Background The anti-phospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with persistent presence of anti-phospholipid antibodies (aPL). Laboratory criteria include aPL detection by coagulation tests for lupus anticoagulant (LAC) or solid phase assays measuring anti-β2 glycoprotein I (aβ2GPI) or anti-cardiolipin (aCL) immunoglobulin (Ig) G/IgM antibodies. External quality control programs illustrate that commercially available aPL assays produce variable results. Objective We aimed to investigate the agreement and diagnostic accuracy of solid phase assays. Materials and Methods In this multi-centre study, 1,168 patient samples were tested on one site for aCL and aβ2GPI IgG/IgM antibodies by four solid phase test systems. Samples included APS patients, controls and monoclonal antibodies (MoAB) against different epitopes of β2GPI. LAC was determined by the local centre. Results aCL IgM assays resulted in the most discrepancies (60%), while aCL IgG and aβ2GPI IgM assays resulted in lower discrepancies (36%), suggesting better agreement. Discrepant samples displayed lower median aPL titers. Dependent on the solid phase test system, odds ratios (ORs) for thrombosis and pregnancy morbidity ranged from 1.98 to 2.56 and 3.42 to 4.78, respectively. Three platforms showed lower sensitivity for MoAB directed against the glycine (Gly) 40-arginine (Arg) 43 epitope of domain I of β2GPI. Conclusion Poor agreement was observed between different commercially available aCL and aβ2GPI IgG/IgM assays, hampering uniformity in the identification of aPL-positive patients. Clinical association was globally concordant between solid phase test systems considering results of the four aPL together. An assay sensitive in detecting the MoAB against Gly40-Arg43 of domain I of β2GPI reached the highest OR for thrombosis.

High platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) are associated with an increased risk of arterial thrombosis, but their role in venous thromboembolism (VTE) has not been fully investigated. A case-control study, of 486 patients with VTE, 100 with cerebral vein thrombosis (CVT), and 299 healthy individuals, was carried out to investigate whether high PLR or NLR values are associated with an increased risk of VTE. Patients with high PLR or NLR did not have an increased risk of VTE (odds ratio [OR] 0.89, 95% confidence interval [CI]: 0.46-1.76; OR: 0.69, 95% CI: 0.34-1.39, respectively) or CVT (OR: 1.65, 95% CI: 0.68-4.00; OR: 0.39, 95% CI: 0.09-1.72, respectively). Subgroups analysis showed that high PLR values were associated with the risk of provoked CVT (OR: 2.65, 95% CI: 1.02-6.92), and there was an interaction with thrombophilia abnormalities (OR: 7.67, 95% CI: 1.67-35.27) in patients with CVT. In conclusion, high PLR and NLR values are not associated with an overall increased risk of VTE or CVT. High PLR values increase the risk of provoked CVT and interact with thrombophilia abnormalities in patients with CVT.

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Summary.  Background:  It is currently unclear whether or not cerebral venous thrombosis, such as splanchnic venous thrombosis, can be the first manifestation of an underlying myeloproliferative neoplasm. Objective:  To determine the prevalence of the JAK2 V617F mutation in patients with a first episode of cerebral venous thrombosis. Patients:  In this retrospective cohort study, patients with cerebral venous thrombosis were tested for the JAK2 V617F mutation and were followed until the development of a myeloproliferative neoplasm or censored at the end of follow‐up. Results:  Ten of 152 patients (6.6%) carried the JAK2 V617F mutation. Three of them had known acquired risk factors for thrombosis, and five had thrombophilia. Six patients met the diagnostic criteria for myeloproliferative neoplasm at the time of cerebral venous thrombosis, and three additional patients developed the disease during the follow‐up (median duration 7.8 years, range 6 months to 21.3 years), giving an annual incidence of 0.26% patient‐years (95% confidence interval 0.05–0.64). The last patient has no evidence of disease after 3 years of follow‐up. Patients without the JAK2 V617F mutation at the time of cerebral venous thrombosis were retested at the end of the follow‐up and remained negative, with normal blood counts (log‐rank test χ2: 159 [P < 0.0001]). Conclusions:  Cerebral venous thrombosis can be the first symptom of a myeloproliferative neoplasm. Patients with cerebral venous thrombosis can carry the JAK2 V617F mutation, irrespective of blood count.

In spite of their recognized risk of thrombosis, patients with myeloproliferative neoplasms (MPN) show little or no abnormalities of traditional coagulation tests, perhaps because these are unable to represent the balance between pro- and anticoagulants nor the effect of platelets and blood cells. We investigated whether global tests such as thrombin generation in platelet-rich plasma (PRP) or thromboelastometry in whole blood were able to detect signs of procoagulant imbalance in MPN. The endogenous thrombin potential (ETP) of 111 patients and 89 controls was measured in PRP with platelet count adjusted to the original patient- or control-count. Testing was performed with and without thrombomodulin (the physiological protein C activator) and results were expressed as ETP ratios (with/without thrombomodulin). High ETP ratios reflect resistance to thrombomodulin and were taken as indexes of procoagulant imbalance. Patients were also investigated by thromboelastometry that provides such parameters as the clot formation time (CFT) and maximal clot firmness (MCF). Short CFT or high MCF were taken as indexes of procoagulant imbalance. ETP ratios were higher in patients than in controls and were directly correlated with platelet counts and inversely with the plasma levels of free protein S, protein C and antithrombin. Patients on hydroxyurea had lower ETP ratios than those on other treatments. CFT was shorter and MCF was greater in patients than controls; CFT and MCF were correlated with platelet counts. In conclusion, patients with MPN display a procoagulant imbalance detectable by thrombin generation and thromboelastometry. These tests might be useful in the frame of clinical trials to assess their association with the occurrence of thrombosis and with the effect of therapeutic strategies in MPN.

BACKGROUND: A bleeding diathesis is a common feature of Noonan syndrome, and various coagulation abnormalities have been reported. Platelet function has never been carefully investigated. METHODS: The degree of bleeding diathesis in a cohort of patients with Noonan syndrome was evaluated by a validated bleeding score and investigated with coagulation and platelet function tests. If ratios of prothrombin time and/or activated partial thromboplastin time were prolonged, the activity of clotting factors was measured. Individuals with no history of bleeding formed the control group. RESULTS: The study population included 39 patients and 28 controls. Bleeding score was ≥2 (ie, suggestive of a moderate bleeding diathesis) in 15 patients (38.5%) and ≥4 (ie, suggestive of a severe bleeding diathesis) in 7 (17.9%). Abnormal coagulation and/or platelet function tests were found in 14 patients with bleeding score ≥2 (93.3%) but also in 21 (87.5%) of those with bleeding score &lt;2. The prothrombin time and activated partial thromboplastin time were prolonged in 18 patients (46%) and partial deficiency of factor VII, alone or in combination with the deficiency of other vitamin K–dependent factors, was the most frequent coagulation abnormality. Moreover, platelet aggregation and secretion were reduced in 29 of 35 patients (82.9%, P &lt; .01 for all aggregating agents). CONCLUSIONS: Nearly 40% of patients with the Noonan syndrome had a bleeding diathesis and &gt;90% of them had platelet function and/or coagulation abnormalities. Results of these tests should be taken into account in the management of bleeding or invasive procedures in these patients.

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