ISI/INR system in Japan: experience from simultaneous measurement of the same plasma at four different laboratories.

In 1984, the Scientific and Standardization Committee (formerly ICTH) recommended the use of the International Sensitivity Index and International Normalized Ratio (ISI/INR) System for the monitoring of oral anticoagulant therapy. This system was introduced because the sensitivity of thromboplastin reagents used for the measurement of prothrombin time (PT) was widely different and comparison among hospitals employing different reagents was virtually impossible. In this study, we simultaneously measured the plasma from 7 patients with warfarin therapy at 4 different institutions for PT seconds, PT-INR, thrombotest (TT) seconds and TT-INR. The comparison between these laboratories revealed clinically important variances between the 4 laboratories even when PT was converted to PT-INR. Laboratory 1 and laboratory 3 were using the same thromboplastin reagents for the measurement of PT. The PT (seconds) in both laboratories showed similar numbers, but when they converted into INR, the variances were significant (maximum coefficient of variance 10.44). We investigated the reason why these differences occurred and found that the PT seconds (11.40) for normal control at laboratory 3 were somewhat larger than those of other laboratories. If we assume that PT-INR is identical to TT-INR, the estimated PT (second) for normal control at laboratory 3 can be calculated from TT-INR, and was found to be 10.56 +/- 0.10 seconds. This was nearly the same as the one that was used at laboratory 1. In conclusion, there still exist some difficulties that must be overcome before the ISI/INR system can be used reliably, and we suggest attention be given to the PT seconds used as normal control plasma.

Optimal therapeutic range for oral anticoagulants in Japanese patients with prosthetic heart valves: a preliminary report from a single institution using conversion from thrombotest to PT-INR.

The thrombotest (TT) technique has been widely used in Japan for monitoring oral anticoagulant therapy (OAT). The therapeutic range was originally recommended to be 10%-25%. However, the International Committee for Standardization in Hematology/International Committee on Thrombosis and Hemostasis (ICSH/ICTH) recommended using the international normalized ratio of prothrombin time (PT-INR) for monitoring OAT. It is necessarv to use a universal standard measure for monitoring OAT in accordance with the ICSH/ISTH recommendation. We simultaneously measured TT and PT in blood samples from 1,157 patients on long-term warfarin therapy, and studied the correlation between TT and PT-INR. An excellent linear correlation was obtained between TT-INR and PT-INR with the regression equation PT-INR = 1.0420 TT-INR - 0.0987 (r = 0.905, P < 0.001). We also examined the correlation between the incidence of thromboembolism in 170 patients receiving warfarin therapy after prosthetic valve replacement; 50.5% received concomitant antiplatelet therapy. Thromboembolism occurred in 9 of 170 patients during a mean follow-up period of 2.44 years. The average TT values in patients with and without thromboembolism were 26.4% (PT-INR: 1.53) and 21.1% (1.73), respectively (P < 0.01). The incidence of thromboembolism did not differ significantly between patients on warfarin alone (average TT: 22.2%) and those on warfarin and antiplatelet agent (average TT: 20.9%). Our results suggest that the incidence of thromboembolism is low in Japan despite a less intensive regimen having been adopted.

[International normalized ratio (INR) for optimal anticoagulant therapy].

Optimal therapeutic ranges for an oral anticoagulant therapy has been discussed for many years. Prothrombin time, prothrombin time ratios (PTR) and thrombotest have been employed so far, but, recently, International Normalized Ratio of prothrombin time (PT-INR or INR) has been introduced. We investigated paying special interest to INR, the effectiveness of oral anticoagulant therapy in 170 prosthetic valve patients and in 157 patients with various cardiovascular diseases who received warfarin at two different centers. The thrombotest, prothrombin time and INR were measured at follow-up visits every month. Regarding the 170 patients with prosthetic valves with a mean follow-up period of 2.44 years, 9 thromboembolisms (TE) were reported. The average TT and INR values in TE-free patients among 101 in whom coagulability could be measured, were 21.1% and 1.73 respectively. The average TT and INR values in 5 patients with TE were 26.4% and 1.53 respectively and this was significantly (p < 0.01) higher (smaller) than in TE-free patients. 157 patients (mean age 55 +/- 12 y.o.) with various cardiovascular diseases (Table 2) were followed up for a mean of 4.9 +/- 3.2 years. As is seen in figure 4, mean INR values in TE patients were 1.28, in patients with bleeding complications 4.1, and in event free patients 2.07 respectively. In conclusion, with INR greater than 2.75, no thromboembolic complication occurred, but several hemorrhagic complications occurred at INR greater than 3. Therefore INR therapeutic ranges between 2.0-3.0 are recommendable both for the prevention of TE and bleeding complications.

[Fifteen-year experience with 24 pregnancies associated with prosthetic valve replacements].

During the past 15 years, we followed 21 patients with prosthetic heart valves who experienced a total of 24 pregnancies at mean age of 31.3 +/- 3.6 years. The course of these patients and their pregnancies were reviewed to evaluate the problems associated with prosthetic heart valves and anticoagulation. Among the 21 patients, the aortic valve (AV) had been replaced in 10 (12 pregnancies), the mitral valve (MV) in nine (10 pregnancies), AV + MV in one (one pregnancy), and the tricuspid valve (TV) in one (one pregnancy). The implanted prosthetic valves were mechanical type in 16 cases (Björk-Shiley 15, Starr-Edwards 1) and bioprosthetic type in six (Hancock 5, Ionescu-Shiley 1). With the exception of one case of intra-uterine fetal death probably related with warfarin therapy, all the patients with bioprosthetic valves underwent successful deliveries. Anticoagulant therapy was employed for 11 pregnancies; warfarin for 10 and subcutaneous heparin for one. No anticoagulant therapy was performed for 13 pregnancies. Ten of the 21 mothers had atrial fibrillation. Eighteen pregnancies (67%) culminated in uneventful deliveries for both mothers and infants. Three mothers (13%) died of thromboembolic complications; two of cerebrovascular accidents and one of acute heart failure caused by thrombus on the replaced valve. All of them had Björk-Shiley valves. Oral warfarin was administered in one of the three, heparin in one and no anticoagulant in the remaining one. Massive maternal bleeding occurred in two cases (8%). There were three cases (12%) of intra-uterine fetal death which were caused by intracranial hemorrhages.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic and scintigraphic improvement after steroid therapy in a case with acute eosinophilic heart disease.

A 70-year-old woman with active hypereosinophilic myocarditis presented with high fever and heart failure. Repeated right ventricular endomyocardial biopsies and 201-T1 myocardial scans before and after steroid therapy suggested that this treatment reversed the cardiac injury. Patients with hypereosinophilia may die from complications of eosinophilic infiltration and fibrosis in target organs, especially the heart. The findings in this patient suggest that steroids have benefit in this disease, at least in the short term.

[A case of aortitis syndrome which presented coarctation of aorta due to intraluminal flap formation in the middle of the thoracic aorta].

We present a rare case of aortitis syndrome associated with dilatation of aorta and coarctation-like effect due to the intraluminal flap formation originated from dissected wall of the aorta. A 31-year-old woman was admitted to our hospital complaining of shortness of breath, palpitation and cough. On admission, her physical status showed congestive heart failure and hypertension of upper extremities and hypotension of lower extremities. Bruits were audible over the neck, the anterior chest and the back. Serological studies showed active inflammation. Chest X-ray film showed upper mediastinal widening, cardiomegaly and pulmonary edema. Aortitis syndrome was strongly suggested by these clinical findings, so that prednisolone therapy was started on 3rd hospital day. Special examinations were performed several days later when inflammatory changes showed a tendency to improve. Chest CT scan, RI angiography and MRI studies showed an aneurysmal dilatation from the ascending aorta to the mid-thoracic aorta. Aortography demonstrated a flap at the terminal portion of this aneurysmal dilatation and grade II (Sellars) aortic regurgitation. There was a pressure difference of 80 mmHg between the parts abutting cranial and caudal sides of the flap. A surgical operation was, then, performed to correct the pressure difference. The dissected wall was extruded toward the aortic lumen creating a flap (2 cm in length). This flap was resected and an artificial graft was inserted. Histologically, the flap consisted of adventitia, media and intima.(ABSTRACT TRUNCATED AT 250 WORDS)

Present status of thromboembolic complications in patients with prosthetic heart valves.

When the incidence of thromboembolism (TE) as a complication was investigated in 171 patients with prosthetic heart valves using pyrolytic carbon, 10 cases were identified in a mean follow-up period of 2.43 years. Of these 10, two patients had died. The incidence of TE as a percentage per patient--year was 2.41 on the whole, 2.15 in patients with aortic valve replacement (AVR), 2.48 in patients with mitral valve replacement (MVR) and 2.52 in patients with double valve replacement (DVR). It is evident that TE is still an important complication following prosthetic heart valve surgery and the patient's return to society. TE tended to occur somewhat more often in cases of MVR and DVR than in those of AVR. TE was apt to appear early in the postoperative period, often within a year, and was often seen in the brain. To prevent TE, it is necessary to carefully control blood coagulation by the administration of anticoagulants.