BY: Dr.Lailmaah Habibi 2016

1. ‫الرحیم‬ ‫الرحمن‬ ‫هللا‬ ‫بسم‬
DIC
By Dr.Lailmaah Habibi 2nd year trainee of KABUL RBH
Leader trainer : Dr. Aadel

2. Coagulation tests
 Tests of the Vascular Platelet Phase
of Hemostasis
 Bleeding Time: Without the aid of external
pressure, bleeding usually stops within 7 to 9
minutes. The bleeding time is an excellent
screening test for the vascular platelet phase
of hemostasis. It depends on an intact
vasospastic response in a small vessel and an
adequate number of functionally active
platelets

3. Continued…..
 Patients with abnormalities of the vascular
platelet phase of hemostasis present with
purpura (petechiae and ecchymoses) and
spontaneous bruising. They may have mucosal
bleeding and fundus hemorrhages.
 The most common acquired platelet function
abnormalities are drug induced (aspirin and the
nonsteroidal anti-inflammatory agents) and
uremia. The most common hereditary
abnormality is von Willebrand's disease

4. Tests of the Coagulation Cascade
 These in vitro tests—the activated partial
thromboplastin time (aPTT), prothrombin time
(PT), and thrombin time (TT)—measure the
time elapsed from activation of the
coagulation cascade at different points to the
generation of fibrin.

6. INR
 Is the patients prothrombin time to a
normal (control) raised by ISI value
 normal 0.8-1.2 sec

7. Activated Partial Thromboplastin
Time
 Measure the time to form a fibrin clot after activation of
citrated plasma by calcium, phospholipid, and
negatively charged particles. Besides heparin, low–
molecular weightn heparin(LMWH), fondaparinux, and
direct anti-Xa and thrombin (IIa) inhibitors, deficiencies
and inhibitors of coagulation factors of the intrinsic
pathway (e.g., high–molecular-weight kininogen,
prekallikrein, factor XII, factor XI, factor IX, and factor
VIII), common pathway (e.g., factor V, factor X,
prothrombin), and fibrinogen prolong the aPTT.
 The normal time is usually reported as less than 30 to
35 seconds (25 to 35)depending on the technique used.

8. Continued…
 The APTT or anti–factor Xa level is used to monitor
heparin
 Up to 25% of patients with VTE are heparin
resistant; they require more than 35,000 units/day
to achieve a therapeutic APTT. It is useful to
measure anti–factor Xa levels in heparin-resistant
patients because many will have a therapeutic anti–
factor Xa level despite a subtherapeutic APTT. This
dissociation in test results occurs because elevated
plasma levels of fibrinogen and factor VIII, both
acute-phase proteins, shorten the APTT but have no
effect on anti–factor Xa levels. Anti– factor Xa levels
are better than the APTT for monitoring heparin in
patients who exhibit this phenomenon

9. continued
 It is usually prolonged if a patient has less
than approximately 30% normal activity.
It can also be abnormal in the presence of
a circulating inhibitor to any of the
intrinsic pathway factors

10. Prothrombin Time
 The test involves the addition of thromboplastin, a
reagent that contains tissue factor, phospholipid,
and calcium, to citrated plasma and determination
of the time until clot formation
 It measures the integrity of the "extrinsic" and
"common" pathways (factors VII, V, X,
prothrombin, and fibrinogen).
 . Each laboratory has its own normal value,
usually between 12 and 15 seconds.
 As with the interpretation of a prolonged aPTT, a
prolonged PT may reflect either factor deficiency or
a circulating inhibitor of coagulation.

11.  The test is more sensitive than the aPTT for
deficient levels of factors, and a relatively small
drop in factor VII levels may prolong the PT.
 Warfarin therapy is most often monitored with
the prothrombin time, a test sensitive to
reductions in the levels of pro- thrombin, factor
VII, and factor X.

12.  Although the INR has helped standardize
anticoagulant practice, problems persist. The
precision of INR determination varies depending
on reagent-coagulometer combinations, which has
led to variability in INR results. Unreliable
reporting of the ISI by thromboplastin
manufacturers also complicates determination of
the INR. Further- more, every laboratory must
establish the mean normal prothrombin time with
each new batch of thromboplastin reagent. To
accomplish this, the prothrombin time must be
measured in fresh plasma samples from at least
20 healthy volunteers via the same coagulometer
that is used for patient samples

13.  For most indications, warfarin is administered at doses
that produce a target INR of 2.0 to 3.0. An exception is
patients with mechanical heart valves in the mitral
position, in whom a target INR of 2.5 to 3.5 is
recommended. Studies in patients with atrial fibrillation
demonstrate an increased risk for cardioembolic stroke
when the INR falls below 1.7 and an increase in
bleeding with INR values higher than 4.5. These
findings highlight the narrow therapeutic window of
vitamin K antagonists. In support of this concept, a
study in patients receiving long-term warfarin therapy
for unprovoked VTE demonstrated a higher rate of
recurrent VTE with a target INR of 1.5 to 1.9 than with
a target INR of 2.0 to 3.0.

14. Thrombin Time
 This test measures the time necessary to drive
the reaction of fibrinogen to fibrin in the
presence of thrombin. It measures the
integrity of this reaction and isolates an
abnormality to either a decrease in normal
fibrinogen or an inhibitor to its activation.
 Time is measured from the addition of
thrombin to the generation of fibrin filaments.
 Abnormalities can be explained in one of three
ways: deficient fibrinogen (< 100 mg/dl),
abnormal fibrinogen, or an inhibitor to the
reaction

15.  Acquired deficiency of fibrinogen is usually due to
a consumptive coagulopathy or, less often,
severe liver disease. Hereditary deficiencies
exist, but with variable clinical presentations.
Afibrinogenemia is an often fatal childhood
condition.
 Abnormal fibrinogen (dysfibrinogenemia) can be
acquired or inherited. The acquired form is
usually found in association with severe liver
disease, but has been reported in other diseases

16. DIC
 DIC is a clinicopathologic syndrome characterized
by widespread intravascular fibrin formation in
response to excessive blood protease activity that
overcomes the natural anticoagulant mechanisms

17. causes
 The most common causes are bacterial
sepsis , malignant disorders , such as
solid tumors or acute promyelocytic
leukemia and obstetric causes of DIC.
 one-half of pregnant women with abruptio
placentae or with amniotic fluid embolism.
Trauma , particularly to the brain，

19. Purpura fulminans
• is a severe form of DIC resulting from
thrombosis of extensive areas of the skin; it
affects predominantly young children following
viral or bacterial infection , particularly those with
inherited or acquired hypercoagulability due to
deficiencies of the components of the protein C
pathway. Neonates homozygous for protein C
deficiency also present high risk for purpura
fulminans with or without thrombosis of large
vessels

20.  The central mechanism of DIC is the uncontrolled
generation of thrombin by exposure of the blood
to pathologic levels of tissue factor Simultaneous
suppression of physiologic anticoagulant
mechanisms and abnormal fibrinolysis further
accelerate the process
 Together， these abnormalities contribute to
systemic fibrin deposition in small and midsize
vessels.

21. Continued…
 The sustained activation of coagulation
results in consumption of clotting factors
and platelets , which in turn leads to
systemic bleeding. This is further
aggravated by secondary hyperfibrinolysis.

22. Clinical manifestations of DIC
• Related to the magnitude of the imbalance of hemostasis
， to the underlying disease or to both.
• The most common findings are bleeding ranging from
oozing from venipuncture sites ,petechiae and
ecchymoses to severe hemorrhage from the
gastrointestinal tract， lung， or into the CNS.
• In chronic DIC， the bleeding symptoms are discrete and
restricted to skin or mucosal surfaces.

23.  The hypercoagulability of DIC manifests as the
occlusion of vessels in the microcirculation and
resulting organ failure. Thrombosis of large
vessels and cerebral embolism can also occur.
Hemodynamic complications and shock are
common among patients with acute DIC.

24. Laboratory Findings
 In early DIC, the platelet count and fibrinogen levels may remain
within the normal range, albeit reduced from base- line levels.
There is progressive thrombocytopenia (rarely severe),
prolongation of the activated partial thromboplastin time (aPTT)
and prothrombin time (PT), and low levels of fibrinogen. D-dimer
levels typically are elevated due to the activation of coagulation
and diffuse cross-linking of fibrin. Schistocytes on the blood
smear, due to shearing of red cells through the microvasculature,
are present in 10–20% of patients. Laboratory abnormalities in
the HELLP syndrome (hemolysis, elevated liver enzymes, low
platelets), a severe form of DIC with a particularly high mortality
rate that occurs in peripartum women, include elevated liver
transaminases and (many cases) kidney injury due to gross
hemoglobinuria and pigment nephropathy

25. Management of DIC
• The underlying causative disorder must be treated (eg,
antimicrobials, chemotherapy, surgery, or delivery of
conceptus
• If clinically significant bleeding is present, hemostasis
must be achieved (table)

27. Continued..
 Blood products should be administered only if
clinically significant hemorrhage has occurred or
is thought likely to occur without intervention
(Table )The goal of platelet therapy for most
cases is greater than 20,000/mcL or greater than
50,000/mcL for serious bleeding, such as
intracranial bleeding

28.  FFP should be given only to patients with a
prolonged aPTT and PT and significant bleeding;
4 units typically are administered at a time, and
the posttransfusion platelet count should be
documented. Cryoprecipitate may be given for
bleeding and fibrinogen levels less than 80–100
mg/dL

29.  In some cases of refractory bleeding despite
replacement of blood products, administration of
low doses of heparin can be considered; it may
help interfere with thrombin generation, which
then could lead to a lessened consumption of
coagulation proteins and platelets. An infusion of
6–10 units/kg/h (no bolus) may be use

30. Source
 Current medical diagnosis & treatment
 Harrison’s text book
 Braunwald ‘s textbook
 Washington’s textbook
 net

31. …END