First diagnosis of factor XI deficiency in a patient with subarachnoid haemorrhage

Aneurismal subarachnoid haemorrhage (SAH) is a devastating event affecting patients at a fairly young age and accounting for significant morbidity and mortality. Although there is progress concerning diagnostic methods and treatment, this case report might add interesting data to the current understanding of this disease and its clinical management with respect to circumstantial deficiency of the coagulation factor XI (FXI). In this report, we present a unique case of aneurismal SAH in a patient with underlying coagulation FXI deficiency which was incidentally identified after patient's admission, as routine blood tests revealed increased activated partial thromboplastin time. Despite early successful treatment with coiling, the patient had a second episode of SAH a few months after his discharge, due to aneurysm revascularization and rupture. Molecular analysis and identification of new mutations were performed. We describe management of SAH with respect to a coexisting bleeding disorder; also testing of patient's family members for FXI deficiency and decisions about screening for intracranial aneurysm are described. Late complications of SAH are - among others - aneurysm revascularization and rebleeding. Although FXI deficiency could be considered an exacerbating factor, it cannot be definitely implicated. Blood CoagulFibrinolysis 20:309-313. © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Long-term treatment with ramipril favourably modifies the haemostatic response to acute submaximal exercise in hypertensives

Introduction: Hypertension links to a prothrombotic state driven by endothelial dysfunction, reduced fibrinolytic potential and platelet hyperactivity. We hypothesized that ramipril treatment would favourably modify the haemostatic response to a submaximal aerobic exercise session in hypertensives. Methods: Twenty-four hypertensive patients underwent a submaximal exercise test before and after 13±2 months of treatment with ramipril ± hydrochlorothiazide. Hypercoagulability (prothrombin fragments [PF1+2], thrombin- antithrombin complex [TAT] and D-dimers [Dd]), fibrinolytic activity (plasmin-a2-antiplasmin complex [PAP]), endothelial function (von Willebrand factor [vWf] and soluble thrombomodulin [sTM]), and platelet function (soluble P-selectin [sPsel]) were measured before, at peak and one hour after exercise. Results: Antihypertensive treatment resulted in an increase of PAP, vWf and sTM. During the first exercise, PF1+2 were mildly increased at peak exercise (p<0.05), while D-dimers, PAP and vWf varied significantly throughout the exercise (p<0.001). During the second exercise session, PF1+2 were decreased post-exercise (p<0.05), PAP was increased at peak and post-exercise (p<0.001) and vWf was increased at peak (p<0.05) and post-exercise (p<0.001). Conclusions: The haemostatic response to exercise in hypertensives after approximately one year of ramipril treatment is characterized by the attenuated activation of coagulation, enhanced fibrinolysis and endothelial activation. © The Author(s) 2012

The immediate effect of aerobic exercise on haemostatic parameters in patients with recently diagnosed mild to moderate essential hypertension

Background: Exercise is frequently recommended for the treatment of patients with arterial hypertension. Previous studies have shown an enhanced coagulation state after exercise. Our study investigates the alterations observed after a single session of submaximal aerobic exercise concerning coagulation, fibrinolysis, platelet activation as well as endothelial function in patients with recently diagnosed essential hypertension. Methods: Twenty non-diabetic patients with recently diagnosed essential hypertension participated in a 45 min submaximal exercise test on a bicycle ergometer. Blood samples were drawn before and after exercise in order to determine parameters of coagulation activation (Prothrombin time [PT], activated Partial Thromboplastin time [aPTT], fibrinogen, D-Dimers, prothrombin fragments 1 + 2 [PF1+2], thrombin-antithrombin III complex [TAT] and factors VII, VIII and XII), platelet activation (Platelet count, Platelet factor 4 [PF4] and β-thromboglobulin [β-TG]), fibrinolysis activation (Plasmin-a2 antiplasmin complex, PAP) and endothelial function (soluble Thrombomodulin [sTM] and von Willebrand factor [vWf]). Soluble P-selectin served as a marker for endothelial and platelet activation. Results: All patients completed the exercise test. aPTT (P < 0.001) and factor VII (P = 0.01) significantly decreased while PT (P = 0.04), fibrinogen (P = 0.008), factor VIII (P < 0.001), platelet count (P = 0.002) and β-TG levels (P = 0.01) significantly increased as a result of exercise. Compared to baseline there was an 11% increase in TAT (P = 0.04) and a 28% increase in PAP (P < 0.001) at peak exercise. One hour post exercise, there was a 43% increase in PAP whereas TAT levels became similar to those at baseline. Additionally vWf (P = 0.01) and sP-selectin (P = 0.02) levels significantly increased throughout the exercise protocol. Conclusions: Patients with recently diagnosed and never treated mild to moderate essential hypertension undergoing submaximal aerobic exercise present evidence of enhanced fibrinolysis compared with a mild increase of coagulation indices. However, whether there is a favourable effect of exercise on fibrinolysis over coagulation and/or endothelial involvement during exercise needs to be further investigated. © Springer Science+Business Media, LLC 2007

Comparative Thrombogenicity of Pacemaker Leads

To evaluate the throm bogenicity of transvenous silicone and polyurethane pacemaker leads, 9 of 12 anesthetized Yorkshire pigs (27–32 kg) were implanted with silicone (n = 5) or polyurethane (n = 4) pacemaker leads via a femoral vein. The remaining three pigs served as controls. All 12 pigs were injected with autologous indium‐111 labeled platelets (300–420 μCi) 24 hours before anesthesia induction. The pigs were monitored for 3 hours under a gamma camera. Radioactivity in blood and lead segments was measured with a gamma counter. Platelet deposits were denser on silicone leads (441.58 ± 915.0 to 2.19 ± 2.07) than on polyurethane leads (1.21 ± 1.33 to 0.27 ± 0.14) (P > 0.05). Denser platelet deposits were detected at the tip of all leads. Density of platelet deposits declined from tip to distal segments in silicone leads. The percentage of injected platelet radioactivity in the lungs of pigs with either silastic leads (12.9 ± 2.3%) or polyurethane leads (10.1 ± 2.2%) was higher than in the controls (4.6 ± 0.5%) (P < 0.05). This difference indicates thrombus formation and embolization in the lungs early after lead implantation. Thrombogenicity of polyurethane leads may be lower than that of silicone leads