Systemic thrombosis with prothrombin Belgrade mutation in a Chinese patient:A case report

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.

Prevention of thromboembolic events after radical prostatectomy in patients with hereditary thrombophilia due to a factor V Leiden mutation by multidisciplinary coagulation management

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.

Are all primary omental infarcts truly idiopathic?Five case reports

BACKGROUND Idiopathic omental infarction(IOI)is challenging to diagnose due to its low incidence and vague symptoms.Its differential diagnosis also poses difficulties because it can mimic many intra-abdominal organ pathologies.Although hypercoagulability and thrombosis are among the causes of omental infarction,venous thromboembolism scanning is rarely performed as an etiological investigation.CASE SUMMARY The medical records of the 5 cases,who had the diagnosis of IOI by computed tomography,were examined.The majority of the patients were male(n=4,80%)and the mean age was 31 years(range:21-38).The patients had no previous abdominal surgery or a history of any chronic disease.The main complaint of all patients was persistent abdominal pain.Omental infarction was detected in all patients with contrast-enhanced computed tomography.Conservative treatment was initially preferred in all patients,but it failed in 1 patient(20%).After discharge,all patients were referred to the hematology department for thrombophilia screening.Only 1 patient applied for thrombophilia screening and was homozygous for methylenetetrahydrofolate reductase(A1298C mutation)and heterozygous for a factor V Leiden mutation.CONCLUSION IOI should be considered in the differential diagnosis in patients presenting with progressive and/or persistent right side abdominal pain.Investigating risk factors such as hypercoagulability in patients with IOI is also important in preventing future conditions related to venous thromboembolism.

Etiology and consequences of thrombosis in abdominal vessels

The thrombophilia which can be either congenital or acquired in adult life has major implications in the abdominal vessels. The resulting portal vein thrombosis, Budd-Chiari syndrome and mesenteric vein thrombosis have a variety of consequences ranging from acute abdomen to chronic hepatomegaly and even totally asymp- tomatic patient in whom the only finding is pancytopenia. The complications like esophageal varices, portal gastropathy, ascites, severe hypersplenism, liver failure requiring liver transplantation are well known. Interesting features of collateral venous circulation showing itself as pseudocholangiocarcinoma sign and its possible clinical reflection as cholestasis are also known from a long time. The management strategies for these complications of intraabdominal vessel thrombosis are not different from their counterpart which is cirrhotic portal hypertension, but the prognosis is unquestionably better in former cases. In this review we presented and discussed the abdominal venous thrombosis, etiology and the resulting clinical pictures. There are controversial issues both in nomenclature, and management including anticoagulation problems and follow up strategies. In light of the current knowledge, we discussed some controversial issues in literature and presented our experience and our proposals about this group of patients.

Changing spectrum of Budd-Chiari syndrome in India with special reference to non-surgical treatment

AIM： To evaluate patterns of obstruction, etiological spectrum and non-surgical treatment in patients with Budd-Chiari syndrome in India. METHODS： Forty-nine consecutive cases of Budd- Chiari syndrome （BCS） were prospectively evaluated. All patients with refractory ascites or deteriorating liver function were, depending on morphology of inferior vena cava （IVC） and/or hepatic vein （HV） obstruction, triaged for radiological intervention, in addition to anticoagulation therapy. Asymptomatic patients, patients with diuretic-responsive ascites and stable liver function, and patients unwilling for surgical intervention were treated symptomatically with anticoagulation. RESULTS： Mean duration of symptoms was 41.5 ± 11.2 （range = 1-240） too. HV thrombosis （HVT） was present in 29 （59.1%）, IVC thrombosis in eight （16.3%）, membranous obstruction of IVC in two （4%） and both IVC-HV thrombosis in 10 （20.4%） cases. Of 35 cases tested for hypercoagulability, 27 （77.1%） were positive for one or more hypercoagulable states. Radiological intervention was technically successful in 37/38 （97.3%）： IVC stenting in seven （18.9%）, IVC balloon angioplasty in two （5.4%）, combined IVC-HV stenting in two （5.4%）, HV stenting in 11 （29.7%）, transjugular intrahepatic portosystemic shunt （TIPS） in 13 （35.1%） and combined TIPS-IVC stenting in two （5.4%）. Complications encountered in follow-up： death in five, re-stenosis of the stent in five （17.1%）, hepatic encephalopathy in two and hepatocellular carcinoma in one patient. Of nine patients treated medically, two showed complete resolution of HVT. CONCLUSION： IN our series, HVT was the predominant cause of BCS. In the last five years with the availability of sophisticated tests for hypercoagulability, etiologies were defined in 85.7% of cases. Non-surgical management was successful in most cases.

Portal hypertension due to portal venous thrombosis:Etiology, clinical outcomes

The thrombophilia in adult life has major implications in the hepatic vessels. The resulting portal vein thrombosis has various outcomes and complications. Esophageal varices, portal gastropathy, ascites, severe hypersplenism and liver failure needing liver transplantation are known well. The newly formed collateral venous circulation showing itself as pseudocholangicarcinoma sign and its possible clinical reflection as cholestasis are also known from a long time. The management strategies for these complications of portal vein thrombosis are not different from their counterpart which is cirrhotic portal hypertension, but the prognosis is unquestionably better in former cases. In this review we present and discuss the portal vein thrombosis, etiology and the resulting dinical pictures. There are controversial issues in nomenclature, management （including anticoagulation problems）, follow up strategies and liver transplantation. In the light of the current knowledge, we discuss some controversial issues in literature and present our experience and our proposals about this group of patients.

Recurrent thrombotic occlusion of a transjugular intrahepatic portosystemic stent-shunt due to activated protein C resistance

The transjugular intrahepatic portosystemic stent-shunt (TIPS) has successfully been used in the management of refractory variceal bleeding and ascites in patients with portal hypertension. Major drawbacks are the induction of hepatic encephalopathy and shunt dysfunction. We present a 59-year-old woman with alcoholic liver cirrhosis who received a TIPS because of recurrent bleeding from esophageal varices. Stent occlusion occurred 4 mo after placement of the TIPS. Laboratory testing revealed resistance to activated protein C (APC). Combination therapy with low-dose enoxaparin and clopidogrel could not prevent her recurrent stent occlusion. Finally, therapy with high-dose enoxaparin was sufficient to prevent further shunt complications up to now (follow-up period of 1 year). In conclusion, early occlusion of a TIPS warrants testing for thrombophilia. If risk factors are confirmed,anticoagulation should be intensified. There are currently no evidence-based recommendations regarding the best available anticoagulant therapy and surveillance protocol for patients with TIPS.

Treatment of Budd-Chiari syndrome with a focus on transjugular intrahepatic portosystemic shunt

AIM:To evaluate long-term complications and survival in patients with Budd-Chiari syndrome (BCS) referred to a Danish transjugular intrahepatic portosystemic shunt (TIPS) centre.METHODS:Twenty-one consecutive patients from 1997-2008 were retrospectively included [15 women and 6 men,median age 40 years (range 17-66 years)].Eighteen Danish patients came from the 1.8 million catchment population of Aarhus University Hospital and three patients were referred from Scandinavian hospitals.Management consisted of tests for underlying haematological,endocrinological,or hypercoagulative disorders parallel to initiation of specific treatment of BCS.RESULTS:BCS was mainly caused by thrombophilic (33%) or myeloproliferative (19%) disorders.Fortythree percents had symptoms for less than one week with ascites as the most prevalent finding.Fourteen (67%) were treated with TIPS and 7 (33%) were manageable with treatment of the underlying condition and diuretics.The median follow-up time for the TIPS-treated patients was 50 mo (range 15-117 mo),and none required subsequent liver transplantation.Ascites control was achieved in all TIPS patients with a marked reduction in the dose of diuretics.A total of 14 TIPS revisions were needed,mostly of uncovered stents.Two died during follow-up:One non-TIPS patient worsened after 6 mo and died in relation to transplantation,and one TIPS patient died 4 years after the TIPS-procedure,unrelated to BCS.CONCLUSION:In our BCS cohort TIPS-treated patients have near-complete survival,reduced need for diuretics and compared to historical data a reduced need for liver transplantation.

Thrombophilia Caused by Beta2-Glycoprotein I Deficiency： In Vitro Study of a Rare Mutation in APOH Gene

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.

Severe venous thromboembolism in the puerperal period caused by thrombosis:A case report

BACKGROUND The incidence of venous thromboembolism(VTE)in pregnant women is significantly higher than that in non-pregnant women.VTE is more common after delivery than before delivery,and this condition can be hidden and develops rapidly.VTE mainly includes deep vein thrombosis and pulmonary embolism.Thrombophilia is an important risk factor for VTE in pregnant women and includes acquired thrombophilia and hereditary thrombophilia.CASE SUMMARY A 24-year-old nulliparous female patient underwent cesarean section of the lower uterus due to fetal distress.Anti-inflammatory rehydration was given after the operation to prevent thrombosis.The patient had no obvious discomfort after surgery.Ten days after the operation,the patient developed a fever.The patient's mother revealed that she had a previous history of a lower extremity venous thrombosis.Color Doppler ultrasound showed deep vein thrombosis in the left lower extremity.The results of computed tomography angiography showed that the patient had a double pulmonary artery embolism.Bilateral lower extremity antegrade venography,inferior vena cava angiography and filter placement were performed.The patient continued to receive anticoagulant therapy.After 2 wk,the patient's condition improved.An anticoagulant protein test was performed 2 mo after discharge,and the results showed that both the patient and her mother had reduced protein S.CONCLUSION Clinicians should learn to recognize the high-risk factors for VTE,improve their understanding of VTE,and actively prevent and diagnose VTE as early as possible.

Outcomes of pregnancy in patients with known Budd-Chiari syndrome

AIM To analyse the risk of pregnancy(a prothrombotic state) in patients with Budd-Chiari Syndrome(BCS). METHODS Retrospective study of pregnancy in women with known BCS at single center from January 2001 to December 2015. RESULTS Out of 53 females with BCS, 7 women had 16 pregnancies. Median age at diagnosis of BCS in these women was 25 years(range 21-34 years). At least one causal factor for BCS was identified in 6 women(86%). Six women had undergone radiological decompressive treatment. All patients had anticoagulation. Six fetuses were lost before 20 wk gestation in 2 women. There were 9 deliveries over 32 wk gestation and one delivery at 27 wk. All infants did well. Seven babies were born by emergency caesarean section. There were no cases of thrombosis. Two patients had notable vaginal(PV) bleeding in 3 pregnancies. None of the patients had variceal haemorrhage. Two patients were diagnosed with pulmonary hypertension, one during pregnancyand the other in the post-partum period. There was no maternal mortality.CONCLUSION Maternal outcomes in patients with treated BCS are favourable and fetal outcomes beyond 20 wk gestation are good. There has been increased rate of caesarean section. Pulmonary hypertension is an important finding that needs further validation. These patients should be managed in centers experienced in treating high-risk pregnancies.

Aspirin responsive platelet thrombophilia in essential thrombocythemia and polycythemia vera

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.

Prevalence of hypercoagulable states in stented thrombotic iliac vein compression syndrome with comparison of re-intervention and anticoagulation regimens

BACKGROUND Endovascular therapy is playing an increasing role in the treatment of iliofemoral venous disease.Iliac stent patency is multifactorial,and current management is based on best clinical practices,varying by institution.AIM To evaluate how thrombophilia influences management and outcomes of patients who undergo venous stenting for thrombotic iliac vein compression syndromes.METHODS A retrospective observational analysis was performed on 65 patients with thrombotic iliac vein compression syndrome that underwent common iliac vein(CIV)stenting between December 2013 and December 2019 at a large academic center.Search criteria included CIV stenting and iliac vein compression.Nonthrombotic lesions and iliocaval thrombosis and/or occlusions were excluded.A total of 65 patients were selected for final analysis.Demographic information,procedural data points,and post-procedural management and outcomes were collected.Statistical analyses included Fisher's exact and Chi-square tests to compare discrete variables and the Wilcoxon rank-sum test to compare continuous variables between thrombophilia positive and negative patients.RESULTS 65 patients underwent successful balloon angioplasty and CIV stenting.Of these patients,33(50.8%)underwent thrombophilia testing,with 16(48.5%)testing positive.Stent patency on ultrasound did not significantly differ between thrombophilia positive and negative patients at 1 mo(92.3%vs 81.3%,P=0.6),6 mo(83.3%vs 80%,P>0.9),or 12 mo(77.8%vs 76.9%,P=0.8).Immediately after stent placement,thrombophilia patients were more likely to be placed on dual therapy(aspirin and anticoagulation)or triple therapy(aspirin,clopidogrel,and anticoagulation)(50%vs 41.2%,P>0.9),and remain on dual therapy at 6 mo(25%vs 12.5%,P=0.5)and 12 mo(25%vs 6.7%,P=0.6).There was no significant difference in re-intervention rates(25%vs 35.3%,P=0.7)or number of reinterventions(average 2.3 vs 1.3 per patient,P=0.4)between thrombophilia positive and negative patients.CONCLUSION Half of patients with stented thrombotic iliac vein compression syndrome and thrombophilia testing were positive.The presence of thrombophilia did not significantly impact stent patency or re-intervention rates.

Acute myocardial infarction after initially diagnosed with unprovoked venous thromboembolism: A case report

BACKGROUND Protein C deficiency is typically associated with venous thromboembolism;however,arterial thrombosis has been reported in several cases.We report the case of a patient with pulmonary thromboembolism and deep vein thrombosis following acute myocardial infarction with high thrombus burden.CASE SUMMARY A 40-year-old man was diagnosed with pulmonary thromboembolism and deep vein thrombosis without any provoking factors.The patient was treated with anticoagulants for six months,which were then discontinued.Three months after the discontinuation of anticoagulant therapy,the patient was hospitalized with chest pain and diagnosed with acute myocardial infarction with high thrombus burden.Additional tests revealed protein C deficiency associated with thrombophilia.The patient was treated with anticoagulants combined with dual antiplatelet agents for 1 year after percutaneous coronary intervention,and no recurrent events were reported during a follow-up period of 5 years.CONCLUSION Recurrent thromboembolic events including acute myocardial infarction with thrombus should be considered an alarming sign of thrombophilia.

Recurrent Implantation Failure and Low Molecular Weight Heparin

Implantation of the embryo into the endometrium is the first step in the establishment of pregnancy. This process is complex, and depends on many factors. Recurrent implantation failure is a source of distress to patients and specialists. It is defined as failure to achieve a viable pregnancy, following “>3 embryo transfers with high quality embryos or the transfer of ≥ 10 embryos in multiple transfers”. Thrombophilic conditions that contribute to recurrent implantation failure are the main concern in this review. The mechanism of implantation failure is believed to be due to decreased blood flow to the endometrium and placenta which can hinder normal endometrial receptivity leading to miscarriage. Defects in early placentation resulting in pregnancy failure, have focused attention on the therapeutic potential of low molecular weight heparin in the implantation process. Heparin has a role at all stages of implantation to improve pregnancy outcomes. There are controversies in literature regarding the association between thrombophilia and recurrent implantation failure and available literature regarding this issue is very heterogeneous. Various investigators, have shown that women with RIF are more likely to have a thrombophilia disorder, yet a clear cause cannot be acknowledged from these studies. Heparin treatment has been evaluated in several studies, showing conflicting evidence. However, several studies have pointed out that it may play a role in a subset of patients who presents a thrombophilia mutation, thus the group of patients that might benefit is needed to be identified. This review is dedicated to evaluate the published literature about the role of low molecular weight heparin in case of recurrent implantation failure with or without the presence of thrombophilia.

Venous thromboembolic risk and protein S deficiency: ethnic difference and remaining issues

Protein S deficiency is an autosomal dominant disorder that results from mutations in the protein S gene (PROS1). Inherited deficiency of protein S constitutes a risk factor for venous thromboembolism. Protein S functions as a nonenzymatic cofactor for activated protein C in the proteolytic degradation of coagulation factors V a and Villa. The frequency of protein S deficiency seems to differ between populations. More than 200 rare mutations in PROS1 have been identified in patients with protein S deficiency. Among the prevalent mutations within PROS1, the S460P substitution (known as Heerlen polymorphism) detected in Caucasians and the K196E substitution (known as protein S Tokushima) found in Japanese have been intensively studied for their structures and potential functions in the disorder of protein S deficiency. Until now, causative mutations in PROS1 have been found in only approximately 50% of cases with protein S deficiency. Co-segregation analysis of microsatellite haplotypes with protein S deficiency in families with protein S deficiency suggests that the causative defects in the PROS1 mutation-negative patients are located in or close to the PROS 1 gene. Large PROS 1 gene deletions have been identified in 3 out of 9 PROS 1 mutation-negative Swedish VTE families with protein S deficiency and 1 out of 6 PROS1 mutation-negative Japanese patients with protein S deficiency. Intensive sequencing of the entire PROS 1 gene, including introns, may be needed to identify the cryptic mutations in those patients, and these efforts might uncover the pathogenesis of protein S deficiency.

Portal vein thrombosis following percutaneous transhepatic cholangiography-An unusual presentation of Prothrombin (Factor Ⅱ) gene mutation

Portal vein thrombosis is an uncommonly reported complication of percutaneous transhepatic cholangiography (PTC). A thorough review of the available literature shows no reported cases. In this case, a 29 year old female presented on two separate occasions with portal vein thrombosis following PTC without drain placement. This unusual complication of image guided percutaneous biliary access is unreported in the literature and prompted evaluation of the patient's coagulation parameters. A thrombophilia screen demonstrated a mutation in the Prothrombin (Factor Ⅱ) gene. A thorough literature review shows no reported cases of portal vein thrombosis following percutaneous biliary access, is an unusual complication, and should raise suspicion of an underlying pro-coagulant state.

Successful treatment in one myelodysplastic syndrome patient with primary thrombocytopenia and secondary deep vein thrombosis:A case report

BACKGROUND The contradictory process of coagulation and anticoagulation maintains normal physiological function,and platelets(PLTs)play a key role in hemostasis and bleeding.When severe thrombocytopenia and deep vein thrombosis(DVT)occur simultaneously,the physician will be confronted with a great challenge,especially when interventional thrombectomy fails.CASE SUMMARY We describe a 52-year-old woman who suffered from myelodysplastic syndrome with severe thrombocytopenia and protein S deficiency with right lower extremity DVT.In this patient,the treatment of DVT was associated with numerous contradictions due to severe thrombocytopenia,especially when interventional thrombectomy was not successful.Fortunately,fondaparinux sodium effectively alleviated the thrombus status of the patient and gradually decreased the D-dimer level.In addition,no increase in bleeding was noted.The application of eltrombopag stimulated the maturation and differentiation of megakaryocytes and increased the peripheral blood PLT count.The clinical symptoms of DVT in the right lower extremities in this patient significantly improved.The patient resumed daily life activities,and the treatment effects were independent of PLT transfusion.CONCLUSION This is a contradictory and complex case,and fondaparinux sodium and eltrombopag may represent a good choice for the treatment of DVT in patients with severe thrombocytopenia.

Common carotid artery thrombosis and malignant middle cerebral artery infarction following ovarian hyperstimulation syndrome:A case report

BACKGROUND Arterial thrombosis is a serious and rare complication of ovarian hyperstimulation syndrome(OHSS).Herein,we describe a case of OHSS complicated by common carotid artery thrombosis and malignant middle cerebral artery infarction after egg retrieval and before embryo transfer.CASE SUMMARY A 32-year-old female with a family history of thrombosis who was undergoing in vitro fertilization due to unexplained infertility,was admitted due to abdominal distension for 3 d and coma for 2 h.She received egg retrieval 7 d ago and embryo transfer had not yet been performed.Blood biochemical analysis showed estrogen of 15781 pmol/L.Gynecological examination showed palpable masses on both sides of the adnexal areas.Ultrasound observed enlarged ovaries and abdominal ascites.Imaging examination of the head and neck revealed fresh malignant middle cerebral artery infarction in the left side of brain and internal carotid artery as well as occlusion in the left carotid artery,internal carotid artery,and middle cerebral artery.The patient was finally diagnosed with severe OHSS,complicated by common carotid artery thrombosis and malignant middle cerebral artery infarction.Liquid replacement,anticoagulation,vascular endothelium protection,brain protection and decompressive craniectomy were carried out.Rehabilitation training was then performed for 6 mo.At present,she has poor speaking ability and decreased muscle strength on the right side.CONCLUSION There is a risk of thrombosis during any period of OHSS.During in vitro assisted reproduction,for cases with a family history of thrombosis,hyperlipidemia and other high-risk factors,serum lipid levels should be controlled as soon as possible to improve metabolic dysfunction.When thrombosis occurs,timely and effective treatment should be performed to improve the prognosis.

Primary myelofibrosis with thrombophilia as first symptom combined with thalassemia and Gilbert syndrome:A case report

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.