian research center of health sciences ²Faculty of Medicine, Academy of Medicine, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009 Kaunas, Lithuania ABSTRACT Thrombophilia, or hypercoagulable state, can cause various thrombotic events. It occurs due to inherited and/or ac- quired factors. Inherited risk factors, such as factor V Leiden, antithrombin, prothrombin, protein S and C mutations, have been associated with increased presence of venous thrombosis and some suggest an increased arterial thrombosis incidence as well. Acquired risk factors are found more often than inherited. The most prominent acquired risk factors include atrial fibrillation, malignancy, sepsis, obesity, diabetes mellitus, antiphospholipid syndrome and COVID-19 infection. All of these risk factors alone can cause thrombotic events, but most of the time thrombosis occurs due to multifactorial interaction of various established risk factors and patients’ overall well-being. With this article we present a case report of intracardial thrombosis in a patient with atrial fibrillation and a brief literature review of the causes of hypercoagulability. Keywords: Thrombophilia, thrombosis, tomography. bus formation. In current times inherited throm- INTRO bophilia can be classified according gene altering Thrombophilia, or hypercoagulable state, refers mutations, which consists of – loss of function to a blood disorder, which can increase clot- and gain of function [4]. The former involves ting and thrombus formation. This was known coagulation inhibitor decrease and it includes since 1856, when Virchow introduced his triad antithrombin (AT), protein C (PC) and protein of mechanisms for thrombosis, which remained S (PS), while the latter incorporates coagulation relevant to modern times [1]. Nowadays, throm- factor increase – the most prominent being fac- bophilia can be classified to inherited or acquired. tor V Leiden (FVL) and prothrombin G20210A Specific genetic mutations have been identified, (PT) mutation [4, 5]. FVL and PT are accounta- which can greatly affect the blood coagulation ble for 50–70% of inherited thrombophilia that and coagulation factor function. There are also has been diagnosed [2]. However, AT, PC and PS various acquired diseases that can increase the can contribute to severely greater thrombosis, risk of either venous or arterial thrombus for- even if they are less frequent [2,4]. Blood group mation [2]. Thrombophilia can predispose var- ABO may also plays a role in thrombophilia. It ious thrombotic events, however thrombosis or has been reported that people with ABO blood thromboembolisms are often multifactorial [3]. group tend to have an increased risk of venous This report analyses the most common inherited thromboembolism [2,6,7]. thrombophilias and focuses on the various dis- eases that can have a risk for hypercoagulability. FACTOR V LEIDEN INHERITED RISK FACTORS FOR HYPER- FVL may depict up to 50% of diagnosed hered- COAGULABILITY itary thrombophilias [4]. Although being the more prevalent, it tends to pose a weaker risk Inherited thrombophilia is a genetically deter- for thrombus formation [2]. Heterozygote carri- mined tendency of venous and/or arterial throm- ers of this trait tend to have a 5-fold higher risk 34 RADIOLOGY UPDATE VOL. 5 (8) ISSN 2424-5755 for VTE disease. For homozygotes this risk can of 55.6% was reported in retrospective study of reach up to 50-fold higher [8]. Furthermore, 18 pregnancies of women with AT, however pa- women with FVL can have an up to 3-fold great- tients treated with anticoagulation were seen to er risk for miscarriage and various gynecologi- have fewer complications [16]. Although, AT is cal complications during pregnancy, however associated with higher venous thrombosis risk, the rate of successful delivery is still high [9]. A arterial thrombosis risk seems to be unaffected study in Argentina concluded that FVL might – meta-analysis of 12 studies found no statistical have a significant effect on fetal growth retarda- significance with AT and arterial ischemic stroke tion, while PT mutations were found insignifi- cases [9]. cant compared to control study [10]. PT is the second most common inherited thrombophilia. PROTEIN S AND C MUTATIONS Carriers of G20210A mutation have an increased Similar to AT deficiency, PC and PS mutations plasma prothrombin of 30% for heterozygous are less frequently found in general population, and 70% for homozygous [8]. In general popula- but both are strong risk factors for thrombosis tion the prevalence for PT mutation is up to 4% [17]. PC and PS role in coagulation is associated with Caucasians being the most affected race [4]. with one another – activated form of PC is a nat- Comparing PT and FVL mutations for people of ural anticoagulant and PS is it co-factor [2]. PC 30 years and younger, PT tends to have a higher deficiency can be asymptomatic or can lead to risk of developing VTE than FVL – 0.44% and extensive thrombosis and disseminated intravas- 0.25% respectively [11]. Both FVL and PT in- cular coagulation [4]. It is reported that people crease the risk for thrombotic events in women with this mutation have a 2-3 times greater risk who use oral contraceptives. Women with FVL of experiencing first episode of VTE than those and PT mutations, who use oral contraceptives who have FVL or PT mutations [18]. About 50% are, respectively, at 35 to 99 times and 16 times of PC mutation carriers experience a thrombotic greater risk than non-carriers who don’t use OCs event as early as 45 years of age [4]. Homozy- [12]. A prospective study of 354 elderly patients gous PC deficiency can also cause a severe life found that FVL and PT were not associated with threatening condition – ischemic necrosis of ex- VTE recurrence [13]. A recent meta-analysis con- tremities, which is due to dermal vessel throm- cluded that both FVL and PT, regardless of zygo- bus manifestation [2]. PC and PS are found only sity, were found in significantly more arterial is- about 0.1-0.2% in general population [4,18]. PS, chemic stroke cases than control studies [14]. however, is more likely to be detected in Asians [8]. Homozygous or double heterozygous PS de- ANTITHROMBIN DEFICIENCY ficiency is very rare and symptoms of this muta- Antithrombin deficiency may be relevant in tion is resembling the same PC deficiency mu- about 1% of VTE cases and even less so in arteri- tations [8]. PS defect has been associated with a al thrombosis cases [15]. However, AT is linked 10-fold greater risk of VTE [19]. Both PC and with a high risk of thrombosis, with spontane- PS in the latest meta-analysis were found to be ous VTE occurring in 60% of cases [4]. With- statistically significantly associated with arterial out anticoagulation therapy the risk for VTE ischemic stroke [5]. occurrence is approximately 10.5% per year. BLOOD GROUP ABO Prescribing long-term anticoagulants reduces this incidence significantly, but still about 2.7% It is well established that people with ABO blood of patients will experience recurrent thrombosis group tend to experience thrombotic events more [8]. AT mutation in pregnant women can be re- frequently. The thought behind it is that VTE and sponsible for first time VTE development up to other thrombotic developments are associated 31% if there are no other risk factors associat- with ABO because von Willebrand factor, which ed with thrombosis and up to 50% if there are is about 25% higher in ABO groups, and factor risk factors present [4]. Poor pregnancy outcome VIII (FVIII) plasma levels [20]. A recent retro- 35 JOURNAL AVAILABLE AT RADIOLOGYUPDATE.ORG spective study in China concluded that patients zation are associated with obesity, which is an with non-O blood types experienced statistical- additional prothrombotic risk factor [30]. The ly significantly more VTE episodes than control mechanism of the obesity related hypercoag- group [21]. ABO blood groups are linked with ulability includes a pro-thrombotic state sec- 2.6-fold greater risk for occurrence of VTE, with ondary to chronic inflammation and decreased blood group A being the most dominant in this clot breakdown via inhibition of the fibrinolytic risk [8]. A study in Denmark established that pathway [31]. The proinflammatory and lesser non-O blood type was the most prevalent risk fibrinolytic response indicates that obesity might factor for VTE and was significantly associated be exacerbated by dysregulated expression and with VTE manifestations [22]. Moreover, people secretion of adipokines and microRNAs, which with non-O blood type accompanied with in- later increase the risk of thrombosis [31]. Obese herited thrombophilia have a risk of VTE up to individuals have shown increased circulating 23.2-fold greater than control cases [2]. levels of von Willebrand factor (VWF), tissue factor, factor VII and VIII, and fibrinogen, caus- ing a mild to moderate hypercoagulable state ACQUIRED RISK FACTORS FOR HYPER- [32]. A case-control study with patients aged COAGULABILITY 18-65 years attending outpatient venous throm- boembolism (VTE) clinics, evaluated that pro- longed work and computer related immobility ANTIPHOSPHOLIPID SYNDROME (APS) increased risk of VTE in adults who were seated One of the acquired risk factors for hypercoag- for at least 10 hours/day, including at