Soluble Fibrin Monomer Complex Levels Research Articles

Possible role of soluble fibrin monomer complex after gastroenterological surgery.

AIMTo examine the role of soluble fibrin monomer complex (SFMC) in the prediction of hypercoagulable state after gastroenterological surgery.METHODSWe collected data on the clinical risk factors and fibrin-related makers from patients who underwent gastroenterological surgery at Hiroshima University Hospital between April 1, 2014 and March 31, 2015. We investigated the clinical significance of SFMC, which is known to reflect the early plasmatic activation of coagulation, in the view of these fibrin related markers.RESULTSA total of 123 patients were included in the present study. There were no patients with symptomatic VTE. Thirty-five (28%) patients received postoperative anticoagulant therapy. In the multivariate analysis, a high SFMC level on POD 1 was independently associated with D-dimer elevation on POD 7 (OR = 4.31, 95%CI: 1.10-18.30, P = 0.03). The cutoff SFMC level was 3.8 μg/mL (AUC = 0.78, sensitivity, 63%, specificity, 89%). The D-dimer level on POD 7 was significantly reduced in high-SFMC patients who received anticoagulant therapy in comparison to high-SFMC patients who did not.CONCLUSIONThe SFMC on POD 1 strongly predicted the hypercoagulable state after gastroenterological surgery than the clinical risk factors and the other fibrin related markers.

Safety of fondaparinux for prevention of postoperative venous thromboembolism in urological malignancy: A prospective randomized clinical trial.

To prospectively evaluate the safety of postoperative fondaparinux in comparison with low molecular weight heparin in patients undergoing uro-oncological surgery. The present study was a prospective, single-blind, non-inferiority randomized trial. A total of 359 patients undergoing surgery for urological malignancy were enrolled from January 2011 to December 2012. A total of 298 of these patients (fondaparinux group, 152; low molecular weight heparin group, 146) were evaluable for the intention-to-treat-analysis. Patients were randomly assigned to low-dose unfractionated heparin, 5000 units twice daily until postoperative day 1 plus either fondaparinux 2.5 mg once daily or low molecular weight heparin 2000 units twice daily until postoperative day 5. The primary end-point was postoperative bleeding as by independent review, and the study was powered to show the non-inferiority of fondaparinux versus low molecular weight heparin. The other adverse events were evaluated. D-dimer and soluble fibrin monomer complex levels were measured perioperatively. Bleeding occurred in 21 patients (12 in the fondaparinux group and 9 in low molecular weight heparin group, respectively). No significant differences were detected in the incidence of postoperative bleeding and the other adverse events between the two groups. The D-dimer was elevated on postoperative day 1 in one patient (16.6 μg/mL). In another patient, the soluble fibrin monomer complex was elevated (109 μg/mL). Fondaparinux is non-inferior to low molecular weight heparin with respect to risk of bleeding. The favorable safety profile of fondparinux supports its prophylactic use as an alternative to low molecular weight heparin after surgery for urological malignancy.

Features of adverse hemostatic factors of atrial fibrillation and metabolic syndrome in patients depending on age

Purpose – determination of coagulation hemostasis parameters depending on age and plasma endogenous insulin (EI) levels in the patients with different forms of atrial fibrillation (AF) and metabolic syndrome (MS). Materials and methods. The study involved 137 patients with paroxysmal, persistent and permanent forms of AF and with MS, including 28 patients – the middle age (group 1); 67 elderly patients (group 2) and 42 old age patients (group 3); 84 patients –with insulin resistance and 53 patients – without insulin resistance. An analysis of coagulation hemostasis plasma parameters was made according to prothrombin index (PtI), fibrinogen, soluble fibrin monomer complexes (SFMC) and D dimer levels by standard methods. Results. It was found that PtI level tends to increase with age. The most significant increase up to 25 % (p<0.05) was in the 3rd group of patients with spontaneous hyperinsulinemia (HI) and with paroxysmal AF. The plasma fibrinogen level tended to increase with age (р<0.1) and was increased by 1,5-2 times under reactive and spontaneous НI compared to the patients without insulin resistance (p<0.05), both in paroxysmal and in permanent forms of AF. Significant increase of SFMC level was detected in all patients, but there was greater extent in patients of the 2nd and 3rd groups with spontaneous HI (p<0.05) and with the permanent form of AF (p<0.05). Increased plasma D-dimer levels appeared typical for 40% of the patients of middle age and almost 50% in elderly and old patients, mainly in spontaneous HI (p<0.05). The presence of D-dimer in plasma was found in 40 %; 42 % and 54 % cases under paroxysmal, persistent and permanent forms of AF, respectively (p<0.05). Conclusions. Patients of older age groups regardless of AF type and under the presence of insulin resistance are characterized by hypercoagulable state formation and that manifested by increased plasma PtI, fibrinogen, SFMC and D-dimer levels compared to patients without insulin resistance.

Abstract 17642: Warfarin versus Dabigatran: The Coagulation Activity in the Left Atrium During Atrial Fibrillation Ablation

Background: Atrial fibrillation (AF) ablation is associated with the potential risk of periprocedural thromboembolic events. Previous studies suggested performing AF ablation with continuous warfarin reduced the risk of thromboembolic events, otherwise the safety and efficacy of periprocedural dabigatran was controversial. We aim to compare the differences of the coagulable state in the left atrium (LA) between the anticoagulation strategies. Methods: We divided 158 patients who underwent AF ablation into 3 groups: ablation with off warfarin (n=100, WF-off group), ablation with perioperative warfarin therapy (n=33, WF group), and ablation with dabigatran therapy (n=25, D group). Warfarin was stopped 1 day before the procedure in WF-off group. Uninterrupted warfarin therapy was used in WF group and interrupted only on the morning of the procedure with dabigatran in D group. During AF ablation, the blood samples from the LA obtained immediately after the trans-septal puncture before heparin administration in each groups. The D-dimer level and soluble fibrin monomer complex (SFMC) level in the LA were evaluated. Results: The prevalence of positive D-dimer (≥ 0.5 μg/ml) in the LA was observed 3% in WF group, 12% in D group, and 23% in WF-off group, respectively. SFMC levels in the LA were significantly lower in WF group compared with WF-off group (p<0.01). SFMC levels in D group tended to be higher compared with WF group, but lower compared with WF-off group. Conclusions: The coagulation activity in the LA was lower with perioperative warfarin therapy than with dabigatran therapy. Even transient interruption of anticoagulant therapy may be associated with hypercoagulable status in the LA.

Less deep vein thrombosis due to transcutaneous fibular nerve stimulation in total knee arthroplasty: a randomized controlled trial.

It has been known for years that deep vein thrombi (DVT) start to develop during total joint arthroplasty. Previously, we reported effective prevention of venous stasis by transcutaneous electrical nerve stimulation (TENS). It is hypothesized that TENS might be a thromboprophylactic tool for the limb undergoing surgery. The purpose of this study is to clarify the clinical efficacy and safety of TENS in patients during total knee arthroplasty (TKA). Ninety patients undergoing primary TKA were involved and randomly allocated to the TENS or control group. In the TENS group, electrical stimulation of the common fibular nerve, which produced a brisk dorsiflexion of the ankle, was performed for the operated leg during surgery. In the control group, no electrical stimulation was applied. Serum D-dimer and soluble fibrin monomer complex (SFMC) levels were measured before surgery, immediately after surgery, and post-operative day (POD) 1. Ultrasonography was performed on POD 1. Immediately after surgery, D-dimer and SFMC levels of each group were significantly lower in the TENS group compared with control (p < 0.05). The incidence of DVT was 11 % (five cases) in the TENS group while 31 % (14 cases) in control (p = 0.02). There were no adverse effects related to TENS. TENS during TKA showed significant effects on preventing DVT. Sustaining muscle pump activation during surgery prevented not only venous stasis, but also hypercoagulability of blood. Intraoperative TENS is a safe and novel strategy against early post-operative thromboembolism, which is difficult to be completed through existing prophylaxis after total joint arthroplasty. Randomized controlled trial, Level I.

PREDICTING PRECLINICAL THROMBOGENIC ABNORMALITIES IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION

Aim. To identify early (preclinical) markers of thrombogenic abnormalities in patients with essential arterial hypertension (EAH). Material and methods. The study included 137 EAH patients, aged 30–60 years. The parameters of both coagulation and platelet haemostasis were assessed. Results. In patients with EAH and obesity (O), the following parameters were elevated: activated partial thromboplastin time (aPTT); fibrinogen; and soluble fibrin monomer complex (SFMC). In EAH patients without O, the levels of spontaneous platelet aggregation were elevated. Among overweight patients, the levels of adreno-reactivity were associated with leptin levels (rs=0,8; р=0,007). In obese patients, there was a significant correlation between insulin and leptin levels (rs=0,7; р=0,0049). The correlation analysis of the neurohumoral and haemostatic parameters demonstrated an association between leptin and SFMC levels (rs=0,8; р=0,0007). In EAH patients, the changes in neurohumoral profile are linked to increased body mass, elevated levels of insulin (Н=9,6; р=0,0082), leptin (Н=12,1; р=0,0024), and adreno-reactivity (Н=8,8; р=0,0122). Conclusion. In patients with EAH and O, the observed haemostatic abnormalities could be characterised as hypercoagulation syndrome. The findings obtained suggest that fibrinogen and SFMC could be regarded as early markers of thrombosis development in patients with EAH and O. Therefore, these parameters can be used in the screening programme, in order to identify the individuals with abnormalities of coagulation haemostasis and fibrinolysis.

Soluble fibrin monomer complex levels during oral anticoagulant therapy do not predict subsequent thromboembolic events in patients with permanent atrial fibrillation

Soluble fibrin monomer complex levels during oral anticoagulant therapy do not predict subsequent thromboembolic events in patients with permanent atrial fibrillation

Edoxaban Versus Enoxaparin for the Prevention of Venous Thromboembolism: Pooled Analysis of Coagulation Biomarkers From Stars E-3 and Stars J-V.

AbstractAbstract 2260 Introduction:Edoxaban is an oral, once-daily, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events. Two randomized, double-blind, double-dummy, phase III studies (STARS E-3 and STARS J-V) have been conducted to evaluate the efficacy and safety of edoxaban compared to enoxaparin for the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA) or total hip arthroplasty (THA). The objective of this pooled analysis was to investigate the effects of edoxaban on key coagulation biomarkers. Methods:Patients (N=1,326) undergoing TKA or THA in Japan and Taiwan were randomized to receive oral edoxaban 30 mg once daily (qd) or subcutaneous enoxaparin 2,000 IU twice daily (bid; equivalent to 20 mg bid) for 11–14 days. Edoxaban was initiated 6–24 hours after surgery and enoxaparin was initiated 24–36 hours after surgery, which is the standard of care in Japan. Blood samples were collected for coagulation biomarker measurements pre-operation, post-operation (pre-treatment, Day 0), Day 7 (prior to administration of the next dose) and completion day (Day 11–14). The primary efficacy outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). The principal safety outcome was the incidence of major and clinically relevant non-major (CRNM) bleeding. Pharmacodynamic endpoints included key coagulation biomarkers such as D-dimer, prothrombin fragment F1+2 (F1+2) and soluble fibrin monomer complex (SFMC). Results:A total of 1,307 patients received at least 1 dose of edoxaban or enoxaparin. There were no clinically relevant differences in baseline characteristics between the treatment groups. The mean age was 68 years, mean body weight was 58.8 kg and 83% of patients were female. Overall, edoxaban significantly reduced the incidence of the composite of symptomatic and asymptomatic DVT and PE compared with enoxaparin (5.1% vs 10.7%, P<0.001). The incidence of major and CRNM bleeding events was 4.6% vs 3.7% in the edoxaban and enoxaparin groups, respectively (P=0.427). For both treatment groups, D-dimer and SFMC levels were reduced at Day 7 compared to post-operation/pretreatment levels, then increased slightly by Day 11–14. Levels of F1+2 also decreased by Day 7 in both treatment groups and further decreased by Day 11–14. However, for each coagulation biomarker, levels were significantly lower in the edoxaban group compared to the enoxaparin group at both Day 7 and Day 11–14. (Table, P<0.001). Conclusion:Edoxaban 30 mg qd is superior to enoxaparin 20 mg bid in the prevention of VTE events with significant reduction of D-dimer, F1+2 and SFMC following TKA and THA.Coagulation Biomarkers, all data mean ± SD (median)Pre-operationPost-operation/Pre-treatmentDay 7Day11-14/end of treatmentD-dimer, μg/mLedoxaban0.73 ±0.82 (0.46)9.42±12.56 (5.49)4.43±2.08 (3.99)*5.37±2.52 (4.86)*enoxaparin0.78±0.96 (0.48)10.92±16.22 (5.83)5.53±2.56 (5.08)6.23±3.12 (5.58)F1+2, pMedoxaban273.9±150.6 (243.0)479.7±741.8 (323.0)362.8±164.2 (327.0)*292.1±167.6 (266.5)*enoxaparin277.8±160.9 (242.0)633.2±3234.9 (325.0)463.3±185.6 (422.0)379.6±174.4 (348.5)SFMC, μg/mLedoxaban5.62±17.86 (3.00)32.25±40.47 (13.20)5.71±9.76 (3.30)*6.15±10.73 (4.20)*enoxaparin4.81±8.42 (3.00)34.72±45.62 (12.9)6.82±13.99 (4.10)7.23±11.78 (5.00)*Wilcoxon test: P<0.001 vs enoxaparin; SFMC = soluble fibrin monomer complex Disclosures:Fuji:Daiichi Sankyo: Consultancy; Bayer: Consultancy; Century Medical: Consultancy; Showa Ikakogyo: Consultancy. Fujita:Daiichi Sankyo: Consultancy; Bayer: Consultancy. Tachibana:Daiichi Sankyo: Consultancy. Kawai:Daiichi Sankyo: Consultancy; Bayer: Consultancy; Toyama Chemical: Consultancy.

The Comparison of Fibrin Monomer (FM) Performance to Other Activation Markers (TAT, PF1.2 and DD)

Abstract 5259In this study, we attempted to determine the performance of the soluble fibrin monomer complex (SFMC) test in comparison to known activation markers, such as prothrombin fragment 1.2 (PF1.2), thrombin antithrombin complex (TAT) and d-dimer (DD). We have used the STA(R)-Liatest FM and STA(R)-Liatest D-Di kits to measure the SFMC and d-dimer levels.A total of 25 patients were included in this study. The data and demographic information are shown in the table below.IDGENDERAGEFMTATPF1.2D-dimer1M660.422.319880.052F3127.93>60.0>120002.393F243.4114.113670.484F612.227.73350.635F184.616.99400.226F38156.5243.5>1200010.377F200.422.21490.668F210.422.41430.249M44>15015.4110435.510F423.4<2.01340.2411M4604.82710.312M7690.7329.41712>20.013F613.413.84840.5214M10.13.81160.3315F334.23763462.0316F353.22.63250.0917F231.14.72320.218M642.32.61890.1519M11.72.92530.4920M642.233.24512.4321M601.62.91260.4222F552.22.61890.9723F651.32.3790.2524F393.68.12220.1825M24.8<2.01090.53Referencerange>6.0 ug/mL<4 mcg/L41–372 pmol/L<0.45 ug/mLThe data indicate that in 16 out 25 patients, the SFMC levels are correlated with TAT and PF1.2. Only 3 out of 25 patients have elevated TAT and PF1.2 with normal SFMC levels. Therefore, our data would tend to indicate that SFMC level could be used as an activation marker to assess an ongoing prothrombotic process. In order to more fully determine the efficacy of the SFMC assay, we will obtain a detailed clinical history for the cases shown above. Disclosures:No relevant conflicts of interest to declare.

Predictive blood coagulation markers for early diagnosis of venous thromboembolism after total knee joint replacement

Pulmonary embolism development may be prevented if asymptomatic venous thromboembolism (VTE) can be predicted and treated preoperatively or soon after total knee arthroplasty (TKA). The purpose of this study was to evaluate whether asymptomatic VTE can be predicted by blood coagulation markers preoperatively or early after TKA. This prospective single-centre study enrolled 68 patients (6 men, 62 women; mean age: 71 years) who underwent TKA between September 2004 and August 2009. Sixteen-row multidetector computed tomography was performed 4 days before and after surgery for diagnosis of asymptomatic VTE. Blood samples were taken to measure the plasma levels of soluble fibrin monomer complex (SFMC), D-dimer and cross-linked fibrin degradation products by leukocyte elastase (e-XDP) at 4 days preoperatively, and at 1 hour, 1 day and 4 days postoperatively. The preoperative SFMC, D-dimer and e-XDP levels did not differ significantly between the thrombus ( n = 36) and no-thrombus ( n = 32) groups. D-dimer and e-XDP levels showed the most significant increases at days 4 and 1, respectively, after surgery in the thrombus group. With cut-off points of 7.5 μg/ml for D-dimer and 8.2 U/ml for e-XDP, the sensitivities were 75% and 75%, and the specificities were 63% and 59%, respectively. By multiple logistic regression analysis, D-dimer at day 4 and e-XDP at day 1 postoperatively were independent markers for early diagnosis of VTE (odds ratio = 1.61 and 1.19, P = 0.01 and 0.04, respectively). The postoperative occurrence of new asymptomatic VTE may be predicted by D-dimer at day 4 and e-XDP at day 1 after TKA.

Changes of the soluble fibrin monomer complex level during the perioperative period of hip replacement surgery

BackgroundVenous thromboembolism (VTE) is a critical complication after hip replacement surgery, so both early diagnosis and prophylaxis are important. The purpose of this study was to clarify the rapid changes of the fibrin monomer complex (FMC) and soluble fibrin (SF) during the perioperative period of hip replacement surgery. MethodsThe subjects were 32 patients (7 men, 25 women) who underwent elective hip replacement surgery between November 2004 and January 2006. Their ages ranged between 34 to 82 years (mean 56.8 years). According to their thromboembolic risk, the patients received different prophylaxis: unfractionated heparin (4 patients), danaparoid sodium (14 patients), or mechanical therapy only (14 patients). ResultsFMC and SF became rapidly elevated during the operation and just after surgery but declined to preoperational levels 3 days after surgery; they were higher in lupus anticoagulant (LA)-positive patients. In contrast, FDP and D-dimer had gradually become elevated 3 and 7 days after surgery. According to venous ultrasonography and lung perfusion scintigraphy, VTE occurred in 7 patients overall (21.9%). The incidence of VTE was 7.1% in the danaparoid group, whereas it was 35.7% in the mechanical therapy group. We also found that danaparoid sodium rapidly decreased FMC and SF within 3 days. ConclusionsFMC and SF were rapidly elevated during hip replacement surgery and differentiated in LA-positive and LA-negative patients.

Use of the New Antioxidant Mexidole for Intensive Care for Ischemic Attacks

The study was conducted in 60 patients with acute ischemic attack. Mexidole included into a complex of intensive care in patients with stroke promoted the abolishment of local disseminated intravascular coagulation and prevented secondary cerebral lesion and the generalization of a systemic inflammatory reaction. The rate of a reduction in the blood levels of soluble fibrin-monomer complexes and fibrinogen was higher than that in mexidole-untreated patients. By day 7, the levels of soluble fibrin-monomer complexes and fibrinogen in survivors decreased on average to 18.0±2.7 mg% and to 2—4 g/l, respectively. Mexidole optimizes the parameters of cerebral blood flow, improves venous outflow from the cranial cavity, and may be recommended for its inclusion into the intensive treatment regimen in patients with cere-brovascular diseases.

Good or poor responses of hemostatic molecular markers in patients with hematopoietic disorders after treatment of disseminated intravascular coagulation.

Changes of hemostatic markers in 226 patients with disseminated intravascular coagulation (DIC) and hematopoietic disorders were examined after treatment of DIC. The changes in prothrombin time (PT) ratio, fibrinogen, fibrin and fibrinogen degradation products (FDP), antithrombin, and protein C, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), and soluble fibrin monomer complex (SFMC) in all patients with DIC were significant during the clinical course of DIC, but those of D-dimer, thrombomodulin (TM), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) were not. Activated partial thromboplastin time (aPTT) and PT were significantly longer in the poor response group than in good response group. Plasma levels of FDP, TAT, PPIC, SFMC, TM, and DIC score were significantly higher in poor response group than in good response. Protein C and antithrombin levels were significantly lower in poor response group than in good response group. The changes of PT ratio, fibrinogen, FDP, DIC score, antithrombin, plasmin inhibitor, and protein C were significant in the good response group, but these levels were not significant in the poor response group. The changes in plasma TAT and SFMC levels were significant in the good response group but were not in poor response group. The changes in D-dimer, TM, TF, or TFPI were not significant in both groups. These findings suggest that anticoagulant agents should be administered at levels below TAT 40 ng/mL or SFMC 300 microgram/mL in patients with DIC and hematopoietic disorders.

Hypercoagulability and DIC in high-risk infants.

Asphyxiated newborns have evidence of disseminated intravascular coagulation (DIC). Several hemostatic parameters were assayed in venous umbilical cord blood of 93 infants, 58 of which suffered from asphyxia due to abruptio placentae, breech delivery, preeclampsia, dead twin, and amniotic fluid embolism. Levels of factor XIII were markedly lower in the high-risk infants; the lowest values coincided with lowest Apgar scores. Plasma levels of thrombin-antithrombin (TAT) complexes, D-dimer, fibrin(ogen) degradation products (FDP), and soluble fibrin monomer complexes (SFMC) were markedly higher in the asphyxiated newborns with good correlations to DIC scores. DIC scores for infants were explained. A significant negative correlation was found between plasma levels of SFMC and Apgar scores. Also primary hemostasis measurements by a Thrombostat 4000 revealed defects in the asphyxiated infants. The data strongly suggest the presence of DIC in the high-risk group of infants.

Inhibition of nitric oxide production increases dimethylnitrosamine-induced liver injury in rats

Intravascular coagulation is involved in the development of certain types of liver injury, including that induced by dimethylnitrosamine. Nitric oxide inhibits platelet aggregation and adhesion; however, its role in protecting against intravascular coagulation has not been clarified. We therefore investigated the effect of blocking the production of NO in a dimethylnitrosamine-induced liver injury model. Wistar male rats received dimethylnitrosamine (50 μg/kg) intraperitoneally, and were treated with N ω-nitro-L-arginine, an inhibitor of nitric oxide synthase, or N ω-nitro-D-arginine, an inactive isomer. Each arginine derivative (40 mg/kg) was injected intraperitoneally every 6 h. Twenty-four hours after dimethyl-nitrosamine administration, we observed a significant increase in the serum level of alanine aminotransferase in the N ω-nitro-L-arginine group compared with the N ω-nitro-D-arginine groups. The N ω-nitro-L-arginine-treated group also exhibited a significant reduction in platelet count, a prolongation of prothrombin time, and an elevation of plasma soluble fibrin monomer complex levels. Sinusoidal congestion, intravascular coagulation, and coagulation necrosis around the central veins were prominent in the N ω-nitro-L-arginine group. In conclusion, the inhibition of nitric oxide production exacerbated the hepatic damage induced by dimethylnitrosamine, mediated by the acceleration of intravascular coagulation.

Stimulation of tissue type plasminogen activator by leukaemic cell homogenates.

In patients with disseminated intravascular coagulation (DIC), hyperfibrinolysis was observed in patients with leukaemia, but hypofibrinolysis was seen in those with sepsis. Although the plasma tissue plasminogen activator (t-PA) level was higher in patients with DIC than in those without DIC, there was no significant difference in t-PA level between the patients with leukaemia and sepsis. Hyperfibrinolysis might not be caused by t-PA derived from leukaemic cells, although the PA antigen level in leukaemic cell homogenates was significantly higher in patients with DIC than in those without DIC. The activation of t-PA by leukaemic cell homogenates in the absence of bromocyan fibrinogen fragments suggested that leukaemic cell homogenates had t-PA stimulator activity. The t-PA stimulator activity was high in both acute myeloblastic leukaemia (AML) and acute lymphoblastic leukaemia (ALL), especially in DIC, but this activity was not detected in chronic myelocytic leukaemia (CML) or normal cells. Since fibrinogen and soluble fibrin monomer complex levels in leukaemic cells were also high in patients with DIC, fibrinogen degradation products might be the major t-PA stimulator in leukaemic cells. This might be one of the causes of hyperfibrinolysis in leukaemia.

Role of leukocytes in the activation of intravascular coagulation in patients with septicemia

To elucidate the role of leukocytes in intravascular coagulation in patients with septicemia, plasma levels of thrombin-antithrombin III complex (TAT), soluble fibrin monomer complex (SFMC) and fibrinogen (Fbg) were determined in 33 patients with septicemia. Twenty of 33 patients revealed marked leukopenia caused by suppression of hematopoiesis by the administration of chemotherapeutic agents for the treatment of hematological malignancies; the total leukocyte count of these patients was less than 1,000/microliters. Thirteen of 33 patients showed normal or increased leukocyte counts. Plasma levels of TAT and SFMC in septicemic patients without leukopenia were significantly higher than in patients with leukopenia. Although plasma TAT and SFMC levels correlated well with the number of leukocytes, a more significant positive correlation was found between the number of monocytes and the levels of TAT and SFMC. Plasma levels of Fbg were significantly lower in patients without leukopenia than in patients with leukopenia. No significant correlation was found between the number of leukocytes and the levels of Fbg. However, a significant negative correlation was found between the number of monocytes and the levels of Fbg. TAT levels did not correlate with the number of platelets. The fibrinolytic system was activated only in septicemic patients without leukopenia, which may be explained by secondary fibrinolysis following leukocyte-activated coagulation. These findings suggest that leukocytes, in particular monocytes, may play a critical role in the pathogenesis of intravascular coagulation in septicemia.

Increased intraglomerular thrombin formation in diabetic microangiopathy

Estimations of soluble fibrin monomer complexes (SFMC) in plasma are a convenient index of thrombin activation. Renal venous-arterial differences in plasma SFMC concentrations were determined in 16 randomly chosen diabetic patients by sampling directly and simultaneously from the renal artery and vein according to the method of Seldinger. In all subjects, SFMC concentrations were higher in the renal vein than in the renal artery, indicating that the kidney is an important source of SFMC. Venous-arterial differences were markedly elevated in patients with severe renal and retinal microangiopathy coupled with hypertension. The hypothesis is advanced that elevated plasma SFMC levels lead to abnormal fibrin deposits in lesioned glomeruli and retinal vessels. It is postulated that plasma SFMC may be a useful parameter for the assessment of diabetic vascular complications.

The effect of glycemic control on plasma soluble fibrin monomer complexes and fibronectin in diabetic patients.

We have shown previously that increased concentrations of plasma soluble fibrin monomer complexes (SFMC) and elevated fibronectin (Fn) levels are closely related to the development of diabetic microangiopathy. The purpose of the present study was to explore whether or not changes in plasma glucose levels could have an effect on these protein constituents. Plasma glucose levels of 25 uncontrolled diabetic patients were brought under control with insulin and serial measurements of SFMC and Fn were made over a period of 4 weeks. Glucose values fell from an average of 312 mg/100 ml to 160 mg/100 ml. Ten patients with macroproteinuria (i.e. greater than or equal to 0.5 g/24 hr) showed initially elevated plasma SFMC and Fn concentrations. These levels fell significantly over the 4 week observation period: from 13.6 mg/100 ml to 9.4 mg/100 ml for SFMC and from 38.4 mg/100 ml to 34.5 mg/100 ml for Fn. The remaining 15 patients had nearly normal levels of both SFMC (7.9 mg/100 ml) and Fn (31.1 mg/100 ml) and glycemic control brought no further reduction. The data indicated that a) elevated SFMC and Fn levels are indeed associated with diabetic microangiopathy, especially in the presence of macroproteinuria; and b) adequate glycemic control is capable of normalizing the plasma concentration of these constituents.

Plasma soluble fibrin monomer complexes in nephrotic syndrome--with reference to hypoalbuminemia.

Plasma soluble fibrin monomer complexes (SFMC) in 10 patients with nephrotic syndrome were measured to demonstrate the contribution of hypoalbuminemia to the SFMC formation. The levels of SFMC as well as plasma fibrinogen (Fbg) levels were significantly higher than those in control subjects. There was a negative correlation between the levels of SFMC and serum albumin, and also between Fbg and serum albumin. The increase in SFMC levels which indicates the intravascular generation of thrombin might be correlated to hypoalbuminemia in nephrotic syndrome with hypercoagulability.