Antithrombotic recombinant antibodies

Coronary syndromes, stroke and other ischaemic arterial diseases are the leading cause of death in the world and will probably remain it at least until 2020. Cardiovascular diseases kill 17 million people each year with an expected increase to 20 million in 2020 and 24 million in 2030. The global impact of recurrence and death during the 6 months following an acute coronary syndrome remains at 8-15% in the present state of medical practice. Acute ischaemic syndromes have a common aetiology that is the formation of a platelet-rich clot at the site of severe coronary stenosis and of eroded atherosclerotic plaques. Therapy consists of medical treatments associating thrombolysis, antiplatelet drugs, and the re-opening of the coronary artery by angioplasty. But these treatments do not prevent morbidity and mortality reaching 15% at 6 months. Finally the treatment of stroke is very limited. There is thus a real clinical need to improve existing treatments and to discover new molecules. Platelet activation is a critical step in ischaemic cardiovascular diseases. This is the reason why antiplatelet drugs are most often prescribed in these cases. Currently, only one recombinant antithrombotic antibody is used in therapy. This is a chimeric Fab, c7E3 or abciximab, which inhibits the final phase of platelet aggregation. Abciximab is prescribed in acute coronary syndromes treated by angioplasty. However, treatment by abciximab can induce severe complications, principally, hemorrages and thrombopenia. Other platelet receptors involved in the earlier steps of platelet activation, such as the phases of contact with and of activation by the subendothelium matrix, have been identified as potential targets for the development of antithrombotic antibodies and are described in this revue.     

Effect of thrombolysis on myocardial injury: recombinant tissue plasminogen activator vs. alfimeprase

Plasmin-dependent thrombolytic agents are potentially prothrombotic and proinflammatory. Alfimeprase, a zinc-containing metalloproteinase, degrades fibrin directly and achieves thrombolysis independent of plasmin formation. This study examines the hypothesis that thrombolysis in the absence of plasmin generation results in improved myocardial salvage on reperfusion. The thrombolytic effects of recombinant tissue plasminogen activator [rt-PA; 0.022 mg/kg, 1/10 of which was administered as a loading dose; the rest (9/10) was infused over 60 min by intracoronary (ic) administration] or alfimeprase (0.5 mg/kg over 1 min ic) were evaluated in a canine model of arterial thrombosis involving electrolytic injury of the left circumflex (LCX) coronary artery. Both agents induced thrombolysis, with onset of reperfusion being more rapid after alfimeprase compared with rt-PA (1.5 +/- 0.6 vs. 10.1 +/- 2.1 min). In the absence of adjunctive therapy, time to reocclusion after alfimeprase was 3.2 +/- 0.5 min compared with 77.5 +/- 31.9 min with rt-PA. The glycoprotein IIb/IIIa platelet receptor antagonist CRL-42796 prolonged reperfusion time after thrombolysis with alfimeprase or rt-PA. The effect of each lytic agent on myocardial infarct size was examined in a separate group of dogs subjected to 60 min of LCX coronary artery ligation and 4 h of reperfusion. Myocardial infarct size, expressed as percentage of the risk region, was larger (32.16 +/- 3.95%) after rt-PA compared with alfimeprase (19.85 +/- 3.61%) or that of the saline control group (18.46 +/- 3.34%). rt-PA in contrast to alfimeprase, a direct-acting fibrinolytic agent, is associated with an increase in myocyte reperfusion injury.     

Prospective evaluation of eligibility for thrombolytic therapy in acute myocardial infarction.

OBJECTIVES--To determine the proportion of patients presenting with acute myocardial infarction who are eligible for thrombolytic therapy. DESIGN--Cohort follow up study. SETTING--The four coronary care units in Auckland, New Zealand. SUBJECTS--All 3014 patients presenting to the units with suspected myocardial infarction in 1993. MAIN OUTCOME MEASURES--Eligibility for reperfusion with thrombolytic therapy (presentation within 12 hours of the onset of ischaemic chest pain with ST elevation > or = 2 mm in leads V1-V3, ST elevation > or = 1 mm in any other two contiguous leads, or new left bundle branch block); proportions of (a) patients eligible for reperfusion and (b) patients with contraindications to thrombolysis; death (including causes); definite myocardial infarction. RESULTS--948 patients had definite myocardial infarction, 124 probable myocardial infarction, and nine ST elevation but no infarction; 1274 patients had unstable angina and 659 chest pain of other causes. Of patients with definite or probable myocardial infarction, 576 (53.3%) were eligible for reperfusion, 39 had definite contraindications to thrombolysis (risk of bleeding). Hence 49.7% of patients (537/1081) were eligible for thrombolysis and 43.5% (470) received this treatment. Hospital mortality among patients eligible for reperfusion was 11.7% (55/470 cases) among those who received thrombolysis and 17.0% (18/106) among those who did not. CONCLUSIONS--On current criteria about half of patients admitted to coronary care units with definite or probable myocardial infarction are eligible for thrombolytic therapy. Few eligible patients have definite contraindications to thrombolytic therapy. Mortality for all community admissions for myocardial infarction remains high.     

Cloning, purification and biochemical characterization of a thrombus-ditargeting thrombolytic agent, comprised of annexin B1, ScuPA-32K and fibrin-adherent peptide

The development of thrombolytic agent could provide invaluable progress for antithrombotic therapy. In this paper, we reported the cloning, purification and biochemical characterization of AnxB1ScuPAFap, a thrombus-ditargeting chimera composed of annexin B1, low molecular single-chain urokinase (ScuPA-32K) and fibrin-adherent peptide (dodecapeptide, Fap). In vitro test showed that, the chimera was a thrombolytic agent with anticoagulant activity and thrombus-ditargeting with the activated-platelet membrane binding and fibrin clot binding activity. Compared to urokinase, the chimera had less reperfusion time, higher reperfusion ratio, and less bleeding effects on coronary thrombolysis by clot lysis assay in dogs. Thus, the chimera appeared to be suitable for thrombolytic therapy of thrombus diseases.     

Risks and Benefits of Early Antithrombotic Therapy after Thrombolytic Treatment in Patients with Acute Stroke

Background

Current guidelines recommend withholding antithrombotic therapy (ATT) for at least 24 h in patients with acute ischemic stroke treated with thrombolytic therapy. Herein, we report a retrospective analysis of a single-centre experience on the safety and efficacy of antithrombotic therapy (ATT) started before or after 24 h of intravenous thrombolysis in a cohort of acute ischemic stroke patients.

Methods

A total of 139 patients (Rapid ATT group) received antithrombotic therapy before 24 h of thrombolysis, and 33 patients (Standard ATT group) after 24 h. The brain parenchyma and vessel status were assessed using simple CT scan on admission, multimodal CT scan at the end of thrombolysis, and angio-CT/MRI scan at day 3. Functional outcome was scored using the modified Rankin Scale (mRS) at day 90.

Results

The two ATT groups had similar demographics, stroke subtypes, baseline NIHSS, thrombolytic strategies, vessel-patency rates at the end of thrombolysis, and incidence of bleeding complications at follow up. At day 3, the Rapid ATT group had a non-significant improved vessel-patency rate than the Standard ATT group. At day 90, a greater proportion of patients in the rapid ATT group had shifted down the mRS, and had improved in the NIHSS score.

Conclusions

ATT initiated before 24 h of intravenous thrombolytic therapy in acute stroke patients disclosed no safety concerns compared with a conventional antithrombotic therapy delay of 24 h and showed better functional outcome at follow up. The value of early initiation of ATT after thrombolysis deserves further assessment in randomized controlled trials.     

Microbial fibrinolytic enzymes: an overview of source, production, properties, and thrombolytic activity in vivo

Accumulation of fibrin in the blood vessels usually results in thrombosis, leading to myocardial infarction and other cardiovascular diseases. For thrombolytic therapy, microbial fibrinolytic enzymes have now attracted much more attention than typical thrombolytic agents because of the expensive prices and the undesirable side effects of the latter. The fibrinolytic enzymes were successively discovered from different microorganisms, the most important among which is the genus Bacillus from traditional fermented foods. The physiochemical properties of these enzymes have been characterized, and their effectiveness in thrombolysis in vivo has been further identified. Therefore, microbial fibrinolytic enzymes, especially those from food-grade microorganisms, have the potential to be developed as functional food additives and drugs to prevent or cure thrombosis and other related diseases.Dr. Yong Peng was invited by the editor-in-chief, Professor Dr. A. Steinbüchel, to write this review     

蜱源抗凝血因子研究进展

蜱是一种人畜共患体表寄生虫,通过叮咬宿主和吸血,将病原体传播给宿主,引发多种疾病。凝血反应是人和动物的重要生理过程,是生理性止血的重要环节。蜱叮咬和吸食宿主血液周期长,在吸血过程中分泌多种抗凝物质,抑制凝血反应,可帮助蜱长时间保持吸血状态。目前,已知的蜱源抗凝物质依据其功能主要包括蛋白酶抑制剂、纤维蛋白(原)溶解剂、血小板聚集抑制剂和血管活性蛋白4大类。这些抗凝血物质可分别作用于凝血级联反应中内源性通路、外源性通路、共同通路中的关键步骤,以及促进纤蛋白溶解和抑制血小板激活,从而抑制宿主血管中的凝血反应。蛋白酶抑制剂主要通过抑制凝血级联反应共同通路中凝血酶和Xa因子活性;纤维蛋白(原)溶解剂引起纤维蛋白原的水解并延迟纤维蛋白凝块的形成;血小板聚集抑制剂通过降解血小板聚集激动剂,并结合血栓素A2(thromboxane A2, TXA2)和血小板上的αIIbβ3整合素抑制血小板聚集;血管活性蛋白抑制宿主血管收缩以及伤口愈合和血管生成。此外,还有一些蜱分泌的其他蛋白分子可通过不同的通路来实现抗凝血作用。本文对迄今为止各类蜱中发现的具有抗凝血活性的蛋白和小分子及其抗凝血作用机制进行总结阐述,将...     

Targets of antithrombotic drugs

New antithrombotic agents are being developed not only to improve efficacy, but also to increase safety in comparison with widely used conventional agents such as the oral anticoagulants. New anticoagulant, antiplatelet, and profibrinolytic compounds are currently under study in drug development programs, and most of those in phase II or III of development are derived from the observation of natural phenomena and merely mimic processes developed by mammalians, including humans, to avoid thrombosis, or by blood-sucking insects or animals to prevent coagulation of the blood their are feeding on. By contrast, drug candidates identified by means of rigorous research and designed to target new pathways and achieve direct and specific inhibition of factors that are presumed to play an important role in thrombogenesis have generally failed to show any benefit and sometimes even induce deleterious effects. The clinical development of new drugs, even those mimicking natural phenomena, improves our knowledge of the pathogenesis of thrombosis and sheds light, retrospectively, on previous conceptual errors. The improvement in our basic knowledge and the development of new types of drugs suggest that, in contrast to the current antithrombotic compounds that are used in a broad range of clinical settings, use of new drugs should be restricted to specific situations in which their mechanisms of action are predicted to deliver the highest medical benefit. A major obstacle resides in the fact that current drug development programs are still required to comply with long obsolete guidelines based on the characteristics of first-generation antithrombotic agents, and that do not take into account the specific mechanisms of action of new drugs. This situation should change, however, and new antithrombotic drugs should soon be able to benefit from adapted development programs that will make it possible to determine their optimal risk-benefit ratio.     

Zebrafish model of photochemical thrombosis for translational research and thrombolytic screening in vivo

Acute thromboembolic diseases remain the major global cause of death or disability. Although an array of thrombolytic and antithrombotic drugs has been approved to treat or prevent thromboembolic diseases, many more drugs that target specific clotting mechanisms are under development. Here a novel zebrafish model of photochemical thrombosis is reported and its prospective application for the screening and preclinical testing of thrombolytic agents in vivo is demonstrated. Through photochemical excitation, a thrombus was induced to form at a selected section of the dorsal aorta of larval zebrafish, which had been injected with photosensitizers. Such photochemical thrombosis can be consistently controlled to occlude partially or completely the targeted blood vessel. Detailed mechanistic tests indicate that the zebrafish model of photochemical thrombosis exhibits essential features of classical coagulation and a thrombolytic pathway. For demonstration, tissue plasminogen activator (tPA), a clinically feasible thrombolytic agent, was shown to effectively dissolve photochemically induced blood clots. In light of the numerous unique advantages of zebrafish as a model organism, our approach is expected to benefit not only the development of novel thrombolytic and antithrombotic strategies but also the fundamental or translational research targeting hereditary thrombotic or coagulation disorders.

     

Debate: Should the elderly receive thrombolytic therapy, or primary angioplasty, for acute myocardial infarction? The case for primary angioplasty

As the population ages the number of elderly patients presenting with acute myocardial infarction (AMI) will continue to increase. There has been no head-to-head trial of thrombolytic therapy versus primary percutaneous coronary intervention (PCI) in this patient cohort, but there is evidence that favors primary PCI. Most elderly patients are candidates for primary PCI, but many have contraindications to thrombolytic therapy. Hemorrhagic complications are more common in the elderly, and many of these patients present with conditions in which thrombolytic agents have decreased efficacy, such as heart failure or prior bypass surgery. PCI can also obviate the need for further risk stratification in most patients.     

Protein engineering of novel plasminogen activators with increased thrombolytic potency in rabbits relative to activase.

Human tissue-type plasminogen activator (t-PA) is a glycoprotein used currently in thrombolytic therapy for patients with acute myocardial infarction. Due to its rapid rate of clearance from the circulation, continuous intravenous administration of approximately 100 mg over 3 h is recommended. We have previously characterized novel thrombolytic variant forms of t-PA which offer the potential of administration by bolus injection and reduced dosage due to their slower rates of clearance, relative to t-PA. This study was undertaken to quantitatively compare the pharmacokinetics, thrombolytic activity, and hemostatic effects of two of these variant forms, called delta FE1X and delta FE3X plasminogen activator (PA), with commercially available recombinant t-PA (Activase). These evaluations were performed in rabbits after bolus intravenous injection of the proteins. Following injection of 0.25 mg of protein/kg of body weight, the rates of clearance for delta FE3X and delta FE1X PA antigen were decreased approximately 9- and 18-fold, respectively, relative to Activase. Plasma plasminogen activator activity was also measured and the rates of clearance of delta FE3X and delta FE1X PA activity were similarly decreased by approximately 9- and 22-fold, respectively, relative to Activase. To quantitate thrombolytic activity we used the rabbit jugular vein thrombosis model and demonstrated that approximately 50% thrombolysis was achieved with delta FE1X and delta FE3X PA at approximately an 8.6- and 3-fold lower dose than Activase, respectively. No major differences in fibrinogen and alpha 2-antiplasmin depletion were observed among the agents at doses required to produce 50% thrombolysis, indicating similarities in fibrin specificities among these agents. These results demonstrate a reciprocal relationship between thrombolysis and rate of clearance for these thrombolytic proteins. The 8.6-fold increase in potency of delta FE1X PA relative to Activase supports the future clinical testing of this novel engineered protein as a thrombolytic agent.     

Coronary revascularization after thrombolytic therapy for myocardial infarction: what caseloads could Canadian centres face?

A simple model was developed to project the potential effect of intravenous thrombolytic therapy on the caseloads of revascularization early after acute myocardial infarction. Published data were used to estimate the proportion of infarct patients eligible for thrombolytic treatment and their subsequent rates of percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass surgery (CABS) within 2 weeks and up to 6 to 12 weeks after treatment. Toronto regional caseload data were obtained from registries and hospital discharge records. Our primary projections, based only on coronary angiography for evidence of spontaneous or exercise-induced ischemia, suggest a 165% increase in the post-thrombolysis use of PTCA within 2 weeks of infarction and even greater increases 6 to 12 weeks after infarction. Adding in selective use of salvage PTCA for some patients with persisting pain despite thrombolysis increases the overall PTCA caseload within 2 weeks by 242%. Data on the current caseload of post-thrombolysis CABS are unavailable. However, our projected caseload for the 30% of infarct patients treated with thrombolytic drugs equals or exceeds the current number of CABS procedures performed on all infarct patients within a month of the event. All these projections are conservative, in that they consider neither procedures 3 to 12 months after infarction nor restenosis after PTCA. This analysis illustrates that current approaches to revascularization after thrombolytic therapy could have a substantial effect on PTCA and CABS caseloads. Further studies with improved caseload data are needed to validate these preliminary projections.     

静脉溶栓时机对急性ST段抬高型心肌梗死患者溶栓效果及主要不良心脏事件发生率的影响

目的:探讨静脉溶栓时机对急性ST段抬高型心肌梗死患者溶栓效果及主要不良心脏事件发生率的影响。方法:将2016年1月至2017年12月我院接诊的314例急性ST段抬高型心肌梗死患者纳入本研究,按照溶栓治疗时间不同分为A组(发病至溶栓时间6 h)172例、B组(发病至溶栓时间为6～12 h)102例和C组(发病至溶栓时间12 h)40例,比较三组患者溶栓效果、溶栓后ST段回落情况以及住院期间主要不良心脏事件发生情况。结果:A组患者梗死冠脉溶通率、溶栓后ST段回落幅度高于B组和C组,且B组高于C组,差异均有统计学意义(P0.05)。A组患者治疗后ST段回落最大幅度所需时间、住院期间主要不良心脏事件总发生率低于B组和C组,且B组低于C组,差异均有统计学意义(P0.05)。结论:急性ST段抬高型心肌梗死患者发病后6 h内静脉溶栓治疗梗死冠脉溶通率更高、ST段回落效果更好,可降低住院期间主要不良心脏事件发生风险。     

Debate: Should the elderly receive thrombolytic therapy or primary angioplasty?

Thrombolysis and primary angioplasty are both recommended reperfusion strategies for elderly patients presenting with myocardial infarction (MI). Primary angioplasty is most beneficial in high-risk patients. While the elderly have a high absolute risk of dying or developing complications after MI, they also have an increased risk of intracranial haemorrhage if they are given thrombolytic therapy. It could therefore be reasonably argued that primary angioplasty is the reperfusion strategy of choice in the elderly. However, primary angioplasty has not been shown to have a greater relative benefit than thrombolytic therapy in the elderly. Recent data from the Fibrinolytic Therapy Trialists' (FTT) Collaborative Group show that thrombolytic therapy significantly reduces mortality compared with control treatment in patients over 75 years of age presenting within 12 h of symptom onset, with ST-segment elevation or bundle branch block. Future advances in adjunctive therapies may improve myocyte perfusion and hence the outcomes achieved by both invasive and noninvasive reperfusion strategies. Better thrombolytic regimens incorporating adjunctive agents such as bivalirudin may reduce the risk of intracranial haemorrhage. Few hospitals can provide a 24-h primary angioplasty service with door-to-balloon times consistently less than 90 min, and thrombolytic therapy is therefore a far more practical option in most instances.     

Evidence-based management of acute myocardial infarction in the elderly--current perspectives

Cardiovascular disease accounts for significant morbidity and mortality in the elderly. Despite several, large cardiovascular clinical trials, data to guide therapy in this growing population subset are relatively limited. This review focuses on treatment approaches and recommendations for the management of elderly patients with acute myocardial infarction (MI) obtained from subgroup analyses from major clinical trials.Treatment options for acute MI in the elderly have changed dramatically since the 1990s. Reperfusion therapy by primary percutaneous coronary intervention has superseded the use of thrombolytic therapy for the treatment of acute ST-elevation myocardial infarction (STEMI). Clinical trial data have demonstrated that even transferring patients to facilities that have primary angioplasty capabilities is better than thrombolytic therapy, if the anticipated transfer time is of acceptable duration. Additionally, adjunctive use of the intravenous glycoprotein (GP) receptor antagonist, abciximab, during primary angioplasty affords a reduction in the composite primary end point of death, reinfarction, and target vessel revascularization, with much of the benefit derived from the latter. Thrombolytic therapy, barring any contraindication, must be used when mechanical revascularization is not available; however, the risk for complications in the elderly is higher, especially for those 75 years and older. Studies investigating the use of thrombolytics plus GP receptor antagonists with and without percutaneous coronary intervention show questionable benefit in the elderly.     

Position and developmental trends in fibrinolytic therapy

Increasing insight into the mechanism of fibrinolysis and particularly into the formation and release of plasminogen activator has led to more effective thrombolytic therapy. The understanding of the mechanism of thrombolysis has provided the possibility to improve the therapeutic effects of the fibrinolytic agents streptokinase and urokinase. Further advances in thrombolytic therapy are expected by the use of the plasminogen activator from tissue endothelium and pro-urokinase. Acylation of fibrinolytic enzymes will lead to beneficial effects (depot effect, protection from intrinsic inhibitors). Due to the extensive research into substances with fibrinolytic and thrombolytic effects a new generation of activators of fibrinolysis is expected that interfere with the biosynthesis and release of plasminogen activator of the vessel wall and that are suited for treatment of hypofibrinolytic states.     

A monoclonal antibody reacting with platelets for monitoring thrombolysis

Thrombus immunoscintigraphy with radiolabeled monoclonal antibodies are presently undergoing intense clinical evaluations. Reports on clinical trials of radiolabeled antifibrins are very encouraging and results of antiplatelet antibody evaluations are forthcoming. Animal studies with antiplatelet antibodies indicate that a diagnosis can be made within the critical “lytic window” of 4–6 h, and thus the imaging procedure may be used as an adjunct to thrombolytic therapy, i.e. screening of patients.We now report on a potentially new application of monoclonal antibodies, immunoimaging for monitoring thrombolysis. In vitro studies were performed with “standardized clots” incubated with ^99mTc 50H.19 and re-incubated with streptokinase (SK), urokinase (UK) or recombinant tissue plasminogen activator (rt-PA). The decrease in clot-bound ^99mTc 50H.19 activity after SK, UK or rt-PA incubation was proportional to the decrease in clot weight (r = 0.90–0.98). The direct effects of these thrombolytic agents on the labeled antibody and the possible interference of aspirin, warfarin and heparin in thrombus immunoimaging were also investigated. Aspirin, heparin and warfarin did not interfere with clot-binding of ^99mTc 50H.19. Thrombolytic agents did not affect the stability of the radiolabel or immunoreactivity of 50H.19. These results indicate that ^99mTc 50H.19 is a promising agent that may enable monitoring thrombolysis in addition to thrombus immunoimaging.     

Antithrombotic therapy

Coronary heart disease is the leading cause of death in the US and the industrialized world. Ever since DeWood in 1980 demonstrated that a thrombus was the primary event leading to acute myocardial infarction and that they may subsequently lyse, the mainstay of therapy for the past 25 years has been antithrombotic therapy aimed at coronary thrombosis. There have been numerous advances in the treatment of acute coronary syndrome with antiplatelet, antithrombotic, and fibrinolytic agents that have significantly reduced morbidity and mortality. The role of various pharmaceutical agents in the different phases of acute coronary syndrome is a complex and ever changing field.7.     

Ultrasound enhancement of thrombolytic therapy: observations and mechanisms

Fibrinolytic therapy is a proven approach for achieving reperfusion of occluded coronary arteries during myocardial infarction, resulting in reduced mortality and preservation of ventricular function. The amount of myocardial muscle loss is proportional to the duration of ischemia. Bleeding complications are not infrequent. Adjuvant therapy by ultrasound might enhance the rate of fibrinolysis and reduce the concentrations of lytic agents required to achieve an equivalent degree of clot lysis. Noninvasive ultrasound at low intensities and high frequencies, parameters that potentially could be applied and tolerated in vivo, have been proven to significantly accelerate the rate of fibrinolysis in both in vitro and in vivo models, in pure fibrin as well as whole blood clots. Such enhancement is not drug-specific. These effects were achieved by nonthermal mechanism. Ultrasound exposure did not cause mechanical fragmentation of the clot, did not alter the size of plasmatic derivates and degradation products. Ultrasound caused increased flow rate through thrombi, probably by cavitation-induced changes in fibrin ultrastructure; disaggregation of uncrosslinked fibrin fibers into smaller fibers has been shown. This resulted in increased transport of the lytic agent into the clot, alteration of binding affinity and increased maximum binding. Presence of echo-contrast agent induced further acceleration of thrombolysis by ultrasound.     

Interference with the Host Haemostatic System by Schistosomes

Schistosomes, parasitic flatworms that cause the tropical disease schistosomiasis, are still a threat. They are responsible for 200 million infections worldwide and an estimated 280,000 deaths annually in sub-Saharan Africa alone. The adult parasites reside as pairs in the mesenteric or perivesicular veins of their human host, where they can survive for up to 30 years. The parasite is a potential activator of blood coagulation according to Virchow''s triad, because it is expected to alter blood flow and endothelial function, leading to hypercoagulability. In contrast, hepatosplenic schistosomiasis patients are in a hypocoagulable and hyperfibrinolytic state, indicating that schistosomes interfere with the haemostatic system of their host. In this review, the interactions of schistosomes with primary haemostasis, secondary haemostasis, fibrinolysis, and the vascular tone will be discussed to provide insight into the reduction in coagulation observed in schistosomiasis patients.Interference with the haemostatic system by pathogens is a common mechanism and has been described for other parasitic worms, bacteria, and fungi as a mechanism to support survival and spread or enhance virulence. Insight into the mechanisms used by schistosomes to interfere with the haemostatic system will provide important insight into the maintenance of the parasitic life cycle within the host. This knowledge may reveal new potential anti-schistosome drug and vaccine targets. In addition, some of the survival mechanisms employed by schistosomes might be used by other pathogens, and therefore, these mechanisms that interfere with host haemostasis might be a broad target for drug development against blood-dwelling pathogens. Also, schistosome antithrombotic or thrombolytic molecules could form potential new drugs in the treatment of haemostatic disorders.