Hemostatic abnormalities in patients with Ehlers-Danlos syndrome.

Essentials Ehlers-Danlos Syndrome (EDS) is a rare heterogeneous group of inherited collagen disorders. A cohort of EDS patients was investigated for bleeding tendency and hemostatic abnormalities. EDS is associated with an increased risk of bleeding. EDS patients have platelet function abnormalities, whose severity correlates with bleeding risk. SUMMARY: Background Ehlers-Danlos syndrome (EDS) includes a heterogeneous group of connective tissue disorders affecting skin, bones, vessels, and other organs. Patients with EDS have an increased risk of bleeding, but a comprehensive study of hemostasis in EDS patients is lacking. Objective To investigate the bleeding tendency of a cohort of patients with EDS by using the Bleeding Assessment Tool of the ISTH, the bleeding severity score (BSS). Methods The BSS was defined as abnormal when it was ≥ 4 in men and ≥ 6 in women. Patients with a bleeding tendency were compared with those without in terms of type and number of hemostatic abnormalities. Results Fifty-nine of 141 patients with EDS (41.7%) had an abnormal BSS. Prothrombin time and activated partial thromboplastin time were slightly prolonged in 10 patients (7.1%) because of mild coagulation factor deficiencies, which were not responsible for the bleeding diathesis. von Willebrand factor antigen, ristocetin cofactor, endogenous thrombin potential and platelet count were normal in all patients. At least one platelet function abnormality was found in 53 patients (90%) with an abnormal BSS and in 64 (78%) with a normal BSS (adjusted odds ratio [OR] 2.55, 95% confidence interval [CI] 0.87-7.48). The risk of bleeding progressively increased with the number of platelet function abnormalities, reaching an OR of 5.19 (95% CI 1.32-20.45) when more than three abnormalities were detected. Conclusions Our results show that nearly half of patients with EDS have an abnormal BSS, which, in 90% of cases, appear, at least in part, to be attributable to platelet function abnormalities. Abnormalities of primary hemostasis may contribute to the risk of bleeding in patients with EDS.

Cerebral venous sinus thrombosis.

The cerebral venous system is an unusual site of thrombosis, with a particularly high incidence in young adults. This incidence has increased in past decades because of the improvement of neuroradiological techniques. Risk factors for cerebral venous sinus thrombosis overlap with those of other venous thromboembolism sites; however, some are specific for this particular anatomical district. Prognosis is favorable in most cases if diagnosis is made rapidly and treatment is promptly initiated, even if acute complications or chronic invalidity still occur in a quarter of patients. The mainstay of treatment is anticoagulation, which is necessary in order to block clot propagation and obtain recanalization. Intracranial bleeding does not contraindicate anticoagulation. Endovascular procedures are reserved for patients with a particularly severe presentation or rapidly declining neurological symptoms despite appropriate anticoagulation, although data from clinical trials are lacking. Specifically, this review addresses the epidemiology, clinical presentation and course, risk factors, and treatment of cerebral venous sinus thrombosis, with a special focus on the pediatric population.

The ISTH Bleeding Assessment Tool and the risk of future bleeding.

Essentials ISTH Bleeding Assessment Tool (ISTH-BAT) is used to assist the diagnosis of bleeding disorders. We examined whether the ISTH-BAT is capable of predicting the risk of future bleeding. 136 subjects were administered the ISTH-BAT and followed for up to four years. The ISTH-BAT score failed to predict the risk of future bleeding. SUMMARY: Background The ISTH Bleeding Assessment Tool (ISTH-BAT) is a diagnostic tool used in subjects with suspected inherited bleeding disorders. Aim To evaluate whether the ISTH-BAT, applied at first work-up in a tertiary-care center, predicts the risk of subsequent bleeding events. Methods This was an observational cohort study including all consecutive subjects, of either sex and any age, referred between 2011 and 2015 because of a suspected bleeding disorder. The analysis was restricted to those with an ISTH-BAT score of ≥ 3. Incidence rates (IRs) of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) events were calculated as the number of events over accrued person-years. The main analysis was performed with Cox regression analysis, assessing an ISTH-BAT score of ≤ 5 versus a score of > 5, as well as the score as a continuous variable, and various covariates (sex, age, and presence/absence of a final diagnosis). Results One hundred and thirty-six subjects had a median ISTH-BAT score of 4 (range 3-18). Eleven subjects (8.1%) had a bleeding event during follow-up (one MB event; 10 CRNMB events). The overall IR of bleeding events per 100 person-years was 3.7 (95% confidence interval [CI] 1.8-6.6). No difference was observed between subjects with an ISTH-BAT score of ≤ 5 and those with a score of > 5 (hazard ratio [HR] 1.2, 95% CI 0.3-4.6). The results were similar when the ISTH-BAT score was considered as a continuous variable (HR 1.1, 95% CI 0.9-1.4). The IR of bleeding was increased in individuals with a diagnosis of a hemostatic defect (IR of 7.5 per 100 person-years; HR 3.0, 95% CI 0.8-11.8). Conclusions The ISTH-BAT does not identify patients at increased risk of future bleeding events.

Pregnancy outcome after a first episode of cerebral vein thrombosis.

Essentials Little is known about recurrences and pregnancy outcome after cerebral vein thrombosis (CVT). We studied a cohort of pregnant women with CVT. Women with CVT appear at increased risk of late obstetrical complications despite prophylaxis. Risks of recurrent thrombosis and bleeding in women on heparin prophylaxis while pregnant are low. SUMMARY: Background The risk of recurrent thrombosis and bleeding episodes in women with previous cerebral vein thrombosis (CVT) on antithrombotic prophylaxis with low-molecular-weight heparin (LMWH) during pregnancy is not established and little information is available on pregnancy outcome. Objectives The aims of this study were to evaluate the risk of obstetrical complications, recurrent venous thrombosis and bleeding in a cohort of pregnant women on LMWH after a first episode of CVT. In addition, to estimate the relative risk of obstetrical complications, patients were compared with healthy women without thrombosis and with at least one pregnancy in their life. Patients We studied a cohort of 52 patients and 204 healthy women. Results The risk of developing late obstetrical complications was 24% (95% CI, 18-38%), leading to a relative risk of 6.09 (95% CI, 2.46-15.05). The risk of miscarriage was not increased. The higher risk of late obstetrical complications in patients appeared unrelated to a previous history of obstetrical complications, to the carriership of thrombophilia abnormalities, or to the presence of co-morbidities. The incidence of termination observed in patients with thrombophilia was double that observed in those without. No recurrent thrombosis or bleeding episodes were observed. Conclusions Women with previous CVT on LMWH prophylaxis during pregnancy have a low risk of developing recurrent thrombosis or bleeding episodes, but seem to have an increased risk of late obstetrical complications.

Stem cells and kidney diseases.

The role of the stem cell (SC) in physiology and physiopathology has recently attracted much interest. SCs may originate from embryos, aborted fetuses, umbilical cord blood, and adult organs and tissues. In the adult, SCs were first defined in tissues with a high cell turnover, like skin and gut. Today, SCs have also been identified in tissues with no or low regenerative potential and turnover. However, the SC concept is changing rapidly: adult SCs not only reside locally in specific niches, but may also be recruited from the circulation to actively participate in the regeneration of various tissues. Furthermore, reverse differentiation has been demonstrated. In the kidney, both glomerular and tubular cells may differentiate into a range of phenotypes during the remodelling process in response to injury. The glomerular and tubulointerstitial scarring processes involve primarily interactions between infiltrating inflammatory cells and resident renal cells that culminate in loss of renal cells and their replacement by extracellular collagenous matrix. Reverse embryogenesis is a key step in renal healing and scarring: intrinsic renal cells regress to primitive/embryonic mesenchymal phenotype. In addition, it is clear that renal remodelling in health and disease involves the migration of hematopoietic SCs into the kidneys. These cells assume various glomerular and tubular epithelial phenotypes. Therefore, a better understanding of some of these key events in renal remodelling may open the way to new interventions based on their manipulations. Cell-based therapy may be a more successful strategy by providing a dynamic and individualized therapeutic approach that responds to the physiopathological condition of the patient. In fact, SCs may provide innovative methods for drug delivery, immunotherapy, tissue regenerative or replacement engineering.