{"id":138,"date":"2019-10-07T18:40:55","date_gmt":"2019-10-07T13:10:55","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=138"},"modified":"2019-10-07T18:40:55","modified_gmt":"2019-10-07T13:10:55","slug":"drugs-affecting-coagulation","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/drugs-affecting-coagulation\/","title":{"rendered":"Drugs Affecting Coagulation"},"content":{"rendered":"\n

Drugs Affecting Coagulation<\/strong><\/p>\n\n\n\n

\"\"<\/figure><\/div>\n\n\n\n

VITAMIN\nK<\/strong><\/h2>\n\n\n\n
  • fat-soluble dietary principle\nrequired for the synthesis of clotting factors.<\/li>
  • Vit K3 \u00e0\nsynthetic<\/li>
  • Dietary sources are\u2014green leafy\nvegetables, such as cabbage, spinach; and liver, cheese, etc.<\/li>
  • Daily requirement \u00e0 50\u2013100 \u03bcg\/day.<\/li>
  • Action <\/strong>\u00e0 acts as a cofactor at a late stage in the synthesis by liver of\ncoagulation proteins\u2014 prothrombin, factors VII, IX and X. <\/li>
  • Utilization <\/strong>\u00e0  absorbed from the intestine\nvia lymph <\/li>
  • Vit K is only temporarily\nconcentrated in liver, but there are no significant stores in the body.<\/li>
  • Deficiency<\/strong> \u00e0\noccurs due to liver disease, obstructive jaundice, malabsorption, long-term\nantimicrobial therapy which alters intestinal flora. <\/li>
  • most important manifestation is\nbleeding tendency due to lowering of the levels of prothrombin and other\nclotting factors in blood.<\/li>
  • Haematuria<\/strong> is usually first to occur;\nother common sites of bleeding are g.i.t., nose and under the skin\u2014ecchymoses.<\/li>
  • only use of vit K is in prophylaxis and treatment of bleeding due to\ndeficiency of clotting factors<\/strong> in the following\nsituations:
    • Dietary deficiency: very rare <\/li><\/ul>
      • Prolonged antimicrobial therapy<\/li><\/ul>
        • Obstructive jaundice or\nmalabsorption syndromes<\/li><\/ul>
          • Newborns:<\/strong> All newborns have low levels\nof prothrombin and other clotting factors. Vit K 1 mg i.m. soon after birth has\nbeen recommended routinely. <\/li><\/ul>
            • Overdose of oral anticoagulants:<\/strong> most\nimportant indication of vit K.
              • Phytonadione (K1) is the preparation of choice, because it acts most\nrapidly. <\/li><\/ul><\/li><\/ul>
                • Prolonged high dose salicylate therapy<\/strong>\ncauses hypoprothrombinemia; vit K should be given prophylactically. If bleeding\noccurs\u2014treat as for oral anticoagulants.<\/li><\/ul>
                  • Liver disease (cirrhosis, viral\nhepatitis)<\/li><\/ul><\/li><\/ul>\n\n\n\n
                    • Menadione and its water-soluble\nderivatives can cause haemolysis in a dose-dependent manner. Patients with\nG-6-PD deficiency and neonates are especially susceptible.<\/li><\/ul>\n\n\n\n
                      • Fibrinogen <\/strong>\u00e0<\/strong>The fibrinogen fraction of human plasma is employed to control\nbleeding in haemophilia, antihaemophilic globulin (AHG) deficiency and acute\nafibrinogenemic states<\/li><\/ul>\n\n\n\n
                        • Desmopressin<\/strong> \u00e0releases\nfactor VIII and von Willebrand\u2019s factor from vascular endothelium and checks\nbleeding in haemophilia and von Willebrand\u2019s disease <\/li><\/ul>\n\n\n\n
                          • Adrenochrome monosemicarbazone<\/strong> \u00e0 It is believed to reduce capillary fragility, control oozing from\nraw surfaces and prevent microvessel bleeding, e.g. epistaxis, haematuria,\nsecondary haemorrhage from wounds, etc. Its efficacy is uncertain.<\/li><\/ul>\n\n\n\n
                            • Rutin <\/strong>\u00e0 plant glycoside claimed to reduce capillary bleeding. <\/li><\/ul>\n\n\n\n
                              • Ethamsylate<\/strong> \u00e0\nreduces capillary bleeding when platelets are adequate; probably exerts\nantihyaluronidase action or corrects abnormalities of platelet adhesion, but\ndoes not stabilize fibrin (not an antifibrinolytic). Ethamsylate has been used\nin the prevention and treatment of capillary bleeding in menorrhagia, after\nabortion, PPH, epistaxis, malena, hematuria and after tooth extraction, but\nefficacy is unsubstantiated.<\/li><\/ul>\n\n\n\n

                                LOCAL HAEMOSTATICS (STYPTICS)<\/h2>\n\n\n\n
                                • After injury to arterioles and\nother smaller blood vessels, normal haemostasis occurs successively by\ncontraction of injured vessel wall (lasting few minutes), <\/li>
                                • adhesion and aggregation of\nplatelets to form a plug, <\/li>
                                • formation of a blood clot, and<\/li>
                                • finally in due course\ndissolution of the clot by fibrinolysis. <\/li>
                                • External bleeding is usually\nstopped by manual pressure, cotton-gauze pressure pack or by suturing. <\/li>
                                • Control of bleeding may be aided by local haemostatics (styptics)\nthat are substances used to stop bleeding from a local and approachable site.<\/strong> <\/li>
                                • They are particularly effective\non oozing surfaces, e.g. tooth socket, abrasions, etc. <\/li>
                                • Absorbable materials like fibrin<\/strong> (prepared from human plasma and\ndryed as sheet or foam), gelatin foam,\noxidized cellulose<\/strong> (as strips which can be cut and placed in the wound)\nprovide a meshwork which activates the clotting mechanism and checks bleeding. <\/li>
                                • Left in situ these materials\nare absorbed in 1\u20134 weeks and generally cause no foreign body reaction.<\/li>
                                • Thrombin obtained from bovine plasma<\/strong> may\nbe applied as dry powder or freshly prepared solution to the bleeding surface\nin haemophiliacs. <\/li>
                                • Vasoconstrictors like 0.1% Adr solution<\/strong>\nmay be soaked in sterile cotton gauze and packed in the bleeding tooth socket or\nnose in case of epistaxis<\/strong> to check\nbleeding when spontaneous vasoconstriction is inadequate.<\/li>
                                • Astringents such as tannic acid\nor metallic salts are occasionally applied for bleeding gums, bleeding piles,\netc.<\/li><\/ul>\n\n\n\n

                                  ANTICOAGULANTS<\/strong><\/h2>\n\n\n\n

                                  These are drugs used to reduce the coagulability of blood. They may be classified into:<\/p>\n\n\n\n

                                  \"\"<\/figure><\/div>\n\n\n\n

                                  HEPARIN<\/strong><\/p>\n\n\n\n

                                  • Howell and Holt (1918) \u00e0 \u2018heparin\u2019 <\/li>
                                  • non-uniform mixture of straight\nchain mucopolysaccharides with MW 10,000 to 20,000. <\/li>
                                  • carries strong electronegative\ncharges and is the strongest organic\nacid present in the body<\/strong>. <\/li>
                                  • heparin is present in all tissues containing mast cells;<\/strong> richest sources are lung,\nliver and intestinal mucosa. <\/li><\/ul>\n\n\n\n

                                    ACTIONS<\/strong><\/p>\n\n\n\n

                                    Anticoagulant\n<\/strong><\/p>\n\n\n\n

                                    • acts indirectly by activating plasma\nantithrombin III <\/li>
                                    • The heparin-AT III complex then\nbinds to clotting factors of the intrinsic and common pathways (Xa, IIa, IXa,\nXIa, XIIa and XIIIa) and inactivates them but not factor VIIa operative in the\nextrinsic pathway. <\/li>
                                    • At low concentrations of heparin, factor Xa mediated conversion of prothrombin\nto thrombin is selectively affected<\/strong>. <\/li>
                                    • anticoagulant action is exerted mainly by inhibition of factor Xa as\nwell as thrombin (IIa)<\/strong> mediated conversion of\nfibrinogen to fibrin.<\/li>
                                    • Low concentrations of heparin prolong aPTT without significantly\nprolonging PT<\/strong>. High concentrations prolong both.<\/li>
                                    • Thus, low concentrations interfere\nselectively with the intrinsic pathway, while high concentrations affect the common\npathway as well.<\/li>
                                    • Heparin enhances action of AT\nIII by two mechanism<\/li>
                                    •  (a) Long heparin molecule provides a\nscaffolding for the clotting factors (mainly Xa and IIa) as well as AT III to\nget bound and interact with each other.<\/li>
                                    • (b) Heparin induces\nconformational change in AT III to expose its interactive sites. <\/li>
                                    • A specific pentasaccharide sequence<\/strong>, which is present in only some of\nthe heparin molecules, binds to AT III with high affinity to induce the\nconformational change needed for rapid interaction with clotting factors \u00e0 synthesized and named fondaparinux.<\/strong><\/li>
                                    • Inhibition of IIa requires both\nthe mechanisms, but Xa inhibition can occur by mechanism \u2018b\u2019 alone. \u00e0 explains why low molecular weight heparin, which is insufficient to\nprovide a long scaffolding, selectively inhibits factor Xa.<\/li><\/ul>\n\n\n\n

                                      Antiplatelet<\/strong> <\/p>\n\n\n\n

                                      • Heparin in higher doses\ninhibits platelet aggregation and prolongs bleeding time.<\/li><\/ul>\n\n\n\n

                                        Lipaemia\nclearing<\/strong><\/p>\n\n\n\n

                                        • Injection of heparin clears\nturbid post-prandial lipaemic plasma by releasing\na lipoprotein lipase<\/strong> from the vessel wall \u00e0\nhydrolyses triglycerides of chylomicron and VLDL to FFA. <\/li>
                                        • This action requires lower concentration\nof heparin than that needed for anticoagulation.<\/li><\/ul>\n\n\n\n

                                          PHARMACOKINETICS<\/strong><\/p>\n\n\n\n

                                          • Heparin is a large, highly\nionized molecule; therefore not absorbed orally. <\/li>
                                          • Heparin does not cross\nblood-brain barrier or placenta (it is the anticoagulant\nof choice during pregnancy<\/strong>). <\/li>
                                          • Heparin released from mast\ncells is degraded by tissue macrophages\u2014it is not a physiologically circulating\nanticoagulant.<\/li>
                                          • Heparin should not be mixed\nwith penicillin, tetracyclines, hydrocortisone or NA in the same syringe or\ninfusion bottle. <\/li>
                                          • Heparinized blood is not\nsuitable for blood counts (alters the shape of RBCs and WBCs), fragility\ntesting <\/li><\/ul>\n\n\n\n

                                            Dosage<\/strong> <\/p>\n\n\n\n

                                            • conventionally given i.v. in a\nbolus dose of 5,000\u201310,000 U, followed by continuous infusion of 750\u20131000 U\/hr.\n<\/li>
                                            • The rate of infusion is\ncontrolled by aPTT<\/strong> measurement which\nis kept at 50\u201380 sec. or 1.5\u20132.5 times\nthe patient\u2019s pretreatment value<\/strong>. <\/li>
                                            • Deep s.c. injection of\n10,000\u201320,000 U every 8\u201312 hrs can be given if i.v. infusion is not possible. <\/li>
                                            • Needle used should be fine and\ntrauma should be minimum to avoid haematoma formation. <\/li><\/ul>\n\n\n\n

                                              ADVERSE\nEFFECTS<\/strong><\/p>\n\n\n\n

                                              • Bleeding due to overdose<\/strong> is the most serious complication<\/strong> of heparin\ntherapy. <\/li>
                                              • Haematuria is generally the\nfirst sign. <\/li>
                                              • Thrombocytopenia<\/strong> is another common\nproblem \u00e0 generally it is mild and transient; occurs due to aggregation of\nplatelets. <\/li>
                                              • Transient and reversible alopecia<\/strong> is infrequent.<\/li>
                                              • Osteoporosis<\/strong> may develop on long-term\nuse of relatively high doses<\/li>
                                              • Hypersensitivity reactions<\/strong> are rare;\nmanifestations are urticaria, rigor, fever and anaphylaxis.<\/li><\/ul>\n\n\n\n

                                                Contraindications\n<\/strong><\/p>\n\n\n\n

                                                • Bleeding disorders, history of heparin\ninduced thrombocytopenia.<\/li>
                                                • Severe hypertension (risk of\ncerebral haemorrhage), threatened abortion, piles, g.i. ulcers (risk of\naggravated bleeding).<\/li>
                                                • Subacute bacterial endocarditis\n(risk of embolism), large malignancies (risk of bleeding in the central\nnecrosed area of the tumour), tuberculosis (risk of hemoptysis).<\/li>
                                                • Ocular and neurosurgery, lumbar\npuncture.<\/li>
                                                • Chronic alcoholics, cirrhosis,\nrenal failure.<\/li>
                                                •  Aspirin and other antiplatelet drugs should be\nused very cautiously during heparin therapy.<\/li><\/ul>\n\n\n\n

                                                  Low molecular\nweight (LMW) heparins<\/strong><\/p>\n\n\n\n

                                                  • Heparin has been fractionated\ninto LMW forms (MW 3000\u20137000) by different techniques.<\/li>
                                                  • LMW heparins have a different\nanticoagulant profile \u00e0 selectively inhibit factor\nXa<\/strong><\/li>
                                                  • act only by inducing conformational change in AT III and not by providing\na scaffolding for interaction of AT III with thrombin<\/strong>. <\/li>
                                                  • As a result, LMW heparins have smaller effect on aPTT<\/strong>\nand whole blood clotting time than unfractionated heparin (UFH). <\/li>
                                                  • Also, they have lesser antiplatelet action<\/strong>\u2014less\ninterference with haemostasis. <\/li>
                                                  • Thrombocytopenia is less<\/strong> frequent.<\/li>
                                                  • lower incidence of haemorrhagic complications <\/strong>compared to UFH <\/li>
                                                  • They are eliminated primarily\nby renal excretion; are not to be used in patients with renal failure. <\/li>
                                                  • more important advantages of\nLMW heparins are pharmacokinetic:<\/li><\/ul>\n\n\n\n

                                                    \u2022 Better subcutaneous bioavailability\n(70\u201390%)<\/strong> compared to UFH (20\u201330%): Variability in response is minimized.<\/p>\n\n\n\n

                                                    \u2022 Longer and more consistent monoexponential t\u00bd:<\/strong> (4\u20136\nhours); making possible once daily s.c. administration.<\/p>\n\n\n\n

                                                    \u2022 Since\naPTT\/clotting times are not prolonged, laboratory\nmonitoring is not needed<\/strong>; dose is calculated on body weight basis.<\/p>\n\n\n\n

                                                    \u2022 Risk of osteoporosis<\/strong> after long term\nuse is much less<\/strong> with LMW heparin\ncompared with UFH.<\/p>\n\n\n\n

                                                    • Most studies have found LMW heparins to be equally efficacious to\nUFH except during cardiopulmonary bypass surgery, in which high dose UFH is\nstill the preferred anticoagulant<\/strong><\/li><\/ul>\n\n\n\n

                                                      Indications\n<\/strong>of LMW heparins are:<\/p>\n\n\n\n

                                                      • Prophylaxis of deep vein\nthrombosis and pulmonary embolism in high-risk patients undergoing surgery;\nstroke or other immobilized patients.<\/li>
                                                      • Treatment of established deep\nvein thrombosis.<\/li>
                                                      • Unstable angina and MI<\/li>
                                                      • To maintain patency of cannulae\nand shunts in dialysis patients.<\/li><\/ul>\n\n\n\n

                                                        LMW heparins \u00e0 Enoxaparin, Reviparin, Nadroparin, Dalteparin, Parnaparin, Ardeparin,\n<\/p>\n\n\n\n

                                                        Fondaparinux:  <\/strong><\/p>\n\n\n\n

                                                        • produced synthetically <\/li>
                                                        • bioavailability of fondaparinux\ninjected s.c. is 100% and it is longer acting (t\u00bd 17 hours). <\/li>
                                                        • Metabolism is minimal, and it\nis largely excreted unchanged by the kidney. As such, it is not to be used in renal\nfailure patients. <\/li>
                                                        • less likely to cause\nthrombocytopenia compared to even LMW heparins. <\/li>
                                                        • Risk of osteoporosis after\nprolonged use is also minimal. <\/li>
                                                        • Does not require laboratory\nmonitoring of aPTT, and is a longer acting alternative to LMW heparins<\/li><\/ul>\n\n\n\n

                                                          DIRECT THROMBIN INHIBITORS<\/strong><\/p>\n\n\n\n

                                                          • Unlike heparin, these bind directly\nto thrombin and inactivate it without\nthe need to combine with and activate AT III.<\/strong><\/li>
                                                          • Lepirudin<\/strong> \u00e0recombinant\npreparation of hirudin (a polypeptide anticoagulant secreted by salivary glands\nof leech)<\/li>
                                                          • Injected i.v., it is indicated only in patients who are at risk of heparin\ninduced thrombocytopenia<\/strong>. <\/li>
                                                          • On repeated\/prolonged\nadministration, antibodies against the lepirudin-thrombin complex may develop\nresulting in prolonged anticoagulant effect and possibility of anaphylaxis. <\/li>
                                                          • Its action cannot be reversed\nby protamine or any other antidote.<\/li><\/ul>\n\n\n\n
                                                            • Bivalirudin<\/strong> \u00e0\nprepared synthetically which has actions and uses similar to lepirudin. <\/li>
                                                            • However, its action is slowly\nreversible <\/li><\/ul>\n\n\n\n
                                                              • Argatroban<\/strong> \u00e0 produces a rapid and short-lasting antithrombin action. Administered by i.v. infusion, it can be used in place of lepirudin for short-term indications in patients with heparin-induced thrombocytopenia.<\/li><\/ul>\n\n\n\n

                                                                HEPARIN ANTAGONIST<\/strong><\/p>\n\n\n\n

                                                                Protamine sulfate<\/strong> <\/p>\n\n\n\n

                                                                • obtained from the sperm of\ncertain fish.<\/li>
                                                                • Given i.v. it neutralises\nheparin weight for weight, i.e. 1 mg is\nneeded for every 100 U of heparin.<\/strong> <\/li>
                                                                • However, it is needed\ninfrequently because the action of heparin disappears by itself in a few hours,\nand whole blood transfusion is needed to replenish the loss when bleeding\noccurs. <\/li>
                                                                • Protamine does not neutralize fondaparinux, and it only partially reverses the anticoagulant\neffect of LMW heparins.<\/strong><\/li>
                                                                • Being basic in nature it can\nrelease histamine in the body. Hypersensitivity reactions have occurred. Rapid\ni.v. injection causes flushing and breathing difficulty.<\/li><\/ul>\n\n\n\n

                                                                  ORAL ANTICOAGULANTS<\/strong><\/p>\n\n\n\n

                                                                  Action and mechanism<\/strong><\/p>\n\n\n\n

                                                                  • Warfarin and its congeners act\nas anticoagulants only in vivo, not in vitro. <\/li>
                                                                  • This is so because they act indirectly by interfering with the\nsynthesis of vit K dependent clotting factors in liver<\/strong>.<\/li>
                                                                  • behave as competitive\nantagonists of vit K and lower the plasma levels of functional clotting factors\nin a dose-dependent manner. <\/li>
                                                                  • In fact, they inhibit the enzyme vit K epoxide reductase (VKOR)<\/strong>\nand interfere with regeneration of the active hydroquinone form of vit K <\/li>
                                                                  • This carboxylation is essential\nfor the ability of the clotting factors to bind Ca2+ and to get bound to\nphospholipid surfaces, necessary for the coagulation sequence to proceed.<\/li>
                                                                  • Factor VII has the shortest\nplasma t\u00bd (6 hr), its level falls first when warfarin is given, followed by\nfactor IX (t\u00bd 24 hr), factor X (t\u00bd 40 hr) and prothrombin (t\u00bd 60 hr). <\/li>
                                                                  • Anticoagulant effect develops\ngradually over the 1\u20133 days as the levels of the clotting factors already\npresent in plasma decline progressively. <\/li>
                                                                  • Thus, there is always a delay\nbetween administration of these drugs and the anticoagulant effect. <\/li>
                                                                  • Therapeutic effect<\/strong> occurs when synthesis\nof clotting factors is reduced by\n40\u201350%.<\/strong><\/li><\/ul>\n\n\n\n

                                                                    Racemic\nWarfarin sod.<\/strong> <\/p>\n\n\n\n

                                                                    • most popular oral\nanticoagulant. <\/li>
                                                                    • The commercial preparation of\nwarfarin is a mixture of R (dextrorotatory) and S (levorotatory) enantiomers. <\/li>
                                                                    • crosses placenta and is\nsecreted in milk; however, quantity of active form is generally insufficient to\naffect the suckling infant.<\/li><\/ul>\n\n\n\n

                                                                      Bishydroxycoumarin (Dicumarol)<\/strong> <\/p>\n\n\n\n

                                                                      Acenocoumarol (Nicoumalone<\/strong>)\n<\/p>\n\n\n\n

                                                                      Adverse effects<\/strong> <\/p>\n\n\n\n

                                                                      • Bleeding<\/strong> \u00e0 extension of the desired pharmacological action \u00e0 causing ecchymosis, epistaxis, hematuria, bleeding in the g.i.t. Intracranial or other internal haemorrhages<\/li>
                                                                      • Cutaneous necrosis is a rare complication that can occur with any oral anticoagulant. <\/li>
                                                                      • Bleeding is more likely if therapy is not properly monitored, or when INR exceeds 4, or interacting \u00a0drugs\/contraindications are present.<\/li>
                                                                      • Treatment:<\/strong> \u00e0 Withhold the anticoagulant.<\/li>
                                                                      • Give fresh blood transfusion \u00e0 supplies clotting factors <\/li>
                                                                      • Alternatively fresh frozen plasma may be used as a source of clotting factors<\/li>
                                                                      • vit K1<\/strong> \u00e0 specific antidote, but it takes 6\u201324 hours for the clotting factors to be resynthesized and<\/li>
                                                                      • Phenindione produces serious toxicity; should not be used.<\/li>
                                                                      • Dose regulation \u00e0 A standardized system called the International Normalized Ratio (INR) based on the use of human brain thromboplastin (Tp) has been developed by WHO and adopted in all countries.<\/li><\/ul>\n\n\n\n
                                                                        \"\"<\/figure><\/div>\n\n\n\n

                                                                        Factors enhancing effect of oral anticoagulants are:<\/strong><\/p>\n\n\n\n

                                                                        \u2022 Debility, malnutrition, malabsorption and prolonged\nantibiotic therapy<\/strong>: the supply of vit K to liver is reduced in these\nconditions.<\/p>\n\n\n\n

                                                                        \u2022 Liver disease, chronic alcoholism:<\/strong> synthesis of clotting factors may be deficient.<\/p>\n\n\n\n

                                                                        \u2022 Hyperthyroidism:<\/strong> the\nclotting factors are degraded faster.<\/p>\n\n\n\n

                                                                        \u2022 Newborns:<\/strong> have low\nlevels of vit K and clotting factors <\/p>\n\n\n\n

                                                                        Factors decreasing effect of oral anticoagulants are:<\/strong><\/p>\n\n\n\n

                                                                        \u2022 Pregnancy:<\/strong> plasma level\nof clotting factors is higher.<\/p>\n\n\n\n

                                                                        \u2022 Nephrotic syndrome:<\/strong> drug\nbound to plasma protein is lost in urine. <\/p>\n\n\n\n

                                                                        \u2022 Genetic warfarin resistance:<\/strong> the affinity of warfarin (as well as of vit K epoxide) to bind to\nthe reductase (VKOR) enzyme, which generates the active vit K hydroquinone, is\nlow.<\/p>\n\n\n\n

                                                                        Contraindications<\/strong> \u00e0 All contraindications to heparin <\/p>\n\n\n\n

                                                                        Warfarin given in\nearly pregnancy increases birth defects, especially skeletal abnormalities. It\ncan produce foetal warfarin syndrome\u2014hypoplasia of nose, eye socket, hand bones,\nand growth retardation. Given later in pregnancy, it can cause CNS defects,\nfoetal haemorrhage, foetal death and accentuates neonatal hypoprothrombinemia.<\/p>\n\n\n\n

                                                                        Drug interactions<\/strong> <\/p>\n\n\n\n

                                                                        A. Enhanced anticoagulant action<\/strong><\/p>\n\n\n\n

                                                                        1. Broad-spectrum antibiotics:\ninhibit gut flora and reduce vit K production.<\/p>\n\n\n\n

                                                                        2. Newer\ncephalosporins (ceftriaxone, cefoperazone) cause hypoprothrombinaemia by the same\nmechanism as warfarin \u2014additive action.<\/p>\n\n\n\n

                                                                        3. Aspirin:\ninhibits platelet aggregation and causes g.i. bleeding\u2014this may be hazardous in\nanticoagulated patients. <\/p>\n\n\n\n

                                                                        4. Long acting\nsulfonamides, indomethacin, phenytoin and probenecid: displace warfarin from\nplasma protein binding.<\/p>\n\n\n\n

                                                                        5.\nChloramphenicol, erythromycin, celecoxib, cimetidine, allopurinol, amiodarone\nand metronidazole: inhibit warfarin metabolism.<\/p>\n\n\n\n

                                                                        6. Tolbutamide and\nphenytoin: inhibit warfarin metabolism and vice versa.<\/p>\n\n\n\n

                                                                        7. Liquid paraffin\n(habitual use): reduces vit K absorption.<\/p>\n\n\n\n

                                                                        B. Reduced anticoagulant action<\/strong><\/p>\n\n\n\n

                                                                        1. Barbiturates\n(but not benzodiazepines), carbamazepine, rifampin and griseofulvin induce the\nmetabolism of oral anticoagulants.<\/p>\n\n\n\n

                                                                        2. Oral\ncontraceptives: increase blood levels of clotting factors.<\/p>\n\n\n\n

                                                                        DIRECT FACTOR Xa INHIBITORS<\/strong><\/p>\n\n\n\n

                                                                        • directly bind to and inactivate\nfactor Xa, instead of inhibiting its synthesis. <\/li>
                                                                        • They, therefore, act rapidly without a lag time (as in case\nof warfarin, etc.),<\/strong> and have short-lasting action.<\/li><\/ul>\n\n\n\n

                                                                          Rivaroxaban<\/strong><\/p>\n\n\n\n

                                                                          • orally active direct inhibitor\nof activated factor Xa<\/li>
                                                                          • advantage is that it requires\nno laboratory monitoring of PT or aPTT, and <\/li>
                                                                          • recommended in a fixed dose of\n10 mg once daily starting 6\u201310 hours after surgery for prophylaxis of venous\nthromboembolism following total knee\/hip replacement. <\/li>
                                                                          • Rivaroxaban has been found\nequally effective as warfarin for preventing stroke in patients with atrial\nfibrillation.<\/li><\/ul>\n\n\n\n

                                                                            ORAL\nDIRECT THROMBIN INHIBITOR<\/strong><\/p>\n\n\n\n

                                                                            Dabigatran\netexilate<\/strong> <\/p>\n\n\n\n

                                                                            • prodrug \u00e0 rapidly hydrolysed to dabigatran, <\/li>
                                                                            • direct thrombin inhibitor <\/li>
                                                                            • no laboratory monitoring is required. <\/li>
                                                                            • trial dabigatran etexilate 150 mg twice daily has yielded superior results to warfarin for prevention of embolism and stroke in patients of atrial fibrillation<\/li><\/ul>\n\n\n\n
                                                                              \"\"<\/figure>\n\n\n\n

                                                                              USES OF ANTICOAGULANTS<\/strong><\/p>\n\n\n\n

                                                                              • to prevent thrombus extension\nand embolic complications by reducing the rate of fibrin formation. <\/li>
                                                                              • do not dissolve already formed clot, but prevent recurrences<\/strong>. <\/li>
                                                                              • Heparin is utilized for rapid\nand shortlived action, while oral anticoagulants are suitable for maintenance\ntherapy.<\/li>
                                                                              • Generally, the two are started\ntogether; heparin is discontinued after 4\u20137 days when warfarin has taken\neffect.<\/li><\/ul>\n\n\n\n

                                                                                Deep\nvein thrombosis (DVT) and pulmonary embolism (PE)<\/strong> <\/p>\n\n\n\n

                                                                                • Because venous thrombi are\nmainly fibrin thrombi, anticoagulants are expected to be highly effective. <\/li>
                                                                                • Prophylaxis is recommended for all\nhigh risk patients including bedridden, elderly, postoperative, postpartum,\npoststroke and leg fracture patients. <\/li>
                                                                                • Three months anticoagulant\ntherapy (continued further if risk factor persists) has been recommended by American\nCollege of Chest Physicians <\/li>
                                                                                • It is based on the premise that\ninhibition of small amount of activated factor X prevents further amplification\nof active products\u2014particularly thrombin.<\/li>
                                                                                • LMW heparin\/fondaparinux have\nnow practically replaced UFH, except in case of major surgery and in high risk\ncases, because action of UFH can be terminated rapidly.<\/li><\/ul>\n\n\n\n

                                                                                  Myocardial\ninfarction (MI)<\/strong> <\/p>\n\n\n\n

                                                                                  • Arterial thrombi are mainly\nplatelet thrombi; anticoagulants are of questionable value. Their use in acute\nMI has declined. <\/li>
                                                                                  • They do not alter immediate\nmortality of MI.<\/li>
                                                                                  • They may benefit by preventing\nmural thrombi at the site of infarction and venous thrombi in leg veins. Thus,\nanticoagulants may be given for a short period till patient becomes ambulatory.\n<\/li>
                                                                                  • For secondary prophylaxis\nagainst a subsequent attack\u2014 anticoagulants are inferior to antiplatelet drugs.<\/li><\/ul>\n\n\n\n

                                                                                    Unstable\nangina <\/strong><\/p>\n\n\n\n

                                                                                    • Short-term use of heparin has\nreduced the occurrence of MI in unstable angina patients; aspirin is equally\neffective.<\/li>
                                                                                    • Current recommendation is to\nuse aspirin + heparin\/LMW heparin followed by warfarin.<\/li><\/ul>\n\n\n\n

                                                                                      Rheumatic\nheart disease; Atrial fibrillation (AF<\/strong>) <\/p>\n\n\n\n

                                                                                      • All atrial fibrillation\npatients should be protected against thromboembolism from fibrillating atria\nand the resulting stroke. <\/li>
                                                                                      • For this purpose, the effective\noptions are warfarin\/low dose heparin\/low dose aspirin.<\/li>
                                                                                      • Current guideline is to give warfarin\nto a target INR of 2\u20133 in AF patients with high risk for stroke (elderly, heart\nfailure, etc.), and to reserve aspirin for low risk patients or for those\nunable to take warfarin. <\/li>
                                                                                      • Anticoagulants are given for\n3\u20134 weeks before and after attempting conversion of AF to sinus rhythm. <\/li><\/ul>\n\n\n\n

                                                                                        Cerebrovascular\ndisease<\/strong> <\/p>\n\n\n\n

                                                                                        • Anticoagulants are of little\nvalue in cerebral thrombosis. <\/li>
                                                                                        • They have been used with the\naim of preventing clot propagation, but all the trials conducted, including International\nStroke Trial (IST), have failed to demonstrate significant benefit. <\/li>
                                                                                        • Oral anticoagulants may be\nbeneficial in transient ischaemic attacks (TIAs), but antiplatelet drugs are simpler\nto use and probably better.<\/li><\/ul>\n\n\n\n
                                                                                          • Vascular surgery, prosthetic heart valves, retinal vessel\nthrombosis, extracorporeal circulation, haemodialysis<\/strong> <\/li>
                                                                                          • Anticoagulants are indicated\nalong with antiplatelet drugs for prevention of thromboembolism.<\/li><\/ul>\n\n\n\n

                                                                                            Defibrination\nsyndrome or \u2018disseminated intravascular coagulation\u2019<\/strong> <\/p>\n\n\n\n

                                                                                            • occurs in abruptio placentae\nand other obstetric conditions, certain malignancies and infections. <\/li>
                                                                                            • The coagulation factors get\nconsumed for the formation of intravascular microclots and blood is incoagulable.\n<\/li>
                                                                                            • Heparin paradoxically checks bleeding in such patients by preserving\nthe clotting factors.<\/strong><\/li>
                                                                                            • However, in some cases heparin\nmay aggravate bleeding.<\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"

                                                                                              Drugs Affecting Coagulation VITAMIN K fat-soluble dietary principle required for the synthesis of clotting factors. Vit K3 \u00e0 synthetic Dietary sources are\u2014green leafy vegetables, such as cabbage, spinach; and liver, cheese, etc. Daily requirement \u00e0 50\u2013100 \u03bcg\/day. Action \u00e0 acts as a cofactor at a late stage in the synthesis by liver of coagulation proteins\u2014[…]\n","protected":false},"author":3,"featured_media":142,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[11],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/138"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=138"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/138\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media\/142"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=138"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=138"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=138"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}