Bleeding and Clotting Disorders in Pediatric Liver Disease

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 170-177 ◽  
Author(s):  
Brian M. Wicklund
Keyword(s):  
Liver Disease ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Thrombin Generation ◽  
Pediatric Patients ◽  
Thromboembolic Disease ◽  
Activated Partial Thromboplastin Time ◽  
Bleeding Tendency ◽  
Clotting Factors ◽  
Pediatric Liver Disease

Abstract The coagulopathy of liver disease in pediatric patients presents an unusual set of challenges. Little pediatric data have been published, so this review is based largely on adult studies. There is a precarious balance between deficiencies of clotting factors and anticoagulation factors in liver disease that result in abnormal prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests that would suggest a bleeding tendency, yet the patients can form a clot and are at risk of thromboembolic disease. Attention has centered on thromboelastography and thrombin-generation assays to clarify the patient's ability to control bleeding, but these tests are not routinely available to many treating physicians.

HD1, a thrombin- and prothrombin-binding DNA aptamer, inhibits thrombin generation by attenuating prothrombin activation and thrombin feedback reactions

2010 ◽  
Vol 103 (01) ◽  
pp. 83-96 ◽  
Author(s):  
Colin Kretz ◽  
Karl Cuddy ◽  
Alan Stafford ◽  
James Fredenburgh ◽  
Robin Roberts ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Thrombin Generation ◽  
Potent Inhibitor ◽  
Lag Time ◽  
Activated Partial Thromboplastin Time ◽  
Dna Aptamer ◽  
Similar Extent ◽  
New Anticoagulants ◽  
Prothrombin Activation

SummaryHD1, a DNA aptamer, binds exosite 1 on thrombin and blocks its clotting activity. Because HD1 also binds prothrombin and inhibits its activation by prothrombinase, we hypothesised that HD1 would be a more potent inhibitor of coagulation than other exosite 1-directed ligands, such as Hir54–65(SO3 -). Supporting this concept, the effect of HD1 on the prothrombin time and activated partial thromboplastin time was twofold greater than that of Hir54–65(SO3 -) even though both agents inhibited thrombin-mediated factor (F) V and FVIII activation to a similar extent. In thrombin generation assays, HD1 (a) delayed the lag time, (b) reduced peak thrombin concentration, and (c) decreased endogenous thrombin potential to a greater extent than Hir54–65(SO3 -). To eliminate thrombin feedback, studies were repeated in FV- and/or FVIII-deficient plasma supplemented with FVa and/or FVIIIa. Only HD1 prolonged the lag time in FV- and FVIII-deficient plasma supplemented with FVa and FVIIIa. In contrast, HD1 and Hir54–65(SO3 -) inhibited the lag time in FVIII-deficient plasma supplemented with FVIIIa and in normal plasma. The more potent anticoagulant properties of HD1, therefore, reflect its capacity to attenuate FV activation by thrombin and inhibit prothrombinase assembly. These findings identify prothrombin as a potential target for new anticoagulants.

scholarly journals Prothrombin Time and Activated Partial Thromboplastin Time in Case of Liver Disease- A Study of 100 Cases

2017 ◽  
Vol 3 (4) ◽  
Author(s):  
Kimi Chhabra ◽  
Ish Kumar Baweja ◽  
Harpal Singh ◽  
Ramesh Kumar Kundal ◽  
Vandana Singla ◽  
...  
Keyword(s):  
Liver Disease ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time

Value of Preoperative Hemostasis Testing in Patients with Liver Disease for Perioperative Hemostatic Management

2017 ◽  
Vol 126 (2) ◽  
pp. 338-344 ◽  
Author(s):  
Ton Lisman ◽  
Robert J. Porte
Keyword(s):  
Platelet Count ◽  
Liver Disease ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Blood Product ◽  
Fibrinogen Level ◽  
Activated Partial Thromboplastin Time

Preoperative hemostasis testing may have limited use in patients with liver disease, and an abnormal platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen level should not trigger prophylactic transfusion of blood product components.

Monitoring Heparin Therapy: Relationships between the Activated Partial Thromboplastin Time and Heparin Assays Based on Ex-Vivo Heparin Samples

1990 ◽  
Vol 63 (01) ◽  
pp. 016-023 ◽  
Author(s):  
A M H P van den Bessekaar ◽  
J Meeuwisse-Braun ◽  
R M Bertina
Keyword(s):  
Partial Thromboplastin Time ◽  
Plasma Sample ◽  
Ex Vivo ◽  
Correlation Coefficients ◽  
Heparin Therapy ◽  
Thromboembolic Disease ◽  
Activated Partial Thromboplastin Time ◽  
Venous Thromboembolic Disease ◽  
Venous Thromboembolic

SummaryFive different APTT reagents, two amidolytic anti-ITa assays, one amidoiytic anti-Xa assay, and one coagulometric anti-Xa/ anti-IIa assay were used to assess the effect of heparin in patients treated for venous thromboembolic disease. Good correlations were observed between lug-transformed APYE> determined with the various reagents (correlation coefficients: 0.92-0.96).Nevertheless there were important differences in the slopes of the lines of relationship between the APTT reagents.Good correlations were observed between the anti-Xa and anti-IIa assay results (correlation coefficients: 0.92-0.97). However, the amidolytic anti-Xa activity was significantly higher (p <0.001) than the two amidolytic anti-IIa activities. Less good correlations were observed between the log-transformed APTTs and the anti-Xa or anti-IIa activities (correlation coefficients: 0.64-0.78). The correlations were improved by transforming the APTT into APTT-ratio, i.e. the ratio of the patient’s APTT to the same patient’s APTT after removal of heparin from the plasma sample by means of ECTEOLA-cellulose treatment. The correlation coefficients of log (AFTT-ratio) with anti-Xa or anti-IIa ranged from 0.76 to 0.87.For both APTT and amidolytic heparin assay, the response to in vitro heparin was different from the response to ex vivo heparin.Therefore, equivalent therapeutic ranges should be assessed by using ex vivo samples rather than in vitro heparin. Because of the response differences between the APTT reagents, it is not adequate to define a therapeutic range for heparin therapy without specification of the reagent.

EFFECTS OF NICKEL CHLORIDE ON INDICES OF HEMOCOAGULATION AND LIPID PEROXIDATION IN RATS

2019 ◽  
pp. 83-90
Author(s):  
Э.М. Гаглоева ◽  
В.Б. Брин ◽  
С.В. Скупневский ◽  
Н.В. Боциева ◽  
Т.В. Молдован
Keyword(s):  
Lipid Peroxidation ◽  
Antioxidant Enzymes ◽  
Platelet Aggregation ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Nickel Chloride ◽  
Activated Partial Thromboplastin Time ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Hemostasis System

Цель исследования - изучить состояние системы гемостаза при хронической интоксикации хлоридом никеля, исследовать взаимосвязь показателей гемокоагуляции с процессами липопероксидации у крыс в эксперименте. Методика. Опыты проводили на крысах-самцах Вистар (n=50, 230-250 г). Раствор NiCl2 (5 мг/кг) вводили внутрижелудочно ежедневно в течение 2 нед, 1 и 2 мес. По завершении эксперимента исследовали состояние тромбоцитарного и коагуляционного звеньев гемостаза, антикоагулянтную и фибринолитическую активность крови, а также определяли активность процессов перекисного окисления липидов и антиоксидантных ферментов. Результаты. Установлено, что через 2 нед и 1 мес интоксикации у крыс отмечались гиперкоагуляционные изменения показателей свертывающей системы крови: повышение агрегационной активности тромбоцитов, увеличение концентрации фибриногена, снижение активированного частичного тромбопластинового времени (АЧТВ) и протромбинового времени. В этот период регистрировалось увеличение антитромбиновой и фибринолитической активности крови. Через 2 мес наблюдалось подавление активности клеточного звена гемостаза - тромбоцитопения, ослабление степени АДФ-индуцируемой агрегации тромбоцитов. Выявлялась тенденция к уменьшению концентрации фибриногена. На фоне снижения АЧТВ и тромбинового времени отмечалось увеличение протромбинового времени. В то же время регистрировалось угнетение противосвертывающего звена системы гемостаза (снижалась активность антитромбина III), наблюдалось истощение резервных возможностей фибринолитического звена (замедление фXIIа-зависимого эуглобулинового лизиса) и увеличение содержания растворимых фибрин мономерных комплексов, что свидетельствует о наличии тромбинемии. Через 2 нед, один и два месяца интоксикации у животных выявлялись корреляционные связи между основными показателями системы гемостаза и активностью процессов перекисного окисления липидов и антиоксидантных ферментов. Заключение. Полученные данные подтверждают наличие взаимосвязи активности процессов липопероксидации и системы гемостаза, в том числе при хронической никелевой интоксикации. Результаты исследования позволяют рекомендовать применение антиоксидантов для разработки способов коррекции гемостатических сдвигов при воздействии на организм тяжелых металлов. The aim. To study the state of the hemostasis system in chronic nickel intoxication and to investigate the relationship between hemocoagulation indices and lipoperoxidation processes in rats. Methods. Experiments were carried out on male Wistar rats (n=50, 230-250 g). A solution of nickel chloride (5 mg/kg) was administered daily intragastrically for two weeks, one and two months. At the end of the experiments, indices of platelet and coagulation hemostasis systems, anticoagulant and fibrinolytic activity of blood plasma, and activities of lipid peroxidation and antioxidant enzymes were studied. Results. Hypercoagulative changes in indices of the coagulation system were observed in rats after two weeks and one month of intoxication, including increased platelet aggregation and fibrinogen concentration and shortened activated partial thromboplastin time and prothrombin time. During the same period, increased antithrombin and fibrinolytic activities were observed. The depressed activity of the cellular component of hemostasis evident as thrombocytopenia and impaired ADP-induced platelet aggregation was detected after two months of intoxication. A tendency to decrease in fibrinogen concentration was observed. The shortened activated partial thromboplastin time and thrombin time were associated with prolonged prothrombin time. At the same time, inhibition of the anticoagulant component of hemostasis (decreased antithrombin III activity), exhaustion of the fibrinolysis system reserve (delayed fXIIa-dependent euglobulin lysis), and a significant increase in soluble fibrin monomeric complexes indicative of thrombinemia were observed. After two weeks, one and two months of nickel intoxication, a correlation was found between the major indices of the hemostasis system and the activities of lipid peroxidation and antioxidant enzymes. Conclusion. The study confirmed a relationship between the lipid peroxidation activity and the hemostasis system, specifically in chronic nickel intoxication. This result allows to recommend the use of antioxidants in developing methods for correction of hemostatic induced affected by heavy metals.

scholarly journals A Rare Cause of Isolated Prolonged Activated Partial Thromboplastin Time: An Overview of Prekallikrein Deficiency and the Contact System

2021 ◽  
Vol 9 ◽  
pp. 232470962110121
Author(s):  
Ivy Riano ◽  
Klaorat Prasongdee
Keyword(s):  
Partial Thromboplastin Time ◽  
Normal Activity ◽  
Fresh Frozen Plasma ◽  
Activated Partial Thromboplastin Time ◽  
Recessive Trait ◽  
Bleeding Tendency ◽  
Contact Activation ◽  
Asymptomatic Patients ◽  
Prolonged Aptt ◽  
Fresh Frozen

Prekallikrein (PK) deficiency, also known as Fletcher factor deficiency, is a very rare disorder inherited as an autosomal recessive trait. It is usually identified incidentally in asymptomatic patients with a prolonged activated partial thromboplastin time (aPTT). In this article, we present the case of a 52-year-old woman, with no prior personal or family history of thrombotic or hemorrhagic disorders, who was noted to have substantial protracted aPTT through the routine coagulation assessment before a kidney biopsy. The patient had an uneventful biopsy course after receiving fresh frozen plasma (FFP). Laboratory investigations performed before the biopsy indicated normal activity for factors VIII, IX, XI, XII, and von Willebrand factor (vWF) as well as negative lupus anticoagulant (LA) screen. The plasma PK assay revealed low activity at 15% consistent with mild PK deficiency. The deficit of PK is characterized by a severely prolonged aPTT and normal prothrombin time (PT) in the absence of bleeding tendency. PK plays a role in the contact-activated coagulation pathway and the inflammatory response. Thus, other differential diagnoses of isolated prolonged aPTT include intrinsic pathway factor deficiencies and nonspecific inhibitors such as LA. We concluded that the initial evaluation of a prolonged aPTT with normal PT should appraise the measurement of contact activation factors and factor inhibitors. PK deficiency should be considered in asymptomatic patients with isolated aPTT prolongation, which corrects on incubation, with normal levels of the contact activation factors and factor inhibitors.

Antihemostatic Effect of Hsien-Ho-T'sao (Agrimonia pilosa)

1984 ◽  
Vol 12 (01n04) ◽  
pp. 116-123 ◽  
Author(s):  
Jih-Pyang Wang ◽  
Mei-Feng Hsu ◽  
Che-Ming Teng
Keyword(s):  
Prothrombin Time ◽  
Blood Coagulation ◽  
Partial Thromboplastin Time ◽  
Bleeding Time ◽  
Fibrinogen Level ◽  
Platelet Rich Plasma ◽  
Water Extract ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Time

Bleeding time in rats was markedly prolonged after the adminstration of the water extract of Hsien-Ho-T'sao. This antihemostatic effect was more marked in the group of i.p. injection of the drug than in the group of p.o. administration for 2 to 7 consecutive days. Blood coagulation studies showed that plasma prothrombin time, activated partial thromboplastin time and stypven time were prolonged, while thrombin time adnd fibrinogen level were not changed. The thromboelastographic recording showed that reation time was prolonged and maximal elasticity of clot was decreased. In addition, ADP- and collagen- induced aggregations of platelet-rich plasma was suppressed. In conclusion, the prolongation of the bleeding time might be due to both anticoagulant and antiplatelet action of the drug.

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