3-Coagulation Disorders by Minwoldu

75 %
25 %
Information about 3-Coagulation Disorders by Minwoldu

Published on February 27, 2014

Author: minwoldu

Source: authorstream.com

PowerPoint Presentation: By Minyahil A Woldu B.Pharm , MSc, Clinical Pharmacy Presentation Outline : Presentation Outline Introduction : Introduction Coagulation disorders result from: decreased number of platelets, decreased function of platelets, coagulation factor deficiency, or enhanced fibrinolytic activity. The coagulation cascade consisted of intrinsic, extrinsic, and common pathways. The extrinsic pathway is initiated by exposure of tissue during trauma. The intrinsic pathway is initiated when circulating factor XII comes in contact with the subendothelial membrane . They converge at the activation of factor X, forming the common pathway. Regulation of Hemostasis: Regulation of Hemostasis Coagulation Factors Can be divided into three groups on the basis of biochemical properties Vit . K–dependent factors (II, VII, IX, and X) Contact activation factors (XI, XII, prekallikrein , high-molecular-weight kininogen ) Thrombin-sensitive factors (V, VIII, XIII, and fibrinogen) The Coagulation Cascade: The Coagulation Cascade The coagulation process that leads to  haemostasis  involves a complex set of protease reactions involving approximately 30 different proteins . These reactions convert fibrinogen , a soluble protein , to insoluble strands of  fibrin , which, together with platelets , form a stable thrombus . Several  coagulation cascade  models have been proposed, including the intrinsic and extrinsic pathway model and the more recent cell-based model. The intrinsic and extrinsic pathway model: The intrinsic and extrinsic pathway model The intrinsic and extrinsic pathway model divides the initiation of coagulation into two distinct parts. The extrinsic pathway is thought to be responsible for the initial generation of activated Factor X (Factor Xa ), whereas the intrinsic pathway leads to amplification of  Factor Xa  generation.  Factor Xa plays a central role in the  coagulation cascade  because it occupies a point where the intrinsic and extrinsic pathways converge. PowerPoint Presentation: Fig. Cascade model of coagulation demonstrate activation via the intrinsic and extrinsic pathway: traditional Fig. Cell based model of hemostasis : modern The cell-based model: The cell-based model The cell-based model better explains the mechanism of  haemostasis  in vivo and includes the important interactions between cells directly involved in  haemostasis  (i.e.  tissue factor  [TF]-bearing cells and platelets) and  coagulation factors . This model more accurately represents the interaction between cellular activity and coagulation proteins that leads to thrombus formation and  haemostasis . The cell-based model identifies the membranes of TF-bearing cells and platelets as the sites where activation of specific  coagulation factors  occurs. This model describes a three-phase process: Initiation Amplification Fibrin formation The cell-based model…: The cell-based model… Initiation occurs after  vascular injury , when TF-bearing cells bind to and activate Factor VII. This leads to production of a small amount of  thrombin , which then activates platelets and co-factors during the amplification phase. The  prothrombinase complex  (comprising  Factor Xa  and co-factors bound to activated platelets) is responsible for the burst of  thrombin  production leading to the third phase of  fibrin formation. The cell-based model…: The cell-based model… The final step of the series of protease reactions leading to thrombus formation involves the conversion of the soluble protein fibrinogen to insoluble  fibrin  strands by  thrombin .  Thrombin  also activates Factor XIII, which stabilizes the thrombus by cross-linking  fibrin . The resulting  fibrin  mesh traps and holds cellular components of the thrombus (platelets and/or red blood cells). The central role of Factor Xa in thrombus formation: The central role of Factor Xa in thrombus formation Factor Xa  plays a central role in the coagulation process that leads to  haemostasis  in both the older, extrinsic/intrinsic model as well as the more recently proposed cell-based model. Factor Xa , with activated Factor V (Factor Va ) as a co-factor, propagates coagulation by converting prothrombin  (Factor II) to  thrombin  (Factor IIa ) Factor Xa is a crucial site of amplification in the coagulation process One molecule of  Factor Xa  catalyses the formation of approximately 1000  thrombin  molecules Development of medications that inhibit  Factor Xa  is, therefore, an attractive area of pharmaceutical research. Fibrinolysis: restoring blood flow: Fibrinolysis : restoring blood flow Fibrinolysis is the process that dissolves  fibrin . By dissolving  fibrin , fibrinolysis leads to dissolution of the thrombus. Plasminogen is the precursor of  plasmin , which breaks up  fibrin  in the thrombus. During initial thrombus formation, plasminogen activators are inhibited. Fibrinolysis: restoring blood flow…: Fibrinolysis : restoring blood flow… Endothelial cells begin to secrete tissue plasminogen activators to start dissolving the thrombus as the structural integrity of the blood vessel wall is restored. Fibrinolysis must occur for normal blood flow to be re­-established. Medications that convert plasminogen to  plasmin  are used to treat acute, life-threatening thrombotic disorders, such as  myocardial infarction  (MI) and  ischaemic stroke . Beyond cells and coagulation factors: the role of microparticles and P-selectin…: Beyond cells and coagulation factors: the role of microparticles and P- selectin … Ongoing research has elucidated other components of the coagulation process. These components include microparticles and P- selectin . Microparticles are irregularly shaped vesicles that are smaller than platelets (i.e. less than 1 μm in diameter). These vesicles arise from the plasma membrane of blood-borne cells during cell activation, programmed cell death or exposure to shear stress. P- selectin is a cell adhesion molecule found on the inner surface of blood vessels and on activated platelets. Beyond cells and coagulation factors: the role of microparticles and P-selectin…: Beyond cells and coagulation factors: the role of microparticles and P- selectin … Both microparticles and P- selectin promote thrombosis during the amplification phase of coagulation. During thrombus formation, platelets accumulate at the site of  vascular injury , become activated and express P- selectin . P- selectin , in turn, binds to TF-bearing microparticles . One of the effects of this binding is to cause those microparticles to bind to activated platelets via platelet-bound P- selectin . TF from the microparticles then binds to and activates Factor VII. TF-bearing microparticles are also implicated in thrombosis associated with diabetes, metabolic syndrome, specific malignancies (e.g. cancer of the colon, pancreas, breast, ovary and lung) and inflammatory and haematological disorders. Imbalances in the coagulation system : Imbalances in the coagulation system ‘ Thrombophilia ’ is an inherited or acquired imbalance in the coagulation system that leads to an increased risk of thrombosis. Thrombophilia may be expected in: Patients with recurrent  VTE  or a life-threatening VTE Patients with  VTE  <45 years of age Patients with  VTE  and a family history of VTE Patients who develop  VTE  with no apparent exposing risk factors Women who experience multiple spontaneous abortions or stillbirths How Thrombi Develop: How Thrombi Develop A thrombus can block the flow of blood through a vein or artery. If it detaches from the vessel wall and lodges in the lungs or other vital organs, it can become a life-threatening embolus.  A pathological thrombus forms when there is an imbalance in the blood coagulation system.  Haemostasis  is necessary for survival, but the pathological formation of a thrombus, poses significant health risks. The coagulation system depends on a delicate balance between: Natural coagulant and anticoagulant factors The coagulation and fibrinolytic system How Thrombi Develop…: How Thrombi Develop… An imbalance in these systems can result in pathological coagulation. The resulting thrombus can potentially obstruct blood flow, leading to a number of serious health conditions including heart attacks and cardioembolic stroke in patients with AF, and  VTE . VTE  can manifest as DVT and/or PE – two distinct but related aspects of the same disease. Virchow's triad: Virchow's triad Over 150 years ago, the German pathologist Rudolph Virchow postulated that thrombus formation and propagation resulted from abnormalities in three areas: Blood flow The vessel wall Blood components Virchow's triad…: Virchow's triad… These three factors are known as Virchow’s triad.  The features of this triad have now been further refined: Blood flow – abnormalities of haemorheology and turbulence at vessel bifurcations and stenotic regions Vessel walls – abnormalities in the endothelium, such as atherosclerosis and associated vascular inflammation Blood components – abnormalities in coagulation and fibrinolytic pathways and in  platelet  function Virchow's triad…: Virchow's triad… Advances in laboratory techniques now enable clinicians to quantify some of these thrombosis-related factors that, when abnormal, confer a ‘ prothrombotic ’ or ‘ hypercoagulable ’ state. This state is associated with an increased risk of  VTE  and other cardiovascular diseases – including coronary artery disease  and heart failure – and of stroke in patients with AF. Virchow's triad…: Virchow's triad… Virchow's triad…: Virchow's triad… Two different types of thrombus can form: Arterial thrombus (white thrombus) Venous thrombus (red thrombus) Arterial and venous thrombi differ in composition and appearance. Arterial thrombi are typically composed mainly of  platelet  aggregates, giving the appearance of ‘white thrombi’. Venous thrombi largely consist of  fibrin  and red blood cells so are known as ‘red thrombi’. Venous thrombi: Venous thrombi Formation of a thrombus within a vein is known as a  venous thrombosis . If the thrombus breaks loose and travels through the blood system, it is known as an embolus. Venous thrombi: Feature enmeshed erythrocytes Tend to fragment, creating an embolus Manifest as deep vein thrombosis (DVT) and pulmonary embolism (PE) Venous thromboembolism The most common type of  VTE  is DVT, which occurs predominantly in the large veins in the leg. Venous thrombi…: Venous thrombi… When part or all of a thrombus breaks away from the blood vessel wall, this thrombus is carried in the direction of blood flow towards the lung and can block one of the arteries in the lung (pulmonary embolus). Patients with DVT are at risk of PE which can potentially be life-threatening. Risk factors: Risk factors VTE   is associated with cancer, trauma and surgery. Idiopathic cases occur where a patient has no clear exposing risk factor (i.e. no triggering event). Important risk factors for  VTE  include: Pre-disposing risk factors: Increasing age (especially >60 years) Pregnancy and postpartum Obesity (body mass index >30 kg/m2) Immobility (including lower extremity paralysis) Personal/family history of VTE Dehydration Use of oestrogen -containing oral contraceptives Use of hormone replacement therapy Complications : Complications VTE  also can lead to serious long-term complications, including: Post-thrombotic syndrome (PTS) Chronic thromboembolic pulmonary  hypertension  (CTPH) PTS is the most common complication of DVT and typically causes chronic pain and swelling in the affected leg, and in severe cases can result in venous ulcers.  After symptomatic DVT, 20–50% of patients develop PTS.  CTPH is an important long-term complication of PE.  CTPH causes the right side of the heart to work harder than normal owing to abnormally high blood pressure in the arteries of the lungs. This can lead to heart failure and other serious consequences. Atrial fibrillation-related thrombi: Atrial fibrillation-related thrombi Atrial fibrillation (AF), a form of cardiac  arrhythmia , is also associated with the formation of ‘venous-type’ thrombi. AF involves a lack of an organized atrial contraction. By reducing the movement of blood, AF creates stagnant blood, which encourages the formation of thrombi. These thrombi can break free and embolize to block a cerebral artery, causing ischaemic injury. Consequently, AF is associated with a major risk of stroke. Despite forming in the left atrium or left atrial appendage of the heart, AF-related thrombi are thought to be more of a 'venous-type thrombus’. The pathogenesis is similar to that in the venous system and leads to fibrin-rich thrombi thereby fulfilling Virchow’s triad for thrombogenesis .  Risk factors: Risk factors The degree of stroke risk varies among patients with AF. Risk factors include: Heart failure History of hypertension Age Diabetes Prior history of stroke or TIA Several scoring systems are available to help clinicians estimate the stroke risk in AF. One popular, validated risk assessment tool is the ‘CHADS 2 ’. This system assigns single points for  C ongestive H eart failure,  hypertension ,  A ge over 75 and  D iabetes, and two points for  S troke or TIA history. A total score over 2 is considered high risk. More recently, the CHA 2 DS 2 -VASc scoring system has been proposed as an improvement on the CHADS 2  score for identification of ‘truly low risk’  patients with AF . Treatment of deep vein thrombosis and pulmonary embolism: Treatment of deep vein thrombosis and pulmonary embolism The most effective and economical approach to decreasing the burden of  VTE  is to prevent the development of DVT and PE in patients at high risk. Traditionally, initial treatment of DVT and PE begins with a  parenteral  anticoagulant, transitioning to longer-term  vitamin K  antagonist (VKA) therapy, often with  warfarin . Because VKAs have a delayed onset of action, the transition requires close monitoring of the international normalized ratio (INR), which should be in the therapeutic range (INR 2.0–3.0) before discontinuation of the  parenteral  agent. Treatment of deep vein thrombosis and pulmonary embolism…: Treatment of deep vein thrombosis and pulmonary embolism… The direct  Factor Xa  inhibitor  rivaroxaban  is the first novel oral anticoagulant approved in the EU for the treatment of DVT, PE and prevention of recurrent DVT and PE in adult patients. Rivaroxaban  can be used for the initial and longer-term treatment of DVT, PE and recurrent  VTE . This single-drug approach removes the need for overlapping administration of  heparin  and a  VKA , which can be complex owing to the requirement for  coagulation monitoring  and dose-adjustment of the  VKA . EU marketing approval for  rivaroxaban  was received following a review of data from the randomized, controlled phase III EINSTEIN clinical trial programme . Approved anticoagulants for treatment of DVT and PE: Approved anticoagulants for treatment of DVT and PE Drug Target Dose/regimen UFH Factor Xa and thrombin (indirect via AT) Weight-adjusted s.c. bolus dose followed by i.v. infusion; overlapping with a VKA for at least 5 days and until INR >2.0 for 2 consecutive days LMWH Factor Xa and thrombin (indirect via AT) Weight-adjusted s.c. regimen; overlapping with a VKA for at least 5 days and until INR >2.0 for 2 consecutive days Fondaparinux Factor Xa (indirect via AT) Weight-adjusted s.c . regimen (standard dose 7.5 mg) od ; overlapping with a VKA for at least 5 days and until INR >2.0 for 2 consecutive days VKA Vitamin K (inhibits synthesis of Factors II, VII, IX and X) Oral, commenced in parallel with initial parenteral agent, which is then discontinued once INR is in the range 2.0–3.0 For warfarin , typical induction 5 mg (for older, frailer patients) or 10 mg (for younger, healthier patients) od for 2 days, followed by adjusted-doses to maintain a target INR of 2.5 (range, 2.0–3.0) Treatment continues for 3–12 months depending on risk factors, or longer if risk factors for recurrence persist Rivaroxaban (Treatment of DVT and prevention of recurrent VTE only Factor Xa (direct) Oral, 15 mg bid for 3 weeks then 20 mg od Oral 15 mg bid for 3 weeks then 15 mg od for patients with moderate ( CrCl 30–49 ml/min) or severe ( CrCl 15–29 ml/min) renal impairment.  A reduction of the dose from 20 mg od to 15 mg od should be considered if the patient’s assessed risk of bleeding outweighs the risk of recurrent DVT and PE AT, antithrombin ; bid, twice daily; CI, confidence interval; DVT, deep vein thrombosis; INR, international normalized ratio; LMWH, low molecular weight heparin; od , once daily; PE, pulmonary embolism; s.c ., subcutaneous; UFH, unfractionated heparin; VKA, vitamin K antagonist. Comparison of the Chemical and Pharmacokinetic Properties of Antithrombotic Drugs Used for Venous Thrombosis: Comparison of the Chemical and Pharmacokinetic Properties of Antithrombotic Drugs Used for Venous Thrombosis Simple Laboratory Tests: Simple Laboratory Tests The most common screening tests include: Activated Partial Thromboplastin Time ( aPTT ) reflects the time required for a fibrin clot to form after a partial thromboplastin , calcium , and an activating agent are added to the patient’s plasma. widely used for monitoring heparin therapy . Prothrombin Time (PT) :  P rothrombin T ime (PT) PT assesses the activity of the vitamin K–dependent proteins (factors II, VII, IX, and X, and proteins C and S) and the common pathway proteins (factors V and X) reflects the time required for fibrin strands to appear after the addition of tissue thromboplastin to the patient’s plasma. provides evidence about the current synthetic capacity of the liver, the adequacy of vitamin K absorption, and the inhibition of clotting factor synthesis by warfarin . Prothrombin Time (PT) …:  Prothrombin Time (PT) … The prothrombin time (PT), also known as the protime and one step Quick test, has been used for decades to monitor the anticoag - ulation effects of warfarin . The PT measures the biologic activityof factors II, VII, and X activity and correlates well to warfarin’s anticoagulation effect. Thrombin Time :  Thrombin T ime Measures the conversion of fibrinogen to fibrin. More clearly, it measures the time required for the formation and appearance of the fibrin clot after thrombin is added to plasma. It can be used to monitor the effect of systemic fibrinolytic therapy and can be modified for monitoring heparin therapy . Platelet count, and bleeding time :  Platelet count, and bleeding time reflects the time to cessation of bleeding following a standardized skin cut. A prolonged bleeding time can be caused by incorrect performance of the test, thrombocytopenia, platelet dysfunction, von Willebrand disease, use of antiplatelet drugs (i.e., aspirin), renal failure (uremia), fibrinogen disorders, abnormal blood vessels, or collagen disorders. PT, aPTT, and thrombin time: PT, aPTT , and thrombin time PT, aPTT , and thrombin time are useful in screening for a deficiency of liver-dependent factors. PT is sensitive to deficiencies in the vitamin K–dependent factors. aPTT helps to determine deficiencies in factor IX and other factors. Thrombin time can help to detect hypofibrinogenemia , dysfibrinogenemia , and the presence of fibrin degradation products (FDPs) that interfere with fibrin polymerization. Defects in polymerization may occur before severe hypofibrinogenemia and may be an indication of the degree of liver dysfunction. The level of D- dimer should be normal unless DIC is present. Coagulation Disorders: Coagulation Disorders Coagulation disorders result from a decreased number of platelets, decreased function of platelets, coagulation factor deficiency, or enhanced fibrinolytic activity. Coagulation Disorders: Coagulation Disorders Inherited Coagulation Disorders Hemophilia Von Willebrand Disease Other Clotting Factor Deficiencies Acquired Coagulation Disorders DIC Vitamin K Deficiency Coagulopathy and Liver Disease HEMOPHILIA :  HEMOPHILIA Coagulation disorders that result from defects in the genes encoding for plasma coagulation proteins. Hemophilia A (classic hemophilia)- Defi . factor VIII Hemophilia B (Christmas disease)- Defi . of factor IX. The incidences of hemophilia A and B are estimated at 1 in 5000 and 1 in 30,000 male births, respectively. INHERITED COAGULATION DISORDERS HEMOPHILIA:  HEMOPHILIA Pathophysiology VIII or IX defi . resulting in inadequate thrombin generation and an impaired intrinsic-pathway coagulation cascade Hemophilias are recessive X-linked diseases, that is, the defective gene is located on the X chromosome. The disease usually affects only males ; females are carriers Hemophilia is not a result of a single genetic mutation PowerPoint Presentation: Ecchymosis Hemarthroses PowerPoint Presentation: Joint destruction LONG-TERM COMPLICATIONS OF HEMOPHILIA Nerve damage Laboratory and Clinical Manifestations of Hemophilia: Laboratory and Clinical Manifestations of Hemophilia Treatment: Treatment Desired Outcomes The short-term goals: Decrease the number of bleeding episodes per year Normalize or improve clotting factor concentrate levels The long-term goals: Maintain clinical joint function Normalize orthopedic joint score Normalize radiologic joint score Maintain quality-of-life measurements General Approach to Treatment: General Approach to Treatment IV factor replacement with recombinant or plasma-derived products to t/t or prevent bleeding is the primary treatment hemophilia. The rationale for primary prophylaxis is that individuals with factor levels of greater than 0.02 unit/ mL (2 IU/ dL ) rarely suffer from spontaneous bleeds and arthropathy . Nonpharmacologic Therapy: Nonpharmacologic Therapy Surgery Synovectomy removes inflamed tissue and joint blood vessels Orthotics supportive measure before or after surgery Pharmacologic Therapy: Pharmacologic Therapy Hemophilia A Desmopressin acetate (DDAVP) for mild to moderate disease and a minor bleeding episode. DDAVP causes release of von Willebrand factor ( vWF ) and factor VIII from endogenous storage sites. Increases plasma factor VIII levels by three- to five fold within 30 minutes. 0.3 mcg/kg intravenously or subcutaneously or 300 mcg intranasally every 12 hrs is the recommended dose. Pharmacologic Therapy…: Pharmacologic Therapy… Factor VIII Replacement For severe hemophilia may receive 1 ry or 2 ry prophylaxis All hemophiliacs with a major bleed require factor VIII replacement The therapy may include recombinant or plasma-derived factor VIII Newer generation plasma-derived coagulation factor concentrates are considerably safer Pharmacologic Therapy: Pharmacologic Therapy Hemophilia B Factor IX Replacement Recombinant or plasma-derived factor IX Recombinant factor IX is often considered the treatment of choice for hemophilia B. Guidelines for choosing the factor-concentrate formulation are similar to hemophilia A Treatment of Pts with Factor VIII or IX Inhibitors: Treatment of Pts with Factor VIII or IX Inhibitors Factor VIII and IX inhibitors are antibodies that develop in 20% and 12% of hemophilia A and hemophilia B pts, respectively, in response to replacement therapy The inhibitors challenges the treatment of bleeding episodes For low-titer inhibitor , administration of high doses of the specific factor For high-titer inhibitor, therapeutic options include Recombinant activated factor VII ( rFVIIa ), prothrombin complex concentrates ( PCCs ), porcine factor VIII, and gene therapy Outcome Evaluation : Outcome Evaluation The main goal of hemophilia treatment is to prevent bleeding episodes and their long-term complications Patients should be evaluated every 6 to 12 months for the following: Musculoskeletal status Number and type of bleeding episodes Use of clotting-factor concentrates to check for the development of inhibitors VON WILLEBRAND DISEASE: VON WILLEBRAND DISEASE Epidemiology and Etiology ( vWD ) is the most common inherited bleeding disorder caused by a deficiency or dysfunction of von vWDf prevalence is estimated at 30 to 100 cases per million Inherited as an autosomal dominant disorder Unlike hemophilia, the bleeding tendency in vWD is less frequent and generally less severe PowerPoint Presentation: equal frequency in male and females vWF is a large multimeric glycoprotein with two main functions in hemostasis : to aid the platelet adhesion to injured blood vessel walls and to carry and stabilize factor VIII in plasma Clinical Presentation and Diagnosis: Clinical Presentation and Diagnosis Treatment: Treatment Desired Outcomes The goal of two mainstay therapeutic options in vWD To stop spontaneous bleeding as necessary To prevent surgical and postpartum bleeding The two systemic approaches stimulates the release of endogenous vWF , or administering products that contain vWF . Pharmacologic Therapy: Pharmacologic Therapy Most patients with type 1 vWD and a minor bleeding Desmopressin dose is the same as factor VIII deficiency t/t Type 3 vWD patients who lack releasable stores of vWF do not respond to DDAVP therapy. Pharmacologic Therapy…: Pharmacologic Therapy… Replacement Therapy with plasma-derived, intermediate- and high-purity factor VIII virus–inactivated factor VIII concentrates containing vWF . This is indicated mainly for ; Type 1 patients unresponsive to desmopressin , patients with types 2 and 3 vWD , and major surgery Ultrahigh-purity plasma-derived products and recombinant factor VIII products contain only negligible amounts of von Willebrand factor Inadequate for t/t of von Willebrand disease Disseminated Intravascular Coagulation (DIC): Disseminated Intravascular Coagulation (DIC) A diffuse response to systemic activation of the coagulation system Is excessive and unregulated generation of thrombin, leading to an aggressive compensatory fibrinolysis Is a Paradoxical clinical “clotting and hemorrhage” Acquired Coagulation Disorders Pathophysiology: Pathophysiology Conditions associated with DIC: Conditions associated with DIC Extrinsic Shock or trauma Infections ( gram positive and gram negative sepsis, aspergillosis ) Obstetric complications ( eclampsia , placenta abruptio , fetal death syndrome) Malignancies: AML, cancers of the lung, colon, breast, prostate) Intrinsic Infectious vasculitis (certain viral infections, rocky mountain spotted fever) Vascular disorders Intravascular hemolysis (hemolytic transfusion reactions) Miscellaneous: snakebite, pancreatitis, liver disease CLINICAL PRESENTATION OF DIC :  CLINICAL PRESENTATION OF DIC Signs and Symptoms ■ Bleeding, thrombosis, or both ■ Petechiae and purpura ■ Peripheral cyanosis ■ Hemorrhagic bullae Purpura Petechiae Diagnosis/Lab Findingsof DIC: Diagnosis/Lab Findingsof DIC Test Platelet count Fibrin degradation product (FDP) Factor assay Prothrombin time (PT) Activated PTT Throbimn time Fibrinogen D- dimer Antithrombin Abnormality Decreased Increased Decreased Prolonged Prolonged Prolonged Decreased Increased Decreased Treatment of DIC: Treatment of DIC Desired Outcomes Replace missing blood components. Interrupt coagulation. Treat underlying disease. Treatment of DIC: Treatment of DIC Pharmacologic Therapy Treat the underlying cause Platelets and Fresh-Frozen Plasma In a bleeding patient, the platelet count should be maintained above 50,000/mm3 platelet concentrates should be given at a dose of 1 unit/10 kg of body weight. PowerPoint Presentation: Fresh-Frozen Plasma ( FFP) is dosed at 10 to 15 mL /kg. Cryoprecipitate (containing factor VIII & fibrinogen) If FFP cannot maintain fibrinogen concentration above 100 mg/ dL (1 g/L) in a symptomatic patient, 1 to 4 units/10 kg of cryoprecipitate may be administered Anticoagulants Anticoagulation with heparin in patients with DIC is controversial Outcome Evaluation : Postinfusion increments (platelets, PT, aPTT , fibrinogen) should be checked within 30 to 60 minutes & every 6 hours Monitor the patient for relief of symptoms and signs of hemorrhage. Outcome Evaluation VITAMIN K DEFICIENCY: VITAMIN K DEFICIENCY Vitamin K is a fat-soluble vitamin cofactor for the activation of factors II, VII, IX, and X in the liver Vitamin K also is necessary for the active forms of proteins C and S, which inhibit factor Va and VIIIa Vitamin K1, phytonadione , is found in green vegetables. Bacteria in the large intestine produce vitamin K2, the menaquinones VITAMIN K DEFICIENCY: VITAMIN K DEFICIENCY Hemorrhagic Disease of the Newborn Almost all neonates are vit . K–deficient at birth as a result of (1) insignificant transplacental vitamin K crossover, (2) lack of colonization of the colon by vit . K– producing bacteria, (3) inadequate dietary vitamin K intake. VKDB refers to bleeding attributable to vitamin K deficiency within first 6 months of life. VITAMIN K DEFICIENCY: VITAMIN K DEFICIENCY It occurs in three general time frames: 1. early ( 0–24 hours) anticonvulsants, rifampin , isoniazid , and warfarin 2. classic (1–7 days) lack of prophylactic vit . K administration 3. late (2–12 weeks): more severe clinically, & has a high incidence In addition to breast-feeding, identified risk factors are cystic fibrosis, hepatitis, and α1- antitrypin deficiency. Symptoms : Symptoms • Dark melena stools • Bleeding from the umbilical stump • Circumcision bleeding • Bloody vomit • Blood-stained urine • Nose bleed • Petecchiae VITAMIN K DEFICIENCY: VITAMIN K DEFICIENCY PT and aPTT are prolonged, but the thrombin time, fibrinogen level, and platelet count are normal infants usually receive 1 mg of phytonadione intramuscularly at birth for prophylaxis. Most infants build up vitamin K1 and K2 stores in the liver during the first month of life. VITAMIN K DEFICIENCY: VITAMIN K DEFICIENCY Malabsorption Patients may become deficient in vitamin K as a result of poor nutrition or malabsorption . Broad-spectrum antibiotics may sterilize the large intestine and prevent vitamin K2 production. TREATMENT Vitamin K Deficiency: TREATMENT Vitamin K Deficiency Phytonadione is used to treat vitamin K deficiency After an oral dose of vitamin K1, blood coagulation factors increase within 6 to 12 hours. parenterally , PT may take 12 to 24 hours to normalize fresh-frozen plasma (FFP) is used to treat life-threatening hemorrhages. Failure of vitamin K1 to correct PT after 48 hours should raise suspicion about the etiology of the coagulation abnormality (e.g., liver disease). Coagulopathy and Liver Disease: Coagulopathy and Liver Disease Bleeding disorders can be associated with acute or chronic liver disease. Clotting factors are decreased in liver failure. PT, aPTT , and thrombin time are useful in screening for a deficiency of liver-dependent factors. PT is sensitive to deficiencies in the vitamin K–dependent factors. aPTT helps to determine deficiencies in factor IX and other factors. TREATMENT Coagulopathy and Liver Disease: TREATMENT Coagulopathy and Liver Disease Factor V is synthesized by hepatic cells but is not dependent on vitamin K. useful in distinguishing vitamin K deficiency from liver disease To ensure that vitamin K deficiency is not contributing to the abnormalities, adults may receive 10 mg of vitamin K for one or more days. TREATMENT Coagulopathy and Liver Disease: TREATMENT Coagulopathy and Liver Disease Fresh-frozen plasma supplies all of the missing coagulation factors, but fluid overload may be a serious problem. THANK YOU: THANK YOU

Add a comment

Related presentations