ACQUIRED COAGULATION ABNORMALITIES

ACQUIRED COAGULATION ABNORMALITIES

ACQUIRED COAGULATION ABNORMALITIES - causes 1. Liver disease 2. Vitamin K deficiency 3. Increased consumption of the clotting factors (disseminated intravascular coagulation (DIC) 4. Clotting factor inhibitors

1. Abnormalities of coagulation in liver diseases LIVER synthesizes all coagulation proteins clears the activated products of coagulation Liver cirrhosis, viral or toxic failure

Abnormalities of coagulation in liver diseases I. Decreased synthesis of coagulation factors 1. Fibrinogen, protrombin, clotting factors: V, VII, IX, X, XI, XII, XIII, prekallikrein, high molecular weight kininogen 2. Antiplasmins, antithrombin, protein C and S II. Aberrant biosynthesis 1. Abnormal fibrinogen 2. Abnormal analogues of prothrombin, factors VII, IX, X, III. Deficient clearance 1. Fibrin monomers, fibrinogen degradation products (FDP) 2. Activated coagulation factors (IXa, Xa, Xia) 3. Plasminogen acivators

2. Coagulation abnormalities vitamin K deficiency dependent Vitamin K plays an essential role as a cofactor for enzymes that participate in carboxylation of coagulation factors: II, VII, IX, X and the physiologic anticoagulants: protein C and protein S

Vitamin K deficiency - etiology I. Inadequate supply: 1. Dietary deficiency 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)

Liver disease and vitamin K deficiency - symptoms of diathesis Bleeding nose, gums, urinary tract, gastrointestinal tract Bruising, petechiae, hematomas Symptoms of underlying disease

Liver disease and vitamin K deficiency - laboratory features prolonged prothrombin time (PT) activated partial thromboplastin time (aptt) is prolonged only in severe, protracted vitamin K deficiency and in severe, advanced liver failure decreased level of clloting factors:

Diathesis in liver disease and vitamin K deficiency THERAPY - Vit. K i.m. / i.v. (10-20 mg) - severe bleeding FFP (10-15 ml/kg)

3. Disseminated intravascular coagulation - DIC An acquired syndrome occurs as a result of significant underlying health condition

Conditions associated with DIC 1. Sepsis and severe infection 2. Massive tissue injury: large traumatic injuries and burns 2. Obstetric disorders (abruptio placentae, eclampsia) 3. Malignancy: acute promyelocytic leukemia M3, advances carcinomas 5. Vascular disorders (giant hemangiomas) 6. Miscellaneous: acute pancreatitis, graft versus host disease, diabetic acidosis, snake bites, )

Pathogenesis of DIC Coagulation Thrombin Release of thromboplastic material into circulation Fibrinogen Fibrinolysis Plasmin Consumption of coagulation factors; presence of FDPs aptt PT TT Fibrinogen Fibrin Monomers Fibrin Clot (intravascular) Fibrin(ogen) Degradation Products Plasmin Presence of plasmin FDP Intravascular clot Platelets Schistocytes

Disseminated intravascular coagulation - DIC Acute - patients need urgent therapy! Chronic (compensated) usually asymptomatic

ACUTE DIC- CLINICAL PRESENTATION symptoms of underlying disease multiorgan dysfunction caused by microthrombi renal, liver, respiratory, CNS dysfunction bleeding caused by consumption of plt and clotting factors

AcuteDIC - laboratory features Prolonged aptt Prolonged prothrombin time (PT) Decreased platelet level Increased D-Dimer level Increased FDP level Decreased AT level Decreased fibrinogen level

Acute DIC - THERAPY 1. Treatment of the underlying disorder 2. Replacement therapy - platelet concentrates - RBC - FFP

4. Circulating anticoagulants Clotting factor inhibitors are autoantibodies (usually IgG) or alloantibodies (in hemophilias) that inactivate coagulation factors and, therefore, act as anticoagulants

Circulating anticoagulants The most common - antibodies against factorviii In patients with hemophilia treated by f.viii - alloantibodies In patients without hemophilia - autoantibodies Other spontaneous inhibitors (rarely) - against factors: V, IX, XIII, fibrinogen

Circulating anticoagulants Autoantibodies against factor VIII = acquired hemophilia associated with older age, autoimmune and malignant disorders, the postpartum period, and use of drugs (penicillin, sulfonamides) very rare; sudden onset one of the major causes of spontaneous life-threatening bleeding in the elderly.