This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophil...This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophilia. The plasma level of β2GPI was measured by ELISA and Western blotting, and anti-β2GPI antibody by ELISA. Lupus anticoagulant （LA） was assayed using the dilute Russell viper venom time. Deficiency of the major natural anticoagulants including protein C （PC）, protein S （PS）, antithrombin （AT） and thrombomodulin （TM） was excluded from the proband. A mutation analysis was performed by amplification and sequencing of the APOH gene. Wild type and mutant （c.112A〉G） APOH expression plasmids were constructed and transfected into HEK293T cells. The results showed that the thrornbin generation capacity of the proband was higher than that of the other family members. Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband. The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation. It was concluded that the recurrent thrombosis of the proband is associated with the coexistence ofp.Lys38Glu mutation in APOH gene and LA in plasma.展开更多
Essential thrombocythemia(ET) and polycythemia vera(PV) frequently present with erythromelalgia and acrocyanotic complications, migraine-like microvascular cerebral and ocular transient ischemic attacks(MIAs) and/or a...Essential thrombocythemia(ET) and polycythemia vera(PV) frequently present with erythromelalgia and acrocyanotic complications, migraine-like microvascular cerebral and ocular transient ischemic attacks(MIAs) and/or acute coronary disease. The spectrum of MIAs in ET range from poorly localized symptoms of transient unsteadiness, dysarthria and scintillating scotoma to focal symptoms of transient monocular blindness, transient mono- or hemiparesis or both. The attacks all have a sudden onset, occur sequentially rather than simultaneously, last for a few seconds to several minutes and are usually associated with a dull, pulsatile or migraine-like headache. Increased hematocrit and blood viscosity in PV patients aggravate the microvascular ischemic syndrome of thrombocythemia to major arterial and venous thrombotic complications. Phlebotomy to correct hematocrit to normal in PV significantly reduces major arterial and venous thrombotic complications, but fails to prevent the platelet-mediated erythromelalgia and MIAs. Complete long-term relief of the erythromelalgic microvascular disturbances, MIAs and major thrombosis in ET and PV patients can be obtained with low dose aspirin and platelet reduction to normal, but not with anticoagulation. Skin punch biopsies from the erythromelalgic area show fibromuscular intimal proliferation of arterioles complicated by occlusive plateletrich thrombi leading to acrocyanotic ischemia. Symptomatic ET patients with erythromelalgic microvascular disturbances have shortened platelet survival, increased platelet activation markers β-thromboglobulin(β-TG), platelet factor 4(PF4) and thrombomoduline(TM), increased urinary thromboxane B2(TXB2) excretion, and no activation of the coagulation markers thrombin fragments F1+2 and fibrin degradation products. Inhibition of platelet cyclooxygenase(COX1) by aspirin is followed by the disappearance and no recurrence of microvascular disturbances, increase in platelet number, correction of the shortened platelet survival times to normal, and reduction of increased plasma levels of β-TG, PF4, TM and urinary TXB2 excretion to normal. These results indicate that platelet-mediated fibromuscular intimal proliferation and platelet-rich thrombi in the peripheral, cerebral and coronary end-arterial microvasculature are responsible for the erythromelalgic ischemic complica-tions, MIAs and splanchnic vein thrombosis. Baseline platelet P-selectin levels and arachidonic acid induced COX1 mediated platelet activation showed a highly significant increase of platelet P-selectin expression(not seen in ADP and collagen stimulated platelets), which was significantly higher in JAK2V617 F mutated compared to JAK2 wild type ET.展开更多
Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)patients.With an incidence of about 5%,factor V Leiden mutation is the most commo...Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)patients.With an incidence of about 5%,factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia.The increased risk of thromboembolic events is three-to seven-fold in heterozygous and to 80-fold in homozygous patients.Methods:Within our prospectively collected database,we analysed 33006 prostate cancer patients treated with RP between December 2001 and December 2020.Of those,patients with factor V Leiden mutation were identified.All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation.Thromboembolic complications(deep vein thrombosis and pulmonary embolism)were assessed during hospital stay,as well as according to patient reported outcomes within the first 3 months after RP.Results:Overall,85(0.3%)patients with known factor V Leiden mutation were identified.Median age was 65(interquartile range:61-68)years.There was at least one thrombosis in 53(62.4%)patients and 31(36.5%)patients had at least one embolic event in their medical history before RP.Within all 85 patients with factor V Leiden mutation,we experienced no thromboembolic complications within the first 3 months after surgery.Conclusion:In our cohort of patients with factor V Leiden mutation,no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept.This may reassure patients with this hereditary condition who are counselled for RP.展开更多
BACKGROUND A 46-year-old Han man first had sigmoid sinus and transverse sinus venous thrombosis at the age of 42.At the age of 44,he once again developed thrombosis.Genetic testing showed heterozygous SERPINC1 mutatio...BACKGROUND A 46-year-old Han man first had sigmoid sinus and transverse sinus venous thrombosis at the age of 42.At the age of 44,he once again developed thrombosis.Genetic testing showed heterozygous SERPINC1 mutation,bone marrow biopsy showed fibrosis grade 1(MF-1),and JAK2 V617F mutation was positive,accompanied by UGT1A1 mutation andβ-thalassemia gene mutation.CASE SUMMARY A 46-year-old Han man was first found to have sigmoid sinus and transverse sinus venous thrombosis at the age of 42 but had no individual or family thrombosis history,and he had been regularly taking warfarin anticoagulant therapy for a long period of time.At the age of 44,venous thrombosis reappeared in parts of the intrahepatic vein,main portal vein,splenic vein,and superior mesenteric vein,and his spleen was obviously enlarged.He had a history of jaundice for many years,and genetic testing revealed that he carried a heterozygous SERPINC1 mutation.Bone marrow biopsy showed multifocal fibrous tissue hyperplasia among trabeculae and focal fibrosis.He was positive for the JAK2 V617F mutation.At the same time,UGT1A1 andβ-thalassemia gene mutations existed,and a SERPINC1 mutation and UGT1A1 mutation were both found in his parents.CONCLUSION The patient in this case had thrombophilia as the primary symptom,JAK2V617-positive myeloproliferative neoplasm(MPN)was the main potential cause,and hereditary AT-III deficiency may have been one of multiple secondary causes.It remains to be determined whether UGT1A1 andβ-thalassemia gene mutations are related to thrombophilia.However,the clinical features of MPN in this patient were hidden,and the relevant clinical features of coexisting thalassemia and hereditary Gilbert syndrome,reported here for the first time domestically and abroad,were complicating factors,causing great difficulties for a clear diagnosis.Thus,when thrombophilia has been determined,it is necessary to screen the relevant latent problems overall.When the clinical features cannot be perfectly explained by one etiology,a relevant comprehensive examination should also be initiated from the perspective of multiple etiologies.展开更多
Inherited thrombophilia has been implicated as a possible cause of recurrent pregnancy loss. Although numerous studies are available in literature, thrombophilia rate seems to vary fromstudy to another. The aim of our...Inherited thrombophilia has been implicated as a possible cause of recurrent pregnancy loss. Although numerous studies are available in literature, thrombophilia rate seems to vary fromstudy to another. The aim of our study was to determine the frequency of FII Prothrombin(G20210A), Factor V Leiden (G1691A), as well as methyl tetrahydrofolate reductase (MTHFR?C677T) polymorphisms, protein C, protein S and antithrombin III deficiency in a series of patients with unexplained RPL compared to control. Patients and Methods: 100 patients of unexplained RPL and 43 age-matched healthy controls were investigated for inherited thrombophilia. Results: MTHFR and Factor V Leiden were the commonest gene defects among cases studied (63%, 60% respectively) and control groups (41.9%, 41.9% respectively) (p = 0.019, p = 0.046 respectively). The least common deficiencies were protein S and protein C deficiency in cases (3%, 2% respectively) as well as in controls (1%, 0% respectively). 4 cases were homozygous for MTHFR and 2 cases homozygous for Factor V Leiden mutation. Odds ratio for MTHFR and Factor V mutation was 2.36 and 2.08 respectively (CI 95%). Combined defects were seen in cases and controls (p < 0.05). Conclusion: Our study found an association between MTHFR and Factor V Leiden mutations in patients with unexplained RPL among Egyptian women. Further studies are needed to define the management of genetic thrombophilia in cases of recurrent pregnancy loss.展开更多
Vaccination against COVID-19 is the most recognised means of containing the pandemic. Vaccines are not without side effects, particularly vascular thrombosis. But before blaming the vaccines, a thorough asse...Vaccination against COVID-19 is the most recognised means of containing the pandemic. Vaccines are not without side effects, particularly vascular thrombosis. But before blaming the vaccines, a thorough assessment of thrombotic risk factors is necessary. We report a case of arterial and venous thrombosis after vaccination with AstraZeneca revealing an exaggeration of factor VIII in a 37-year-old female patient. The angioscanner showed a venous thrombosis of the right subclavian, a pulmonary embolism and the presence of a thrombus in the aorta. The biology was in favour of a high level of factor VIII. The patient was treated with an antivitamin K, and the clinical evolution was favourable.展开更多
Thrombophilia is described as a tendency to develop thrombosis as a consequence of predisposing factors that may be genetically determined, acquired, or both. The risk factors associated with venous thromboembolism ar...Thrombophilia is described as a tendency to develop thrombosis as a consequence of predisposing factors that may be genetically determined, acquired, or both. The risk factors associated with venous thromboembolism are different from those associated with arterial thrombosis.展开更多
Thrombophilia encompasses a spectrum of disorders characterized by a predisposition to a hypercoagulable state,frequently culminating in thromboembolism.1 Among these,hereditary thrombophilia is defined as conditions ...Thrombophilia encompasses a spectrum of disorders characterized by a predisposition to a hypercoagulable state,frequently culminating in thromboembolism.1 Among these,hereditary thrombophilia is defined as conditions arising from genetic mutations that disrupt hemostatic equilibrium.The clinical manifestations of thrombophilia primarily involve venous thromboembolism(VTE).Certain genetic variants may also predispose individuals to arterial thrombotic events.While previous articles have provided guidance on indications for thrombophilia screening,discussions are largely confined to whether such screening informs the“duration of anticoagulation therapy.”1 This guideline,focusing specifically on hereditary thrombophilia,seeks to delineate the impact of diverse genetic factors on the selection of anticoagulant drug types and their duration.This work primarily addresses major hereditary thrombophilias.Gene polymorphisms with minimal contributions to disease,such as those associated with the ABO blood group,as well as exceedingly rare genetic mutations like F9 Padua,are not discussed here due to their limited clinical relevance or scant supporting evidence.The panel adopts the 2011 Oxford Center for Evidence-Based Medicine framework to assess the level of evidence(LoE)and make recommendations.展开更多
Protein C(PC)is an important physiological anticoagulant protein that is a vitamin K-dependent serine protease precursor that is synthesized mainly by the liver and released into the blood.It is activated by the throm...Protein C(PC)is an important physiological anticoagulant protein that is a vitamin K-dependent serine protease precursor that is synthesized mainly by the liver and released into the blood.It is activated by the thrombin/thrombomodulin complex to form activated protein C(APC),which exerts physiological anticoagulant functions by inactivating activated coagulation factors Ⅴ and Ⅷ.1 PC is encoded by the protein C gene(PROC),which is located in the q13-q14 region of chromosome 2 and consists of 9 exons and 8 introns and is approximately 11.2 kb in length.2 Individuals carrying the PROC gene variant have a risk of developing venous thrombosis that is approximately 7 times greater than that of normal individuals.PC deficiency caused by homozygous or compound heterozygous variations in the PROC gene is extremely rare.3 The prevalence rate of protein C deficiency among healthy people in China is approximately 0.29%.4 Here,we report a teenage patient with multiple recurrent deep venous thromboses associated with protein C deficiency caused by compound heterozygous variants that have not been previously reported.展开更多
BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such a...BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.展开更多
BACKGROUND Thrombophilia contributes to a significant increased risk of venous thromboembolism and can be either inherited or acquired.Hereditary thrombophilia may arise from various gene mutations,some of which have ...BACKGROUND Thrombophilia contributes to a significant increased risk of venous thromboembolism and can be either inherited or acquired.Hereditary thrombophilia may arise from various gene mutations,some of which have not even been adequately reported or poorly understood.Previous studies reported a rare and novel missense mutation in the prothrombin gene(p.Arg596Gln),known as prothrombin Belgrade.The mechanisms and therapeutic strategies associated with prothrombin Belgrade mutation have not been fully elucidated.CASE SUMMARY We present the case of a 26-year-old woman with recurrent systemic thrombosis induced by prothrombin Belgrade mutation.The patient suffered from cerebral venous sinus thrombosis that rapidly progressed to systemic thrombosis,alongside a family history of cerebral thrombosis,and no traditional risk factors or abnormal coagulation function.Whole-genome sequencing detected a novel and rare heterozygous prothrombin missense mutation,c.1787G>T(p.Arg596Gln),which was responsible for the major etiology of the systemic thrombosis.CONCLUSION This case strengthens our understanding about hereditary basis of thrombophilia and provokes considerations for therapeutic options on prothrombin Belgrade mutation.展开更多
文摘This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophilia. The plasma level of β2GPI was measured by ELISA and Western blotting, and anti-β2GPI antibody by ELISA. Lupus anticoagulant （LA） was assayed using the dilute Russell viper venom time. Deficiency of the major natural anticoagulants including protein C （PC）, protein S （PS）, antithrombin （AT） and thrombomodulin （TM） was excluded from the proband. A mutation analysis was performed by amplification and sequencing of the APOH gene. Wild type and mutant （c.112A〉G） APOH expression plasmids were constructed and transfected into HEK293T cells. The results showed that the thrornbin generation capacity of the proband was higher than that of the other family members. Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband. The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation. It was concluded that the recurrent thrombosis of the proband is associated with the coexistence ofp.Lys38Glu mutation in APOH gene and LA in plasma.
文摘Essential thrombocythemia(ET) and polycythemia vera(PV) frequently present with erythromelalgia and acrocyanotic complications, migraine-like microvascular cerebral and ocular transient ischemic attacks(MIAs) and/or acute coronary disease. The spectrum of MIAs in ET range from poorly localized symptoms of transient unsteadiness, dysarthria and scintillating scotoma to focal symptoms of transient monocular blindness, transient mono- or hemiparesis or both. The attacks all have a sudden onset, occur sequentially rather than simultaneously, last for a few seconds to several minutes and are usually associated with a dull, pulsatile or migraine-like headache. Increased hematocrit and blood viscosity in PV patients aggravate the microvascular ischemic syndrome of thrombocythemia to major arterial and venous thrombotic complications. Phlebotomy to correct hematocrit to normal in PV significantly reduces major arterial and venous thrombotic complications, but fails to prevent the platelet-mediated erythromelalgia and MIAs. Complete long-term relief of the erythromelalgic microvascular disturbances, MIAs and major thrombosis in ET and PV patients can be obtained with low dose aspirin and platelet reduction to normal, but not with anticoagulation. Skin punch biopsies from the erythromelalgic area show fibromuscular intimal proliferation of arterioles complicated by occlusive plateletrich thrombi leading to acrocyanotic ischemia. Symptomatic ET patients with erythromelalgic microvascular disturbances have shortened platelet survival, increased platelet activation markers β-thromboglobulin(β-TG), platelet factor 4(PF4) and thrombomoduline(TM), increased urinary thromboxane B2(TXB2) excretion, and no activation of the coagulation markers thrombin fragments F1+2 and fibrin degradation products. Inhibition of platelet cyclooxygenase(COX1) by aspirin is followed by the disappearance and no recurrence of microvascular disturbances, increase in platelet number, correction of the shortened platelet survival times to normal, and reduction of increased plasma levels of β-TG, PF4, TM and urinary TXB2 excretion to normal. These results indicate that platelet-mediated fibromuscular intimal proliferation and platelet-rich thrombi in the peripheral, cerebral and coronary end-arterial microvasculature are responsible for the erythromelalgic ischemic complica-tions, MIAs and splanchnic vein thrombosis. Baseline platelet P-selectin levels and arachidonic acid induced COX1 mediated platelet activation showed a highly significant increase of platelet P-selectin expression(not seen in ADP and collagen stimulated platelets), which was significantly higher in JAK2V617 F mutated compared to JAK2 wild type ET.
文摘Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)patients.With an incidence of about 5%,factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia.The increased risk of thromboembolic events is three-to seven-fold in heterozygous and to 80-fold in homozygous patients.Methods:Within our prospectively collected database,we analysed 33006 prostate cancer patients treated with RP between December 2001 and December 2020.Of those,patients with factor V Leiden mutation were identified.All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation.Thromboembolic complications(deep vein thrombosis and pulmonary embolism)were assessed during hospital stay,as well as according to patient reported outcomes within the first 3 months after RP.Results:Overall,85(0.3%)patients with known factor V Leiden mutation were identified.Median age was 65(interquartile range:61-68)years.There was at least one thrombosis in 53(62.4%)patients and 31(36.5%)patients had at least one embolic event in their medical history before RP.Within all 85 patients with factor V Leiden mutation,we experienced no thromboembolic complications within the first 3 months after surgery.Conclusion:In our cohort of patients with factor V Leiden mutation,no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept.This may reassure patients with this hereditary condition who are counselled for RP.
文摘BACKGROUND A 46-year-old Han man first had sigmoid sinus and transverse sinus venous thrombosis at the age of 42.At the age of 44,he once again developed thrombosis.Genetic testing showed heterozygous SERPINC1 mutation,bone marrow biopsy showed fibrosis grade 1(MF-1),and JAK2 V617F mutation was positive,accompanied by UGT1A1 mutation andβ-thalassemia gene mutation.CASE SUMMARY A 46-year-old Han man was first found to have sigmoid sinus and transverse sinus venous thrombosis at the age of 42 but had no individual or family thrombosis history,and he had been regularly taking warfarin anticoagulant therapy for a long period of time.At the age of 44,venous thrombosis reappeared in parts of the intrahepatic vein,main portal vein,splenic vein,and superior mesenteric vein,and his spleen was obviously enlarged.He had a history of jaundice for many years,and genetic testing revealed that he carried a heterozygous SERPINC1 mutation.Bone marrow biopsy showed multifocal fibrous tissue hyperplasia among trabeculae and focal fibrosis.He was positive for the JAK2 V617F mutation.At the same time,UGT1A1 andβ-thalassemia gene mutations existed,and a SERPINC1 mutation and UGT1A1 mutation were both found in his parents.CONCLUSION The patient in this case had thrombophilia as the primary symptom,JAK2V617-positive myeloproliferative neoplasm(MPN)was the main potential cause,and hereditary AT-III deficiency may have been one of multiple secondary causes.It remains to be determined whether UGT1A1 andβ-thalassemia gene mutations are related to thrombophilia.However,the clinical features of MPN in this patient were hidden,and the relevant clinical features of coexisting thalassemia and hereditary Gilbert syndrome,reported here for the first time domestically and abroad,were complicating factors,causing great difficulties for a clear diagnosis.Thus,when thrombophilia has been determined,it is necessary to screen the relevant latent problems overall.When the clinical features cannot be perfectly explained by one etiology,a relevant comprehensive examination should also be initiated from the perspective of multiple etiologies.
文摘Inherited thrombophilia has been implicated as a possible cause of recurrent pregnancy loss. Although numerous studies are available in literature, thrombophilia rate seems to vary fromstudy to another. The aim of our study was to determine the frequency of FII Prothrombin(G20210A), Factor V Leiden (G1691A), as well as methyl tetrahydrofolate reductase (MTHFR?C677T) polymorphisms, protein C, protein S and antithrombin III deficiency in a series of patients with unexplained RPL compared to control. Patients and Methods: 100 patients of unexplained RPL and 43 age-matched healthy controls were investigated for inherited thrombophilia. Results: MTHFR and Factor V Leiden were the commonest gene defects among cases studied (63%, 60% respectively) and control groups (41.9%, 41.9% respectively) (p = 0.019, p = 0.046 respectively). The least common deficiencies were protein S and protein C deficiency in cases (3%, 2% respectively) as well as in controls (1%, 0% respectively). 4 cases were homozygous for MTHFR and 2 cases homozygous for Factor V Leiden mutation. Odds ratio for MTHFR and Factor V mutation was 2.36 and 2.08 respectively (CI 95%). Combined defects were seen in cases and controls (p < 0.05). Conclusion: Our study found an association between MTHFR and Factor V Leiden mutations in patients with unexplained RPL among Egyptian women. Further studies are needed to define the management of genetic thrombophilia in cases of recurrent pregnancy loss.
文摘Vaccination against COVID-19 is the most recognised means of containing the pandemic. Vaccines are not without side effects, particularly vascular thrombosis. But before blaming the vaccines, a thorough assessment of thrombotic risk factors is necessary. We report a case of arterial and venous thrombosis after vaccination with AstraZeneca revealing an exaggeration of factor VIII in a 37-year-old female patient. The angioscanner showed a venous thrombosis of the right subclavian, a pulmonary embolism and the presence of a thrombus in the aorta. The biology was in favour of a high level of factor VIII. The patient was treated with an antivitamin K, and the clinical evolution was favourable.
文摘Thrombophilia is described as a tendency to develop thrombosis as a consequence of predisposing factors that may be genetically determined, acquired, or both. The risk factors associated with venous thromboembolism are different from those associated with arterial thrombosis.
基金supported by the Chang Jiang Scholars Program(No.2022161).
文摘Thrombophilia encompasses a spectrum of disorders characterized by a predisposition to a hypercoagulable state,frequently culminating in thromboembolism.1 Among these,hereditary thrombophilia is defined as conditions arising from genetic mutations that disrupt hemostatic equilibrium.The clinical manifestations of thrombophilia primarily involve venous thromboembolism(VTE).Certain genetic variants may also predispose individuals to arterial thrombotic events.While previous articles have provided guidance on indications for thrombophilia screening,discussions are largely confined to whether such screening informs the“duration of anticoagulation therapy.”1 This guideline,focusing specifically on hereditary thrombophilia,seeks to delineate the impact of diverse genetic factors on the selection of anticoagulant drug types and their duration.This work primarily addresses major hereditary thrombophilias.Gene polymorphisms with minimal contributions to disease,such as those associated with the ABO blood group,as well as exceedingly rare genetic mutations like F9 Padua,are not discussed here due to their limited clinical relevance or scant supporting evidence.The panel adopts the 2011 Oxford Center for Evidence-Based Medicine framework to assess the level of evidence(LoE)and make recommendations.
基金supported by the Natural Science Foundation of China(No.82300492)the Scientific Research Project of Health Commission in Shanxi Province,China(Nos.2023XG009 and 2023RC008)+2 种基金the China Postdoctoral Science Foundation(No.2023M732154)the Research Project Supported by Shanxi Scholarship Council of China(No.2023-181)the Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province,China(No.20230054).
文摘Protein C(PC)is an important physiological anticoagulant protein that is a vitamin K-dependent serine protease precursor that is synthesized mainly by the liver and released into the blood.It is activated by the thrombin/thrombomodulin complex to form activated protein C(APC),which exerts physiological anticoagulant functions by inactivating activated coagulation factors Ⅴ and Ⅷ.1 PC is encoded by the protein C gene(PROC),which is located in the q13-q14 region of chromosome 2 and consists of 9 exons and 8 introns and is approximately 11.2 kb in length.2 Individuals carrying the PROC gene variant have a risk of developing venous thrombosis that is approximately 7 times greater than that of normal individuals.PC deficiency caused by homozygous or compound heterozygous variations in the PROC gene is extremely rare.3 The prevalence rate of protein C deficiency among healthy people in China is approximately 0.29%.4 Here,we report a teenage patient with multiple recurrent deep venous thromboses associated with protein C deficiency caused by compound heterozygous variants that have not been previously reported.
文摘BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.
文摘BACKGROUND Thrombophilia contributes to a significant increased risk of venous thromboembolism and can be either inherited or acquired.Hereditary thrombophilia may arise from various gene mutations,some of which have not even been adequately reported or poorly understood.Previous studies reported a rare and novel missense mutation in the prothrombin gene(p.Arg596Gln),known as prothrombin Belgrade.The mechanisms and therapeutic strategies associated with prothrombin Belgrade mutation have not been fully elucidated.CASE SUMMARY We present the case of a 26-year-old woman with recurrent systemic thrombosis induced by prothrombin Belgrade mutation.The patient suffered from cerebral venous sinus thrombosis that rapidly progressed to systemic thrombosis,alongside a family history of cerebral thrombosis,and no traditional risk factors or abnormal coagulation function.Whole-genome sequencing detected a novel and rare heterozygous prothrombin missense mutation,c.1787G>T(p.Arg596Gln),which was responsible for the major etiology of the systemic thrombosis.CONCLUSION This case strengthens our understanding about hereditary basis of thrombophilia and provokes considerations for therapeutic options on prothrombin Belgrade mutation.
