Full colour reproduction of figures originally submitted in colour

Case reports on three patients who underwent vitrectomy assisted t-PA injection for the management of branch retinal vein occlusion. Three-port, 20-gauge vitrectomy was performed under local anesthesia. After posterior vitreous detachment and fluid-air exchange, 50 μ g t-PA/0.5 ml were injected in the eye. All patients were instructed for strict supine position for 6 hours. Main outcome measure was visual acuity. Three patients with branch vein occlusion (BVO) were studied, with duration of symptoms less than 25 days, and mean follow-up period of 18.8 months. Although no intraoperative complications were noticed, no one showed any significant improvement of vision. One patient required a second operation for the management of intravitreal hemorrhage, and another developed an epiretinal membrane. Vitrectomy assisted t-PA injection does not seem to improve the course of branch retinal vein occlusion in this small case series. Future research on intravitreal thrombolysis needs to be focused on additional mechanical approaches and modalities that can facilitate the access of the drug into the vascular lumen.     

Thrombotic microangiopathic hemolytic anemia in systemic lupus erythematosus associated with antiphospholipid antibodies: usefulness of monitoring coagulation–fibrinolysis markers

Abstract

We report on a 24-year-old woman with systemic lupus erythematosus and lupus anticoagulant who developed chronic thrombotic microangiopathic hemolytic anemia. The patient responded well to a combination of plasma exchange and anticoagulant therapy. Changes in the molecular markers for coagulation and fibrinolysis corresponded with the disease activity. We suggest that thrombotic microangiopathic hemolytic anemia should be suspected when anemia and thrombocytopenia of unknown etiologies occur in systemic lupus erythematosus. In such cases, the evaluation of molecular markers for coagulation and fibrinolysis might be helpful both for diagnosis and for assessing the response to therapy.     

Enhanced Streptokinase-Induced Thrombolysis Using Heparin in a Rabbit Model

Heparin potentiation of clot lysis by streptokinase was studied in a rabbit model. Clot was initiated in the rabbit aorta with stasis and thrombin and allowed to naturally propagate proximally until stasis met flow. The clot was allowed to age for 1 h before assigning treatment. Fifteen rabbits (group I) were given streptokinase (10,000 IU/h) and 11 rabbits (group II) were given streptokinase (10,000 IU/h) plus sodium-heparin (120 IU/h). Thrombolytic therapy was continued for 5 h. Clot lysis averaged 30% in group I and 70% in group II. Ten of 11 rabbits in group II had more than 50% clot lysis, whereas only 4 of 15 in group I had this degree of lysis. One group II rabbit and four group I rabbits died prematurely; each was noted to have clot propagation at the time of death. While a trend for amelioration of hypofibrinogenemia was observed in the group receiving both streptokinase and heparin, this difference was not statistically significant. We conclude, in the animal model, that thrombolysis by a combination of heparin und streptokinase is more effective than streptokinase alone. Systemic effects are apparently no worse with the combination.     

狼疮性肾炎患者凝血纤溶指标的检测分析

目的:检测分析狼疮性肾炎患者凝血纤溶指标的变化及临床意义。方法:选择已确诊的狼疮性肾炎患者(狼疮性肾炎组)及原发性肾小球肾炎患者(肾小球肾炎组)各30例,平行检测两组凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、纤维蛋白原(FIB)及D二聚体(DD)水平以及不同病程狼疮性肾炎患者上述指标变化。结果:狼疮性肾炎组FIB、DD水平均高于肾小球肾炎组(P0.05),但PT、APTT差异无统计学意义(P0.05)。病程5年的狼疮性肾炎患者较病程≤5年的患者PT、APTT缩短,FIB增高,差异均有统计学意义(P0.05)。结论:狼疮性肾炎患者存在高凝状态,且病程延长,高凝加重。     

Post‐partum haemorrhage and tranexamic acid: a global issue

Post‐partum haemorrhage (PPH) remains the major cause of maternal death worldwide, with the overwhelming majority of bleeding deaths occurring in low income countries. These bleeding deaths occur due to a complex network of biological and socioeconomic factors, including changes to haemostasis and fibrinolysis during pregnancy. Tranexamic acid (TxA) has been shown to reduce death in bleeding trauma patients safely and is effective in reducing bleeding in surgical patients, however its role in PPH has been less well established. We discuss the impact of the recently published World Maternal Antifibrinolytic (WOMAN) trial, which demonstrated a significant reduction in bleeding deaths (Risk ratio 0·81) in women with PPH who received intravenous TxA compared to those receiving placebo. There were no increases in post‐partum thrombotic rates in mothers or breast‐fed babies. This trial has shown that intravenous TxA can be used safely and effectively to treat PPH, and should be implemented widely to reduce death due to PPH. However, for the full benefit of TxA to be fully realised in resource‐constrained settings, the effectiveness of oral or topical administration and/or pre‐emptive dosing need to be investigated.     

The incidence and magnitude of fibrinolytic activation in trauma patients

Summary. Background:  Trauma is a global disease, with over 2.5 million deaths annually from hemorrhage and coagulopathy. Overt hyperfibrinolysis is rare in trauma, and is associated with massive fatal injuries. Paradoxically, clinical trials suggest a much broader indication for antifibrinolytics. Objective: To determine the incidence and magnitude of fibrinolytic activation in trauma patients and its relationship to clot lysis as measured by thromboelastometry. Methods: A prospective cohort study of 303 consecutive trauma patients admitted between January 2007 and June 2009 was performed. Blood was drawn on arrival for thromboelastometry (TEM) and coagulation assays. Follow‐up was until hospital discharge or death. TEM hyperfibrinolysis was defined as maximum clot lysis of > 15%. Fibrinolytic activation (FA) was deterined according to plasmin–antiplasmin (PAP) complex and D‐dimer levels. Data were collected on demographics, mechanism, severity of injury, and baseline vital signs. The primary outcome measure was 28‐day mortality. The secondary outcome measures were 28‐day ventilator‐free days and 24‐h transfusion requirement. Results: Only 5% of patients had severe fibrinolysis on TEM, but 57% of patients had evidence of ‘moderate’ fibrinolysis, with PAP complex levels elevated to over twice normal (> 1500 μg L^?1) without lysis on TEM. TEM detected clot lysis only when PAP complex levels were increased to 30 times normal (P < 0.001) and antiplasmin levels were < 75% of normal. Patients with FA had increased 28‐day mortality as compared with those with no FA (12% vs. 1%, P < 0.001), fewer ventilator‐free days, and longer hospital stay. Conclusions: FA occurs in the majority of trauma patients, and the magnitude of FA correlates with poor clinical outcome. This was not detected by conventional TEM, which is an insensitive measure of endogenous fibrinolytic activity.     

Do determinants of platelet function co-segregate with genetic markers of type 1 diabetes mellitus?: Analysis of platelet and fibrinolytic parameters in families with type 1 diabetes mellitus

This study examined the significance of selected parameters of primary haemostasis to discriminate between relatives of children with insulin-dependent diabetes mellitus (IDDM). Platelet function, including markers of spontaneous and agonist-induced platelet activation (CD62), platelet consumption (microparticles) and clumping (aggregates), as well as selected parameters of the fibrinolytic system (t-PA and PAI-1), were studied in IDDM children (n = 45), their parents (n = 65), siblings (n = 17) and unrelated healthy controls (n = 51). The fraction of activated platelets circulating in whole blood amounted to 4.3±2.1% in IDDM children, and significantly exceeded the level found in parents (1.3±0.7%, P < 0.002), siblings (1.2±1.0%, P < 0.002), and controls (1.2±0.6%, P < 0.002). Furthermore, an enhanced formation of platelet microparticles was observed in the IDDM group, both in resting platelets and also when platelets were stimulated with thrombin. Significantly decreased total PAI-1 occurred in IDDM children (P < 0.02 versus parents); also slightly lowered active PAI-1 and t-PA antigen were noticed in IDDM subjects compared to other groups, however, the differences were not statistically significant. To assess dissimilarities between the groups of subjects we applied the forward stepwise model of discriminant function analysis, which included platelet flow cytometry parameters. The best separation and the highest discrepancy (expressed as the so called squared Mahalanobis distances, d_M) was revealed between controls and IDDM patients (P ? 0.0001) and between controls and parents (P ? 0.0001). The values of d_M found between IDDM children and their siblings (P < 0.001), as well as parents (P < 0.01), were of much lower significance. The finding that the control group, representing unrelated subjects, remains particularly well separated from the other groups, more or less clustered together, implies the possible involvement of genetic factor(s) which might potentially affect platelet activation and reactivity. In addition, the distinguished distribution of HLA DQAI⁵² and HLA DQBI⁵⁷ genotypes in the groups further validates the suspicion that the altered platelet function and response in diabetes might be associated with some independent genetic factor(s), and is not likely to result from HLA DQAI⁵² and HLA DQBI⁵⁷ impact.