Prediction of vitamin K response using the Echis time and Echis-prothrombin time ratio.

Echis carinatus venom contains proteases capable of activating both normal and descarboxy prothrombin. We showed this venom (Sigma) principally activates prothrombin with almost no factor X activation. Echis time in combination with prothrombin time can predict vitamin K responsiveness since the Echis time is usually normal in the presence of descarboxy prothrombin associated with vitamin K deficiency. 38 patients with abnormal routine prothrombin times (PT) had both coagulant and immunogenic factor II assays along with Echis times done before and after vitamin K. Of 22 patients responding to vitamin K, based on correction of PT, 21 had normal initial Echis times and of 16 not responding, 11 had abnormal Echis times, giving a sensitivity of 95.4% and specificity of 68.8% for vitamin K responsiveness. 90% of patients with a PT/Echis time ratio less than 1.3 and a prolonged Echis time did not correct their PTs with vitamin K therapy. The 5 non-responders with normal Echis times all showed normal initial coagulant and antigenic prothrombin, but 3 had low F V and/or F VII.

Measurement of crosslinked fibrin derivatives--use in the diagnosis of venous thrombosis.

The measurement of crosslinked fibrin derivatives in plasma has received evaluation as a screening test in the diagnosis of venous thrombosis. Plasma samples were taken from 104 patients undergoing venography because of clinical suspicion of lower limb venous thrombosis. The samples were assayed using a monoclonal antibody identifying an epitope on D dimer and larger crosslinked fibrin derivatives in an enzyme immunoassay. 100% of patients with positive venograms had elevated levels of these molecules. While a percentage of patients with negative venograms also had increased levels, alternative clinical explanations were apparent in most. A normal D dimer value excludes the diagnosis of venous thrombosis, while an increased value supports it. The measurement of crosslinked fibrin derivatives in plasma may play a role in the selection of patients for venography.

Sweet's syndrome, acute leukemia, and t(3;5).

We report herein the case of a 36-year-old woman who was diagnosed as having Sweet's syndrome 13 months prior to developing acute myeloid leukemia (FAB type M2). Her bone marrow karyotype was 46,XX,t(3;5)(q21;q31). Translocation t(3;5) has been reported in seven other cases of acute nonlymphocytic leukemia. None of these cases have been associated with Sweet's syndrome.

Transient severe hypoplastic anemia in Q fever.

A case of severe transient marrow hypoplasia as a complication of Q fever is described. This caused marked thrombocytopenia and anemia. The patient recovered fully over the period of 1 wk. The initial marrow showed severe hypoplasia. The subsequent regenerating marrow showed numerous epithelioid granulomas one of which had a characteristic fibrin ring.

Hemolytic uremic syndrome following taipan envenomation with response to plasmapheresis.

We report a case of hemolytic uremic syndrome (HUS) in a 33 year old male who was bitten by a taipan, with apparent massive envenomation. The microangiopathic hemolytic anemia (MAHA) and thrombocytopenic aspects of his HUS appeared to respond to plasmapheresis, but his anuric renal failure persisted. He also had prolonged severe muscular paralysis which gradually began to resolve over the course of two weeks. At this point he suffered a cardiac arrest sustaining severe and subsequently fatal hypoxic brain injury. This case raises the possibility that the taipan venom may have induced HUS by damaging the renal endothelium. His cardiac arrest was not apparently related to his HUS.

The use of two different APC resistance assay systems provides optimal sensitivity and specificity for diagnosing genetic APC resistance.

We compared the performance characteristics of a commercial dilute Russell's viper venom (DRVV)-based APC resistance assay (Gradipore PC Impedance Test) to a routinely utilized commercial APTT based assay (Coatest APC Resistance Assay). The DRVV based assay offers improved sensitivity and specificity for the factor V Leiden mutation. However, the routine use of both assays provides optimum reliability for diagnosis of genetic APC resistance. Our results suggest that when both tests are either positive or negative, DNA analysis is unnecessary. Interference by lupus anticoagulants is dramatically minimized by the phospholipid rich DRVV reagent used in the assay and it is insensitive to high factor VIII activity. Additionally, discrepant functional assay results allow identification of patients who may have an acquired APC resistant phenotype.

High-dose gamma-globulin therapy in the reactive haemophagocytic syndrome.

Reactive haemophagocytic syndrome (RHS) is a disorder characterized by systemic proliferation of non-malignant histiocytes occurring most commonly in patients with pre-existing immunological abnormalities or neoplasms. Patients, particularly those with immunosuppression, often have a rapidly progressive fatal course. Treatment is directed at the underlying disorder. In the absence of identifiable cause, the therapy is less satisfactory. We report here three cases of RHS successfully treated with high-dose gamma-globulin therapy. Two of the three patients were immunocompromised and the third occurred during pregnancy. The improvement occurred within 24-72 h and all patients recovered. High-dose i.v. gamma-globulin therapy may be beneficial in RHS.

Fluctuating symptomatic cryofibrinogenaemia in a patient with left atrial myxoma.

We report a case of left atrial myxoma associated with a fluctuating level of cryofibrinogen. Her initial symptoms and signs were consistent with primary cryofibrinogenaemia, but a repeat episode occurred without the cryofibrinogen being detectable. A more typically embolic cerebro-vascular accident (CVA) occurred, with the subsequent discovery of the patient's myxoma. The cryofibrinogen was again present but it disappeared with resection of the myxoma. We propose that the degree of activation of the coagulation system around the myxoma fluctuated, causing variable conversion of fibrinogen to fibrin, so that at times partially cross-linked fibrin(ogen) resulted in cryofibrinogen, but at other times frank emboli from more complete clotting occurred.

A simple method for synthesis of B-cell clonospecific probes.

A sensitive PCR-based method was developed to produce B-cell clonogenic probes without the need for sequencing and specific oligonucleotide synthesis. Specificity and sensitivity were assessed and found to be comparable to that achieved using established methods. Possible applications include the detection of MRD, bone marrow involvement with lymphoma, and the contamination of autologous bone marrow or peripheral blood progenitor cell harvests with malignant cells carrying IgH rearrangements.

Patterns of failure with increasing intensification of induction chemotherapy for acute myeloid leukaemia.

Patterns of failure were studied in two consecutive randomized trials of intensified induction therapy carried out by the Australian Leukaemia Study Group (ALSG) between 1984 and 1991 to determine the impact of dose intensification. Patients received standard dose cytarabine and daunorubicin (7-3), 7-3 plus etoposide (7-3-7) or 7-3 plus high-dose cytarabine (HIDAC-3-7) chemotherapy. Patients with FAB M3 morphology were excluded. Time to failure (TTF) was defined as the time from randomization to induction death or removal from study for non-responders, or to relapse or death in complete response (CR) for complete responders. An estimated 86% of 470 de novo patients with acute myeloid leukaemia failed within 10 years of randomization, as a result of death in induction in 17% of the randomized patients, failure to achieve CR in a further 17%, relapse in 44% and death in CR in 8% of patients. An estimated 66% of patients failed as a result of refractory disease or relapse within that period (disease-related failures). Multifactor analysis identified age and peripheral blast count as the most significant pretreatment factors associated with overall TTF. These factors, together with cytogenetics, were significantly associated with disease-related failures. High-dose cytarabine in induction significantly decreased the disease-related failure rate as did allogeneic transplantation in first CR. The impact of high-dose cytarabine did not depend on the cytogenetic risk group.