Antifibrinolytic Agents
Aminocaproic Acid
Aminocaproates
Aprotinin
Blood Transfusion
Carboxypeptidase U
Postoperative Hemorrhage
Carboxypeptidase B
Hemostatics
Thrombomodulin
Blood Coagulation
alpha-2-Antiplasmin
Carboxypeptidases
Hemostasis
Cardiopulmonary Bypass
Relationship of plasmin generation to cardiovascular disease risk factors in elderly men and women. (1/402)
Plasmin-alpha2-antiplasmin complex (PAP) marks plasmin generation and fibrinolytic balance. We recently observed that elevated levels of PAP predict acute myocardial infarction in the elderly, yet little is known about the correlates of PAP. We measured PAP in 800 elderly subjects who were free of clinical cardiovascular disease in 2 cohort studies: the Cardiovascular Health Study and the Honolulu Heart Program. Median PAP levels did not differ between the Cardiovascular Health Study (6.05+/-1.46 nmol/L) and the Honolulu Heart Program (6.11+/-1.44 nmol/L), and correlates of PAP were similar in both cohorts. In CHS, PAP levels increased with age (r=0. 30), procoagulant factors (eg, factor VIIc, r=0.15), thrombin activity (prothrombin fragment F1+2, r=0.29), and inflammation-sensitive proteins (eg, fibrinogen, r=0.44; factor VIIIc, r=0.37). PAP was associated with increased atherosclerosis as measured by the ankle-arm index (AAI) (P for trend, +info)Usefulness of D-dimer, blood gas, and respiratory rate measurements for excluding pulmonary embolism. (2/402)
BACKGROUND: A study was undertaken to assess the usefulness of the SimpliRED D-dimer test, arterial oxygen tension, and respiratory rate measurement for excluding pulmonary embolism (PE) and venous thromboembolism (VTE). METHODS: Lung scans were performed in 517 consecutive medical inpatients with suspected acute PE over a one year period. Predetermined end points for objectively diagnosed PE in order of precedence were (1) a post mortem diagnosis, (2) a positive pulmonary angiogram, (3) a high probability ventilation perfusion lung scan when the pretest probability was also high, and (4) the unanimous opinion of an adjudication committee. Deep vein thrombosis (DVT) was diagnosed by standard ultrasound and venography. RESULTS: A total of 40 cases of PE and 37 cases of DVT were objectively diagnosed. The predictive value of a negative SimpliRED test for excluding objectively diagnosed PE was 0.99 (error rate 2/249), that of PaO2 of > or = 80 mm Hg (10.7 kPa) was 0.97 (error rate 5/160), and that of a respiratory rate of < or = 20/min was 0.95 (error rate 14/308). The best combination of findings for excluding PE was a negative SimpliRED test and PaO2 > or = 80 mm Hg, which gave a predictive value of 1.0 (error rate 0/93). The predictive value of a negative SimpliRED test for excluding VTE was 0.98 (error rate 5/249). CONCLUSIONS: All three of these observations are helpful in excluding PE. When any two parameters were normal, PE was very unlikely. In patients with a negative SimpliRED test and PaO2 of > or = 80 mm Hg a lung scan is usually unnecessary. Application of this approach for triage in the preliminary assessment of suspected PE could lead to a reduced rate of false positive diagnoses and considerable resource savings. (+info)Tranexamic acid increases peritoneal ultrafiltration volume in patients on CAPD. (3/402)
OBJECTIVE: The preservation of ultrafiltration (UF) capacity is crucial to maintaining long-term continuous ambulatory peritoneal dialysis (CAPD).The aim of the present study was to investigate whether the antiplasmin agent tranexamic acid (TNA) increases UF volume in CAPD patients. PATIENTS AND METHODS: Fifteen patients on CAPD, 5 with UF loss and 10 without UF loss, were recruited for the study. The effect of TNA was evaluated with respect to changes in UF volume, peritoneal permeability, peritoneal clearance, bradykinin (BK), and tissue plasminogen activator (tPA) concentration. SETTING: Dialysis unit of the Saiseikai Central Hospital. RESULTS: In patients with UF loss, 2 weeks of treatment with oral TNA produced a significant increase in UF volume in all subjects (5/5).TNA also produced a significant increase in peritoneal clearances of urea and creatinine (Cr). However, the peritoneal equilibration test (PET) revealed that TNA had no effect on dialysate/plasma (D/P) Cr, Kt/V, or the protein catabolic rate (PCR).TNA also had no effect on net glucose reabsorption. In contrast, significant decreases in BK and blood tPA concentrations in response to TNA treatment were noted. BK concentration in drainage fluid was also reduced. In the case of patients without UF loss,TNA produced an increase in UF volume in 70% (7/10). However, no differences were found in blood and drainage BK and tPA concentrations between theTNA treatment and nontreatment periods in these patients. A comparison of basal BK and tPA concentration showed that there were no differences in these parameters between patients with UF loss and those without loss of UF. Furthermore,TNA given intraperitoneally to a patient also produced a marked increase in UF volume. CONCLUSION: The present study suggests thatTNA enhances UF volume in patients both with and without UF loss. SinceTNA did not affect peritoneal permeability and glucose reabsorption, the mechanism by which TNA exerts an enhancing action on UF is largely unknown. We speculate that it may be associated with suppression of the BK and/or tPA system, at least in patients with UF loss. (+info)Randomised controlled trial of educational package on management of menorrhagia in primary care: the Anglia menorrhagia education study. (4/402)
OBJECTIVE: To determine whether an educational package could influence the management of menorrhagia, increase the appropriateness of choice of non-hormonal treatment, and reduce referral rates from primary to secondary care. DESIGN: Randomised controlled trial. SETTING: General practices in East Anglia. SUBJECTS: 100 practices (348 doctors) in primary care were recruited and randomised to intervention (54) and control (46). INTERVENTIONS: An educational package based on principles of "academic detailing" with independent academics was given in small practice based interactive groups with a visual presentation, a printed evidence based summary, a graphic management flow chart, and a follow up meeting at 6 months. OUTCOME MEASURES: All practices recorded consultation details, treatments offered, and outcomes for women with regular heavy menstrual loss (menorrhagia) over 1 year. RESULTS: 1001 consultation data sheets for menorrhagia were returned. There were significantly fewer referrals (20% v 29%; odds ratio 0. 64; 95% confidence interval 0.41 to 0.99) and a significantly higher use of tranexamic acid (odds ratio 2.38; 1.61 to 3.49) in the intervention group but no overall difference in norethisterone treatment compared with controls. There were more referrals when tranexamic acid was given with norethisterone than when it was given alone. Those practices reporting fewer than 10 cases showed the highest increase in prescribing of tranexamic acid. CONCLUSIONS: The educational package positively influenced referral for menorrhagia and treatment with appropriate non-hormonal drugs. (+info)Pharmacokinetics of epsilon-aminocaproic acid in patients undergoing aortocoronary bypass surgery. (5/402)
BACKGROUND: Epsilon-aminocaproic acid (EACA) is commonly infused during cardiac surgery using empiric dosing schemes. The authors developed a pharmacokinetic model for EACA elimination in surgical patients, tested whether adjustments for cardiopulmonary bypass (CPB) would improve the model, and then used the model to develop an EACA dosing schedule that would yield nearly constant EACA blood concentrations. METHODS: Consenting patients undergoing elective coronary artery surgery received one of two loading doses of EACA, 30 mg/kg (group I, n = 7) or 100 mg/kg (group II, n = 6) after CPB, or (group III) a 100 mg/kg loading dose before CPB and a 10 mg x kg(-1) x h(-1) maintenance infusion continued for 4 h during and after CPB (n = 7). Two patients with renal failure received EACA in the manner of group III. Blood concentrations of EACA, measured by high-performance liquid chromatography, were subjected to mixed-effects pharmacokinetic modeling. RESULTS: The EACA concentration data were best fit by a model with two compartments and corrections for CPB. The elimination rate constant k10 fell from 0.011 before CPB to 0.0006 during CPB, returning to 0.011 after CPB. V1 increased 3.8 l with CPB and remained at that value thereafter. Cl1 varied from 0.08 l/min before CPB to 0.007 l/min during CPB and 0.13 l/min after CPB. Cl2 increased from 0.09 l/min before CPB to 0.14 l/min during and after CPB. Two patients with renal failure demonstrated markedly reduced clearance. Using their model, the authors predict that an EACA loading infusion of 50 mg/kg given over 20 min and a maintenance infusion of 25 mg x kg(-1) x h(-1) would maintain a nearly constant target concentration of 260 microg/ml. CONCLUSIONS: EACA clearance declines and volume of distribution increases during CPB. The authors' model predicts that more stable perioperative EACA concentrations would be obtained with a smaller loading dose (50 mg/kg given over 20 min) and a more rapid maintenance infusion (25 mg x kg(-1) x h(-1)) than are typically employed. (+info)The effect of prophylactic epsilon-aminocaproic acid on bleeding, transfusions, platelet function, and fibrinolysis during coronary artery bypass grafting. (6/402)
BACKGROUND: Antifibrinolytic medications administered before skin incision decrease bleeding after cardiac surgery. Numerous case reports indicate thrombus formation with administration of epsilon-aminocaproic acid (epsilon-ACA). The purpose of this study was to examine the efficacy of epsilon-ACA administered after heparinization but before cardiopulmonary bypass in reducing bleeding and transfusion requirements after primary coronary artery bypass surgery. METHODS: Seventy-four adult patients undergoing primary coronary artery bypass surgery were randomized to receive 125 mg/kg epsilon-ACA followed by an infusion of 12.5 mg x kg(-1) x h(-1) or an equivalent volume of saline. Coagulation studies, thromboelastography, and platelet aggregation tests were performed preoperatively, after bypass, and on the first postoperative day. Mediastinal drainage was recorded during the 24 h after surgery. Homologous blood transfusion triggers were predefined and transfusion amounts were recorded. RESULTS: One patient was excluded for surgical bleeding and five patients were excluded for transfusion against predefined criteria One patient died from a dysrhythmia 2 h postoperatively. Among the remaining 67, the epsilon-ACA group had less mediastinal blood loss during the 24 h after surgery, 529+/-241 ml versus 691+/-286 ml (mean +/- SD), P < 0.05, despite longer cardiopulmonary bypass times and lower platelet counts, P < 0.05. Platelet aggregation was reduced in both groups following cardiopulmonary bypass but did not differ between groups. Homologous blood transfusion was similar between both groups. CONCLUSIONS: Prophylactic administration of epsilon-ACA after heparinization but before cardiopulmonary bypass is of minimal benefit for reducing blood loss postoperatively in patients undergoing primary coronary artery bypass grafting. (+info)The effects of hydrostatic pressure on the conformation of plasminogen. (7/402)
Plasminogen undergoes a large conformational change when it binds 6-aminohexanoate. Using ultraviolet absorption spectroscopy and native PAGE, we show that hydrostatic pressure brings about the same conformational change. The volume change for this conformational change is -33 mL.mol-1. Binding of ligand and hydrostatic pressure both cause the protein to open up to expose surfaces that had previously been buried in the interior. (+info)Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. (8/402)
BACKGROUND: Although improved epicardial blood flow (as assessed with either TIMI flow grades or TIMI frame count) has been related to reduced mortality after administration of thrombolytic drugs, the relationship of myocardial perfusion (as assessed on the coronary arteriogram) to mortality has not been examined. METHODS AND RESULTS: A new, simple angiographic method, the TIMI myocardial perfusion (TMP) grade, was used to assess the filling and clearance of contrast in the myocardium in 762 patients in the TIMI (Thrombolysis In Myocardial Infarction) 10B trial, and its relationship to mortality was examined. TMP grade 0 was defined as no apparent tissue-level perfusion (no ground-glass appearance of blush or opacification of the myocardium) in the distribution of the culprit artery; TMP grade 1 indicates presence of myocardial blush but no clearance from the microvasculature (blush or a stain was present on the next injection); TMP grade 2 blush clears slowly (blush is strongly persistent and diminishes minimally or not at all during 3 cardiac cycles of the washout phase); and TMP grade 3 indicates that blush begins to clear during washout (blush is minimally persistent after 3 cardiac cycles of washout). There was a mortality gradient across the TMP grades, with mortality lowest in those patients with TMP grade 3 (2.0%), intermediate in TMP grade 2 (4.4%), and highest in TMP grades 0 and 1 (6.0%; 3-way P=0.05). Even among patients with TIMI grade 3 flow in the epicardial artery, the TMP grades allowed further risk stratification of 30-day mortality: 0.73% for TMP grade 3; 2.9% for TMP grade 2; 5.0% for TMP grade 0 or 1 (P=0.03 for TMP grade 3 versus grades 0, 1, and 2; 3-way P=0.066). TMP grade 3 flow was a multivariate correlate of 30-day mortality (OR 0.35, 95% CI 0.12 to 1.02, P=0.054) in a multivariate model that adjusted for the presence of TIMI 3 flow (P=NS), the corrected TIMI frame count (OR 1.02, P=0.06), the presence of an anterior myocardial infarction (OR 2.3, P=0.03), pulse rate on admission (P=NS), female sex (P=NS), and age (OR 1.1, P<0.001). CONCLUSIONS: Impaired perfusion of the myocardium on coronary arteriography by use of the TMP grade is related to a higher risk of mortality after administration of thrombolytic drugs that is independent of flow in the epicardial artery. Patients with both normal epicardial flow (TIMI grade 3 flow) and normal tissue level perfusion (TMP grade 3) have an extremely low risk of mortality. (+info)Antifibrinolytic agents are a class of medications that inhibit the breakdown of blood clots. They work by blocking the action of enzymes called plasminogen activators, which convert plasminogen to plasmin, the main enzyme responsible for breaking down fibrin, a protein that forms the framework of a blood clot.
By preventing the conversion of plasminogen to plasmin, antifibrinolytic agents help to stabilize existing blood clots and prevent their premature dissolution. These medications are often used in clinical settings where excessive bleeding is a concern, such as during or after surgery, childbirth, or trauma.
Examples of antifibrinolytic agents include tranexamic acid, aminocaproic acid, and epsilon-aminocaproic acid. While these medications can be effective in reducing bleeding, they also carry the risk of thromboembolic events, such as deep vein thrombosis or pulmonary embolism, due to their pro-coagulant effects. Therefore, they should be used with caution and only under the close supervision of a healthcare provider.
Aminocaproic acid is an antifibrinolytic medication, which means it helps to prevent the breakdown of blood clots. It works by blocking plasmin, an enzyme in your body that dissolves blood clots.
This drug is used for the treatment of bleeding conditions due to various causes, such as:
1. Excessive menstrual bleeding (menorrhagia)
2. Bleeding after tooth extraction or surgery
3. Hematuria (blood in urine) due to certain medical procedures or conditions like kidney stones
4. Intracranial hemorrhage (bleeding inside the skull)
5. Hereditary angioedema, a genetic disorder that causes swelling of various parts of the body
Aminocaproic acid is available in oral and injectable forms. Common side effects include nausea, vomiting, diarrhea, and headache. Serious side effects are rare but may include allergic reactions, seizures, or vision changes. It's essential to use this medication under the supervision of a healthcare professional, as improper usage might lead to blood clots, stroke, or other severe complications.
Tranexamic acid is an antifibrinolytic medication that is used to reduce or prevent bleeding. It works by inhibiting the activation of plasminogen to plasmin, which is a protease that degrades fibrin clots. By preventing the breakdown of blood clots, tranexamic acid helps to reduce bleeding and promote clot formation.
Tranexamic acid is available in various forms, including tablets, capsules, and injectable solutions. It is used in a variety of clinical settings, such as surgery, trauma, and heavy menstrual bleeding. The medication can be taken orally or administered intravenously, depending on the severity of the bleeding and the patient's medical condition.
Common side effects of tranexamic acid include nausea, vomiting, diarrhea, and headache. Less commonly, the medication may cause allergic reactions, visual disturbances, or seizures. It is important to follow the prescribing physician's instructions carefully when taking tranexamic acid to minimize the risk of side effects and ensure its safe and effective use.
Aminocaproates are a group of chemical compounds that contain an amino group and a carboxylic acid group, as well as a straight or branched alkyl chain with 6-10 carbon atoms. They are often used in medical settings as anti-fibrinolytic agents, which means they help to prevent the breakdown of blood clots.
One example of an aminocaproate is epsilon-aminocaproic acid (EACA), which is a synthetic analogue of the amino acid lysine. EACA works by inhibiting the activation of plasminogen to plasmin, which is an enzyme that breaks down blood clots. By doing so, EACA can help to reduce bleeding and improve clot stability in certain medical conditions, such as hemophilia or following surgery.
Other aminocaproates include tranexamic acid (TXA) and 4-aminoethylbenzoic acid (AEBA), which also have anti-fibrinolytic properties and are used in similar clinical settings. However, it's important to note that these medications can increase the risk of thrombosis (blood clots) if not used properly, so they should only be administered under the close supervision of a healthcare provider.
Aprotinin is a medication that belongs to a class of drugs called serine protease inhibitors. It works by inhibiting the activity of certain enzymes in the body that can cause tissue damage and bleeding. Aprotinin is used in medical procedures such as heart bypass surgery to reduce blood loss and the need for blood transfusions. It is administered intravenously and its use is typically stopped a few days after the surgical procedure.
Aprotinin was first approved for use in the United States in 1993, but its use has been restricted or withdrawn in many countries due to concerns about its safety. In 2006, a study found an increased risk of kidney damage and death associated with the use of aprotinin during heart bypass surgery, leading to its withdrawal from the market in Europe and Canada. However, it is still available for use in the United States under a restricted access program.
It's important to note that the use of aprotinin should be carefully considered and discussed with the healthcare provider, taking into account the potential benefits and risks of the medication.
Surgical blood loss is the amount of blood that is lost during a surgical procedure. It can occur through various routes such as incisions, punctures or during the removal of organs or tissues. The amount of blood loss can vary widely depending on the type and complexity of the surgery being performed.
Surgical blood loss can be classified into three categories:
1. Insensible losses: These are small amounts of blood that are lost through the skin, respiratory tract, or gastrointestinal tract during surgery. They are not usually significant enough to cause any clinical effects.
2. Visible losses: These are larger amounts of blood that can be seen and measured directly during surgery. They may require transfusion or other interventions to prevent hypovolemia (low blood volume) and its complications.
3. Hidden losses: These are internal bleeding that cannot be easily seen or measured during surgery. They can occur in the abdominal cavity, retroperitoneal space, or other areas of the body. They may require further exploration or imaging studies to diagnose and manage.
Surgical blood loss can lead to several complications such as hypovolemia, anemia, coagulopathy (disorders of blood clotting), and organ dysfunction. Therefore, it is essential to monitor and manage surgical blood loss effectively to ensure optimal patient outcomes.
A blood transfusion is a medical procedure in which blood or its components are transferred from one individual (donor) to another (recipient) through a vein. The donated blood can be fresh whole blood, packed red blood cells, platelets, plasma, or cryoprecipitate, depending on the recipient's needs. Blood transfusions are performed to replace lost blood due to severe bleeding, treat anemia, support patients undergoing major surgeries, or manage various medical conditions such as hemophilia, thalassemia, and leukemia. The donated blood must be carefully cross-matched with the recipient's blood type to minimize the risk of transfusion reactions.
Carboxypeptidase U is also known as thiol protease or thiol carboxypeptidase. It is a type of enzyme that belongs to the peptidase family, specifically the serine proteases. This enzyme plays a role in the regulation of blood pressure by cleaving and inactivating bradykinin, a potent vasodilator peptide. Carboxypeptidase U is primarily produced in the kidneys and is released into the circulation in response to various stimuli, such as renin and angiotensin II. It functions by removing the C-terminal arginine residue from bradykinin, thereby reducing its biological activity and helping to maintain blood pressure homeostasis.
Fibrinolysis is the natural process in the body that leads to the dissolution of blood clots. It is a vital part of hemostasis, the process that regulates bleeding and wound healing. Fibrinolysis occurs when plasminogen activators convert plasminogen to plasmin, an enzyme that breaks down fibrin, the insoluble protein mesh that forms the structure of a blood clot. This process helps to prevent excessive clotting and maintains the fluidity of the blood. In medical settings, fibrinolysis can also refer to the therapeutic use of drugs that stimulate this process to dissolve unwanted or harmful blood clots, such as those that cause deep vein thrombosis or pulmonary embolism.
Postoperative hemorrhage is a medical term that refers to bleeding that occurs after a surgical procedure. This condition can range from minor oozing to severe, life-threatening bleeding. Postoperative hemorrhage can occur soon after surgery or even several days later, as the surgical site begins to heal.
The causes of postoperative hemorrhage can vary, but some common factors include:
1. Inadequate hemostasis during surgery: This means that all bleeding was not properly controlled during the procedure, leading to bleeding after surgery.
2. Blood vessel injury: During surgery, blood vessels may be accidentally cut or damaged, causing bleeding after the procedure.
3. Coagulopathy: This is a condition in which the body has difficulty forming blood clots, increasing the risk of postoperative hemorrhage.
4. Use of anticoagulant medications: Medications that prevent blood clots can increase the risk of bleeding after surgery.
5. Infection: An infection at the surgical site can cause inflammation and bleeding.
Symptoms of postoperative hemorrhage may include swelling, pain, warmth, or discoloration around the surgical site, as well as signs of shock such as rapid heartbeat, low blood pressure, and confusion. Treatment for postoperative hemorrhage depends on the severity of the bleeding and may include medications to control bleeding, transfusions of blood products, or additional surgery to stop the bleeding.
Carboxypeptidase B is a type of enzyme that belongs to the peptidase family. It is also known as carboxypeptidase B1 or CpB. This enzyme plays a crucial role in the digestion of proteins by cleaving specific amino acids from the carboxyl-terminal end of polypeptides.
Carboxypeptidase B preferentially removes basic arginine and lysine residues from protein substrates, making it an essential enzyme in various physiological processes, including blood clotting, hormone processing, and neuropeptide metabolism. It is synthesized as an inactive zymogen, procarboxypeptidase B, which is converted to its active form upon proteolytic activation.
In addition to its physiological functions, carboxypeptidase B has applications in research and industry, such as protein sequencing, peptide synthesis, and food processing.
Hemostatics are substances or agents that promote bleeding cessation or prevent the spread of bleeding. They can act in various ways, such as by stimulating the body's natural clotting mechanisms, constricting blood vessels to reduce blood flow, or forming a physical barrier to block the bleeding site.
Hemostatics are often used in medical settings to manage wounds, injuries, and surgical procedures. They can be applied directly to the wound as a powder, paste, or gauze, or they can be administered systemically through intravenous injection. Examples of hemostatic agents include fibrin sealants, collagen-based products, thrombin, and oxidized regenerated cellulose.
It's important to note that while hemostatics can be effective in controlling bleeding, they should be used with caution and only under the guidance of a healthcare professional. Inappropriate use or overuse of hemostatic agents can lead to complications such as excessive clotting, thrombosis, or tissue damage.
Thrombomodulin is a protein that is found on the surface of endothelial cells, which line the interior surface of blood vessels. It plays an important role in the regulation of blood coagulation (clotting) and the activation of natural anticoagulant pathways. Thrombomodulin binds to thrombin, a protein involved in blood clotting, and changes its function from promoting coagulation to inhibiting it. This interaction also activates protein C, an important anticoagulant protein, which helps to prevent the excessive formation of blood clots. Thrombomodulin also has anti-inflammatory properties and is involved in the maintenance of the integrity of the endothelial cell lining.
Blood coagulation, also known as blood clotting, is a complex process that occurs in the body to prevent excessive bleeding when a blood vessel is damaged. This process involves several different proteins and chemical reactions that ultimately lead to the formation of a clot.
The coagulation cascade is initiated when blood comes into contact with tissue factor, which is exposed after damage to the blood vessel wall. This triggers a series of enzymatic reactions that activate clotting factors, leading to the formation of a fibrin clot. Fibrin is a protein that forms a mesh-like structure that traps platelets and red blood cells to form a stable clot.
Once the bleeding has stopped, the coagulation process is regulated and inhibited to prevent excessive clotting. The fibrinolytic system degrades the clot over time, allowing for the restoration of normal blood flow.
Abnormalities in the blood coagulation process can lead to bleeding disorders or thrombotic disorders such as deep vein thrombosis and pulmonary embolism.
Alpha-2-antiplasmin (α2AP) is a protein found in the blood plasma that inhibits fibrinolysis, the process by which blood clots are broken down. It does this by irreversibly binding to and inhibiting plasmin, an enzyme that degrades fibrin clots.
Alpha-2-antiplasmin is one of the most important regulators of fibrinolysis, helping to maintain a balance between clot formation and breakdown. Deficiencies or dysfunction in alpha-2-antiplasmin can lead to an increased risk of bleeding due to uncontrolled plasmin activity.
Surgical hemostasis refers to the methods and techniques used during surgical procedures to stop bleeding or prevent hemorrhage. This can be achieved through various means, including the use of surgical instruments such as clamps, ligatures, or staples to physically compress blood vessels and stop the flow of blood. Electrosurgical tools like cautery may also be used to coagulate and seal off bleeding vessels using heat. Additionally, topical hemostatic agents can be applied to promote clotting and control bleeding in wounded tissues. Effective surgical hemostasis is crucial for ensuring a successful surgical outcome and minimizing the risk of complications such as excessive blood loss, infection, or delayed healing.
Carboxypeptidases are a group of enzymes that catalyze the cleavage of peptide bonds at the carboxyl-terminal end of polypeptides or proteins. They specifically remove the last amino acid residue from the protein chain, provided that it has a free carboxyl group and is not blocked by another chemical group. Carboxypeptidases are classified into two main types based on their catalytic mechanism: serine carboxypeptidases and metallo-carboxypeptidases.
Serine carboxypeptidases, also known as chymotrypsin C or carboxypeptidase C, use a serine residue in their active site to catalyze the hydrolysis of peptide bonds. They are found in various organisms, including animals and bacteria.
Metallo-carboxypeptidases, on the other hand, require a metal ion (usually zinc) for their catalytic activity. They can be further divided into several subtypes based on their structure and substrate specificity. For example, carboxypeptidase A prefers to cleave hydrophobic amino acids from the carboxyl-terminal end of proteins, while carboxypeptidase B specifically removes basic residues (lysine or arginine).
Carboxypeptidases have important roles in various biological processes, such as protein maturation, digestion, and regulation of blood pressure. Dysregulation of these enzymes has been implicated in several diseases, including cancer, neurodegenerative disorders, and cardiovascular disease.
Hemostasis is the physiological process that occurs to stop bleeding (bleeding control) when a blood vessel is damaged. This involves the interaction of platelets, vasoconstriction, and blood clotting factors leading to the formation of a clot. The ultimate goal of hemostasis is to maintain the integrity of the vascular system while preventing excessive blood loss.
Cardiopulmonary bypass (CPB) is a medical procedure that temporarily takes over the functions of the heart and lungs during major heart surgery. It allows the surgeon to operate on a still, bloodless heart.
During CPB, the patient's blood is circulated outside the body with the help of a heart-lung machine. The machine pumps the blood through a oxygenator, where it is oxygenated and then returned to the body. This bypasses the heart and lungs, hence the name "cardiopulmonary bypass."
CPB involves several components, including a pump, oxygenator, heat exchanger, and tubing. The patient's blood is drained from the heart through cannulas (tubes) and passed through the oxygenator, where it is oxygenated and carbon dioxide is removed. The oxygenated blood is then warmed to body temperature in a heat exchanger before being pumped back into the body.
While on CPB, the patient's heart is stopped with the help of cardioplegia solution, which is infused directly into the coronary arteries. This helps to protect the heart muscle during surgery. The surgeon can then operate on a still and bloodless heart, allowing for more precise surgical repair.
After the surgery is complete, the patient is gradually weaned off CPB, and the heart is restarted with the help of electrical stimulation or medication. The patient's condition is closely monitored during this time to ensure that their heart and lungs are functioning properly.
While CPB has revolutionized heart surgery and allowed for more complex procedures to be performed, it is not without risks. These include bleeding, infection, stroke, kidney damage, and inflammation. However, with advances in technology and technique, the risks associated with CPB have been significantly reduced over time.
Serine proteinase inhibitors, also known as serine protease inhibitors or serpins, are a group of proteins that inhibit serine proteases, which are enzymes that cut other proteins in a process called proteolysis. Serine proteinases are important in many biological processes such as blood coagulation, fibrinolysis, inflammation and cell death. The inhibition of these enzymes by serpin proteins is an essential regulatory mechanism to maintain the balance and prevent uncontrolled proteolytic activity that can lead to diseases.
Serpins work by forming a covalent complex with their target serine proteinases, irreversibly inactivating them. The active site of serpins contains a reactive center loop (RCL) that mimics the protease's target protein sequence and acts as a bait for the enzyme. When the protease cleaves the RCL, it gets trapped within the serpin structure, leading to its inactivation.
Serpin proteinase inhibitors play crucial roles in various physiological processes, including:
1. Blood coagulation and fibrinolysis regulation: Serpins such as antithrombin, heparin cofactor II, and protease nexin-2 control the activity of enzymes involved in blood clotting and dissolution to prevent excessive or insufficient clot formation.
2. Inflammation modulation: Serpins like α1-antitrypsin, α2-macroglobulin, and C1 inhibitor regulate the activity of proteases released during inflammation, protecting tissues from damage.
3. Cell death regulation: Some serpins, such as PI-9/SERPINB9, control apoptosis (programmed cell death) by inhibiting granzyme B, a protease involved in this process.
4. Embryonic development and tissue remodeling: Serpins like plasminogen activator inhibitor-1 (PAI-1) and PAI-2 regulate the activity of enzymes involved in extracellular matrix degradation during embryonic development and tissue remodeling.
5. Neuroprotection: Serpins such as neuroserpin protect neurons from damage by inhibiting proteases released during neuroinflammation or neurodegenerative diseases.
Dysregulation of serpins has been implicated in various pathological conditions, including thrombosis, emphysema, Alzheimer's disease, and cancer. Understanding the roles of serpins in these processes may provide insights into potential therapeutic strategies for treating these diseases.