RESUMO
Patients with paroxysmal nocturnal hemoglobinuria (PNH) may present with thrombosis at unusual sites, of which cerebral sinovenous thrombosis (CSVT) is one and screening for PNH is recommended in this condition. Though many patients diagnosed with PNH develop CSVT, it is unclear how many patients with PNH would present for the first time with thrombosis. We analysed the results of screening for PNH by flowcytometry in our patients with CSVT. The laboratory data of patients referred for thrombophilia and PNH testing in CSVT was examined to assess the frequency of PNH at presentation in these patients. FLAER and CD24 on granulocytes and FLAER and CD14 on monocytes respectively were used to screen the leucocytes for PNH by flowcytometry. The data for Protein C, S and Antithrombin deficiency, antiphospholipid antibodies and the Factor V Leiden mutation was examined and circumstantial risk factors were also assessed. Of the 180 cases of CSVT screened by flowcytometry for PNH, not a single case tested positive. Positivity for anti-phospholipid antibodies was the most common thrombophilic risk factor (5%). Pregnancy was the most common circumstantial risk factor. Our data on FLAER based flowcytometry in the North Indian population with CSVT suggests that PNH is not a common risk factor in our patients with thrombosis at this unusual site.
Assuntos
Hemoglobinúria Paroxística/diagnóstico , Trombose Intracraniana/etiologia , Adolescente , Adulto , Feminino , Citometria de Fluxo/métodos , Hemoglobinúria Paroxística/sangue , Hemoglobinúria Paroxística/complicações , Humanos , Trombose Intracraniana/sangue , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações Cardiovasculares na Gravidez/sangue , Complicações Cardiovasculares na Gravidez/etiologia , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/diagnóstico , Estudos Retrospectivos , Adulto JovemAssuntos
Comportamento Aditivo , Mídias Sociais , Criança , Humanos , Flebotomia , Gravação em VídeoRESUMO
A single guanosine deletion/insertion (4G/5G) polymorphism in the promoter region of plasminogen activator inhibitor-1 (PAI-1) gene encoding PAI-1 protein has been investigated in deep vein thrombosis (DVT) patients. The association between PAI-1 4G/5G polymorphism and increased risk of DVT has been reported in some studies, while others have reported a lack of association. The present study aimed to investigate if the PAI-1 4G/5G polymorphism is associated with an increased risk of DVT in the Indian population and to assess its association with thrombophilic risk factors. Fifty-two adult patients with a history of chronic or recurrent DVT and 52 healthy adult controls were genotyped for PAI-1 4G/5G polymorphism. Plasma levels of PAI-1 and other thrombophilic risk factors were also measured. PAI-1 4G/5G polymorphism was not significantly associated with an increased risk of DVT. Protein C deficiency was significantly associated with the 4G/4G genotype. Patients with the 4G/4G genotype had significantly reduced PAI-1 levels as compared to the controls. PAI-1 4G/5G polymorphism did not significantly contribute to an increased risk of DVT in the Indian population. However, in the presence of thrombophilic risk factor abnormalities, the risk of DVT is increased in individuals with the 4G/4G genotype in the Indian cohort. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01660-3.
RESUMO
The association of the fibrinolytic markers with deep vein thrombosis (DVT) is still a matter of debate. The present study aimed to investigate the association between fibrinolytic markers and DVT. This observational study recruited 52 adult cases with lower limb DVT and 52 healthy adult volunteers as controls. The quantitative determination of plasminogen activator inhibitor-1 (PAI-1), plasminogen, thrombin activable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA) and α2-antiplasmin (α2-AP) was performed by ELISA. TAFI, plasminogen and t-PA were significantly higher in cases than controls and PAI-1 was significantly lower in cases than controls. In addition, TAFI, plasminogen and t-PA levels were significantly increased in unprovoked and idiopathic DVT cases than controls. The present study suggests that the fibrinolytic markers tested in patients with a remote history of DVT are different than in individuals with no history of DVT and, with further study, may prove useful as screening assays for DVT risk.
Assuntos
Ativador de Plasminogênio Tecidual , Trombose Venosa , Adulto , Fibrinólise , Humanos , Plasminogênio , Inibidor 1 de Ativador de Plasminogênio , Trombose Venosa/diagnóstico , alfa 2-AntiplasminaRESUMO
BACKGROUND: Platelet aggregation studies using conventional light transmission aggregometry (LTA) have several disadvantages and require strict pre-analytical measures for reliable results. We aimed to examine the utility of flow cytometric platelet aggregation (FCA) assay in detecting platelet function defects (PFDs) in patients with a history of bleeding symptoms. METHODS: Sixty-four participants (24 patients and 40 healthy controls) were included in this study. LTA and FCA assay were performed simultaneously in patients and healthy controls. In the FCA assay, two portions of platelets from the same individual were labeled separately with CD31-FITC and CD31-PE. After mixing and stimulation with agonists, the double- colored platelet aggregates were visualized using a flow cytometer. The results generated using the two techniques were compared and correlated. RESULTS: The patients' median age was 17 years (range, 3â72 yr) with a male-to-female ratio of 1:1.7. There was substantial agreement between LTA and FCA assay in detecting a PFD (ï«=0.792). Four patients showing a Glanzmann thrombasthenia-like pattern on LTA exhibited an abnormal FCA. A functional defect in collagen binding was detected on the FCA assay conducted in two immune thrombocytopenic patients with severe bleeding. CONCLUSION: FCA assay can be used to identify functional defects in platelets, with potential applications in thrombocytopenic individuals. It also facilitates the diagnosis of inherited bleeding disorders with platelet defects.
RESUMO
Splanchnic vein thrombosis (SVT) is a rare and lethal form of venous thrombosis. The role of platelet indices (PI's) is not well studied in SVT. The present study was aimed to assess if the PI's have a significant association with SVT. This was a prospective case control study from coagulation laboratory of Hematology department. A total 100 cases of SVT and 80 controls were screened for PI's (MPV, PCT & PDW) and platelet count (PC) along with routine thrombophilic risk factors. The SVT cases were divided into 3 subgroups, that comprised of EHPVO/ PVT (n = 69), BCS (n = 27), and MVT (n = 4). The mean PC and PCT were significantly lower in patients than the controls. The PDW was significantly higher in cases than in the controls and MPV was relatively higher in cases however did not show statistical significance. In addition, 16 patients were found to have deranged thrombophilic risk factors. Among these, 8 cases had inherited risk factors (2: FVL; 5: PC; 1: PS) and 8 cases had acquired risk factors (2: APL; and 5: multiple factors and one case had both FVL mutation and APL positivity). The PDW and PCT together with PC were found to significantly differ in SVT cases than in controls, particularly in idiopathic cases. It may be worthwhile to explore the utility of PI's as a potential risk factor in SVT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1007/s12288-021-01400-5).
RESUMO
Glanzmann thrombasthenia (GT) is an autosomal recessive platelet function disorder characterized by mucocutaneous bleeding as the most common clinical phenotype. Patients with GT have normal platelet counts, platelet morphology but reduced platelet aggregation in response to various agonists. Homozygosity or compound heterozygosity for variants in the ITGA2B/ITGB3 genes is the genetic basis for GT. Establishing a molecular diagnosis is definitive and is important for predictive testing. Using multi-gene panels is an accurate, faster, and cost-effective mode as compared to Sanger sequencing in large genes. We used a targeted resequencing based approach to identify pathogenic variants in eight cases in seven families. These variants were validated using Sanger sequencing in patients as well as family members and were predicted probably pathogenic using in-silico prediction tools. The variants include three missense (3/7 = 43%) (ITGA2B:c.1028 T > C, ITGA2B:c.1186G > A, ITGB3:c.1388G > C), two deletions (ITGA2B:c.559delG, ITGA2B:c.3092delT), one duplication (ITGA2B:c.1424_1427dupAGGT) and nonsense variant (ITGA2B:c.2578C > T, p.Gln860Ter). Except for one case which was compound heterozygous, the rest of the cases were homozygous. We found two novel variants that are reported for the first time in GT. The targeted resequencing based approach revealed varied genetic variants in North Indian patients, including two novels ones. The high yield of our panel indicates its suitability for usage in larger cohorts for the genetic diagnosis of GT patients. This approach is cost-effective and less cumbersome as compared to Sanger sequencing for these large size genes with multiple exons. The information so obtained is helpful in prenatal testing, carrier analysis, and genetic counseling.
RESUMO
Splanchnic vein thrombosis is an uncommon life-threatening form of venous thrombosis. It is one the common complication among MPN's. In the western studies the prevalence of JAK2V617F mutation among SVT patient is high and ranges from 7 to 59%. The frequency of this mutation among Indian SVT patients is heterogenous. This was a prospective case control study. A total 52 cases of SVT and 40 controls were screened for JAK2V617F mutation along with other routine thrombophilic risk factors. Out of total 52 cases, 10 had BCS, 2 had MVT and rest 40 were of PVT/EHPVO. The JAK2V617F mutation was seen in two cases and not in controls. Among the thrombophilic markers, heterozygous FVL mutation, PC, PS and presence of APA were seen in 2, 3, 1 and 3 cases respectively. In addition, eight cases also showed deranged risk factors (5 inherited and 3 acquired), however the repeat testing was not performed due to loss of follow up. Among controls, one person showed presence of APA and one person showed multiple thrombophilic risk factor deficiency. JAK2V617F mutation was observed in 3.8% among north Indian SVT patients. The frequency of mutation is on the lower side as compared to the available Indian data. The other thrombophilia markers (both inherited and acquired) are more frequent (18%) and patients should be routinely screened for these thrombophilia markers.
RESUMO
Elevated levels of coagulation factor VIII have been associated with increased risk for venous thromboembolism (VTE). The role of Von Willebrand factor (VWF) in VTE is unclear. In this study, we investigated the association of raised levels of VWF and factor VIII in patients with VTE. 100 patients of VTE and 100 age and gender matched controls were tested for levels of VWF antigen, coagulation factor VIII:C, Protein C, Protein S, antithrombin, antiphospholipid antibodies and for the presence of Factor V Leiden mutation. The mean level of VWF was significantly higher amongst patients of VTE (177.3 IU/dl) when compared to controls (129.7 IU/dl) (P < 0.001). Similarly, the mean level of FVIII:C was significantly higher amongst patients of VTE (199.1 IU/dl) when compared to controls (145.2 IU/dl) (P < 0.001). On logistic regression analysis, after adjusting for FVIII:C, Protein S, factor V Leiden and trauma, the association of raised VWF with VTE remained significant (P = 0.001). Similarly higher levels of FVIII:C persisted to have an independent association with VTE (P = 0.004). Both, higher levels of VWF and FVIII:C levels, are independently associated with VTE.
RESUMO
Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction caused by heparin. HIT occurs due to IgG antibodies directed against heparin-bound platelet factor 4 (PF4). The aim of this study was to evaluate the STic® Expert HIT for detection of anti-PF4/heparin antibodies in comparison with ID-PaGIA™ kit. The results were further confirmed by Heparin-induced platelet aggregation test (HIPA). A total of 17 patients with a suspected diagnosis of HIT were enrolled. The 4 T scoring of each case was performed. Testing for HIT was carried out by ID-PaGIA™, STic® Expert HIT, and HIPA. Testing by STic® Expert HIT test demonstrated positivity in three cases while testing by ID-PaGIA™ test kit revealed four positive cases. Two of these cases were confirmed as HIT by HIPA. The study suggests that STic® Expert HIT an equally effective test, in combination with the 4T scoring system for detecting/excluding the diagnosis of HIT. A large number of cases are needed for validation.
RESUMO
Acquired hemophilia A (AHA) is an uncommon bleeding disorder infrequently reported among Indians. The present retrospective data comprises eight cases of AHA over a period of 15 years. The mean age of patients was 59.7 years. The activated partial thromboplastin time was prolonged in all cases and the inhibitor screen showed the presence of inhibitors. Factor VIII: C assay was performed in 7 cases and all cases demonstrated low levels. Lupus anticoagulant was negative. Six patients were managed with steroids and symptomatic supportive care. These patients were followed up for a mean period of 3.5 years (range 1-5 years). Of these, there was one fatality prior to initiation of therapy and one patient continues to have inhibitors.