High Factor Levels Research Articles

Alternative complement pathway deregulation is correlated with dengue severity.

BackgroundThe complement system, a key component that links the innate and adaptive immune responses, has three pathways: the classical, lectin, and alternative pathways. In the present study, we have analyzed the levels of various complement components in blood samples from dengue fever (DF) and dengue hemorrhagic fever (DHF) patients and found that the level of complement activation is associated with disease severity.Methods and ResultsPatients with DHF had lower levels of complement factor 3 (C3; p = 0.002) and increased levels of C3a, C4a and C5a (p<0.0001) when compared to those with the less severe form, DF. There were no significant differences between DF and DHF patients in the levels of C1q, immunocomplexes (CIC-CIq) and CRP. However, small but statistically significant differences were detected in the levels of MBL. In contrast, the levels of two regulatory proteins of the alternative pathway varied widely between DF and DHF patients: DHF patients had higher levels of factor D (p = 0.01), which cleaves factor B to yield the active (C3bBb) C3 convertase, and lower levels of factor H (p = 0.03), which inactivates the (C3bBb) C3 convertase, than did DF patients. When we considered the levels of factors D and H together as an indicator of (C3bBb) C3 convertase regulation, we found that the plasma levels of these regulatory proteins in DHF patients favored the formation of the (C3bBb) C3 convertase, whereas its formation was inhibited in DF patients (p<0.0001).ConclusionThe data suggest that an imbalance in the levels of regulatory factors D and H is associated with an abnormal regulation of complement activity in DHF patients.

Sclerotherapy of varicose veins in patients with documented thrombophilia: a prospective controlled randomized study of 105 cases

The aim of this study was to assess thrombotic complications following sclerotherapy in thrombophilic patients in combination with thromboprophylaxis, in two randomized arms using low molecular weight heparin (LMWH) or warfarin. Patients and methods This study received approval from the Ethics Committee. A total of 105 patients (81 females, 24 males) ranging in age from 20 to 82 years (mean 50) were selected: 75 with Factor V Leiden mutation, 18 with prothrombin 20210A mutation, 7 with high level of Factor VIII, 5 combinations of these. After randomization, 51 and 54 patients received warfarin and LMWH, respectively. A total of 199 sclerotherapy sessions were performed. Foam was used in 160 treatments. No episodes of symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) occurred; no instances of DVT were revealed by ultrasound-monitoring. This study suggests that in the three most common forms of thrombophilia, sclerotherapy, in combination with thromboprophylaxis, can be performed safely. Prophylaxis with LMWH is easier to use than warfarin.

Hypercoagulable State in Cushing’s Syndrome: A Systematic Review

It has been debated whether an increased risk of venous thromboembolism (VTE) exists in patients with Cushing's syndrome. We aimed to summarize published literature on the effects of endogenous hypercortisolism on coagulation and fibrinolysis, as well as on the clinical outcome of VTE. We searched the MEDLINE and EMBASE databases up to July 2008. Review of reference lists further identified candidate studies. Two investigators independently performed study selection and data extraction. Eligible studies had to include Cushing's syndrome patients and either evaluate hemostatic parameters in comparison with control persons or posttreatment levels or describe the occurrence of VTE. The Newcastle-Ottawa Scale was used to assess study quality. A scoring system divided studies into categories of low, medium and high quality. Of 441 identified publications, 15 reports were included. They contained information on eight cross-sectionals, two intervention, and eight cohort studies. No high-quality studies were identified. Hypercoagulability was suggested by high levels of factor VIII, factor IX, and von Willebrand factor and by evidence of enhanced thrombin generation. A risk of 1.9 and 2.5% was reported for VTE not provoked by surgery, whereas risk of postoperative VTE varied between 0 and 5.6%, with one outlier of 20%. VTE was reported as the cause of death in 0-1.9% of Cushing's syndrome patients. Available studies suggest a high risk of venous thrombosis in patients with Cushing's syndrome. Glucocorticoid-induced hypercoagulability as well as surgery and obesity almost certainly contribute to this thrombotic tendency.

Assessing the Coagulation Factor Levels, Inherited Thrombophilia, and ABO Blood Group on the Risk for Venous Thrombosis Among Brazilians

Increased coagulation factor levels have been demonstrated to be a risk factor for venous thromboembolism in patients of Caucasian origin. Coagulation factors, hereditary thrombophilia, and ABO blood group were evaluated for venous thrombosis risk in a heterogeneous Brazilian population consisting of 122 women and 53 men, with a median age of 36 years (range 13-63), matched to a control group by age, sex, and ethnicity. Increased levels of factor VIII (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.6-6.0), von Willebrand factor (OR, 2.8; 95% CI, 1.4-5.4), non-O blood group (OR, 2.1; 95% CI, 1.3-3.4), and thrombophilia (OR, 3.4; 95% CI, 1.6-7.1) emerged as independent risk factors for venous thromboembolism. The interaction of high levels of factor IX and factor XI with other independent variables increased the potential for thrombosis synergistically. Therefore, the ability of identifying underlying thrombophilia risk factors in our population was enhanced by the inclusion of these factors in the prothrombotic laboratory workup.

High levels of factor VIII and risk of extra-hepatic portal vein obstruction

High levels of coagulation factor VIII are a risk factor for lower-limb deep vein thrombosis (DVT). Their role in extra-hepatic portal vein obstruction (EHPVO) is not established. Factor VIII was measured in 85 patients with EHPVO (primary in 58 and complicating liver cirrhosis in 27), in 200 with lower-limb DVT, in 108 with liver cirrhosis without thrombosis and in 200 healthy controls. Factor VIII levels were significantly higher in patients with primary EHPVO (138 IU/dL, range 86-366), EHPVO and cirrhosis (147 IU/dL, 95-242), lower-limb DVT (140 IU/dL, 64-400) and cirrhosis alone (160 IU/dL, 43-446) than in controls (112 IU/dL, 62-250, p<0.001). When factor VIII exceeded 129 IU/dL (66th percentile), the odds ratios were 10.5 (95%CI 3.3-33.4) for primary EHPVO, 6.0 (1.2-30.7) for EHPVO and cirrhosis, 5.0 (2.6-9.4) for lower-limb DVT. After exclusion of the effect of the acute phase reaction, the odds ratio for primary EHPVO was 4.2 (0.8-22.7), and was 8.7 (0.9-80.5) after exclusion also of patients with chronic myeloproliferative disorders. High factor VIII levels are independently associated with an increased risk for EHPVO. The risk of EHPVO increased with increasing factor VIII levels and was only partially dependent on the acute phase reaction.

High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin

Hereditary deficiencies of protein S, protein C and antithrombin are known risk factors for first venous thromboembolism. We assessed the absolute risk of recurrence, and the contribution of concomitant thrombophilic defects in a large cohort of families with these deficiencies. Annual incidence of recurrence was estimated in 130 deficient patients, with separate estimates for those with each of protein S, protein C, and antithrombin deficiency, and in eight non-deficient patients with prior venous thromboembolism. All patients were also tested for factor V Leiden, prothrombin G20210A, high levels of factors VIII, IX and XI, and hyperhomocysteinemia. There were 81 recurrent events among 130 deficient patients. Median follow-up was 4.6 years. Annual incidences (95% confidence interval) of recurrent venous thromboembolism were 8.4% (5.8-11.7) for protein S deficiency, 6.0% (3.9-8.7) for protein C deficiency, 10.0% (6.1-15.4) for antithrombin deficiency, and overall 7.7% (6.1-9.5). Relative risk of recurrence in patients with a spontaneous versus provoked first event was 1.5 (0.95-2.3). Cumulative recurrence rates at 1, 5 and 10 years were 15%, 38% and 53%. Relative risk of recurrence with concomitant defects was 1.4 (0.7-2.6) (1 defect) and 1.4 (0.8-2.7) (> or =2 defects). Annual incidence was 1.0% (0.03-5.5) in eight non-deficient patients. Annual incidence of major bleeding in deficient patients on oral anticoagulant treatment was 0.5% (0.2-1.0). We conclude that patients with a hereditary protein S, protein C or antithrombin deficiency appear to have a high absolute risk of recurrence. This risk is increased after a first spontaneous event, and by concomitance of other thrombophilic defects.

Thrombophile Gerinnungsstörungen bei unter 60-jährigen Patienten mit nichtarteriitischer anteriorer ischämischer Optikusneuropathie

The potential impact of coagulation abnormalities on non-arteritic ischaemic optic neuropathy (NAION), individually and in combination with cardiovascular risk factors, remains unclear. In a prospective case-control study a cohort of 26 NAION patients < 60 years at the time of the NAION or a previous thromboembolic event and 50 subjects matched for age and sex were prospectively screened for thrombophilic risk factors. Overall, thrombophilic defects were found to be present in 12 of 26 patients (46.2 %) and in 9 of 50 (18 %) controls (p = 0.01). The most frequent coagulation disorders were high levels of factor VIII (p = 0.04) and lipoprotein (a) (p = 0.03). Moreover, we identified two patients with homozygous resistance to activated protein C, which is the first description of this coagulation disorder associated with NAION. Patients without cardiovascular risk factors had a statistically significant higher frequency of coagulation disorders than patients with these risk factors (p = 0.038). Our results indicate that thrombophilic disorders are associated with the development of non-arteriitic ischaemic optic neuropathy in patients < 60 years of age at the time of a first thromboembolic event. Selective screening of young patients and patients without cardiovascular risk factors may be helpful in identifying NAION patients with thrombophilic defects.

Thrombophilia, Hypofibrinolysis, the eNOS T-786C Polymorphism, and Multifocal Osteonecrosis

We examined the hypothesis that thrombophilia, hypofibrinolysis, and the endothelial nitric oxide synthase (eNOS) T-786C polymorphism are common, potentially treatable, and similar pathophysiologic causes of multifocal (three sites or more) and unifocal (single-site) osteonecrosis. We prospectively evaluated twenty-six consecutively referred adults with multifocal osteonecrosis, who included thirteen with idiopathic multifocal osteonecrosis and thirteen with secondary multifocal osteonecrosis (resulting from steroid therapy in ten and alcoholism in three). We compared these patients with race, sex, and age-matched normal control subjects and with patients with idiopathic unifocal and secondary unifocal osteonecrosis, respectively. Using polymerase chain reaction and serologic measures, we studied thrombophilic and hypofibrinolytic mutations and the eNOS T-786C polymorphism. The total number of polymerase chain reaction and serologic thrombophilic-hypofibrinolytic abnormalities and the eNOS T-786C polymorphism did not differ between patients with idiopathic (p > 0.5) or secondary (p > 0.5) multifocal and unifocal osteonecrosis. The frequency of low free protein-S levels (<66%) in patients with secondary multifocal osteonecrosis (four of eleven patients) was higher than that in the control subjects (one of fifty-nine) (risk ratio = 21.5; 95% confidence interval, 2.6 to 174; p = 0.0016, Benjamini-Hochberg adjusted p [Bp] = 0.004). Factor-V Leiden heterozygosity was present in two of thirteen patients with secondary multifocal osteonecrosis compared with none of sixty-four control subjects (p = 0.027, Bp = 0.008). For eleven patients with secondary multifocal osteonecrosis, the eNOS T-786C polymorphism was present in nine of twenty-two alleles compared with eight of forty-four alleles in twenty-two normal control subjects (risk ratio = 2.3; 95% confidence interval, 1.0 to 5.0; p = 0.047, Bp = 0.016). The frequency of homocystinemia (>13.5 mumol/L) was higher in patients with idiopathic multifocal osteonecrosis (two of thirteen patients) than in normal controls (none of fifty-one) (p = 0.039, Bp = 0.004). A high level of factor VIII (>150%) was seen in four of eight patients with idiopathic multifocal osteonecrosis and in seven of forty-eight normal controls (risk ratio = 3.4; 95% confidence interval, 1.3 to 9.1; p = 0.04, Bp = 0.008). The eNOS T-786C mutant allele was present in seven of twelve alleles in the six patients with idiopathic multifocal osteonecrosis who were tested, compared with twenty-five of 108 alleles in fifty-four control subjects (risk ratio = 2.5; 95% confidence interval, 1.4 to 4.5; p = 0.015, Bp = 0.008). Limited by the small numbers of patients with multifocal osteonecrosis, this exploratory study suggested that thrombophilia was associated with both idiopathic multifocal osteonecrosis and secondary multifocal osteonecrosis, as was the eNOS T-786C polymorphism. Multifocal and unifocal osteonecrosis are similarly associated with thrombophilia, hypofibrinolysis, and the eNOS T-786C polymorphism, which are potentially treatable pathophysiologic conditions, requiring further study.

Pulmonary thromboembolism in childhood: A single-center experience from Turkey

This study was designed to evaluate the clinical characteristics, acquired and congenital risk factors, treatment strategies, and long-term outcome in pediatric pulmonary thromboembolism (PTE) cases followed in our center in Turkey. Of the total 470 pediatric patients with thrombosis referred to our center, 16 (3.4%) had PTE. The mean age of the children with PTE was 10.3 +/- 6.8 years (range: 1.5-20.0, median: 10.5), and 12 (75.0%) were boys. The mean follow-up period was 28.9 +/- 21.0 months (range: 3-66, median: 22). During the follow-up period, recurrence was observed in three children (18.8%). The mean time from the appearance of symptoms to accurate diagnosis was 6.4 +/- 4.0 days (range: 2-10). Six patients (37.5%) were initially diagnosed as having pneumonia. After they were hospitalized and showed no clinical improvement with broad-spectrum antibiotic treatment, the accurate diagnosis of PTE was established. Of these 16 patients with PTE, 8 (50%) had associated thrombosis and 6 (37.5%) had congenital heart diseases. Infections including septic arthritis and osteomyelitis (n = 1), cytomegalovirus infection (n = 1), and infective endocarditis (n = 2) were detected in our patient group. In addition, two patients had a central venous line and one patient had obesity associated with malignancy. Other underlying diseases included thalassemia major, Behçet disease, antiphospholipid antibody syndrome, and autoimmune lymphoproliferative disorder in one patient each. Factor V G1691A heterozygous mutation was detected in two children, and methylene tetrahydrofolate reductase C677T homozygous mutation was detected in one child. A high level of factor VIII was the most common (8/16, 50%) laboratory risk factor in our patient group, and 12 children (75.0%) had a high D-dimer level. Among 16 children with PTE, one child had one, three children had two, five children had three, three children had four, and four children had five laboratory and/or clinical risk factors. Therefore, all children with PTE had at least one laboratory and/or clinical risk factor that facilitated development of thrombosis. In addition, according to the risk assessment for persistence or recurrence of venous thrombosis in children conducted by Manco-Johnson, 12 children (75%) with PTE in the present study had high-risk criteria. When a child with thrombosis at any site of the body develops unexpected respiratory symptoms or pneumonia unresponsive to antibiotic treatment, imaging studies should be performed for diagnosis of PTE. Furthermore, thrombotic children with high-risk criteria should be followed closely for the development of PTE.

In Vitro Modeling of the Influence of FVIII Activity and Heparin Induced Prolongation of APTT

Anticoagulant therapy is most commonly assessed by measuring the effect of the drug on global clotting assay, such as APTT. It is known that response of the APTT to heparin may be decreased in patients with high levels of factor VIII. In this work, we have attempted to determine in vitro conditions of experiment for obtaining relationship between different concentrations of heparin and values of APTT, and to investigate influence of factor VIII on correlation between concentrations of heparin and APTT. Measurement of the effect of heparin, added in vitro in normal coagulation control plasma (NCCP) showed that heparin in concentrations from 0.1 to 1.0 IU/mL prolonged APTT from 0.73 s to 99.26 s. Linearity of the relation of natural logarithm of APTT and concentration of added heparin in plasma for concentrations from 0.5 to 1.0 IU/mL (r = 0.995), and other characteristics of the validated method (RSD = 1.17%), made possible investigation of the influence of factor VIII addition in the solution. The addition of the Factor VIII concentrate, markedly influenced these APTT results. Increased factor VIII activity shortened the APTT, having more pronounced effect in the presence of the large amounts of heparin. Increased factor VIII was associated with downward shift in the concentration -- logAPTT response curve (y = 24644 x + 30.17 vs. y = 10.864 x + 27.256). This finding suggests the possibility for modeling of ex vivo establishment of correlation between plasma activity of FVIII and needed doses of heparin for appropriate management of heparin therapy.

A Case Report of Recurrent Vascular Access Thrombosis in a Hemodialysis Patient Reveals Combined Acquired and Inherited Thrombophilia

Vascular access thrombosis represents a serious and unfortunately common problem in hemodialysis patients. Usually, but not always, this complication can be attributed to low access blood flow. However, there are some patients who experience thrombosis despite a well functioning vascular access. We describe the case of a 31-year-old Caucasian male, who was hemodialyzed via an arteriovenous fistula for two years due to Alport's syndrome. During this time period he had two episodes of vascular access thrombosis that destroyed two arteriovenous fistulas. Both fistulas were functioning well and the thrombosis events took place in days between the hemodialysis sessions. Thrombophilia was suspected and the relative investigation revealed high levels of factor VIII procoagulant, which is frequent in hemodialysis patients, and resistance to activated protein C. Polymerase chain reaction detected that the patient was heterozygous for factor V Leiden, which is quite common in general population. Thereafter, a new arteriovenous fistula was formed and the patient started oral anticoagulation therapy with warfarin. Now, three years after the last arteriovenous fistula formation, the patient is hemodialyzed without vascular access problems. In conclusion, evaluation of the coagulation cascade in hemodialysis patients with recurrent vascular access thrombosis is necessary.

Association of venous thromboembolism and olanzapine

Aims:Venous thromboembolism (VTE) has been associated with the diagnosis of a psychiatric disease, as well as with the treatment with psychotropic drugs. Recent reports suggest an association between several atypical antipsychotics agents (eg. olanzapine) and an increased risk for VTE.Methods:We prospectively analysed and consequently followed-up olanzapine users in a cohort of 138 consecutive patients under 60 years of age (male=72, mean age 45 years) suffering from objectively confirmed VTE over a three-year period (2004 - 2006). Data on known acquired or genetic risk factors for VTE were recorded for each patient.Results:Four Caucasian patients (one female, three males; mean age 49 years, range 37-55 years) with spontaneous VTE treated with olanzapine were registered. Two patients were obese. The hospitalization was extended in the female patient. We found coagulation abnormalities in all our subjects (elevated levels of factor VIII:C, mild hyperhomocysteinemia, FV Leiden and prothrombin gene G20210A mutations).Conclusions:These cases indicate that VTE might be associated with the use of olanzapine, at least in the presence of several acquired or inherited risk factors such as immobilization, obesity and disorders of coagulation homeostasis including factor V Leiden, prothrombin gene G20210A mutations, high levels of factor VIII and hyperhomocysteinemia. Subjects treated with olanzapine should be monitored clinically for VTE. Interestingly, in three patients symptoms occurred in the first six months of olanzapine treatment.

Absolute risk of venous and arterial thromboembolism in thrombophilic families is not increased by high thrombin-activatable fibrinolysis inhibitor (TAFI) levels

High levels of thrombin-activatable fibrinolysis inhibitor (TAFI) are a supposed risk factor for thrombosis. However, results from previous studies are conflicting. We assessed the absolute risk of venous and arterial thromboembolism in subjects with high TAFI levels (>126 U/dl) versus subjects with normal levels, and the contribution of other concomitant thrombophilic defects. Relatives from four identical cohort studies in families with either deficiencies of antithrombin, protein C or protein S, prothrombin 20210A, high factor VIII levels, or hyperhomocysteinemia were pooled. Probands were excluded. Of 1,940 relatives, 187 had high TAFI levels. Annual incidences of venous thromboembolism were 0.23% in relatives with high TAFI levels versus 0.26% in relatives with normal TAFI levels (adjusted relative risk [RR] 0.8; 95% confidence interval [CI], 0.5-1.3). For arterial thrombosis these were 0.31% versus 0.23% (adjusted RR 1.4; 95% CI, 0.9-2.2). High levels of factor VIII, IX and XI were observed more frequently in relatives with high TAFI levels. Only high factor VIII levels were associated with an increased risk of venous and arterial thrombosis, independently of TAFI levels. None of these concomitant defects showed interaction with high TAFI levels. High TAFI levels were not associated with an increased risk of venous and arterial thromboembolism in thrombophilic families.

Hemostatic Dysfunction in Paraproteinemias and Amyloidosis

Thrombotic and hemorrhagic complications frequently have been observed in patients with monoclonal gammopathy, Waldenström macroglobulinemia, amyloidosis, multiple myeloma (MM), and myeloma. Chemotherapy in combination with the use of antiangiogenic agents can further enhance the risk of cardiovascular complications. A malignancy-associated thrombophilic state (in particular, cytokine-induced high levels of factor VIII and von Willebrand factor) can also explain the high rate of thrombosis reported in these patients. Impaired fibrinolysis and a transient downregulation of the protein C system are recently discovered pathogenetic mechanisms. At diagnosis, when the highest VTE risk is present, baseline coagulation tests such activated protein C resistance may be helpful to identify patients who can benefit the most from anticoagulation; with the emerging evidence of a positive effect on survival of low molecular weight heparin, prospective trials are needed in this group of diseases.

High FVIII Level Is Associated with Idiopathic Portal Vein Thrombosis in South India

Background In the majority of the cases of portal vein thrombosis in India, the etiology cannot be determined. A high level of factor VIII (FVIII) is a risk factor for venous thromboembolism. Methods In this study from South India, FVIII was estimated in 32 patients with idiopathic portal vein thrombosis (PVT), 12 healthy controls and 12 disease controls with chronic liver disease. Results Eighty-four percent of the patients with portal vein thrombosis (27/32) vs 17% of healthy controls (2/12) had high factor VIII levels ( P <.0001). FVIII levels were significantly different between the subset of PVT patients with normal liver function compared with healthy controls ( P <.001) and also between the subset of PVT patients with abnormal liver function compared with disease controls ( P <.05). Conclusions A high factor VIII level seems to contribute to the development of portal vein thrombosis in India.

Thrombosis in multiple myeloma

Multiple myeloma, as with other malignancies, has been associated with the development of venous thromboembolic events. Chemotherapy or steroids in combination with antiangiogenic agents can further enhance this risk. The identification of measurable factors associated with this prothrombotic state could help in the selection of patients who need antithrombotic prophylaxis. Malignancy-associated thrombophilic state, paraprotein-specific mechanisms and treatment-induced changes can explain the high rate of thrombosis in this cancer population. While the release of inflammatory cytokines induces high levels of factor VIII, von Willebrand factor and downregulate the protein C system, elevated plasma immunoglobulin can impair fibrinolysis. Strategies of thromboprophylaxis with low molecular weight heparin, warfarin or aspirin in patients treated with thalidomide/chemotherapy or lenalidomide and dexamethasone have shown efficacy. Early data indicate that the effect of low molecular weight heparin on multiple myeloma is not confined to the anticoagulant effect but could extend to survival; a similar positive trend in overall survival has also been reported in patients treated with aspirin.

Elevated Factor XI Activity Levels Are Associated With an Increased Odds Ratio for Cerebrovascular Events

High levels of factor XI have been implicated as a risk factor for deep venous thrombosis and possibly cardiovascular disease; however, the relationship between elevated factor XI activity and stroke has yet to be established. We retrospectively evaluated factor XI activity, factor XI antigen, and high-sensitivity C-reactive protein (hs-CRP) values in samples from 65 patients with stroke, 13 with transient ischemic attack (TIA), and 17 with venous thrombosis, younger than 55 years with normal prothrombin and partial thromboplastin times who underwent evaluation for a hypercoagulable state. Factor XI activity levels were more than normal in 22% of patients with stroke or TIA and 18% of patients with venous thrombosis, producing odds ratios of 5.3 and 4.1 for stroke or TIA and venous thrombosis, respectively. Factor XI activity levels correlate with factor XI antigen levels by Deming regression analysis (slope, 1.3; R = 0.667) and a lack of correlation of both with hs-CRP suggests that factor XI is not an acute phase reactant. Our findings suggest an association between elevated factor XI activity and stroke.

Portal Vein Thrombosis and High Factor VIII in Turner Syndrome

Backgrounds/Aims: Turner syndrome is not usually associated with thrombotic events. The aim of this study is to report 3 Turner syndrome patients with portal vein thrombosis and, in 2 of them, high factor VIII. These findings are compared to values in Turner syndrome patients without thrombosis and controls. Methods: In different years, 3 patients with Turner syndrome were initially seen at the Gastroenterology Clinic of Hospital de Clínicas de Porto Alegre, Brazil, for portal vein thrombosis. After the most common causes of portal vein thrombosis and thrombophilias had been excluded, the 2 surviving patients were studied for clotting factors VIII, IX and von Willebrand factor. The same factors were also assessed in 25 Turner syndrome patients without thrombosis and 25 normal girls. Results: One of the patients with portal vein thrombosis died before the study. In the 2 surviving patients, factors VIII and von Willebrand levels were >150 IU/dl, which is considered to be high. In Turner syndrome patients without thrombosis, the mean factor VIII level was 127.2 ± 41.1 IU/dl and for von Willebrand factor 101.2 ± 26.9 IU/dl, while in control girls these were 116.0 ± 27.6 and 94.28 ± 27.5 IU/dl, respectively. Factor VIII and von Willebrand factor were not different between these 2 groups. When non-O blood group Turner syndrome patients and normal girls were compared, the former had significantly higher levels of factor VIII. Conclusions: This is the first report on the unusual finding of portal thrombosis in patients with Turner syndrome in whom high levels of factor VIII and von Willebrand factor were found. Factor VIII is higher in the non-O blood group Turner syndrome patients without thrombosis when compared to normal girls.

Factor V Leiden mutation, deficiency of antithrombin III and elevation of factor VIII in a child with ischemic stroke: A case report

A 4-year-old boy was admitted with left hemiplegia. Thrombophilia marker examination resulted with factor V Leiden mutation heterozygosity, a deficiency of antithrombin III and a high level of factor VIII. Cranial computed tomography scan revealed an ischemic infarct in the region of right anterior cerebral artery. In the literature, combinations of multiple thrombophilia risk factors that trigger cerebral ischemic stroke in children have been emphasized. To our knowledge, this is the first child with these combinations of thrombophilia risk factors and ischemic stroke to be reported in the literature.

Increased Sensitivity of Prothrombin Time Using Recombinant Tissue Thromboplastin Reagents: Implications for Plasma Transfusion.

Acquired coagulopathies are often treated with fresh frozen plasma (FFP) transfusion. Standards for the tranfusion of FFP vary, but are often based on coagulation tests, especially prothrombin time (PT). Previously, the PT test was performed using tissue thromboplastin (TT) reagents derived from human or animal tissue homogenates (hTT). These preparations were fairly crude and varied between manufacturers and lots. Recently, these have been replaced with recombinant TT (rTT) reagents that are more consistent. However, anecdotal reports suggest that rTT is more sensitive to mildly decreased clotting factor levels, leading to longer PTs and increases in FFP transfusion. The purpose of this study is to test the hypothesis that rTT reagents are more sensitive and to determine if thresholds for FFP transfusion should be increased. Fifty plasma samples from patients with prolonged PTs (range 13.0–27.6 seconds; normal 9.2–12.8 seconds) were randomly selected. PTs for each sample were re-measured using rTT (Innovin, Dade-Behring, Liederbach, Germany; ISI=0.91) and hTT (Thromboplastin Reagent, Helena Laboratories, Beaumont, Texas; ISI=2.07) on the same instrument (Start 4 benchtop coagulation analyzer, Diagnostica Stago, Parsippany, New Jersey). These measured PTs are compared in Fig. 1. At the lower end of the PT range (beginning at ~13 seconds), the rTT PTs are shorter, on average, than the hTT PTs. However, the average rTT PT increases at a 1.4 times greater rate than the hTT PT, such that the average PT of the two reagents is equivalent at 16.4 seconds and longer for rTT thereafter. This suggests that the rTT reagent is indeed more sensitive. A similar pattern is seen when factor II and VII levels for each sample are plotted against the corresponding PT (Fig. 2). At high factor levels, the rTT PT is lower, on average, than the hTT PT. However, as factor levels decrease, the rTT PT rises about twice as fast as the hTT PT. The PTs for the two reagents are equivalent at 66% factor II (PT=15.7) and 46% factor VII (PT=17.7). The important thresholds for risk of surgical bleeding are 40% factor II and 25% factor VII. The equivalent PTs in this study are 20.5 (rTT) and 18.1 (hTT) for 40% factor II and 22.3 (rTT) and 19.6 (hTT) for 25% factor VII. These differences are not corrected by converting PTs to the international normalized ratio (INR). Instead, INRs are higher for hTT than rTT, and the degree of difference between the two reagents is greater. The equivalent INRs are 1.90 (rTT) and 2.54 (hTT) for 40% factor II activity, and 2.05 (rTT) and 2.98 (hTT) for 25% factor VII activity. The results of this study confirm that PTs measured using rTT are more sensitive to changes in clotting factor levels than those measured using hTT, especially at clinically significant factor levels. This suggests that thresholds for the transfusion of FFP should be raised at those institutions using rTT. [Display omitted] [Display omitted]