Proteolytic enzymes in coagulation, fibrinolysis, and complement activation. Part A. Mammalian blood coagulation factors and inhibitors.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Blood Coagulation Factor Inhibitors”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Stability of blood coagulation factors and inhibitors in blood drawn into half-strength citrate anticoagulant.
Drawing of blood into a citrate-phosphate-dextrose (CPD) solution with a reduced citrate concentration has been shown to improve the maintenance of coagulation factor VIII (F VIII) in plasma and to give possibilities to improve erythrocyte preservation. We studied the quality of plasma obtained from whole blood drawn under continuous mixing into CPD in which the citrate concentration was reduced by 50% (0.5CPD). The blood was stored at room temperature for 8 h before component preparation. We confirmed improved stability of F VIII by 0.5CPD. We found no clinically significant changes in inhibitors to the coagulation and kallikrein systems, and no signs of activation of these systems, during the 8-hour holding time. In control blood drawn into CPD, F VIII and coagulation factor IX decreased by 0.09 IU/ml (8%) and 0.07 U/ml (7%), respectively, otherwise we found no significant differences between 0.5CPD plasma and CPD plasma.
Anticoagulants↗
Bacterial expression, purification, and partial characterization of amino acids 94-155 of human tissue factor pathway inhibitor (TFPI) as an inhibitor of blood coagulation factor Xa.
Tissue factor pathway inhibitor (TFPI) is a plasma-derived protein which inhibits two of the active serine proteases present during normal blood coagulation. Inhibition of both of these proteases, factors VIIa and Xa, is thought to require a factor Xa-TFPI complex. To begin to investigate the interactions between factor Xa and TFPI, amino acids 94-155, which encode for the second Kunitz domain (K2) of TFPI, were expressed, purified, and partially characterized. Expression of the recombinant peptide was accomplished using an E. coli expression system which produced the peptide at an expression level of approximately 2-5% of total cell protein. The peptide was localized to disulfide-linked refractile bodies which were solubilized by reduction in the presence of denaturant and the soluble protein refolded. Oxidized K2 was purified from the refold mixture using a two-step procedure employing gel filtration chromatography and reverse-phase HPLC. The unprocessed form of the recombinant peptide, Met-Ala-K2 (rMA-K2), was characterized. This peptide was purified to apparent homogeneity as determined by SDS-PAGE, quantitative amino acid, Edman degradation, and electrospray mass spectrometry analyses (> 95% pure). The product bound to factor Xa covalently coupled to a solid support in the presence of 2M sodium chloride demonstrating its affinity for this enzyme. Preincubation of rMA-K2 peptide with factor Xa neutralized, with 1.1:1 stoichiometry, the ability of factor Xa to hydrolyze a small chromogenic substrate. Additionally, rMA-K2 prolonged the time to clot formation in a plasma-based assay dependent on factor Xa concentration. Finally, this peptide mildly prolonged the prothrombin and modified prothrombin times of normal pooled plasma. Taken together this data demonstrates that this region of TFPI inhibits factor Xa activity and allows for further characterization of this enzyme-inhibitor complex.
Amino Acid Sequence↗
Anti-inhibitor coagulant complex for the rescue therapy of acquired inhibitors to factor VIII: case report and review of the literature.
A 62-year-old African-American man with a history of hypertension, asthma, and prostate cancer, but no prior history of haemophilia presented with gross haematuria following a motor vehicle accident. Coagulation studies revealed a prolonged partial thromboplastin time. Subsequent mixing study and factor analysis confirmed factor VIII (FVIII) deficiency. The patient subsequently developed a knee haemarthrosis associated with persistent haematuria and a profoundly elevated FVIII inhibitor titre. Fresh frozen plasma was initiated upon presentation. Once FVIII inhibitor was discovered, immunosuppressive agents were started. Concurrent treatment with acute bypass agents including porcine FVIII, and recombinant human factor VIIa (rFVIIa;NovoSeven), was also given. Ultimately, anti-inhibitor coagulant complex (Autoplex T) was administered, stabilizing the haematuria and haemarthrosis. There was no additional bleeding 6 months after the last dose of anti-inhibitor coagulant complex. This case is consistent with others in which anti-inhibitor coagulant complex therapy was used successfully to manage patients with serious acute bleeding problems who are found to have acquired inhibitors to factor VIII.
Accidents, Traffic↗
Post-trauma coagulation and fibrinolysis in children suffering from severe cerebro-cranial trauma.
UNLABELLED: The present study was designed to evaluate the post-trauma haemostatic changes in 27 children with severe cranio-cerebral trauma defined by a modified Glasgow Coma Score (GCS) < 10. Blood samples for coagulation studies (fibrinogen, von Willebrand factor (vWf), factor VIII:C, antithrombin, protein C, plasminogen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI), D-dimer) were obtained within two hours of admission, 24 h later, and on days 3-5, 7-9, 21 and 35. Data of this study indicate that alterations of coagulation in paediatric patients are similar to those in adults: On hospitalisation, activated haemostasis was found with decreased fibrinogen, antithrombin and protein C along with enhanced t-PA and PAI. Twenty-four hours later, hypercoagulability with significantly increased vWF and fibrinogen started, with a peak level within the second week. Within 24 h of admission, 17 children developed disseminated intravascular coagulation (DIC) with a clear-cut decrease of antithrombin and fibrinogen together with platelet consumption and enhanced D-dimer. The outcome of children with DIC was significantly poorer than in those without DIC. Complete recovery was seen in five patients; sequelae no handicap and moderate disability were each found in six patients. Severe disability was diagnosed in two children, and fulminant DIC with lethal outcome occurred in eight patients. The GCS (P < 0.01) and the occurrence of DIC (P < 0.005) showed the strongest association with the patients' clinical outcome. CONCLUSION: Our data underline the significance of post-trauma disturbances of the haemostatic system for the clinical course and outcome in children with severe cranio-cerebral injuries.
Adolescent↗
The effects of perioperatively administered crystalloids and colloids on concentrations of molecular markers of activated coagulation and fibrinolysis.
To explore whether intravenous administration of routinely used crystalloid or colloid solutions differently affects the coagulation system, we investigated orthopaedic patients. Since crystalloid solutions might cause hypercoagulability, we here present our results on molecular markers of coagulation and fibrinolysis. Patients undergoing knee replacement surgery randomly received isovolemic amounts of lactated Ringer's solution, 6% hydroxyethyl starch 200/0.5 or 4% modified gelatine. Arterial blood samples for determination of specific molecular markers of activated coagulation (thrombin/antithrombin complex, D-dimer, prothrombin fragment F1 + 2), fibrinolysis (plasmin/alpha 2-antiplasmin complex, tissue plasminogen activator, plasminogen activator inhibitor-1), and concentrations of coagulation factor XIII were obtained at baseline, before tourniquet release, at the end of surgery and 2 h after operation. During the observation period, thrombin/antithrombin complex increased from 4.8 to 54.7 microg/l, D-dimer increased from 0.3 to 6.0 mg/ml, prothrombin fragment F1 + 2 increased from 1.7 to 5.9 nmol/l, tissue plasminogen activator decreased from 7.3 to 6.7 ng/ml, plasminogen activator inhibitor-1 increased from 68.4 to 71.0 ng/ml, plasmin/alpha 2-antiplasmin complex increased from 281.5 to 884 microg/l and factor XIII decreased from 89.0 to 58.5%. All parameters changed significantly but without any detectable difference in the response profile between the groups receiving different intravenous fluids. During knee replacement surgery a pronounced activation of the coagulation/fibrinolytic system was observed, regardless of whether patients received crystalloid or colloid fluids. Thus, these results cannot confirm the hypothesis that crystalloid fluids per se cause hypercoagulability in vivo.
Aged↗
Prothrombotic factors in children with stroke or porencephaly.
OBJECTIVE: This study compared the frequencies of genetic and functional coagulation abnormalities in children with arterial ischemic stroke or porencephaly with frequencies in previously published studies. METHODS: A series of 59 children (age 0-18 years) with arterial ischemic stroke or porencephaly were referred to the National Institutes of Health. A blood sample, buccal smear sample, questionnaire, and pedigree were requested for each child. Blood samples were analyzed for protein C (PC); protein S; antithrombin (AT); activated PC resistance (APCR); lipoprotein (a) [Lp(a)]; lupus anticoagulant; anticardiolipin antibodies; and the methylenetetrahydrofolate reductase C677T (MTHFR), factor V G1619A, factor II G20210A (PT), plasminogen activator inhibitor-1 4G6755G, and tissue factor pathway inhibitor C536T mutations. The frequency of each coagulation abnormality was compared with published international pediatric stroke case and control rates. RESULTS: At least 1 prothrombotic abnormality was identified in 63% (36 of 57) of children studied, including plasminogen activator inhibitor-1 4G6755G (15 of 56), MTHFR (12 of 56), elevated Lp(a) (12 of 59), APCR (11 of 58), factor V G1619A (5 of 57), PT (3 of 57), PC deficiency (1 of 59), and AT deficiency (1 of 59). The MTHFR mutation, elevated Lp(a), the PT mutation, and AT deficiency rates were similar to rates in cases and more common than control subjects in previously published studies. The rate of children with APCR or multiple abnormalities was higher than in previous pediatric stroke studies. A family history of early thrombosis was identified in one third of the children with a prothrombotic abnormality. CONCLUSIONS: Two thirds of children in this study had at least 1 of the prothrombotic risk factors tested, and several children had multiple risk factors. These results provide additional evidence that prothrombotic abnormalities are common among children with AIS or porencephaly.
Adolescent↗
Lupus anticoagulant and protein S deficiency in otherwise healthy children with acute varicella infection.
UNLABELLED: Acquired protein S deficiency and lupus anticoagulant have been described in children with varicella who had purpura fulminans, disseminated intravascular coagulation or thrombosis. The aim of this study was to investigate the natural anticoagulants, hypercoagulability markers, other parameters of coagulation and fibrinolytic systems, and the presence of the lupus anticoagulant in otherwise healthy children with acute varicella infection. Blood samples were obtained from 17 children with varicella without thrombosis during acute varicella infection and 1 mo after onset. Coagulation tests included determinations of the prothrombin time, the activated partial thromboplastin time, the thrombin time, the thrombin antithrombin complex, the prothrombin fragment F 1 + 2, the tissue plasminogen activator, the plasminogen activator inhibitor-1, protein C activity and free protein S antigen. Antiphospholipid antibodies were determined in enzyme-linked immunosorbent assays. The mean free protein S concentration in the acute phase (0.63 +/- 0.16 U/ml) was significantly lower than that of the concentration determined 1 mo later (0.82 +/- 0.17 U/ml). The children with acquired free protein S deficiency also had a lupus anticoagulant. Elevated concentrations of the prothrombin fragment F 1 + 2, the thrombin antithrombin complex, D-Dimer, tissue plasminogen activator and plasminogen activator inhibitor-1 were detected in most of the children. CONCLUSION: There is a significantly increased prevalence of lupus anticoagulant, a significantly reduced plasma concentration of free protein S and elevations in coagulation and fibrinolytic parameters in otherwise healthy children with acute varicella infection.
Acute Disease↗
Inhibition of coagulation by macromolecular complexes.
The role of vertebrate blood coagulation is to rapidly prevent the loss of body fluids following vascular injury without compromising blood flow through either the uninjured or damaged vessels. To achieve this the coagulation network is initiated and regulated by a complex network of interactions that are under the control of both positive and negative feedback loops that result in controlled fibrin deposition and platelet activation only at the site of injury. Anticoagulant molecules play key roles in preventing inappropriate initiation of coagulation as well as down-regulating thrombin generation at the site of injury. Tissue factor pathway inhibitor (TFPI) inhibits the initiation complex, antithrombin (AT) inhibits the active serine proteases directly, whereas the activated protein C pathway inhibits coagulation by inactivating the cofactors V and VIII. In this review the structure and function of these anticoagulant molecules and their inhibitory complexes is discussed.
Amino Acid Sequence↗
Associations of haemostatic variables with body mass index: a community-based study.
Obesity is a risk factor for venous and arterial thrombosis. We examined relationships between body mass index (BMI) and a number of haemostatic and inflammatory variables in a community-based study of 150 adults (73 male, 77 female; age range, 23-80 years). Associations with BMI were sought after adjustment for age, smoking and diurnal variation. There were significant interactions of gender on the associations of BMI with fibrinogen (P = 0.002) and C-reactive protein (P = 0.02). In women, there were strong positive associations of BMI with fibrinogen (r = 0.57, P < 0.0001) and C-reactive protein (r = 0.40, P = 0.001). In men, these associations were non-significantly inverse. For all other variables there were no sex differences, so results for men and women were combined. Significant positive associations with BMI were seen for factor VIIc, activated factor XII, antithrombin activity, protein C activity and plasminogen activator inhibitor-1 activity. Inverse associations with BMI were seen for tissue plasminogen activator activity and activated protein C ratio. Increasing BMI is associated with elevation of certain coagulation factors, inhibitors of fibrinolysis, and inhibitors of coagulation, the latter potentially reflecting a compensatory response. Gender influences the association of certain inflammatory variables with BMI so the sexes should be considered separately in studies of inflammation and obesity.
Adult↗
Procoagulant and anticoagulant mechanisms in human placenta.
The placenta is a highly vascularized organ functioning as the interface between fetal blood, which is confined within the villous blood vessels, and maternal blood, which flows in decidual arteries and washes the intervillous spaces in contact with syncytiotrophoblast (STB) cells. The STB adopts vascular characteristics such as the presence of von Willebrand factor (vWF), CD31 markers, adhesion molecules, and coagulation components. The special structure of the placenta requires efficient mechanisms for fast activation and localized regulation of coagulation. The presence of procoagulant and anticoagulant components on placental vascular endothelial cells (EC) and STB is essential for hemostasis. Activation of coagulation may be a favored process, as suggested by elevated fibrin depositions documented in some pathologic states. Increased localized procoagulant components such as tissue factor (TF) and plasminogen activator inhibitors (PAI-1, PAI-2), are associated with some pregnancy complications. Several anticoagulants regulate placental coagulation: tissue factor pathway inhibitor (TFPI) is primarily produced in EC; TFPI-2, a variant of TFPI, has been purified from the placenta and was identified in the STB lining the villi; thrombomodulin, a membrane glycoprotein that activates protein C, is localized in EC and apical membranes of STB; annexin V, an anticoagulant that binds to negative membrane phospholipids, is abundant on normal placental STB, whereas reduced STB annexin V was associated with the presence of antiphospholipid antibodies. The placenta is a putative source of coagulation components. However, the interplay between local procoagulant and anticoagulant mechanisms and their association with pregnancy complications need to be assessed.
Blood Coagulation↗
Insulin resistance: an atherothrombotic syndrome. The Leeds family study.
The insulin resistance syndrome (IRS) is a clustering of atherothrombotic traits associated with increased vascular risk. We investigated the degree to which the phenotypic correlations between these traits are due to shared genetic and environmental factors. A multivariate genetic analysis was performed in 537 adults from 89 healthy white north European families. All traits showed significant heritability. BMI had significant genetic correlations with fasting insulin, systolic blood pressure (sBP), plasminogen activator activator inhibitor-1 (PAI-1) and fibrinogen and triglyceride. Fasting insulin had a significant genetic correlation with fibrinogen and triglyceride and Factor VII (FVII). Significant genetic correlations were shown between triglyceride and PAI-1, fibrinogen and FVII. PAI-1 and tissue plasminogen activator (t-PA) showed significant genetic correlation with sBP and with each other. Pleiotropy was demonstrated between fibrinogen and PAI-1, t-PA and FVII. Significant environmental correlations were also demonstrated. This study demonstrates pleiotropy between coagulation and fibrinolytic factors. Shared genetic and environmental factors influencing haemostatic, metabolic and anthropometric traits underlie the atherothrombotic nature of the IRS.
Adult↗
Structural basis for inhibition promiscuity of dual specific thrombin and factor Xa blood coagulation inhibitors.
BACKGROUND: A major current focus of pharmaceutical research is the development of selective inhibitors of the blood coagulation enzymes thrombin or factor Xa to be used as orally bioavailable anticoagulant drugs in thromboembolic disorders and in the prevention of venous and arterial thrombosis. Simultaneous direct inhibition of thrombin and factor Xa by synthetic proteinase inhibitors as a novel approach to antithrombotic therapy could result in potent anticoagulants with improved pharmacological properties. RESULTS: The binding mode of such dual specific inhibitors of thrombin and factor Xa was determined for the first time by comparative crystallography using human alpha-thrombin, human des-Gla (1--44) factor Xa and bovine trypsin as the ligand receptors. The benzamidine-based inhibitors utilize two different conformations for the interaction with thrombin and factor Xa/trypsin, which are evoked by the steric requirements of the topologically different S2 subsites of the enzymes. Compared to the unliganded forms of the proteinases, ligand binding induces conformational adjustments of thrombin and factor Xa active site residues indicative of a pronounced induced fit mechanism. CONCLUSION: The structural data reveal the molecular basis for a desired unselective inhibition of the two key components of the blood coagulation cascade. The 4-(1-methyl-benzimidazole-2-yl)-methylamino-benzamidine moieties of the inhibitors are able to fill both the small solvent accessible as well as the larger hydrophobic S2 pockets of factor Xa and thrombin, respectively. Distal fragments of the inhibitors are identified which fit into both the cation hole/aromatic box of factor Xa and the hydrophobic aryl binding site of thrombin. Thus, binding constants in the medium-to-low nanomolar range are obtained against both enzymes.
Animals↗
Hemostatic and fibrinolytic indices in neonatal foals with presumed septicemia.
Thirteen coagulation tests evaluating hemostatic and fibrinolytic indices and serum cytokine and plasma endotoxin concentrations were obtained in 34 foals with a positive sepsis score (septic group) and 46 age-matched healthy foals. Compared to healthy foals, the prothrombin, activated partial thromboplastin, and whole blood recalcification times were significantly longer in septic foals. The fibrinogen and fibrin degradation products concentrations, percent plasminogen, alpha-2 antiplasmin, and plasminogen activator inhibitor activities, and tumor necrosis factor and interleukin-6 activities were greater in septic foals. Protein C antigen and antithrombin III activity were significantly lower in septic foals. Blood cultures were positive for growth and endotoxin was detected in 19 of 29 and 15 of 30 septic foals, respectively. In septicemic foals with detectable endotoxin in the plasma, the prothrombin and activated partial thromboplastin times were significantly longer and the plasminogen and antithrombin III activities were significantly less than in septic foals in which endotoxin was not detected. Twenty-three of the 34 septic foals did not survive. Septic foals that did not survive were most likely to have a positive blood culture in which a gram-negative organism was isolated. Histopathologic evidence of hemorrhage was evident in 11 foals at postmortem examination and thrombosis was identified in 2 foals. The prothrombin time was significantly longer in foals that had multisite hemorrhage at postmortem examination. The results of this study indicate that clinically relevant alternations in hemostatic and fibrinolytic indices occur in neonatal foals with septicemia and that derangements can be correlated with the presence of endotoxin in plasma. Derangements in hemostatic or fibrinolytic indices were helpful in identification of septic foals with increased risk of coagulopathy, but were not helpful in predicting hemorrhage as compared to thrombus formation. Survival of septicemic foals was correlated with gram-negative bacteremia, but not with the presence of endotoxin or coagulopathy.
Aging↗
Gene polymorphisms of the haemostatic system and the risk of arterial thrombotic disease.
Explore the source record for details and available documents.
Arteriosclerosis↗
Surgery in patients with hemophilia and inhibitors: a review of the Norwegian experience with FEIBA.
Surgical interventions in patients with hemophilia and inhibitors have often been postponed as long as possible due to difficulties in maintaining intra- and postoperative hemostatic control. Nonactivated and activated prothrombin complex concentrates have been successful in controlling acute bleeding in patients with inhibitors and have been useful in the surgical setting. At the Rikshospitalet-Radiumhospitalet University Hospital in Oslo, Norway, 17 minor and seven major surgical procedures were performed in nine patients with congenital hemophilia A and two patients with acquired hemophilia. Patients are generally treated according to the following dosing regimen, with changes made on a case-by-case basis: a preoperative loading dose of 100 U/kg of Factor Eight Inhibitor Bypassing Activity, Anti-Inhibitor Coagulant Complex, Vapor Heated (FEIBA; Baxter AG, Vienna, Austria), followed by 200 U/kg per day for 3 days. The dose is then tapered to 150 U/kg per day and subsequently to 100 U/kg per day. Hemostatic control was attained in all cases and only 1 major adverse event was observed. A 69-year-old patient experienced a non-ST-elevation myocardial infarction 3 days after undergoing a sigmoidectomy. He continued on FEIBA therapy and was stabilized with nitrates, opioid analgesia, and diuretics without clinical signs of heart failure.
Adult↗
Lower androgenicity is associated with higher plasma levels of prothrombotic factors irrespective of age, obesity, body fat distribution, and related metabolic parameters in men.
The purpose of this study was to examine the relationships between androgenic status and plasma levels of both prothrombotic and antithrombotic factors in men, irrespective of obesity, body fat distribution, and metabolic parameters. Sixty-four apparently healthy men, 40 with a body mass index (BMI) greater than 25 kg/m2 (overweight and obese [OO]) and 24 non-obese controls with a BMI less than 25, were selected and evaluated for (1) plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) antigen, PAI-1 activity, fibrinogen, von Willebrand factor (vWF) antigen, vWF activity, and factor VII (FVII) as the prothrombotic factors; (2) plasma levels of tissue plasminogen activator (TPA) antigen, protein C, and antithrombin III as the antithrombotic factors; (3) fasting plasma concentrations of insulin and glucose and the lipid pattern (triglycerides [TG] and total and high-density lipoprotein [HDL] cholesterol) as the metabolic parameters; and (4) free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) serum levels as the parameters of androgenicity. Body fat distribution was evaluated by the waist to hip ratio (WHR). In OO and non-obese subjects taken together, plasma levels of PAI-1 antigen, fibrinogen, and FVII were inversely associated with FT (r = .255, P < .05, r = -3.14, P < .05, and r = -.278, P < .05, respectively), and the negative relationships of both fibrinogen and FVII with FT were maintained after stepwise multiple regression analysis. Plasma concentrations of PAI-1 antigen and PAI-1 activity were also negatively correlated with SHBG (r = -.315, P < .05 and r = -.362, P < .01, respectively), and these associations held irrespective of the other parameters investigated. None of the antithrombotic and fibrinolytic factors were independently related to serum androgen levels. Subjects with a BMI higher than 25 kg/m2 had higher plasma concentrations of PAI-1 antigen, PAI-1 activity, and fibrinogen as compared with non-obese controls (P < .001, P < .001, and P < .01, respectively). In addition, in OO and control subjects as a whole, multiple stepwise regression analysis showed that the associations of BMI with PAI-1 activity, fibrinogen, vWF antigen, and vWF activity were independent of any other metabolic and hormonal parameters. Plasma concentrations of PAI-1 antigen, PAI-1 activity, and fibrinogen were also directly correlated with WHR in all subjects taken together, irrespective of the other parameters investigated. Evaluation of antithrombotic factors showed that OO subjects had higher TPA plasma concentrations than non-obese controls (P < .001), whereas protein C and antithrombin III did not differ in the two groups. TPA was also directly correlated with BMI (r = .415, P < .001) and WHR (r = .393, P < .001) in all subjects. The results of this study indicate that (1) men with lower FT serum levels have higher fibrinogen and FVII plasma concentrations, and those with lower SHBG serum levels also have higher levels of PAI-1 antigen and activity; (2) irrespective of other factors, obesity per se may account for higher concentrations of PAI-1, fibrinogen, and vWF; (3) plasma levels of PAI-1 (antigen and activity) and fibrinogen correlate independently with WHR; and (4) among the investigated antithrombotic factors (TPA antigen, protein C, antithrombin III), only TPA antigen plasma concentrations are higher in men with abdominal obesity. Thus, because of the increase in several prothrombotic factors, men with central obesity, particularly those with lower androgenicity, seem to be at greater risk for coronary heart disease (CHD). Apparently, this risk is not counteracted by a parallel increase in plasma concentrations of antithrombotic factors.
Adult↗
Inherited thrombophilia.
Inherited thrombophilia can be defined as a genetically determined predisposition to the development of thromboembolic complications. Since the discovery of activated protein C resistance in 1993, several additional disorders have been described and, at present, it is possible to identify an inherited predisposition in about 60 to 70% of patients with such complications. These inherited prothrombotic risk factors include qualitative or quantitative defects of coagulation factor inhibitors, increased levels or function of coagulation factors, defects of the fibrinolytic system, altered platelet function, and hyperhomocysteinemia. In this review, the main inherited prothrombotic risk factors are analyzed from epidemiological, laboratory, clinical, and therapeutic points of view. Finally, we discuss the synergism between genetic and acquired prothrombotic risk factors in particular conditions such as childhood and pregnancy.
Afibrinogenemia↗