Enhanced fibrinolysis was considered to be the important defense mechanism in preventing the development of MOF in DIC. The increases in plasma levels of t-PA and PAI were poor prognostic markers in DIC. Further careful study may be useful to clarify whether the fibrinolytic therapy is beneficial in clinical DIC patients with MOF.

A genomic DNA obtained from a female patient with complete b-subunit deficiency was examined by Southern blotting analysis and in vitro amplification. Nucleotide sequence analysis showed that adenosine-4161 at the acceptor splice junction of intron A/exon II was deleted in half of the amplified DNAs, resulting in a loss of the obligatory AG splicing sequence. The absence of adenosine-4161 was confirmed by cleavage with TaqI endonuclease of the amplified DNAs. Moreover, sequence analysis showed that guanosine-11499 coding for Cys 430 (TGC) in exon VIII was replaced by thymidine in half of the amplified DNAs, resulting in an amino acid change to Phe (TTC) and the destruction of a disulfide bond in the seventh Sushi domain. This mutation was also confirmed by cleavage with MboII endonuclease. Thus, the proband turned out to be a compound heterozygote of two separate defective alleles. Although half of the amplified DNAs for exon VIII of her daughter or son were cleaved by MboII, those for intron A were not cleaved by TaqI. The replacement of guanosine-11499 by thymidine in their exon VIII has also been confirmed by sequence analysis, indicating that they are heterozygous for one normal and one defective allele.

Pregnancy with paroxysmal nocturnal hemoglobinuria (PNH) is associated with significant risk of complications, such as life-threatening thrombosis. Recently, eculizumab has come into clinical use and revolutionized the treatment of PNH. However, clinical information regarding eculizumab use for PNH during pregnancy is limited. The present report describes pregnancies with PNH treated with eculizumab that were registered with the Japan PNH study group and reviews the literature. In case 1, the patient received eculizumab throughout pregnancy and delivered a healthy neonate at term, although breakthrough hemolysis occurred at 20 weeks of gestation. In case 2, the patient discontinued eculizumab before pregnancy and developed preeclampsia at 27 weeks of gestation. She received eculizumab and delivered a preterm, but healthy, neonate by cesarean section. In case 3, the patient received eculizumab from 18 weeks of gestation and delivered a healthy neonate at term without any complications. Reports of 11 pregnant women treated with eculizumab were identified in the literature. Of 14 pregnancies, including our own cases, breakthrough hemolysis and preeclampsia occurred in five and two cases, respectively. There were no thrombotic complications, maternal or neonatal deaths, or fetal structural abnormalities. Thus, eculizumab appears to be safe and effective for managing PNH during pregnancy.

We investigated whether depressed plasma antithrombin and protein C activity, considered as a specific finding of disseminated intravascular coagulation (DIC), is due to consumption coagulopathy in septic patients with DIC. An analysis of hemostatic parameters was performed in 139 septic patients (68 with DIC and 71 without DIC). Plasma activity of antithrombin and protein C tended to be significantly decreased in septic patients with DIC but not in those without DIC (p < 0.001). However, when the septic patients were classified into three groups according to the albumin (or choline esterase) level, no significant differences in antithrombin activity or protein C activity were observed between the patients with and without DIC in any of the subgroups. Notably, neither the plasma activity of antithrombin nor protein C was decreased even in septic patients with DIC who had normal plasma levels of albumin (or choline esterase). No significant correlation was observed between plasma levels of thrombin-antithrombin complex (TAT) and antithrombin activity, or between plasma levels of TAT and protein C activity either in septic patients with DIC or without DIC. It is reasonable to conclude that the markedly reduced plasma activity of antithrombin and protein C is not due to consumption coagulopathy in septic patients with DIC.

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A questionnaire on COVID-19-related thrombosis in patients hospitalized before Aug 31, 2020, was sent to 399 hospitals throughout Japan. Responses were received from 111 (27.8%) with information on 6,202 COVID-19 patients. Of these, 333 and 56 required ventilation or extracorporeal membrane oxygenation (ECMO), respectively, and 212 died (3.4%). D-dimer levels were measured in 75.0% of the patients, revealing that 9.2% and 7.6% exhibited D-dimer increases of 3-8-fold and ≥8-fold the reference value, respectively. Thrombotic events occurred in 108 patients (1.86% of the 5,807 patients with available data) including symptomatic cerebral infarction in 24, myocardial infarction in 7, deep vein thrombosis in 41, pulmonary thromboembolism in 30, and other thrombotic events in 22. Some patients developed multiple thrombotic events. Thrombosis occurred in 32 patients with mild or moderate COVID-19 severity (0.59% of those with data available) and in 52 patients on ventilation or ECMO (13.5% of severe patients for whom data were available). Thrombosis occurred in 67 patients during worsening clinical condition and in 26 during recovery. Anticoagulant therapy was provided to 893 patients (14.6% of the 6,119 patients with available data), the main reasons being provided as elevated D-dimer levels and worsening clinical condition. patients, other venous thromboses in 3, cerebral infarction in 5 and peripheral arterial thrombosis in 2 patients 1). However, data on COVID-19-related thrombosis in Japan are limited. Thus, in order to gather data on this topic and elucidate how COVID-19-related thrombosis is diagnosed and treated in Japan, a Joint Team of the Japanese Society of Thrombosis and Hemostasis, the Japanese Atherosclerosis Society, and the Research Study Team for Intractable Disease (Blood Coagulation Abnormalities) supported by the Ministry of Health, Labour and Welfare of

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