D.I.

C (Disseminated Intravascular Coagulopathy)

Specific Learning Objectives

 Understand pregnancy as a hypercoagulable state
 Understand the pathophysiology of DIC
 List obstetric conditions associated with DIC
 Describe clinical features associated with DIC
 List complications associated with DIC
 Describe the management of DIC
Pathophysiology of DIC

Def: A condition associated with inappropriate activation of

coagulation & fibrinolytic systems.

Physiology of coagulation cascade mechanism

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 XII- Hageman factor, a serine protease
XI –Plasma thromboplastin, antecedent serine protease
IX – Christmas factor, a serine protease
VII – Stable factor, serine protease
VIII – Fibrin stabilizing factor, a transglutaminase
IV (PL) – Platelet membrane phospholipid
Ca++- Calcium ions
TF –Tissue factor

Physiology of coagulation cascade mechanism

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Thrombin – Proteolytic enzyme:
 Splits fibrinogen chains into fibrinoid peptides leading
 Formation of fibrin monomer

NB: Activation of coagulation system:

 Stimulates conversion of plasminogen into plasmin as
 Protective mechanism against intravascular thrombosis

Plasmin
 Inactivates factors V & VIII
 Lyses fibrin & fibrinogen to form degradation products

Thus, normal physiologic haemostasis represents a delicate & complex

balance between coagulation & fibrinolytic systems

Pregnancy Changes
Pregnancy represents a hypercoagulable state
 Overall increased activity of coagulation factors except XI & XIII.
 Fibrinogen rises as early as 12/52 with peak 400 –465mg/dl in late
pregnancy
 Fibrinolytic system depressed during pregnancy & labour but back to
normal within 1hr after 3rd stage.
 Early puerperium

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  Secondary rise in fibrinogen, factors VIII, IX, X and
antithrombin III
 Return to non-pregnancy levels by 3-4/52 post partum.

Pathophysiology of DIC – Especially Widespread

 Complex & characterized by:

1. Procoagulation system activation.

 By massive or prolonged release of soluble tissue factors
and/or endothelial derived thromboplastins into circulation
 Tumours may release tissue factors due to necrosis or may
produce thromboplastins
 Endothelial damage
- Release or thromboplastins into circulation
- Synthesis of prostacyclin
- Exposure of collagen.
2. Fibrinolytic system activation
3. Consumption of inhibitors e.g. antithrombin III by
activated clotting factors
4. Cytokine release – Cytokines secretory products of T.
lymphocytes & macrophages

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  Include interferon – for macrophage activation,
interleukin 1, interleukin 6 (hepatic protein synthesis
regulation); tumour necrosis factor (TNF )
 Interleukin 1 & TNF act on endothelial cells to regulate
expression of adhesion molecules, thus
 Promoting leucocyte – endothelial adhesion
 Significant in chronic inflammation, healing & repair.
5. Cellular activation
 Damaged endothelial cells, platelets & WBC convert
 Plasminogen to plasmin → degrade fibrin to FDP
 Fibrin deposited in small vessels depending on
 Fibrinolytic response efficiency but,
 Fibrinolysins, not entirely beneficial because
 Plasmin digests fibrinogen, V & VIII further
 Reducing levels of coagulation factors in blood
6. Resultant end-organ damage
 Platelet aggregates
 Fibrin deposition

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 Causes of Acute & Chronic DIC
Acute Chronic
Shock Disseminated malignancy
Septicaemia Ca. pancreas, lung & stomach
Accidental trauma Leukaemia
Burns Liver disease
Acute intravascular haemolysisRenal disease.
Snake bites
Acute pancreatitis
Amniotic fluid embolism
Placental abruption
Septic abortion
Retained IUFD
PET/ET
Viraemia (e.g HIV, Varicella, CMV, hepatitis)
Drugs
Acidosis

Pathophysiological Basis
 Endothelia cell wall injury
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  Thromboplastin liberation from injured tissue
 Phospholipid release from RBC & platelets.
DIC effect
 Increased platelet aggregation
 Coagulation factors consumption
 Secondary fibrinolytic system activation
 Fibrin deposition into multiple organ sites →Ischaemia
tissue damage.
* Thrombocytopenia + FDP → impair haemostasis

Specific Obstetric Conditions

Placental abruption
 Liberation of tissue thromboplastin or
 Possible intrauterine consumption of fibrinogen & coagulation
factors due to formation of retroplacental clot.
 Hence activation of extrinsic system.
Retained IUFD
 Liberation of tissue thromboplastin from non-viable tissue.
Amniotic fluid embolism
 Release of tissue thromboplastin & also
 Intrinsic procoagulant properties of amniotic fluid
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  Associated hypotension, hypoxaemia & tissue acidosis
 Could encourage activation of coagulation factors
PET/ET
 Associated with chronic coagulation abnormalities that
 May lead to thrombocytopaenia & increase FDP
 Endothelial damage activates procoagulation proteins &
platelets
 ET & HELLP associated with damage in 11% & 15%
respectively
 PET & placental abruption significantly increase this
association
Saline or septic abortion
 Saline- induced abortion associated with subclinical DIC
 Due to release of thromboplastins from placenta
 Septic abortion – release of
 Tissue thromboplastin or
 Bacterial endotoxins (phospholipids)
Clinical Findings
Symptoms & Signs
 Acute variable & include
 Generalized bleeding
 Localized bleeding
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  Purpura, petechiae
 Thromboembolic phenomena
 Fever, hypotension, proteinuria, hypoxia, haemorrhagic
bullae & frank gangrene
 Widespread fibrin deposits in any organ system
o Including lungs, kidneys, brain &liver
 Chronic e.g. IUFD associated with thrombin production &
 May be associated with minimal or absent clinical S & S
Lab Findings
 Histologic diagnosis of fibrin deposits the only
 Definitive manner by which DIC may be confirmed
 Indirect clinical evaluation of coagulopathy can be evaluated by:
 Platelets – Decrease (<100,000/ml) in > 90% of cases
 In absence of other causes of thrombocytopaenia,
 Usually no spontaneous purpura if counts >30,000/ml
 Prothrombin time (PT)
 Measures time required for clotting by extrinsic pathway.
 Dependent on ultimate conversion of fibrinogen to fibrin
 Prolonged in only 50 – 75% of patients with DIC
 Why normal PT?
o Presence of circulating activated clotting factors like
thrombin or Xa that accelerate fibrin formation
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 o Presence of early FDP, rapidly clotted by thrombin.
 Partial Thromboplastin Time (PTT)
 Frequently normal in DIC (40-50%)
 Measures function of intrinsic & final common pathways
of the coagulation cascade
 Thrombin Time (TT)
 Elevated in 80% of patients with DIC
 Affected by amount of circulating
o Fibrinogen or presence of
o Thrombin inhibitors e.g.such as FDPs and heparin
 Specifically measures time necessary for
o Conversion of fibrinogen to fibrin
 Fibrinogen.
 Often decreased; approximately 70% of pts with DIC
o Have serum level < 150mg/dl
 Normally increases in pregnancy hence
o Reduction level could be deceptive
 Fibrin split (Degradation) Products – FDPs
 Values > 40mg/ml suggestive of DIC
 Elevated in ≥ 85% of patients with DIC
 Only indicate presence of fibrin

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 Clotting time & Clot retraction
 2ml blood in 5ml glass test tube (bedside)
 Provide qualitative evidence of hypofibrigenaemia
 If within 1/2hr clot doesn’t retract with
o Volume of serum exceeding that of formed clot,then
o Low serum fibrinogen levels can be suspected
 Peripheral Blood smear
 Reveals reticulocytes in approx. 46% of pts with DIC
 Bleeding time
 Progressively prolonged as platelet count <100,000/ml
 Spontaneous if platelet count <30,000/ml
 Newer Tests
 D-dimer
o Antigen formed as result of plasmin digestion of cross-
linked fibrin when
o Thrombin initiates transition of fibrinogen to fibrin &
o Activates factor XIII to cross-link fibrin formed
o Test specific for FDPs abnormal in 90% of cases.
 Antithrombin III level – abnormal in 89% of cases
 Fibrinopeptide A – abnormal in 70% of time.

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Differential Diagnosis
 Pregnancy related
 Idiopathic thrombocytopaenic purpura
 Haemophilia – factor VIII deficiency
 Von willebrands disease
 A protein synthesized by endothelial cells &
polymerized prior to secretion to bind to factor VIII
 Acts to promote platelets adhesion to collagen &
between themselves
 Autosomal dorminant trait
 Abruptio placentae – DIC usually after 5/52 of IUFD.
 Amniotic fluid embolism – associated with acute onset of
respiratory distress & shock
 PET/ET – Increase BP & proteinuria – eclamptic seizures.
DIC – Complications
 Complications associated with uncontrolled haemorrhage
 Widespread fibrin deposition in any major organ system
 Liver (hepatic failure)
 Kidneys (tubular necrosis) and
 Lungs (hypoxia)

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Treatment:
 Individual measures dictated by specific obstetric condition
 Primary most important treatment of pregnancy related DIC is
correction of underlying cause.
 Moderate or low-grade DIC – often just close observation
 Supportive therapy
 Correct shock, ischaemia (tissue) & acidosis
 Cardiopulmonary support
 Blood replacement
 Assisted ventilation
 Foetal monitoring, maternal fluid balance &
 Serial evaluation of coagulation parameters
 Sepsis suspected – antibiotics
 Delivery without episiotomy better than C/S
 No coagulopathy improvement hours after delivery, possible
 Sepsis, liver disease, retained POCS or congenital coagulation
defect
 Fibrinogen replacement with cryoprecipitate
 Fresh frozen plasma – limited & specific conditions include
 Massive haemorrhage
 Isolated factor deficiencies
 Warfarin reversal
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  Antithrombin III deficiency
 Immunodeficiencies
 Thrombocytopoenic purpura.
 Platelets if bleeding & count < 50,000/ml or prophylactic with ≤20-
30,000/ml or following massive transfusion (>2times blood volume)
 S/C low-dose heparin of low molecular weight
 In treating intravascular clotting process of DIC
 Heparin acts as anticoagulant by activating antithrombin III
 But has little affect on activated coagulant factors
 Heparin may to useful in IUFD, DIC with intact vascular
system otherwise anticoagulation is contraindicated in:
 Fulminating DIC & CNS insults
 Fulminant liver failure
 Obstetric accidents.
Prognosis
 Improvement with delivery of foetus or evacuation of uterus
 Maternal & foetal prognosis associated with obstetric condition
other than coagulopathy

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DR D.K NGOTHO – S/L RH

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