acquired coagulation abnormalities

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ACQUIRED COAGULATION ABNORMALITIES. ACQUIRED COAGULATION ABNORMALITIES - causes. 1 . Vitamin K deficiency 2. Liver disease Clotting factor inhibitors : circulating anticoagulants complications of anticoagulant therapy 4. Incraesed consumption or loss of the clotting factors : - PowerPoint PPT Presentation

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  • ACQUIRED COAGULATION ABNORMALITIES

  • ACQUIRED COAGULATION ABNORMALITIES - causes

    1. Vitamin K deficiency 2. Liver disease Clotting factor inhibitors:circulating anticoagulants complications of anticoagulant therapy 4. Incraesed consumption or loss of the clotting factors: a) disseminated intravascular coagulation ( DIC) b) fibrinogenolysis (primary fibrinolysis)

  • Coagulation abnormalities of vitamin K deficiency

    vitamin K is essential for the final postribosomal carboxylation of F II, VII, IX, X and the physiologic anticoagulants, protein C and protein S Laboratory features: PT (prothrombin time) and F II, VII, IX, X aPTT (activated partial thromboplastin time) may be prolonged in severe, protracted vitamin K deficiencyLevels of PIVKA-II (Proteins induced in vitamin K absence) are more sensitive than PT

  • Vitamin K deficiency-etiology

    I. Inadequate supply: 1. Dietary deficiency (leafy green vegetables 90-120mcg) 2. Destroying the gut flora by administration of broad-spectrum antibiotics II. Impaired absorption of vitamin K: 1. Biliary obstruction (gallstone, strictures, tumor) 2. Malabsorption of vitamin K(sprue, celiac disease, ulcerative colitis) 3. Drugs (cholestyramine)III. Pharmacologic antagonists of vitamin K (coumarins, warfarin)

  • Abnormalities of hemostasis and coagulation in liver diseases (1)

    I. Decreased synthesis of coagulation factors 1. Fibrinogen, protrombin, clotting F V, VII, IX, X, XI, XII, XIII, prekallikrein, high molecular weight kininogen 2. Antiplasmins, antithrombin, protein C and protein SII. Aberrant biosynthesis 1. Of abnormal fibrinogenu 2. Of abnormal analogues of prothrombin, F VII, IX, X

  • Abnormalities of hemostasis and coagulation in liver diseases (2)

    III. Deficient clearance 1. Of fibrin monomers, fibrinogen degradation products (FDP) 2. Of activated coagulation factors (IXa, Xa, Xia) 3. Of plasminogen acivatorsIV. Accelerated destruction of coagulation factors 1. Intravascular coagulation 2. Localized coagulation (hepatic cell necrosis) 3. Abnormal fibrinolysis V. Thrombocytopenia and platelet dysfunction (splenomegaly)

  • TreatmentVitamin K doses 10mg FFP (invasive procedure)Prothrombin complex concentratesPlatelet transfusionAntifibrynolytic agents (dental extraction)

  • Circulating anticoagulants

    Clotting factor inhibitors are autoantibodies (usually IgG) or alloantibodies (in hemophilia A) that inactivate coagulation factors

    - Laboratory test: prolonged aPTT

  • Circulating anticoagulantsI. Antibodies to factor VIII (prolonged aPTT, normal INR) 1. In hemophilia A 2. Postpartum -several months after parturition in asociation with a first pregnancy 3. Various immunologic disorders (rheumatoid arthritis, SLE, penicillin allergy) 4. Older patients without underlying disease II. Other spontaneous inhibitors (rarely)- against factors: V, IX, XIII, fibrinogen,III. Lupus anticoagulant (in 30% SLE, rheumatoid arthritis, HIV infection, in lymphoproliferative disorders, after drugs hydralazine, quinidine, penicillin)

  • Acquired hemophilia ACommon bleeding sites are soft tissue, skin, and mucous membrane

    Treatment Factor VIII bypassing agents:Recombinant activated factor VIIPlasma-derived factor eight-inhibitor bypassing agent (FEIBA, also called activated prothrombine complex concentrate)

    To eradicate the inhibitor is recommended

  • Disseminated intravascular coagulation

    is an acquired syndrome characterized by systemic intravascular activation of coagulation, leading to fibrin deposition in the microvasculature and small-vessels, contributing to organ dysfunction

    consumption of platelets and coagulation factors lead to thrombocytopenia and impaired coagulation and may result in bleeding complications

    DIC

  • Clinical conditions that may be complicated by DICSepsis/severe infectionTraumaMalignancyAcute leukemiasKasabach-Merritt syndromeVascular abnormalities

    Severe alergic/toxic reactionObstetrical conditionsAmniotic fluid embolismAbruptio placentaeHELLP syndromeSolid tumors

  • ACUTE DIC-CLINICAL PRESENTATION

    symptoms of underlying disease symptom of local thrombosis hemorrhagic diathesis shock

  • Diffuse intravascular coagulation

    Microthrombosis secondary fibrinolysis platelets FDP clotting factors

    Ischemic tissue damage Microangiopathic Bleeding anemia tendency

  • Acute DIC - laboratory features: Increased D-Dimer level FDP level AT level platelet levelBload smear - schistocytes fibrinogen level TT (Thrombin time) aPTT PT (Prothrombin time)

  • Acute DIC diagnosis

    The basis of the diagnosis is the knowledge of the underlying diseasesPatients suffering from acute DIC need urgent therapyDIC should always be taken into consideration if a complex coagulation defect in combination with a underlying disease is observed

  • Diagnostic algorithm for the diagnosis of overt DIC (1)Risk assessment:Does the patient have an underlying disorder known to be associated with overt DIC?If yes, proceed

  • Diagnostic algorithm for the diagnosis of overt DIC (2) - Order global coagulation tests Platelet count (>100=0,
  • CHRONIC (compensated) DIC

    In chronic DIC, the activation of the hemostatic system is minimal since negative feedback mechanisms as well as inhibitors can limit the activation process so that microthrombi do not occur and bleeding episodes are rare phenomena

  • Chronic DIC - etiology

    1. Obstetric complications: eclampsia, the death fetus syndrom2. Vascular disorders: giant hemangiomas (Kasabach Merrit syndrome), Leriche syndrome, Raynaud,s disease3. Carcinomas4. Hematology disorders: myelofibrosis, polycythemia vera, PNH5. Reumathoid disorders: SLE, sclerodermia6. Kidneys disorders: glomerulonephritis, HUS7. Another: vasculitis allergica, diabetes mellitus

  • PRIMARY FIBRINOLYSIS (FIBRINOGENOLYSIS)

    DEFINITION: primary fibrinolysis occurs when plasmin is generated in the absence of DIC

    This has been described in hepatic disorders, prostatic carcinomas, and cases without apparent cause At present, most cases of primary fibrynolysis are iathrogenically induced during thrombolytic therapy

  • Plasminogen

    intrinsic extrinsic exogenous activation activation activationfactor XIa, XIIa, kallikrein tPA, uPA streptokinasekininogen or APSAC

    Plasmin

    Fibrinogen Fibrin

    FDP FDP + D-Dimer

  • Acquired coagulation abnormalities - diagnostics

    I HistoryII Physical examinationIII Laboratory features- morphology- blood smear- bleeding time- prothrombin time (PT), INR- aPTT- thrombin time (TT)- fibrinogen- fibrin(ogen) degradation products (FDP)- D-dimer- antithrombin

  • PT aPTT Platelet Fibrinogen TT FDP D-Dimer AT count

    Acute DIC Chronic DIC N N N N N Fibrinogenolysis N N N N N

    Heparin overdosage N N N N N N

    Dicumarol N N N N N N overdosage or prothrombin complex factors defficiencyDiferentiation of aquired coagulation abnormalities

  • ACA DIC THERAPY1. Treatment of the underlying disorder2. Treatment of shock3. Replacement therapy - platelet concentrates - RBC - FFP - Cryoprecipitate (fibrinogen) - Activated protein C (drotrecogin alfa)Heparin treatment unfractioned heparin or low-molecular weight heparin acrocyanoza, purpura fulminans, dermal necrosis, venous thromboembolism

  • Treatment thrombosis predominantesContinous infusion of UFHProphilactic doses of heparin or LMWHEspecially, severe purpura fulminans, acral ischemia, vascular skin infarction

  • Treatment - bleedingsTransfusion of platelets or plasma (components) including FFP and/or prothrombin complex concentrate (fluid overload)Severe hipofibrynogeneamia (

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