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Causes And Treatment Of Pathological Fibrinolysis And Disseminated Intravascular Coagulation (DIC)

Updated on February 4, 2014

A Patient With Pathological Fibrinolysis

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Causes And Clinical Manifestations Of pathological Fibrinosis

Healthy individuals may show minor variations in fibrinolytic activity without any deleterious effects, but gross increase in fibrinolytic activity causes hemorrhage. Excessive fibrinolysis may be primary phenomenon or develop as consequence of disseminated intravascular coagulation (DIC).

Causes of excessive fibrinolysis

  1. Obstetric causes: Abruptio placentae and amniotic fluid embolism.
  2. Surgical causes: Gastrectomy, lung resection, nephrectomy, prostatectomy, cardiopulmonary bypass, splenectomy and pancreatectomy.
  3. Medical causes such as:
    1. Liver disease such as cirrhosis of liver.
    2. Leukemias, especially in acute leukemia and chronic granulocytic leukemia
    3. Anaphylactic shock.
    4. Autoimmune diseases such as systemic lupus erythematosus

Pathogenesis: Fibrinolytic activity may be enhanced as a result of excessive release of plasminogen activator or reduction in the inhibitor.

Clinical features

The clinical features depend on the predominant mechanism. If thrombocytopenia is pronounced, capillary bleeding predominates. If coagulation mechanism is defective, the bleeding is more serious and deep-seated. The severity and clinical presentation may vary from case to case.

Diagnosis

Normal bleeding time, slightly prolonged clotting time, and poor quality of the clot should suggest the possibility of excessive fibrinolysis. Primary fibrinolysis has to be distinguished from disseminated intravascular coagulation (DIC). In primary fibrinolysis, platelet count is normal and this distinguishes it from DIC in which distinguish these two conditions since treatment is different.

Bleeding Due To Pathological Fibrinolysis

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Treatment

Laboratory Tests

These tests for fibrinolysis are as follows:

  1. Euglobulin lusis time for detecting the presence of increased levels of circulating plasminogen activator.
  2. The detection of excess of fibrin split products (FDP) by immunological methods.
  3. Circulating levels of plasminogen which will be low in fibrinolysis.

Treatment

Primary fibrinolysis can be readily controlled by the use of antifibrinolytic agents. Commonly used antifibrinolytic agents are epsilon-aminocaproic acid (EACA) and tranexamic acid which are synthetic amino acids and aprotinin (Trasylol) which is a polypeptide. When given orally, EACA is rapidly absorbed and a single oral dose is effective for 4 hours. It is contraindicated in advanced renal disease. For immediate effect, 5 to 10 g is given intravenously in the first hour followed by 2 g hourly for the next 2 to 3 hours. This is then followed by oral therapy with 4 g every 4 hours. The total dose in 24 hours should not exceed 30g. Since the drug is excreted by the Kidneys, its concentration in Urine is higher than in plasma.

In disseminated intravascular coagulation (DIC), fibrinolysis occurs as a defence mechanism helping to remove the clots formed, and inhibition of fibrinolysis is harmful since it may lead to widespread thrombosis. Administration of EACA should not be undertaken without concurrent heparin therapy if the distinction between primary fibrinolysis and DIC is not clear. Thrombotic complications, particularly renal cortical necorsis, may develop when EACA is used alone in patients with DIC.

Tranexamic acid is ten times as potent as EACA and it is used in menorrhagia and upper gastrointestinal bleeding. Aprotinin is given in a dose of 200,000 untis as intravenous infusion every four hours.

Streptase- An Antifibrinolytic Drug

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Clinical Application Of Fibrinolytic Agents

Fibrinolytic agents are used therapeutically to hasten clearance of thrombi. Urokinase present in normal urine and streptokinase (derived from streptococci) are activators of plasminogen. Initial dose of streptokinase is 125,000 units. Subsequently smaller doses are given every 1 hour. Streptokinase is very effective in dissolving clots. Repeated doses are antigenic. Urokinase is more advantageous in being nontoxic and no antigenic, but it is more costly. The initial dose is 14,400 units/Kg body weight. Indications for fibrinolytic therapy include pulmonary embolism and various types of acute and chronic arterial occlusions. Local infusion into blocked blood vessels is effective in restoring patency and this is being tried extensively. It is risky to use streptokinase and urokinase in cerebrovascular occlusions.

While undertaking therapy drugs like EACA should be available readily to treat overdosage of streptokinase.

Symptoms Of DIC

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DIC Manifestation

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Disseminated Intravascular Coagulation (DIC)

This is also known as Defibrination syndrome, Consumption coagulopathy. Due to the liberation of a large amount of thromboplastic material into the circulation, widespread thrombosis develops with extensive occlusion of the small blood vessels.

Common causes of DIC

  1. Obstetric: Abruptio placentae, intrauterine fetal death, septic abortion and amniotic fluid embolism
  2. Infection: Falciparum malaria, gram negative septicemia, meningococcemia, septic shock, rickettsial infections, viral infections, etc.
  3. Malignant disease: Diseases of prostrate, breast, lung and pancreas.
  4. Hematological malignancies: Acute promyelocytic leukemia.
  5. Mismatched blood transfusion with hemolytic transfusion reaction.
  6. Cavernous hemangioma.
  7. Miscellaneous: Trauma, fat embolism, burns hypothermia, viper bites, and scorpion bite.

Disseminated intravascular coagulation is associated with depletion of plasma fibrinogen, platelets, prothrombin and factors V and VIII. Depletion of these factors makes the blood incoagulable. This condition manifests as an acute generalized hemorrhagic state which supervenes on the underlying disorder. Occlusion of the renal vessels lead to hemolytic uremic sundrome. Disseminated intravascular coagulation leads to microangiopathic hemolytic anemia in which fragmented erythrocytes are demonstrable in peripheral blood.

Laboratory findings

Diagnostic findings are reduction in platelets, fibrinogen and factos II, V and VIII. The prothrombin time and partial thromboplastin time are prolonged. Fibrin degradation products (FDP) are markedly increased in blood and urine. These (FDPs) further inhibit coagulation and platelet aggregation and this worsens the hemorrhagic state. The combination of prolonged prothrombin time and thrombin time, hypofibrinogenemia and thrombocytopenia is strong evidence of DIC.

Treatment

Heparin is the drug of choice in those who are not bleeding. The initial dose is 5000 units intravenously followed by 1000 units intravenously every hour and the dosage is maintained to keep the whole blood clotting time twice the normal. The etiological factors that precipitated the DIC have to be attended to. If renal failure sets in hemodialysis may be required. The depletion of coagulation factors and platelets may necessitate replacement therapy in those in whom bleeding is severe. Anemia due to hemolysis is corrected by fresh blood transfusion.

© 2014 Funom Theophilus Makama

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