BACKGROUND

Cryosupernatant plasma (CSP) is used in Canada for plasma exchange in thrombotic thrombocytopenic purpura. The refrigerated storage time for thawed CSP is limited in many areas to not more than 24 hours postthaw. Because large volumes of CSP are needed for plasma exchange, procedural postponement can lead to product wastage. To determine if CSP storage could be extended, we measured coagulation-related activities in CSP thawed and stored at 1 to 6°C for up to 5 days.

METHODS

Thirty-six CSP units were thawed, refrigerated, and sampled aseptically at 0, 24, 48, and 120 hours postthaw. Clotting factor activities (Factor [F]V, FVII, FVIII, and fibrinogen) and prothrombin time were measured using an automated coagulation analyzer, and von Willebrand factor (vWF) and ADAMTS13 activities using enzyme-linked immunosorbent assay.

RESULTS

Fibrinogen, FVIII, and vWF activities were unchanged from thaw values after 120 hours of storage; ADAMTS13, FV, and FVII activities were significantly lower than at thaw, but mean reductions were only -2.6, -7.7, and -12%, respectively. Losses were proportionately greater in the first 24 hours of refrigerated storage.

CONCLUSIONS

Extending the refrigerated storage of CSP from 1 to 5 days had little impact on product quality. The retention of more than 97% of initial mean ADAMTS13 activity after 5 days of refrigerated storage suggests that the shelf life of thawed refrigerated CSP could be extended without meaningful losses of its likely most important ingredients. CSP postthaw storage could be aligned to that of refrigerated thawed frozen plasma, currently available for transfusion in some jurisdictions for up to 5 days postthaw.

Tissue factor (TF) on monocyte and macrophage surfaces is a nonproteolytic cofactor for factor VIIa (FVIIa)-induced coagulation. Monocyte-derived macrophages in atherosclerotic plaques express TF, which, after plaque disruption or rupture, may complex with FVII/VIIa from the bloodstream, resulting in activation of extrinsic coagulation. We studied the effect of TF expression on human monocytes on arterial thrombus formation in a model system of thrombogenesis. Thawed, cryopreserved human monocytes adherent to plastic coverslips were stimulated with lipopolysaccharide (0.5 microgram/mL) to express TF and subsequently exposed to flowing nonanticoagulated human blood in a parallel-plate perfusion chamber. The wall shear rate at the cell surface was 650 seconds-1, corresponding to that of average-sized coronary arteries. The stimulated monocytes elicited pronounced fibrin deposition and platelet-thrombus formation. The platelet-thrombus volume was as large as that triggered by human type III collagen fibrils under similar experimental conditions. In contrast, the monocytes elicited much more fibrin deposition than the collagen surface. However, inclusion of an anti-TF monoclonal antibody that blocks the complexation of FVII/FVIIa with TF virtually abolished the fibrin deposition (P < .03) and reduced platelet-thrombus formation by more than 70% (P < .04). Thus, arterial thrombus formation induced by stimulated monocytes was almost completely blocked by the anti-TF antibody, suggesting that inhibition of TF/FVIIa complex formation on monocytes and macrophages at sites of plaque rupture or after percutaneous transluminal coronary angioplasty procedures may reduce intravascular thrombotic complications.

Congenital Factor VII (FVII) deficiency can be divided into two groups: cases of "true" deficiency, or cross-reactive material (CRM) negative and variants that are cross-reactive material positive.The first form is commonly recognized as Type I condition whereas the second one is known as Type II. FVII deficiency has been occasionally associated with thrombotic events, mainly venous. The reasons underlying this peculiar manifestation are unknown even though in the majority of associated patients thrombotic risk factors are present. The purpose of the present study was to investigate if a thrombotic event was more frequent in Type I or in Type II defect.The majority of patients with FVII deficiency and thrombosis belong to Type II defects. In the following paper we discuss the possible role of the dysfunctional FVII cross-reaction material as a contributory cause for the occurrence of thrombosis.

Inhibition of thrombin formation in flowing native blood reduces thrombus formation on subendothelium, dacron, or collagen fibrils at arterial wall shear rates of 450 to 650 s-1. In the present study, we have investigated the role of low levels of factor VII (FVII) in thrombus formation on collagen fibrils at arterial wall shear rates of 650 s-1 (coronary arteries), 2,600 s-1 (mildly stenosed arteries), and 10,510 s-1 (severely stenosed arteries) in parallel-plate perfusion chambers. In the perfusion chamber with the highest wall shear rate, thrombus formation took place at the apex of an eccentric stenosis, which reduced the cross-sectional area of the blood flow channel by 80%, thus simulating thrombus formation at an atherosclerotic plaque rupture. Native blood from 21 healthy volunteers and 12 homozygous FVII-deficient patients was drawn by a pump directly from an antecubital vein over a surface of fibrillar collagen positioned in the respective perfusion chambers. The patients had FVII coagulant activities ranging from 1.3% to 4.5% and FVII antigen levels of 16% to 23% of normal. Immunoaffinity purification of the patients' FVII followed by electrophoresis (sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]) and immunoblotting showed a protein with similar molecular mass as normal FVII. In the perfusion studies, a reduction in thrombus volume of 54% of normal (P < .007) at 10,510 s-1 was observed. The deposition of fibrin on the thrombogenic surface and the plasma level of fibrinopeptide A (FPA) in blood samples collected distal to the perfusion chamber were concomitantly reduced (P < .002 and P < .04, respectively). The plasma FPA level was also reduced at 2,600 s-1 (P < .04), but not at 650 s-1. However, at the lower shear conditions, the thrombus volume and the fibrin deposition were within the ranges observed in normal blood. The platelet-collagen adhesion was not affected at any of the three shear conditions. Thus, low plasma levels of FVII result in significantly less formation of thrombin and fibrin in and around growing platelet masses at high shear condition. This may weaken the thrombus stability and reduce platelet recruitment, thereby lowering thrombus volume. In support of this theory, one patient with afibrinogenemia had an 83% reduction in thrombus volume at this high shear condition.

OBJECTIVE

To investigate the prevalence and type of thrombotic events reported in patients with congenital factor XI (FXI) or factor VII (FVII) deficiency.

METHODS

Data on all patients with congenital FXI or FVII deficiency and a thrombotic event were gathered by means of a time unlimited PubMed search carried out in June 2014 and in February 2015. Appropriate keywords including the medical subject headings were used in both instances. Side tables were also consulted and cross-checking of the references was carried out to avoid omissions. The thrombosis event had to be proven by objective methods.

RESULTS

Forty-three patients with FXI deficiency had arterial thrombosis and only eight had venous thrombosis. On the contrary, only five patients with FVII deficiency had arterial thrombosis whereas 31 patients had venous thrombosis. The arterial/venous ratios were 5.37 and 0.17 for FXI or FVII, respectively.

CONCLUSIONS

Arterial thrombosis is frequent in FXI deficiency whereas venous thrombosis is rare. The reverse is true for FVII deficiency. The significance of these findings is discussed especially in view of the recent use of synthetic anti-FXI compounds in the prophylaxis of post-orthopedic surgery of venous thrombosis complications.

OBJECTIVE

To study whether locally administered recombinant inactivated human coagulation factor VIIa (FFR-rFVIIa) would reduce the thrombus formation and improve patency in an experimental venous thrombosis model without inducing systemic changes in the coagulation.

METHODS

Experimental double-dummy randomised study.

METHODS

In 20 healthy New Zealand White rabbits both jugular veins were exposed under general anaesthesia.

METHODS

The thrombi were induced in a 10 mm long jugular vein segment with a combination of chemical destruction of the intima and a restriction of the bloodflow. Each segment was treated with either FFR-rFVIIa or placebo injected directly into the vein.

RESULTS

1.5 mg topically applied FFR-rFVIIa significantly reduced the thrombus weight (p < 0.001). The 30 and the 120 min patency tests were significantly improved (p < 0.05 and p < 0.001, respectively) Plasma analyses (APTT, dilute-TF time, FVII protein) were evaluated as baseline, 3 min after declamping and at sacrifice. No prolongation of the clotting times were seen. FFR-rFVIIa protein was detected in minute amounts (ng/ml); however, this was not enough to prolong the dilute-TF time.

CONCLUSIONS

Local application of recombinant active-site inhibited human FVIIa reduced both thrombus weight and improved patency significantly in an experimental venous thrombosis model without affecting the systemic clotting times.

Hemostatic disorders can often complicate transplantation procedures. Moreover, antihemmorhagic drugs may not efficiently control bleeding that occurs in such cases. We report on a patient who underwent kidney transplantation complicated by bone marrow aplasia and gastric bleeding who was successfully treated with recombinant activated FVII (Novoseven). In May 2005, a 53-year-old man affected by chronic renal insufficiency underwent kidney transplantation. At the beginning of June, laboratory tests showed progressive reduction in the blood cell count with anemia, granulocytopenia, and thrombocytopenia related to the development of marrow insufficiency. We commenced transfusion therapy and administered hematologic growth factors. On June 3, 2005, the patient underwent surgical procedure to repair the abdominal wall. Two days thereafter, the postsurgical period was complicated by an episode of melena. The patient received additional treatment with packed red cells, platelets, and fresh-frozen plasma. The gastrointestinal bleeding continued until June 9, 2005, when therapy with recombinant activated FVII (Novoseven) was commenced at an initial dose of 90 microgr/kg. The first bolus did not significantly reduce the blood loss; it was therefore administered as a successive bolus at the same dosage that was able to stop bleeding. Endoscopic examination performed the day after showed the absence of the hemorrhagic lesion in the gastric mucosa. In the subsequent days, the need for transfusion was dramatically reduced with no episode of bleeding. At the same time, the laboratory and clinical findings of marrow insufficiency disappeared. Our case report showed that the use of a global antihemorrhagic factor, such as Novoseven, can successfully control gastrointestinal bleeding even in complicated patients despite failure of traditional antihemostatic therapy.

Acquired hemophilia is rarely observed in a pediatric population. We report a case of a 14-year-old girl presented with ecchymoses and macrohematuria. She developed factor VIII and factor IX inhibitors, and was diagnosed with simultaneous acquired hemophilia and systemic lupus erythematosus (SLE). Recombinant-activated FVII and corticosteroid were prescribed due to macrohematuria-related hypovolemia and anemia, which resolved satisfactorily. This case is a reminder that the rare concurrent presence of factor VIII and factor IX inhibitors could be associated with SLE in a pediatric population. Children with SLE-associated-acquired hemophilia may develop macrohematuria as well.

BACKGROUND

Biological variation is usually estimated in healthy individuals during steady-state conditions. The aim of this study was to estimate the in-treatment biological variation of the International normalised ratio (INR) and to investigate to what extent the different levels of coagulation factors could explain this variation.

METHODS

Blood samples were collected from randomly included patients on warfarin treatment. INR was determined on a laboratory instrument (STA Compact(®)) and on three point-of-care instruments (Simple Simon(®)PT, CoaguChek(®)XS and INRatio(™)). The level of fibrinogen, and the activity of coagulation factors II, V, VII and X were determined.

RESULTS

The in-treatment within- and between-subject coefficients of variation of INR were dependent on the method and varied between 18 and 24% and 13 and 19%, respectively, and were reduced to 3.9-5.1% and 2.3-5.8%, after correction for coagulation factors which could explain 91-95% of the variance of INR.

CONCLUSIONS

The in-treatment biological variation of INR was higher than reported for healthy individuals as well as patients in a steady-state condition, but by correcting for appropriate coagulation factors it was reduced. The association between INR and coagulation factors was different for the different PT methods mainly due to different sensitivity towards FII and FVII.

We sequenced the factor VII gene (F7) in two unrelated Japanese patients with factor VII (FVII) deficiency. In the first (an asymptomatic 46-year-old man with FVII activity and antigen levels of 1.2% and 21% of normal respectively), novel E25K and H348Q mutations were identified in the doubly heterozygous state. In transiently transfected HEK293 cells, the level of FVII-E25K mutant activity in the culture media was significantly lower than that of FVII wild type, whereas the antigen levels of both proteins were similar. This suggests that the E25K mutation is associated with a dysfunctional FVII molecule. In the second patient (a 47-year-old woman with FVII activity and antigen levels of less than 1% and 6% respectively), an IVS4+1 mutation and a novel -96C to T transition were detected in the double heterozygous state. In electrophoretic mobility shift assays, the -96T mutation was shown to disrupt binding of Sp1.

Factor VII (FVII) deficiency is a rare autosomal recessive hereditary disorder characterized by a normal partial thromboplastin time and a prolonged prothrombin time. For definitive diagnosis, the specific FVII level should be investigated. We report on a 7-month-old boy with congenital FVII deficiency suffering from convulsions and intracerebral hemorrhage. Hematologic tests revealed prolonged prothrombin time associated with a decreased FVII level of 1.7%. Computerized tomography of the brain revealed multifocal hemorrhagic lesions. To our knowledge, multifocal intracranial hemorrhages at the time of a transiently prolonged partial thromboplastin time of unknown origin in a child with congenital FVII deficiency of about 2% has not been reported so far.

A two stage method for the determination of prothrombin is described in which the potent synthetic thrombin-inhibitor MD805 is used to suppress the inactivation process of thrombin by antithrombins in plasma. In the activation stage, prothrombin was activated almost instantaneously after the addition of tissue thromboplastin in 20-times diluted plasma and then the generated thrombin was inactivated progressively. Addition of MD805 suppressed the inactivation process of thrombin in a dose-dependent manner, while it hardly affected the complete activation of prothrombin. Thus, the generated thrombin was maintained stable in the presence of 50 microM MD805, and was measured by using 0.5 mM S-2238 as substrate. The method exhibited a linear relationship to the dilution of plasma. The decreased level of the other extrinsic coagulation factors such as FVII, FV, FX and tissue thromboplastin did not cause any significant changes until their activities were decreased to 3, 12, 12 and 20% of their controls. In addition, the method is very simple and easy for standardization.

OBJECTIVE

To investigate the pathogenesis of inherited coagulation factor VII (FVII) deficiency.

METHODS

The diagnosis was validated by coagulant parameter assay. FVII gene mutations were analysed in the proband by DNA direct sequencing of PCR products of all exons, exon-intron boundaries and the 3', 5'untranslated sequences. The mutations were confirmed by reverse sequencing. The ectopic transcripts of RT-PCR were used to confirm the characteristics of the mutation in non-canonical splice site (IVS1a + 5g>> a).

RESULTS

Double heterozygous mutations in the propositus were identified: a T to G mutation at position 10961, resulting in His348Gln substitution, a non-canonical splice site (IVS1a + 5g>> a) mutation, causing the new model of splice and frameshift mutation.

CONCLUSIONS

Double heterozygous mutations of His348Gln and IVS1a + 5g>> a were identified in a propositus, the splicing pattern of the IVS1a + 5g>> a mutation was reported for the first time.

BACKGROUND

Hypercoagulability is one of the commonly exhibited endotoxemia septic symptoms; it could contribute to the manifestation of disseminated intravascular coagulation presenting threats to cardiovascular functions. The underlying mechanism, however, remains largely complex and unknown.

OBJECTIVE

We herein determine whether bacterial endotoxin (LPS) upregulates the activities of clotting factors in plasma, contributing to extrinsic hypercoagulation. Compound 48/80 (48/80) is also tested for its ability to suppress hypercoagulation.

METHODS

In an in vitro infection model, we exposed whole blood to LPS (Escherichia coli 0111:B04; 100 ng/ml) for 2 h. Thrombin time (TT), prothrombin time (PT), and the activities of clotting factors ( FVII, FIX, FX ) in plasma contributing to the extrinsic coagulation were determined. Peripheral blood monocytes were isolated from Histoplaque 1077 gradient centrifugation, and the procoagulant activity was determined by a single-stage clotting assay on a Fibrometer.

RESULTS

LPS drastically activated monocytic procoagulant activity which was defined as tissue factor (TF) activity, whereas LPS had no effect on TT, PT, and the activities of clotting factors in plasma. 48/80 not only instantaneously offset LPS-induced monocytic TF activation, but also significantly inhibited PT including the activities of clotting factors (FVII, FIX, and FX) in plasma, whereas TT remained unaffected.

CONCLUSIONS

Monocytic TF activation was solely responsible for the extrinsic hypercoagulation in response to LPS. 48/80 effectively suppressed LPS-induced monocyticTF-initiated extrinsic coagulation at multiple sites, possibly presenting a new therapy for an instantaneous relief of hypercoagulation under septic conditions.

BACKGROUND

In recent years much attention has been paid to the possibly significant role of the activity differences of factor VII (FVII) in the etiology of recurrent miscarriages.

OBJECTIVE

The aim of study was to evaluate the frequency of Arg353Gln genetic polymorphism of coagulation factor VII and the role of presence of Gln353 allele in the group of women with two or more spontaneous abortions in the first trimester of pregnancy.

METHODS

104 women (average age 30.15 +/- 4.07 years), with two or more spontaneous abortions in the first trimester (between 6 and 13 weeks of gestation) of pregnancy, and 163 healthy women (average age 29,40 +/- 3,56 years), with at least one pregnancy which had ended with the delivery of a healthy newborn, have been analyzed. The frequency of genotypes has been determined by means of polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) methods.

RESULTS

In the group of recurrent miscarriages, higher frequency of homozygotic Arg353/Arg353 genotype (82.69 vs 74.85%) and lower frequency of heterozygotic Arg353/Gln353 (17.31 vs 25.15%) genotype have been noted, comparing to the control group. Frequency of mutated Gln353 allele was lower in the group of spontaneous abortions (8.65 vs. 12.58%, ns). Observed frequency of mutated Gln353 allele in the control group (12.58%) was compatible with th frequency for Caucasian observed by other authors. In the subgroup of women with two (80 women), three or more abortions (24 women), the frequency of heterozygous genotype Arg353/Gln353 was lower if compared to the controls (16.25% and 20.83%, respectively) (controls 25.15%, ns). Lower frequency of heterozygous genotype Arg353/Gln353 in the subgroup of women with abortions in the early (6-9 week of gestation) period of the first trimester (13.85 vs 25.15%, p=0.04) has been observed.

CONCLUSIONS

Research and investigation which have been carried out suggest a weak connection of Arg353Gln polymorphism of coagulation factor VII with the frequency of recurrent miscarriages. However, higher frequency of Gln353 allele in the control group of healthy women suggests its protective role in coagulation changes and recurrent miscarriages. A visibly lower frequency of heterozygous genotype Arg353/Gln353 in the miscarriages in the early period of the first trimester, which might suggest potentially great protective significance of Gln353 allele presence in this period of pregnancy, remains an interesting fact.

BACKGROUND

The in vivo recovery and half-life of intermediate-purity, vapor-heated factor VII (FVII) concentrate were determined in patients having a congenital deficiency for FVII according to the 1991 guidelines of the International Society for Thrombosis and Haemostasis.

METHODS

A total of 11 patients received a single infusion of the FVII concentrate. Blood was drawn before infusion and 15 and 30 minutes and 1, 2, 4, 8, 12, and 24 hours after. Recoveries were calculated from the highest FVII activity of the first four blood samples drawn after infusion. The two-phase linear regression method was used to estimate the half-life according to the two-compartment model. In addition, a noncompartmental approach was applied.

RESULTS

The mean recovery value obtained for FVII concentrate, 110.53 percent (SD, +/- 26.37), indicates rapid and efficient incorporation into the blood stream. Equivalent results were obtained with both pharmacokinetics methods and indicate a very short half-life for FVII. A half-life of 6.49 hours (SD, +/- 2.42) was obtained with the compartmental method and a half-life of 5.25 hours (SD, +/- 2.42) with the noncompartmental method.

CONCLUSIONS

The half-life and recovery reported here, along with the specificity of the replacement therapy, the earlier anecdotal cases of clinical efficacy, and the clinical safety of the concentrate with regard to viral infections, recommend vapor-heated FVII concentrate for the treatment of patients with hereditary FVII deficiency.

Factor VII (FVII) activity should be measured in order to evaluate the risk for coronary artery disease. The measurement of FVII by means of a standardized clotting method seems to be influenced by the thromboplastins used, while the FVII-deficient plasmas do not affect the results.

OBJECTIVE

To investigate the inhibitory effect of NF-kappaB decoy on tissue factor (TF) expression and FVII activation in cultured human umbilical vein endothelial cells (HUVEC), and to explore new methods for prevention and treatment of coronary heart disease.

METHODS

NF-kappaB decoy transfection efficiency was detected by flow cytometry, NF-kappaB decoy's mechanism was analyzed by electrophoretic mobility shift assay (EMSA), TF mRNA was detected by RT-PCR, TF antigen expression on the surface of HUVEC by flow cytometry, FVIIa level in plasma incubated with HUVEC stimulated by TNF-alpha by rsTF one stage clotting method.

RESULTS

NF-kappaB decoy could be successfully transfected into HUVEC. It could compete with the endogenous kappaB cis sequence element in the regulatory regions of TF promoter to bind transcriptional factor NF-kappaB. It could also significantly inhibit the TF mRNA, TF antigen expression on the cell surface and TF function leading to activation of FVII.

CONCLUSIONS

NF-kappaB decoy could inhibit TF gene expression and FVII activation in cultured HUVEC and might be a potential new strategy for prevention and treatment of coronary heart disease.

Heart failure is a serious condition, and it is, therefore, important to identify patients at high risk as early as possible in order to initiate appropriate treatment. The condition results in complicated disease mechanisms including disturbances in blood coagulation. The aim of the present study was to evaluate whether low plasma concentrations of coagulation factors (F) II, VII and XI influence cardiovascular mortality in an elderly population with possible heart failure. A cardiologist evaluated 450 elderly patients who attended primary healthcare because of symptoms associated with heart failure. He recorded new patient history, conducted a clinical examination, took blood samples, determined concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed Doppler echocardiography. The patients were followed over almost a 10-year period during which all mortality was registered. In patients with suspected heart failure, those with low plasma concentrations of FII, FVII, FXI or all had a significantly higher mortality rate during the follow-up period of 10 years as compared with those with higher plasma concentrations, in contrast with findings in previous reports on patients with acute coronary syndromes. In the group with a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or all, the risk of cardiovascular mortality increased two to three times.

We report two novel factor VII (FVII) gene mutations in a Chinese family with FVII deficiency. The proband, a 55-year-old woman. was incidentally found to have right shoulder arthritis consistent with chronic haemophilic arthropathy. FVII studies showed a FVII activity of 0.02 iu/ml and a FVII antigen of 49%. Molecular analysis showed a double heterozygous state, with an exon 4 nonsense mutation (C6003->>A; Cys61->>Term) and an exon 8 missense mutation (T10902->>G; Cys329->>Gly) that disrupted a Cys310/Cys329 disulphide bond. The genotypes and phenotypes were correlated in the patient's daughters. Two daughters were heterozygous for the Cys61->>Term mutation and showed a type 1 FVII gene mutation phenotype consistent with a nonsense mutation. One daughter was heterozygous for the Csy329->>Gly mutation and showed a type 2 mutation phenotype consistent with a missense mutation. These are the first reported FVII gene mutations in the Chinese people.

Smoking is an important and preventable risk factor of cardiovascular diseases with effects on blood coagulation. Our aim was to analyze the influence of smoking on coagulation parameters. Concentrations or activities of blood coagulation factors were compared in 777 active smokers and 1,178 lifetime non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. The association with mortality was examined using Cox regression. The findings show that AS had a tendency toward thrombosis. They displayed significantly higher values for fibrinogen, soluble fibrinogen, factor XIII, and tissue factor pathway inhibitor; whereas FVII, FVIII, FXII, von Willebrand factor (vWF), and thrombomodulin were decreased. The Cox regression analysis showed fibrinogen, FVIII, vWF, thrombomodulin, and tissue factor pathway inhibitor to be independent risk factors for mortality in active smokers with hazard ratios of 1.16 (95% CI: 1.02-1.31), 1.40 (1.22-1.59), 1.37 (1.22-1.56), 1.19 (1.07-1.31), and 1.22 (1.06-1.40) per increase of one standard deviation. We conclude that active smokers have an increased thrombogenic potential associated with significant changes in the coagulation system. Individual parameters of the coagulation system are independent predictors of mortality. Therefore, parameters of the coagulation system, apart from other risk factors for cardiovascular disease (e.g., lipids or life-style) should be determined for risk prediction in active smokers.

OBJECTIVE

The development of thrombotic disorders is a major threat for young women during pregnancy. It is one of the main causes of pregnancy-related disorders, which may also result in harm for the conceptus. Successful pregnancies require an even balance of coagulation and fibrinolysis, in order to secure stabilization of the basal plate as well as adequate placental perfusion. Broad spectrum assays which measure a range of thrombin/fibrin formation in serum have become an established means of identifying activation of blood coagulation and/or fibrinolysis. There is considerable interest in the application of these assays to the diagnosis of other hypercoagulable states, such as thrombophilia during pregnancy. We investigated coagulation/fibrinolysis parameters for significant differences between pregnant women during their gestation (first, second and third trimester) with or without pregnancy loss and healthy nonpregnant women.

METHODS

Thirty-nine pregnant women, aged 24-39 years, were studied. They were subdivided according to pregnancy trimester: 15 patients in the first trimester; 13 in the second and 11 in the third. The selection of patients was carried out in cooperation with the Transfusion Center of the Second University of Naples in order to obtain a homogeneous sample group. The control group included 400 healthy patients. Biochemical and blood coagulation tests were performed for each patient and the results obtained were compared with the control group.

RESULTS

A decrease in free protein S (PS) and fibrinolysis (t-PA/PAI-1) activities and an increase in Factor VII, Factor VIII, prothrombin fragment 1+2 (F1+2), D-dimer (D-dimer) were observed in pregnant women during the follow-up of gestation. However, there were statistical differences between the groups of women with one or more pregnancy loss where it was found the lowest values in t-PA and PAI and the highest values in FVII and F1+2. Among subjects with more than one abortion, coagulation/fibrinolysis derangements before the partum were more prominent. A significant association exists between consecutive recurrent abortions and pregnancy complications such as placental abruption, hypertensive disorders and CS. This association persists after controlling for variables considered to coexist with recurrent abortions.

CONCLUSIONS

These findings suggest that an excessive hypercoagulable state is associated with the termination of pregnancy resulting into a moderate risk for thrombosis during the different trimesters of pregnancy. The follow-up of fibrinolytic markers could represent a useful diagnostic tool for termination of pregnancy.