Hemostasis in patients with rheumatoid arthritis

AIM: To study hemostasis with reference to rheumatoid arthritis (RA) activity, extraarticular manifestations and vascular damage. MATERIAL AND METHODS: We studied hemostasis in 104 RA patients. The following parameters were tested: partial thromboplastin time activation (PTTA), fibrinolytic activity (FA), prothrombin index, lupus anticoagulant (LA), mean platelet volume (PV), antibodies against cardiolipin (aCL) and antibodies against beta2-glycoprotein 1 (alphabeta2-GP1). The disease activity index was estimated by DAS-28 including tender and swelling joints count, erythrocyte sedimentation rate and disease global activity rated by the patient. RESULTS: We found out an increased number of platelets in 54.4%, prolongation of FA and PTTA in 72.5 and 12.5% patients. The rest blood coagulation tests were normal in most the examinees. The LA antibodies were absent, while aCL and alphabeta2-GP1 antibodies were identified in 10.6 and 14.4%, respectively. The number of platelets increased while hemoglobin decreased in relation to higher disease activity and PV was significantly lower in patients with extraarticular manifestations. No significant influence of vascular damage or comorbidities on hemostasis was found. CONCLUSION: No relation was established between coagulation factors and the disease activity except for increased number of platelets in patients with higher activity and lower PV in patients with extraarticular manifestations. However, patients with aCL and alphabeta2-GP1 need constant monitoring because of the risk to develop thrombosis.     

Platelet matching for alloimmunized patients

<正>Platelets play an essential role in blood coagulation,hemostasis and maintenance of vascular integrity. Platelets are utilized primarily to prevent or treat bleeding in thrombocytopenic patients and patients with impaired platelet production in the bone marrow and/or with dysfunctional platelets. In current practice,platelet transfusion begins with randomly selected platelet products:either pooled platelets prepared from whole blood derived platelets; or single donor platelets prepared by apheresis procedures.     

急性颅脑创伤患者血浆FⅦ活性变化及其与凝血功能相关性

[目的]探讨急性颅脑创伤患者血浆凝血因子Ⅶ(FⅦ)活性变化及其与凝血功能的相关性.[方法]选取2014年3月至2016年3月本院收治的急性颅脑创伤患者92例作为观察组,同时选择同期在本院体检健康的92例健康志愿者作为对照组,检测两组血浆FⅦ活性值,并检测活化部分凝血活酶时间(AFFF)、血小板(PLT)、D-二聚体、纤维蛋白原(FIB)、血红蛋白(Hb)、血乳酸(Lac)等相关凝血指标,计算国际标准化比值(INR),并检测颅内压(ICP).比较观察组和对照组血浆FⅦ活性及其与凝血功能指标的相关性.[结果]观察组血浆FⅦ活性值为(91.45±32.10)%,对照组为(97.20±16.03)%,两组比较差异无统计学意义(t=-1.537,P>0.05).血浆FⅦ活性低患者INR、APTT、Lac显著高于血浆FⅦ活性高的患者,血浆FIB水平显著低于血浆FⅦ活性高者,差异均具有统计学意义(均P<0.05).观察组伴凝血功能异常患者共计35例,其血浆FⅦ活性为(86.70±28.84)%,观察组不伴凝血功能异常患者57例,其血浆FⅦ活性为(97.83±30.16)%,两组比较差异具有统计学意义(t=-2.176,P<0.05).[结论]急性颅脑创伤患者血浆FⅦ活性与凝血功能有一定联系,凝血功能异常患者血浆FⅦ活性有所降低,值得临床进一步研究.     

Clinico-pathogenetic variants of DIC syndrome in patients with severe craniocerebral trauma]

Detection of clinical and pathogenetic variants of the DIC syndrome for development of its differentiated therapy in multiple-modality treatment of severe craniocerebral injury was the purpose of this study. A total of 170 patients with grave craniocerebral injury were examined. The hemostasis system was studied by the following methods: analysis of platelet hemostasis, general coagulation tests, fibrinolysis evaluation, detection of physiological anticoagulants and markers of intravascular blood coagulation and fibrinolysis. Based on the clinical (intra- and extracranial) symptoms and results of studies of the hemostasis system, 3 clinical pathogenetic variants of the DIC syndrome were distinguished, which should be borne in mine when treating patients with severe craniocerebral injury developing the DIC syndrome.     

Effect of the radiographic contrast material iopamidol on hemostasis: an observational study in thirty cardiac patients

Background: In vitro studies have shown that nonionic radiographic contrast material may induce the generation of thrombin in blood, whereas ionic contrast agents, such as iohexol, do not. However, knowledge of the effects of contrast material on coagulation and fibrinolytic systems in vivo is limited.Objective: This study was designed to assess the effects of the nonionic radiographic contrast material iopamidol on hemostasis in patients undergoing coronary angiography or cardiac catheterization.Methods: Patients aged ≥18 years with chest pain and/or dyspnea who underwent coronary angiography or cardiac catheterization with intra-arterial contrast material were assessed for hemostasis. Blood samples were drawn before and 3 minutes after injection of iopamidol. Complete blood count and coagulation profile (bleeding time, clotting time, clot retraction time, euglobulin lysis time [ELT], prothrombin and partial thromboplastin times, coagulation factor I [CFI] level, and platelet factor 3 [PF-3] availability) were assessed. The natural coagulation inhibitors protein C, protein S, and antithrombin III (AT-III) also were measured.Results: Thirty patients (7 males, 23 females; mean [SD] age, 51.3 [20.2] years; range, 17-79 years) were included in this single-center study. All hematologic variables (hemoglobin, white blood cell count, and platelet count) decreased significantly (P<0.001, P<0.001, and P<0.05, respectively) after administration of iopamidol but remained within normal limits. Mean levels of protein C, protein S, and AT-III did not change significantly after administration of iopamidol. Bleeding time was not changed significantly, and PF-3 availability was prolonged in both groups, but the changes were not statistically significant.Conclusions: In this study population, although hemostasis remained grossly intact after injection of nonionic contrast material, the coagulation system may have been affected by the accelerated consumption of CFI and platelets. The affected variables were platelets, clot retraction time, ELT, and natural coagulation inhibitors (protein C, protein S, and AT-III). Although the natural coagulation inhibitors remained within the normal range, the correlations were found significant. These changes in hemostasis affected the vascular phase. If the vascular compartment, especially the endothelium, remained intact, the infusion of nonionic agents in low concentrations might be safe for angiography and other procedures; however, more studies are needed.     

TRANSFUSION PRACTICE: Thrombin generation in trauma patients

BACKGROUND: Trauma patients are at risk of developing an acute coagulopathy of trauma (ACT) related to tissue injury, shock, and hemodilution. ACT is incompletely understood, but is similar to disseminated intravascular coagulation (DIC) and is associated with poor outcome. STUDY DESIGN AND METHODS: Thrombin generation assays were used to evaluate plasma hemostasis in 42 trauma patients, 25 normal subjects, and 45 patients on warfarin and in laboratory‐prepared factor reduced plasma. RESULTS: Prolonged prothrombin time (PT), more than 18 seconds, or an international normalized ratio of greater than 1.5 was present in 15 trauma patients indicating possible ACT. Native thrombin generation (no activator added, contact activation blocked) showed that Trauma with ACT patients had lag times 68% shorter and peak thrombin generation threefold higher than normal patients indicating the presence of circulating procoagulants capable of initiating coagulation systemically. Trauma patients had lower platelet counts and fibrinogen and Factor (F)II levels putting them at increased risk of bleeding. In laboratory‐prepared isolated factor‐reduced samples and in patients with vitamin K–dependent factor deficiency due to warfarin, thrombin generation decreased in direct proportion to FII levels. In contrast, in diluted plasma and in trauma patients with reduced factor levels, thrombin generation was increased and associated with slower inhibition of thrombin generation (prolonged termination time) and decreased antithrombin levels (43% of normal in Trauma with ACT). CONCLUSIONS: Thrombin generation studies indicate that Trauma with ACT patients show dysregulated hemostasis characterized by excessive non–wound‐related thrombin generation due to a combination of circulating procoagulants capable of activating coagulation systemically and reduced inhibitor levels allowing systemic thrombin generation to continue once started.     

Hemostasis during the early stages of trauma: comparison with disseminated intravascular coagulation

Introduction

We tested two hypotheses that disseminated intravascular coagulation (DIC) and acute coagulopathy of trauma-shock (ACOTS) in the early phase of trauma are similar disease entities and that the DIC score on admission can be used to predict the prognosis of patients with coagulopathy of trauma.

Methods

We conducted a retrospective study of 562 trauma patients, including 338 patients whose data were obtained immediately after admission to the emergency department. We collected serial data for the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) DIC scoring system, and ACOTS was defined as a prothrombin-time ratio of >1.2.

Results

The higher levels of fibrin/fibrinogen degradation products (FDP) and D-dimer and greater FDP/D-dimer ratios in the DIC patients suggested DIC with the fibrinolytic phenotype. The DIC patients with the fibrinolytic phenotype exhibited persistently lower platelet counts and fibrinogen levels, increased prothrombin time ratios, higher FDP and D-dimer levels, and lower antithrombin levels compared with the non-DIC patients on arrival to the emergency department and during the early stage of trauma. Almost all ACOTS patients met the criteria for a diagnosis of DIC; therefore, the same changes were observed in the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels as noted in the DIC patients. The JAAM DIC score obtained immediately after arrival to the emergency department was an independent predictor of massive transfusion and death due to trauma and correlated with the amount of blood transfused.

Conclusions

Patients who develop DIC with the fibrinolytic phenotype during the early stage of trauma exhibit consumption coagulopathy associated with increased fibrin(ogen)olysis and lower levels of antithrombin. The same is true in patients with ACOTS. The JAAM DIC score can be used to predict the prognosis of patients with coagulopathy of trauma.     

The role of the system of hemostasis in the development of vascular lesions in diabetes mellitus

The examination of 179 patients with diabetes mellitus has shown that the mechanisms of vascular wall damage and changes in the system of hemostasis are different in type I and II diabetes mellitus. In type I diabetes mellitus vascular wall damages are associated with carbohydrate metabolic derangements, changes in the platelet link of hemostasis and blood coagulation system. In type II diabetes mellitus vascular wall damages are associated with lipid metabolic derangements and changes in the erythrocytic link of hemostasis.     

Vessel-platelet and coagulation components of hemostasis in patients with chronic tubulointerstitial nephritis

AIM: To study vessel-platelet and coagulation parts of hemostasis system, their correlation with clinical characteristics and activity of chronic tubulointerstitial nephritis (CTIN). MATERIAL AND METHODS: 128 patients 15 to 65 years of age with CTIN were included in the study. The diagnosis was confirmed morphologically in 42 patients. The patients were divided into subgroups by activity of the disease at the moment of examination (active and inactive CTIN), by arterial pressure (normotensive and hypertensive patients), intact and low renal function, by duration of the disease (up to 60 months, 61-120 months, more than 120 months). Complex study of hemostasis system was carried out by a set of standard techniques. RESULTS: CTIN runs with activation of vessel-platelet hemostasis characterised by a decrease in platelets count (p < 0.001), persistent platelet hyperaggregation and activation (p < 0.001). Severity of platelet aggregative activity is related with endothelial affection manifesting with high level and activity of Willebrand factor (p < 0.001). The most typical changes of coagulation in CTIN were acceleration of activated partial thrombin time (p < 0.001) closely related with activation of thrombocytic hemostasis and background thrombinemia the presence of which was confirmed by elevated blood level of soluble fibrin-monomeric complexes (SFMC). THE CONCLUSION: Hypercoagulation, suppression of fibrinolytic plasma activity, increase of SFMC and fibrinogen levels in the blood as well as detected enhancement of platelet aggregation testify to a latent course of renal intravascular blood coagulation in CTIN. Hemostasis system activation in CTIN helps assessment of the disease activity.     

Extracellular protein disulfide isomerase regulates feedback activation of platelet thrombin generation via modulation of coagulation factor binding

Summary. Background: Protein disulfide isomerase (PDI) controls platelet integrin function, tissue‐factor (TF) activation, and concentrates at fibrin and thrombus formation sites of vascular injury. Objective: To investigate the involvement of surface thiol isomerases and especially PDI, in thrombin‐mediated thrombin amplification on human platelets. Methods/results: Using a newly developed thrombin‐dependent platelet thrombin generation assay, we observed that the feedback activation of thrombin generation on the platelet surface does not depend on TF, as anti‐TF antibodies inhibiting TF‐induced thrombin formation in platelet‐depleted plasma had no effect compared with vehicle‐treated controls. Feedback activation of thrombin generation in the presence of platelets was significantly diminished by membrane impermeant thiol blockers or by the thiol isomerase‐inhibitors bacitracin and anti‐PDI antibody RL90, respectively. Platelet thrombin formation depends on binding of coagulation factors to the platelet surface. Therefore, involvement of thiol isomerases in this binding was investigated. As shown by confocal microscopy and flow cytometry, thrombin‐stimulated platelets exhibited increased surface‐associated PDI as well as extracellular disulfide reductase activity compared with unstimulated platelets. Flow cytometric analysis revealed that membrane impermeant thiol blockers or PDI inhibitors, which had been added after platelet stimulation and after phosphatidylserine exposure to exclude their influence on primary platelet activation, significantly inhibited binding of all coagulation factors to thrombin‐stimulated platelets. Conclusions: Thus, surface‐associated PDI is an important regulator of coagulation factor ligation to thrombin‐stimulated platelets and of subsequent feedback activation of platelet thrombin generation. Cell surface thiol isomerases might be therefore powerful targets to control hemostasis and thrombosis.     

Lactadherin blocks thrombosis and hemostasis in vivo: correlation with platelet phosphatidylserine exposure

Summary.  Background:  Platelet membrane phosphatidylserine (PS) is considered to be essential for hemostasis and thrombosis, but the in vivo topography of platelet PS has not been characterized. We hypothesized that platelet PS exposure would be identified on adherent platelets at the site of vascular injury and that blockade of PS would impede hemostasis and thrombosis. Objective:  To localize and estimate the extent of platelet PS exposure and evaluate the impact of PS blockade in vivo . Methods:  Lactadherin, a PS-binding milk protein, was utilized together with annexin  V to detect both partial and complete membrane PS exposure on platelets in a mouse model of thrombosis and to evaluate the functional need for PS. Preliminary experiments were performed with synthetic membranes and with purified platelets. Results:  The number of lactadherin-binding sites on synthetic membranes was proportional to PS content, whereas annexin  V required a threshold of 2.5–8% PS. Approximately 95% of thrombin-stimulated platelets exposed PS, but the quantity was below the threshold for annexin  V binding at physiologic Ca²⁺ concentrations. In mice, most adherent and aggregated platelets on the walls of ferric chloride-treated mesenteric veins exposed low levels of PS, rather than having complete exposure. In mice, blockade of PS with lactadherin inhibited platelet prothrombinase and factor Xase activity, and prolonged tail bleeding time and the time to carotid artery thrombosis. Conclusions:   In vivo PS exposure contributes to both hemostasis and thrombosis. In this model of vascular injury, most platelets exhibit partial rather than complete PS exposure.     

血清神经元特异性烯醇化酶对重型颅脑损伤患者功能预后的评价

目的颅脑损伤后伤情及功能预后的评估目前尚缺乏一种可靠的生化指标。通过对重型颅脑损伤患者的血清神经元特异性烯醇化酶(NSE)进行动态检测,旨在探讨NSE与重型颅脑损伤患者功能预后的关系。方法选择苏州大学附属第三医院神经外科2001-01/06重型颅脑损伤(GCS≤8)患者41例,男32例,女9例,年龄19～92岁,平均45岁。正常对照组20例,男10例,女10例,年龄20～52(平均33)岁,均经本院健康体检无异常。应用ELISA法测定41例重型颅脑损伤(GCS≤8)患者血清NSE并动态观察其变化的规律。结果预后不良的患者NSE初始值及峰值犤(66±10)μg/L,(94±14)μg/L犦均明显高于预后良好患者犤(32±4)μg/L,(34±4)μg/L犦,t值分别为3.090,4.207,P<0.01。初测NSE>60μg/L者,预后不良为75%(6/8),初测NSE<60μg/L者,预后良好为85%(28/33),χ2=22.586,P<0.001;初测NSE与预后负相关,r=-0.501,P<0.01。预后良好患者NSE值3d内迅速降至正常,而预后不良患者NSE值可持续高达5d以上;NSE持续高(初测NSE>60μg/L,下降缓慢)或继发性升高(初测NSE<60μg/L,NSE峰值>60μg/L)的患者预后不良占90%(9/10),NSE持续低(初测NSE<60μg/L)或迅速下降(初测NSE>60μg/L)的患者预后良好占94%(29/31),χ2=22.797,P<0.001。结论重型颅脑损伤后急性期血清NSE水平     

重型颅脑损伤大鼠急性期胰岛素敏感性的研究

【目的】探讨重型颅脑损伤大鼠急性期胰岛素敏感性的变化。【方法】采用大鼠自由落体脑损伤模型(Feeney‘s model),分别在伤前0．5h及伤后6h、12h、24h、48h、72h测定重型脑损伤动物的血糖和血清胰岛素值。运用正常血糖一高血胰岛素钳夹技术,检测大鼠重型脑损伤后24h BG60-120、GIR60-120、ISI等三个反映胰岛素敏感性的指标。【结果】重型脑损伤大鼠血糖含量升高的同时血清胰岛素水平升高,大鼠重型脑损伤后24h的BG60-120显著地升高,GIR60-120、ISI显著降低。【结论】在重型颅脑损伤急性期,大鼠血糖和血清胰岛素水平均显著地升高,高水平的胰岛素未能起到相应的降低血糖的作用,这可能与机体胰岛素敏感性降低有关。     

Comparative efficacy of tiklid and aspirin in patients with unstable angina

AIM: To evaluate effects of tiklid and aspirin on hemostasis, antithrombogenic activity of vascular wall in patients with unstable angina (UA). MATERIAL AND METHODS: An open randomized trial enrolled 30 UA patients given tiklid (n = 16) or aspirin (n = 14). Hemostasis, platelet aggregation, antithrombogenic activity of the vascular wall were examined on the treatment day 1 and 20. The response was assessed by the number of anginal attacks, dose of nitroglycerine, data of Holter monitoring. RESULTS: Tiklid was more effective than aspirin in UA patients as it by the treatment day 20 lowered platelet aggregation more, higher elevated anticoagulation potential of the blood and vessels, and stronger activated fibrinolytic hemostasis. CONCLUSION: Compared to aspirin, tiklid is more potent antiaggregant, has greater effect on antithrombogenic properties of the vascular wall.     

缺血性脑卒中溶栓患者出凝血变化规律的探讨

目的通过观察急性缺血性脑卒中患者组织型纤溶酶原激活物(rt-PA)静脉溶栓前后凝血及血小板指标变化的规律,进一步探讨与病情转归及临床预后的关系。方法选取2017年11月至2018年10月在本院就诊的急性缺血性卒中并进行rt-PA静脉溶栓治疗患者54例,检测患者溶栓前及溶栓后24 h的凝血及血小板指标,包括血小板(PLT)、平均血小板体积(MPV)、血小板分布宽度(PDW)、凝血酶原时间(PT)、活化的部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、凝血酶时间(TT)、D二聚体(DD)、纤维蛋白/原降解产物(FDP)、纤溶酶原(PLG)、血管性血友病因子含量(vWF:Ag)、血管性血友病因子活性(vWF:A)、凝血因子Ⅱ、凝血因子Ⅶ、凝血因子Ⅷ、凝血因子Ⅹ,同时记录患者入院时及静脉溶栓24 h的美国国立卫生研究院卒中量表(NIHSS)评分。分析患者溶栓前和溶栓后24 h凝血及血小板指标的变化;轻型卒中(NIHSS评分≤5分)和重型卒中(NIHSS评分≥6分)2组患者溶栓前各项指标变化;溶栓后24 h的NIHSS评分升高组及降低组患者各项指标变化。结果溶栓后24 h跟溶栓前相比,PT、APTT、MPV增高,FIB、PLG、vWF:Ag、vWF:A、凝血因子Ⅷ降低,差异有统计学意义(P<0.05)。重型卒中和轻型卒中2组患者相比,凝血因子Ⅱ、凝血因子Ⅶ明显增高,差异有统计学意义(P<0.05)。溶栓后24 h时NIHSS评分升高组和NIHSS评分降低组相比,PLG明显降低,vWF:Ag、vWF:A明显升高,差异有统计学意义(P<0.05)。结论急性缺血性脑卒中溶栓后24 h的凝血指标及血小板功能有较为明显的变化,并与病情的严重程度及预后均有较密切的联系,通过对以上指标进行观察能辅助预后和评估出血转化,对指导治疗有积极的临床意义。     

Optimization of the components of regulation of vascular tone and microcirculatory hemostasis during prolonged regional block in local cold injury

The impact of prolonged conduction block of the brachial plexus on the regulatory components of vascular tone, the state of vascular platelet hemostasis, and the activity of an inflammatory process was studied in patients with second-to-fourth degree local arm frostbites. The block alleviated arterial spasm, indirectly lowered myogenic tone, and decreased shunt blood flow. Nutritive circulation increased in the presence of a total increase in blood flow to the arm. There were increases in the intensity, rate, and potential of platelet aggregation. The concentration of proinflammatory cytokines reduced. This resulted in more efficient treatment.     

Microcirculation, hemostasis, and hemorheology in influenza and acute respiratory viral infections in patients with hypertension]

AIM: To study microcirculation (MC), hemostasis (HS) and blood viscosity (BV) in influenza and acute respiratory viral infection (ARVI) in hypertensive patients. MATERIAL AND METHODS: The study group consisted of 67 hypertensive patients with influenza or ARVI. 45 influenza and ARVI normotensive subjects served control. HS and BV tests were made, conjunctival biomicroscopy was performed. RESULTS: Patients with influenza and ARVI in the acute period had distinct perivascular and vascular abnormalities, sludge phenomenon in the majority of postcapillary venules and capillaries. In convalescence microcirculation improved. HS in the acute stage of infections was characterized by fast coagulation, depression of fibrinolysis; in convalescence, a significantly enhanced platelet aggregation was seen. The highest BV occurred at low shift speeds. Hypertensive patients had higher vascular permeability and more severe intravascular changes which presented with disseminated intravascular red cell aggregation, slowing down of blood flow, its partial block. In hypertension there was also significantly higher platelet aggregation, lower disaggregation, higher BV increase in convalescence. CONCLUSION: Hypertensive patients with influenza or ARVI had serious disorders of microcirculation, HS and BV threatening cardiovascular complications in such patients.     

Transfusion practice in military trauma

summary .  Modern warfare causes severe injuries, and despite rapid transportation to theater regional trauma centers, casualties frequently arrive coagulopathic and in shock. Conventional resuscitation beginning with crystalloid fluids to treat shock causes further dilutional coagulopathy and increased hemorrhagic loss of platelets and coagulation factors. Established coagulopathy was difficult to reverse in the face of uncontrolled hemorrhage. Because many of the casualties met conventional plasma and platelet transfusion criteria on admission, thawed AB plasma was prepositioned in the trauma receiving area and used in a 1:1 ratio with red cells for resuscitation and fresh whole blood was used as a source of platelets. Retrospective assessments of this 1:1 therapy strongly suggested that it resulted in improved hemostasis, shorter ventilator times, and improved survival. Component therapy, when available, appears to be as effective as fresh whole blood. In field emergencies, fresh whole blood can be lifesaving.     

rFVIIa and a new enhanced rFVIIa-analogue, NN1731, reduce bleeding in clopidogrel-treated and in thrombocytopenic rats

Summary.  Background: The pharmacological effect of rFVIIa occurs at the surface of activated platelets by enhancing thrombin generation at the site of vascular damage. It is therefore important to study the effects of rFVIIa in platelet-related bleeding situations. We examined the effect of rFVIIa and an rFVIIa-analogue, NN1731, on clopidogrel-induced and thrombocytopenic bleeding in rats. Methods and results: Clopidogrel [10 mg kg⁻¹; per oral (p.o.)] severely inhibited platelet aggregation and increased blood loss after tail-transection four hours after administration. Treatment with rFVIIa (5, 10, 20 mg kg⁻¹) or NN1731 (1, 5, 10 mg  kg⁻¹), administered five minutes after induction of bleeding, reduced blood loss significantly and dose-dependently. NN1731 had an increased hemostatic potential compared with rFVIIa, reducing blood loss to the control level, whereas this was not even achieved with the highest dose of rFVIIa. Antibody-induced thrombocytopenia reduced platelet numbers by more than 90% and increased the blood loss after tail-transection. Treatment with 10 and 20 mg kg⁻¹ rFVIIa significantly reduced blood loss, whereas 10 mg kg⁻¹ NN1731 reduced the bleeding to control levels. Conclusions: The hemostatic effect of rFVIIa and NN1731 was demonstrated in thrombocytopenic and clopidogrel-treated rats, showing efficacy in situations with decreased platelet number or functionality. Our findings are consistent with the hypothesis that rFVIIa/NN1731 contribute to hemostasis by thrombin generation even in situations with platelet disorders. Furthermore, NN1731 demonstrated a higher hemostatic potential than rFVIIa.