A correlation between cancer and hypercoagulability has been described for more than a century. Patients with cancer are at increased risk for thrombotic complications, and the clotting initiator protein, tissue factor (TF), is possibly involved in this process. In addition to TF, the presence of negatively charged phospholipids, particularly phosphatidylserine (PS), is necessary to support some of the blood-clotting reactions. There are few reports describing PS exposure by tumor cells. In this study, we characterized the procoagulant properties of the murine B16F10 and the human WM-266-4 melanoma cell lines. Flow cytometry analyses showed constitutive TF expression by both cell lines, in contrast to negative staining observed for the nontumorigenic melanocyte lineage, melan-A. In addition, tumor cells accelerate plasma clotting in a number-dependent manner. For WM-266-4, this ability was partially reversed by an anti-TF antibody but not by aprotinin, a nonspecific serine-protease inhibitor. Furthermore, flow-cytometric analyses showed the presence of PS at the outer leaflet of both cell lines. This phenomenon was determinant for the assembly of the intrinsic tenase (FIXa/FVIIIa) and prothrombinase (FXa/FVa) complexes, resulting in the activation of FX to FXa and prothrombin to thrombin, respectively. As a result, incubation of WM-266-4 with human plasma produces robust thrombin generation. In conclusion, simultaneous TF expression and PS exposure are responsible for the highly procoagulant pattern of the aggressive melanoma cell lines B16F10 and WM-266-4. Therefore, these cell lines might be regarded as useful models for studying the role of blood coagulation proteins in tumor biology.

While it has been established that anti‐phospholipid antibodies (aPL) are associated with recurrent miscarriage (RM), the importance of anti‐β2 glycoprotein 1 (GP1) IgG and anti‐annexin V IgG antibodies as risk factors for RM is undefined. We have investigated the prevalence of anti‐β2 GP1 IgG and anti‐annexin V IgG antibodies in 54 aPL‐positive and 48 aPL‐negative women with RM. The prevalence of IgG anti‐β2 GP1 antibodies was not significantly different in persistently aPL‐positive women with RM (7%), aPL‐negative women with RM (6%) and the normal parous control group (3%). Anti‐annexin V IgG antibody prevalence was significantly increased in aPL‐positive women with RM compared with aPL‐negative women with RM (P = 0·01). The elevations were found in 35%, 19% and 16% of aPL‐positive women with RM, aPL‐negative women with RM and the control group respectively. No women showed positivity for both anti‐β2 GP1 IgG and anti‐annexin V antibodies. Anti‐β2 GP1 IgG antibodies do not appear to be contributory to the investigation of women with RM. Anti‐annexin V antibody positivity, although associated with aPL positivity in women with RM, is not an independent risk marker.

Many recurrent pregnancy losses appear to have a thrombotic etiology. We have investigated the prevalence of the G20210A prothrombin gene mutation in 122 women with a history of three or more early (≤12 weeks gestation; n = 91), late (> 12 weeks gestation; n = 2). or mixed (n = 29) consecutive pregnancy losses. A control group of 66 healthy parous women with no history of thrombosis or miscarriage was also studied. Four heterozygotes that suffered only early pregnancy losses were detected in the patient group giving a prevalence of 3.3%. Three of the control group women were heterozygous for the mutation, giving a prevalence of 4.5% (p = 0.32; odds ratio 0.71; 95% confidence interval [CI] 0.15-3,27). When only Caucasians were analyzed, a prevalence of 3.9% (4/103) was observed in the patient group and 4.2% (2/48) in the control group ( p = 0.28; odds ratio 0.89; 95% CI 0.16-5.05). The prevalence of the G20210A prothrombin gene mutation is not increased in women with recurrent miscarriage, although it was only found in women who had suffered early pregnancy losses. However, it remains possible that this mutation is relevant in a selected subgroup of women with recurrent miscarriage, additional thrombophilic defects, and in whom fetal loss is associated with placental infarction and thrombosis.

Objective: To determine the prevalence of antiphospholipid (aPL) and anti-beta 2 glycoprotein I (anti-β2-GPI) antibodies in women referred for IVF and to prospectively evaluate the effect of these antibodies on IVF outcome.

Methods of monitoring heparin in pregnancy are problematic. The aim of this study was to assess the plasma HEPTEST as a rapid and reliable test for heparin monitoring in pregnancy. HEPTEST, activated partial thromboplastin time (APTT) and chromogenic anti-Xa assays were performed on individual heparin-spiked plasma samples from two groups: normal non-pregnant women (n = 6) and normal pregnant women during the third trimester (n = 6). Heparin activity curves were established in plasma from both groups for low (< 0.3 IU/ml), intermediate (0.3-0.7 IU/ml) and high (> 0.7 IU/ml) heparin concentrations and validated by comparison with the anti-Xa chromogenic assay. Both the APTT and HEPTEST demonstrated good correlation with anti-Xa levels across all heparin concentrations in both plasma groups (r range = 0.879-0.945). In comparison with the APTT, the HEPTEST showed better correlation with anti-Xa levels at low concentrations of heparin (r values 0.933 vs. 0.772, respectively). For both the APTT and HEPTEST there were significant differences between the clotting times in pregnant and non-pregnant plasma at a number of heparin concentrations. This data supports the plasma HEPTEST as an acceptable alternative to the chromogenic anti-Xa assay for monitoring heparin thromboprophylaxis in pregnancy.

We present a series of 5 intravenous drug users (4 male, age range 24–47 years) with glomerular deposition of a lipid-like material. Three patients presented with the nephrotic syndrome, 1 with acute renal failure and 1 with hypertension and an active urinary sediment. All were continuing to use opiates intravenously (mixed with lemon juice or acetic anhydride and sodium bicarbonate). Investigations: plasma creatinine 0.10–0.30 mmol/l, urinary protein excretion 1.0–6.75 g/24 h, hepatitis C antibody positive (4), all seronegative for hepatitis B and HIV. Renal biopsy showed large vacuolated areas consistent with heavy deposition of lipid-like material in all glomerular cells and infiltrating macrophages. Two showed ATN and another FGS. We suggest that these changes are due to the pattern of illicit drug availability and preparation peculiar to these users.

The duration and characteristics of fibrinolytic "shut-down" were studied in 40 patients serially for a 9-week period after acute myocardial infarction (AMI). Patients were randomized into four equal groups to receive streptokinase (SK), SK plus heparin (SK + H), recombinant tissue plasminogen activator (rt-PA) or recombinant t-PA plus heparin (rt-PA + H). All patients received oral aspirin. Plasma fibrinolysis was assessed by performance of the following tests: fibrin plate lysis (FPL), tissue plas. minogen activator (t-PA) activity and t-PA antigen (Ag), plasminogen (plg) and α2-antiplasmin (α2-AP) activity, Clauss fibrinogen, and D-dimer. Prethrombolysis global fibrinolysis was normal in most patients, although plasminogen activator inhibitor (PAI) activity and PA inhibitor-1 antigen (PAI-I Ag) were increased 37.5% of the patients. Fibrin plate lysis was significantly decreased for the first 48 h in all four groups (p < 0.05-0.002) compared with normal controls (n = 10); the decrease persisted longest (5 days) in the group receiving rt-PA alone. The decreased fibrin plate lysis was accompanied by significantly increased D-dimer levels (p < 0.003-0.0002) as well as decreased plg and α2-AP activities (p < 0.05-0.0002), which persisted longer. (≤72 h) in patients receiving SK, indicating a more widespread activation of fibrinolysis in this group. Fibrinogen levels showed a rebound increase which began ≤24 h after thrombolysis while levels of plg and a2-AP were at their lowest. The fibrinogen rebound persisted for at least 6 weeks (p < 0.05-0.002). t-PA activity remained unchanged, and t-PA Ag levels were variable and showed no consistent pattern over the study period. PAI-1 Ag and PAI activity levels were significantly increased (p < 0.02-0.0005) in all four groups for the first 24 h, and individual patients showed increased levels at various times over the study period. The only significant prethrombolysis fibrinolytic change was increased PAI activity and PAI-1 Ag. The only significant effect of heparin was a shortening of the period of decreased global fibrinolysis observed in the rt-PA group from 5 to 2 days. Our findings show that the fibrinolytic shut-down after AMI in patients receiving thrombolysis is short-lived, lasting only a few days. Key Words : Thrombolysis—Myocardial infarction-Fibrinolysis-Heparin.

Five hundred consecutive women (median age 33 years; range 19-45) with a history of recurrent miscarriage (median 4; range 3-16) were screened for the presence of antiphospholipid antibodies (APA)-lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACA). The prevalence of persistently positive tests for LA was 9.6% and for immunoglobulin G (IgG) and immunoglobulin M (IgM) ACA was 3.3 and 2.2% respectively. Only seven women (1.4%) were LA and ACA positive. Repeat testing, after an interval of at least 8 weeks, demonstrated that only 65.7% of LA positive, 36.6% IgG ACA positive and 36.0% IgM ACA positive women on initial testing had a second positive test result. The dilute Russell's viper venom time detected the LA significantly more often than either the activated partial thromboplastin time or the kaolin clotting time (P < 0.001). There was no difference in the gestation of previous miscarriages between APA positive and APA negative women. There was no difference in the plasma beta(2)-glycoprotein-I concentrations between APA positive and APA negative women with miscarriages and normal women. All women with a history of recurrent miscarriage should be tested for the presence of both LA and ACA. A second confirmatory test should be performed in those with an initial positive test result.