Recent X-ray crystallography studies on fragments D and DD from fibrinogen and fibrin have revealed the nature of the interaction at the ends of the individual fibrin units. Additionally, cocrystallization of fragments with synthetic peptides patterned on the sequences exposed by the thrombin-catalyzed removal of the fibrinopeptides has provided the details of knob-hole interactions. Interestingly, fragments complexed with the synthetic peptide corresponding to the B knob (GHRPam) exhibit a large conformational change in the presence of the ligand, adding to the intrigue of the still not well understood role of fibrinopeptide B removal.

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Combined factors V and VIII deficiency, a rare hereditary coagulopathy, was found in a 64-year-old woman suffering from a chronic neutrophilic leukemia (CNL), also a rare myeloproliferative disease. Despite of a marked splenomegaly and mature neutrophilia both in the peripheral and bone marrow blood, neither Ph¹ chromosome nor BCR/ABL gene arrangement was found to be present. These findings allowed us to make a diagnosis of CNL. A cytogenetic study showed an abnormal karyotype of del (11) (q23). The observed hemorrhagic diathesis and the elongated prothrombin and partial thromboplastin times may well be attributed to a combined factos V and VIII deficiency, i. e., 22% and 45% of normal in activity, and 10% and 51% of normal in antigen for respective factors in plasma.
None of the circulating anticoagulants, the factor VIII inhibitor, the lupus anticogulant or an anti-cardiolipin antibody was detectable in her plasma. The coagulant activities of factors V and VIII and the peripheral leukocyte counts were not correlated with each other all through her clinical course. Thus, the factors V and VIII deficiency may not have resulted from CNL. On the basis of family studies, the combined factors V and VIII deficiency is unlikely to be an incidental combination of independent deficiencies of factors V and VIII.
Thus, this paper seems to deal with a new type of hitherto unreported association of a combined factors V and VIII deficiency and CNL.

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A 24-year-old Japanese woman with congenital factor VII deficiency (factor VII less than 0.01U/ml) developed a large cyst in the right ovary. She had a history of recurrent joint bleeding and menorrhagia that had been treated with prothrombin complex concentrate (PCC, Proplex^® ST). She underwent right adnectomy successfully with repeated replacement therapy using Proplex^® ST (1, 755 U of FVII: C per vial). Pharmacokinetics study of Proplex^® ST revealed that the biological half-life and in vivo recovery of FVII: C were 5.6h and 152%, respectively. Two vials of Proplex^® ST were given prior to surgery and every 8 hours until 48 hours after surgery, yielding a peak plasma FVII: C level of approximately 1.62U/ml and a trough level of 0.16U/ml. Subsequently, one vial was given every 8 hrs until 16 hours after surgery, resulting in a peak level of 1.07U/ml and a trough level of 0.08U/ml. The administration interval of PCC was prolonged thereafter and the replacement therapy was terminated on the 6th postoperative day. No abnormal bleeding or thrombotic events occurred during the perioperative course.

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Background: Argatroban, a selective and competitive antithrombin agent, produces antithrombotic effects without aggravating bleeding tendency. We used argatroban as an anticoagulant during extracorporeal membrane oxygenation (ECMO) in two pediatric patients with low output syndrome following open heart surgery.
Patients and Results: Patient 1; A 1-year-old boy underwent a radical operation for repair of a common atrioventricular canal. Following surgery, ECMO was successfully performed with argatroban (1.5 to 7.0μg/kg/min) for 4 days. Patient 2; A 3-year-old girl underwent intraventricular baffle repair for double-outlet right ventricle. ECMO was started with heparin, but it was replaced with argatroban (5.0μg/kg/min) on day 2 because of massive gastrointestinal bleeding. This treatment resulted in a gradual decrease in bleeding. ECMO could be carried out without further bleeding for another 3 days.
Conclusions: Our clinical findings suggest that argatroban may be a useful anticoagulant for ECMO.

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