A dyspnea patient with abnormal prolonged prothrombin time and activated partial thromboplstin time, but without bleeding symptoms

A patient with erythrocytosis secondary to chronic obstructive pulmonary disease (COPD) was admitted to hospital because of dyspnea. The coagulation tests revealed abnormal prolonged prothrombin time (PT) and activated partial thromboplstin time (APTT), however, it could not be explained by the patient's medical history or physical signs of coagulation disorder. High hematocrit (Hct), which leads to reduced plasma-to-anticoagulant rate and increased final plasma anticoagulant concentration, was identified as the reason for false prolongation of PT and APTT.     

The varied sensitivity of partial thromboplastin and prothrombin time reagents in the demonstration of the lupus-like anticoagulant.

An acquired inhibitor of blood coagulation, similar to that described in patients with Systemic Lupus Erythematosus (SLE), was detected during routine coagulation screening in 10 patients who did not meet the criteria for a diagnosis of SLE. The lupus-like anticoagulant (LLAC) was diagnosed on the basis of prolonged activated partial thromboplastin time (APTT) and/or prothrombin time (PT) which failed to correct when patient plasma was added to normal plasma; an additional criterion was an abnormal tissue thromboplastin inhibition test. No patient had a specific inhibitor directed against factors VIII and IX. Demonstration of LLAC was highly dependent upon the type of reagents adopted in the APTT and PT: the abnormality was detected consistently by one reagent only. One-stage assays of factors VIII and IX were characteristic of the presence of an inhibitor, showing non-parellel dose-response curves or decreased activity at low dilutions which were partially corrected at higher dilutions. Although 7 patients were free of abnormal bleeding, unequivocal signs of haemorrhagic tendency after a surgery were present in the remaining 3 patients. The findings suggest that LLAC is a non-exceptional cause of prolonged coagulation screening tests, and that it may sometimes be associated with impaired haemostasis.     

晚期血吸虫病肝硬化患者凝血功能检测分析

目的 对比检测晚期血吸虫病与慢性血吸虫病患者的凝血指标,探讨晚血病人的凝血功能机制,及时监测晚血病人的出血倾向并为临床指导用药提供依据。方法 运用国产雷杜RT-2204C 血凝仪检测37 例晚血病人和80 例慢血病人的血浆凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）和凝血酶时间（TT）。结果 晚血病人PT、APTT 和TT 值均大于慢血病人,差异有统计学意义（P 均<0.01）。结论 晚血患者凝血功能明显异常,处于低凝状态且纤溶系统受损,检测该指标对监测晚血病人出血倾向与指导临床用药具有重要的意义。     

How to minimize blood loss during liver surgery in patients with cirrhosis

Patients with liver disease frequently have substantial changes in their haemostatic system. This is reflected in abnormal test results on routine coagulation screening assays such as the prothrombin time (PT), activated thromboplastin time (APTT) and platelet count. Traditionally, attempts were made to correct abnormalities in the haemostatic system as measured by routine coagulation assays prior to invasive procedures by infusion of platelets or fresh frozen plasma (FFP). Recent laboratory and clinical data have indicated that the haemostatic reserve in cirrhotic patients is relatively well maintained although the coagulation screening assays suggest otherwise. Pre-procedural correction of coagulation tests with blood products may therefore not be necessary, and may even have harmful side-effects. In particular, fluid overload resulting in exacerbation of portal hypertension by infusion of blood products may in fact promote bleeding. In recent years, it has become clear that reduction of the central and portal venous pressure by fluid restriction and avoidance of blood product transfusion is a beneficial strategy in minimizing bleeding during liver surgery in cirrhotic patients. Some investigators have even taken this a step further and suggested pre-procedural phlebotomy in liver transplant recipients. The aim of this review is to provide an overview of recent studies and developments which have changed our understanding of the clinical relevance of abnormal coagulation tests in patients with cirrhosis, and which have contributed to a reduction in blood loss and transfusion requirements when liver surgery is needed in these patients.     

Significance and causes of abnormal preoperative coagulation test results in children

To prevent bleeding related to adenoidectomy and tonsillectomy, coagulation screening tests were, until recently, performed routinely in the Czech Republic for all paediatric patients. The aim of this study was to evaluate benefit of preoperative coagulation screening tests in children. We retrospectively analysed laboratory and clinical data of children referred for abnormal preoperative coagulation test results (aPTT, PT) to the outpatient haematology clinic. A total of 274 paediatric patients were retrospectively evaluated due to abnormal preoperative coagulation tests results. In 140 of 274 patients (51.1%), coagulation tests were normal on repeated testing in a specialized haematology clinic. Ten patients had decreased factor XII. Five patients had a suspected bleeding disorder which was confirmed in two of them. One patient had low levels of von Willebrand factor, and one patient had mild factor VII deficiency. Both these patients had positive personal and/or family history of bleeding. Each case history was taken individually, without use of standardized questionnaires. Bleeding complications were not observed, and coagulation factor replacement was not needed perioperatively in our cohort. The majority of abnormal findings in aPTT and PT appeared only transiently. All the bleeding disorders found in our cohort of patients were mild in nature. Our findings provide supportive evidence for the current national Czech recommendation: laboratory coagulation screening should be performed only in patients with positive family and/or personal bleeding history.     

The Varied Sensitivity of Partial Thromboplastin and Prothrombin Time Reagents in the Demonstration of the Lupus-Like Anticoagulant

An acquired inhibitor of blood coagulation, similar to that described in patients with Systemic Lupus Erythematosus (SLE), was detected during routine coagulation screening in 10 patients who did not meet the criteria for a diagnosis of SLE. The lupus-like anticoagulant (LLAC) was diagnosed on the basis of prolonged activated partial thromboplastin time (APTT) and/or prothrombin time (PT) which failed to correct when patient plasma was added to normal plasma; an additional criterion was an abnormal tissue thromboplastin inhibition test. No patient had a specific inhibitor directed against factors VIII and IX. Demonstration of LLAC was highly dependent upon the type of reagents adopted in the APTT and PT: the abnormality was detected consistently by one reagent only. One-stage assays of factors VIII and IX were characteristic of the presence of an inhibitor, showing non-parellel dose-response curves or decreased activity at low dilutions which were partially corrected at higher dilutions. Although 7 patients were free of abnormal bleeding, unequivocal signs of haemorrhagic tendency after a surgery were present in the remaining 3 patients. The findings suggest that LLAC is a non-exceptional cause of prolonged coagulation screening tests, and that it may sometimes be associated with impaired haemostasis.     

Acquired coagulation disorders: revisited using global coagulation/anticoagulation testing

Acquired coagulation defects are characterized by a decrease of both pro- and anti-coagulants. Because of this, we hypothesise that global tests, such as the prothrombin and partial thromboplastin times (PT and APTT), might be unsuitable for their investigation. Indeed, these tests are not good predictors of bleeding in acquired coagulopathies as they are in the congenital ones. This article discusses the possible reasons for this, using cirrhosis and the neonatal period as epitomes of acquired coagulation defects. Both display normal thrombin generation in the presence of thrombomodulin, in spite of prolonged PT and APTT. We surmise that, because of their design, the PT and APTT are responsive to thrombin generated as a function of pro-coagulants, but much less to thrombin inhibited by the anti-coagulants, especially protein C, which is activated to a limited extent in the absence of thrombomodulin. In conclusion, the PT and APTT can tell us whether or not a patient is deficient in one or more pro-coagulants, but not whether this deficiency is counterbalanced by a parallel deficiency of anti-coagulants. Thrombin generation assays are more suitable than PT and APTT for use in acquired coagulation defects.     

Should plasma be transfused prophylactically before invasive procedures?

PURPOSE OF REVIEW: Plasma transfusion to correct abnormal coagulation test results prior to an invasive procedure is a common clinical practice; however, there are no evidence-based guidelines. This review aims to analyze the most recent publications to either support or disprove such practice. RECENT FINDINGS: Due to heightened awareness of transfusion-related acute lung injury and volume overload in susceptible patients, clinicians are increasingly questioning the validity of prophylactic plasma transfusion. Recently, several articles, reviews and clinical studies (although small and poorly designed) have shown no benefit of prophylactic plasma transfusion in either correcting abnormal coagulation tests or reducing perceived risk of hemorrhage. SUMMARY: The use of sensitive reagents (especially for prothrombin time) has resulted in increased incidence of abnormal preprocedure coagulation screening test results - tests that are not designed to assess risk of bleeding in patients without a history of bleeding. Transfusion of plasma prior to an invasive procedure to correct mild to moderate abnormal test results neither corrects the abnormality nor reduces the perceived bleeding risk.     

Prothrombin Time and Partial Thromboplastin Time Tests Are Unnecessary Before Routine Cardiac Catheterization

Prothrombin time and partial thromboplastin time tests are commonly obtained prior to cardiac catheterization but the usefulness of the tests in these patients has not been examined. The records of 1,462 consecutive patients undergoing diagnostic catheterization were reviewed. All patients had received prothrombin time and partial thromboplastin time tests. The prevalence of abnormal test values was determined. The coagulation test values were correlated with history and physical evidence of bleeding risk, and also with bleeding complications. Abnormal coagulation values were found in 72/1,462, a prevalence of 4.9%. The history and physical exam predicted 63/72 (87.5%) of abnormal values, yielding a sensitivity of 87.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99.3%. The nine unpredicted abnormal values (0.6%, 9/1,462) were minimally abnormal and clinical decision making was not affected by the test result in any of the nine patients. There was no correlation between abnormal values and bleeding complications. Abnormal test values have a low prevalence in catheterization patients, 4.9% in this series, are highly predictable from history and physical exams, and in the absence of history or physical findings do not predict procedural bleeding complications. The tests should, therefore, be obtained only in a small percentage of patients, 4.3% in this series, who have an increased bleeding risk indicated by history or physical findings of anticoagulant use, excessive bleeding, liver disease, or malabsorption.     

Clinical bleeding events and laboratory coagulation profiles in acute promyelocytic leukemia

Background: Bleeding is the leading cause of death for patients with acute promyelocytic leukemia (APL). Blood component transfusion to correct coagulopathy is the keystone in reducing bleeding. The benefit of fresh frozen plasma transfusion is unproven. Using laboratory profiles to predict bleeding is important guidance for the determination of transfusion policies in the treatment of APL. Design and methods: For 116 patients of APL, bleeding events were collected and correlated with various hematologic and coagulation parameters, including leukemic cell percentages, white blood cell (WBC) and platelet counts, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen levels, and disseminated intravascular coagulation (DIC) scores. Results: Overt DIC occurred in 77.6% of patients. Severity of DIC was associated with bone marrow leukemic cell percentages but unrelated to bleeding. Patients with bleeding had significantly higher WBC counts (26.73 ± 6.18 vs. 13.03 ± 3.03 per μL, P = 0.026) and more prolonged PT (4.85 ± 0.70 vs. 2.59 ± 0.28 s, P = 0.002) and APTT (3.98 ± 1.68 vs. 0.96 ± 0.93 s, P = 0.017). Fibrinogen levels, platelet counts, and leukemia cell percentages were not significantly different between bleeding and non‐bleeding patients. PT is valuable in prediction of bleeding. Patients with PT ≧ 5 s had a relative risk of 6.14 for bleeding. Seven patients had severe bleeding before initiation of all‐trans retinoic acid (ATRA). Conclusions: Patients with APL are susceptible to DIC and subsequent bleeding events. Prompt ATRA administration is crucial in preventing hemorrhagic events. High WBC counts, prolonged PT, and APTT are associated with clinical bleeding in our series. PT is the most accurate parameter in predicting bleeding. Based on these findings, supportive care should be directed toward correction of coagulopathy to prevent bleeding complications and fresh frozen plasma appears to be indicated for coagulopathy associated with APL.     

Coagulation disorders in patients with locally advanced head and neck cancer - should they really be disregarded?

The aim of the study was to analyse coagulation disorders in patients with locally advanced cancer of the head and neck (CHN)and with no other clinical cause for coagulation disorders treated with radiation therapy alone or concurrent chemoradiotherapy. We also assessed the duration of disorders in the course of therapy. The analysed group consisted of 33 patients with locally advanced CHN documented as stage T3 or T4 acc. to the TNM classification. Coagulology tests (activated partial thromboplastic time /APTT/, prothrombin time, fibrinogen concentration, euglobulin lysis time, C - reactive protein and anti-thrombin III concentration, d-dimer level, PAI-1, plasminogen level and plasmin-anti-plasmin assays) were performed before, during and after the completion of treatment. In all cases pre-tratment abnormal fibrinolysis was observed. We observed elevated PAI-1 levels in all blood tests regardless of the treatment stage, while elevated plasminogen concentration and euglobulin lysis time was observed in a majority of tests. Increased PAI-1 level persisted independently of tumor regression during treatment. Half of our patients also presented with a tendency towards shortened APTT. One patient had a significantly higher d-dimer level at the end of the treatment. Decreased APTT was the sole factor influencing overall survial (OS) confirmed in multivariate analysis (Cox's proportinal hazard model). Despite the occurence of abnormal fibrinolysis and decreased APTT, we did not observe an increased risk of coagulation disorders. We conclude that among caogulation tests only a decrease in APTT is, at present, a stasistically confirmed predective factor of shorter OS in CHN patients. Autothrombotic prophylactic treatment may be an effective option in this clinical setting. There is need for further studies on large patient groups.     

Unexpected,isolated activated partial thromboplastin time prolongation: A practical mini-review

A common inquiry in coagulation laboratories is how to interpret an unexpected, isolated prolonged activated partial thromboplastin time (APTT). In this context, isolated means together with a normal prothrombin time (PT) and/or normal international normalized ratio (INR). This finding may lead to contact with laboratory doctors for further advice on a diagnostic strategy. Occasionally, the need for a diagnostic algorithm can be subacute, where surgery has to be postponed until an explanation for the isolated, prolonged APTT has been established. Activated partial thromboplastin time as a coagulation test was developed to monitor patients with hemophilia. Different APTT reagents display considerable differences in their sensitivity to deficiencies of coagulation factors. An isolated, prolonged APTT is seen in (a) individuals/patients with lupus anticoagulants, (b) patients in treatment with anticoagulants, mainly heparin, and (c) patients with deficiencies of specific coagulation factors. In this tutorial review, we summarize what may cause an isolated prolonged APTT and we present a simple diagnostic algorithm to differentiate between lupus anticoagulants (common) and factor deficiencies (rare). The identification of an isolated prolonged APTT as well as the underlying cause can be of the utmost importance in ensuring the correct therapeutic follow-up.     

24例心肺转流术后出血原因的分析

为了探讨心肺转流（简称ＣＰＢ）术后出血原因，对２４例肝素化前，肝素化１０’，ＣＰＢ停机（简称停机）即刻，静注鱼精蛋白锌（简称鱼精）后（关胸前）及术后２４小时凝血与抗凝血活性进行了检测：１．肝素化前凝血酶元时间（ＴＰ）及凝血酶元活动度（ＰＡ），纤维蛋白原（ＦＩＢ）定量，部分凝血活酶生成时间（ＡＰＴＴ），抗凝血酶Ⅲ（ＡＴ＿Ⅲ）活性均正常。２．肝素化１０’时ＡＴ＿Ⅲ活性升高，ＰＴ、ＡＰＴＴ均显示活性消失。３．停机即刻２１例ＰＴ显示活性恢复，并伴ＰＡ、ＦＩＢ，ＡＴ＿Ⅲ活性明显下降；而２４例ＡＰＴＴ、３例ＰＴ显示活性消失。４．静注鱼精后ＰＴ、ＡＰＴＴ凝固时间仍明显延长；ＰＴ、ＦＩＢ、ＡＴ＿Ⅲ活性翁明显下降。５．术后２４小时除ＦＩＢ定量明显增加外余均恢复正常，上述结果表明：肝素化不能完全抑制凝血酶的产生。因此转流中凝血和纤溶亢进导致凝血活性消耗下降为术后出血原因之一。     

不同阶段肝病患者血栓弹力图与常规凝血检测的一致性研究

目的对不同阶段肝病患者的血栓弹力图(thrombelastograph,TEG)参数R值和常规凝血功能指标PT和APTT进行对比研究。方法将2016年2月—2017年1月解放军第三〇二医院住院患者232例作为研究对象,其中慢性肝炎患者41例,肝硬化代偿期患者69例,肝硬化失代偿期患者79例,慢性肝衰竭患者43例。检测上述各类患者TEG参数R值和常规凝血指标PT、APTT,并对2种检测方法的检测结果进行对比研究。结果慢性肝炎患者R值与PT、APTT进行一致性分析后,kappa值分别为-0.135(P0.05)、0.105(P0.05),一致率分别为34.15%和60.98%。肝硬化代偿期患者R值与PT、APTT一致性分析后,kappa值分别为0.175(P0.05)、0.038(P0.05),一致率均为60.90%。肝硬化失代偿期患者R值与PT、APTT一致性分析后,kappa值分别为0.023(P0.05)、0.038(P0.05),一致率分别为43.04%和49.37%。慢性肝衰竭患者R值与PT、APTT一致性分析,kappa值均为-0.049(P0.05),一致率均为13.95%。结论因TEG是从不同角度检测凝血功能,TEG检测结果可为评估不同阶段肝病患者凝血因子状态提供更加全面的依据。     

Delayed hemostatic changes following cardiopulmonary bypass.

A variety of hemostatic abnormalities has been reported in patients following open-heart surgery. Since surgery itself may induce changes in the coagulation system, the analyses of postoperative coagulation assays in the bleeding patients may be extremely difficult to interpret without an understanding of the coagulation dynamics in the nonhemorrhagic postoperative patients. Thus, we studied the pattern of change in several coagulation assays performed on 36 consecutive patients before and during the first two postoperative weeks. Approximately one third of the patients has some clotting abnormality before surgery. Shortened prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed within the first three postoperative days. Only following warfarin therapy (initiated on the third postoperative day) was significant prolongation of PT and APTT observed. During the 14 postoperative days, fibrinogen levels and fibrinogen degradation products progressively increased without prolongation of the thrombin time or decrease in the euglobulin clot lysis time. On the first postoperative day, the platelet count and platelet adhesiveness values were significantly less than before surgery (p less than 0.01 and p less than 0.05). Over the following two weeks, the platelet count and platelet adhesiveness returned to normal. Although there was slight lengthening of the Ivy bleeding time on the first postoperative day, this assay was never abnormal. Thus, we conclude that the following cardiopulmonary bypass there is (1) probably activation of circulating procoagulants, (2) progressive increase in fibrinogen levels, (3) activation to the fibrinolytic system, and (4) transient thrombocytopenia with a superimposed platelet defect.     

Comparability of the results of PT-INR with local MNPT and APTTR with MNAPTT on different coagulation analyzers in China

The prothrombin time (PT), International normalized ratio (INR) and activated partial thromboplastin time (APTT) are the most used coagulation tests in China, where more than one type of automated coagulation analyzer is often used in the clinical laboratory. The PT-INR results of 109 samples were compared with local mean normal PT (MNPT) and APTT ratio (APTTR) with mean normal APTT (MNAPTT) on two different coagulation analyzers in the same laboratory. The two different coagulation analyzers showed no significant difference (P > 0.05) in PT and INR determination, but there was a significant difference (P < 0.01) for APTT. The INR with local MNPT and APTTR with MNAPTT, obtained with the ACL Futura and CA 510, showed much better agreement; 98.8% (82/83) of bias for INR with local MNPT was less than 15% compared with 90.4% (75/83) of bias for INR; and 100% of bias for APTTR (62/62) was less than 15% compared with only 6.5% (4/62) of bias for APTT. Meanwhile, there was no significant difference (P = 0.865) for APTTR with MNAPTT compared with APTT (P = 0.002) between the ACL Futura and CA 510. In conclusion, these analyzers showed very poor agreement for both the PT and APTT, but the calculation of ratios significantly improved agreement.     

血栓弹力图在主要外科手术围手术期中的应用

影响围手术期凝血功能的因素具有多样性,目前检测凝血功能的方法包括凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、血小板(PLT)计数、纤维蛋白原(FIB)浓度等传统凝血检测项目和血栓弹力图(TEG),而传统的凝血检测只能监测凝血过程中的一部分,不能反映凝血的动态变化,无法准确判断凝血异常的原因。TEG可以快速、准确、全面、动态地监测血液凝固的全过程,合理地评估围手术期的凝血功能,为临床治疗提供理论依据。     

湖北省凝血试验室间质量评价和质量控制现状分析

目的：对湖北省二级以上医疗机构临床实验室实施凝血试验室间质量评价活动,了解全省凝血试验项目,包括凝血酶原时间（PT）、国际正常化比值（INR）、活化部分凝血活酶时间（APTT）、纤维蛋白原（FIB）检测的现状,提出改进的措施,促进检测质量,以期更好地为临床服务。方法：对全省近190个临床实验室1年2次发放室间质量评价质评物（包括正常、中度异常和高度异常3种水平）,收集各检测数据,对参加实验室按使用仪器、试剂情况进行分组,采用美国PT评分方法进行统计评价。结果：全省各参控实验室合格率2005年为41%,2006年为55%,2007年为67%,2008年为79.2%,逐年上升。分析各项目各组变异系数（CV%）,发现质评物异常程度越高,检测结果的变异系数CV值越大,及格率越低。使用与仪器配试剂的检测系统变异系数比非配套检测系统小,及格率高。结论：实验室通过参加室间质评活动及开展室内质量控制,及时发现、分析实验中存在的问题,采取相应的措施,提高检测质量。     

Persistently Elevated Laboratory Markers of Thrombosis and Fibrinolysis After Clinical Recovery in Malaria Points to Residual and Smouldering Cellular Damage

Screening coagulation tests and assays for thrombosis and fibrinolysis were performed in 80 cases of malaria at presentation and during the course of the disease. Close correlation between the degree of thrombocytopenia (observed in >97% cases) and the presence hemorrhagic manifestations at presentation, and improvement in the platelet count in parallel with clinical recovery emphasised the role of platelets in the pathogenesis of coagulopathy in malaria. A potential selection bias resulting from inclusion of only patients admitted at a tertiary care hospital could explain the higher incidence (27.5%) of clinical bleeding observed in this study compared to that reported in the literature. Although a significant correlation between overt bleeding and abnormal PT/INR and APTT (observed in 20–37% cases) could not be demonstrated, a good correlation existed between normal screening coagulation tests and the absence of bleeding complications. Elevated D-Dimer and FDP levels in almost all cases (90%) of both types of malaria confirmed the high prevalence of disseminated intravascular coagulation and fibrinolysis. A correlation between rising D-Dimer levels and the incidence of bleeding was observed. Follow up studies in six cases with complications showed normalization of platelet counts and of screening coagulation assays with clinical recovery. D-Dimer and FDP levels however, remained elevated in most of these cases indicating the continuation of a smouldering coagulopathy even after full clinical recovery possibly due to the persistence of residual damage to the cells caused by the parasitic infection. Knowledge of this fact is important for avoiding unnecessary investigations and longer hospital stay in patients admitted with malaria.     

Does glycemic regulation affect hypercoagulable states in diabetic patients?

Diabetes is a common disorder, and many studies have shown that patients with diabetes mellitus have increased thrombotic complications including arterial and venous thromboses. Poorly controlled diabetes increases the risk of thrombosis. Recent reports have shown that a shortened activated partial thromboplastin time (APTT) and increased fibrinogen levels indicate a procoagulant condition. In this study, we evaluated the differences in global coagulation test values such as APTT, prothrombin time (PT), or fibrinogen levels, between well and poorly controlled diabetes. Three hundred forty-nine patients with type 2 diabetes mellitus were included. APTT, PT, fibrinogen, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), complete blood count (CBC), serum lipids, and HbA1c have been measured. Those with APTT <22 s and PT <10.5 s were identified. Furthermore, patients were divided into two groups based on HbA1c levels as follows: regulated diabetic group (HbA1c ≤7.0 %) and dysregulated diabetic group (HbA1c >7.0 %). No significant differences were found between the two groups in terms of shortened APTT (<22 s), PT (<10.5 s), or fibrinogen levels. Although inexpensive and widely available, global coagulation assays such as APTT, PT, and fibrinogen levels did not prove useful for evaluating hypercoagulable states in patients with diabetes.