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BACKGROUND: Protein S (PS) is an anticoagulant that functions as a cofactor for activated protein C (APC) and tissue factor pathway inhibitor. PS deficiency is a risk factor for venous thromboembolism. PS activity is commonly measured using clot-based assays involving fibrin and thrombin production, but improvements are needed. OBJECTIVES: To develop a new assay for measuring plasma PS activity by quantifying the amount of activated coagulation factor V (FVa) cleaved by APC. METHODS: We designed a recombinant, modified FV (FVm) that mimicked FVa. We analyzed 160 purposively selected plasma samples from the Biobank of the National Cerebral and Cardiovascular Center. RESULTS: The assay using mixed normal and PS-deficient plasma detected FVm cleavage in a PS concentration-dependent manner. The correlation between PS activity, measured using the FVm cleavage assay, and free PS antigen levels was relatively weak. We then sequenced all exons of PROS1 from 47 subjects with <60% activity in either the FVm cleavage assay or the clot-based assay. Nonsynonymous variants were identified in 12 of 24 subjects with <60% activity in both assays and in 2 of 7 subjects with <60% activity in the FVm cleavage assay alone. No variants were identified in 16 subjects with <60% activity in the clot-based assay alone. Unlike the clot-based assay, the FVm cleavage assay was not affected by the presence of rivaroxaban in the plasma. CONCLUSIONS: An assay using the FVm substrate may be less susceptible to interference and provide a more accurate evaluation of plasma PS activity than clot-based assays.

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Hypercoagulable states, also called thrombophilia, can either be congenital or acquired. Congenital thrombophilia, associated mainly with venous thrombosis, is either secondary to coagulation-inhibitor deficiencies, i.e., antithrombin, protein C and Protein S, or gain of function mutations, i.e., factor V Leiden and prothrombin G20210A mutations. Despite the relative frequency of these two mutations, they have not been associated with venous thrombosis recurrence. Most prevalent thrombophilia have a limited impact and usually does not change indications for duration of antithrombotic treatment or prophylaxis compared to decisions based on clinical factors. However, rare inherited thrombophilia such as antithrombin deficiency could justify a long-term anticoagulation. The main acquired thrombophilia, the Antiphospholipid syndrome (APS), is associated with both arterial and venous thrombosis. Its impact on patient management is significant: choice of the anticoagulant (DOAC vs. warfarin), duration of anticoagulation, screening of any organ involvement and systemic autoimmune disease, introduction of immunosuppressive therapy.

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BACKGROUND: Fondaparinux sodium can prevent and treat acute illnesses and venous thromboembolism in patients undergoing surgery. At present, no studies have reported on treating subchorionic hematoma combined with protein S deficiency using fondaparinux sodium. OBJECTIVE: To investigate the clinical efficacy of fondaparinux sodium in the treatment of patients with subchorionic hematoma combined with protein S deficiency. METHODS: This single-center, open-ended, and prospective study enrolled 78 patients with subchorionic hematoma and protein S deficiency. They were randomly assigned to the treatment and control groups. The control group received conventional treatment, and the observation group received subepithelial injections of fondaparinux sodium (2.5 mg/day) based on conventional treatment. After 30 days of continuous treatment, the hematoma was evaluated by ultrasonography. RESULTS: After treatment with fondaparinux sodium, a significant improvement in subchorionic hematoma was observed in the observation group compared with that in the control group (p< 0.05). A substantial improvement in prothrombin time and activated partial thromboplastin time was observed in the observation group after fondaparinux sodium treatment (p< 0.05). Furthermore, after fondaparinux sodium treatment, the duration of hematoma maintenance and incidence of adverse pregnancy outcomes were significantly reduced in the observation group compared with that in the control group (p< 0.05). CONCLUSION: With a favorable safety profile, fondaparinux sodium is effective in treating subchorionic hematoma combined with protein S deficiency. The results provide new ideas and methods for treating this disease, which is worthy of further promotion and application in clinical practice.

RESUMEN

Protein S deficiency (PSD) is an autosomal dominant disorder characterized by congenital thrombophilia. Studies on PSD are limited yet, resulting in a lack of clarity about molecular changes during abnormal coagulation. Proteomics and metabolomics analyses were conducted on the plasma of PSD patients based on liquid and gas chromatography-mass spectrometry (LC- and GC-MS). Differential proteins and metabolites of PSD were then filtered by univariate statistical analysis and subjected to network analysis using the ingenuity pathway analysis (IPA) platform. The proteome and metabolome of PSD were obviously disturbed, and the biological pathway of coagulation and complement cascades was the most affected. During PSD, overall levels of anticoagulant protein decreased and negative regulation of thrombin production was reduced, causing the formation of fibrin clots and platelet aggregation. Furthermore, 9 differential proteins correlated significantly with protein S, comprising A2M, AGT, APOE, FGG, GPLD1, IGHV1-69, CFHR5, CPN2, and CA1. The biological networks suggested that the pathways of acute phase response, FXR/RXR activation, serotonin receptor signaling, and p70S6K signaling were associated with PSD, indicating an interaction disorder of inflammatory immune and lipid metabolism. The findings may contribute to knowledge of available functional molecules and biological pathways of familial PSD and help with treatment improvement. Data are available via ProteomeXchange with identifier PXD055111 and MetaboLights with reference number MTBLS2653.

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Cerebral venous thrombosis (CVT) is an uncommon but potentially severe condition, typically affecting younger individuals, pregnant women, and those with underlying thrombophilia. We report a rare case of a 63-year-old female who presented with altered mental status, facial droop, and slurred speech and was found to have an extensive dural venous thrombosis complicated by intracerebral and subarachnoid hemorrhage due to protein S deficiency. Given her diagnosis of protein S deficiency and thrombosis, careful anticoagulation was initiated, resulting in both clinical and radiographic improvement.

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This study aimed to explore the effects of S-nitrosylation on caspase-3 modification and its subsequent effects on beef myofibril degradation in vitro. Recombinant caspase-3 was reacted with different concentrations of S-nitrosoglutathione (GSNO, nitric oxide donor) at 37 °C for 30 min and subsequently incubated with purified myofibrillar protein from bovine semimembranosus muscle. Results indicated that the activity of caspase-3 was significantly reduced after GSNO treatments (P < 0.05) and showed a dose-dependent inhibitory effect, which was attributed to the increased S-nitrosylation extent of caspase-3. LC-MS/MS analysis revealed that caspase-3 was S-nitrosylated at cysteine sites 116, 170, 184, 220, and 264. Moreover, the degradation of desmin and troponin-T was notably suppressed by S-nitrosylated caspase-3 (P < 0.05). To conclude, protein S-nitrosylation could modify the cysteine residues of caspase-3, which accounts for the reduced caspase-3 activity and further represses its proteolytic ability on beef myofibrillar protein.

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Direct Oral Anticoagulants (DOACs) are the first line anticoagulants for the secondary prevention of venous thromboembolism (VTE). However, patients with severe inherited thrombophilias represent a group where the efficiency and safety of DOACs is poorly studied. In this communication, we focus on the utility of DOACs in the secondary prevention of VTE in patients with severe thrombophilia. Current evidence is based only on cohort or single center studies, and poor data is available on compliance of the patients in the studies. Analysis of the studies suggested that full-dose DOACs and vitamin K antagonists (VKAs) have a similar efficacy and bleeding risk in the secondary prevention of VTE in patients with thrombophilia; with a low hazard ratio for recurrent VTE calculated from cohort studies for DOAC vs warfarin, ranging from 0.3 to 0.75. We wish to highlight that treatment failure is greater in those with severe forms of Protein S deficiency (below 20%), and possibly in AT deficiency Type II HBS homozygous Budapest 3. In summary, the current approach to using DOACs in patients with severe thrombophilia is dependent on clinical judgment and experience. Limited evidence suggests that for those with severe thrombophilias, full dose DOACs have similar utility as VKAs. We recommend caution in using low - dose DOACs due to lack of evidence. Ideally large randomized multicenter studies are required to develop a reliable treatment algorithm.

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La púrpura fulminante adquirida postinfecciosa es una entidad aguda y grave, poco frecuente, caracterizada por necrosis cutánea asociada a coagulopatía intravascular diseminada (CID), en ausencia de infección activa o alteraciones previas de la coagulación. Afecta fundamentalmente a la población pediátrica y, en el 90 % de los casos, está precedida por un proceso infeccioso. El mecanismo fisiopatológico es un déficit transitorio de proteína S mediado por autoanticuerpos que favorece un estado de hipercoagulabilidad. Se presenta el caso de un varón de 8 años previamente sano, con lesiones cutáneas purpúricas características de púrpura fulminante asociada a CID en ausencia de sepsis. Se constató deficiencia plasmática transitoria de proteína S. Requirió tratamiento sustitutivo con plasma fresco congelado y anticoagulación; la evolución fue favorable. La actividad de la proteína S permaneció disminuida durante 2 meses.

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Acquired postinfectious purpura fulminans is a rare, acute, and severe disease characterized by skin necrosis associated with disseminated intravascular coagulation (DIC) in the absence of active infection or previous coagulation disorders. It mainly affects the pediatric population and, in 90% of cases, it is preceded by an infectious process. The pathophysiological mechanism is a transient autoantibodymediated protein S deficiency that favors a hypercoagulable state. Here we describe the case of a previously healthy 8-year-old boy with purpuric skin lesions typical of purpura fulminans associated with DIC in the absence of sepsis. A transient plasma protein S deficiency was confirmed. He required replacement therapy with fresh frozen plasma and anticoagulation; he had a favorable course. Protein S activity remained decreased for 2 months.

Asunto(s)

Humanos , Masculino , Niño , Púrpura Fulminante/diagnóstico , Púrpura Fulminante/etiología , Deficiencia de Proteína S/complicaciones , Deficiencia de Proteína S/diagnóstico , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/etiología

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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.

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INTRODUCTION: Protein S deficiency resulting in mesenteric vein thrombosis has been reported in previous studies however those causing SMA thrombosis has been rarely reported. Multidisciplinary approach involving general surgeon, a vascular surgeon, an interventional radiologist, and an intensivist are crucial for management of SMA thrombosis. CASE PRESENTATION: A 39-year-old non-smoker hypertensive female who was diagnosed with partially occlusive thrombus in the superior mesenteric artery via Contrast-enhanced computed tomography (CECT) re-presented after 5 days and CECT revealed a partially occlusive thrombus in the superior mesenteric artery and Protein S deficiency (free protein S:15 %). She was managed by lysis of thrombus with streptokinase by interventional radiology team. The patient is on anticoagulants and without abdominal complaints on follow-up at 24 months. DISCUSSION: Computed tomography angiography should be done immediately in any patient suspected of AMI since delay in diagnosis accounts for high mortality rates of 30-70 %. The surgical treatment of the condition is well established and consists of revascularization and/or resection of nonviable bowel. Endovascular techniques have emerged as an alternative for occlusion of the SMA. Patients with protein C and/or S deficiency treated for AMI require lifelong anticoagulant/antiplatelet therapy to prevent relapse. CONCLUSION: Hereditary thrombophilia should be suspected in young people with unusual thrombotic presentations. Earlier diagnosis and aggressive antithrombotic therapy in individuals with hypercoagulable states can improve outcomes. Treatment involving a multidisciplinary approach improves outcomes.

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A 54-year-old male with biopsy-confirmed Gleason 4+4 prostate cancer underwent 18F-DCFPyL-PSMA PET scan to identify occult metastatic disease. This scan revealed abnormal radionuclide uptake not only in the prostate but also within the patient's vasculature. The scan was repeated after a week with a separate tracer batch, yielding the same result. Standard staging was performed using computed tomography and a Technetium-99 bone scan, revealing no metastatic disease. The patient's protein S deficiency is thought to have caused this peculiar tracer distribution. With the advent of PSMA PET for staging in prostate cancer, clinicians must be familiar with situations that may render unusual results.

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Potato late blight is the most devastating pre- and post-harvest crop disease in the world, which is widespread and difficult to control, causing serious economic losses. Cultivating resistant varieties is a major way to prevent and control late blight in a green way. However, due to the rapid evolution of pathogens, the plant resistance is losing. Therefore, mining effective and durable genes involved in disease resistance is crucial for breeding resistant varieties against late blight. In this study, we took "potato-Phytophthora infestans" as the "host-pathogen" model system to discover the potential disease resistance-related genes and elucidate their molecular functional mechanism. Through yeast two-hybridization, bimolecular fluorescence complementation, Co-immunoprecipitation assays, and gene function validation etc., we found that ribosomal protein S6 kinase 2 (StS6K2) is a key resistant protein, which is interacted with StWRKY59 transcription factor. Overexpression of StS6K2 and StWRKY59 both enhanced the plants resistance to P. infestans, and promoted the host immune response, such as ROS burst and callose deposition. In OEStWRKY59 lines, DEGs involved in secondary metabolites synthesis, plant hormone signaling transduction and plant-pathogen interaction were significantly enriched. These findings provide novel genetic resources for the breeding of resistant varieties.

Asunto(s)

Resistencia a la Enfermedad , Phytophthora infestans , Enfermedades de las Plantas , Proteínas de Plantas , Solanum tuberosum , Factores de Transcripción , Regulación de la Expresión Génica de las Plantas , Interacciones Huésped-Patógeno , Phytophthora infestans/patogenicidad , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Solanum tuberosum/microbiología , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética

RESUMEN

To reveal the interaction of oxidative stress and protein S-nitrosylation on mitochondrial pathway apoptosis and tenderness development in postmortem yak meat. Herein, we selected yak longissimus dorsi muscle as the research object and treated hydrogen peroxide (H2O2) with S-nitrosoglutathione agent (GSNO) as well as Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) in mixed injections with 0.9 % saline as a control group, followed by incubation at 4 °C for 12, 24, 72, 120 and 168 h. Results showed that this interaction significantly increased mitochondrial ROS and NO content (P < 0.05) while weakening the antioxidant capacity of GSH and TRX redox response systems or accelerating the Ca2+ release process, leading to mitochondrial functional impairment and increased apoptosis rate. Notably, the H2O2 + L-NAME group showed more pronounced apoptosis. Hence, we suggest that the interaction between oxidative stress and protein S-nitrosylation could positively regulate yak meat tenderization.

Asunto(s)

Apoptosis , Peróxido de Hidrógeno , Estrés Oxidativo , Animales , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Bovinos , Peróxido de Hidrógeno/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Óxido Nítrico/metabolismo , Carne/análisis , Cambios Post Mortem , Especies Reactivas de Oxígeno/metabolismo , S-Nitrosoglutatión/farmacología , S-Nitrosoglutatión/metabolismo , Antioxidantes/metabolismo , Antioxidantes/farmacología

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Idiopathic purpura fulminans (IPF) is a rare and severe form of purpura fulminans caused by acquired protein S deficiency. It can lead to severe thrombotic complications, such as large skin necrosis and amputation. The lesions almost exclusively affect the lower limbs, and their distribution is similar among patients with IPF, unlike classical purpura fulminans lesions. Our hypothesis is that vascular structures called perforasomes may be involved in IPF, possibly caused by protein S deficiency. We analyzed all case reports and case series published in the literature that provided sufficient data for an anatomical study of limb injuries. For precise localization of areas of necrosis, we examined each case using descriptions and images to determine whether they overlapped with vascular territories that include perforasomes. We analyzed twelve cases from the literature and identified six vascular territories: the anterolateral, anteromedial, and posterior territories of the upper leg, as well as the anterolateral, anteromedial, and posterolateral territories of the lower leg. For each territory, we described the most probable vascular damage and the corresponding perforasome. IPF is a complex multifactorial disease in which a direct involvement of perforating arteries may be suspected and taken into account in the surgical of lesions.

RESUMEN

In plants, nitric oxide (NO) has been widely accepted as a signaling molecule that plays a role in different processes. Among the most relevant pathways by which NO and its derivatives realize their biological functions, post-translational protein modifications are worth mentioning. Protein S-nitrosylation has been the most studied NO-dependent regulatory mechanism; it is emerging as an essential mechanism for transducing NO bioactivity in plants and animals. In recent years, the research of protein S-nitrosylation in plant growth and development has made significant progress, including processes such as seed germination, root development, photosynthetic regulation, flowering regulation, apoptosis, and plant senescence. In this review, we focus on the current state of knowledge on the role of S-nitrosylation in plant growth and development and provide a better understanding of its action mechanisms.

Asunto(s)

Óxido Nítrico , Desarrollo de la Planta , Proteínas de Plantas , Procesamiento Proteico-Postraduccional , Óxido Nítrico/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Plantas/metabolismo , Germinación , Fotosíntesis , Raíces de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Transducción de Señal

RESUMEN

BACKGROUND: SARS-CoV2 virus, responsible for the COVID-19 pandemic, has four structural proteins and 16 nonstructural proteins. S-protein is one of the structural proteins exposed on the virus surface and is the main target for producing neutralizing antibodies and vaccines. The S-protein forms a trimer that can bind the angiotensin-converting enzyme 2 (ACE2) through its receptor binding domain (RBD) for cell entry. AIMS: The goal of this study was to express in HEK293 cells a new RBD recombinant protein in a constitutive and stable manner in order to use it as an alternative immunogen and diagnostic tool for COVID-19. MATERIALS & METHODS: The protein was designed to contain an immunoglobulin signal sequence, an explanded C-terminal section of the RBD, a region responsible for the bacteriophage T4 trimerization inducer, and six histidines in the pCDNA-3.1 plasmid. Following transformation, the cells were selected with geneticin-G418 and purified from serum-fre culture supernatants using Ni2+-agarand size exclusion chromatography. The protein was structurally identified by cross-linking and circular dichroism experiments, and utilized to immunize mice in conjuction with AS03 or alum adjuvants. The mice sera were examined for antibody recognition, receptor-binding inhibition, and virus neutralization, while spleens were evaluated for γ-interferon production in the presence of RBD. RESULTS: The protein released in the culture supernatant of cells, and exhibited a molecular mass of 135 kDa with a secondary structure like the monomeric and trimeric RBD. After purification, it formed a multimeric structure comprising trimers and hexamers, which were able to bind the ACE2 receptor. It generated high antibody titers in mice when combined with AS03 adjuvant (up to 1:50,000). The sera were capable of inhibiting binding of biotin-labeled ACE2 to the virus S1 subunit and could neutralize the entry of the Wuhan virus strain into cells at dilutions up to 1:2000. It produced specific IFN-γ producing cells in immunized mouse splenocytes. DISCUSSION: Our data describe a new RBD containing protein, forming trimers and hexamers, which are able to induce a protective humoral and cellular response against SARS-CoV2. CONCLUSION: These results add a new arsenal to combat COVID-19, as an alternative immunogen or antigen for diagnosis.

Asunto(s)

Enzima Convertidora de Angiotensina 2 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Proteínas Recombinantes , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , Humanos , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/química , Ratones , Anticuerpos Neutralizantes/inmunología , SARS-CoV-2/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Células HEK293 , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra la COVID-19/inmunología , Ratones Endogámicos BALB C , Femenino , Multimerización de Proteína , Dominios Proteicos/inmunología , Unión Proteica

RESUMEN

Hereditary protein S (PS) deficiency is a rare condition associated with increased risk of venous thromboembolism (VTE). In 2020, the coronavirus disease 2019 (COVID-19) pandemic prompted development of vaccinations to protect against the virus. PS deficiency is not a contraindication to COVID-19 vaccinations, but there are no studies regarding potential adverse effects in this population. We report two cases, a 43-year-old mother and her 18-year-old son, who developed VTE shortly after their first COVID-19 vaccines. Testing confirmed hereditary PS deficiency with a previously undescribed mutation in both cases. The temporal association between COVID-19 vaccination and VTE in these patients with hereditary PS deficiency suggests a potential causal relationship. However, it is unclear if this applies to all patients with hereditary PS deficiency. This highlights the importance of reporting adverse events following COVID-19 vaccinations in this population to evaluate the risks and benefits of vaccination.

RESUMEN

BACKGROUND: Inherited antithrombin, protein C, and protein S deficiency increase the risk of venous thromboembolism. The presence of defects can be identified by clinical laboratory assays. In most Chinese clinical laboratories, the screening tests for antithrombin, protein C, and protein S deficiency are their activity assays. Ensuring appropriate pre-analytical storage conditions for activity tests is essential. This study aimed to assess the effects of storage conditions on antithrombin, protein C, and protein S activity in frozen plasma. METHODS: We collected the remaining plasma of 29 patients. The baseline of antithrombin, protein C, and protein S activity values were tested within 4 h. Then, each sample was sub-packaged into 4 EP tubes, and was stored at -20 °C for 3 days, -20 °C for 7 days, -80 °C for 3 days, and - 80 °C for 7 days, respectively. After thawing, samples were tested by two systems. RESULTS: The percentage deviation of antithrombin and protein C activity assay was<10% compared with the initial values. Protein S activity showed a significant reduction in frozen plasma, with a deviation > 10%. Some samples, initially within the normal range, were classified as abnormal after freezing storage. CONCLUSIONS: Our study indicated that antithrombin and protein C remain stable when stored at -20 °C or -80 °C in a week. We argued that Protein S activity is not stable in frozen plasma. The use of frozen-thawed plasma for PS activity assay may result in overdiagnosis of protein S deficiency.

RESUMEN

Inherited Protein S (PS) deficiency is an autosomal dominant thrombotic disorder. We encountered a case of inherited type I PS deficiency following a close examination for recurrent pregnancy loss and identified the mutation responsible; a novel splice donor site mutation in intron 13 of the PROS1 gene appeared to have caused a frameshift with premature termination at amino acid +551. These results will contribute to the creation of an accurate database and define the molecular basis for PS deficiency.

RESUMEN

The clotting system has evolved as an adaptive mechanism to prevent blood loss during vascular damage. However, the intricate nature of the clotting cascade and the complexities of human life can sometimes lead to the unnatural activation of this delicate cascade. This can result in blood clot formation within the cardiovascular system, contributing to a wide range of pathological conditions. Abnormal intravascular coagulation most commonly occurs in the deep veins of the lower extremities, and can emboli to other organs, hence, it is termed "venous thromboembolism" (VTE). In this report, we introduce a challenging case of VTE that poses a dilemma for current medical management. The patient with possible protein S deficiency underwent various guideline-directed medical treatments, yet experienced recurrent VTE episodes, including deep vein thrombosis (DVT) and pulmonary embolism (PE), leading to hospital readmissions. This case report sheds light on our challenges in effectively treating VTE.