|
Disseminated
Intravascular Coagulation (DIC)
by Young Choi, ECFVG
Student
|
|
Disseminated Intravascular
Coagulation(DIC) is a thrombohemorrhagic disorder characterized by
primary thrombotic and secondary hemorrhagic diathesis causing multi-organ
failure. DIC is not a primary disease. It is a complication of a variety
of diseases which cause pathologic activation of the extrinsic and/or intrinsic
coagulation pathways.
Thus, major mechanisms for triggering DIC include release of tissue
factor or thrombo-plastic substances into the circulation (activation of
extrinsic pathway of coagulation), injury to endothelial cells exposing
subendothelial collagen (activation of intrinsic and extrinsic pathways
of coagulation), systemic hypercoagulopathy (renal disease with loss of
antithrombin III) and hepatic disease (decreased synthesis of coagulation
factors and anticoagulants). Release of tissue factor and/or thromboplastic
substances in the circulation is often triggered by sepsis, severe tissue
destruction (trauma, burns), pancreatitis, neoplasms (mucinous carcinomas,
leukemia, lymphoma, hemangiosarcoma) and/or obstetric complications.
Endothelial injury can initiate DIC by release of tissue factor and promoting
platelet aggregation to exposed collagen. Causes of endothelial injury
include vasculitis due to deposition of antigen-antibody complexes (lupus
erythematosus, feline infectious peritonitis), temperature extremes (heat
stroke, burns) and/or direct damage by trauma, toxins, rickettsiae, bacteria,
or their toxins and/or viruses.
Endotoxemia (gram negative sepsis, intestinal infarction) is one of
the most important and often fatal causes of DIC. In macrophages
and monocytes, bacterial endotoxins stimulate increased synthesis and release
of tissue factor and the proinflammatory mediators interleukin 1 (IL1) and
TNFα, which in turn induce procoagulatory functions of endothelial cells
such as increased expression of tissue factor and decreased expression
of thrombomodulin. In addition, TNFα also upregulates expression
of adhesion molecules on endothelial cells and, thus, promotes adhesion
of leukocytes which may damage endothelial cells by release of proteolytic
enzymes and oxygen-derived free radicals. Bacterial endotoxins can
also directly activate factor XII.
Mucus released from some carcinomas acts as thromboplastic substance
and directly activates factor X and, thus, is the common pathway of coagulation.
In acute promyelocytic leukemia, granules of neoplastic leukocytes release
thrombo-plastic substances. Tissue destruction (trauma, burns) causes
release of thromboplastin in circulation. Release of proteolytic enzymes
in the circulation and thus marked tissue destruction, is caused by pancreatitis.
Thromboplastins derived from placenta, dead fetus and/or amniotic fluid
may enter the maternal circulation in obstetric complications.
Activation of intravascular coagulation is followed by formation of
thrombi within the microcirculation of multiple organs such as brain, renal
glomeruli and/or pulmonary capillaries leading to microinfarction and tissue
hypoxia. DIC is also called consumptive coagulopathy, since excessive
intravascular coagulation leads to consumption of platelets and nonenzymatic
coagulation factors. The sequelae to excessive intravascular coagulation
are systemic hemorrhagic diathesis due to thrombocytopenia, reduced quantities
of coagulation factors and initiation of fibrinolysis. Initiation
of fibrinolysis is caused by a plasminogen activator, which cleaves plasminogen
bound to fibrin to plasmin. Plasmin degradates fibrin to FDPs, which
can bind to fibrinogen receptors on platelets and prevent further platelet
aggregation. In addition, thrombin binding to thrombomodulin results
in activation of protein C, which cleaves and inactivates plasminogen activator
inhibitor and coagulation factors V and VIII.
Finally, DIC is characterized by concurrent thrombocytopenia and depletion
of coagulation factors and antiboagulants such as antithrombin III, protein
C and protein S. The formation of fibrin within the microcirculation
causes microangiopathic hemolytic anemia with schistozyte and keratocyte
formation due to damaged membranes of erythrocytes.
Clinical features: DIC may present as acute, subacute or
chronic disease. Whereas acute and subacute cases have clinical symptoms
of multiorgan involvement such as respiratory signs (dyspnea, cyanosis),
neurological signs (convulsions, coma), renal symptoms (oliguria, acute
renal failure), chronic DIC usually causes only minor clinical signs or
is subclinical. DIC is based on evaluation of blood parameters.
Hemorrhagic diathesis predominates commonly in acute DIC and thrombotic
complications are the main feature of subacute or chronic DIC. Acute
DIC may develop primarily (e.g. caused by sepsis), or secondary to decompensation
of chronic DIC. Acute DIC is often fatal with multiorgan failure and
circulatory collapse.
Acute DIC is more commonly observed in dogs and is rare in cats.
Diagnosis: Diagnostics for DIC include concurrent prolongation
of coagulation profiles (APTT, PT) and thrombocytopenia. In addition,
there may be an increase in fibrin degradation products (FDPs), increase
or decrease of fibrinogen, decreased antithrombin III, regenerative hemolytic
anemia with schistocyte and keratocyte formation, neutrophilia with left
shift or neutropenia and hypoalbuminemia. Increased FDPs may be observed
in DIC, but is also seen in inflammatory diseases without concurrent DIC.
Most commonly, fibrinogen is decreased in DIC; however, increased fibrinogen
levels do not rule out DIC since fibrinogen is an acute phase protein synthesized
in the liver and is often elevated in inflammatory conditions. Regenerative
hemolytic anemia results from fibrin deposition in microcirculation and/or
internal bleeding. Neutrophilia with left shift is a sequela to inflammation
and/or marked tissue necrosis. Overwhelming inflammation may cause
neutropenia. Inflammation may be the cause of DIC or develop secondarily
in the course of DIC due to organ damage and immuno-suppression. Hypoalbuminemia
may be a sequela to inflammation and/or excessive external bleeding.
edited by Dr. Sandra Schoeniger, ADDL Graduate Student
References:
Pathologic Basis of Disease, 6th ed: 1999. Cotran RS, Kumar V and
Collins T (eds) S.B. Saunders Co.
Veterinary Laboratory Medicine, 3rd ed): 1994. Duncan JR, Prasse
KW and Mahaffey EA (eds). Iowa State University Press
--------------------------------------------------------------------------------
Disseminated intravascular coagulation (DIC) is a potentially fatal
condition in which platelet aggregation occurs followed by activation of
coagulation, and the fibrinolytic and complement cascades resulting in
hyaline microthrombi in arterioles and capillaries.
DIC has been reported to be precipitated by a number of infections
including :
Angiostrongylus
Babesia
Dirofilaria
Feline infectious peritonitis virus
Gram-positive bacteria
Gram-negative bacteria (endotoxins)
Infectious canine hepatitis virus
Rickettsia
Screening tests for these diseases should be performed in cases presenting
with signs of DIC which include :
Ecchymotic haemorrhages
Epistaxis
Hypofibrinogenaemia
Petechial haemorrhages
Prolonged clotting times
Thrombocytopenia
Schistocytes in blood smears
Other causes of DIC need to be ruled out, and include:
Acute pancreatitis
Heat stroke
Liver disease
Neoplasia (disseminated carcinomas, haemangiosarcomas or
leukaemia).
Severe Trauma
This information is
provided by Provet for educational purposes only.
You should seek the advice of your veterinarian if your pet is ill
as only he or she can correctly advise on the diagnosis and recommend the
treatment that is most appropriate for your pet.
****************************************************************
08/02/2007
Eleven week old pup Peggy Sue suffers with a rare blood disorder, and
as a result the ends of her tiny ears have fallen off and her paws deformed.
Just four days ago unwanted Peggy Sue was sent to the Dogs Trust in Leeds
to be re-homed. To tell us more about Peggy Sue's condition is our resident
Vet, Dr Scott Miller.
About Peggy Sue
Peggy Sue is just eleven weeks old and has been living with the Dogs
Trust for just four days. She's described as playful, mischievous, loving
and cheeky! Tan coloured Peggy Sue is a cross breed pup. The Dog Trust
aren't sure what breed she is as they say she's too tiny to tell.
The Condition
Sadly, Peggy Sue was born with a rare blood condition called Disseminated
Intravascular Coagulation (DIC). Her ears and her paws are deformed as
a result of her disability. However, her mobility and hearing remains unaffected,
and she's just like any other puppy. The condition means that her blood
clots more readily in extremities of her body. The Dogs Trust say Peggy
Sue won't be needing an operation, treatment or medication, and can't foresee
her experiencing any more deformity in the future.
The Future’s Bright for Peggy Sue!
The Dogs Trust say at the moment there's no reason to believe that
Peggy Sue's condition will get any worse as she gets older, and hopefully
as she grows bigger her mobility will not be affected. She will, however
have to be monitored closely (approximately every 6 months) but Dogs Trust
say they will cover any related future medical bills needed.
All Peggy Sue needs right now is a dedicated and understanding family
who will love her despite being slightly disfigured. The Dogs Trust Leeds
Re-homing Centre Manager, Amanda Sands, says 'Peggy is the most playful
and wonderful puppy who will make a great family pet. All she needs is lots
of understanding of her condition and loads of love.'
The Dogs Trust
The Dogs Trust is the UK's largest dog welfare charity, and cares for
over 15,000 dogs every year through a network of 17 re-homing centres. Dogs
Trust never destroys a healthy dog in its care.
To find out more about the work at Dogs Trust Leeds please call
the Re-homing Centre directly on 01132814920
http://www.dogstrust.org.uk
The above information is simply informational.
It's intent is not to replace the advice of a veterinarian nor to assist you
in making a diagnosis of your pet. Please consult with your own veterinarian
for confirmation of any diagnosis. Your pets life may depend on it.