DISSEMINATED INTRAVASCULAR COAGULATION CONSUMPTION COAGULOPATHY DEFIBRINATION SYNDROME ACQUIRED BLEEDING DISORD

1. DISSEMINATED INTRAVASCULAR COAGULATION �CONSUMPTION COAGULOPATHY� DEFIBRINATION SYNDROME �ACQUIRED BLEEDING DISORDER�  Dr.Aidah Abu Elsoud Alkaissi Link�ping University /Sweden An-Najah National University/- Palestine

2. Definition Disseminated intravascular coagulation (DIC) is a pathophysiological process and not a disease in itself. a systemic process producing both thrombosis and hemorrhage. Is a Paradoxical Clinical Presentation �clotting and hemorrhage� (Porth, C.M. (2004) Essentials of Pathophysiology) & (Otto, S. (2001). Oncology Nursing) Reportedly complicates 1% of all hospital admissions. The major initiating factors are the release or expression of tissue factor, usually involving entry of tissue thromboplastins into the circulation, extensive injury to vascular endothelium exposing tissue factor, or enhanced expression of tissue factor by monocytes in response to endotoxin and various cytokines. Intrinsic pathway activation may also occur in some settings- but it appears to contribute more to the development of hypotension than to DICReportedly complicates 1% of all hospital admissions. The major initiating factors are the release or expression of tissue factor, usually involving entry of tissue thromboplastins into the circulation, extensive injury to vascular endothelium exposing tissue factor, or enhanced expression of tissue factor by monocytes in response to endotoxin and various cytokines. Intrinsic pathway activation may also occur in some settings- but it appears to contribute more to the development of hypotension than to DIC

9. Pathophysiology Thrombosis-brief period of hypercoagulability Coagulation cascade is initiated, causing widespread fibrin formation Microthrombi are deposited throughout he microcirculatory Fibrin deposits result in tissue ischemia, hypoxia, necrosis Leads to multi organ dysfunction (Porth, 2004) & (Otto, 2001) Fibrinolysis-period of hypocoagulability (the hemorrhagic phase) Activates the complement system (helps, or �complements�, the ability of antibodies to clear pathogens from an organism). Byproducts of fibrinolysis (fibrin/fibrin degradation products(FDP)) further enhance bleeding by interfering with platelet aggregation, fibrin polymerization, & thrombin activity Leads to Hemorrhage

10. Underlying pathology creates a triggering event: Either- endothelial tissue injury (Extrinsic) blood vessel injury (Intrinsic) (Porth, 2004)

13. Integumentary system SIGNS AND SYMPTOMS OF MICROVASCULAR THROMBOSIS ? Temperature, sensation; ? pain; cyanosis in extremities, nose, earlobes; focal ischemia, superficial gangrene SIGNS AND SYMPTOMS OF MICROVASCULAR AND FRANK BLEEDING Petechiae, including periorbital and oral mucosa; bleeding: gums, oozing from wounds, previous injection sites, around catheters (IVs, tracheostomies); epistaxis; diffuse ecchymoses; subcutaneous hemorrhage; joint pain

14. Respiratory system SIGNS AND SYMPTOMS OF MICROVASCULAR THROMBOSIS Hypoxia (secondary to clot in lung); dyspnea; chest pain with deep inspiration; ? breath sounds over areas of large embolism SIGNS AND SYMPTOMS OF MICROVASCULAR AND FRANK BLEEDING High-pitched bronchial breath sounds; tachypnea; ? consolidation; signs and symptoms of acute respiratory distress syndrome

15. Gastrointestinal system SIGNS AND SYMPTOMS OF MICROVASCULAR THROMBOSIS Gastric pain; �heartburn� Hematomesis (heme?� NG output) melana (heme? stools?tarry stools ?bright-red blood from rectum) retroperitoneal bleeding (abdomen firm and tender to palpation; distended; ? abdominal girth) SIGNS AND SYMPTOMS OF MICROVASCULAR AND FRANK BLEEDING

16. Renal system SIGNS AND SYMPTOMS OF MICROVASCULAR THROMBOSIS ? Urine output; ? creatinine, ? blood urea nitrogen Hematuria SIGNS AND SYMPTOMS OF MICROVASCULAR AND FRANK BLEEDING

19. Fibrin degradation product (FDPs), also known as fibrin split products, are components of the blood produced by clot degeneration. These are produced by the action of plasmin on deposited fibrin. The most notable subtype of fibrin degradation products is D-dimer. The levels of these FDPs rises after any thrombotic event. It can be used to test for disseminated intravascular coagulation.

20. D-dimer is a fibrin degradation product, a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two crosslinked D fragments of the fibrinogen protein.

21. D-dimer concentration may be determined by a blood test to help diagnose thrombosis. Since its introduction in the 1990s, it has become an important test performed in patients suspected of thrombotic disorders. While a negative result practically rules out thrombosis, a positive result can indicate thrombosis but does not rule out other potential causes. Its main use, therefore, is to exclude thromboembolic disease where the probability is low. In addition, it is used in the diagnosis of the blood disorder disseminated intravascular coagulation.[

22. D-dimers are not normally present in human blood plasma, except when the coagulation system has been activated, for instance because of the presence of thrombosis or disseminated intravascular coagulation. The D-dimer assay depends on the binding of a monoclonal antibody to a particular epitope on the D-dimer fragment. Several detection kits are commercially available

23. Lab Diagnosis Elevated d-dimer levels (D-dimer �r en degradation product of fibrin, reflecting cross linked fibrin degradation are the most common abnormal parameter in patients with DIC. blood test to diagnose thrombosis Prolonged prothrombin time (PT): Prothrombin time refelects reduced activity of the components of the extrinsic and common pathway. These include factors VII, X, V, and prothrombin, which are the most freq decreased clotting proteins

24. Lab Diagnosis Prolonged Activated partial thromboplastin time(aPTT): measures the intrinsic and common pathways of coagulation. - sensitive to deficiencies of factors XII, XI, IX, and VIII. Fibrinogen - low in acute DIC, - may be elevated as an acute phase reactant in certain chronic conditions, including pregnancy

25. Lab Diagnosis Thrombocytopenia. Increased fibrin formation Stimulates compensatory process of secondary fibrinolysis, Plasminogen activators generate plasmin to digest fibrin (and fibrinogen) into fibrin(ogen) degradation products (FDPs). FDPs are potent circulating anticoagulants that contribute further to the bleeding manifestations of DIC. Intravascular fibrin deposition can cause fragmentation of red blood cells and lead to the appearance of schistocytes in blood smears

29. Platelets transfusion and fresh frozen plasma No evidence to support the administration of platelets and coagulation factors in patients who are not at high risk for bleeding In patient with bleeding and hypofibrinogenemia Attempt to maintatin fibrinogen >100 mg/dl give content of fibrinogen =250 mg Gnereally 4 g are required to increase the fibrinogen concentration by 100 mg/dl

30. Heparin The use and dosage of heparin in DIC is controversial. Heparin inhibition of thrombin may theoretically inhibit formation of microvascular thrombi, which fuel DIC. The goal of heparin use is to suppress coagulation, increase fibrinogen levels, and decrease D-dimer levels.

31. Heparin Uncontrolled trials using low-molecular-weight heparins in DIC have also been reported.

32. Activated Protein C  Inhibits Factors Va and VIIIa. Indirect profibrinolytic activity through its ability to inhibit plasminogen activator inhibitor-1 (PAI-1) Limits generation of activated thrombin-activatable-fibrinolysis-inhibitor. may exert an anti-inflammatory effect Limits the thrombin-induced inflammatory responses within the microvascular endothelium.

33. Antithrombin IIIatenativ� - Is a natural inhibitor of coagulation that inactivates thrombin and factor Xa. Few randomized trials have been performed, and improvement in laboratory tests has not led to clinically relevant benefits.

34. Study Treatment of DIC with antithrombin III concentrates. Sakata Y, Yoshida N, Matsuda M, Aoki N. Abstract administered AT III concentrates to 21 patients with DIC who failed to respond initially to heparin therapy. About 60% of these 21 patients were effectively treated with AT III concentrates by enhancing the effect of heparin and alleviating the burden of excessive plasma transfusions on the cardiovascular system

35. rFVIIa Recombinant Factor VIIA Factor VII is a natural initiator of haemostasis, which binds to Tissue Factor (TF) at the site of vascular injury leading to the generation of thrombin. rFVIIa activates factor X on the surface of activated platelets at the site of vascular injury, resulting in a localised thrombin burst, leading to a rapid formation of stable fibrin clots at the site of vascular injury.

36. Antifibrinolytic agents  e-aminocaproic acid and tranexamic acid (Cyklokapron) Generally are contraindicated May precipitate thrombosis May be effective in decreasing life-threatening bleeding

37. XIGRIS� (Lilly) Drotrecogin alfa (activated) Recombinant form of human Activated Protein C

38. XIGRIS� Clinical study (PROWESS) 1690 patients with severe sepsis Entry criteria included a systemic inflammatory response presumed due to infection and at least one associated acute organ dysfunction The study was terminated after a planned interim analysis due to significantly lower mortality in patients on Xigris than in patients on placebo

39. XIGRIS� INDICATIONS AND USAGE Xigris is indicated for the reduction of mortality in adult patients with severe sepsis (sepsis associated with acute organ dysfunction) who have a high risk of death

40. XIGRIS� Contraindications Active internal bleeding Recent (within 3 months) hemorrhagic stroke Recent (within 2 months) intracranial or intraspinal surgery, or severe head trauma Trauma with an increased risk of life-threatening bleeding Presence of an epidural catheter Intracranial neoplasm or mass lesion or evidence of cerebral herniation

41. Xigris DOSAGE AND ADMINISTRATION Xigris should be administered intravenously at an infusion rate of 24 �g/kg/hr for a total duration of infusion of 96 hours.

42. Xigris Drotrecogin alfa (activated) (Xigris, is a recombinant form of human activated protein C that has anti-thrombotic, anti-inflammatory, and profibrinolytic properties. Drotrecogin alpha (activated) belongs to the class of serine proteases. It is used mainly in intensive care medicine as a treatment for severe sepsis. However, further evidence is required before it becomes the standard of care

43. Nursing Diagnosis � Risk for deficient fluid volume related to bleeding � Risk for impaired skin integrity related to ischemia or bleeding � Potential for excess fluid volume related to excessive blood/factor component replacement � Ineffective tissue perfusion related to microthrombi � Anxiety and fear of the unknown and possible death

44. COLLABORATIVE PROBLEMS/POTENTIAL COMPLICATIONS may include: Renal failure Gangrene Pulmonary embolism or hemorrhage Altered level of consciousness Acute respiratory distress syndrome Stroke