Thrombophilia Profile Research Articles

Long-term impact of transcatheter closure interatrial shunts on disabling migraine

Backgrounds Effectiveness of patent foramen ovale (PFO) closure on relief of migraine, is still unclear. We sought to analyse the long-term (>10 years) effects of interatrial septal shunt repair on disabling migraine performing a retrospective non-randomised study. Methods Clinical records of patients with disabling, medication-refractory migraine and PFO or significant ASD referred to our centre for closure from 2006 to 2018, were analysed. Results Forty -six patients (38 female, mean age 40.0 ± 3.7 years) with PFO and 32 patients with significant ASD (28 female, mean age 38.0 ± 4.1 years) submitted to transcatheter closure had a pre-existing disabling migraine with mean Migraine Disability Assessment Score (MIDAS) of 35.8 ± 4.7. After a mean follow-up of 118.2 ± 19.1 months (range 96 to 144), 72 out of 78 patients were still followed-up: in all subjects, aura was abolished, and migraine improved also in patients without aura. The mean MIDAS significantly decreased from baseline value (p < 0.01). Complete migraine resolution was associated in PFO patients with a shorter history of migraine, a more severe thrombophilic profile, a more severe Right-to-Left Shunt (RLS) and larger left atrial diameter and volume, and in ASD patients with bidirectional shunt. Conclusions Device-based repair of PFO/ASD in patients with migraine was associated with abolition of aura and symptoms reduction in the long-term period.

The Etiology of the Thrombotic Phenomena Involved in the Process of Coronary Artery Disease-What Is the Role of Thrombophilic Genes in the Development of This Pathology?

Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at determining the risk factors involved recognizes a group of "traditional" risk factors, but also more recent studies identified over 100 "novel" ones which may have a role in the disease. Among the latter is the thrombophilia profile of a patient, a pathology well-established for its involvement in venous thromboembolism, but with less studied implications in arterial thrombosis. This paper reviews the literature, explaining the pathophysiology of the thrombophilia causes associated most with coronary thrombosis events. Results of several studies on the subject, including a meta-analysis with over 60,000 subjects, determined the significant involvement of factor V Leiden, prothrombin G20210A mutation, plasminogen activator inhibitor-1 and antiphospholipid syndrome in the development of coronary artery disease. The mechanisms involved are currently at different stages of research, with some already established and used as therapeutic targets.

Safety and efficacy of extended thrombophilia screening directed venous thromboembolic events (VTE) prophylaxis in live liver donors: do we really need extended thrombophilia screening routinely?

The study aimed to determine the prevalence of hereditary thrombophilia, and stratify its severity among live liver donors in Pakistan. Also, the authors evaluated the safety and efficacy of thrombophilia profile testing directed venous thromboembolic events (VTE) prophylaxis while balancing bleeding risk and the need for routine thrombophilia testing before live liver donation among living donor candidates. Protein S (PS), protein C (PC), anti-thrombin (AT) III, and anti-phospholipid antibody panel (APLA) levels were measured in 567 potential donor candidates. Donors were divided into normal, borderline and high-risk groups based on Caprini score. The safety endpoints were VTE occurrence, bleeding complications or mortality. Among 567 donors, 21 (3.7%) were deficient in protein C, and 14 (2.5%) were deficient in anti-thrombin-III. IgM and IgG. Anti-phospholipids antibodies were positive in 2/567 (0.4%) and 2/567 (0.4%), respectively. IgM and IgG lupus anticoagulant antibodies were positive in 3/567 (0.5%) and 3/567 (0.5%), respectively. VTE events, bleeding complications and postoperative living donors liver transplantation-related complications were comparable among the three donor groups (P>0.05). One donor in the normal donor group developed pulmonary embolism, but none of the donors in either borderline or high-risk group developed VTE. The mean length of ICU and total hospital stay were comparable. No donor mortality was observed in all donor groups. Due to thrombophilia testing directed VTE prophylaxis, VTE events were comparable in normal, borderline and high-risk thrombophilia donor groups, but more evaluations are required to determine the lower safe levels for various thrombophilia parameters including PC, PS and AT-III before surgery among living donor candidates.

A clinico-etiological profile of adult extrahepatic portal venous obstruction in patients from Northern India. Is it a novel subset of occult extrahepatic portal vein obstruction?

Background: Extrahepatic portal vein obstruction (EHPVO) is caused by occlusion and cavernomatous transformation of the portal vein. The EHPVO is well characterized in children. However, the same is not valid for adults. We aimed to evaluate the clinico-etiological profile along with the management of adult patients. Aims and Objectives: We evaluated the clinico-etiological profile along with the management and outcomes of adult patients presenting with EHPVO. Materials and Methods: In a descriptive, observational study, patients between ages 15 and 75 years diagnosed with EHPVO on ultrasonography abdomen were included in the study. Liver cirrhosis and malignancy were considered as an exclusion criterion. There was evaluation of clinical and imaging findings along with biochemical analysis, workup for thrombophilia, treatment given to the patients, and follow-up. Results: Out of total 109 patients enrolled in the study, the median age of patients was ±40.25. Main clinical features were dyspepsia, abdominal discomfort, and splenomegaly. Out of 109, 27.5% patients showed fatty liver and 5.5% had both splanchnic vein thrombosis and fatty liver. Idiopathic EHPVO in majority of patients (80%), adult EHPVO with polycythemia rubra vera in 7.33% patients, adult EHPVO with heterozygous MTHFR mutation in 7.33% patients, and adult EHPVO with antiphospholipid antibody in 3.66%. No mortality was seen in this 5-year observational study and majority of the patients, i.e., 96 (88.1%) did not require any treatment. Conclusion: Relatively benign nature of adult EHPVO was found in the selected group of patients. Majority of the cases in our study were idiopathic and few had positive thrombophilia profile.

Successful Treatment of Massive Pulmonary Embolism with Rescue Fibrinolysis in Young Patient with Homocystinemia - Case Report

Abstract Pulmonary embolism (PE) is the most frequently missed diagnosis in the urgent clinical department with serious consequences. Patients with unprovoked PE have increased risk of recurrent PE. Approximately 5 to 8% of PE patients have inherited thrombophilias. A solated homocystinemia is a rare cause of unprovoked acute pulmonary embolism. Timely diagnosis and proper treatment can prevent complications, costs and mortality and provide patient better quality of life. We are presenting a 42-year-old woman was admitted to our emergency department with the first episode of severe dyspnea and chest pain. She had no history of previous cardiovascular or respiratory disease and no history of previous pulmonary embolism (PE) or deep vein thrombosis (DVT). Urgent echocardiography showed indirect signs of pulmonary embolism which was confirmed by the pulmonary artery CT angiography performed one day after the patient’s admission. After two days of heparin infusion, she developed a hemodynamic instability with cardiogenic shock and was treated successfully with fibrinolysis. After the clinical stabilization, she was put on the rivaroxaban therapy, which was recommended for additional six months. The thrombophilia profile was done two weeks after stopping the therapy with rivaroxaban. The thrombophilia panel came back positive for high levels of homocysteine (67 μmol/L), with other thrombophilia results within normal limits. The patient was stable during the follow-up period. Pulmonary embolism should be always suspected in younger patients with acute severe dyspnea even without provocable risk factors. High suspicion level and fast diagnosis are lifesaving. In younger patients presented with unprovoked pulmonary embolism, clinicians should consider inherited prothrombotic factors and homocystinemia as a potential cause. Rescue fibrinolysis is a lifesaving therapy in hemodynamic worsening in intermediate high-risk PE patients. A longer anticoagulation therapy should be considered in these cases with novel oral anticoagulants that are recommended as safer and superior therapy.

C50 VERY LONG TERM FOLLOW UP OF PRIMARY TRANSCATHETER PATENT FORAMEN OVALE CLOSURE FOR MIGRAINE CURE

Abstract Background Results of previous trials about PFO closure as a treatment for migraine are still doubtful and inconclusive. We sought to evaluate the long–term (&amp;gt;10 years) effectiveness of migraine treatment by means of patent foramen ovale (PFO) closure. Methods From 2006 to 2010, 86 patients (68 female, mean age 40.0 ±3.7 years) with disabling, medication–refractory migraine and PFO were enrolled in a prospective study over a 48–month period. Criteria for transcatheter closure were all the following: presence of a permanent right–to–left shunt (RLS) having a shower/curtain pattern, presence of interatrial septal aneurysm and Eustachian valve, 3 to 4 class Migraine Disability Assessment Score (MIDAS), coagulation abnormalities, and medication–refractory migraine with or without aura. Results Forty patients (46.5%) (34 females, mean age 35.0±6.7 years, mean MIDAS 35.8 ± 4.7) underwent transcatheter closure. After a mean follow–up of 118.2 ±19.1 months (range 96 to 144), 37 patients continued the follow–up and experienced symptomatic improvement: aura was abolished in the totality of patients along with a durable improvement of migraine throughout the extended follow up also in patients without aura. The mean MIDAS significantly decreased in the closure group (p&amp;lt;0.0001) (Figure 1). Patients with complete migraine resolution presented a shorter history of migraine, a more severe thrombophilic profile, more severe RLS and larger left atrial diameter and volume. Conclusions Primary transcatheter PFO closure in selected high–risk patients having disabling refractory migraine resulted in abolition of aura and in a sustained reduction in migraine in the very long–term period.

Extra-hepatic portal vein thrombosis in children: Single center experience.

We aimed to discuss our experience in management of children with extra-hepatic portal vein thrombosis (EHPVT). This retrospective cohort study included 62 children with EHPVT. All patients' records were reviewed. The patients' socio-demographic data, post-natal history, disease presentation and clinical examination were collected. Data from laboratory investigations - complete blood count, liver function tests, renal function tests, abdominal ultrasound/Doppler studies, upper endoscopic findings and treatment regimens - were collected whenever available. Of the 62 patients, 62.9% were male and 37.1% were female. The mean age at disease presentation was 3.5 ±2.7 years. The main initial clinical presentation of the disease was hematemesis and/or melena (30 cases; 48.4%). History of umbilical catheterization (UVC) was present in 60% of cases. The thrombophilia profile was assessed in 17 patients, of whom 12 (70.6%) were found to have a coagulation disorder. Splenomegaly was present in 91.7% of the patients. Hematological abnormalities in the form of cytopenias were present in most cases. Ultrasound revealed the presence of collaterals in 76.2%. Upper endoscopy showed the presence of varices in 45 cases, all of which needed endoscopic intervention, while in 11 cases the varices were either low grade or absent and thus were subjected only to medical treatment with propranolol and 6 cases were lost to follow-up. Splenectomy was done in only one case and 2 cases underwent the Rex operation. Variceal bleeding is the most common clinical presentation of EHPVT in children. UVC is still the main etiological factor of EHPVT in our cohort especially with presence of thrombophilic disorder.

P164 VERY LONG TERM FOLLOW UP OF PRIMARY TRANSCATHETER PATENT FORAMEN OVALE CLOSURE FOR MIGRAINE CURE

Abstract Background and Purpose Results of previous trials about PFO closure as a treatment for migraine are still doubtful and inconclusive. We sought to evaluate the long–term (&amp;gt;10 years) effectiveness of migraine treatment by means of patent foramen ovale (PFO) closure. Method From 2006 to 2010, 86 patients (68 female, mean age 40.0 ±3.7 years) with disabling, medication–refractory migraine and PFO were enrolled in a prospective study over a 48–month period. Criteria for transcatheter closure were all the following: presence of a permanent right–to–left shunt (RLS) having a shower/curtain pattern, presence of interatrial septal aneurysm and Eustachian valve, 3 to 4 class Migraine Disability Assessment Score (MIDAS), coagulation abnormalities, and medication–refractory migraine with or without aura. Results Forty patients (46.5%) (34 females, mean age 35.0±6.7 years, mean MIDAS 35.8 ± 4.7) underwent transcatheter closure. After a mean follow–up of 118.2 ±19.1 months (range 96 to 144), 37 patients continued the follow–up and experienced symptomatic improvement: aura was abolished in the totality of patients along with a durable improvement of migraine throughout the extended follow up also in patients without aura. The mean MIDAS significantly decreased in the closure group (p &amp;lt; 0.0001). Patients with complete migraine resolution presented a shorter history of migraine, a more severe thrombophilic profile, more severe RLS and larger left atrial diameter and volume. Conclusions Primary transcatheter PFO closure in selected high–risk patients having disabling refractory migraine resulted in abolition of aura and in a sustained reduction in migraine in the very long–term period.

Cerebral venous sinus thrombosis following trans-sphenoidal excision of pituitary adenoma: A case report

A 52-year-old female diagnosed to harbour a non-functioning pituitary adenoma underwent trans-sphenoidal excision of the tumour. On the 8th post-operative day, the patient developed severe headaches and had an episode of generalised convulsion. Post-ictally, the patient was drowsy, irritable, apahasic and developed right-sided hemiparesis. Computed tomography of the brain revealed a left parietal venous infarct. Magnetic resonance venography confirmed thrombosis of the straight sinus, left transverse sinus, left sigmoid sinus, left internal jugular vein and cortical veins in the left high parietal region. The patient's thrombophilia profile was positive only for heterozygous Factor V Leiden mutation. The patient was treated conservatively with anticonvulsants and low-molecular-weight heparin. The patient recovered completely within a week and was discharged. Cerebral venous sinus thrombosis (CVST) has been rarely reported in the post-operative period following trans-sphenoidal surgery for pituitary adenoma. Early diagnosis and treatment of CVST is necessary for a favourable outcome.

Antiphospholipid syndrome and antiphospholipid antibody profile in patients with retinal vein occlusion

IntroductionData on prevalence, association with vascular risk factors, clinical management and outcome of antiphospholipid syndrome (APS) in retinal vein occlusion (RVO) are scarce. MethodsPatients diagnosed with RVO at a tertiary-care hospital, and two additional groups; population-based controls and patients with APS (RVO-APS) were studied. Prevalence, association with vascular risk factors, antiphospholipid antibody profile, clinical management, genetic thrombophilia profile, carotid ultrasound and outcome of RVO-APS patients were assessed and compared with controls. ResultsSome 331 consecutive patients with RVO and 281 controls were included. Overall, aPLs were more prevalent in RVO-patients than in controls (33, 10% vs. 12, 4.3%; adjusted OR 2.47; 95% CI 1.25–4.88; p = 0.009). Patients with RVO-APS showed a high-risk “aPL profile” (lupus anticoagulant or triple-positive). We did not find any difference regarding classic vascular risk factors, hyperhomocysteinemia, prior vascular events, and carotid plaque, in RVO-patients with or without APS. The phenotype of RVO-APS also differed from APS. Seven patients received anticoagulation and 24 were on low-dose aspirin. After a median follow-up of 62 months, 7 patients suffered a RVO relapse (4 of them had APLs) and no RVO-APS patient had a new thrombotic or vascular event outside the retina. ConclusionsaPLs were more prevalent in RVO-patients than in controls, and in all patients, APS was not associated with any connective-tissue disease. RVO in the setting of APS seems not only related to atherosclerosis, but also to the “aPL profile”. In most of our RVO-patients with APS, low-dose aspirin was effective to prevent new or recurrent thrombotic events outside the retinal vessels. In these patients, we suggest that RVO could behave as an organ-specific manifestation of APS.

Hereditary thrombophilia in the puerperiu a retrospective review of 11 cases complicated by cerebral venous thrombosis

Purpose of Investigation: The purpose of this study was to conduct a multidisciplinary analysis of a 11 cases of cerebral venous thrombosis in the puerperium associated with hereditary thrombophilia. Materials and Methods: The medical records of patients with ereditary thrombophilia and cerebral venous thrombosis in the puerperium were reviewed retrospectively. Clinical suspicion of cerebral venous thrombosis had been confirmed by CT or MRI. Results: Only in 11 cases the authors found the association between hereditary thrombophilia and cerebral thrombosis. The evaluation of the thrombophilic profile revealed that MTHFR C677T in combination with Factor V Leiden G1691A and Prothrombin G20210A were the commonest gene defects among cases studied. Conclusion: Hereditary thrombophilia may increase the risk of cerebral venous thrombosis in the puerperium.

A study of clinical,radiological and thrombophilia profile in cerebral venous sinus thrombosis

A study of clinical,radiological and thrombophilia profile in cerebral venous sinus thrombosis

Role of inherited thrombophilic profile on survival of patients with sepsis

The existence of various coagulation and/or fibrinolytic system disorders (such as inherited thrombophilia) in patients with sepsis could possibly modify host response to infection as well as patient outcome. The...

An uncommon presentation of hyperhomocysteinemia and vitamin B12 deficiency: a case report

IntroductionCerebral venous thrombosis is relatively rare and characterized by a wide spectrum of clinical features. It is more common in young adults with women affected more than men. The diagnosis of cerebral venous thrombosis is easier nowadays due to easy access to advanced neuroimaging techniques. Abnormalities in thrombophilic profile are associated with enhanced risk of cerebral venous thrombosis. It has varied etiologies such as hypercoagulable states, infection, dehydration, pregnancy, and substance abuse. Hyperhomocysteinemia is found to be closely associated with an enhanced risk of cerebral venous thrombosis.Case presentationHere we report a case of cerebral venous thrombosis secondary to hyperhomocysteinemia caused by vitamin B12 deficiency in a 32-year-old Indo-Aryan man. A detailed coagulation workup led us to find the etiology of cerebral venous thrombosis in this patient who followed a strict vegetarian diet and had vitamin B12 deficiency leading to hyperhomocysteinemia.ConclusionThere are conflicting reports in the literature about the association of hyperhomocysteinemia, B12 deficiency, and cerebral venous thrombosis but some reports point to a significant association. We conclude that further studies with a large sample size are required to analyze the effect of hyperhomocysteinemia and low vitamin B12 on the risk of cerebral venous thrombosis.

A new complement evasion strategy: How S. pyogenes exploits IgGs to recruit more C4BP

Neurological symptoms of patients with p.Cys89Tyr mutation in the CD59 gene include recurrent peripheral neuropathy resembling Guillain-Barré syndrome, characterized by sensory-motor demyelinating neuropathy with secondary axonal damage and moderate enhancement of the nerve roots on spine MRI, together with recurrent strokes and retinal involvement. Three additional mutations in CD59, leading to loss of function, have been described, and overall, 12/12 (100%) of patients with any mutation presented with neurological symptoms; 11/12 (92%) patients presented with recurrent peripheral neuropathy, 6/12 (50%) with recurrent strokes, and 1/12 (8%) with retinal involvement. We review the possible thrombophilic profile associated with the mutations. In these patients, excessive intravascular hemolysis saturates scavenger mechanisms resulting in free hemoglobin in plasma that irreversibly reacts with nitric oxide to form nitrate and methemoglobin, leading to arterial thrombosis. CD59 loss of function is also one of the major thrombophilic mechanisms in patients with paroxysmal nocturnal hemoglobinuria. We then describe the relationship with demyelination. The lack of CD59 allows uncontrolled complement amplification following low-level spontaneous-, viral-, or post viral-induced complement activation, resulting in severe demyelination in the peripheral nervous system. It is interesting, and certainly encouraging, that after 3 years, following 4 patients with Cys89Tyr mutations who are treated with eculizumab, no strokes occurred and non-permanent neurological insults underwent resolution without any new neurological exacerbations.

Budd-Chiari syndrome secondary to polycythemia vera with inferior vena cava thrombosis

A middle aged male presented with abdominal distension since one month. Further workup showed plasma hemoglobin of 18.1 g/dL with a high pack cell volume (PCV), raised urea, creatinine and disturbed liver function tests. Abdominal ultrasonography showed an enlarged caudate lobe with thrombi in the inferior vena cava while CT scan of abdomen confirmed the same findings and was suggestive of Budd-Chiari syndrome. Further workup was conducted to rule out other causes and to find out the possible cause of Budd-Chiari syndrome. A peripheral film was requested, which showed hyper-segmented neutrophils. Later on JAK2 mutation and thrombophilia profile was ordered, which was positive for JAK2 mutation. Even though the patient was started on low molecular weight heparin but he eventually passed away. Key point Budd-Chiari syndrome is due to the obstruction of the hepatic efferent outflow tract from either the hepatic veins to where the inferior vena cava meets the right atrium. Its pathogenesis is due to the decreased outflow of the liver, leading to increase in pressure, stasis and later on damage induced by hypoxia and thrombus in the portal veins. Citation: Majid Z, Tasneem AA, Luck NH, Ul Haque MM, Mandhwani RK, Laeeq SM, et al. Budd-Chiari syndrome secondary to polycythemia vera with inferior vena cava thrombosis Immunopathol Persa. 2018;4(1):e04. DOI: 10.15171/ipp.2018.04.

Inherited and Acquired Thrombophilia As a Modifier of Clinical Course of Chronic Idiopathic Thrombocytopenia - a Prospective Study

Background: Patients with idiopathic thrombocytopenia exhibit striking heterogeneity in bleeding manifestations even at similar platelet counts. Proposed mechanisms are generation of platelet microparticles, complement activation, NO depletion, and impact of various treatment modalities. In the present study, we studied the prevalence of thrombophilic markers in persistent and chronic ITP patients and that whether the presence of such markers modifies the clinical course of these patients.Methods: Patients diagnosed as persistent or chronic ITP (of any age group) were eligible. All patients were evaluated at baseline and at regular follow-up visits using newly available Bleeding Assessment Tool (ITP-BAT, version 1.0) proposed by International Working Group on ITP. For analyses, severity of bleeding was defined as no bleeding (bleeding score zero at all domains I.e. skin, mucosa and organ), mild bleeding (skin and mucosal bleeding score 0-2, organ bleeding score 0-1) and severe bleeding (skin and mucosa bleeding score >2, and organ bleeding score >1). Baseline thrombophilia profile was obtained for all patients, that included clot-based assays for protein C (PC), protein S (PS), ProCGlobal, FVIII levels (F8), and lupus anticoagulant assay (LA). We then compared the patients expressing atleast one thrombophilia marker (TM+) and those without (TM-), for the number of times patients in each group presented with a bleeding episode. We derived the parameter bleeding episodes per visit to estimate severity of bleeding in each group [mild bleeding episode/visit (MBE/visit) and severe bleeding/visit (SBE/visit)].Statistical analysis was done using odds ratio calculation and correlation regression analysis.Results: Of the total 88 patients enrolled, 21 were males (23.4%), and remaining 67 (76.5%) were females. Out the total, 57 patients (64.7%) tested positive for at least one thrombophilic marker, and remaining 31 patients (35.2%) were negative for all markers. Raised factor VIII was found in 36 patients (40.9%), low protein S in 29 patients (32.9%), low protein C in 14 patients (15.9%), abnormal Pro® C global in 22 patients (25%), and lupus anticoagulant positive in 9 patients (10.2%). Thirty three (37.5%) patients expressed thrombophilic markers in various combinations. Evaluation for impact of thrombophilia marker on bleeding is as shown in Table 1.Summary: Sixty-five percent of patients had thrombophilia marker positive in various combinations. Those with thrombophilia had lower bleeding tendency compared to those with none. Patients with low protein C and S, abnormal ProcGlobal and lupus positivity had significantly lower bleeding tendencies, while FVIII abundance did not impact the bleeding scores.Conclusion: We conclude that a part of the heterogeneity in the clinical presentation of persistent and chronic ITP can be explained by the presence or absence of thrombophilia, and that work-up of patients with ITP should include thrombophilia evaluation, the results of which may have a role in therapeutic decision making. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical features, risk factors, and outcome of cerebral venous thrombosis in Tehran, Iran.

Introduction:Despite increasing the use of magnetic resonance imaging (MRI), cerebral venous sinus thrombosis (CVST) has remained an under-diagnosed condition. In this study, characteristics and frequency of various risk factors of CVST patients in a tertiary referral hospital were closely assessed.Methods:Patients with an unequivocal diagnosis of CVST confirmed by MRI and magnetic resonance venography during 6 years of the study were included. All data from the onset of symptoms regarding clinical signs and symptoms, hospital admission, seasonal distribution, medical and drug history, thrombophilic profile, D-dimer, neuroimaging, cerebrospinal fluid findings, mortality, and outcome were collected and closely analyzed.Result:A total of 53 patients with female to male ratio of 3.07 and mean age of 33.7 years were included in the study. Headache and papilledema were the most frequent clinical features (44 and 36 patients, respectively). An underlying disease (diagnosed previously or after admission) was the most common identified risk factor for CVST in both females and males (21 patients). A total of 15 women used the oral contraceptive pill (OCP) where 12 of them had simultaneously other predisposing factors. Overall, 19 patients (36%) had more than one contributing factor. D-dimer had a sensitivity of 71.4% in CVST patients. The mortality of patients in this study was 3.7% (n = 2). Focal neurologic deficit and multicranial nerve palsy were associated with poor outcome which defined as death, recurrence, and massive intracranial hemorrhage due to anticoagulation (P = 0.050 and 0.004, respectively).Conclusion:Unlike most of the CVST studies in which OCP was the main factor; in this study, an underlying disease was the most identified cause. Considering the high probability of multiple risk factors in CVST that was shown by this study, appropriate work up should be noted to uncover them.

Molecular thrombophilic profile in Mexican patients with idiopathic recurrent pregnancy loss.

Idiopathic recurrent pregnancy loss (IRPL) is defined by three or more consecutive miscarriages occurring before the twentieth week of gestation as a result of unidentified etiological factors. The results of previous studies have indicated that prothrombotic factors play a pathogenic role in early and late pregnancy. This study aimed to identify inherited prothrombotic and hypofibrinolytic risk factors in Mexican-Mestizo patients with IRPL. Fifty-six women with IRPL and 50 control women with at least two full-term pregnancies and no history of RPL were included in this case-control study. Four prothrombotic (F5 G1691A, F2 G20210A, MTHFR C677T-A1298C) and one hypofibrinolytic (PAI1 4G/5G) restricted fragment length polymorphisms were subjected to molecular analysis. In the case of hypofibrinolytic ACE Ins/Del (I/D), identification was performed by direct PCR. The independent risk correlated with the presence of polymorphisms in IRPL patients was estimated using odds ratio (OR) with a 95% confidence interval (CI). MTHFR 677TT was the most frequent prothrombotic factor in the IRPL group (23%), followed by the compound-heterozygous C677T-A1298C (16%) and heterozygous F2 20210GA (3.6%). The heterozygous ACE I/D (62%) was the main hypofibrinolytic risk factor of IRPL, followed by the homozygote PAI1 4G/4G (18%). The ACE I/D polymorphism was the only significantly different factor among the cases and controls. The dominant genetic model D/D+I/D vs I/I showed an OR (95%CI) of 2.89 (1.22-6.89) and P = 0.019 in Mexican-Mestizo women. The results of this study support an association between the ACE I/D polymorphism and IRPL risk in a Mexican population.

Clinical presentation of extrahepatic portal vein obstruction: 10-year experience at a tertiary care hospital in Pakistan.

ObjectiveTo evaluate the clinical presentation, possible etiological factors, management and outcome of patients in our hospital with extrahepatic portal vein obstruction (EHPVO).Materials and MethodsThis study included patients with EHPVO followed up in our department during last 10 years. Patients of cirrhosis with EHPVO were excluded. Patients’ clinical presentation, etiology of EHPVO, management and outcome results were analyzed.ResultsOf 30 patients, 19 (67.9%) were males. Median age was 12 years. Of 14 patients who underwent liver biopsy 9 had histological activity index stage of 1/6. History of omphalitis and pulmonary tuberculosis was present in one case each. Of 22 patients with the available thrombophilia profile, nine patients had a deficiency of protein C, five patients had a deficiency of protein S, one each had reduced level S of anti-thrombin III and factor V mutation. The predominant presenting symptom was hematemesis (15 patients, 53.6%). Seven patients (25%) had splenomegaly. Three patients (10.7%) had no esophageal varices on endoscopy. Three patients underwent splenectomy due to severe pancytopenia. Endoscopic retrograde cholangipancreatography was performed in four patients (14.3%) due to portal biliopathy. Common bile duct stenting was performed in all four patients. Of them, one patient underwent splenorenal shunt operation for indication of hemobilia. One patient died at the age of 40 years, due to cholangitis and sepsis.ConclusionsResults from this study show that the anticoagulant deficiency is a common cause of EHPVO in our setup. Hematemesis is a common presenting symptom. Some of these patients have symptomatic portal biliopathy.