DISSEMINATED INTRAVASCULAR COAGULATION

1
DISSEMINATED INTRAVASCULAR COAGULATION
CONSUMPTION COAGULOPATHY DEFIBRINATION
SYNDROME ACQUIRED BLEEDING DISORDER

• Dr.Aidah Abu Elsoud Alkaissi
• Linköping University /Sweden
• An-Najah National University/- Palestine

1
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
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)

2
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
3
3
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
4
Pathophysiology
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
4
5
Clinical manifestations of coagulation
abnormalities in disseminated intravascular
coagulation.
5
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
6
6
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
7
7
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
8
8
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
9
Pathophysiology

• 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

• 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)

9
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
10
Underlying pathology creates a triggering event
Either- endothelial tissue injury (Extrinsic)
blood vessel injury (Intrinsic)

• (Porth, 2004)

10
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
11
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
11
12
Signs and Symptoms
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
12
13
Integumentary system

• 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

• SIGNS AND SYMPTOMS
• OF MICROVASCULAR THROMBOSIS
• ? Temperature, sensation ? pain cyanosis in
  extremities, nose, earlobes focal ischemia,
  superficial gangrene

13
14
Respiratory system

• SIGNS AND SYMPTOMS
• OF MICROVASCULAR THROMBOSIS

• SIGNS AND SYMPTOMS OF
• MICROVASCULAR AND FRANK BLEEDING

• Hypoxia (secondary to clot in lung) dyspnea
• chest pain with deep inspiration ? breath sounds
  over areas of large embolism

• High-pitched bronchial breath sounds tachypnea
• ? consolidation signs and symptoms of acute
  respiratory distress syndrome

14
15
Gastrointestinal system

• SIGNS AND SYMPTOMS
• OF MICROVASCULAR THROMBOSIS

• SIGNS AND SYMPTOMS OF
• MICROVASCULAR AND FRANK BLEEDING

• 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)

15
16
Renal system

• SIGNS AND SYMPTOMS
• OF MICROVASCULAR THROMBOSIS

• SIGNS AND SYMPTOMS OF
• MICROVASCULAR AND FRANK BLEEDING

• ? Urine output ? creatinine, ? blood urea
• nitrogen

• Hematuria

16
17
WELCOME TO LINKÖPING- SWEDEN
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
17
18
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
18
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 är 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

23
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
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

Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
24
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

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
25
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
26
26
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
27
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
27
28
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
28
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 gt100 mg/dl
• give content of fibrinogen 250 mg
• Gnereally 4 g are required to increase the
  fibrinogen concentration by 100 mg/dl

29
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
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.

30
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
31
Heparin

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

Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
31
32
Activated Protein C
Antithrombotic effect

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

Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
32
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.

33
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
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

Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
34
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.

35
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
36
Antifibrinolytic agents

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

36
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
37
XIGRIS (Lilly)

• Drotrecogin alfa (activated)
• Recombinant form of human
• Activated Protein C

37
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
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

38
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
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

39
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
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

40
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
41
Xigris

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

41
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
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

Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
42
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

43
44
COLLABORATIVE PROBLEMS/POTENTIAL COMPLICATIONS

• may include
• Renal failure
• Gangrene
• Pulmonary embolism or hemorrhage
• Altered level of consciousness
• Acute respiratory distress syndrome
• Stroke

44
45
Thank You
Dr. Aidah Abu Elsoud Alkaissi Linköping
University- Swedebn
45