Prolonged activated partial thromboplastin time of unknown etiology: a prospective study of 100 consecutive cases referred for consultation

The activated partial thromboplastin time (aPTT) is frequently used to assess overall competency of the intrinsic pathway of coagulation. An abnormal value may be caused by any of several abnormalities along this pathway or by many other variables including the presence of inhibitors, poor collection of the sample, or variables in the laboratory. When the cause for the prolongation is unknown to the requesting physician, the hematologist may be consulted. In this prospective study, the cause and perceived hemostatic risk to 100 consecutive patients referred to use for consultation regarding a prolonged aPTT of previous unknown cause were evaluated. We found that these abnormal aPTTs may be either indicative of a hemostatic defect, in 50% of the cases, or of no particular risk, in 36% of the cases. In 14%, the aPTT was artifactually prolonged. Most (81%) patients with a prolonged aPTT due to a hemostatic defect had an abnormal hemostatic history but some (19%) did not. Even among true abnormal tests, the degree of abnormality indicated little or nothing about hemostatic competency. We conclude that the cause of an abnormal aPTT is more important than the result itself. These data may be of use to those who consult on such matters.     

Diagnostic uses of the activated partial thromboplastin time and prothrombin time

The activated partial thromboplastin time (APTT) and prothrombin time (PT) have three principal uses. In screening for coagulation disorders (or increased risk of postoperative hemorrhage), the tests add no information to the preoperative care of patients without clinical findings indicative of increased bleeding risk. Furthermore, the prevalence of asymptomatic congenital coagulopathies is so low that false-positive test results greatly outnumber true-positive results. Thus, clinicians may use clinical assessment to screen and should reserve coagulation tests to investigate patients with abnormal findings. In evaluating abnormal bleeding, these tests are sufficiently sensitive that if both are negative, further investigation of the coagulation system is obviated. If one or both tests are positive, the pattern of results directs further attention to limited segments of the coagulation sequence. In monitoring anticoagulation therapy, the APTT and PT tests appear to contribute to the safety and effectiveness of heparin and warfarin therapies, respectively.     

Prolonged activated partial thromboplastin time after prophylactic-dose unfractionated heparin in the post-operative neurosurgical setting: case series and management recommendations

Journal of Thrombosis and Thrombolysis - Primary brain tumors, both benign and malignant, pose a high risk of perioperative venous thromboembolism (VTE) due to the development of a prothrombotic...     

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.     

Relationship between activated partial thromboplastin time,heparin and potassium levels

We performed a meta-analysis of five randomized, placebo-controlled trials to characterize the impact of plant sterols/stanols on plasma lipids in patients with type 2 diabetes. Upon meta-analysis, plant sterols/stanols significantly reduced total and LDL cholesterol, with a trend towards improvement in HDL. No beneficial effect on triglycerides was apparent.     

The activated partial thromboplastin time in early diagnosis of myocardial infarction.

Intracoronary thrombosis is fundamental to the pathogenesis of acute myocardial infarction (MI), yet few studies have examined the diagnostic value of routine coagulability markers, such as the activated partial thromboplastin time (aPTT), in patients with chest pain. We hypothesized that the initiation of thrombosis early in MI would shorten the aPTT, and conducted a retrospective cohort study of patients admitted with a diagnosis of chest pain through the emergency department of one community hospital between 1 January and 30 August 1998. Patients were diagnosed as MI positive or negative based on World Health Organization (WHO) criteria. The aPTT obtained on arrival (prior to anticoagulation therapy) was retrieved from the electronic medical record. Of 120 eligible patients (49% female, mean age 63.7 years), 27 (23%) were diagnosed with MI. Patients with an aPTT control (RR = 2.83, 95% confidence interval 1.15 to 6.96, P = 0.013). A shortened aPTT (相似文献   

Thrombolytic fibrin specificity influences activated partial thromboplastin time prolongation in vitro.

Despite limited comparative data, guidelines suggest the same concomitant unfractionated heparin (UFH) dose for all fibrin-specific thrombolytic agents in acute myocardial infarction. Since a supratherapeutic activated partial thromboplastin time (aPTT) correlates with adverse outcomes, clarifying effects of various agents on aPTT are needed. The present in vitro study evaluated the influence of alteplase (rt-PA), reteplase (r-PA), and tenecteplase (TNK) on aPTT prolongation. Blood samples from healthy volunteers (n = 12) were treated with equipotent concentrations of rt-PA, r-PA, and TNK, with and without UFH. Samples of each treatment group were incubated at 37 degrees C; aPTT and fibrinogen activity were measured after 4 h. Mean aPTT values for rt-PA alone and r-PA alone were prolonged versus those of TNK alone (P = 0.001 for both). Combined with UFH, rt-PA and r-PA increased the aPTT versus UFH alone (P < 0.05 for both). Interestingly, TNK + UFH reduced the aPTT versus UFH alone (P < 0.001). A negative correlation existed between fibrinogen activity and aPTT for all treatments, except TNK alone. The present investigation illustrates that an agent with maximal fibrin specificity (TNK) has minimal effect on the aPTT, while agents with less fibrin specificity are more likely to prolong the aPTT, with and without UFH present.     

健康老年人活化部分凝血活酶时间参考值与海拔高度的关系

目的为制定中国健康老年人活化部分凝血活酶时间(APTT)参考值标准提供科学依据。方法搜集全国72个市县级医院和有关研究单位测定的10 053例健康老年人APTT参考值,研究其与7项地理指标的关系,通过逐步回归及曲线估计建立并选取最优预测模型,选用克里金法进行插值并绘制健康老年人APTT预测参考值的空间分布图。结果与健康老年人APTT参考值相关系数最大的地理因素是海拔高度,呈显著正相关关系,与海拔高度的最优预测模型为y=30.78+0.002 999X1±0.451。我国健康老年人APTT预测参考值的空间分布规律为西高东低,呈阶梯状分布。结论我国健康老年人APTT预测参考值的空间分布规律与海拔高度的总体分布规律一致,已知中国某地的海拔高度,可通过此模型估算该地健康老年人APTT预测参考值。     

Laboratory controls of heparin therapy with thrombin time, partial thromboplastin time and activated recalcification time

For the laboratory control of a heparin therapy thrombin time, partial thromboplastin time and activated recalcification time are used. On account of distinct differences in the heparin sensitivity of these reactions an indication-related application is necessary. The ability of evidence and the possibility of establishing test-specific therapeutic regions are restricted by differences caused by reagents, individual variability and influence by accompanying haemostasiological changes. The own approach, taking into consideration the so-called heparin resistance, it presented.     

Effect of argatroban on the activated partial thromboplastin time: a comparison of 21 commercial reagents.

Argatroban is a direct thrombin inhibitor used for the treatment of heparin-induced thrombocytopenia. The drug is administered by continuous infusion, at a recommended initial dose of 2 microg/kg per min, to achieve activated partial thromboplastin times (aPTTs) 1.5-3.0 times baseline. We evaluated the effect of argatroban, at clinically relevant concentrations, on aPTTs using 21 commercially available reagents. The aPTTs of plasma containing argatroban at 0.125-8.0 microg/ml (final concentration) were assessed using each reagent and an ACL 3000+ coagulation analyzer. Argatroban increased aPTTs (and aPTT ratios relative to control) in a broadly comparable fashion among reagents. Concentration-aPTT ratio profiles linearized well using logarithmic-logarithmic transformation (r > 0.98), with the regression slope taken as the reagent's sensitivity to argatroban. Sensitivity ranged from 0.304 +/- 0.006 to 0.364 +/- 0.007. Only the least and two most sensitive reagents (all now unavailable in the United States) differed significantly in sensitivity from the other reagents (P < 0.05). aPTT ratios of 2.25 occurred for all reagents at 0.41-0.92 mug/ml argatroban, and for 14 (67%) reagents at 0.53-0.67 microg/ml. This corresponds to a approximately 0.5 microg/kg per min dose difference in healthy subjects. We conclude that most aPTT reagents are similarly sensitive to argatroban, and reagent choice is unlikely to significantly affect argatroban monitoring in patients with heparin-induced thrombocytopenia.     

The clinical significance of a shortened activated partial thromboplastin time in patients with connective tissue disease

Introduction

Connective tissue disease (CTD) patients have been reported to have an increased risk of venous thromboembolism (VTE). Deep venous thrombosis represents a potential emergency that may have a fatal outcome. The D-dimer test is the most widely accepted screening marker for VTE; however, elevation of the plasma D-dimer level without demonstrable thrombosis sometimes accompanies CTD activity itself, infection, and other conditions. Thus, the accuracy of a diagnosis of VTE based on a D-dimer test result is lower in CTD patients. The activated partial thromboplastin time (APTT) test is a very common and simple test.

Method

The medical records of 535 CTD patients were retrospectively investigated. The following data were extracted: APTT, D-dimer, thrombotic events, laboratory data, and systemic corticosteroid therapy.

Results

The rates of thrombotic events and VTE were significantly increased in patients with a shortened APTT (<?26 s) (PSAPTT) in comparison to those without a shortened APTT (p?=?0.004, 0.0009, respectively). The number of PSAPTTs was significantly increased in patients with VTE in comparison to those without VTE (p?=?0.0009). In the diagnosis of VTE in CTD patients, the specificity and positive predictive value (PPV) of the D-dimer test were 71.6% and 83.8% and 12.7% and 19.4%, respectively. The combination of a shortened APTT and elevated plasma D-dimer level improved the specificity and PPV to 94.7% and 97.3% and to 25.0% and 36.4%, respectively.

Conclusions

For the evaluation of possibility of accompanying VTE in CTD patients, APTT shortened was useful and should be evaluated with careful attention.

Key Points

? Regarding the specificity for diagnosing VTE in CTD patients, a shortened APTT showed a value (84.3%) comparable or superior to that of the D-dimer test.

? The combination of a shortened APTT and elevated D-dimer level improved the specificity of the diagnosis of VTE in CTD patients to (94.7% or 97.3%) in comparison to the D-dimer test alone (71.6% or 83.8%).

? The positive predictive value of the combination of a shortened APTT and plasma D-dimer elevation for the diagnosis of VTE in CTD patients increased to 25.0% or 36.4%.

? In the management of CTD patients, physicians should pay attention when they encounter patients with a shortened APTT, as it may indicate VTE.

     

Comparison of four commercially available activated partial thromboplastin time reagents using a semi-automated coagulometer.

Large numbers of activated partial thromboplastin time (aPTT) reagents are sold in the market. The phospholipid content and its source, nature and the amount of activators are highly varied in different aPTT reagents. The present study was undertaken to evaluate which of the four aPTT reagents commonly used is suitable as an all-purpose reagent for a modest haemostasis laboratory. Four aPTT reagents (reagent A, Platelin LS; reagent B, Silimat; reagent C, Actin FSL; reagent D, CK Prest) were tested against 75 different plasmas obtained from normal patients as well as from patients with different haemostatic problems. All the tests were conducted by one of us (S.S.) in duplicates. Different aPTT reagents missed different proportions of mild factor VIII and factor IX deficiency (36.4, 18.2, 4.6 and 13.6% for reagents A, B, C and D, respectively) and showed abnormal results with normal plasmas (i.e. more than 5 s prolongation) (29.2, 25, 8.3 and 12.5% for reagents A, B, C and D, respectively). All the reagents faithfully picked up moderate and severe factor VIII and factor IX deficiency. There was no difference among the four aPTT reagents regarding their ability to prolong aPTT to therapeutic dosage of heparin or in their ability to give comparable factor VIII or factor IX levels in one-stage aPTT-based assays. There were differences in aPTT reagents in their ability to pick up mild deficiency of coagulation factor VIII and factor IX. Some reagents showed abnormal aPTT results in mild cases of factor VIII and factor IX deficiency without producing a large number of falsely prolonged aPTT with normal plasma.