dissemenatted intravascular coagulation

1. Last updates in diagnosis and mangement
of DIC
dr. AMAL ABD ALSSALAM ELHASSY
SHO IN RESPIRATORY UNIT

2. The Internationa Society on Thrombosis and
Haemostasis has
suggested the following definition for DIC:
An acquired syndrome characterized by the
intravascular activation of coagulation with loss of
localization arising from different causes. It can
originate from and cause damage to the
microvasculature, which if sufficiently severe, can
produce organ dysfunction.

3. Pathophysiology of DIC
• Several disease states may lead to the development of
DIC generally via one of the following two pathways:
• A systemic inflammatory response, leading to
activation of the cytokine network and subsequent
activation of coagulation (eg, in sepsis or major
trauma)
• Release or exposure of procoagulant material into the
bloodstream (eg, in cancer, crush brain injury, or in
obstetric cases)
• In some situations (eg, major trauma or severe
necrotizing pancreatitis), both pathways may be
presen

5. Forms of DIC

6. Acute DIC
sudden exposure of blood
to procoagulants (eg,
tissue factor [TF], or tissue
thromboplastin) generates
intravascular coagulation
Compensatory hemostatic
mechanisms
severe consumptive
coagulopathy
hemorrhage develops
Abnormalities of blood
coagulation parameters are
readily identified, and organ
failure frequently results.

7. chronic DIC
blood is continuously or intermittently
exposed to small amounts of TF
Compensatory mechanisms in the liver
and bone marrow are not
overwhelmed,
little obvious clinical or laboratory
indication of the presence of DIC

9. DIC is not itself a specific illness
It is always secondary to an underlying disorder
and is associated with a number of clinical
conditions, generally involving activation of
systemic inflammation. Such conditions include
the following

10. Sepsis and severe infection
• . DIC affects about 35% of patients who have sepsis.
• Sepsis and septic shock can result from an infection
anywhere in the body, such as pneumonia,
influenza, or urinary tract infections. Worldwide,
• one-third of people who develop sepsis die
• . Many who do survive are left with life-changing
effects, such as post-traumatic stress
disorder (PTSD), chronic pain and fatigue, and organ
dysfunction and/or amputations.

11. Trauma (neurotrauma)
• DIC associated with traumatic injury results from
multiple independent but interplaying mechanisms,
involving tissue trauma, shock, and inflammation
• The zenith of the problem is typically seen in
patients with head injuries and in those who are
massively injured and transfused. The resulting
coagulopathy is characterized by nonsurgical
bleeding from mucosal lesions, serosal surfaces,
and wound and vascular access sites

12. MalignancY
• unexplained low platelet count, a low fibrinogen level, an elevated D-
dimer level, and a prolonged prothrombin time.
• patients with solid tumors often present without symptoms and only
laboratory abnormalities that suggest the diagnosis of DIC. Other
patients with solid tumors and DIC may present with excessive
bleeding, venous or arterial thromboembolism, or nonbacterial
endocarditis. An occasional patient may present with
microangiopathic hemolytic anemia, thrombocytopenia, or both
• The dominant tumor type associated with DIC is adenocarcinoma,
and the tumors usually originate in the gastrointestinal tract
(frequently signet ring cell type), pancreas, lung, breast, or prostate

13. Severe transfusion reactions
• present as adverse signs or symptoms during or within 24 hours of a
blood transfusion.
• fever, chills, pruritus, or urticaria, which typically resolve promptly
without specific treatment or complications
• severe shortness of breath, red urine, high fever, or loss of
consciousness may be the first indication of a more severe
potentially fatal reaction.

14. • Acute hemolytic transfusion
reactions may be either
immune-mediated or
nonimmune-mediated.
Immune-mediated hemolytic
transfusion reactions caused by
immunoglobulin M (IgM) anti-A,
anti-B, or anti-A,B typically
result in severe, potentially fatal
complement-mediated
intravascular hemolysis
• Tumor necrosis factor appears
to be the most commonly
identified mediator of
intravascular coagulation and
end-organ injury

15. Vascular abnormalities
• a few patients with extensive venous
malformations, mainly affecting an extremity,
have a severe LIC with a very high D-dimer level
(>1.8μg/ml) and a low fibrinogen level. These
patients are at risk of potential aggravation of LIC
to disseminated intravascular coagulopathy (DIC)
with dramatic bleeding during a surgical excision,
and marked consumption of platelets,
coagulation factors and fibrinogen.
• Venous malformation is the only disease that can
permanently highly increase D-dimer levels in
otherwise healthy patients.

16. Severe hepatic failure
• most coagulation factors are synthesized by liver
parenchymal cells and the liver's reticuloendothelial
system serves an important role in the clearance of
activation products
• During liver failure, there is a reduced capacity to clear
activated haemostatic proteins and protein inhibitor
complexes from the circulation. Portal hypertension with
collateral circulation and secondary splenomegaly causes
thrombocytopenia due to splenic sequestration.
Thrombocytopenia may also be caused by decreased
hepatic thrombopoietin synthesis. There may also be
impaired platelet function. Complications of cirrhosis such
as variceal bleeding or infection/sepsis may lead to the
onset of bleeding.

17. Gynecologic and obstetric complications
• Amniotic fluid embolism
• Placental abruption
• Placenta previa
• Pre-eclampsia
• Eclampsia
• Hemolysis, elevated liver enzymes, and low
platelet count (HELLP) syndrome
• Retained fetus syndrome
• Retained products of conception
• Abortion

18. Hemorrhagic skin necrosis (purpura
fulminans)
• rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin
that is rapidly progressive and is accompanied by vascular collapse and
disseminated intravascular coagulation
• Manifestations of idiopathic purpura fulminans may include the following:
• Sudden development 7-10 days after the onset of the precipitating infection
• Progressively enlarging, well-demarcated purplish areas of hemorrhagic cutaneous
necrosis with derangements in coagulation factors
• Erythematous macules that progress within hours to sharply defined areas of
purpura
• Impaired perfusion of limbs and digits
• Major organ dysfunction (eg, lungs, heart, or kidneys)
• The 4 primary features of acute infectious purpura fulminans are as follows:
• Large purpuric skin lesions
• Fever
• Hypotension
• Disseminated intravascular coagulation (DIC)

20. Catastrophic antiphospholipid syndrome
((rare
• During the 10th International Congress on aPL in
2002, preliminary classification criteria for CAPS
were proposed] and validated in 2005
• defined as thromboses in three or more organs
developing in less than a week, microthrombosis
in at least one organ and persistent aPL positivity.
• The clinical manifestations of CAPS may evolve
gradually, commonly overlapping with other
thrombotic microangiopathies, requiring a high
index of clinical suspicion.

21. Clinical presentation
History
Physical examination

22. History
• Symptoms of underlying disease
• history of bleeding in areas such the gingivae and the
gastrointestinal (GI) system along with
• blood loss from intravenous (IV) lines and catheters.
• In postoperative DIC, bleeding can occur in the surgical sites,
drains, and tracheostomies
• symptoms of thrombosis in large vessels (eg, deep vein
thrombosis [DVT])
• Bleeding from at least 3 unrelated sites is particularly
suggestive of DIC.
• Patients with pulmonary involvement can present with
dyspnea, hemoptysis, and cough. Comorbid liver disease as
well as rapid hemolytic bilirubin production may lead to
jaundice. Neurologic changes (eg, coma, obtunded mental
status, and paresthesias) are also possible.

23. Main Features of Disseminated
Intravascular Coagulation in Series of
118 Patients
Affected paitientsfeatures
64%Bleeding
25%Renal dysfunction
19%Hepatic dysfunction
16%Respiratory dysfunction

24. Physical Examination

25. Circulatory signs include the following
• Signs of spontaneous and life-
threatening hemorrhage
• Signs of diffuse or localized
thrombosis
• Bleeding into serous cavities

26. Central nervous system signs include the
following
• Nonspecific altered consciousness or stupor
• Transient focal neurologic deficits

27. Cardiovascular signs include the following:
• Hypotension
• Tachycardia
• Circulatory collapse

28. Respiratory signs include the following
• Pleural friction rub
• Signs of acute respiratory distress syndrome
(ARDS

29. Gastrointestinal signs include the
following:
• Hematemesis
• Hematochezia

30. Genitourinary signs include the
following:
• Signs of renal failure
• Acidosis
• Hematuria
• Oliguria
• Metrorrhagia
• Uterine hemorrhage

31. Dermatologic signs include the
following
• Petechiae
• Jaundice (liver dysfunction or
hemolysis)
• Purpura
• Hemorrhagic bullae
• Acral cyanosis
• Skin necrosis of lower limbs (purpura
fulminans)
• Localized infarction and gangrene
• Wound bleeding and deep
subcutaneous hematomas
• Thrombosis

32. Diagnosis of DIC
• SCORING SYSTEMS
• LAB STUDIES
• HISTOLOGICAL FINDINGS

33. Scoring systems
• The International Society on Thrombosis and
Haemostasis (ISTH) developed a simple
scoring system for the diagnosis of overt DIC
that makes use of laboratory tests available in
almost all hospital laboratories

35. A score of 5 or higher indicates overt
DIC, whereas a score of less than 5 does
not rule out DIC but may indicate DIC
that is not overt. [4]
The sensitivity of the DIC score for a
diagnosis of DIC is 91-93%, and the
specificity is 97-98%.

36. Lab studies
1-prolonged coagulation times
2-thrombocytopenia
3-high levels of FDP
4- D-dimer
5- schistocytes in PBS
ALL OF THEM ARE SUGGESTIVE FINDINGS

37. Histologic Findings
Micrograph showing an acute thrombotic
microangiopathy, the histologic correlate
of DIC, in a kidney biopsy. A thrombus is
present in the hilum of the glomerulus
(center of image). PAS stain

38. • The cornerstone of the treatment of DIC is
treatment of the underlying condition
• if infection is the underlying etiology, the
appropriate administration of antibiotics and
source control is the first line of therapy
• in case of an obstetric catastrophe, the
primary approach is to deliver appropriate
obstetric care, in which case the DIC will
rapidly subside.
TREATMENT

39. Management of the DIC itself has the
following basic features
• Monitor vital signs
• Assess and document the extent of
hemorrhage and thrombosis
• Correct hypovolemia
• Administer basic hemostatic procedures
when indicated

40. Administration of Blood Components and
Coagulation Factors

41. scoring system correlates with key clinical
observations and outcomes
It is important to repeat the tests to monitor
the dynamically changing scenario based on
laboratory results and clinical observations

42. In cases of DIC where the bleeding predominates
• patients with DIC and bleeding or at high
risk of rative patients or patients due to
undergo an invableeding (e.g. postopesive
procedure) and a platelet count of <50 ·
109/l transfusion of platelets should be
considered.
• In non-bleeding patients with DIC,
prophylactic platelet transfusion is not given
unless it is perceived that there is a high risk
of bleeding
• There is no evidence that infusion of plasma
stimulates the ongoing activation of
coagulation

43. • In bleeding patients with DIC and
prolonged prothrombin time (PT)
and activated partial thromboplastin
time (aPTT), administration of fresh
frozen plasma (FFP) may be useful..
should be considered only in those
with active bleeding and in those
requiring an invasive procedure
• If transfusion of FFP is not possible in
patients with bleeding because of
fluid overload, consider using factor
concentrates such as prothrombin
complex concentrate,(only partially
correct the defect because they
contain only selected factors,
whereas in DIC there is a global
deficiency of coagulation factors)

44. • Severe hypofibrinogenaemia (<1 g/l) that
persists despite FFP replacement may be
treated with fibrinogen concentrate or
cryoprecipitate

46. In cases of DIC where thrombosis predominates
• arterial or venous thromboembolism, severe purpura fulminans
associated with acral ischemia or vascular skin infarction,
therapeutic doses of heparin should be considered.
• In these patients where there is perceived to be a co-existing high
risk of bleeding there may be benefits in using continuous infusion
unfractionated heparin (UFH) due to its short half-life and
reversibility. Weight adjusted doses (e.g. 10 l/kg/h) may be used
• observation for signs of bleeding is important

47. • In critically ill, non-bleeding
patients with DIC,
prophylaxis for venous
thromboembolism with
prophylactic doses of heparin
or low molecular weight
heparin is recommended

48. • Consider treating patients with
severe sepsis and DIC with
recombinant human activated
protein C (continuous infusion, 24
lg/kg/h for 4 d
• Patients at high risk of bleeding
should not be given recombinant
human activated protein C.
Current manufacturers guidance
advises against using this product
in patients with platelet counts of
<30 · 109/l.

50. • In the absence of further prospective evidence from
randomised controlled trials confirming a beneficial
effect of antithrombin concentrate on clinically
relevant endpoints in patients with DIC and not
receiving heparin, administration of antithrombin
cannot be recommended

51. • general, patients with DIC should
not be treated with antifibrinolytic
agents. Patients with DIC that is
characterised by a primary
hyperfibrinolytic state and who
present with severe bleeding could
be treated with lysine analogues,
such as tranexamic acid (e.g. 1 g
every 8 h).

52. complications
• Complications of DIC include the following:
• Acute kidney injury
• Change in mental status
• Respiratory dysfunction
• Hepatic dysfunction
• Life-threatening thrombosis and hemorrhage (in patients
with moderately severe–to–severe DIC)
• Cardiac tamponade
• Hemothorax
• Intracerebral hematoma
• Gangrene and loss of digits
• Shock
• Death

53. Long-Term Monitoring
• Patients who recover from acute DIC should
follow up with their primary care provider or a
hematologist.

54. Prognosis
• DIC is estimated to be present in as many as 1% of hospitalized
patients.
• Prognosis varies depending on the underlying disorder, and the
extent of the intravascular thrombosis (clotting). The prognosis for
those with DIC, regardless of cause, is often grim: Between 10% and
50% of patients will die
• DIC with sepsis (infection) has a significantly higher rate of death
than DIC associated with trauma
• . [1] In some cases, such as abruptio placentae, DIC will quickly
resolve itself after elimination of the underlying condition.

55. References
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intravascular coagulation based on current understanding of the pathophysiology.
Ann Med. 2004. 36(1):41-9. [Medline].
• Branson HE, Katz J, Marble R, Griffin JH. Inherited protein C deficiency and
coumarin-responsive chronic relapsing purpura fulminans in a newborn infant.
Lancet. 1983 Nov 19. 2(8360):1165-8. [Medline].