Recombinant factor VIIa corrects prothrombin time in cirrhotic patients: A preliminary study

BACKGROUND & AIMS: Cirrhotic patients with a prolonged prothrombin time (PT) are known to have low levels of factor VII. Because the current modalities to correct this problem are not ideal, recombinant factor VIIa (rFVIIa) may be useful in correcting the prolonged PT observed in the coagulopathy of cirrhosis. The aim of this study was to evaluate the effectiveness of rFVIIa in nonbleeding volunteer patients with the coagulopathy of cirrhosis. METHODS: A preliminary, single-center, dose- escalation trial was performed. Cirrhotic patients with a PT of > 2 seconds above the upper limit of the reference value received an intramuscular injection of vitamin K. Ten patients whose PT did not correct to within 2 seconds above the control of the upper limit of the reference value were given three successive dosages of rFVIIa (5, 20, and 80 micrograms/kg) during a 3-week period. RESULTS: The mean PT transiently corrected to normal in all three dosage groups. No adverse effects were noted. There was no evidence of the induction of disseminated intravascular coagulation. CONCLUSIONS: This preliminary trial shows rFVIIa to be effective in transiently reversing the prolonged PT in a select group of nonbleeding cirrhotic patients. These preliminary observations support conducting a large-scale efficacy trial. (Gastroenterology 1997 Dec;113(6):1930-7)     

Mutation of the prothrombin gene and thrombotic events in patients with polycythemia vera or essential thrombocythemia: a cohort study

The association between a prothrombin mutation and the risk of thrombosis was analyzed in 214 patients with polycythemia vera or essential thrombocythemia. The rate for venous thrombotic events was 14.7/100 patient-years in patients with the prothrombin mutation compared to 0.8 in patients without the mutation (rate ratio 17.5).     

Home prothrombin time monitoring after the initiation of warfarin therapy. A randomized, prospective study

STUDY OBJECTIVE: To evaluate the efficacy and accuracy of monitoring prothrombin times at home. DESIGN: Randomized, prospective cohort study. SETTING: Outpatients discharged from a university hospital or a community hospital. PATIENTS: Fifty patients started on warfarin for the first time who demonstrated an ability to use the monitor and who had not achieved a stable response to warfarin in the hospital. INTERVENTION: Oral anticoagulation therapy managed using a portable prothrombin time monitor compared with specialized anticoagulation clinic care. MEASUREMENTS AND MAIN RESULTS: In the 46 patients who completed the 8-week study, the median percentage of time that patients in the home-monitor group (n = 23) were within a range equal to the target prothrombin ratio +/- 0.3, but always above 1.25, was 93%, compared with 75% for patients in the clinic group (n = 23) (P = 0.003). There was no significant difference between groups in the percentage of time above the therapeutic range; however, the percentage of time that patients were subtherapeutic was significantly greater in the clinic group (P less than 0.001). There were no major thromboembolic or hemorrhagic complications in either group. Differences between home monitor measurements and corresponding clinical laboratory measurements using blood samples drawn within 4 hours of the home test were comparable to differences observed between measurements using two different clinical laboratory instruments. CONCLUSIONS: Use of a portable prothrombin time monitor by patients at home is feasible and provides accurate measurements. Patients doing home monitoring achieve superior anticoagulation control compared with those receiving standard anticoagulation clinic care.     

Abnormal prothrombin consumption time in ulcerative colitis

Summary The prothrombin consumption time was assayed in 40 patients suffering from ulcerative colitis and compared with that of 30 control patients who did not have clinical evidence of a hemorrhagic disease. Prothrombin time was also measured in each patient. Platelets were examined on a blood smear, and peripheral capillary fragility was evaluated in the diseased patients.Ulcerative colitis patients had abnormal prothrombin consumption times and prothrombin times. They had normal platelets and normal peripheral capillary fragility. The prothrombin consumption time was normal when ulcerative colitis was mild. Most abnormal prothrombin consumption times occurred in patients with severe ulcerative colitis.     

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.     

An analysis of the one-stage prothrombin time

An analysis of the one-stage prothrombin time using thromboplastins highly (Thrombotest) and slightly (Normotest) sensitive to the Pivka (protein induced by vitamin K absence) inhibitor is presented. A one-tenth dilution of blood with 0.1 mol/l Na3 citrate was satisfactory even at an extreme packed cell volume (PCV). Whole blood and plasma were equally satisfactory as test materials; however, their accuracy and precision were greatly improved when a small sample size at a high coagulation activity and a large sample size at a low coagulation activity were used. The PCV correction method which corrected for the different Pivka inhibitor sensitivities of thromboplastins was preferable.     

中晚期肝病患者凝血酶原时间标准化形式探讨

目的 探讨中晚期肝病患者凝血酶原时间(PT)的标准化形式。方法 收集慢性重型肝炎患者l6例，肝硬化失代偿患者50例，口服抗凝治疗4～6周患者30例。用6种不同凝血活酶国际敏感化指数(ISI)值的组织凝血活酶检测这些患者的PT，凝血酶原时间活动度(PTA)．凝血酶原时间比率(PTR)与国际标准化比率(INR)。结果 慢性重型肝炎患者6组间PTA差异较小，平均值波动于24％～34％，上限值波动于47％～61％；而INR组间差异非常显著，平均值波动丁2．55～5．13，上限值波动于4．65～l2．77。单因素方差分析PPTA(0．489)＞1NR(0．120)。肝硬化患者6组间PTA平均值波动于50％～59％，上限值波动于82％～90％；INR平均值波动于1．40～1．80，上限值波动于1．97～3．69。单因素方差分析PPTA(0．102)＞PINR(0．01)。PTA的波动范围均小于INR。但对口服抗凝治疗的患者，INR的波动范围最小。以STAR血凝仪的配套试剂Neoplastine所测PT值与其它5种试剂所测值进行相关分析，中晚期肝病患者PTA作为PT的表达方式时，相关性最好，而其它形式较为弥散。口服抗凝治疗患者INR作为PT的表达方式时，相关性最好。结论 PTA可将中晚期肝病患者PT标准化。     

Comparison of the native prothrombin antigen and the prothrombin time for monitoring oral anticoagulant therapy

We have measured the fully carboxylated (native) prothrombin antigen and the undercarboxylated (abnormal) prothrombin antigen in patients treated with sodium warfarin using specific immunoassays to evaluate a new approach for monitoring oral anticoagulant therapy. Plasma and serum samples (391) were assayed for the prothrombin time, native prothrombin antigen, and abnormal prothrombin antigen. The results were correlated with the presence of bleeding or thromboembolic complications at the time of phlebotomy. The native prothrombin antigen correlated with the occurrence of complications in 95% of samples. Of 13 samples from patients with bleeding complications, 13/13 (100%) had a native prothrombin of 12 micrograms/mL or lower. Of seven samples from patients with thromboembolic complications, 6/7 (86%) had a native prothrombin of 24 micrograms/mL or greater. By comparison, a prothrombin time index of 1.5 to 2.5, 1.5 to 2.2, 1.5 to 2.0, or 1.3 to 1.8 identified 6/20 (30%), 9/20 (45%), 11/20 (55%), or 12/20 (60%) patients at risk, respectively. Although the prothrombin time index did correlate with the presence of bleeding complications, the native prothrombin antigen correlated closely with the presence of bleeding and thromboembolic complications. According to these results, the native prothrombin antigen, maintained in a range of 12 to 24 micrograms/mL by regular adjustment of the warfarin dosage, may be associated with a reduced risk of complications due to excessive or insufficient warfarin therapy. On the basis of these preliminary data, we recommend that the native prothrombin antigen be considered to monitor warfarin therapy.