The investigation of a prolonged APTT with specific clotting factor assays is unnecessary if an APTT with Actin FS is normal

Introduction: An isolated prolongation to the activated partial thromboplastin time (APTT) can be caused by the presence of the lupus anticoagulant or an intrinsic or contact factor deficiency, of which only deficiencies of factors VIII, IX or XI are associated with bleeding. Our local protocol states that further investigation of a prolonged APTT by specific assays of FVIII, FIX and FXI should only be undertaken where the APTT with one reagent (Synthasil) is more than 3 s prolonged, and further investigation by an APTT with a second reagent (Actin FS) is also prolonged, unless there is a history of bleeding in the patient, in which case assays are indicated irrespective of the APTT. Methods: We retrospectively reviewed the results of all APTTs performed over a 36 ‐month period to evaluate whether strictly applying our protocol would reduce the number of unnecessary clotting factor assays performed, without leaving patients with potentially significant bleeding disorders undiagnosed. Results: Of a total number of 587 samples tested for coagulation factors VIII, IX and XI, only 117 samples yielded an abnormal result. Thus, 80% of all the assays requested in the 3 ‐year period audited gave a result within the reference range for factors VIII, FIX and XI. Three quarters of the abnormal results revealed mild FXI deficiency. Conclusion: This review has demonstrated that no significant coagulation factor deficiency would be left undiagnosed if the protocol was followed. This would have considerably reduced the cost and time spent performing these assays.     

Assessment of Actin FS and Actin FSL sensitivity to specific clotting factor deficiencies

We present a two centre study designed to assess the sensitivity of Actin FS and Actin FSL to deficiencies of factor VIII, IX, XI or XII. The study was undertaken at two centres to avoid bias due to the investigations being undertaken on one analyser. Samples from patients with a factor VIII (n = 36, F VIII = < 1.0–50 iu/dl), factor IX (n = 22, F IX = 2–48 iu/dl), factor XI (n = 23, F XI = 5–50 u/dl) or a factor XII (n = 18, F XII = 1–50 u/dl) deficient state were studied. Activated partial thromboplastin times (APTT) were determined using two batches of Actin FS and of Actin FSL; comparison of APTT results between centres was facilitated by the conversion of clotting times to ratios (test ÷geometric mean normal clotting time). APTT ratios were considered to be elevated if greater than two standard deviations above the mean normal. The factor deficient status of each sample was verified by assaying all samples for factors VIII, IX, XI and XII. Clotting factor assays were performed on a Sysmex CA-1000^? fitted with research software, which permitted the auto-dilution and testing of three serial dilution of both a reference preparation and each patient's sample. Assay results were calculated using parallel-line Bioassay principles. This procedure allowed for variation in clotting times due to the effect of temporal drift of any of the reagents within the assay system. Actin FS and Actin FSL demonstrate acceptable sensitivity to factor VIII deficiency, however, both reagents failed to detect a large proportion of factor XI (17.4% and 30.4% of samples, respectively) and factor XII (66.7% and 72.2%, respectively) deficiencies. The detection rate with Actin FSL for factor IX deficiency was also poor (36.4% not detected). As factor IX and XI deficiencies are both associated with haemorrhagic disorders, the inability of these reagents to detect such abnormalities gave cause for concern.     

Influence of factor VIII:C and factor IX activity in plasmas of haemophilic dogs on the activated partial thromboplastin time measured with two commercial reagents

The present study is based on 145 plasma samples with a reduced activity of factor VIII:C (range: 0.009-0.62 IU mL-1) and 28 samples with a reduced factor IX activity (range: 0.035-0.55 IU mL-1). The samples were collected from dogs with haemophilia A (n=22) or haemophilia B (n=3), some of these during substitution therapy. For all samples the activated partial thromboplastin time (APTT) was measured with two commercial reagents containing kaolin as a contact activator. In each case, the deficiency of factor VIII:C or IX was reflected in abnormal results of the APTT. This was true for both reagents. A significant correlation (P < 0.001) was found between factor VIII:C activity and APTT (reagent 1, Pathromtin(R); Spearman's rank correlation coefficient, rS=-0.731, reagent 2, PTT-Reagenz; rS=-0.875) as well as between factor IX activity and APTT (reagent 1, rS=-0.819; reagent 2, rS=-0.955]. In each case, the relationship between coagulation factor activity and APTT could be proven most precisely by geometric regression. The results of this study illustrate the applicability of commercial APTT test kits as a sensitive screening test of factor VIII:C and IX deficiencies in canine plasma.     

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.     

A comparison of two APTT reagents which use silica activators

The Ortho activated partial thromboplastin time (APTT) reagent, Thrombosil 1 (TS), was compared to the General Diagnostics automated APTT reagent (GD). TS produced more precise results over a 38-day period of testing a normal control plasma, indicating that the upper limit of the normal range could be more precisely set with TS. This normal range was better represented if the normal values with both reagents were logarithmically transformed before calculating the mean +/- 2 SD. TS was more sensitive to plasma which had been heparinized in vitro. This was also demonstrated in vivo by the testing of 100 plasmas from heparinized patients. On testing of in-vitro dilutions of normal plasma with factor-deficient plasmas, TS was more sensitive to decreasing levels of factors VIII, IX and XI but less sensitive to decreasing factor XII. This was demonstrable in vivo in 71% of cases with plasmas from factor-deficient patients. GD was more sensitive to the lupus anticoagulant in most cases.     

Haemarthrosis in patients with mild coagulation factor deficiency.

While haemarthrosis is a common finding in severe factor VIII or IX deficiency, it is unusual in mild coagulation factor deficiencies. We describe three patients with mild factor IX, X or XI deficiency who presented with spontaneous haemarthrosis. All underwent joint puncture with subsequent worsening of the haemarthrosis in the affected joint. This report indicates that: (i) even mild coagulation factor deficiency may be associated with haemarthrosis; (ii) patients with suspected haemarthrosis should undergo routine screening coagulation tests before joint puncture; and (iii) any abnormalities in the screening tests indicate a need for further evaluation of the coagulation status. In such cases puncture of the joint should be deferred and specific therapy started immediately.     

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.     

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.     

Laboratory performance of haemophilia centres in developing countries: 3 years' experience of the World Federation of Hemophilia External Quality Assessment Scheme

A World Federation of Hemophilia External Quality Assessment Scheme has been established to promote high standards of laboratory performance in haemophilia centres worldwide. Results from 21 International Haemophilia Training Centres (IHTCs) provide target values for the prothrombin time (PT), activated partial thromboplastin time (APTT), factor VIII:C, IX:C and von Willebrand factor (VWF) assays, against which the performance of Haemophilia Centres in developing countries (HCs) can be assessed.
Eight surveys were distributed over a 3-year period between 1994 and 1997. A higher proportion of HCs failed to identify an abnormal PT or APTT in samples from donors with mild deficiencies of the extrinsic and intrinsic systems, respectively. For factor VIII:C and IX:C assays, agreement between HC results was consistently poorer than between IHTCs. However, improvement in between-centre agreement could be seen for two samples distributed on more than one occasion. A minority of HCs perform assays for VWF, and a questionnaire revealed equipment and reagent costs as limiting the range of assays which could be carried out in several centres. However, agreement was in some cases better between those HCs that did perform VWF assays than between IHTCs. The problems of screening test sensitivity and between-centre agreement for factor assays need to be addressed, together with the limitations which prevent HCs from performing a full range of tests in the diagnosis and treatment of bleeding disorders.     

Performance characteristics of a new synthetic APTT reagent

Performance characteristics of a totally synthetic activated partial thromboplastin time (APTT) reagent, recently available commercially, were evaluated and compared with a rabbit-brain extracted reagent. We found that the synthetic reagent, Synthasil, returned significantly higher normal APTT values than the brain-extracted reagent, Thrombosil. APTT ratios (APTT patients/normal mean APTT), yielded by Synthasil were higher in the majority of patients receiving heparin therapy. Synthasil also returned longer APTT values than did Thrombosil on normal plasma spiked with heparin. On patients with lupus anticoagulants, APTTs assayed with Synthasil were generally longer than with Thrombosil. However, the differences disappeared when APTT values were converted to ratios. Factors XII-, XI-, IX- and VIII-deficient plasmas supplemented with normal plasma to yield activities of 2–50%, generally gave longer APTTs with Synthasil than with Thrombosil. However, this was not always the case on plasmas from haemophilias A and B patients. No reduction in Synthasil activity was noted after the reagent had been left at 24 °C for 28 days.     

Activated Partial Thromboplastin Time

An internationally standardized preparation and 10 commercial kits widely used to perform the activated partial thromboplastin time (APTT) were compared in 4 laboratories for the purpose of assessing their ability to detect mild deficiencies of factor VIII activity. The participating laboratories were asked to carry out with each APTT reagent quadruplicate readings of 3 coded lyophilized plasmas containing varying levels of factor VIII (109, 26 and 17 U/dl respectively). An analysis of variance of clotting times showed significant differences between reagents and laboratories. All the reagents detected the abnormality of the plasma containing 17 U/dl, whereas a number of failures were found when the plasma with 26 U/dl was tested. When analysis of variance was carried out on ratios of factor-VIII deficient to normal plasma clotting times, the results showed less difference between laboratories and reagents. Clotting times of plasma with normal factor VIII level (109 U/dl) usually fell within the normal range indicated by manufacturers of the commercial reagents.     

Spectrum of changes in endogenous thrombin potential due to heritable disorders of coagulation

The modern thrombin generation tests describe different phases of generation of thrombin that is initiation, amplification and inhibition of thrombin generation as well as the integral amount of generated thrombin. We investigated 55 patients with congenital deficiencies of different coagulation factors and analysed the relationship between the nature and the concentration of clotting factors, with different parameters of thrombin generation curve that is lag time, peak, time to peak and the area under curve or endogenous thrombin potential. The endogenous thrombin potential was unaffected by severe deficiency of factors XI and XII, and reduced in factor IX, VII and factor V and VIII deficiencies. The lag time was significantly prolonged in cases of severe factor VII, X and V deficiencies, and was almost normal in cases of factors VIII, IX, combined factors V and VIII, factor XI, XII and XIII deficiencies. The peak height was severely affected in cases of severe factor X, V, VIII and IX deficiency and combined deficiency of multiple vitamin K dependant coagulation factors, and significantly reduced in factor VIII, V, X, XIII and combined vitamin K deficiency.In all the patients with less than 40% thrombin generation, the clinical symptoms were severe. Bleeding symptoms were restricted to epistaxis and ecchymosis when thrombin generation was more than 90% of the normal. In the cases of combined deficiency of factors V and VIII all the values were intermediate as they exhibit mild deficiencies of both factors V and VIII and correlated well with the clinical symptoms. Endogenous thrombin potential of inherited isolated deficiencies of coagulation factors may thus provide an interesting insight about involvement of the deficient factor(s) at different phases of thrombin generation.     

An attempt to standardize APTT reagents used to monitor heparin therapy.

Citrated samples from 100 patients on i.v. heparin and 20 normal patients were tested with three batches each of three activated partial thromboplastin time (APTT) reagents: Thrombosil I (Ortho); Automated APTT (Organon Teknika) and Actin FSL (Baxter). The ratio of APTT over the geometric mean normal APTT for each heparinized sample was calculated. One batch of reagent arbitrarily chosen as a reference gave the ratios APTRREF (y). The remaining reagents to be standardized against the reference system gave the ratios APTRTEST (x). The best correlation between systems was given by log vs log x. Standard curves were prepared from the APTT ratios of the 20 normal patients and 65 of the heparinized samples. On plotting log APTRTEST vs log APTRREF the y intercept was close to zero so x was expressed in terms of y using; log x = HSI. log y, where HSI (Heparin Sensitivity Index) = slope. The APTRTEST results of the remaining 35 heparinized samples were transformed using; APTRTRANS = (APTRTEST)HSI.APTRTRANS was then compared to APTRREF to determine whether the transformation brought the results closer to the reference. We conclude that although some improvement was found by using the transform, it was not possible to mathematically relate APTT results due to a high degree of variation between results using different reagents. A standard APTT reagent for the monitoring of heparin therapy is recommended. A separate APTT reagent may be required for the screening of factor deficiencies and lupus anticoagulants.     

Evaluation of the activated partial thromboplastin time assay for clinical monitoring of PEGylated recombinant factor VIII (BAY 94‐9027) for haemophilia A

Patients with haemophilia (PWH) are usually monitored by the one‐stage activated partial thromboplastin time (aPTT) factor VIII (FVIII) assay. Different aPTT activators may affect clotting time (CT) and FVIII:C levels in patients treated with PEGylated FVIII. To evaluate the characteristics of PEGylated FVIII (BAY 94‐9027) in various aPTT clotting assays, and to identify suitable aPTT reagents for monitoring BAY 94‐9027 during the treatment of PWH, BAY 94‐9027 and World Health Organization (WHO) 8th FVIII standards (WHO‐8) were spiked into pooled and individual severe haemophilia A plasma at 1.0, 0.25 and 0.05 IU mL^?1. Five commercial aPTT reagents widely used in clinical laboratories were compared and evaluated for BAY 94‐9027 activity in plasma from PWH. BAY 94‐9027 and WHO‐8 bestowed similar CT and excellent precision when ellagic acid (SynthAFax, Dade Actin, and Cephascreen) aPTT reagents were used. In contrast, BAY 94‐9027 showed significantly prolonged CT and poor precision compared with WHO‐8 using silica aPTT reagents (APTT‐SP and STA PTT 5). Furthermore, free 60‐kDa polyethylene glycol (PEG), used for the conjugation of FVIII, showed a dose‐dependent prolongation of CT in the APTT‐SP assay. There was no effect on the SynthAFax‐APTT, prothrombin time, or FXIa‐initiated thrombin generation assay, demonstrating that the PEG moiety on FVIII has no general effect on the coagulation cascade. In summary, ellagic aPTT reagents (SynthAFax, Dade Actin, and Cephascreen) are most suitable for evaluating potency of BAY 94‐9027 and should be the preferred aPTT reagents used in clinical laboratories for monitoring FVIII activity after infusion of BAY 94‐9027 to PWH.     

Fibrin formation, fibrinopeptide A release, and platelet thrombus dimensions on subendothelium exposed to flowing native blood: greater in factor XII and XI than in factor VIII and IX deficiency

Fibrin deposition and platelet thrombus dimensions on subendothelium were studied in four groups of patients with coagulation factor deficiencies. Five patients with factor VIII deficiency (APTT 120 +/- 8 sec) and three patients with factor IX deficiency (APTT 125 +/- 11 sec) were severe bleeders, whereas four patients with factor XII deficiency and seven with factor XI deficiency were either asymptomatic or only mild bleeders despite APTT values of 439 +/- 49 and 153 +/- 13 sec, respectively. Everted segments of deendothelialized rabbit aorta were exposed at a shear rate of 650 sec(-1) for 5 and 10 min to directly sampled venous blood in an annular chamber. Blood coagulation was evaluated by measuring fibrin deposition (percent surface coverage) on the subendothelium and post-chamber fibrinopeptide A levels; platelet thrombus dimensions on the subendothelium were evaluated by determining the total thrombus volume per surface area (using an optical scanning technique) and the average height of the three tallest thrombi. Consistent differences were observed among the patient groups for both the 5-min and 10-min exposure times. The larger of the 5- and 10-min exposure-time values was used to calculate group averages. Fibrin deposition in normal subjects was 81% +/- 5% surface coverage, and post- chamber fibrinopeptide A values were 712 +/- 64 ng/ml. Markedly decreased fibrin deposition and fibrinopeptide A levels were observed in factor VIII deficiency (2% +/- 1% and 102 +/- 19 ng/ml) and factor IX deficiency (11% +/- 7% and 69 +/- 11 ng/ml). In contrast, significantly higher values were obtained in patients deficient in factor XI (33% +/- 5% and 201 +/- 57 ng/ml) and factor XII (66% +/- 12% and 306 +/- 72 ng/ml). Differences in thrombus dimensions were also observed. In normal subjects, the value for thrombus volume and average height of the tallest thrombi were 8.3 +/- 1.3 cu micron/sq micron and 145 +/- 11 micron, respectively, and in patients were as follows: FVIII, 2.7 +/- 0.6 and 71 +/- 7; FIX, 4.5 +/- 1.8 and 88 +/- 14; FXI, 11.8 +/- 1.9 and 125 +/- 10; and FXII, 7.9 +/- 3.1 and 130 +/- 25. Platelet thrombus dimensions were normal in a patient with fibrinogen deficiency, indicating that the smaller thrombi in factor VIII and factor IX deficiencies were probably due to impaired evolution of thrombin rather than diminished fibrin formation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Assessment of a new instrument (Coag-A-Mate X2) for performing global clotting tests and specific factor assays

Coag-A-Mate X2 (General Diagnostics) is an automated photo-optical system for detection of clots, which can be used for measuring prothrombin time (PT) and activated partial thromboplastin time (APTT) and assaying coagulation factors. We have compared results obtained with this instrument with those obtained by the manual method used routinely in our specialized laboratory. The instrumental results showed good precision (PT: between-assay CV from 1.3 to 3.0, APTT: from 2.2 to 3.1), and high degree of correlation with the manual results (for PT r = 0.99, for APTT r = 0.95). There was also good correlation between the two methods (0.98-0.99) for factor assays (V, VII, VIII, IX, X, XI, and XII). High output, reproducibility, comparability and flexibility make this instrument suitable for both clinical and research laboratories.     

A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism

Hypercoagulability due to high coagulation factors XI, VIII, IX, II, and fibrinogen is recognized as a risk factor of venous thromboembolism (VTE). These factors are cumulatively explored by the activated partial thromboplastin time (APTT). To test the hypothesis that a short APTT increases the risk of VTE, a case-control study was carried out in 605 patients referred for thrombophilia testing after documented VTE and in 1290 controls. Median APTT ratio (coagulation time of test-to-reference plasma) values were 0.97 (range: 0.75-1.41) for patients and 1.00 (range: 0.72-1.33) for controls (P < .001). In patients who had an APTT ratio smaller than the fifth percentile of the distribution in controls, the odds ratio (OR) for VTE was 2.4 (95% confidence interval [CI]: 1.7-3.6) and was independent of inherited thrombophilic abnormalities. Further statistical analyses in 193 patients and 259 controls for whom factor VIII (FVIII) levels were available showed a decrease of the OR from 2.7 (95% CI: 1.4-5.3) to 2.1 (95% CI: 1.0-4.2), indicating that the risk was only partially mediated by high FVIII levels. In conclusion, hypercoagulability detected by a shortened APTT is independently associated with VTE. This inexpensive and simple test should be considered in the evaluation of the risk of VTE.     

Fletcher Factor Deficiency: Family Study and Detection

Eight of 11 children of a known Fletcherfactor-deficient individual were found tohave normal activated partial thromboplastin times, normal levels of factors VIII,IX, XI, and XII, and a mean Fletcher factorlevel of 53% (range 40%-72%), suggesting a heterozygous state for the genecontrolling Fletcher factor production. Allpartial thromboplastin time reagents containing celite or kaolin were sensitive toFletcher factor deficiency, while one reagent containing ellagic acid did not detect this abnormality. The finding of anabnormal partial thromboplastin time thatis corrected by a 10-min incubation periodis presumptive evidence for Fletcher factordeficiency.

Submitted on July 13, 1973 Revised on October 28, 1973 Accepted on November 5, 1973     

A novel congenital haemostatic defect: combined factor VII and factor XI deficiency.

Isolated deficiencies of factors VII and XI are both rare. Not surprisingly, therefore, combined factor VII and XI deficiency has not been reported previously. We report here a kindred with a combined heterozygous deficiency for both factors VII and XI. The proposita is a 28-year-old woman who had both a prolonged prothrombin time (PT) and a prolonged activated partial prothrombin time (APTT) associated with a mild bleeding tendency. Coagulation studies were performed on the six available members of this kindred. The PT and APTT were normal or mildly abnormal in five of these individuals. Factor VII coagulant activity (VII:C) varied from 0.33 to 0.77 units/ml in affected subjects. In contrast, the concentration of factor VII-related antigen for the six individuals ranged from 0.68 to 2.10 units/ml. Comparable factor VII:C levels were obtained when each subject's plasma was tested with either a rabbit or a human thromboplastin reagent. Factor XI coagulant activity was less than 0.5 units/ml in three of the six subjects and normal (approximately 1.0 units/ml) in the other three. The concentrations of thrombin-antithrombin-III and prothrombin fragment 1.2 were within normal limits for all individuals. In addition to being associated with heterozygous factor XI deficiency, the abnormal factor VII molecule in the plasma of affected individuals in this kindred appears to represent a newly described mutation. This is suggested by the pattern of reactivity with thromboplastin from different species, the normal tissue factor binding and the bleeding tendency in heterozygous individuals in this kindred.     

Automated amidolytic method for evaluating the activated partial thromboplastin time compared with a conventional coagulation method

We report studies of the validity and clinical application of a new amidolytic method for evaluating the activated partial thromboplastin time (APTT) compared with a conventional clotting method. The results with the two methods were well correlated for normal plasma and plasma from hemophilia patients. Congenital deficiencies of of the intrinsic coagulation pathway other than hypo- and dysfibrinogenemia detected by the amidolytic method agreed with those detected by the clotting APTT. The results with the two methods for plasma from patients under heparin treatment were statistically different, suggesting a lesser sensitivity of the amidolytic method to heparinization. The use of the amidolytic APTT reagent in combination with factor VIII and IX deficient plasma allowed the measurement of both factors. The results obtained with normal and hemophilic plasma were in agreement with those obtained with the one-stage clotting method in all except two occasions. Even though the amidolytic method demonstrated the presence of the lupus anticoagulant in the majority of tested samples of known lupus subjects, it was less sensitive to the abnormality than the clotting method.